patients with multiple disorders case study 98

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Winningham's Critical Thinking Cases in Nursing

Barbara a preusser, julie s snyder, mariann m harding, patients with multiple disorders - all with video answers.

Section 136

Name Class/Group Date Group Members INSTRUCTIONS All questions apply to this case study. Your responses should be brief and to the point. When asked to provide several answers, list them in order of priority or significance. Do not assume information that is not provided. Please print or write clearly. If your response is not legible, it will be marked as ? and you will need to rewrite it.

As you perform your initial assessment, you note superficial partial-thickness burns on A.N.'s right anterior leg, left anterior and posterior leg, and anterior torso. Shade the affected areas, then using the “rule of nines,” calculate the extent of A.N.'s burn injury.

Because you are concerned about possible smoke inhalation, what signs will you monitor A.N. for?

Interpret A.N.'s laboratory results.

A.N. is undergoing burn fluid resuscitation using the standard Baxter (Parkland) formula. She was admitted at 0400. She weighs 110 pounds. Calculate her fluid requirements, specify the fluids used in the Baxter (Parkland) formula, specify how much will be given, and indicate what time intervals will be used.

A.N. is in severe pain. What is the drug of choice for pain relief following burn injury, and how should it be given?

Because of her significant burn injury, A.N. is at high risk for infection. What measures will you institute to prevent this?

A.N.'s burns are to be treated by the open method with topical application of silver sulfadiazine (Silvadene). When caring for A.N., which interventions will you perform? (Select all that apply.) a. Maintain the room temperature at 85° F (29.4° C). b. Use clean technique when changing A.N.'s dressings. c. Monitor CBC frequently, particularly the white blood cells. d. Do not allow her to bathe for the initial 72 hours following injury. e. Apply a 1 ?16-inch film of medication, covering entire burn. f. Shave all hair within the wound beds.

A.N. has one area of circumferential burns on her right lower leg. What complication is she in danger of developing, and how will you monitor for it?

What interventions will facilitate maintaining A.N.'s peripheral tissue perfusion?

A special burn diet is ordered for A.N. She has always gained weight easily and is concerned about the size of the portions. What diet-related teaching will you provide?

Describe interventions that you could use to assist in meeting A.N.'s nutrition goals.

• Open access
• Published: 30 August 2024

Research landscape analysis on dual diagnosis of substance use and mental health disorders: key contributors, research hotspots, and emerging research topics

• Waleed M. Sweileh 1  

Annals of General Psychiatry volume  23 , Article number:  32 ( 2024 ) Cite this article

Metrics details

Substance use disorders (SUDs) and mental health disorders (MHDs) are significant public health challenges with far-reaching consequences on individuals and society. Dual diagnosis, the coexistence of SUDs and MHDs, poses unique complexities and impacts treatment outcomes. A research landscape analysis was conducted to explore the growth, active countries, and active journals in this field, identify research hotspots, and emerging research topics.

A systematic research landscape analysis was conducted using Scopus to retrieve articles on dual diagnosis of SUDs and MHDs. Inclusion and exclusion criteria were applied to focus on research articles published in English up to December 2022. Data were processed and mapped using VOSviewer to visualize research trends.

A total of 935 research articles were found. The number of research articles on has been increasing steadily since the mid-1990s, with a peak of publications between 2003 and 2012, followed by a fluctuating steady state from 2013 to 2022. The United States contributed the most articles (62.5%), followed by Canada (9.4%). The Journal of Dual Diagnosis , Journal of Substance Abuse Treatment , and Mental Health and Substance Use Dual Diagnosis were the top active journals in the field. Key research hotspots include the comorbidity of SUDs and MHDs, treatment interventions, quality of life and functioning, epidemiology, and the implications of comorbidity. Emerging research topics include neurobiological and psychosocial aspects, environmental and sociocultural factors, innovative interventions, special populations, and public health implications.

Conclusions

The research landscape analysis provides valuable insights into dual diagnosis research trends, active countries, journals, and emerging topics. Integrated approaches, evidence-based interventions, and targeted policies are crucial for addressing the complex interplay between substance use and mental health disorders and improving patient outcomes.

Introduction

Substance use disorders (SUDs) refer to a range of conditions characterized by problematic use of psychoactive substances, leading to significant impairment in physical, psychological, and social functioning [ 1 ]. These substances may include alcohol, tobacco, illicit drugs (e.g., cocaine, opioids, cannabis), and prescription medications. The global burden of SUDs is substantial, with far-reaching consequences on public health, socio-economic development, and overall well-being. For instance, alcohol abuse accounts for 3 million deaths worldwide annually, while the opioid crisis has escalated to unprecedented levels in certain regions, such as North America, resulting in tens of thousands of overdose deaths per year [ 2 , 3 , 4 ]. Mental health disorders (MHDs) encompass a wide range of conditions that affect mood, thinking, behavior, and emotional well-being [ 5 ]. Examples of MHDs include depression, anxiety disorders, post-traumatic stress disorder (PTSD), bipolar disorder, schizophrenia, and eating disorders. These conditions can significantly impair an individual's ability to function, negatively impacting their quality of life, relationships, and overall productivity [ 6 , 7 , 8 ]. Furthermore, certain MHD such as major depressive disorder and anxiety are often associated with specific affective temperaments, hopelessness, and suicidal behavior and grasping such connections can help in crafting customized interventions to reduce suicide risk [ 9 ]. In addition, a systematic review of 18 studies found that demoralization with somatic or psychiatric disorders is a significant independent risk factor for suicide and negative clinical outcomes across various populations [ 10 ]. The coexistence of SUDs and MHDs, often referred to as dual diagnosis or comorbidity, represents a complex and prevalent phenomenon that significantly impacts affected individuals and healthcare systems [ 11 , 12 , 13 , 14 , 15 ]. For instance, individuals with depression may be more likely to self-medicate with alcohol or drugs to cope with emotional distress [ 16 ]. Similarly, PTSD has been linked to increased rates of substance abuse, as individuals attempt to alleviate the symptoms of trauma [ 17 , 18 ]. Moreover, chronic substance use can lead to changes in brain chemistry, increasing the risk of developing MHDs or exacerbating existing conditions [ 17 , 19 , 20 , 21 ]. The coexistence of SUDs and MHDs presents unique challenges from a medical and clinical standpoint. Dual diagnosis often leads to more severe symptoms, poorer treatment outcomes, increased risk of relapse, and higher rates of hospitalization compared to either disorder alone [ 22 ]. Additionally, diagnosing and treating dual diagnosis cases can be complex due to overlapping symptoms and interactions between substances and psychiatric medications. Integrated treatment approaches that address both conditions simultaneously are essential for successful recovery and improved patient outcomes [ 20 ]. Patients grappling with dual diagnosis encounter a multifaceted web of barriers when attempting to access essential mental health services. These barriers significantly compound the complexity of their clinical presentation. The first barrier pertains to stigma, where societal prejudices surrounding mental health and substance use disorders deter individuals from seeking help, fearing discrimination or social repercussions [ 23 ]. A lack of integrated care, stemming from fragmented healthcare systems, poses another significant hurdle as patients often struggle to navigate separate mental health and addiction treatment systems [ 24 ]. Insurance disparities contribute by limiting coverage for mental health services and imposing strict criteria for reimbursement [ 25 ]. Moreover, there is a shortage of adequately trained professionals equipped to address both substance use and mental health issues, creating a workforce barrier [ 26 ]. Geographical disparities in access further hinder care, particularly in rural areas with limited resources [ 27 ]. These barriers collectively serve to exacerbate the clinical complexity of patients with dual diagnosis, and ultimately contributing to poorer outcomes.

A research landscape analysis involves a systematic review and synthesis of existing literature on a specific topic to identify key trends, knowledge gaps, and research priorities [ 28 , 29 ]. Scientific research landscape analysis, is motivated by various factors. First, the rapid growth of scientific literature poses a challenge for researchers to stay up-to-date with the latest developments in their respective fields. Research landscape analysis provides a structured approach to comprehend the vast body of literature, identifying crucial insights and emerging trends. Additionally, it plays a vital role in identifying knowledge gaps, areas with limited research, or inadequate understanding. This pinpointing allows researchers to focus on critical areas that demand further investigation, fostering more targeted and impactful research efforts [ 30 ]. Furthermore, in the realm of policymaking and resource allocation, evidence-based decision-making is crucial. Policymakers and funding agencies seek reliable information to make informed decisions about research priorities. Research landscape analysis offers a comprehensive view of existing evidence, facilitating evidence-based decision-making processes [ 28 ]. When it comes to the research landscape analysis of dual diagnosis of SUDs and MHDs, there are several compelling justifications to explore this complex comorbidity and gain a comprehensive understanding of its interplay and impact on patient outcomes. Firstly, the complexity of the interplay between SUDs and MHDs demands a comprehensive examination of current research to unravel the intricacies of this comorbidity [ 31 ]. Secondly, dual diagnosis presents unique challenges for treatment and intervention strategies due to the overlapping symptoms and interactions between substances and psychiatric medications. A research landscape analysis can shed light on effective integrated treatment approaches and identify areas for improvement [ 18 ]. Moreover, the public health impact of co-occurring SUDs and MHDs is substantial, resulting in more severe symptoms, poorer treatment outcomes, increased risk of relapse, and higher rates of hospitalization. Understanding the research landscape can inform public health policies and interventions to address this issue more effectively [ 32 ]. Lastly, the holistic approach of research landscape analysis enables a comprehensive understanding of current knowledge, encompassing epidemiological data, risk factors, treatment modalities, and emerging interventions. This integrative approach can lead to more coordinated and effective care for individuals with dual diagnosis [ 22 ]. Based on the above argument, the current study aims to conduct a research landscape analysis of dual diagnosis of SUDs and MHDs. The research landscape analysis bears a lot of significance for individuals and society. First and foremost, it’s a beacon of hope for individuals seeking help. Research isn’t just about dry statistics; it's about finding better ways to treat and support those facing dual diagnosis. By being informed about the latest breakthroughs, healthcare professionals can offer more effective, evidence-backed care, opening the door to improved treatment outcomes and a brighter future for those they serve. Beyond the individual level, this understanding has profound societal implications. It has the power to chip away at the walls of stigma that often surround mental health and substance use issues. Greater awareness and knowledge about the complexities of dual diagnosis can challenge stereotypes and biases, fostering a more compassionate and inclusive society. Additionally, society allocates resources based on research findings. When we understand the prevalence and evolving nature of dual diagnosis, policymakers and healthcare leaders can make informed decisions about where to channel resources most effectively. This ensures that the needs of individuals struggling with co-occurring disorders are not overlooked or under-prioritized. Moreover, research helps identify risk factors and early warning signs related to dual diagnosis. Armed with this information, we can develop prevention strategies and early intervention programs, potentially reducing the incidence of co-occurring disorders and mitigating their impact. Legal and criminal justice systems also stand to benefit. Understanding dual diagnosis trends can inform policies related to diversion programs, treatment alternatives to incarceration, and the rehabilitation of individuals with co-occurring disorders, potentially reducing rates of reoffending. Moreover, dual diagnosis research contributes to public health planning by highlighting the need for integrated mental health and addiction services. This knowledge can guide the development of comprehensive healthcare systems that offer holistic care to individuals with co-occurring disorders. Families and communities, too, are vital players in this narrative. With a grasp of research findings, they can provide informed, empathetic, and effective support to their loved ones, contributing to better outcomes.

The present research landscape analysis of dual diagnosis of SUDs and MHDs was conducted using a systematic approach to retrieve, process, and analyze relevant articles. The following methodology outlines the key steps taken to address the research questions:

Research Design The present study constitutes a thorough and robust analysis of the research landscape concerning the dual diagnosis of SUD and MHD. It's important to note that the research landscape analysis differs from traditional systematic or scoping reviews. In conducting research landscape analysis, we made deliberate methodological choices aimed at achieving both timely completion and unwavering research quality. These choices included a strategic decision to focus our search exclusively on a single comprehensive database, a departure from the customary practice of utilizing multiple databases. Furthermore, we streamlined the quality control process by assigning specific quality checks to a single author, rather than following the conventional dual-reviewer approach. This approach prioritized efficiency and expediency without compromising the rigor of our analysis. To expedite the research process further, we opted for a narrative synthesis instead of a quantitative one, ensuring that we provide a succinct yet highly informative summary of the available evidence. We place a premium on research transparency and, as such, are committed to sharing the detailed search string employed for data retrieval. This commitment underscores our dedication to fostering reproducibility and transparency in research practices.

Ethical considerations Since the research landscape analysis involved the use of existing and publicly available literature, and no human subjects were directly involved, no formal ethical approval was required.

Article retrieval Scopus, a comprehensive bibliographic database, was utilized to retrieve articles related to the dual diagnosis of SUDs and MHDs. Scopus is a multidisciplinary abstract and citation database that covers a wide range of scientific disciplines, including life sciences, physical sciences, social sciences, and health sciences. It includes content from thousands of scholarly journals.

Keywords used To optimize the search process and ensure the inclusion of pertinent articles, a set of relevant keywords and equivalent terms were employed. Keywords for “dual diagnosis” included dual diagnosis, co-occurring disorders, comorbid substance use, comorbid addiction, coexisting substance use, combined substance use, simultaneous substance use, substance use and psychiatric, co-occurring substance use and psychiatric, concurrent substance use and mental, coexisting addiction and mental, combined addiction and mental, simultaneous addiction and mental, substance-related and psychiatric, comorbid mental health and substance use, co-occurring substance use and psychiatric, concurrent mental health and substance use, coexisting mental health and substance use, combined mental health and substance use, simultaneous mental health and substance use, substance-related and coexisting psychiatric, comorbid psychiatric and substance abuse, co-occurring mental health and substance-related, concurrent psychiatric and substance use, coexisting psychiatric and substance abuse, combined psychiatric and substance use, simultaneous psychiatric and substance use, substance-related and concurrent mental, substance abuse comorbidity. Keywords for “Substance use disorders” included substance abuse, substance dependence, drug use disorders, addiction, substance-related disorders, drug abuse, opioid use disorder, cocaine use disorder, alcohol use disorder, substance misuse, substance use disorder, substance-related, substance addiction. Keywords for “Mental health disorders” included psychiatric disorders, mental illnesses, mental disorders, emotional disorders, psychological disorders, schizophrenia, depression, PTSD, ADHD, anxiety, bipolar disorder, eating disorders, personality disorders, mood disorders, psychotic disorders, mood and anxiety disorders, mental health conditions. To narrow down the search to focus specifically on dual diagnosis, we adopted a strategy that involved the simultaneous presence of SUDs and MHDs in the presence of specific keywords in the titles and abstracts such as “dual,” “co-occurring,” “concurrent,” “co-occurring disorders,” “dual disorders,” “dual diagnosis,” “comorbid psychiatric,” “cooccurring psychiatric,” “comorbid*,” and “coexisting”.

Inclusion and exclusion criteria To maintain the study’s focus and relevance, specific inclusion and exclusion criteria were applied. Included articles were required to be research article, written in English, and published in peer-reviewed journals up to December 31, 2022, Articles focusing on animal studies, internet addiction, obesity, pain, and validity of instruments and tools were excluded.

Flow chart of the search strategy Supplement 1 shows the overall search strategy and the number of articles retrieved in each step. The total number of research articles that met the inclusion and exclusion criteria were 935.

Validation of search strategy The effectiveness of our search strategy was rigorously assessed through three distinct methods, collectively demonstrating its ability to retrieve pertinent articles while minimizing false positives. First, to gauge precision, we meticulously examined a sample of 30 retrieved articles, scrutinizing their alignment with our research question and their contributions to the topic of dual diagnosis. This manual review revealed that the majority of the assessed articles were highly relevant to our research focus. Second, for a comprehensive evaluation, we compared the articles obtained through our search strategy with a set of randomly selected articles from another source. This set comprised 10 references sourced from Google Scholar [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], and the aim was to determine if our strategy successfully identified articles selected at random from an alternative database. Impressively, our analysis showed that the search strategy had a notably high success rate in capturing these randomly selected articles. Lastly, to further corroborate the relevance of our retrieved articles, we investigated the research interests of the top 10 active authors and the subject scope of the top 10 active journals. This exploration confirmed that their areas of expertise and the journal scopes were in alignment with the field of mental health and/or substance use disorders. These three validation methods collectively reinforce the reliability of our search strategy, affirming that the vast majority of the retrieved articles are indeed pertinent to our research inquiry.

Data processing and mapping Data extracted from the selected articles were processed and organized using Microsoft Excel. Information on the titles/abstracts/author keywords, year of publication, journal name, authors, institution and country affiliation, and number of citations received by the article were extracted. To visualize and analyze the research landscape, VOSviewer, a bibliometric analysis tool, was employed [ 43 ]. This software enables mapping and clustering of co-occurring terms, authors, and countries, providing a comprehensive overview of the dual diagnosis research domain.

Interpreting VOSviewer maps and generating research topics

We conducted a rigorous analysis and generated a comprehensive research landscape using VOSviewer, a widely acclaimed software tool renowned for its expertise in mapping research domains. We seamlessly integrated pertinent data extracted from the Scopus database, including publication metadata, into VOSviewer to delve into the frequency of author keywords and terminologies. The resulting visualizations provided us with profound insights into the intricate web of interconnected research topics and their relationships within the field. Interpreting VOSviewer maps is akin to navigating a vibrant and interconnected tapestry of knowledge. Each term or keyword in the dataset is depicted as a point on the map, represented by a circle or node. These nodes come in varying sizes and colors and are interconnected by lines of differing thicknesses. The size of a node serves as an indicator of the term’s significance or prevalence within the dataset. Larger nodes denote that a specific term is frequently discussed or plays a pivotal role in the body of research, while smaller nodes signify less commonly mentioned concepts. The colors assigned to these nodes serve a dual purpose. Firstly, they facilitate the categorization of terms into thematic groups, with terms of the same color typically belonging to the same cluster or sharing a common thematic thread. Secondly, they aid in the identification of distinct research clusters or thematic groups within the dataset. For instance, a cluster of blue nodes might indicate that these terms are all associated with a particular area of research. The spatial proximity of nodes on the map reflects their closeness in meaning or concept. Nodes positioned closely together share a robust semantic or contextual connection and are likely to be co-mentioned in research articles or share a similar thematic focus. Conversely, nodes situated farther apart indicate less commonality in terms of their usage in the literature. The lines that link these nodes represent the relationships between terms. The thickness of these lines provides insights into the strength and frequency of these connections. Thick lines indicate that the linked terms are frequently discussed together or exhibit a robust thematic association, while thinner lines imply weaker or less frequent connections. In essence, VOSviewer maps offer a visual narrative of the underlying structure and relationships within your dataset. By examining node size and color, you can pinpoint pivotal terms and thematic clusters. Simultaneously, analyzing the distance between nodes and line thickness unveils the semantic closeness and strength of associations between terms. These visual insights are invaluable for researchers seeking to unearth key concepts, identify research clusters, and track emerging trends within their field of study.

Growth pattern, active countries, and active journals

The growth pattern of the 935 research articles on dual diagnosis of substance use disorders and mental health disorders shows an increasing trend in the number of published articles over the years. Starting from the late 1980s and early 1990s with only a few publications, the research interest gradually picked up momentum, and the number of articles has been consistently rising since the mid-1990s. Table 1 shows the number of articles published in three different periods. The majority of publications (52.2%) were produced between 2003 and 2012, indicating a significant surge in research during that decade. The subsequent period from 2013 to 2022 saw a continued interest in the subject, accounting for 35.5% of the total publications. The number of articles published per year during the period from 2013 to 2022 showed a fluctuating steady state with an average of approximately 33 articles per year. The earliest period from 1983 to 2002 comprised 12.3% of the total publications, reflecting the initial stages of research and the gradual development of interest in the field.

Out of the total 935 publications, the United States contributed the most with 585 publications, accounting for approximately 62.5% of the total research output. Canada follows with 88 publications, making up around 9.4% of the total. The United Kingdom and Australia also made substantial contributions with 70 and 53 publications, accounting for 7.5 and 5.7%, respectively. Table 2 shows the top 10 active countries.

Based on the list of top active journals in the field of dual diagnosis of substance use and mental health disorders, it is evident that there are several reputable and specialized journals that focus on this important area of research (Table  3 ). These journals cover a wide range of topics related to dual diagnosis, including comorbidity, treatment approaches, intervention strategies, and epidemiological studies. The Journal of Dual Diagnosis appears to be a leading and comprehensive platform for research on dual diagnosis. It covers a broad spectrum of studies related to substance use disorders and mental health conditions. The Journal of Substance Abuse Treatment ranked second while the Mental Health and Substance Use Dual Diagnosis journal ranked third and seems to be dedicated specifically to the intersection of substance use disorder and mental health disorders, providing valuable insights and research findings related to comorbidities and integrated treatment approaches.

Most frequent author keywords

Mapping author keywords with a minimum occurrence of five (n = 96) provides insights in research related to dual diagnosis. Figure  1 shows the 96 author keywords and their links with other keywords. The number of occurrences represent the number of times each author keyword appears in the dataset, while the total link strength (TLS) indicates the combined strength of connections between keywords based on their co-occurrence patterns. The most frequent author keywords with high occurrences and TLS represent the key areas of focus in research on the dual diagnosis of substance use and mental health disorders.

“Comorbidity” is the most frequent keyword, with 144 occurrences and a high TLS of 356. This reflects the central theme of exploring the co-occurrence of substance use disorders and mental health conditions and their complex relationship. “Substance use disorder” and “dual diagnosis” are also highly prevalent keywords with 122 and 101 occurrences, respectively. These terms highlight the primary focus on studying individuals with both substance use disorders and mental health disorders, underscoring the significance of dual diagnosis in research. “Co-occurring disorders” and “substance use disorders” are frequently used, indicating a focus on understanding the relationship between different types of disorders and the impact of substance use on mental health. Several specific mental health disorders such as “schizophrenia,” “depression,” “bipolar disorder,” and “PTSD” are prominent keywords, indicating a strong emphasis on exploring the comorbidity of these disorders with substance use. “Mental health” and “mental illness” are relevant keywords, reflecting the broader context of research on mental health conditions and their interaction with substance use. “Treatment” is a significant keyword with 34 occurrences, indicating a focus on investigating effective interventions and treatment approaches for individuals with dual diagnosis. “Addiction” and “recovery” are important keywords, highlighting the interest in understanding the addictive nature of substance use and the potential for recovery in this population. The mention of “veterans” as a keyword suggests a specific focus on the dual diagnosis of substance use and mental health disorders in the veteran population. “Integrated treatment” is an important keyword, indicating an interest in studying treatment approaches that address both substance use and mental health disorders together in an integrated manner.

Network visualization map of author keywords with a minimum occurrence of five in the retrieved articles on dual diagnosis of substance use and mental health disorders

Most impactful research topics

To have an insight into the most impactful research topics on dual diagnosis, the top 100 research articles were visualized and the terms with the largest node size and TLS were used to. To come up with the five most common investigated research topics:

Dual diagnosis and comorbidity of SUDs and MHDs: This topic focuses on the co-occurrence of substance use disorders and various mental health conditions, such as schizophrenia, bipolar disorder, PTSD, anxiety disorders, and major depressive disorder. This research topic explored the prevalence, characteristics, and consequences of comorbidity in different populations, including veterans, adolescents, and individuals experiencing homelessness [ 13 , 19 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ].

Treatment and interventions for co-occurring disorders: This topic involves studies on different treatment approaches and interventions for individuals with dual diagnosis. These interventions may include motivational interviewing, cognitive-behavioral therapy, family intervention, integrated treatment models, assertive community treatment, and prolonged exposure therapy. The goal is to improve treatment outcomes and recovery for individuals with co-occurring substance use and mental health disorders [ 48 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ].

Quality of life and functioning in individuals with dual diagnosis: This research topic explores the impact of dual diagnosis on the quality of life and functioning of affected individuals. It assesses the relationship between dual diagnosis and various aspects of well-being, including social functioning, physical health, and overall quality of life [ 60 , 61 , 62 , 63 , 64 ].

Epidemiology and prevalence of co-occurring disorders: This topic involves population-based studies that investigate the prevalence of comorbid substance use and mental health disorders. It examines the demographic and clinical correlates of dual diagnosis, as well as risk factors associated with the development of co-occurring conditions [ 50 , 52 , 60 , 65 , 66 , 67 ].

Implications and consequences of comorbidity: This research topic explores the consequences of comorbidity between substance use and mental health disorders, such as treatment utilization, service access barriers, criminal recidivism, and the impact on suicidality. It also investigates the implications of comorbidity for treatment outcomes and the potential risks associated with specific comorbidities [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ].

Emerging research topics

Upon scrutinizing the titles, abstracts, author keywords, and a visualization map of the 100 recently published articles, the research themes listed below came to the forefront. It’s worth noting that some of the research themes in the 100 recently published articles were not groundbreaking; rather, they represented a natural progression of ongoing research endeavors, and that is why they were not listed as emerging research themes. For instance, there was a continuation of research into the prevalence and epidemiology of co-occurring mental illnesses and substance use disorders and characteristics of various cases of co-morbid cases of SUDs and MHDs. The list below included such emergent themes. It might seem that certain aspects within these research themes duplicate the initial research topics, but it’s crucial to emphasize that this is not the case. For example, both themes delve into investigations concerning treatment, yet the differentiation lies in the treatment approach adopted.

Neurobiological and psychosocial aspects of dual diagnosis: This research topic focuses on exploring the neurobiological etiology and underlying mechanisms of comorbid substance use and mental health disorders. It investigates brain regions, neurotransmitter systems, hormonal pathways, and other neurobiological factors contributing to the development and maintenance of dual diagnosis. Additionally, this topic may examine psychosocial aspects, such as trauma exposure, adverse childhood experiences, and social support, that interact with neurobiological factors in the context of comorbidity [ 76 ].

Impact of environmental and sociocultural factors on dual diagnosis: This research topic delves into the influence of environmental and sociocultural factors on the occurrence and course of comorbid substance use and mental health disorders. It may explore how cultural norms, socioeconomic status, access to healthcare, and societal attitudes toward mental health and substance use affect the prevalence, treatment outcomes, and quality of life of individuals with dual diagnosis [ 77 , 78 ].

New interventions and treatment approaches for dual diagnosis: This topic involves studies that propose and evaluate innovative interventions and treatment approaches for individuals with dual diagnosis. These interventions may include novel psychotherapeutic techniques, pharmacological treatments, digital health interventions, and integrated care models. The research aims to improve treatment effectiveness, adherence, and long-term recovery outcomes in individuals with comorbid substance use and mental health disorders [ 79 , 80 , 81 , 82 , 83 , 84 ].

Mental health and substance use in special populations with dual diagnosis: This research topic focuses on exploring the prevalence and unique characteristics of comorbid substance use and mental health disorders in specific populations, such as individuals with eating disorders, incarcerated individuals, and people with autism spectrum disorder. It aims to identify the specific needs and challenges faced by these populations and develop tailored interventions to address their dual diagnosis [ 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].

Public health implications and policy interventions for dual diagnosis: This topic involves research that addresses the public health implications of dual diagnosis and the need for policy interventions to address this complex issue. It may include studies on the economic burden of comorbidity, the impact on healthcare systems, and the evaluation of policy initiatives aimed at improving prevention, early intervention, and access to integrated care for individuals with dual diagnosis [ 81 , 96 , 97 , 98 , 99 , 100 , 101 ].

Comparison in research topics

The comparison between the most impactful research topics and emerging research topics in the field of dual diagnosis reveals intriguing insights into the evolving landscape of this critical area of study (Table  4 ). In the most impactful research topics, there is a strong emphasis on the epidemiology of dual diagnosis, indicating a well-established foundation in understanding the prevalence, characteristics, and consequences of comorbid SUDs and MHDs. Treatment and interventions also receive considerable attention, highlighting the ongoing efforts to improve outcomes and recovery for individuals with dual diagnosis. Quality of life and medical consequences are additional focal points, reflecting the concern for the holistic well-being of affected individuals and the health-related implications of comorbidity.

On the other hand, emerging research topics signify a shift towards newer methods and interventions. The exploration of neurobiology in the context of dual diagnosis reflects a growing interest in unraveling the underlying neurobiological mechanisms contributing to comorbidity. This shift suggests a deeper understanding of the neural pathways and potential targets for intervention. The consideration of dual diagnosis in special groups underscores a recognition of the unique needs and challenges faced by specific populations, such as individuals with autism spectrum disorder. This tailored approach acknowledges that one size does not fit all in addressing dual diagnosis. Finally, the exploration of environmental and psychosocial contexts highlights the importance of socio-cultural factors, policy interventions, and societal attitudes in shaping the experience of individuals with dual diagnosis, signaling a broader perspective that extends beyond clinical interventions. In summary, while the most impactful research topics have laid a strong foundation in epidemiology, treatment, quality of life, and medical consequences, the emerging research topics point to a promising future with a deeper dive into the neurobiology of dual diagnosis, a focus on special populations, and a broader consideration of the environmental and psychosocial context. This evolution reflects the dynamic nature of dual diagnosis research as it strives to advance our understanding and improve the lives of those affected by comorbid substance use and mental health disorders.

The main hypothesis underlying the study was that dual diagnosis, or the comorbidity of SUDs and MHDs, was historically underrecognized and under-researched. Over time, however, there has been a significant increase in understanding, appreciation, and research into this complex interplay in clinical settings. This was expected to manifest through a growing number of publications, increased attention to integrated treatment approaches, and a heightened recognition of the complexities and public health implications associated with dual diagnosis. The study aims to analyze this progression and its implications through a research landscape analysis, identifying key trends, knowledge gaps, and research priorities. The research landscape analysis of the dual diagnosis of SUDs and MHDs has unveiled a substantial and evolving body of knowledge, with a notable rise in publications since the mid-1990s and a significant surge between 2003 and 2012. This growing research interest underscores the increasing recognition of the importance and complexity of dual diagnosis in clinical and public health contexts. The United States has emerged as the most active contributor, followed by Canada, the United Kingdom, and Australia, with specialized journals such as the Journal of Dual Diagnosis playing a pivotal role in disseminating research findings. Common keywords such as “comorbidity,” “substance use disorder,” “dual diagnosis,” and specific mental health disorders highlight the primary focus areas, with impactful research topics identified as the comorbidity of SUDs and MHDs, treatment and interventions, quality of life, epidemiology, and the implications of comorbidity. Emerging research themes emphasize neurobiological and psychosocial aspects, the impact of environmental and sociocultural factors, innovative treatment approaches, and the needs of special populations with dual diagnosis, reflecting a shift towards a more holistic and nuanced understanding. The study highlights a shift from traditional epidemiological studies towards understanding the underlying mechanisms and broader social determinants of dual diagnosis, with a need for continued research into integrated treatment models, specific needs of diverse populations, and the development of tailored interventions.

The findings of this research landscape analysis have significant implications for clinical practice, public health initiatives, policy development, and future research endeavors. Clinicians and healthcare providers working with individuals with dual diagnosis can benefit from the identified research hotspots, as they highlight crucial aspects that require attention in diagnosis, treatment, and support. The prominence of treatment and intervention topics indicates the need for evidence-based integrated approaches that address both substance use and mental health disorders concurrently [ 102 , 103 , 104 ]. The research on the impact of dual diagnosis on quality of life and functioning underscores the importance of holistic care that addresses psychosocial and functional well-being [ 63 ]. For public health initiatives, understanding the prevalence and epidemiological aspects of dual diagnosis is vital for resource allocation and the development of effective prevention and early intervention programs. Policymakers can use the research landscape analysis to inform policies that promote integrated care, reduce barriers to treatment, and improve access to mental health and substance abuse services [ 15 , 105 ]. Furthermore, the identification of emerging topics offers opportunities for investment in research areas that are gaining momentum and importance.

The present study lays a robust groundwork, serving as a catalyst for the advancement of research initiatives and the formulation of comprehensive policies and programs aimed at elevating the quality of life for individuals grappling with the intricate confluence of SUDs and MHDs. Within the realm of significance, it underscores a critical imperative—the urgent necessity to revolutionize the landscape of tailored mental health services offered to patients harboring this challenging comorbidity. The paper distinctly illuminates the exigency for a heightened quantity of research endeavors that delve deeper into unraveling the temporal intricacies underpinning the relationship between SUDs and MHDs. In so doing, it not only unveils potential risk factors but also delves into the far-reaching consequences of treatment modalities over the extended course of time. This illumination, therefore, not only beckons but virtually ushers in a promising trajectory for prospective research endeavors, a path designed to uncover the intricate and evolving journey of dual diagnosis. A profound implication of this study is the direct applicability of its findings in the corridors of policymaking. By leveraging the insights encapsulated within the paper, policymakers stand uniquely equipped to sculpt policies that unequivocally champion the cause of integrated care. The remarkable emphasis on themes of treatment and intervention, permeating the research's core, emphatically underscores the urgent demand for dismantling barriers obstructing access to mental health and substance abuse services. It is incumbent upon policymakers to heed this call, for policies fostering the integration of care can inexorably elevate the outcomes experienced by patients grappling with dual diagnosis. Furthermore, this study artfully directs policymakers to allocate their resources judiciously by identifying burgeoning areas of research that are surging in prominence and pertinence. These emergent topics, discerned within the study, are not just topics; they are emblematic of windows of opportunity. By investing in these areas, policymakers can tangibly bolster research initiatives that are primed to tackle the multifaceted challenges inherent in the realm of dual diagnosis, addressing both current exigencies and future prospects. Additionally, the paper furnishes the foundational blueprint essential for the development of screening guidelines and clinical practice protocols that truly grasp the complexity of dual diagnosis. Clinical practitioners and healthcare establishments would be remiss not to harness this invaluable information to augment their own practices, thereby delivering more effective and empathetic care to individuals contending with dual diagnosis. In essence, this study serves as the compass guiding the way toward a more compassionate, comprehensive, and efficacious approach to mental health and substance abuse care for those in need.

The current landscape analysis of reveals significant implications and highlights the growing research interest in this field since the late 1980s. This increasing trend underscores the complexities and prevalence of comorbid conditions, which necessitate focused research and intervention strategies. The results can be generalized to guide future research priorities, inform clinical guidelines, shape healthcare policies, and provide a framework for other countries to adapt and build upon in their context.

The key take-home message emphasizes the importance of recognizing the high prevalence and intricate relationship between SUDs and MHDs, necessitating integrated and tailored treatment approaches. Additionally, the study advocates for employing efficient research methodologies to synthesize vast amounts of literature and identify emerging trends, focusing on quality of life, treatment outcomes, and the broader socio-cultural and policy contexts to improve care and support for individuals with dual diagnosis. Finally, the research underscores the critical need for continued focus on dual diagnosis, advocating for comprehensive, integrated, and innovative approaches to research, clinical practice, and policymaking to improve outcomes for affected individuals.

Despite the comprehensive approach adopted in this research landscape analysis, several limitations must be acknowledged. The exclusive reliance on Scopus, while extensive, inherently limits the scope of the analysis, potentially omitting relevant articles indexed in other databases such as the Chinese scientific database, thus not fully representing the entire research landscape on dual diagnosis of SUDs and MHDs. Assigning quality control responsibilities to a single author, rather than employing a dual-reviewer system, may introduce bias and affect the reliability of the quality assessment. Although this approach was chosen to expedite the process, it might have compromised the thoroughness of quality checks. The use of narrative synthesis instead of a quantitative synthesis limits the ability to perform meta-analytical calculations that could provide more robust statistical insights. This choice was made for efficiency, but it may affect the depth of the analysis and the generalizability of the conclusions. The reliance on specific keywords to retrieve articles means that any relevant studies not containing these exact terms in their titles or abstracts may have been overlooked, potentially leading to an incomplete representation of the research domain. The restriction to English-language articles and peer-reviewed journals may exclude significant research published in other languages or in non-peer-reviewed formats, introducing linguistic and publication type bias that could skew the results towards predominantly English-speaking regions and established academic journals. The inclusion of articles up to December 31, 2022, means that any significant research published after this date is not considered, potentially missing the latest developments in the field. The validation of the search strategy using a small sample of 30 articles and a comparison with 10 randomly selected articles from Google Scholar may not be sufficient to comprehensively assess the effectiveness of the search strategy; a larger sample size might provide a more accurate validation. Some of the research topics and findings may be specific to particular populations (e.g., veterans) and might not be generalizable to other groups, highlighting the need for caution when extrapolating the results to broader contexts. Although no formal ethical approval was required due to the use of existing literature, ethical considerations related to the interpretation and application of findings must still be acknowledged, particularly in terms of representing vulnerable populations accurately and sensitively. Acknowledging these limitations is crucial for interpreting the findings of this research landscape analysis and for guiding future research efforts to address these gaps and enhance the robustness and comprehensiveness of studies on the dual diagnosis of SUDs and MHDs.

In conclusion, the research landscape analysis of dual diagnosis of substance abuse and mental health disorders provides valuable insights into the growth, active countries, and active journals in this field. The identification of research hotspots and emerging topics informs the scientific community about prevailing interests and potential areas for future investigation. Addressing research gaps can lead to a more comprehensive understanding of dual diagnosis, while the implications of the findings extend to clinical practice, public health initiatives, policy development, and future research priorities. This comprehensive understanding is crucial in advancing knowledge, improving care, and addressing the multifaceted challenges posed by dual diagnosis to individuals and society.

Availability of data and materials

All data presented in this manuscript are available on the Scopus database using the search query listed in the methodology section.

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Sweileh, W.M. Research landscape analysis on dual diagnosis of substance use and mental health disorders: key contributors, research hotspots, and emerging research topics. Ann Gen Psychiatry 23 , 32 (2024). https://doi.org/10.1186/s12991-024-00517-x

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Evolution from viral encephalitis to autoimmune encephalitis to multiple sclerosis: a case report

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• Katharina Wurdack   ORCID: orcid.org/0000-0003-0952-5658 1 ,
• Harald Prüss   ORCID: orcid.org/0000-0002-8283-7976 1 , 2 &
• Carsten Finke   ORCID: orcid.org/0000-0002-7665-1171 1 , 3  

There are established associations between viral and autoimmune encephalitis as well as between autoimmune encephalitis and demyelinating central nervous system (CNS) diseases. Here, we report the evolution from varicella zoster virus (VZV) encephalitis to limbic autoimmune encephalitis (AIE) to multiple sclerosis (MS) in one patient.

• Case report

A woman in her mid-thirties presented with headache, aphasia, and a generalized tonic–clonic seizure. Cerebrospinal fluid (CSF) VZV polymerase chain reaction was positive and treatment with acyclovir was administered for VZV encephalitis. Five months later, the patient presented with cognitive deficits and MRI showed new bilateral hippocampal T2-hyperintensities. CSF analyses revealed pleocytosis and neuropil antibodies in tissue-staining. A diagnosis of limbic AIE was established and treatment with IV steroids and IV immunoglobulins initiated. One year later, the patient developed paresthesia of both legs and magnetic resonance imaging studies now showed new supratentorial and spinal demyelinating lesions. The patient was diagnosed with MS and treatment was changed to rituximab.

Conclusions

This unique case report links three important neuroimmunological entities in characterizing the evolution from infectious to autoimmune encephalitis to multiple sclerosis in one patient. Identification of such rare clinical constellations is critical for correct treatment choice and provides important novel insights into the pathophysiology of neuroimmunological disorders including viral triggers and overlap manifestations of autoimmune CNS diseases.

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Introduction

Autoimmune encephalitis (AIE) can be triggered by viral infections of the CNS, which is best described for herpes simplex virus encephalitis (HSVE) [ 1 ]. A recent study showed that up to 27% of HSVE patients develop AIE, of which around half manifest as encephalitis with antibodies directed against the NMDA receptor (NMDARE) and half as encephalitis with antibodies against unknown neural epitopes [ 2 ]. Additional suspected viral triggers of AIE include the varicella zoster virus (VZV) [ 3 , 4 , 5 ]. Furthermore, overlap syndromes between NMDARE and demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are increasingly reported and manifest in up to 3% of NMDARE patients [ 6 , 7 ]. Here, we report on a patient with VZV encephalitis and subsequent limbic AIE with neuropil antibodies, followed by MS.

A woman in her mid-thirties without any relevant previous medical history presented with sudden-onset motor aphasia followed by a generalized epileptic seizure, and recurring headaches accompanied by photo- and phonophobia as well as difficulties concentrating during the last two months. Neurologic examination revealed expressive aphasia with impaired language processing. Routine blood tests were normal; MRI showed a left angular gyrus FLAIR hyperintensity (Fig.  1 , panel A) without evidence for diffusion restriction. CSF analyses revealed increased white blood cell count (WBC, 21/µl), while red blood cell count (RBC, 2/µl), protein (419 mg/l), and lactate (1.33 mmol/l) were normal. Semiquantitative PCR from CSF was negative for HSV1/2, but positive for VZV, and anti-VZV-IgG was elevated. Serologically, acute infection with EBV, HIV, HCV, borreliosis, and syphilis were ruled out. OCB were positive in both serum and CSF (type 4). Testing for anti-NMDAR antibodies from CSF as well as anti-CASPR2 antibodies and anti-Hu antibodies from serum was negative. An angiogram showed no signs of vasculitis or vasculopathy. IV acyclovir was started with 1,000 mg every 8 h for VZV encephalitis and continued for 14 days, resulting in reduced headache severity and improved concentration. In addition, the patient was started on levetiracetam 1,000 mg daily and no further seizures occurred.

Cerebral and spinal MRI findings. At onset of VZV encephalitis, a hyperintense lesion under the left angular gyrus was present (panel A ). Five months later, limbic encephalitis manifested with bilateral (left > right) hippocampal FLAIR hyperintensity, which reverted to left hippocampal atrophy under immunomodulating treatment (panel B ). Seventeen months after onset of VZV encephalitis and twelve months after onset of limbic AIE, new periventricular, callosal, and spinal T2 hyperintense lesions supported the additional diagnosis of multiple sclerosis (panel C ). White arrows indicate FLAIR hyperintense lesions, black arrow indicates atrophy. AIE autoimmune encephalitis; MRI magnetic resonance imaging; FLAIR fluid attenuated inversion recovery; VZV varicella zoster virus

Five months after initial symptom onset, the patient was admitted for a focal seizure with aphasia, epigastric auras, concentration deficits, and memory impairment. CSF studies showed pleocytosis (WBC 15/µl), normal RBC (0/µl), protein (285 mg/l), and lactate (1.41 mmol/l) as well as negative VZV and HSV1/2 PCR. OCB were positive in CSF but not in serum (type 2). Extensive conventional testing for anti-neuronal autoantibodies in CSF and serum was negative. However, immunohistological mouse brain staining with CSF in our laboratory showed neuropil-directed autoantibodies. MRI revealed new bilateral (left > right) hippocampal FLAIR hyperintensities (Fig.  1 , panel B). The patient was diagnosed with definite limbic AIE [ 8 ] and received treatment with IV methylprednisolone 1,000 mg daily for 5 days and IV immunoglobulins (150 mg total). Immunotherapy led to an improvement in cognitive function, headache severity, and seizures (in addition to adapted anti-seizure medication with levetiracetam 3,000 mg daily and lacosamide 200 mg) but was escalated to plasmapheresis given persistent fatigue, concentration difficulties, and headache. At this point, the patient was transferred to our hospital for further treatment after an anaphylactic reaction during the fifth plasmapheresis cycle.

Eighteen months after initial symptom onset (twelve months after onset of limbic AIE), the patient reported fluctuating leg paresthesia. Follow-up MRI revealed new T2/FLAIR hyperintense lesions suggestive of MS, i.e., lesions in the corpus callosum, periventricular lesions, and a spinal cord lesion (Fig.  1 , panel C). Anti-AQP4 and anti-MOG-antibodies were negative in serum. The patient was referred to our neuroimmunological outpatient clinic and was diagnosed with MS upon fulfilling the McDonald criteria [ 9 ]. Treatment was now switched to 1,000 mg rituximab to address both AIE and MS, which improved fatigue severity, memory deficits, headache, hyperacusis, and paresthesia after six months. The patient also received cognitive training and benefitted from cognitive behavioral therapy after hospital discharge.

At last follow-up, the patient reported an improvement in overall symptom severity. Persisting symptoms included fatigue and intermittent headache. She lives independently and plans occupational rehabilitation. Cerebral and spinal MRI 36 months after first presentation showed persistent left hippocampal atrophy and constant MS-associated T2/FLAIR lesion load.

The patient has provided written informed consent to the submission of the case report to the journal. Approval was obtained from the ethics committee of Charité – Universitätsmedizin Berlin.

This case presents a unique clinical constellation, i.e., viral encephalitis followed by autoimmune encephalitis and multiple sclerosis. Diagnosis of VZV encephalitis was established based on the presence of headaches with photo- and phonophobia as well as concentration difficulties, CSF pleocytosis, positive semiquantitative VZV-PCR, and elevated VZV-IgG in CSF. MRI revealed a FLAIR-hyperintense angular gyrus lesion. Indeed, while MRI is often unremarkable in VZV encephalitis, up to 15% of patients develop post-inflammatory lesions of deep-gray matter or supratentorial white-matter structures [ 10 ]. Notably, VZV encephalitis in our patient followed a mild disease course. However, it has been suggested that due to underreporting of mild encephalitic manifestations, the frequency of VZV encephalitis may be underestimated [ 10 ]. Furthermore, viral triggers including HSV and VZV infections have been established in the pathophysiology of AIE [ 11 ]. Following HSVE, anti-neuronal autoantibodies are present in up to 42% of patients (around half of which are directed against unknown neural epitopes), and 23% of patients develop AIE within a median of 30–39 days. However, the observed delay between HSVE and onset of AIE ranges up to 510 days [ 2 , 12 ], indicating significant variability in the time course of post-viral AIE manifestation. Similarly, several cases of NMDARE following other viral CNS infections including VZV encephalitis have been reported [ 3 , 4 , 5 ]. However, the exact mechanisms inducing the production of autoantibodies associated with AIE remain unclear. Potential factors include antigen-independent viral stimulation of B cells (e.g., via Toll-like receptors), molecular mimicry, or exposure to tissue destruction-related neoantigens [ 11 ]. Here, we report a novel association between VZV encephalitis and AIE with antibodies directed against unknown neuropil epitopes.

Overlap syndromes of AIE with demyelinating CNS diseases have almost exclusively been investigated in patients with NMDARE, where they have been reported in up to 3% of cases, exceeding the expected frequency based on reported prevalence rates for the most common demyelinating disorder, i.e., MS [ 13 ]. AIE can precede the first demyelinating episode or vice versa with a delay of up to several years between the two disorders, or both can occur simultaneously [ 6 ]. Importantly, the presence of isolated OCB in CSF can occur both in AIE as well as in MS, and is included in both the diagnostic criteria for autoantibody-negative probable AIE [ 8 ] and the diagnostic criteria for MS [ 9 ]. Future studies are needed to explore the dynamics of CSF parameters including OCB in larger patient cohorts with overlap syndrome. Most cases of overlap syndrome have been observed so far as association of NMDARE with MOGAD or NMOSD [ 6 ], although overlaps between NMDARE and MS were reported in a systematic literature review [ 7 ]. It seems plausible that an individual predisposition for autoimmune disorders is of relevance in the development of these overlap syndromes. In addition, viral infections might be shared triggers between demyelinating CNS diseases and AIE. For example, Eppstein-Barr virus infection has been suggested to play a causal role in MS pathophysiology through molecular mimicry with glial or myelin proteins and B cell induction [ 14 , 15 ]. So far, only one case of limbic AIE without detection of known autoantibodies and concomitant MS has been reported, although no tissue-based testing for autoantibodies was conducted in this patient [ 16 ]. The current case thus confirms that overlap syndromes extend beyond NMDARE and should be considered in patients with AIE or demyelinating diseases presenting with atypical symptoms.

In conclusion, AIE should be considered in patients presenting with recurrent or new neurologic symptoms following infectious encephalitis. Post-infectious AIE will most often occur after HSVE, but can also manifest after other viral CNS infections and can arise in association with different autoantibodies. Patients exhibiting autoantibodies directed against unknown neural antigens have likely been underreported due to limited availability of tissue-based antibody-testing. The presence of these yet-uncharacterized antibodies in around one fifth of HSVE patients [ 2 ] underlines the importance of tissue-based testing in patients with suspected AIE and negative conventional antibody-testing. Importantly, established clinical criteria [ 8 ] should be employed to inform treatment decisions in suspected AIE. In addition, while overlap syndromes with demyelinating CNS diseases occur most often in association with NMDARE, they can likewise affect patients with other AIE variants. Importantly, AIE and demyelinating episodes can occur sequentially or simultaneously [ 6 , 7 ], so increased awareness for atypical symptoms in patients with AIE or demyelinating CNS disease is warranted.

Concerning the pathophysiology of AIE and demyelinating CNS diseases, both external and individual factors must be considered. While many environmental risk factors for MS have been identified [ 17 ], data to address this question in AIE is still lacking due to the much lower incidence. However, both the development of AIE and demyelinating CNS disease have been associated with innate and acquired alterations of the immune system [ 11 , 17 ]. Viral infections may represent an influential external element that, taken together with individual susceptibility to immune system dysregulation, could trigger neuroimmunological disease [ 2 , 11 , 14 , 15 ]. The identification of exceptional cases such as our patient, with the transition from infectious to autoimmune neurologic disease and the additional development of demyelinating CNS disease, may help to increase our understanding of shared mechanisms of immune dysregulation across infectious and neuroimmunological diseases.

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Wurdack, K., Prüss, H. & Finke, C. Evolution from viral encephalitis to autoimmune encephalitis to multiple sclerosis: a case report. J Neurol (2024). https://doi.org/10.1007/s00415-024-12659-9

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An Exploratory Case-Control Study for Mitochondrial DNA G10398A in Bipolar I Disorder Patients with a Family History of Affective Disorders

Affiliations.

• 1 Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India.
• 2 Department of NDDTC, All India Institute of Medical Sciences, New Delhi, India.
• PMID: 39219346
• DOI: 10.4103/npmj.npmj_119_24

Background: The mitochondrial DNA (mtDNA) G10398A polymorphism has been associated with bipolar disorder (BD). It leads to an amino acid substitution within NADH dehydrogenase subunit, thereby altering the mitochondrial complex I function. This exploratory case-control study assesses the association of mtDNA G10398A with the risk of BD and its relationship to clinical variables in Indian patients.

Methods: Cases met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of BD-I in remission and had a family history of BD or recurrent unipolar disorder in biological relatives. The healthy controls (HC) had no known illness and were screened negative for Family Interview for Genetic Studies. Participants were assessed using Clinical Pro forma, NIMH-Life Chart Method and Alda lithium response scale. The mtDNA G10398A was assessed with real-time polymerase chain reaction using TaqMan assay.

Results: A total of 82 participants were recruited across cases and controls, with 42 patients (50% with maternal history) and 40 healthy individuals with similar demographic profiles. The mean age of onset was 25.16 (standard deviation [SD] 7.6) years, with illness for 11.59 years (SD: 7.18). Allele A was found in 50% of cases compared to 32.5% HC (odds ratio = 2.08; 95% confidence interval [CI]: 0.85-5.09). Findings remain non-significant for patients with maternal mood disorders (allele A: 38.9%; 21/42). Cases with allele G had significantly higher body mass index (BMI) (P = 0.008) than those with allele A.

Conclusion: The study adds information on mtDNA 10398A amongst Indian patient samples and healthy individuals. No significant group difference was found with respect to mtDNA G10398A. The positive association of allele G with higher BMI has potential clinical relevance that can be further investigated in larger samples.

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• Ferrari AJ, Stockings E, Khoo JP, Erskine HE, Degenhardt L, Vos T, et al. The prevalence and burden of bipolar disorder: Findings from the Global Burden of Disease Study 2013. Bipolar Disord 2016;18:440–50.
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Case Examples

Examples of recommended interventions in the treatment of depression across the lifespan.

Children/Adolescents

A 15-year-old Puerto Rican female

The adolescent was previously diagnosed with major depressive disorder and treated intermittently with supportive psychotherapy and antidepressants. Her more recent episodes related to her parents’ marital problems and her academic/social difficulties at school. She was treated using cognitive-behavioral therapy (CBT).

Chafey, M.I.J., Bernal, G., & Rossello, J. (2009). Clinical Case Study: CBT for Depression in A Puerto Rican Adolescent. Challenges and Variability in Treatment Response. Depression and Anxiety , 26, 98-103.  https://doi.org/10.1002/da.20457

Sam, a 15-year-old adolescent

Sam was team captain of his soccer team, but an unexpected fight with another teammate prompted his parents to meet with a clinical psychologist. Sam was diagnosed with major depressive disorder after showing an increase in symptoms over the previous three months. Several recent challenges in his family and romantic life led the therapist to recommend interpersonal psychotherapy for adolescents (IPT-A).

Hall, E.B., & Mufson, L. (2009). Interpersonal Psychotherapy for Depressed Adolescents (IPT-A): A Case Illustration. Journal of Clinical Child & Adolescent Psychology, 38 (4), 582-593. https://doi.org/10.1080/15374410902976338

© Society of Clinical Child and Adolescent Psychology (Div. 53) APA, https://sccap53.org/, reprinted by permission of Taylor & Francis Ltd, http://www.tandfonline.com on behalf of the Society of Clinical Child and Adolescent Psychology (Div. 53) APA.

General Adults

Mark, a 43-year-old male

Mark had a history of depression and sought treatment after his second marriage ended. His depression was characterized as being “controlled by a pattern of interpersonal avoidance.” The behavior/activation therapist asked Mark to complete an activity record to help steer the treatment sessions.

Dimidjian, S., Martell, C.R., Addis, M.E., & Herman-Dunn, R. (2008). Chapter 8: Behavioral activation for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: A step-by-step treatment manual (4th ed., pp. 343-362). New York: Guilford Press.

Reprinted with permission from Guilford Press.

Denise, a 59-year-old widow

Denise is described as having “nonchronic depression” which appeared most recently at the onset of her husband’s diagnosis with brain cancer. Her symptoms were loneliness, difficulty coping with daily life, and sadness. Treatment included filling out a weekly activity log and identifying/reconstructing automatic thoughts.

Young, J.E., Rygh, J.L., Weinberger, A.D., & Beck, A.T. (2008). Chapter 6: Cognitive therapy for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: A step-by-step treatment manual (4th ed., pp. 278-287). New York, NY: Guilford Press.

Nancy, a 25-year-old single, white female

Nancy described herself as being “trapped by her relationships.” Her intake interview confirmed symptoms of major depressive disorder and the clinician recommended cognitive-behavioral therapy. 

Persons, J.B., Davidson, J. & Tompkins, M.A. (2001). A Case Example: Nancy. In Essential Components of Cognitive-Behavior Therapy For Depression (pp. 205-242). Washington, D.C.: American Psychological Association. http://dx.doi.org/10.1037/10389-007

While APA owns the rights to this text, some exhibits are property of the San Francisco Bay Area Center for Cognitive Therapy, which has granted the APA permission for use.

Luke, a 34-year-old male graduate student

Luke is described as having treatment-resistant depression and while not suicidal, hoped that a fatal illness would take his life or that he would just disappear. His treatment involved mindfulness-based cognitive therapy, which helps participants become aware of and recharacterize their overwhelming negative thoughts. It involves regular practice of mindfulness techniques and exercises as one component of therapy.

Sipe, W.E.B., & Eisendrath, S.J. (2014). Chapter 3 — Mindfulness-Based Cognitive Therapy For Treatment-Resistant Depression. In R.A. Baer (Ed.), Mindfulness-Based Treatment Approaches (2nd ed., pp. 66-70). San Diego: Academic Press.

Reprinted with permission from Elsevier.

Sara, a 35-year-old married female

Sara was referred to treatment after having a stillbirth. Sara showed symptoms of grief, or complicated bereavement, and was diagnosed with major depression, recurrent. The clinician recommended interpersonal psychotherapy (IPT) for a duration of 12 weeks.

Bleiberg, K.L., & Markowitz, J.C. (2008). Chapter 7: Interpersonal psychotherapy for depression. In D.H. Barlow (Ed.) Clinical handbook of psychological disorders: a treatment manual (4th ed., pp. 315-323). New York, NY: Guilford Press.

Peggy, a 52-year-old white, Italian-American widow

Peggy had a history of chronic depression, which flared during her husband’s illness and ultimate death. Guilt was a driving factor of her depressive symptoms, which lasted six months after his death. The clinician treated Peggy with psychodynamic therapy over a period of two years.

Bishop, J., & Lane , R.C. (2003). Psychodynamic Treatment of a Case of Grief Superimposed On Melancholia. Clinical Case Studies , 2(1), 3-19. https://doi.org/10.1177/1534650102239085

Several case examples of supportive therapy

Winston, A., Rosenthal, R.N., & Pinsker, H. (2004). Introduction to Supportive Psychotherapy . Arlington, VA : American Psychiatric Publishing.

Older Adults

Several case examples of interpersonal psychotherapy & pharmacotherapy

Miller, M. D., Wolfson, L., Frank, E., Cornes, C., Silberman, R., Ehrenpreis, L.…Reynolds, C. F., III. (1998). Using Interpersonal Psychotherapy (IPT) in a Combined Psychotherapy/Medication Research Protocol with Depressed Elders: A Descriptive Report With Case Vignettes. Journal of Psychotherapy Practice and Research , 7(1), 47-55.

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Collaborative Care for patients with severe borderline and NOS personality disorders: A comparative multiple case study on processes and outcomes

Barbara stringer.

1 Department of Psychiatry and EMGO institute, VU University Medical Center/GGZ inGeest, Amsterdam, the Netherlands

2 Research Group Mental Health Nursing, Inholland University for Applied Sciences, Amsterdam, the Netherlands

Berno van Meijel

Bauke koekkoek.

3 Propersona, Centre for Education and Science, ProPersona, Wolfheze, the Netherlands

4 Research Group Social Psychiatry & Mental Health Nursing, HAN University of Applied Science, Nijmegen, the Netherlands

5 Department of Clinical Psychology and EMGO institute, VU University Medical Center, Amsterdam, the Netherlands

Aartjan Beekman

Associated data.

Structured psychotherapy is recommended as the preferred treatment of personality disorders. A substantial group of patients, however, has no access to these therapies or does not benefit. For those patients who have no (longer) access to psychotherapy a Collaborative Care Program (CCP) is developed. Collaborative Care originated in somatic health care to increase shared decision making and to enhance self management skills of chronic patients. Nurses have a prominent position in CCP's as they are responsible for optimal continuity and coordination of care. The aim of the CCP is to improve quality of life and self management skills, and reduce destructive behaviour and other manifestations of the personality disorder.

Methods/design

Quantitative and qualitative data are combined in a comparative multiple case study. This makes it possible to test the feasibility of the CCP, and also provides insight into the preliminary outcomes of CCP. Two treatment conditions will be compared, one in which the CCP is provided, the other in which Care as Usual is offered. In both conditions 16 patients will be included. The perspectives of patients, their informal carers and nurses are integrated in this study. Data (questionnaires, documents, and interviews) will be collected among these three groups of participants. The process of treatment and care within both research conditions is described with qualitative research methods. Additional quantitative data provide insight in the preliminary results of the CCP compared to CAU. With a stepped analysis plan the 'black box' of the application of the program will be revealed in order to understand which characteristics and influencing factors are indicative for positive or negative outcomes.

The present study is, as to the best of our knowledge, the first to examine Collaborative Care for patients with severe personality disorders receiving outpatient mental health care. With the chosen design we want to examine how and which elements of the CC Program could contribute to a better quality of life for the patients.

Trial registration

Netherlands Trial Register (NTR): NTR2763

A personality disorder is a severe and complex psychiatric illness. The borderline personality disorder (BPD) and the personality disorder not otherwise specified (NOS) both belong to the two most prevalent personality disorders. The lifetime prevalence of borderline personality disorders is estimated at 1-2% in the general population, whereas in patient samples the prevalence is approximate 10-20%. The personality disorder NOS has an estimated prevalence of 8-13% in patient samples [ 1 , 2 ].

Structured psychotherapy is recommended as the preferred treatment of personality disorders. Several studies report modest positive treatment results [ 3 - 9 ]. Psychotherapy contributes to higher quality of life, reduced psychopathology and destructive behaviour, and sustainable changes in personality.

A substantial group of patients, however, does not benefit from these psychotherapies [ 10 - 13 ]. Besides limitations in availability of these therapies, some patients do not meet the inclusion criteria or they drop out during treatment. Others need more psychosocial support for their many complex social problems. Most patients who do not benefit have a chronic and unstable course of illness with disruptive and destructive behaviour [ 10 , 13 , 14 ]. They put a high demand on the health care services provided for rather long, but often discontinuous periods of time [ 15 ]. These patients often receive community mental health care (often referred to as a team: CMHC team), mostly provided by (community) mental health nurses [ 10 , 14 ]. The treatment delivered by CMCH teams is, however, not standardized and highly unstructured [ 16 , 17 ].

Research indicates that especially nurses in particular experience caring for people with severe (borderline) personality disorders as highly stressful [ 18 - 21 ]. Strong emotional responses towards the patient arise frequently, particularly when the disruptive behaviour of the patient is unpredictable and difficult to understand. This contributes to condemnation of the patient by the nurse and a less empathic attitude. Ambivalent care seeking of these patients, shifting between dependency from and condemnation of professionals, can be explained out of their disorder and the irregular course of the therapeutic process. This same ambivalent care seeking, however, is difficult for care providers to accept and to cope with and it often leads to ineffective professional behaviour [ 22 , 23 ]. On the one hand, while balancing between autonomy and safety of the patient, nurses easily feel forced and responsible to protect the patient. Nurses may apply restrictive interventions to control the patient's destructive behaviour [ 24 - 26 ]. On the other hand, nurses may underestimate the needs and disabilities of their patients and perceive them as able but unwilling to change [ 27 , 28 ]. To keep the balance between playing a waiting game on the one hand, and being overly supportive and protective on the other hand is considered to be difficult with regard to these patients [ 13 , 27 ]. Studies reveal that patients and care providers set different priorities during treatment, including the specific needs of patients that require attention [ 29 - 33 ]. These, at times, conflicting priorities can cause miscommunication between patients and care providers and, hence, adversely affect outcomes of care [ 29 , 31 ].

As a response to these challenges, we developed a structured easily accessible intervention program for this subpopulation of patients, provided by (community) mental health nurses. For this intervention program we have adapted the principles of Collaborative Care (CC) [ 34 - 36 ]. Collaborative Care Programs originated in somatic health care to increase shared decision making and to enhance self management skills of chronic patients. Collaborative relationships come into existence when patients, their informal carers, and care providers have shared goals and mutual understanding of roles, expectations and responsibilities. As a consequence of more effective self management, patients report that their quality of life improves, because they feel they can better cope with problems derived from their disorder [ 35 , 36 ]. To date, Collaborative Care Programs (CCP) have proven to be effective for depressive and bipolar disorders [ 37 - 45 ].

Nurses have a prominent position in Collaborative Care Programs as they function as collaborative care managers. In this position they are responsible for optimal continuity and coordination of care. To optimize the continuity and coordination of care, intensive partnership working is needed within a Collaborative Care team (CCT). The CCT consists of the patient, his/her informal carer, the nurse, and the psychiatrist and/or psychologist. The CCT can optionally be expanded with others who possibly could contribute to effective treatment and care of the patient. The CCT lends support to the patient and it is in this team that crucial decisions regarding treatment will be made.

A Collaborative Care Program for patients with severe personality disorder has as to the best of our knowledge not yet been developed or tested. In this stage of intervention development, insights in both the feasibility and as well as the preliminary results of the intervention are needed. Therefore, we combine quantitative and qualitative data in a comparative multiple case study, which makes it possible to test the feasibility of the CCP in clinical practice, and also provides insight into the preliminary outcomes of CCP [ 46 , 47 ]. This study functions as a pre stage for a future RCT. The following research objectives are formulated:

(1). To describe the processes of the application of a Collaborative Care Program for patients with a severe borderline or NOS personality disorder in comparison with Care as Usual (CAU) from the perspective of patients, their informal carers and nurses;

(2). To describe the preliminary outcomes of the CCP in comparison with Care as Usual;

(3). To explain which characteristics of the CCP are indicative for the occurrence of positive or negative outcomes compared to CAU.

Methods/Design

A comparative multiple case study may be used for the thorough evaluation of complex intervention programs [ 46 - 48 ]. The research generates descriptive and explanatory data regarding treatment processes and outcomes of the intervention program. Different perspectives are integrated in the evaluation: the perspective of patients, their informal carers and nurses. In our multiple case study two treatment conditions will be compared: one functions as the experimental condition in which the Collaborative Care Program is provided; the other condition functions as the control condition in which Care as Usual (CAU) is offered. Different types of data collection will be used: questionnaires, documents, and interviews. A case is defined as the treatment process of one patient in which integrated data from the three perspectives (patient, informal carers and nurse) concerning the application and the outcomes of the CCP or CAU will be gathered and analysed.

Within a comparative multiple case study, data are analyzed at the individual case level, group level, as well as between groups level [ 46 - 48 ]. The process of treatment and care within both research conditions is described with qualitative research methods. Additional quantitative data provide insight in the preliminary results of the CCP compared to CAU. By means of data triangulation, the connection between the application and the preliminary outcomes of the Collaborative Care Program will be explained in comparison with Care as Usual. With a stepped analysis plan the 'black box' of the application of the intervention program will be revealed in order to understand which characteristics and influencing factors are indicative for positive or negative outcomes.

Participants

Participants are recruited from two comparable community mental health care (CMHC) teams of a large mental health organisation in the Netherlands. One team is indicated as the experimental condition and the other as the control condition.

Both CMHC teams provide long-term outpatient care for patients with various severe mental disorders. Patients that will be included should be between 18 and 65 years of age, have a main diagnosis of borderline or NOS personality disorder (DSM-IV-TR), have a score of 15 or higher on the Borderline Personality Disorder Severity Index (BPDSI, range 0-90) [ 5 , 49 ] and have received psychiatric care for at least two years. Participants are required to speak and read Dutch sufficiently well to fill in the questionnaires.

Participants are excluded when they currently participate in a structured psychotherapeutic program or when it is expected they will participate in such a program within a period of nine months from the start of the study. All participants will be asked to sign for informed consent based on oral and written information about the research project.

Informal carers

The participating patients will be asked to give their permission for approaching one of their informal carers to also participate in the study. The carers need to be in contact with the patient (physically or by telephone/email) for at least one hour a week. When the collaboration with an informal caregiver impedes the treatment process or negatively influences the safety of the patient, carers can be excluded. This will only take place after consultation with the patient.

Ten mental health nurses from the experimental condition and five nurses from the control condition will be included in the study. Participation takes place on a voluntary basis. Nurses who participate in the experimental condition will receive a three-days training in providing the Collaborative Care Program. Nurses in the control condition will offer Care as Usual.

Selection of patients

The required number of cases for a multiple case study depends upon the heterogeneity among the cases (more heterogeneity requires more cases) and is therefore arbitrary. To take into account the variety in presentation of the disorder and the variety of problems, this study will include at least sixteen patients in each condition. This adds up to 32 cases.

Intervention

Collaborative care program.

This Collaborative Care Program is developed to improve the quality of care for patients with severe personality disorders within a community mental health care setting. The expectation is that the Collaborative Care Program (1) improves quality of life, (2) reduces destructive behaviour (suicidal, self harm, aggressive or addictive behaviour) and other manifestations of the (borderline or NOS) personality disorder, (3) improves mastery of the patient, and (4) enhances satisfaction with care by both patients and informal caregivers. Finally, we aim for a positive effect on attitudes, knowledge and skills of nurses.

Collaborative Care for patients with severe borderline or NOS personality disorders consists of five integrated components (see Figure ​ Figure1). 1 ). The different components of the execution stage can be applied in a flexible order, dependent on the priorities in unmet needs and the preferences of the patient. Although CCP offers a goal-oriented structure, it comes to the professionalism of the nurses to adjust this structure to the preferences of the patient, the patient's cognitive capacities, and to the extent of illness insight/acceptance of each individual patient. The different components of the CCP will be briefly elucidated. The Collaborative Care Program is elaborated in a workbook for patients and nurses and in a separate manual for nurses. More detailed information about the content of the CC Program is available (see Additional file 1 ).

the five integrated components of the Collaborative Care program .

1. Organization and contracting

A Collaborative Care Team will be put together for adequate coordination of care, with optimal collaboration between the main team partners: i.e. the patient, his/her informal carer(s), a psychiatric nurse and a psychiatrist and/or psychologist. Because discontinuity of care increases the risk of drop-out and a negative course of the psychiatric illness (with possible suicide as the extreme negative outcome), Collaborative Care demands pro-active collaboration between all partners to minimize this discontinuity of care. The nurse is responsible to inform and involve all those partners, whenever necessary. The execution stage of the CCP should not start before a treatment plan is established to which all collaborative partners commit [ 37 , 40 , 42 ]. Due to the ambivalent care seeking of most of the patients, this stage is therefore crucial and requires a careful preparation. This preparation stage consists of several activities (see Additional File 1 ).

Within Collaborative Care the patient is perceived as the one who shapes his own life, and hence his own treatment. Active involvement of the patient is required to reach the objectives of improved self management skills and shared decision making [ 36 ]. Patients, however, often have a long history of contacts with health care providers, with divergent success. To learn from previous experiences, an inventory is made of life events and of former treatments, based on the medical record. This inventory will be discussed with the patient and with the other members of the Collaborative Care Team to identify effective coping strategies with life events, effective elements in treatment, and relationships. Patients are invited to express their expectations about care providers and treatment and to speak aloud about disappointing (sometimes even traumatic) experiences, which still may hamper the relationships with care providers. Informal carers are invited to share their view upon past life events and expectations with regard to collaboration and treatment. Mutual expectations and responsibilities are made explicit between patients, informal carers and care providers, in order to promote a strong relationship [ 26 , 50 ]. The agreements about the collaboration are recorded in the treatment plan.

Health care needs will be assessed with the Camberwell Assessment of Needs (CAN) [ 51 ]. Based on the CAN results priorities in treatment goals will be set within the Collaborative Care Team. Unmet needs, goals and related activities are recorded in the treatment plan. In anticipation of possible crises, a crisis card will be compiled [ 26 ]. The use of a crisis card fits in the philosophy of collaborative care because it communicates that patients are (at least partly) able to cope with crisis themselves. If not, a back up of professional care is always available 24/7. The content of the crisis card is communicated with the crisis services and informal carers. Additionally, contracting will be used, based on shared decision making about the collaboration, the treatment process and the treatment plan [ 26 , 50 ]. The final step in the preparation stage is to confirm the goals, activities and agreements about collaboration in the treatment plans, which are evaluated every three months.

2. Destructive behaviour

To reduce destructive behaviours a method of early recognition and early intervention will be implemented [ 26 , 52 - 54 ]. These destructive behaviours may have different forms: suicidal, self harm, addictive or aggressive behaviours. The central aim of the intervention strategy is the recognition of early warning signs (thoughts, feelings and/or behaviours) of the destructive behaviour of the patient. The aim is to help the patient gain a better insight in the process of destructive behaviour and to enhance coping with this behaviour. A relapse prevention plan will be drafted in which early signs are described, as well as actions how to respond to raising stress, despair and imminent crisis.

3. Problem Solving Treatment

To reduce daily life problems Problem Solving Treatment (PST) will be applied [ 55 ]. The amount of daily life problems is often overwhelming in this subpopulation of patients, through which they may loose their sense of control. Learning and applying problem solving skills regarding daily problems enhances mastery and may result in a better quality of life. Mastery reflects the extent to which individuals perceive themselves in control of forces that significantly impact on their lives. PST has proven to be effective in different studies and is part of different treatments for personality disorders [ 50 , 55 , 56 ]. It is an essential element of Collaborative Care Programs [ 34 , 39 , 45 ].

4. Life orientation

As counterbalance to the prominent attention to problems and destructive behaviour, the focus of CCP is also aimed at a more positive orientation in a person's life. Elements of Solution Focused Treatment will therefore be used to encounter and expand positive experiences which is expected to be stimulating for a renewed and more positive life orientation [ 57 , 58 ].

5. Psycho-education

By means of psycho education, the patient (and their carer) is provided with knowledge about his or her psychological condition, the causes and consequences of that condition, ways of coping with it, and the treatment possibilities including the expected effects of it. Patients and their carers also will be prepared to the enduring character of the illness and to expected relapses. Psycho education is an integral element of Collaborative Care [ 36 , 39 , 42 ].

Treatment integrity

The nurses who participate in the experimental condition will receive a three-day training program from three of the authors (BS, BvM en BK) in the principles and skills of the CC Program. During the provision of the CC Program, supervision for the nurses will be provided for continuing education on attitude and skills. Bi-weekly individual consultation and coaching (by telephone or email) will be offered based on the work sheets of the workbook and the manual to further support treatment integrity. Supervision, consultation and coaching are provided by the first author (BS).

Control Condition

Patients in the control condition receive care as usual from their current care providers. During the study period, nurses in both conditions are not permitted to receive any extra training that might interfere with the content of the CCP.

Data collection

There are three measurements in this study: when participants enter the study (T0), after five months (T1) and after nine months (T2). To achieve the formulated objectives of this study, the data collection is divided into two parts. Quantitative data are collected with questionnaires to describe the outcomes of the CC Program in comparison with the CAU (summarized in table ​ table1). 1 ). Qualitative data, such as interviews, and records of the supervision sessions are used to analyse the implementation process of the application of the CCP in comparison with CAU. Data will be collected among patients, their informal carers and nurses, as mentioned below.

Summary of the used questionnaires.

Questionnaires for patients

Sample characteristics.

Information will be gathered at baseline on demographic characteristics (age, gender, education level, marital status, work and ethnicity), history of illness, current medication use and diagnostic characteristics (DSM-IV Axis II by means of the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) [ 59 ], the other axes are obtained from the medical records).

Primary outcome indicators

Quality of life.

The Manchester Short Appraisal (MANSA) is a self-report scale, which measures quality of life. It is a short version (16 items) of the Lancashire Quality of Life Profile (LQoLP). Priebe et al. [ 60 ] found an adequate correlation between the results on both QoL scales.

Borderline Personality Disorder Severity Index (BPDSI)

The BPDSI is a DSM-IV BPD criteria-based semi-structured interview consisting of 70 items. It represents the current severity and frequency of the DSM-IV BPD manifestations. This instrument showed excellent psychometric features [ 5 , 49 , 61 ].

Secondary outcome and process indicators

Destructive behaviours.

Four frequently observed destructive behaviours are measured. The BPDSI contains subscales measuring parasuicidal behaviour, including self harm, and aggressive behaviour. Additionally, the Beck Scale for Suicidal Ideation is used to measure suicidal thoughts, ideas and behaviours. It is a self-report scale of 21 items and has good psychometric properties [ 62 , 63 ]. The CAGE questions Adapted to Include Drugs (CAGE-AID) is a composed questionnaire describing the consequences of alcohol and drugs use [ 64 ].

Health care use

The Trimbos/iMTA questionnaire for Costs associated with Psychiatric Illness (TiC-P) is developed to measure health care consumption (part 1) and costs (part 2) [ 65 ]. In this study only part 1 of the questionnaire, concerning health care consumption, is used.

Psychosocial symptoms

The Brief Symptom Inventory (BSI) is a shorted version of the SCL-90 with 53 items (self report). Reliability and validity are almost identical to the SCL-90 [ 66 ].

Patient satisfaction

For the measurement of patient satisfaction the Consumer Quality-Index (CQ-Index) for outpatient mental health care is used [ 67 ]. It comprises items about information provision, involvement in treatment decisions, expertise and availability of professionals, and outcomes of treatment.

Quality of the therapeutic relationship

The S cale t o A sses Therapeutic R elationships in Community Mental Health Care (STAR) is a questionnaire which measures the quality of the therapeutic relationship [ 68 ]. A professional and patient version of the scale is available and a Dutch translation of this questionnaire will be used in this study.

Pearlin and Schooler's Personal Mastery Scale (PMS, 1978) is a commonly used instrument to measure the external locus of control, also referred to as mastery. It consists of five items on a four point Likert scale (self report). The PMS has adequate validity and reliability [ 69 , 70 ].

Questionnaires for informal carers

Process indicators, carer satisfaction with care.

For the measurement of carer satisfaction an adapted version of the CQ-index is used [ 67 ].

Involvement/social support

The Involvement Evaluation Questionnaire (IEQ) [ 71 , 72 ] is a self report list of 81 items, divided among seven sections. It measures consequences of care giving in informal carers.

Questionnaires for nurses

Information is gathered at baseline on demographic characteristics (age, gender, education), working experience in mental health care and with this specific patient population.

Complementary to the patient's view on the quality of the therapeutic relationship, nurses will be asked to fill in the professional version of the STAR [ 68 ].

Attitudes towards destructive behaviours

The Suicide Behavior Attitude Questionnaire (SBAQ) consists of 21 items to be scored on visual analogue scales. Three subscale are differentiated: (1) feelings in relation with the care for suicidal patients, (2) professional skills and (3) the right for suicide [ 73 ].

Attitudes towards self harm are measured with the Attitudes Towards Deliberate Self-Harm Questionnaire (ADSHQ) as developed by McAllister et al . [ 74 ].

Process forms

Nurses in both conditions fill in process forms in which the number and content of contacts will be registered. In the experimental group items are added which provide additional insight in the treatment integrity. The process form follows the elements of the intervention and will systematically remind them on the structure and objectives of the CC Program.

Qualitative data

Individual interviews with patients, their carers and nurses (in this fixed order) will take place after the follow up measurement (T2). In the in-depth interviews the process of the application of the CC Program, and the relationship between this application and outcomes will be examined and compared to the application of CAU. In the interviews participants are first asked to reflect on the quantitative outcomes and on which changes they perceive as most beneficial. Subsequently, the underlying (neutrally formulated) principles of the CCP will be discussed, e.g. problem solving, coping with destructive behaviour, quality of the therapeutic relationship, and self-management. Next, exemplifications will be asked to identify characteristics of these principles which may explain the individual outcomes. Finally, the participants are asked to identify hampering or fostering components in the application of CCP or CAU.

The interviews will be audio taped and transcribed verbatim. The data will be analysed using WINMAX qualitative text analysis software. The credibility and dependability of the data will be ensured by peer debriefing, member checking, and thick descriptions [ 75 ].

Supervision records

During the execution of the CCP nurses receive supervision. It focuses on the individual application of the CCP and on the promoting and impeding factors regarding the execution of CC. The supervisions will be audio taped and transcribed verbatim. The records of these supervisions will be examined using content analysis.

Data analysis

A distinctive feature of a comparative multiple case study is the analysis of data on three different levels:

Firstly at individual case level, secondly at group level and thirdly at the level of the comparison between the two conditions. At case level the combined quantitative and qualitative data will be used to gain insight in how the application of the CCP in an individual participant has evolved and how this is related to the outcomes. Hence, in first instance a within case analysis of the data from different data sources and different perspectives will be made for each individual case. Secondly, within the experimental and the control condition cross case analyses will be performed to formulate statements about the observed processes and outcomes per condition. Cases will be subdivided in three categories: (1) a group of cases with positive outcomes; (2) a group of cases with none or minimal changes in outcomes and (3) a group of cases with negative outcomes. Within these three subgroups patient characteristics and the process of application will be compared to explain the different outcomes.

Finally, at an aggregated group level the observed differences in outcomes and process indicators will be examined between the experimental and the control condition ( cross case synthesis ) in order to assess the value of the intervention compared to care as usual and to explain differences in outcomes between the two treatment conditions.

Qualitative analyses

To describe and understand the process of the application of the CCP versus CAU, the qualitative interviews with patients, their carers and nurses will be analyzed, following the three steps as described above. Beforehand, as preparation for the interviews, the supervision records will be analysed and the quantitative outcomes will be assessed at an individual level.

For the within case analyses , the data from the interviews are coded and categorized following the structure as described above. As said, for the cross case analysis the participants of both research conditions are divided in three subgroups. Based on the interview data, similarities and differences in the process of the application are described for the three subgroups. The different perspectives of patients, informal caregivers and nurses will be taken into account in this analysis. The degree, to which these perspectives differ from each other, might be indicative for the obtained outcomes. For the cross case synthesis , the data from the interviews will be examined to identify group differences between the two research conditions: Which statements do participants make about the underlying principles of the CCP? How do they value these principles? How do they value the outcomes of the CCP resp. CAU?

A content analysis of the supervision records will be performed to identify hampering and fostering characteristics in the process of the application of the CCP from a nursing perspective. For the within case analysis this information will be used as a preparation for the interviews. When performing the cross case analysis and synthesis , this information exemplifies and partially explains observed outcomes of the application of CCP.

Quantitative analyses

The used questionnaires provide quantitative data about the outcome indicators from different perspectives. For the within case analyses the quantitative data are assessed to describe the individual outcomes. To facilitate the cross case analysis , differences in characteristics of the participants within the three subgroups are described. Descriptive analysis of the process forms will give additional information, which will be used for the cross case analysis and synthesis .

Statistical analyses will be performed to examine the differences at group level between the experimental and the control condition at the different measurements ( cross case synthesis ). Parametric and non-parametric comparisons of mean scores will be used. These analyses are used to identify preliminary results and to support the qualitative data. These quantitative data combined with the qualitative data provide insights in the value of CC and in the feasibility of the intervention from different perspectives.

A substantial group of patients with borderline or NOS personality disorders does, for different reasons, not participate in evidence based psychotherapeutic programs aimed at structural changes in personality and recovery. Poor quality of life, severe suffering, high risk of suicidal behaviour, and high health care use (and corresponding costs) of this population without access to these psychotherapies, justify the development of a structured, easy-accessible intervention program. Our Collaborative Care Program may function as a valuable alternative for the relatively unstructured treatment which dominates the care as usual within existent community mental health care teams [ 16 , 17 ]. Within these CMHC teams nurses are the main care providers, although they are not always equipped to meet this responsibility. Collaborative Care (CC) will offer them a structured method in providing care for patients with severe personality disorder.

The present study is, as to the best of our knowledge, the first to examine Collaborative Care for patients with severe personality disorders receiving outpatient mental health care. Currently, health care research on the outcomes of interventions is dominated by randomized clinical trials. However, depending on the development stage of interventions other designs are desirable and available [ 76 , 77 ]. With the chosen design we want to examine how and which elements of the CC Program could contribute to a better quality of life for the patients and whether it will give better results for their carers and the staff than care as usual. Based on the results of our study, the CC Program can be adapted in such a way that the chance for effectiveness will be maximized in a following RCT. This comparative multiple case study, hence, precedes the question of effectiveness. The start of this study is anticipated for January 2011 with results available in April 2012.

Ethical considerations

This research project has been approved by the Medical Ethics Committee of the VU Medical Centre in Amsterdam, the Netherlands.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

BS is responsible for the initial draft of this article, and for the development, organization and implementation of the study. BvM and BK have contributed to the design and the development of the CC Program. The supervisors AB, AK, BK and BvM have reviewed the design and the workbook and manual of the CC Program, and revised earlier versions of the manuscript. All authors read and approved the final manuscript.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-244X/11/102/prepub

Supplementary Material

A Collaborative Care Program for patients with severe borderline or NOS personality disorders . This additional file elucidates the content of the Collaborative Care Program in more detail.

Acknowledgements

The study is funded by VU University Medical Center and GGZ inGeest, Amsterdam, the Netherlands, and Inholland University for Applied Research, Amsterdam, the Netherlands.

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• Research article
• Open access
• Published: 27 June 2016

A case series of 223 patients with depersonalization-derealization syndrome

• Matthias Michal 1 ,
• Julia Adler 1 ,
• Jörg Wiltink 1 ,
• Iris Reiner 1 ,
• Regine Tschan 1 ,
• Klaus Wölfling 1 ,
• Sabine Weimert 1 ,
• Inka Tuin 1 ,
• Claudia Subic-Wrana 1 ,
• Manfred E. Beutel 1 &
• Rüdiger Zwerenz 1  

BMC Psychiatry volume  16 , Article number:  203 ( 2016 ) Cite this article

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Depersonalization-derealization syndrome (DDS) is an underdiagnosed and underresearched clinical phenomenon. In Germany, its administrative prevalence is far below the threshold for orphan diseases, although according to epidemiological surveys the diagnosis should be comparable frequent as anorexia nervosa for instance. Against this background, we carried out a large comprehensive survey of a DDS series in a tertiary mental health center with a specialized depersonalization-derealization clinic. To reveal differential characteristics, we compared the DDS patients, who consulted the specialized depersonalization-derealization clinic, with a group of patients with depressive disorders without comorbid DDS from the regular outpatient clinic of the mental health center.

The sample comprised 223 patients with a diagnosis of depersonalization-derealization-syndrome and 1129 patients with a depressive disorder but without a comorbid diagnosis of DDS. DDS patients were described and compared with depressive outpatients in terms of sociodemographic characteristics, treatment history, treatment wishes, clinical symptomatology, prevailing psychosocial stressors, family history of common mental disorders and history of childhood trauma.

Despite the high comorbidity of DDS patients with depressive disorders and comparable burden with symptoms of depression and anxiety, the clinical picture and course of both patient groups differed strongly. DDS patients were younger, had a significant preponderance of male sex, longer disease duration and an earlier age of onset, a higher education but were more often unemployed. They tended to show more severe functional impairment. They had higher rates of previous or current mental health care utilization. Nearly all DDS patients endorsed the wish for a symptom specific counseling and 70.7 % were interested in the internet-based treatment of their problems. DDS patients had lower levels of self-rated traumatic childhood experiences and current psychosocial stressors. However, they reported a family history of anxiety disorders more often.

In consideration of the selection bias of this study, this case series supports the view that the course of the DDS tends to be long-lasting. DDS patients are severely impaired, utilizing mental health care to a high degree, which nevertheless might not meet their treatment needs, as patients strongly opt for obtaining disorder specific counseling. In view of the size of the problem, more research on the disorder, its course and its optimal treatment is urgently required.

Depersonalization-derealization syndrome as named in the ICD-10 [ 1 ] (or depersonalization-derealization disorder as termed in the DSM-5 [ 2 ] is an underresearched clinical phenomenon [ 3 , 4 ]. Depersonalization-derealization syndrome (DDS) is defined by feeling detached from the own feelings and/or experiences (depersonalization, DP) and/or experiencing objects, people, and/or surroundings as unreal, distant, artificial, and lifeless (derealization, DR) while reality testing remains intact (ICD-10 [ 1 ]). Further, symptoms of depersonalization and derealization are not better explained by another mental disorder or medical condition and the symptoms cause significant impairment (DSM-5 [ 2 ]). The typical DDS patient, reports that the disorder started before age 25, and that the DP/DR symptoms are present all day long since several years [ 5 – 7 ]. Epidemiological surveys suggest that the current prevalence rate of the depersonalization-derealization syndrome is approximately 1 % in the general population [ 5 – 7 ]. However, the disorder is severely underdiagnosed. For example, in the year 2006 the administrative 1-year-prevalence of the ICD-10 diagnosis “depersonalization-derealization syndrome” was as low as 0.007 % according to the registry of a statutory health insurance fund in Germany [ 4 ]. Experts assume this huge diagnostic gap is due to the following reasons: Many clinicians are unfamiliar with the clinical picture and the diagnostic criteria of the disorder. They universally consider symptoms of DP/DR as secondary to a depressive or anxiety disorder, even if these symptoms are all day long present for months and years, or they even misinterpret these symptoms as psychotic although patients are free from any psychotic sings (such as hallucinations, delusions, severe thought disorders, catatonia etc.) [ 3 – 5 , 8 – 10 ]. Moreover, diagnostic awareness is hampered by the patients themselves because many of them are “reluctant to divulge their symptoms out of fears of being thought mad” [ 8 ]. Therefore, it usually takes many years from the initial contact with a mental health service until the right diagnosis is made [ 3 , 4 , 11 ].

The current nosological knowledge about the DDS, as it is reported in the recent version of the DSM-5, is largely based on historic descriptions of the disorder, small case-control studies and two descriptive case series with a total sum of 321 patients from specialized clinics or research units in London (UK) and New York (USA). Concerning the etiology of DDS, it has been found that harm-avoidant temperament was associated with DDS in a cross-sectional study [ 12 ]. Another cross-sectional study comparing healthy controls with 49 DDS patients demonstrated that emotional abuse was associated with severity of DP/DR but not severe forms of childhood maltreatment [ 13 ]. A prospective cohort study found that the only risk factor for severe adult depersonalization at the age of 36 was teacher-estimated childhood anxiety 20 years before. Exposition to environmental risk factors such as socio-economic status, parental death or divorce, and self-reported accidents did not predict later DDS [ 14 ]. From an evolutionary perspective, symptoms of DP/DR are considered as a hard-wired response to severe stress, which is perpetuated according to various disease models of DDS by personality factors such as low capacities of self-regulation (e.g., low self-esteem, low affect tolerance, low cohesiveness of the self) [ 3 , 8 , 15 ]. Previous case series from specialized treatment units in London (UK) and New York (USA) reported a sex ratio of 1:1 or even a slight male preponderance [ 6 ], with an early age of onset usually before age 25, and a high comorbidity with anxiety and depressive disorders [ 6 , 16 ]. Both case series demonstrated that the condition had a high chronicity and tended to be resistant to pharmacological and psychotherapeutic treatments [ 6 , 16 ]. To date, there is no approved medication for the treatment of DDS and there is no randomized controlled trial on the psychotherapeutic treatment of DDS [ 3 ].

As the current disease knowledge of DDS has only a small empirical basis, at least as compared to mental disorders with similar prevalence rates and mental health impact, the principle aim of our study was to support and extend the knowledge about the clinical features of the DDS. For that purpose, we examined a large consecutive outpatient sample of DDS patients from the depersonalization-derealization clinic of our department, which has been established in 2005. Patients usually become aware of the clinic by online research about their main complaints (e.g. “feeling unreal”), they are usually self-referred and they typically seek a second opinion regarding their diagnoses and treatment options.

With our study we aimed to address two main questions. Firstly, we sought to describe the typical clinical features and demographic characteristics of patients with DDS as depicted in our clinical standard assessment. Although our case series study is primarily meant as a descriptive study, we included a comparison group form our outpatient clinic in order to bring out the putative differential characteristics of the DDS patients more clearly. For the latter purpose we used a large comparison group of patients suffering from depression without comorbid DDS. We compared both groups in terms of sociodemographic characteristics, treatment history, treatment wishes, clinical symptomatology, level of disability, prevailing psychosocial stressors, family history of common mental disorders, and severity of childhood trauma. We choose a sample of depressed patients for comparison for several reasons: First, this diagnostic entity represents the largest diagnostic group in our department. Second, depression is the most prevalent comorbid condition of DDS patients [ 6 ]. Third, depression is a well described and popular disorder thus making it easier for clinicians to acknowledge the similar and differential features of the two groups.

We expected that our case series will constitute an important confirmation and extension of the two previous case series and that it will stimulate further studies on the course, mechanisms and treatment of the disorder.

We consecutively included outpatients between January 2010 and December 2013, who consulted the Department of Psychosomatic Medicine and Psychotherapy of the University Medical Center Mainz (Germany). In Germany, Departments of Psychosomatic Medicine and Psychotherapy, usually established at most of all University Medical Centers, are mainly treating patients with depressive disorders, anxiety disorders, somatoform disorders and eating disorders. All patients received a routine psychometric assessment and a clinical interview.

DDS patients who consulted the depersonalization-derealization clinic usually become aware of the clinic by internet research, that is to say, almost all were self-referred. The website of the clinic gives a vivid description of the symptoms and the clinical picture of the disorder. Further, all patients had a short telephone interview with M.M. prior to their consultation, to ensure that they suffer from severe depersonalization/derealization (e.g. as opposed to DP/DR attacks in the context of panic disorder) and to inform them about the focus of the consultation and the therapeutic options of the clinic. Patients from all over Germany were consulting the specialized clinic.

Patients from the comparison group were either self-referred or referred by local physicians and psychotherapist to receive a psychotherapeutic evaluation and treatment recommendations (usually regarding outpatient psychotherapy, inpatient or day clinic psychotherapy). The catchment area of the department is the Rhine-Main-area.

Patients who were treated in the context of the consultation and liaison service (e.g. cancer patients in cancer care units), or who were below age 18 or who had no standardized assessment, or who had no depressive disorder or DDS were excluded.

The sample comprised 223 patients with a definite diagnosis of depersonalization-derealization-syndrome (ICD-10: F48.1 [ 1 ]) and 1129 patients with a depressive disorder (dysthymia F34.1, or unipolar depression F32.x, or F33.x [ 1 ]) but without a comorbid diagnosis of DDS. The latter group will be indicated below as the “Only-Depressed-Group” (ODG). A total of 197 of the 223 patients diagnosed with DDS consulted the depersonalization-derealization clinic of the Department of Psychosomatic Medicine and Psychotherapy of the University Medical Center Mainz, the remaining 26 patients were diagnosed and treated in the general outpatient unit.

Clinical interview

All patients received a full clinical interview of at least 50 min duration by a psychological or medical psychotherapist. Clinical diagnoses of mental disorders were based on the diagnostic criteria for research of the ICD-10 [ 1 ]. The focus of the clinical interview was on the primary presenting problems of the patients and symptom diagnoses. The diagnosis of depersonalization-derealization syndrome was only given, if symptoms of DP/DR were persistent and lasted continuously for at least 1 month and if these symptoms were not better explained by another mental disorder (e.g., unipolar depression, dissociative disorder, anxiety disorder, PTSD) or a medical condition (e.g., seizure disorder). Although the diagnostic criteria of the DDS do not demand specifications about the duration of the symptoms, most clinicians agree that the diagnosis should be only given if the symptoms persist for at least 1 month [ 3 ] (see Additional file 1 for comprehensive information about the diagnostic procedure).

Due to the peculiarities of the clinical interview, personality disorders were underreported in our medical records. This was mainly due to the time restriction of the clinical interview. As each patient received a written report about the diagnostic findings, each diagnosis in the record had to be explained to the patient in advance. The diagnosis of personality disorders was rarely made, as most clinicians believed that informing adequately about the diagnosis of a personality disorder requires more time. Because of this bias of underdiagnosing personality disorders in our records, we did not consider personality disorders in this paper.

Further, clinicians rated the social, occupational, and psychological functioning level of psychological functioning by means of the Global Assessment of Functioning (GAF) scale [ 17 , 18 ]. Lower scores indicate lower levels of functioning. Scores in the range of 51–60 indicate moderate impairment due to symptoms (e.g., flat affect and circumlocutory speech, occasional panic attacks) or moderate difficulty in social, occupational, or school functioning (e.g., few friends, conflicts with peers or co-workers). In Germany, patients with indication for inpatient psychotherapy usually have a current functional level below GAF 50 [ 19 ].

Severity of DP/DR was assessed with the CDS-2, the two-item version of the Cambridge Depersonalization Scale (CDS [ 20 , 21 ]). The CDS-2 comprises the following two items of the CDS [ 22 ]: “My surroundings feel detached or unreal, as if there was a veil between me and the outside world” and “Out of the blue, I feel strange, as if I were not real or as if I were cut off from the world”. The response format of the CDS-2 was adopted from the Patient Health Questionnaire (“Over the last 2 weeks, how often have you been bothered by any of the following problems?/Not at all = 0/Several days = 1/More than half the days = 2/Nearly every day = 3”). The CDS-2 showed high reliability (Cronbach’s Alpha = 0.92) and was able to differentiate patients with clinically significant DP well from other groups (cut-off of CDS-2 ≥ 3, sensitivity = 78.9 %, specificity = 85.7 %). The CDS-2 sum score (range 0–6) correlated strongly ( r  = 0.77 [ 22 ]) with depersonalization severity according to a structured clinical interview of depersonalization severity [ 23 ]. Immediately after the CDS-2 items, the patient questionnaire presented the following two questions with a yes/no response: Have you ever consulted a doctor or psychotherapist because of the above symptoms? Do you wish counseling about the above symptoms of depersonalization and derealization?

Severity of depression was measured with the depression module PHQ-9 of the Patient Health Questionnaire [ 24 ]. PHQ-9 scores ≥ 10 identified depressive disorders with a sensitivity of 81 % and a specificity of 82 %. Severity of anxiety was measured with the Generalized Anxiety Disorder-7 (GAD-7). The GAD-7 has seven items depicting various signs of generalized and other anxiety disorders (e.g. PTSD, panic disorder). GAD-7 scores range from 0 to 21, with scores of ≥5, ≥10, and ≥15 representing mild, moderate, and severe anxiety symptom levels [ 25 , 26 ]. The Mini-Social Phobia Inventory (Mini-Spin; [ 27 ]) was used for the measurement of social anxiety. The Mini-Spin has three items, which are rated on a 5-point-Likert scale from 0 = “not at all” to 4 = “extremely”. A cut-off score of 6 (range 0–12) separates individuals with social anxiety disorder from controls with good sensitivity (89 %) and specificity (90 %). Somatic symptoms severity was assessed with the 15 items of the PHQ-15. Scores range between 0–30. Scores above 15 identify individuals with high levels of somatic symptom severity respectively somatization severity [ 28 ]. The overall mental distress level was measured by the Global Severity Index (GSI) of the German version of the short Symptom Check List (SCL-9) [ 29 ]. The range of the GSI is 0 to 4 with higher values reflecting more dysfunction. The ten most common psychosocial stressors (e.g., financial status, family relationships, work, health) were assessed by the corresponding PHQ module on a three-point scale (not bothered = 0, bothered a little =1, bothered a lot =2) [ 30 , 31 ]. We also calculated the sum score of psychosocial stressors (possible range from 0 to 20). Further, we dichotomized the items (“not bothered” or “little bothered” = 0 versus bothered “a lot” = 1) for the use in a regression analysis. The Childhood Trauma Questionnaire (CTQ) is a 28-item self-report inventory for the assessment of the extent of traumatic childhood experiences. The CTQ has a global score and scores for the subscales emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect and minimization [ 32 ]. For determining clinically significant levels of traumatization critically cut-points for the subscales have been determined [ 33 , 34 ]: emotional neglect (≥15), sexual abuse (≥8), physical abuse (≥8), physical neglect (≥10), emotional abuse (≥10). Further, patients gave written information about their socioeconomic details, their treatment history and family history.

Statistical analysis

Data were presented as mean ± standard deviation, or age and sex adjusted mean, standard error and 95 % confidence interval, or numbers (n) and percentage. Continuous distributed scores were compared by students T -test. Categorical variables were compared by Chi-square tests. Associations of continuous data were tested by Pearson correlations. Correlations coefficients of the two groups were compared by the Fisher r-to-z transformation, which controls the correlation coefficients for the effect of different sample sizes. In order to control group differences for the effects of age and sex, we applied logistic regression analyses for binary variables and analysis of covariance (ANCOVA) for continuous variables. In order to evaluate the distinctiveness of the symptom dimensions depression, anxiety, social anxiety and DP/DR we performed a principal component analysis with varimax rotation on the pooled items of the CDS-2, PHQ-9, GAD-7 and Mini-Spin. Tests were considered to be significant at a p  < 0.05, and all significance tests were two-tailed. Due to the large sample size, the interpretation of the results should focus on effect-sizes rather than p -values. SPSS 22.0 was used for the main statistical analysis and VassarStats for the Fisher r-to-z transformation ( http://vassarstats.net ).

Sociodemographic characteristics

Table  1 shows the sociodemographic characteristics of the sample. The group of DDS patients was of younger age and more often male than the “Only-Depressed-Group” (ODG). There was a significant preponderance of men in the DDS group with a female-to-male ratio of 98 to 125 (≈2 : 3). The DDS patients were living less often in a current partnership, were more often still living with their parents, more often holder of the German citizenship, had a higher educational level, but were more often unemployed.

Comorbid conditions, symptom burden and clinical course

DDS patients had a very high comorbidity with depressive disorders (84.8 %). As compared with ODG, DDS patients had a higher comorbidity with anxiety disorders, whereas somatoform disorders and PTSD were more prevalent in the ODG. The DDS group had more clinical Axis-I disorders than the controls (2.8 ± 1.0 versus 2.3 ± 1.1, T = 6.920, p  < 0.0001). Only 21 from 223 DDS-patients (9.4 %) had no comorbid Axis-I disorder. DDS patients had an earlier age of onset and longer disease duration as the ODG (Table  2 ). DDS had its onset in 63.7 % ≤ age 25, in 17.9 % between age 26 and ≤ 40 and in 4.9 % > 40. There was no valid information about the age of onset for 20 DDS patients.

Table  3 shows that after adjustment for age and sex, DDS patients were comparably bothered like the ODG by symptoms of depression (PHQ-9) and anxiety (GAD-7), and they had a similar global severity index (GSI). They had a lower burden with somatic symptoms (PHQ-15) and a slightly lower severity of social anxiety (Mini-Spin). However, severity of depersonalization (CDS-2) strongly separated both patient groups.

In order to evaluate the distinctiveness of the scales we performed a principal component analysis with varimax rotation on the pooled items of the CDS-2, PHQ-9, GAD-7 and Mini-Spin. The Factors were retained in the model based on inspection of the screeplot and eigenvalues > 1. Five factors were identified explaining 61 % of the variance. The items of the CDS-2 were clearly separated from the other scales (data not presented, see Additional file 2 ). Regarding the association of DP/DR with other symptom dimensions we found that the correlation coefficients of the severity of depersonalization (CDS-2) with anxiety (GAD-7, Mini-Spin), depression, general distress (GSI) and somatization were significantly weaker in the DDS group (Table  4 ).

Functional impairment

Both patient groups were markedly impaired by their symptoms (Table  5 ). After adjustment for age and sex, DDS patients endorsed that their symptoms disrupted their work and social life more strongly than ODG, while the impairment of home life was comparable. These differences were in the range of small to medium effect sizes (Cohen’s d 0.24 to 0.28). Clinicians rated the current and 1-year global level of functioning (GAF) of DDS patients significantly lower than those of the ODG. The difference of GAF was in the range of large effect sizes (Cohen’s d 0.54 to 0.67). Overall, the mean GAF of both groups was in the range of serious to moderate impairment of psychological, social and occupational functioning (GAF 50-60). In the DDS group, 35.2 % had a GAF below 50 which, in Germany, is considered as a criterion for inpatient psychotherapy.

Current psychosocial stressors

Overall, DDS patients endorsed being less bothered by psychosocial stressors than the ODG (Table  6 ). In the sex and age adjusted logistic regression model the following stressors were inversely associated with DDS: weight or appearance worries, difficulties with partners, stress at work or school, financial worries, having no one to turn to, as well as recent or past bad events. The same picture emerged regarding the total burden with psychosocial stressors (i.e. the sum score of the scale): 7.7 ± 3.6 in the DDS group versus 9.7 ± 4.0 in the ODG (T = 7.34, p  < 0.0001). In the DDS group, there was no correlation between the severity of psychosocial stressors with severity of depersonalization (Pearson correlation between the psychosocial stressor sum score and CDS-2: r  = 0.06, p  = 0.39). In the ODG, however, CDS-2 correlated significantly with the sum of psychosocial stressors ( r  = 0.31, p  < 0.0001). The correlations coefficients differed significantly (Fisher r-to-z transformation: z = 3.53, p  = 0.0004).

Family history and childhood adversities

In the age and sex adjusted regression analysis, only a FH of any anxiety disorder was significantly associated with DDS (Table  7 ). Regarding childhood adversities, DDS patients showed a similar level of traumatic childhood experiences; only, they endorsed slightly lower levels of physical and sexual abuse than ODG in the age and sex adjusted ANCOVA. Overall, the mean level of traumatic childhood experiences was in the range of minimal to low levels of traumatic childhood experiences (Table  8 ). Based on the critical cut-points of the CTQ [ 33 , 34 ], DDS patients reported the following rates of clinically significant levels of traumatization: Emotional abuse 44.7 %, emotional neglect 35.8 %, physical abuse 12.3 %, physical neglect 15.1 %, and sexual abuse 6.1 %. Altogether, 57.8 % of the DDS patients reported at least one significant traumatic childhood experience and 42.2 % none. In the DDS group, there was no association between severity of childhood traumatic experiences with severity of depersonalization (Pearson correlation of the CTQ total score with CDS-2: r  = 0.05, p  = 0.44). In the ODG, although weakly, CDS-2 correlated with the CTQ total score ( r  = 0.20, p  < 0.0001). The correlations coefficients of the two groups differed significantly (Fisher r-to-z transformation, z = 2.07, p  = 0.0385).

Treatment history and health care wishes

Overall, DDS had a high treatment rate (Table  9 ). In the age and sex adjusted regression analysis, previous psychiatric inpatient treatment was much more likely in DDS patients than in the comparison group. The vast majority of the DDS patients endorsed firstly that they had previously consulted a doctor or psychotherapist because of DP/DR symptoms (92.7 % ( n  = 202) versus 25.3 % ( n  = 494)), and secondly that they were interested in DP/DR specific counseling (97.3 % ( n  = 213) versus 35.0 % ( n  = 446)). Those individuals of the ODG, who endorsed the wish for a DP/DR specific counseling, had higher CDS-2 scores than those denying this question (3.1 ± 1.9 versus 0.9 ± 1.3, T = 20.2, p  < 0.0001). Further, DDS patients more often used the internet for searching information about their symptoms and specialists and were much more interested in internet-based treatment approaches.

We investigated a consecutive sample of 223 DDS-patients, who consulted a specialized depersonalization-derealization clinic and compared these patients with a large group of patients with depressive disorders. At the time of the consultation, DDS patients were of younger age, had a significant preponderance of male sex, longer disease duration, an earlier age of onset, and a higher education but they were more often unemployed. Their burden with symptoms of depression and anxiety was comparable, however, they tended to show more severe functional impairment, especially at work/school and in social life. Concerning health care utilization, DDS patients had extraordinary high rates of previous inpatient treatments during the last 12 months (25.6 %) and ongoing outpatient psychotherapy (40.4 %). Despite their high health care utilization, nearly all DDS patients endorsed the wish for a symptom specific counseling (92.7 %) and 70.7 % were interested in an internet-based treatment approach of their problems. With regard to risk factors, DDS patients tended to report lower levels of self-rated traumatic childhood experiences and current psychosocial stressors. However, they more often reported a family history of anxiety disorders. These findings both enhance and extend those of two earlier case series from other countries and health care systems reported by Simeon et al. ([ 16 ]) and Baker et al. ([ 6 ]).

Very similar to the London case series by Baker et al. ([ 6 ]), we found a preponderance of men (125 men to 98 women; Baker et al.: 112 men to 92 women [ 6 ]) and almost the same mean age of onset of 22.9 ± 9.7 years (22.8 ± 11.9 years [ 6 ]). A similar preponderance of male sex has been recently found for clinically significant DP/DR in a representative questionnaire based survey of pupils in the age of 12 to 18 after adjustment for general distress [ 35 ]. The determinants of this putative sex difference in the etiology of DDS warrant further research.

Compared with previous case series, we had a higher proportion of DDS patients reporting an age of onset > 25 years (22.8 %). This finding needs replication, because previous reports assumed that an onset after age of 25 is very rare (less than 5 %) [ 6 , 16 ]. The larger proportion of DDS patients with a late age of onset in our sample may reflect the increasing use of the internet for health research since 2003, as nearly all DDS patients were referred by themselves or “Dr. Google” respectively.

Similar to Simeon et al. ([ 16 ]) and Baker et al. ([ 6 ]) the main comorbid conditions were depressive and anxiety disorders. In the current sample only 9.4 % of the DDS in the current sample had no comorbid Axis-I disorder which is very close to 11 % in the case series of Simeon et al. [ 16 ]. Despite their high comorbidity and equal symptom burden with symptoms of depression and anxiety, the clinical picture and course of both patient groups differed strongly regarding sociodemographic variables, treatment history and treatment wishes, and risk factors. Again, a principal component analysis substantiated clearly the distinctiveness of DP/DR symptoms from anxiety and depression [ 36 ], thus contradicting a commonly held view that symptoms of DP/DR are only a negligible variant of depression and anxiety. The low correlation coefficients of depression or anxiety with DP/DR severity in the DDS group are pointing in the same direction. The much stronger correlation coefficients in the group of the only depressed patients might constitute one reason why many clinicians generally tend to lump together DP/DR symptoms with depression and anxiety. Concerning somatic symptoms severity, DDS patients endorsed significantly less somatic symptoms as compared to the controls. This is in accordance with a recent study, which found that DDS patients endorsed less bodily symptoms of anxiety than pure anxiety patients [ 37 ]. The lower burden by bodily symptoms may reflect DDS patients’ detachment from their body.

Although 57.8 % of the DDS patients reported at least one clinically significant traumatic childhood experience, the overall rate of childhood adversities was rather low among DDS patients and even lower than in the comparison group. In line with previous studies [ 6 , 13 , 14 ] this finding makes it unlikely that traumatic childhood experiences play a crucial role in the etiology of DDS. This highlights an apparent contradiction: Although symptoms of DP/DR are typically reactions to severe stress and trauma (e.g. in the case of PTSD [ 38 ]), DDS is usually not associated with severe forms of childhood traumatization or recent traumatic events. This suggests that for the development of DDS other factors play a superior role as compared to the exposition to severe traumatic events.

There was a high rate of a parental history of anxiety disorders in the DDS group. Akin to the findings of Baker et al. ([ 6 ]), DDS patients had a high rate of psychiatric disorders in a first degree relative (Baker et al.: 30 %; 35.8 % in this sample). This may point to an increased genetic vulnerability of the DDS group on the one hand and on the other hand to an increased environmental risk of being exposed to parents with anxiety disorders [ 39 ].

DDS patients endorsed that they were significantly less bothered by current psychosocial stressors than only depressed patients. This either indicates that they have less psychosocial stressors or that they tend to be less aware how psychosocial factors affect them. The latter interpretation would correspond to our clinical experience. Similar to patients with somatoform disorders, DDS patients initially are often unable to consider psychological problems and interpersonal conflicts as relevant causes, and they are convinced by a physical causation of their symptoms [ 3 ]. Frequently patients assume a brain tumor, an eye disease or drug induced brain damage as the cause of their symptoms and thus initially consult neurologists, ophthalmologists and other somatic specialists before visiting a mental health specialist [ 5 , 40 ]. The lack of any correlation between the severity of DP/DR symptoms with the level of current or past stressors might be interpreted in the same way. Severe depersonalization may constitute a “ceiling” effect, which prevents the patients from seeing relations between stressors and their maladaptive stress-response in form of DP/DR. This reminds strongly to a recent study of 291 DDS patients, which found that despite comparable high levels of anxiety, depersonalization and anxiety correlated only in patients with less severe symptoms of DP/DR but not in patients with very high levels of DP/DR [ 41 ]. That is to say, therapeutic progress would implicate that patients become aware how the DP/DR symptoms wax and wane depending on the level of the mobilized anxieties [ 3 ]. However, in order to test this hypothesis, a longitudinal investigation of these relationships would be necessary.

Making the above considerations, the following major limitations have to be kept in mind. First, our approach implicated a strong selection bias: The DDS-patients were mostly referred by themselves after they have searched the internet for their main complaints, while the comparison group represents patients largely from the near catchment area. This limits the generalizability of our results. For example, we cannot rule out that only DDS patients with a chronic course, poor satisfaction with their current treatment and poor treatment response consulted the depersonalization-derealization clinic of our department. A further bias may constitute the high educational level of the DDS patients. This high educational level could explain the high rate of self-referral among DDS patients coming to a specialized DDS clinic. Highly educated persons may have lower barriers to use the internet for information about health issues. However, the findings concerning chronicity and the high rate of previous health care utilization corresponded well with previous reports from the specialized units in London [ 6 ] and New York [ 16 ]. Secondly, the diagnoses were based on clinical interviews and not on structured clinical interviews as applied in research settings, thus limiting the validity of our diagnoses. However, diagnoses were enhanced by using the diagnostic research criteria of the ICD-10 and by the correlation of the findings with validated rating scales. Thirdly, family history of mental disorders and history of previous treatments was questionnaire based and not corroborated by independent sources.

Conclusions

Keeping the above limitations in mind, we found that DDS patients are severely impaired, are utilizing mental health care to a high degree, which nevertheless might not meet their treatment needs, as the patients are taking strong efforts for obtaining symptom specific counseling. This all may reflect the fact that many clinicians are not familiar with the diagnostic features of DDS and its treatment [ 3 ]. In Germany, a first step towards the improvement of DDS care may constitute the implementation of the guideline recommendations for the diagnosis and treatment of the depersonalization-derealization syndrome, which have been recently published by the Association of the Scientific Medical Societies in Germany [ 42 ]. In view of the size of the problem, much more research on the disorder, its course and its optimal treatment is urgently required.

Abbreviations

ANCOVA, analysis of covariance; CDS-2, 2-item scale of the Cambridge Depersonalization Scale; CTQ, Childhood Trauma Questionnaire; DDS, Depersonalization-derealization syndrome; DP, depersonalization; DR, derealization; DSM-5, 5th edition of the Diagnostic and Statistical Manual of Mental Disorders; FH, family history; GAD-7, Generalized Anxiety Disorder 7-item scale; GAF, Global Assessment of Functioning; GSI, Global Severity Index; Mini-Spin, Mini-Social Phobia Inventory; OGD, Only-Depressed-Group; OR, odds ratio; PHQ-15, Somatic symptom scale from Patient Health Questionnaire; PHQ-9, depression module of the Patient Health Questionnaire; PTSD, Posttraumatic Stress Disorder; SD, standard deviation; SDS, Sheehan Disability Scale; SE, standard error.

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Acknowledgement

The authors thank Jasmin Schlax for her help with drafting the revisions of the manuscript.

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Availability of the data and materials

The authors confirm that, for approved reasons, access restrictions apply to the data underlying the findings. Due to ethical restrictions, the data cannot be made publicly available (approval of the Ethics Committee of the State Board of Physicians of Rhineland-Palatinate, Mainz, Germany ((837.191.16 (10510)).

Authors’ contributions

MM wrote the first version of the Manuscript; MM, RZ, JW, SW, MEB made the statistical analysis, MM, JA, JW, IR, RT, KW, IT, CS-W, MEB, RZ were involved in the clinical assessment of the patients, all authors contributed substantially to the conception of the study; all authors revised the manuscript critically and all authors gave their approval of the final version of the manuscript.

Competing interests

The authors declare that they have no competing interests.

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Ethics approval and consent to participate.

The study was approved by the Ethics Committee of the State Board of Physicians of Rhineland-Palatinate, Mainz, Germany ((837.191.16 (10510)). According to the approval of the Ethics Committee, there was no need for written consent because the study analyzed clinical data obtained by clinical standard assessment (i.e., not within the context of an epidemiological or clinical study).

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Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, Germany

Matthias Michal, Julia Adler, Jörg Wiltink, Iris Reiner, Regine Tschan, Klaus Wölfling, Sabine Weimert, Inka Tuin, Claudia Subic-Wrana, Manfred E. Beutel & Rüdiger Zwerenz

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Additional files

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Additional information about the diagnostic procedure. (DOC 37 kb)

Additional file 2:

Principal component analysis with varimax rotation of the items of the CDS-2, PHQ-9, GAD-7 and Mini-Spin. (DOCX 21 kb)

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Michal, M., Adler, J., Wiltink, J. et al. A case series of 223 patients with depersonalization-derealization syndrome. BMC Psychiatry 16 , 203 (2016). https://doi.org/10.1186/s12888-016-0908-4

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Received : 26 February 2015

Accepted : 20 June 2016

Published : 27 June 2016

DOI : https://doi.org/10.1186/s12888-016-0908-4

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• Depersonalization
• Derealization
• Health care utilization
• Childhood trauma
• Parental history of mental disorders

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