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Case Presentation: A 23-Year-Old With Bipolar Disorder

Gus Alva, MD, DFAPA, presents the case of a 23-year-old female diagnosed with bipolar 1 disorder.

case study on bipolar disorder pdf

EP: 1 . Case Presentation: A 23-Year-Old With Bipolar Disorder

Ep: 2 . clinical impressions from the patient case, ep: 3 . clinical insights regarding the management of bipolar disorder.

Gus Alva, MD, DFAPA: Psychiatric Times presents this roundtable on the management of bipolar disorder, a phenomenal dialogue allowing clinicals a perspective regarding current trends and where we may be headed in the future.

This is an interesting case, as we take a look at this 23-year-old female who first comes in to see her psychiatrist with moderate depressive symptoms. At the time of the interview, her chief complaint included feeling like she’s lacking energy, she’s feeling depressed. She’s also reporting difficulty in paying attention, organizing her day, and accomplishing her tasks at work. Notably these symptoms started abruptly. Three weeks early, prior to that, she had been functioning better than usual, requiring very little sleep and getting more accomplished. Of significance, she reported two brief episodes of depression over the past 2 years. Each lasting about 2 months. And although the patient reported these depressive episodes as coming out of the blue, she learned after consulting with her therapist that they were related to significant psychosocial stress, stemming from the loss of her job and the deaths of 2 uncles, both of which were related to the COVID-19 pandemic. The patient reported that she still finds enjoyment talking to friends and socializing and she has hope of finding a new job and she’s constantly looking.

It’s noteworthy to bear in mind that in her first depressive episode she was treated with methylphenidate 25mg titrated up to 50 m and she stated feeling improved on this does with psychotherapy. Her second depressive episode, her does was bumped up to 100 mg which we saw improvement in depression, but she noted she felt a little activated and had trouble sleeping. With her third depressive episode, the therapist and PCP referred the patient over to a psychiatrist. Of great note should be her past psychological history: she was diagnosed with ADHD in middle school, during which time she responded well to methylphenidate. She continued to do well until her college years at which time she began experiencing difficulty falling asleep as well as irritability. At that time, she discontinued methylphenidate and was psychiatric drug free. She found that practicing mindfulness and yoga on a daily basis helped her residual ADHD symptoms. Of note, she had no history of suicidal thoughts or behavior, self-injurious behaviors, psychiatric hospitalization, or problems with substance abuse. Of note, regarding medical comorbidities, she was diagnosed a year earlier with type 2 diabetes, which was managed with metformin 1000 mg twice daily and her hemoglobin A1C was not poorly controlled. She was also diagnosed with high blood pressure 2 years earlier, that is managed by lisinopril 20 mg once daily. We noted that her BMI is 31, which is indicative of obesity. All other lab values were within normal limit. Significantly, her TSH was in the normal range and her urine toxicology screening was negative. Upon further querying of her family history, her maternal grandmother was diagnosed with a nervous breakdown and spent 2 months in a psychiatric hospital in her 30s. Her mother required little sleep, had a history of impulsive spending, and had a history of starting projects that she didn’t finish. The patient’s paternal uncles had a history of depression as well as alcohol abuse. Upon doing assessments, her PHQ9 is indicative of 18 points and her mood questionnaire she scored an 8.

Transcript Edited for Clarity

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case study on bipolar disorder pdf

  • Open access
  • Published: 06 November 2018

The challenges of living with bipolar disorder: a qualitative study of the implications for health care and research

  • Eva F. Maassen   ORCID: orcid.org/0000-0003-0211-0994 1 , 2 ,
  • Barbara J. Regeer 1 ,
  • Eline J. Regeer 2 ,
  • Joske F. G. Bunders 1 &
  • Ralph W. Kupka 2 , 3  

International Journal of Bipolar Disorders volume  6 , Article number:  23 ( 2018 ) Cite this article

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In mental health care, clinical practice is often based on the best available research evidence. However, research findings are difficult to apply to clinical practice, resulting in an implementation gap. To bridge the gap between research and clinical practice, patients’ perspectives should be used in health care and research. This study aimed to understand the challenges people with bipolar disorder (BD) experience and examine what these challenges imply for health care and research needs.

Two qualitative studies were used, one to formulate research needs and another to formulate healthcare needs. In both studies focus group discussions were conducted with patients to explore their challenges in living with BD and associated needs, focusing on the themes diagnosis, treatment and recovery.

Patients’ needs are clustered in ‘disorder-specific’ and ‘generic’ needs. Specific needs concern preventing late or incorrect diagnosis, support in search for individualized treatment and supporting clinical, functional, social and personal recovery. Generic needs concern health professionals, communication and the healthcare system.

Patients with BD address disorder-specific and generic healthcare and research needs. This indicates that disorder-specific treatment guidelines address only in part the needs of patients in everyday clinical practice.

Bipolar disorder (BD) is a major mood disorder characterized by recurrent episodes of depression and (hypo)mania (Goodwin and Jamison 2007 ). According to the Diagnostic and Statistical Manual 5 (DSM-5), the two main subtypes are BD-I (manic episodes, often combined with depression) and BD-II (hypomanic episodes, combined with depression) (APA 2014 ). The estimated lifetime prevalence of BD is 1.3% in the Dutch adult population (de Graaf et al. 2012 ), and BD is associated with high direct (health expenditure) and indirect (e.g. unemployment) costs (Fajutrao et al. 2009 ; Michalak et al. 2012 ), making it an important public health issue. In addition to the economic impact on society, BD has a tremendous impact on patients and their caregivers (Granek et al. 2016 ; Rusner et al. 2009 ). Even between mood episodes, BD is often associated with functional impairment (Van Der Voort et al. 2015 ; Strejilevich et al. 2013 ), such as occupational or psychosocial impairment (Huxley and Baldessarini 2007 ; MacQueen et al. 2001 ; Yasuyama et al. 2017 ). Apart from symptomatic recovery, treatment can help to overcome these impairments and so improve the person’s quality of life (IsHak et al. 2012 ).

Evidence Based Medicine (EBM), introduced in the early 1990s, is a prominent paradigm in modern (mental) health care. It strives to deliver health care based on the best available research evidence, integrated with individual clinical expertise (Sackett et al. 1996 ). EBM was introduced as a new paradigm to ‘de - emphasize intuition’ and ‘ unsystematic clinical experience’ (Guyatt et al. 1992 ) (p. 2420). Despite its popularity in principle (Barratt 2008 ), EBM has also been criticized. One such criticism is the ignorance of patients’ preferences and healthcare needs (Bensing 2000 ). A second criticism relates to the difficulty of adopting evidence-based treatment options in clinical practice (Bensing 2000 ), due to the fact that research outcomes measured in ‘the gold standard’ randomized-controlled trials (RCTs) seldom correspond to the outcomes clinical practice seeks and are not responsive to patients’ needs (Newnham and Page 2010 ). Moreover, EBM provides an overview on population level instead of individual level (Darlenski et al. 2010 ). Thus, adopting research evidence in clinical practice entails difficulties, resulting in an implementation gap.

To bridge the gap between research and clinical practice, it is argued that patients’ perspectives should be used in both health care and research. Patients have experiential knowledge about their illness, living with it in their personal context and their care needs (Tait 2005 ). This is valuable for both clinical practice and research as their knowledge complements that of health professionals and researchers (Tait 2005 ; Broerse et al. 2010 ; Caron-Flinterman et al. 2005 ). This source of knowledge can be used in the process of translating evidence into clinical practice (Schrevel 2015 ). Moreover, patient participation can enhance the clinical relevance of and support for research and the outcomes in practice (Abma and Broerse 2010 ). Hence, it is argued that these perspectives should be explicated and integrated into clinical guidelines, clinical practice, and research (Misak 2010 ; Rycroft-Malone et al. 2004 ).

Given the advantages of including patients’ perspectives, patients are increasingly involved in healthcare services (Bagchus et al. 2014 ; Larsson et al. 2007 ), healthcare quality (e.g. guideline development) (Pittens et al. 2013 ) and health-related research (e.g. agenda setting, research design) (Broerse et al. 2010 ; Boote et al. 2010 ; Elberse et al. 2012 ; Teunissen et al. 2011 ). However, patients’ perspectives on health care and on research are often studied separately. We argue that to be able to provide care focused on the patients and their needs, care and research must closely interact.

We hypothesize that the challenges BD patients experience and the associated care and research needs are interwoven, and that combining them would provide a more comprehensive understanding. We hypothesize that this more comprehensive understanding would help to close the gap between clinical practice and research. For this reason, this study aims to understand the challenges people with BD experience and examine what these challenges imply for healthcare and research needs.

To understand the challenges and needs of people with BD, we undertook two qualitative studies. The first aimed to formulate a research agenda for BD from a patient’s perspective, by gaining insights into their challenges and research needs. A second study yielded an understanding of the care needs from a patient’s perspective. In this article, the results of these two studies are combined in order to investigate the relationship between research needs and care needs. Challenges are defined as ‘difficulties patients face, due to having BD’. Care needs are defined as that what patients ‘desire to receive from healthcare services to improve overall health’ (Asadi-Lari et al. 2004 ) (p. 2). Research needs are defined as that what patients ‘desire to receive from research to improve overall health’.

Study on research needs

In this study, mixed-methods were used to formulate research needs from a patient’s perspective. First six focus group discussions (FGDs) with 35 patients were conducted to formulate challenges in living with BD and hopes for the future, and to formulate research needs arising from these difficulties and aspirations. These research needs were validated in a larger sample (n = 219) by means of a questionnaire. We have reported this study in detail elsewhere (Maassen et al. 2018 ).

Study on care needs

This study was part of a nationwide Dutch project to generate a practical guideline for BD: a translation of the existing clinical guideline to clinical practice, resulting in a standard of care that patients with BD could expect. The practical guideline (Netwerk Kwaliteitsontwikkeling GGZ 2017 ) was written by a taskforce comprising health professionals, patients. In addition to the involvement of three BD patients in the taskforce, a systematic qualitative study was conducted to gain insight into the needs of a broader group of patients.

Participants and data collection

To formulate the care needs of people with BD, seven FGDs were conducted, with a total of 56 participants, including patients (n = 49) and caregivers (n = 9); some participants were both patient and caregiver. The inclusion criteria for patients were having been diagnosed with BD, aged 18 years or older and euthymic at time of the FGDs. Inclusion criteria for caregivers were caring for someone with BD and aged 18 years or older. To recruit participants, a maximum variation sampling strategy was used to collect a broad range of care needs (Kuper et al. 2008 ). First, all outpatient clinics specialized in BD affiliated with the Dutch Foundation for Bipolar Disorder (Dutch: Kenniscentrum Bipolaire Stoornissen) were contacted by means of an announcement at regular meetings and by email if they were interested to participate. From these outpatient clinics, patients were recruited by means of flyers and posters. Second, patients were recruited at a quarterly meeting of the Dutch patient and caregiver association for bipolar disorder. The FGDs were conducted between March and May 2016.

The FGDs were designed to address challenges experienced in BD health care and areas of improvement for health care for people with BD. The FGDs were structured by means of a guide and each session was facilitated by two moderators. The leading moderator was either BJR or EFM, having both extensive experience with FGD’s from previous studies. The first FGD explored a broad range of needs. The subsequent six FGDs aimed to gain a deeper understanding of these care needs, and were structured according to the outline of the practical guideline (Netwerk Kwaliteitsontwikkeling GGZ 2017 ). Three chapters were of particular interest: diagnosis, treatment and recovery. These themes were discussed in the FGDs, two in each session, all themes three times in total. Moreover, questions on specific aspects of care formulated by the members of the workgroup were posed. The sessions took 90–120 min. The FGDs were audiotaped and transcribed verbatim. A summary of the FGDs was sent to the participants for a member check.

Data analysis

To analyze the data on challenges and needs, a framework for thematic analysis to identify, analyze and report patterns (themes) in qualitative data sets by Braun and Clarke ( 2006 ) was used. First, we familiarized ourselves with the data by carefully reading the transcripts. Second, open coding was used to derive initial codes from the data. These codes were provided to quotes that reflected a certain challenge or care need. Third, we searched for patterns within the codes reflecting challenges and within those reflecting needs. For both challenges and needs, similar or overlapping codes were clustered into themes. Subsequently, all needs were categorized as ‘specific’ or ‘generic’. The former are specific to BD and the latter are relevant for a broad range of psychiatric illnesses. Finally, a causal analysis provided a clear understanding of how challenges related to each other and how they related to the described needs.

To analyze the data on needs regarding recovery, four domains were distinguished, namely clinical, functional, social and personal recovery (Lloyd et al. 2008 ; van der Stel 2015 ). Clinical recovery refers to symptomatic remission; functional recovery concerns recovery of functioning that is impaired due to the disorder, particularly in the domain of executive functions; social recovery concerns the improvement of the patient’s position in society; personal recovery concerns the ability of the patient to give meaning to what had happened and to get a grip on their own life. The analyses were discussed between BR and EM. The qualitative software program MAX QDA 11.1.2 was used (MaxQDA).

Ethical considerations

According to the Medical Ethical Committee of VU University Medical Center, the Medical Research Involving Human Subjects Act does not apply to the current study. All participants gave written or verbal informed consent regarding the aim of the study and for audiotaping and its use for analysis and scientific publications. Participation was voluntary and participants could withdraw from the study at any time. Anonymity was ensured.

This section is in three parts. The first presents the participants’ characteristics. The second presents the challenges BD patients face, derived from both studies, and the disorder-specific care and research needs associated with these challenges. The third part describes the generic care needs that patients formulated.

Characteristics of the participants

In the study on care needs, 56 patients and caregivers participated. The mean age of the participants was 52 years (24–75), of whom 67.8% were women. The groups varied from four to sixteen participants, and all groups included men and women. Of all participants 87.5% was diagnosed with BD, of whom 48.9% was diagnosed with BD I. 3.5% was both caregivers and diagnosed with BD. Of 4 patients the age was missing, and from 6 patients the bipolar subtype.

Despite the fact that participants acknowledge the inevitable diagnostic difficulties of a complex disorder like BD, in both studies they describe a range of challenges in different phases of the diagnostic process (Fig.  1 ). Patients explained that the general practitioner (GP) and society in general did not recognize early-warning signs and mood swings were not well interpreted, resulting in late or incorrect diagnosis. Patients formulated a need for more research on what early-warning signs could be and on how to improve GPs’ knowledge about BD. Formulated care needs were associated with GPs using this knowledge to recognize early-warning signs in individual patients. One participant explained that certain symptoms must be noticed and placed in the right context:

figure 1

Challenges with diagnosis (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

I call it, ‘testing overflow of ideas’. [….] When it happens for the first time you yourself do not recognize it. Someone else close to you or the health professional, who is often not involved yet, must signal it. (FG6)

Moreover, these challenges are associated with the need to pay attention to family history and to use a multidisciplinary approach to diagnosis to benefit from multiple perspectives. The untimely recognition of early symptoms also results in another challenge: inadequate referral to the right specialized health professional. After referral, people often face a waiting list, again causing delay in the diagnostic process. These challenges result in the need for research on optimal referral systems and the care need for timely referral. One participant described her process after the GP decided to refer her:

But, yes, at that moment the communication wasn’t good at all. Because the general practitioner said: ‘she urgently has to be seen by someone’. Subsequently, three weeks went by, until I finally arrived at depression [department]. And at that department they said: ‘well, you are in the wrong place, you need to go to bipolar [department ]’. (FG1)

The challenge of being misdiagnosed is associated with the need to be able to ask for a second opinion and to have a timely and thorough diagnosis. On the one hand, it is important for patients that health professionals quickly understand what is going on, on the other hand that health professionals take the time to thoroughly investigate the symptoms by making several appointments.

From both studies, two main challenges related to the treatment of BD were derived (Fig.  2 ). The first is finding appropriate and satisfactory treatment. Participants explained that it is difficult to find the right medication and dosage that is effective and has acceptable side-effects. One participant illustrates:

figure 2

Challenges with treatment (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

I think, at one point, we have to choose, either overweight or depressed. (FG1)

Some participants said that they struggle with having to use medication indefinitely, including the associated medical checks. The difficult search for the right pharmacological treatment results in the need for research on long-term side-effects, on the mechanism of action of medicine and on the development of better targeted medication with fewer adverse side-effects. In care, patients would appreciate all the known information on the side-effects and intended effects. One participant explained the importance of being properly informed about medication:

I don’t read anything [about medication], because then I wouldn’t dare taking it. But I do think, when you explain it well, the advantages, the disadvantages, the treatment, the idea behind it, that would help a lot in compliance. (FG1)

A second aspect is the challenge of finding non-pharmacological therapies that fit patients’ needs. They said they and the health professionals often do not know which non-pharmacological therapies are available and effective:

But we found the carefarm ourselves Footnote 1 [….]. You have to search for yourself completely. Yes, I actually hoped that that would be presented to you, like: ‘this would be something for you’. (FG3)

Participants mentioned a variety of non-pharmacological therapies they found useful, namely cognitive behavior therapy (CBT), EMDR, running therapy, social-rhythm training, light therapy, mindfulness, psychotherapy, psychoeducation, and training in living with mood swings. They formulated the care need to receive an overview of all available treatment options in order to find a treatment best suited to their needs. They would appreciate research on the effectiveness of non-pharmacological treatments.

A third aspect within this challenge is finding the right balance between non-pharmacological and pharmacological treatment. Participants differed in their opinion about the need for medication. Whereas some participants stated that they need medication to function, others pointed out that they found non-pharmacological treatments effective, resulting in less or no medication use. They explained that the preferred balance can also change over time, depending on their mood. However, they experience a dominant focus on pharmacological treatment by the health professionals. To address this challenge, patients need support in searching for an appropriate balance.

Next to the challenge of finding appropriate and satisfactory treatment, a second treatment-related challenge is hospitalization. Participants often had a traumatic experience, due to seclusion, the authoritarian attitudes of clinical staff, and not involving their family. Patients therefore found it important to try preventing being hospitalized, for example by means of home treatment, which some participants experienced positively. Despite the challenges relating to hospitalization, participants did acknowledge that in some cases it cannot be avoided, in which case they urged for close family involvement, open communication and being treated by their own psychiatrist. Still, in the study on research needs, hospitalization did not emerge as an important research theme.

In both studies, participants described challenges in all four domains of recovery: clinical, functional, social and personal (Fig.  3 ). In relation to clinical recovery, participants struggled with the symptoms of mood episodes, the psychosis and the fear of a future episode. In contrast, some participants mentioned that they sometimes miss the hypomanic state they had experienced previously due to effective medical treatment. In the domain of functional recovery, participants contended with having to function below their educational level due to residual symptoms, such as cognitive problems, due to the importance of preventing stress in order to reduce the risk of a new episode, and because of low energy levels. This leads to the care need that health professionals should pay attention to the level of functioning of their patients.

figure 3

Challenges with recovery (squares) including relating research needs (white circles) and care needs (grey circles). (1): mentioned in study on research needs; (2): mentioned in study on care needs. Dotted lines: division of challenges into sub challenges. Arrows: causal relation between challenges

In the domain of social recovery, participants described challenges with maintaining friendships, due to stigma, being unpredictable and with deciding when to disclose the disorder. The latter resulted in the care need for tips on disclosure. Moreover, patients experienced challenges with reintegration to work, due to colleagues’ lack of understanding, problems with functioning during an episode, the complicating policy of the (Dutch) Employee Insurance Agency Footnote 2 in relation to the fluctuating course of BD and the negative impact of stress. These challenges are associated with the care need that health professionals should pay attention to work and the need for research on how to improve the Social Security Agency’s policy.

For their personal recovery, participants struggled with acceptance of the disorder, due to shame, stigma, having to live by structured rules and disciplines, and the chronic nature of BD. This results in care needs for grief counselling and attention to acceptance and the need for research on the impact of being diagnosed with BD. Limited understanding within society also causes problems with acceptance, corresponding with the care need for education for caregivers and for research on how to increase social acceptance. Another challenge in personal recovery was discovering what recovery means and what constitute meaningful daily activities. Patients appreciated the support of health professionals in this area. One participant described the difficult search for the meaning of recovery:

I have been looking to recover towards the situation [before diagnosis] for a long time; that I could do what I always did and what I liked. But then I was confronted with the fact that I shouldn’t expect that to happen, or only with a lot of effort. (…) Then you start thinking, now what? A compromise. I don’t want to call that recovery, but it is a recovered, partly accepted, situation. But it is not recovery as I expected it to be. (FG5)

In general, participants considered frequent contact with a nurse or psychiatrist supportive, to help them monitor their mood and help them find (efficient) self-management strategies. Most participants appreciated the involvement of caregivers in the treatment and contact with peers.

Generic care needs

We have described BD-specific needs, but patients mentioned also mentioned several generic care needs. The latter are clustered into three categories. The first concerns the health professionals . Participants stressed the importance of a good health professional, who carefully listens, takes time, and makes them feel understood, resulting in a sense of connection. Furthermore, a good health professional treats beyond the guideline, and focuses on the needs of the individual patient. When there is no sense of connection, it should be possible to change to another health professional. The second category concerns communication between the patient and the health professional . Health professionals should communicate in an open, honest and clear way both in the early diagnostic phase and during treatment. Open communication facilitates individualized care, in which the patient is involved in decision making. In addition, participants wanted to be treated as a person, not as a patient, and according to a strength-based approach. The third category concerns needs at the level of the healthcare system . Participants struggled with the availability of the health professionals and preferred access to good care 24/7 and being able to contact their health professional quickly when necessary. Currently, according to the participants, the care system is not geared to the mood swings of BD, because patients often faced waiting lists before they could see a health professional.

Is adequate treatment also having a number from a mental health institution you can always call when you are in need, that you can go there? And not that you can go in three weeks, but on a really short notice. So at least a phone call. (FG3)

Participants were often frustrated by the limited collaboration between health professionals, within their own team, between departments of the organization, and between different organizations, including complementary health professionals. They would appreciate being able to merge their conventional and complementary treatment, with greater collaboration among the different health professionals. Furthermore, they would like continuity of health professionals as this improves both the diagnostic phase and treatment, and because that health professional gets to know the patient.

We hypothesized that research and care needs of patients are closely intertwined and that understanding these, by explicating patients’ perspectives, could contribute to closing the gap between research and care. Therefore, this study aimed to understand the challenges patients with BD face and examine what these imply for both healthcare and research. In the study on needs for research and in the study on care needs, patients formulated challenges relating to receiving the correct diagnosis, finding the right treatment, including the proper balance between non-pharmacological and pharmacological treatment, and to their individual search for clinical, functional, social and personal recovery. The formulated needs in both studies clearly reflected these challenges, leading to closely corresponding needs. Another important finding of our study is that patients not only formulate disorder-specific needs, but also many generic needs.

The needs found in our study are in line with the current literature on the needs of patients with BD, namely for more non-pharmacological treatment (Malmström et al. 2016 ; Nestsiarovich et al. 2017 ), timely recognition of early-warning signs and self-management strategies to prevent a new episode (Goossens et al. 2014 ), better information on treatment and treatment alternatives (Malmström et al. 2016 ; Neogi et al. 2016 ) and coping with grief (Goossens et al. 2014 ). Moreover, the need for frequent contact with health professionals, being listened to, receiving enough time, shared decision-making on pharmacological treatment, involving caregivers (Malmström et al. 2016 ; Fisher et al. 2017 ; Skelly et al. 2013 ), and the urge for better access to health care and continuity of health professionals (Nestsiarovich et al. 2017 ; Skelly et al. 2013 ) are confirmed by the literature. Our study added to this set of literature by providing insights in patients’ needs in the diagnostic process and illustrating the interrelation between research needs and care needs from a patient’s perspective.

The generic healthcare needs patients addressed in this study are clustered into three categories: the health professional , communication between the patient and the health professional and the health system. These categories all fit in a model of patient-centered care (PCC) by Maassen et al. ( 2016 ) In their review, patients’ perspectives on good care are compared with academic perspectives of PCC and a model of PCC is created comprising four dimensions: patient, health professional, patient – professional interaction and healthcare organization. All the generic needs formulated in this study fit into these four dimensions. The need to be treated as a person with strengths fits the dimension ‘patient’, and the need for a good health professional who carefully listens, takes time and makes them feel understood, resulting in a good connection with the professional, fits the dimension ‘health professional’ of this model. Furthermore, patients in this study stressed the importance of open communication in order to provide individualized care, which fits the dimension of ‘patient–professional interaction’. The urge for better access to health care, geared to patients’ mood swings and the need for better collaboration between health professionals and continuity of health professionals fits the dimension of ‘health care organization’ of the model. This study confirms the findings from the review and contributes to the literature stressing the importance of a patient-centered care approach (Mills et al. 2014 ; Scholl et al. 2014 ).

In the prevailing healthcare paradigm, EBM, the best available evidence should guide treatment of patients (Sackett et al. 1996 ; Darlenski et al. 2010 ). This evidence is translated into clinical and practical guidelines, which thus facilitate EBM and could be used as a decision-making tool in clinical practice (Skelly et al. 2013 ). For many psychiatric disorders, treatment is based on such disorder - specific clinical and practical guidelines. However, this disease-focused healthcare system has contributed to its fragmented nature Stange ( 2009 ) argues that this fragmented care system has expanded without the corresponding ability to integrate and personalize accordingly. We argue that acknowledging that disorder - specific clinical and practical guidelines address only parts of the care needs is of major importance, since otherwise important aspects of the patients’ needs will be ignored. Because there is an increasing acknowledgement that health care should be responsive to the needs of patients and should change from being disease-focused towards being patient-focused (Mead and Bower 2000 ; Sidani and Fox 2014 ), currently in the Netherlands generic practical guidelines are written on specific care themes (e.g. co-morbidity, side-effects, daily activity and participation). These generic practical guidelines address some of the generic needs formulated by the patients in our study. We argue that in addition to disorder-specific guidelines, these generic practical guidelines should increasingly be integrated into clinical practice, while health professionals should continuously be sensitive to other emerging needs. We believe that an integration of a disorder-centered and a patient-centered focus is essential to address all needs a patient.

Strengths, limitations and future research

This study has several strengths. First, it contributes to the literature on the challenges and needs of patients with BD. Second, the study is conducted from a patient’s perspective. Moreover, addressing this aim by conducting two separate studies enabled us to triangulate the data.

This study also has several limitations. First, this study reflects the challenges, care needs and research needs of Dutch patient with BD and caregivers. Despite the fact that a maximum variation sampling strategy was used to derive a broad range of challenges and needs throughout the Netherlands, the Dutch setting of the study may limit the transferability to other countries. To understand the overlap and differences between countries, similar research should be conducted in other contexts. Second, given the design of the study, we could not differentiate between patients and caregivers since they participated together in the FGDs. More patients than caregivers participated in the study. For a more in-depth understanding of the challenges and needs faced by caregivers, in future research separate FGDs should be conducted. Third, due to the fixed outline of the practical guideline used to conduct the FGDs, only the healthcare needs for diagnosis, treatment and recovery of BD are studied. Despite the fact that these themes might cover a broad range of health care, it could have resulted in overlooking certain needs in related areas of well-being. Therefore, future research should focus on needs outside of these themes in order to provide a complete set of healthcare needs.

Patients and their caregivers face many challenges in living with BD. Our study contributes to the literature on care and research needs from a patient perspective. Needs specific for BD are preventing late or incorrect diagnosis, support in search for individualized treatment, and supporting clinical, functional, social and personal recovery. Generic healthcare needs concern health professionals, communication and the healthcare system. This explication of both disorder-specific and generic needs indicates that clinical practice guidelines should address and integrate both in order to be responsive to the needs of patients and their caregivers.

Care farm: farms that combine agriculture and services for people with disabilities (Iancu 2013 ). These farms are used as interventions in mental care throughout Europe and the USA to facilitate recovery (Iancu et al. 2014 ).

A government agency involved in the implementation of employee insurance and providing labor market and data services.

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Authors’ contributions

EFM designed the study, contributed to the data collection, managed the analysis and wrote the first draft of the manuscript. BJR designed the study and contributed to the data collection, data analysis, and writing of the manuscript. JFGB contributed to the study design and critical revision of the manuscript. EJR contributed to the study conception and critical revision of the manuscript. RWK contributed to the study design, acquisition of data, and critical revision of the manuscript. All authors contributed to the final manuscript. All authors read and approved the final manuscript.

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Altrecht Institute for Mental Health Care, Nieuwe Houtenseweg 12, 3524 SH, Utrecht, Netherlands

Eva F. Maassen, Eline J. Regeer & Ralph W. Kupka

Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Psychiatry, De Boelelaan 1117, Amsterdam, Netherlands

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Maassen, E.F., Regeer, B.J., Regeer, E.J. et al. The challenges of living with bipolar disorder: a qualitative study of the implications for health care and research. Int J Bipolar Disord 6 , 23 (2018). https://doi.org/10.1186/s40345-018-0131-y

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5 Psychiatric Treatment of Bipolar Disorder: The Case of Janice

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Chapter 5 covers the psychiatric treatment of bipolar disorder, including a case history, key principles, assessment strategy, differential diagnosis, case formulation, treatment planning, nonspecific factors in treatment, potential treatment obstacles, ethical considerations, common mistakes to avoid in treatment, and relapse prevention.

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A Case Report of Mania and Psychosis Five Months after Traumatic Brain Injury Successfully Treated Using Olanzapine

Giordano f. cittolin-santos.

1 Faculty of Medicine, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil

Jesse C. Fredeen

2 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA

Robert O. Cotes

There are few published pharmacologic trials for the treatment of acute mania following traumatic brain injury (TBI). To our knowledge, we present the first case report of an individual being treated and stabilized with olanzapine monotherapy for this condition.

Case Presentation

We describe the case of a 53-year-old African American male admitted to an inpatient psychiatric hospital with one month of behavioral changes including irritability, decreased need for sleep, hyperverbal speech, hypergraphia, and paranoia five months after TBI. Using Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria, he was diagnosed with bipolar disorder due to traumatic brain injury, with manic features. He was serially evaluated with clinical rating scales to measure symptom severity. The Young Mania Rating Scale (YMRS) score upon admission was 31, and the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) score was initially 9. After eight days of milieu treatment and gradual titration of olanzapine to 15 mg nightly, his symptoms completely abated, with YMRS and CRDPSS scores at zero on the day of discharge.

Olanzapine was effective and well tolerated for the treatment of mania following TBI.

1. Introduction

Mania develops in 1.9–9% of individuals after experiencing traumatic brain injury (TBI) [ 1 , 2 ]. Yet, there is a dearth of literature on pharmacologic treatment options for mania following TBI. The guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury, published in 2006, concluded there was insufficient evidence to support the development of standards or guidelines in the treatment of TBI related mania [ 3 ]. Four studies were included in the review, including three case series (each with two patients) and one case report. Treatments successful in treating mania included clonidine [ 4 ], thioridazine/amitriptyline [ 5 ], electroconvulsive therapy [ 5 ], lithium [ 6 ], and valproate [ 6 ]. In addition to the studies presented in the 2006 guidelines, successful trials have been published with carbamazepine/lithium [ 7 ], lithium/thioridazine [ 8 ], lithium monotherapy [ 9 – 11 ], valproate/olanzapine [ 12 – 14 ], valproate monotherapy [ 15 ], carbamazepine/chlorpromazine [ 16 , 17 ], haloperidol [ 16 ], haloperidol/chlorpromazine [ 18 ], haloperidol/clonazepam [ 19 ], and quetiapine [ 20 ]. Here, we present the first case report of successful treatment with olanzapine monotherapy for mania after a traumatic brain injury.

2. Case Presentation

A 53-year-old African American male was brought by Emergency Medical Services (EMS) to the Emergency Room (ER) of an urban, public teaching hospital, due to threatening behavior, irritability, and an inability to care for himself. During the initial psychiatric consultation in the ER, the patient was hyperverbal with pressured speech and a tangential thought process. His mood was elevated, and his affect was labile with sudden and inappropriate bouts of tearfulness. He endorsed decreased need for sleep over the past few days and paranoid and persecutory delusions regarding strange noises around his apartment and his brother stealing money from his father. Per the EMS report, the patient was also emailing and texting neighbors paranoid and threatening messages, which resulted in multiple crisis hotline calls and the patient being brought to the hospital.

His past medical history was significant for a depressive episode treated successfully 25 years ago with sertraline and TBI five months prior to presentation. After the injury, he was followed by an outpatient neurologist for postconcussive syndrome. A brain MRI was ordered three months after TBI, which showed signs of mild white matter small vessel ischemic changes, but no other significant findings. The initial ER workup included a urinalysis, urine drug screen, complete metabolic panel, and thyroid function, all of which were unremarkable. A noncontrast CT scan of the brain was obtained and was unremarkable. He was admitted for inpatient psychiatric hospitalization. Using Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria [ 21 ], he was diagnosed with bipolar disorder due to traumatic brain injury, with manic features.

The patient was started on olanzapine 2.5 mg by mouth at bedtime upon admission. Manic features remained prominent, as he continued to demonstrate decreased need for sleep (three to five hours per night), pressured speech, irritability, emotional dysregulation, and labile affect. He often arose early in the morning and spent multiple hours writing questions for his treatment team. He refused valproate and lithium despite the team's suggestions. Olanzapine was gradually titrated and reached 15 mg on hospital day (HD) 6. Aside from one instance of refusal on HD 5, he was adherent with olanzapine throughout the hospitalization. Olanzapine was well tolerated. He was evaluated with serial clinical rating scales which included the Young Mania Rating Scale (YMRS) and the Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). On HD 1, the YMRS score was 31 and CRDSS was 9. On HD 6, the YMRS score decreased to 30 and CRDPSS decreased to 7. On HD 7, he displayed significant clinical improvement. He slept throughout the night and on interview no longer had pressured speech. His thought process was logical, linear, and goal-directed, and the psychotic symptoms had also fully abated. On HD 8, the YMRS and CRDPSS scores were 0. He was subsequently discharged from hospital with appropriate outpatient follow-up.

3. Discussion

Mania due to TBI is a challenging diagnosis to make with confidence, and this can make the limited research challenging to interpret. TBI may be an independent risk factor for the development of bipolar disorder [ 1 , 22 – 24 ] and the DSM-5 does not report a definitive time course for which the diagnosis of TBI must take place and symptoms must emerge in order for the disorder to be characterized as mania due to TBI [ 21 ]. As in our case, the majority of individuals who ultimately develop bipolar disorder report a depressive episode first [ 25 ], but the later age of onset of manic symptoms and temporal relationship to TBI lends credence to the TBI's primary role in the development of manic symptoms. In the case presented here, the patient exhibited a combination of manic and psychotic symptoms, but manic symptoms were predominant. The duration of the manic episode (likely around 2 months) was within range of other manic episodes reported after TBI. In study of six patients following head injury who experienced mania, the duration of the episode was 2 months, and the mean estimated duration of elevated mood was 5.7 months [ 2 ].

Olanzapine is a second-generation antipsychotic medication effective for the treatment of acute bipolar mania [ 26 ] and recommended for acute mania by various guidelines across the world [ 27 – 29 ]. However, few pharmacologic (and no randomized) trials exist for the treatment of mania following TBI. Olanzapine has been used for acute mania following TBI in several reported cases. Grenne et al. [ 30 ] described a case of a 13-year-old boy treated with olanzapine 10 mg daily and zonisamide who had improvement of auditory hallucinations but continued mania and delusions. A 60-year-old man was treated with an unspecified dose of olanzapine and 2500 mg of valproate five months after a head injury [ 12 ]. A 42-year-old man was treated with olanzapine 15 mg daily and valproate 1000 mg daily for mania emerging three years after a head trauma [ 13 ]. A 69-year-old man eighteen months after TBI was treated with 7.5 mg of olanzapine and 250 mg of valproate three times daily [ 14 ]. In each of these cases, olanzapine was combined with another medication, and of note, valproate alone has been effective in treating mania secondary to TBI [ 15 ], making it challenging to know if the patient improved related to olanzapine or valproate. Furthermore, olanzapine monotherapy has been shown to be effective in treating psychotic symptoms following traumatic brain injury in two case reports [ 31 , 32 ]. In the case presented here, the patient was not agreeable to other pharmacologic treatments despite being offered lithium and valproate augmentation. In a 2014 review article, Jorge and Arciniegas recommended valproate or quetiapine as first-line therapies for bipolar disorder due to TBI [ 33 ]. We conclude that olanzapine could also be considered for this population, as it was effective and well tolerated in this case.

Conflicts of Interest

Dr. Robert O. Cotes has accepted research funding, consultation fees, and/or honoraria from Alkermes, Janssen, and Otsuka Pharmaceuticals. Drs. Giordano F. Cittolin-Santos and Jesse C. Fredeen have nothing to disclose.

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  • Published: 29 May 2024

Network analysis of comorbid aggressive behavior and testosterone among bipolar disorder patients: a cross-sectional study

  • Hong Cai   ORCID: orcid.org/0000-0002-7915-1092 2 ,
  • Tian Han 1 ,
  • Yi-Fan Wang 1 ,
  • Juan Li 1 ,
  • Xiao-meng Xie   ORCID: orcid.org/0000-0001-6759-9685 1 &
  • Xiao Ji   ORCID: orcid.org/0009-0006-9248-0719 1  

Translational Psychiatry volume  14 , Article number:  224 ( 2024 ) Cite this article

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  • Bipolar disorder
  • Prognostic markers

Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%–38.7%), level III aggression was 29.5% (95%CI = 26.3%–32.6%), and level VI aggression was 7.0% (95%CI = 5.4%–8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, “Increased motor activity-energy” emerged as the central symptom, with the highest centrality expected influence, followed by “Emotional Instability” and “Disruptive/aggression behavior”. Notably, “Emotional Instability” appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, “Speech rate and amount” exhibited the strongest positive correlation with testosterone levels, followed closely by “Disruptive/aggression behavior”. The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, “Increased motor activity-energy” stood out as the most influential symptom, and “Speech rate and amount” acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.

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Introduction.

Bipolar disorder (BD) is a potentially lifelong condition characterized by extreme changes in mood with high incidences of hyperactivity, irritability, grandiosity, poor judgment, and other symptoms, all of which are highly likely to lead to aggressive behavior [ 1 ]. Impulsive aggression is common amongst BD patients. Notably, aggressive behavior in BD patients show a direct prognostic value, which links to suicidal behaviors, more frequent hospitalizations, higher severity of mania symptoms, mixed symptoms, and comorbid borderline personality disorder [ 2 ]. A characteristic of BD emerges as hindrance towards an individual’s ability to perceive risk and protect themselves, which make them vulnerable to physical assault [ 3 ]. Given the risk of hurting others and self-harm, patients with BD have profound effects on society and family numbers.

The etiology of BD is unknown; however, factors such as genetics, biological traits, and environment have been proposed for consideration in the pathogenesis of BD [ 4 ]. For patients with BD who are experiencing disease episode, emergency departments or psychiatric emergency department (PED) are often their preferred choice for medical treatment. The highest prevalence of aggressive behavior occur in acute care settings (12.5–61.8%) [ 5 , 6 ]. Psychiatric emergency department is suitable place to study the relationship for testosterone levels, aggressive behavior, and manic symptoms among patients with BD.

Several lines of evidence indicates that testosterone may be involved in the pathophysiology of aggressive behavior [ 7 , 8 ]. Testosterone, an androgenic steroid hormone that is regulated by the hypothalamus-pituitary-gonadal (HPG) axis, has traditionally been associated with the manifestation of aggression, partly due to its close relationship with dominance behavior and competitive tendencies [ 9 ]. A study reported that administering exogenous testosterone can rapidly increase aggressive behavior in adult males [ 10 ]. Testosterone maintains have a complex relationship with BD; it can impact emotions, with elevated levels of testosterone associated with increasing incidences of depressive and hypomania symptoms [ 11 ]. Some gender differences have been observed with respect to the clinical course in patients with BD [ 12 ]. This evidence suggests a relationship between testosterone levels and aggressive behavior need to be discuss.

Hence, we need to establish a interaction assessment model, which is helpful for understanding the pathogenesis of aggressive behavior in patients with BD. Clinicians could then establish suitable biomarkers for the purposes of screening, risk appraisal, and subsequent therapeutic interventions [ 13 ]. In recent years, network analysis has experienced an expanding application in the field of psychology and psychiatry [ 14 ]. Network analysis is an innovative and analytical method that elucidates a biological system by anticipating the inter-relationships among multiple syndromes [ 15 ]. To further probe the inter-relationship between testosterone and aggressive behavior in BD patients, we incorporated network analysis into this investigation and identify symptoms as robust central symptoms, bridge symptoms and short paths between testosterone and aggrresive behavior within such populations in psychiatric emergency care. We hypothesize that high levels of testosterone may represent a key link point in neurobiological activity, which might contribute to aggression by exacerbating emotional instability.

Patients and study sites

A cross-sectional survey was conducted between January 2021 and March 2022 in Beijing Anding Hospital’s psychiatric emergency department, which is the only 24-h psychiatric hospital emergency service in the Beijing municipality and neighboring provinces. During the study, all patients who had received psychiatric emergency service were recruited consecutively for the survey. Eligible participants had to meet the following criteria: (1) receiving emergency maintenance treatment for a major psychiatric disorder; (2) provided written informed consent; (3) clinical diagnosis of a manic episode (F30–F39 in the ICD-10) (i.e., the Young Mania Rating Scale (YMRS) total score of ≥20 (Ouyang et al. [ 41 ]). Ethical approval was obtained from the Ethics Committee of Beijing Anding Hospital.

The basic socio-demographic and clinical data (e.g., age, onset age, gender, education level, marital status, employment status, illness duration, family history of psychiatric disorders) were collected using a form designed for this study through a review of medical records and confirmation from a clinical interview.

Blood collection and assays of testosterone

The routine blood collections were performed for clinical evaluations during psychiatric emergency visits. Serum samples were collected from all patients between 7:30 AM and 8:30 AM. Controlling for age and gender, the levels of 8 (7.30–8.30) AM serum were assayed for Testosterone (μg/dl) using chemiluminescence. The laboratory personnel were blind to all clinical information. Samples and data were processed following standard operating procedures with the appropriate approval of the Ethics and Scientific Committee of Capital Medical University, and all subjects provided written informed consent.

Measurement

In this study, aggressive behavior was assessed through interviews conducted by a trained attending psychiatrist within 12 h after admission. The aggressiveness of the subjects was graded using the standardized scale delineated by the local health authority and extensively employed in Chinese clinical practice. The severity of aggression is assessed in three domains: verbal aggression, aggression towards property, and physical aggression towards individuals. Verbal aggression, in this context, pertains to yelling or screaming, exhibiting hostile or offensive gestures, or uttering profanities. The standardized scale determines the intensity of each possible form of aggression on a scale of I to VI, with a level above II considered as aggression. We also used the aggression subscale of the PANSS scale (PANSS-AG), which includes supplementary components for the risk aggression profile (such as anger, difficulty in delaying gratification, and emotional instability) [ 16 ]. The PANSS had been validated in the Chinese population and demonstrates satisfactory psychometric properties (Cronbach’s alpha = 0.84) [ 17 ].

The Youth Mania Rating Scale (YMRS) [ 18 ] is an 11-item clinical rating scale used to assess the severity of manic symptoms. Seven of the eleven individual YMRS items were scored on a 0–4 scale: appearance, insight, language-thought disorder, increased motor activity-energy, elevated mood, sleep, and sexual interest, while the remaining four items were scored on a 0–8 scale: disruptive/aggressive behavior, content of morbid thinking, irritability, and speech–rate and amount. The YMRS total score, with a range of 0–60, is a summation of each of the eleven individual scores, with higher total scores signifying a more severe manifestation of mania.

Statistical analyses

Data were analyzed with the IBM Statistical Package for Social Science (SPSS) software version 24.0 and R software version 4.2.3. Normality of the data was assessed using the Kolmogorov–Smirnov test. Using the R software [ 19 ], a network model of aggression severity and testosterone level was built. To examine the edges of the network, we computed the polychoric correlations between all items and estimated the Graphical Gaussian Model (GGM) using the graphic least absolute shrinkage and selection operator (LASSO), and the Extended Bayesian Information Criterion (EBIC) using the R package graph [ 20 ].

The importance of each node in the network was examined by estimating centrality indices of the network structure with the R package “graph” [ 21 ]. Specifically, the centrality index of expected influence (EI) was computed for each node in the network (i.e., the sum of the weights of the connections, in absolute value), because EI is the most stable and interpretable centrality index [ 20 ]. The thickness of the edge represents the strength of the association. Additionally, previous studies [ 22 ] on comorbid psychiatric syndromes found that “Testosterone” was commonly reported to link different symptom communities as a key node. Therefore, the node-specific predictive betweenness of “Testosterone” (i.e., how often a node lies on the pathways between two other nodes, always with the “Testosterone” node as either of them across 1000 nonparametric bootstrap iterations) was estimated [ 23 ]. To identify particular symptoms that were directly associated with “Testosterone”, the “flow” function in the R package ‘qgraph’ was used [ 21 ].

Following previous studies [ 24 , 25 ], the differences in network characteristics between male and female participants were compared using the R “NetworkComparisonTest” package (Version 2.2.1) [ 26 ] with 1000 permutations. The difference in network structure (e.g., distributions of edge weights), global strength (e.g., total absolute connectivity among the symptoms), and each specific edge between subsamples (i.e., females vs. males) were also examined.

A total of 915 patients were invited to participate in this study; 898 patients met the study criteria and were included in analyses, in which the response rate was 98.1%, the rest of them were not included in the analysis due to incomplete information. The prevalence of level II aggression was 35.6% (95%CI = 32.5%–38.7%), level III aggression was 29.5% (95%CI = 26.3%–32.6%), and level VI was 7.0% (95%CI = 5.4%–8.8%). The male participants had a mean testosterone level of 391.71 ± 223.39 ng/dl (reference range 260–1590 ng/dl for ♂) compared to 36.90 ± 30.50 ng/dl for female participants (reference range 15–80 ng/dl for ♀). The demographic and clinical characteristics of the study population are summarized in Table 1 .

Network structure

Figure 1 illustrates the network structure representing the comorbid severity of aggression, manic symptoms, and testosterone levels in participants diagnosed with BD. The network model reveals that the strongest positive association among manic symptoms is between YMRS1 (“Elevated mood”) and YMRS2 (“Increased motor activity-energy”), followed by YMRS7 (“Language-thought disorder”) and YMRS8 (“Content of morbid thinking”), as well as YMRS5 (“Irritability”) and YMRS9 (“Disruptive/aggression behavior”).

figure 1

AS aggression severity, FE facial expression, SI anger, S2D delyed graftification, S3E Emotional instability, T testosterone, YMRS1 high mood, YMRS2 increased behavioral activity, YMRS3 sexual interest, YMRS4 sleep, YMRS5 ittitability, YMRS6 language speed and quantity, YMRS7 language thinking disturbed, YMRS8 patients thinking, YMRS9 attack and sabotage, YMRS10 appearance, YMRS11 self-control.

Regarding EI centrality, the node YMRS2 (“Increased motor activity-energy”) exhibits the highest value, followed by S3E (“Emotional instability”) and YMRS9 (“Disruptive/aggression behavior”) within the network (Fig. 1 ). In terms of bridge EI, S3E (“Emotional instability”) emerges as the most critical bridge symptom connecting aggression and manic symptoms, succeeded by YMRS9 (“Disruptive/aggression behavior”) and S2D (“Delaying gratification”) (Fig. 1 ). Furthermore, the flow network model demonstrates that YMRS6 (“Speech–rate and amount”) exhibits the strongest positive correlation with testosterone, followed by YMRS1 (“Elevated mood”) (Fig. 2 ). In addition, we found that YMRS6 (“Speech–rate and amount”) has the strongest positive association with testosterone in the flow network model, followed by the YMRS1 (“Elevated mood”) (Fig. 2 ).

figure 2

Flow network of Testosterone.

Regarding network stability, the EI centrality demonstrates an exceptional level of stability (i.e., CS-coefficient = 0.75 (95% CI: 0.675-1)), indicating that the network structure would not change significantly even if 75% of the sample was removed (Fig. 3 ). The bootstrap difference test revealed that most comparisons between edge weights were statistically significant.

figure 3

The stability of centrality and bridge centrality indices using case-dropping bootstrap.

Node-specific predictive betweenness measure

Researchers have found that “Testosterone” plays an important role in aggressive behavior in previous studies [ 22 ]. Figure 4 shows the node-specific predictive betweenness values for each node in the network. The white dots represent the node-specific predictive betweenness in the study sample, while the black lines represent the variability of the measure across 1000 nonparametric bootstrap iterations. YMRS6 (“Speech–rate and amount”) has the highest node-specific predictive betweenness score, followed by YMRS5 (“Irritability”). This finding suggests that “Speech–rate and amount” and “Irritability” may be the main bridge symptoms between testosterone levels, manic symptoms, and aggression (Fig. 4 ).

figure 4

Node-specific predictive betweenness.

Network comparison tests by gender

The comparison of the network model by gender did not reveal significant differences in network global strength (network strength: 11.37 in female participants; 11.40 male participants; M = 0.214, P = 0.571) and edge weights (S = 0.026, P = 0.969, Supplementary Figs. S1 – S4 ).

The study is the first network analysis of the association between testosterone levels and aggressive behavior among patients with BD in China PED. Within the assessed network model, “Increased motor activity-energy”, “Emotional instability” and “Disruptive/aggressive behavior” stood out as the most influential symptoms. Notably, “Speech rate and amount” acted as the main bridge symptom linking testosterone levels, manic symptoms, and aggression, followed by “Elevated Mood” and “Difficulty in delaying gratification”.

Our network analysis highlighted “Increased motor activity-energy” and “Emotional instability” as central symptoms in patients arriving at the emergency room due to aggressive tendencies. Patients with BD often displays alcohol or substance abuse, which can increase behavioral activity, leadings to an increased prevalence of aggressive behavior possibly up to 12% [ 27 ]. Consistent with previous findings, aggression was associated with more severe manic symptoms, as measured by the YMRS in acute manic episodes [ 28 ]. People in the manic phase are often highly motivated to engage in goal-oriented activities. However, due to lack of insight, patients may not realize their behavior is abnormal and prone to harmful consequences. Patients become extremely aggressive and irritable, and are more likely to harm themselves or others and destroy property through verbal or physical aggression [ 29 ]. This observation also shed light on the identification of “Difficulty in delayed gratification” as another bridge symptom. Previous functional magnetic resonance imaging (fMRI) studies have observed responses in the amygdala, periaqueductal gray matter, and the prefrontal lobe when BD patients were frustrated by the denial of a reward. This neural response can potentially stimulate aggressive impulses, transforming unfulfilled desires into the urge to attack [ 30 ].

“Speech–rate and amount” acted as the main bridge symptoms linking testosterone levels, manic symptoms, and aggression, succeeded by “Elevated Mood”. “Speech–rate and amount” and “Elevated mood” are typical symptoms of manic episodes, and previous imaging studies have shown abnormalities in neuronal coupling in the sensory-motor subcortical-cortical circuit in patients with highly excited brains, compared to healthy controls [ 31 ]. Testosterone may act through receptors located in key regulatory regions to increase the connectivity between subcortical regions of the brain while weakening connections between the cortex and subcortical regions [ 32 ], causing the patient in highly excited state. Abnormal regulation of the HPG axis is critical for homeostatic regulation of synthesis and secretion of testosterone and the most potent androgen dihydrotestosterone (DHT) by the testis [ 33 ]. Dysregulation of the HPG axis may cause depressive symptoms, which are associated with high cortisol inhibition [ 34 ]. Moreover, compared to bodybuilders who did not take exogenous testosterone, there was a higher rate of hypomanic episodes among those who did [ 35 ]. The release of testosterone will increase the motivation of BD patients to seek dominance and take impulsive risks, which are often poorly thought-out and prone to adverse consequences [ 36 ]. High levels of testosterone have been found to reduce activity and functional connectivity in the prefrontal cortex, altering the function of prefrontal-mediated emotion regulation, thereby impairing the ability to control aggressive impulses [ 37 ].

Regarding the gender for the network model of comorbid aggression severity, manic symptoms, and testosterone levels among patients with BD, there were none significant differences shown in this study. The existing evidence suggests that testosterone concentrations in early life influence the development of some human behaviors, with certain gender differences [ 38 ]. One study from community recruiters suggested that adolescent males with higher plasma testosterone levels were more irritable and likely to overreact to provocation and threats [ 39 ]. Previous studies on depressive episode status in patients with BD have found that male patients have significantly lower testosterone levels, while female patients have significantly higher levels [ 40 ].

The strengths of this study include a substantial sample size, the utilization of standardized assessment instruments, and the employment of network analysis techniques. These techniques were tailored to investigate the structure of the model assessing testosterone levels and aggressive behavior in patients with BD. Such insights may pinpoint potential targets for treatment and prevention measures, particularly for patients with BD in psychiatric emergencies exhibiting these problems. Nonetheless, several methodological limitations in our study warrant attention. First, the cross-sectional design precludes establishing causal relationships between variables, and there was an absence of a control/naive group. Future longitudinal research is essential to elucidate the time-bound causal links between testosterone levels and aggressive behavior in patients with BD. Secondly, though routine blood collections were performed for clinical evaluations during psychiatric emergency visits, additional measurements, such as thyroxine, should be added to the study analysis. Subsequently, we hope to carry out relevant radiological research to further explore the specific relationship between testosterone levels and aggressive behavior in BD patients. Lastly, our sample was consecutively drawn from one major psychiatric emergency department (PED) in China, which may limit the generalizability of our findings in other psychiatric contexts.

To summarize, within the aggression-bipolar disorders network model, as well as the association with testosterone levels, “Increased motor activity-energy,” “Emotional instability,” and “Disruptive/aggressive behavior” were the most pivotal symptoms among BD patients in PED. Our study showed no significant gender differences in testosterone levels observed in BD patients during the manic episode phase. These specific symptoms, which are potential intervention targets, should be at the forefront of physicians’ evaluation protocols.

Data availability

The data of the investigation will be made publicly available if necessary.

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Yi Liu, Tian Han, Yi-Fan Wang, Juan Li, Xiao-meng Xie & Xiao Ji

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(I) Conception and design: Xiao Ji, Xiao-meng Xie. (II) Administrative support: Xiao Ji, Yi Liu, Yi-Fan Wang. (III) Provision of study materials or patients: Cai Hong, Yi Liu, Tian Han, Juan Li. (IV) Collection and assembly of data: Yi-Fan Wang, Yi Liu, Tian Han, Juan Li. (V) Data analysis and interpretation: Yi-Fan Wang, Xiao-meng Xie, Cai Hong. (VI) Manuscript writing: All authors. (VII) Final approval of manuscript: All authors.

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Liu, Y., Cai, H., Han, T. et al. Network analysis of comorbid aggressive behavior and testosterone among bipolar disorder patients: a cross-sectional study. Transl Psychiatry 14 , 224 (2024). https://doi.org/10.1038/s41398-024-02957-1

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Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder

  • 1 Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, and Stockholm Health Care Services, Region Stockholm, Karolinska University Hospital, Stockholm, Sweden
  • 2 Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden
  • 3 Department of Clinical Sciences/Psychiatry, Umeå University, Umeå, Sweden
  • 4 Sence Research, Uppsala, Sweden

Question   What is the association of age at major depressive disorder (MDD) onset with progression to bipolar disorder (BD) in adolescents and adults?

Findings   In this cohort study of 228 individuals in the Stockholm MDD Cohort (2010-2013), youths with MDD were found to be more than 50% less likely to transition early to BD compared with adults, with notable reductions in inpatient care and antidepressant use following BD diagnosis for both groups and without an increase in lithium prescriptions.

Meaning   These findings suggest that adolescents may experience delayed BD progression and that diagnosis is associated with a substantial reduction in inpatient care in all age groups, coinciding with a decreased use of antidepressants.

Importance   Bipolar disorder (BD) often first appears in adolescence after onset of major depressive disorder (MDD), but diagnosis and treatment are commonly delayed. This delay is a concern because untreated BD is associated with adverse long-term outcomes, a more recurrent disease course and difficult-to-treat illness, and suicide attempts and deaths.

Objective   To examine the association of age at MDD onset with early transition to BD and the subsequent use of psychiatric inpatient services as a severity indicator.

Design, Setting, and Participants   This retrospective cohort study analyzed comprehensive data sourced from the Stockholm MDD Cohort data from 1997 to 2018, which encompass both outpatient and inpatient care. Individuals with an initial MDD episode from January 1, 2010, to December 31, 2013, who transitioned to BD by December 31, 2018, were identified. Data were analyzed between September 5 and December 28, 2023.

Exposures   Post MDD assessments included a depression severity index, comorbidities, psychotherapy, psychotropic drugs, and electroconvulsive therapy.

Main Outcomes and Measures   The main outcome was the transition from MDD to BD, dichotomized as occurring early (within 3 years of MDD onset) or late (3 years after MDD onset). Secondary outcomes encompassed the use of psychiatric inpatient services post transition and patterns of medication usage. A robust propensity score matching framework was used to estimate outcomes.

Results   The final balanced cohort included 228 individuals, with an equal distribution between adults (n = 114; mean [SD] age, 24.5 [6.3] years; 96 female [84.2%]; 20 experiencing an early transition to BD [17.5%]) and youths (n = 114; mean [SD] age, 15.3 [1.6] years; 93 female [81.6%]; 8 experiencing an early transition to BD [7.0%]). Youths were substantially less likely to transition early (odds ratio, 0.42; 95% CI, 0.20-0.88; P  = .02), despite having more outpatient visits (mean [SD] visits per month, 1.21 [1.07] vs 0.97 [0.98] for adults; P  = .01). Both groups experienced substantially reduced inpatient care following a BD diagnosis, concurring with a marked decline in antidepressant use without increased lithium use.

Conclusions and Relevance   These findings suggest that adolescents may experience delayed BD progression and that diagnosis substantially reduced inpatient care in all age groups, which coincided with a reduction in the use of antidepressants. These findings may inform pharmacologic strategies in patients with first-episode MDD at risk for BD.

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Desai Boström AE , Cars T , Hellner C , Lundberg J. Adolescent and Adult Transitions From Major Depressive Disorder to Bipolar Disorder. JAMA Psychiatry. Published online May 29, 2024. doi:10.1001/jamapsychiatry.2024.1133

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    DS47-2 Case Study 47 Bipolar Disorder Age of onset for both BPI and BPII varies greatly from childhood to age 50 years with a mean age of approximately 21 years. Most cases are diagnosed when individuals are age 15-30 years. Significance Bipolar disorder is often a serious, chronic, and recurring struggle for both patients and their families.

  19. PDF Bipolar Disorder

    Bipolar disorder is a mental illness that can be chronic (persistent or constantly reoccurring) or episodic (occurring occasionally and at irregular intervals). People sometimes refer to bipolar disorder with the older terms "manic-depressive disorder" or "manic depression.". Everyone experiences normal ups and downs, but with bipolar ...

  20. (PDF) Case Study: Eric and Bipolar Disorder I

    Bipolar Disorder (BPD) is a mood disorder involving periods of either depressed or elevated and expansive moods (American Psychology Association [APA], 2000). These changes in polarity are ...

  21. A Case Report of Mania and Psychosis Five Months after Traumatic Brain

    As in our case, the majority of individuals who ultimately develop bipolar disorder report a depressive episode first , but the later age of onset of manic symptoms and temporal relationship to TBI lends credence to the TBI's primary role in the development of manic symptoms. In the case presented here, the patient exhibited a combination of ...

  22. Network analysis of comorbid aggressive behavior and ...

    This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric ...

  23. Adolescent and Adult Transitions From Major Depressive Disorder to

    This cohort study examines the association of age at onset of major depressive disorder with early transition to bipolar disorder and subsequent inpatient ... management, and treatment of bipolar disorder in Sweden: a retrospective observational registry study.  Bipolar Disord. 2015;17(1):76-85. doi:10. ... Get unlimited access and a ...

  24. Bipolar Affective Disorder -Mania with Psychotic Symptoms: A Case Study

    Abstract. Bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental disorder that causes unusual shifts in mood, energy, activity levels, concentration, and the ...

  25. Evaluation des Troubles Cognitifs Chez des Patients Tunisiens Atteints

    This study showed that bipolar patients in remission presented significantly more marked cognitive impairments, affecting various cognitive domains, than the controls, and these cognitive impairments appear to be linked to clinical and therapeutic factors that are themselves considered to be factors of poor prognosis in BD. OBJECTIVES Our aims were to assess cognitive impairment in bipolar ...

  26. (PDF) A Case Study on Bipolar Affective Disorder Current Episode Manic

    According to the diagnostic criteria of DSM -5, symptoms. of a depressive episode include depressed mood, sign ificant. changes in sleep patterns and appetite, psychomoto r agitation or ...