The big five model in bipolar disorder: a latent profile analysis and its impact on longterm illness severity.

BACKGROUND: Using a personality typing approach, we investigated the relationship between personality profiles and the prediction of longterm illness severity in patients with bipolar disorder (BD). While previous research suggests associations between BD and traits from the NEO-FFI profiles, the current study firstly aimed to identify latent classes of NEO-FFI profiles, and, secondly, to examine their impact on the longterm prognosis of BD. METHODS: Based on the NEO-FFI profiles of 134 euthymic patients diagnosed with BD (64.2% female, mean age = 44.3 years), successive latent profile analyses were conducted. Subsequently, a subsample (n = 80) was examined prospectively by performing multiple regression analysis of the latent classes to evaluate the longitudinal course of the disease (mean: 54.7 weeks) measured using a modified Morbidity Index. RESULTS: The latent profile analyses suggested a 3-class model typifying in a resilient (n = 68, 51%), vulnerable (n = 55, 41%) and highly vulnerable (n = 11, 8%) class. In the regression analysis, higher vulnerability predicted a higher longterm Morbidity Index (R2 = 0.28). CONCLUSIONS: Subgroups of patients with BD share a number of discrete personality features and their illness is characterized by a similar clinical course. This knowledge is valuable in a variety of clinical contexts including early detection, intervention planning and treatment process.

Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden.

BACKGROUND: Early identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences. METHODS: We examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences. RESULTS: Out of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD. CONCLUSION: This analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.

Improving early recognition and intervention in people at increased risk for the development of bipolar disorder: study protocol of a prospective-longitudinal, naturalistic cohort study (Early-BipoLife).

BACKGROUND: Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD. METHODS: Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15-35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPIbipolar) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD. DISCUSSION: Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.

Prevalence of Prediabetes and Diabetes Mellitus Type II in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is characterized by recurrent episodes of depression and mania and affects up to 2% of the population worldwide. Patients suffering from bipolar disorder have a reduced life expectancy of up to 10 years. The increased mortality might be due to a higher rate of somatic diseases, especially cardiovascular diseases. There is however also evidence for an increased rate of diabetes mellitus in BD, but the reported prevalence rates vary by large. MATERIAL AND METHODS: 85 bipolar disorder patients were recruited in the framework of the BiDi study (Prevalence and clinical features of patients with Bipolar Disorder at High Risk for Type 2 Diabetes (T2D), at prediabetic state and with manifest T2D) in Dresden and Würzburg. T2D and prediabetes were diagnosed measuring HBA1c and an oral glucose tolerance test (oGTT), which at present is the gold standard in diagnosing T2D. The BD sample was compared to an age-, sex- and BMI-matched control population (n = 850) from the Study of Health in Pomerania cohort (SHIP Trend Cohort). RESULTS: Patients suffering from BD had a T2D prevalence of 7%, which was not significantly different from the control group (6%). Fasting glucose and impaired glucose tolerance were, contrary to our hypothesis, more often pathological in controls than in BD patients. Nondiabetic and diabetic bipolar patients significantly differed in age, BMI, number of depressive episodes, and disease duration. DISCUSSION: When controlled for BMI, in our study there was no significantly increased rate of T2D in BD. We thus suggest that overweight and obesity might be mediating the association between BD and diabetes. Underlying causes could be shared risk genes, medication effects, and lifestyle factors associated with depressive episodes. As the latter two can be modified, attention should be paid to weight changes in BD by monitoring and taking adequate measures to prevent the alarming loss of life years in BD patients.

Efficacy of cognitive-behavioral group therapy in patients at risk for serious mental illness presenting with subthreshold bipolar symptoms: Results from a prespecified interim analysis of a multicenter, randomized, controlled study.

OBJECTIVE: Most patients with bipolar disorders (BD) exhibit prodromal symptoms before a first (hypo)manic episode. Patients with clinically significant symptoms fulfilling at-risk criteria for serious mental illness (SMI) require effective and safe treatment. Cognitive-behavioral psychotherapy (CBT) has shown promising results in early stages of BD and in patients at high risk for psychosis. We aimed to investigate whether group CBT can improve symptoms and functional deficits in young patients at risk for SMI presenting with subthreshold bipolar symptoms. METHOD: In a multicenter, randomized, controlled trial, patients at clinical risk for SMI presenting with subthreshold bipolar symptoms aged 15-30 years were randomized to 14 weeks of at-risk for BD-specific group CBT or unstructured group meetings. Primary efficacy endpoints were differences in affective symptomatology and psychosocial functioning at 14 weeks. At-risk status was defined as a combination of subthreshold bipolar symptomatology, reduction of psychosocial functioning and a family history for (schizo)affective disorders. A prespecified interim analysis was conducted at 75% of the targeted sample. RESULTS: Of 128 screened participants, 75 were randomized to group CBT (n = 38, completers = 65.8%) vs unstructured group meetings (n = 37, completers = 78.4%). Affective symptomatology and psychosocial functioning improved significantly at week 14 (P < .001) and during 6 months (P < .001) in both groups, without significant between-group differences. Findings are limited by the interim character of the analysis, the use of not fully validated early detection interviews, a newly adapted intervention manual, and the substantial drop-outs. CONCLUSIONS: Results suggest that young patients at-risk for SMI presenting with subthreshold bipolar symptoms benefit from early group sessions. The degree of specificity and psychotherapeutic interaction needed requires clarification.

Personal continuity versus specialisation of care approaches in mental healthcare: experiences of patients and clinicians-results of the qualitative study in five European countries.

BACKGROUND: The current debate on organisation of the mental health care raises a question whether to prioritise specialisation of clinical teams or personal continuity of care. The article explores the experiences of patients and clinicians regarding specialisation (SC) and personal continuity (PCC) of care in five European countries. METHODS: Data were obtained via in-depth, semi-structured interviews with patients (N = 188) suffering from mental disorders (F20-49) and with clinicians (N = 63). A maximum variation sampling was applied to assume representation of patients and of clinicians with different characteristics. The qualitative data from each country were transcribed verbatim, coded and analysed through a thematic analysis method. RESULTS: Many positive experiences of patients and clinicians with the PCC approach relate to the high quality of therapeutic relationship and the smooth transition between hospital and community care. Many positive experiences of patients and clinicians with the SC approach relate to concepts of autonomy and choice and the higher adequacy of diagnosis and treatment. Clinicians stressed system aspects of providing mental health care: more effective management structure and higher professionalization of care within SC approach and the lower risk of disengagement from treatment and reduced need for coercion, restraint, forced medication or involuntary admission within PCC. CONCLUSIONS: Neither the PCC, nor the SC approach meets the needs and expectations of all patients (and clinicians). Therefore, future reforms of mental health services should offer a free choice of either approach, considering that there is no evidence of differences in patient outcomes between PCC and SC approaches.

Creativity in persons at-risk for bipolar disorder-A pilot study.

AIM: The association between bipolar disorder and creativity may be related to symptoms of the disorder itself or personality traits present before the onset. To further explore the relationship between creativity and clinical risk for bipolar disorder, creativity among individuals with a history of depressive disorder and varying risk for future (hypo-)manic episodes was assessed and compared. METHODS: Thirty-eight participants completed the diagnostic process, including Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Diagnosis, Hamilton Depression Scale and Young Mania Rating Scale. The early detection tools Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P), Early Phase Inventory for Bipolar Disorders (EPIbipolar) and bipolar-at-risk-(BAR) criteria were used to assign participants into different at-risk groups. Assessment of creativity included Barron-Welsh Art Scale (BWAS) and Creative Achievement Questionnaire (CAQ). Scores were compared between low- and high-risk groups for the development of bipolar disorder. RESULTS: Participants meeting BAR criteria scored significantly higher on the BWAS than the non-BAR group (P = 0.03). EPIbipolar groups did not differ significantly in creativity scores. Participants with mood swings, especially when associated with increased activity and euphoric features, had significantly higher BWAS scores compared to individuals without mood swings (P = 0.04). Sleep disturbances, substance abuse, anxiety, ADHD and behavioural disturbances in childhood or adolescence had no effect on creativity level or achievement scores. Generalisability was reduced by small sample size and inclusion of depressive participants only considered at-risk for bipolar disorder. CONCLUSIONS: There is evidence of increased creativity, but not of higher creative achievements, in persons at-risk of bipolar disorder. Mood swings are strongly associated with creativity.

Impulsivity predicts illness severity in long-term course of bipolar disorder: A prospective approach.

BACKGROUND: Bipolar disorder is a common, severe and chronic mental illness. Despite this, predictors of illness severity remain poorly understood. Impulsivity is reported to be associated with bipolar disorder and aggravating comorbidities. This study therefore sought to examine the predictive value of impulsivity for determining illness severity in euthymic bipolar disorder patients. METHODS: Baseline trait impulsivity of 120 bipolar euthymic patients (81 bipolar disorder I [68%], 80 female [67%]) and 51 healthy controls was assessed using Barratt Impulsiveness Scale 11. The impact of impulsivity on illness severity (measured with morbidity index) was prospectively tested in 97 patients with sufficient follow-up data (average observation time: 54.4 weeks), using linear regression analysis. RESULTS: Barratt Impulsiveness Scale 11 total (ß = 0.01; p < 0.01) and in particular Barratt Impulsiveness Scale 11 attentional subscale scores (ß = 0.04; p < 0.001) predicted illness severity in bipolar disorder, while controlling for other clinical variables. Only age at onset persisted as an additional, but less influential predictor. Barratt Impulsiveness Scale 11 total scores and Barratt Impulsiveness Scale 11 attentional subscale scores were significantly higher in euthymic patients compared to controls. This was not observed for the motor or non-planning subscale scores. LIMITATIONS: The average year-long observation time might not be long enough to account for the chronic course of bipolar disorder. CONCLUSION: Trait impulsivity and particularly attentional impulsivity in euthymic bipolar patients can be strong predictors of illness severity in bipolar disorder. Future studies should explore impulsivity as a risk assessment for morbidity and as a therapeutic target in bipolar disorder patients.

Comparison of Subjective and Objective Sleep Estimations in Patients with Bipolar Disorder and Healthy Control Subjects.

Background. Several studies have described but not formally tested discrepancies between subjective and objective measures of sleep. Study Objectives. To test the hypothesis that patients with bipolar disorder display a systematic bias to underestimate sleep duration and overestimate sleep latency. Methods. Actimetry was used to assess sleep latency and duration in 49 euthymic participants (bipolar = 21; healthy controls = 28) for 5-7 days. Participants simultaneously recorded estimated sleep duration and sleep latency on a daily basis via an online sleep diary. Group differences in the discrepancy between subjective and objective parameters were calculated using t-tests and corrected for multiple comparisons. Results. Patients with bipolar disorder significantly underestimated their sleep duration but did not overestimate their sleep latency compared to healthy controls. Conclusions. Studies utilizing diaries or questionnaires alone in patients with bipolar disorders may systematically underestimate sleep duration compared to healthy controls. The additional use of objective assessment methods such as actimetry is advisable.

Type 2 diabetes and pre-diabetic abnormalities in patients with bipolar disorders.

BACKGROUND: Abnormalities in the glucose metabolism cause nervous and organic damage and are a cardiovascular risk factor. They could be a main cause for the increased morbidity and mortality rates found in patients with bipolar disorders. The exact prevalence of diabetes and pre-diabetic abnormalities, however, is not clear. METHODS: 85 euthymic outpatients with bipolar disorders from two university hospitals in Germany underwent an oral glucose tolerance test, laboratory screening and clinical measurements. Socio-demographic data, medication, severity of illness, global functioning and life quality were assessed. RESULTS: Diabetes mellitus was found in 7% of the patients, pre-diabetic abnormalities in 27%. The group of patients with abnormalities in the glucose metabolism had significantly lower quality of life and global functioning. Higher BMI, leptin, triglycerides and CRP levels significantly increased the likelihood for pre-diabetes/diabetes. LIMITATIONS: The low sample size did only allow limited assessment of impact of medication on the results. No healthy controls were assessed. CONCLUSIONS: One-third of the patients with bipolar disorders showed abnormalities in the glucose metabolism and this was associated with impaired global functioning and lower quality of life. Early detection and intervention strategies fitting the needs of patient with bipolar disorder are needed to improve both physical and mental health.

Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.

BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.

Characteristics, symptomatology and naturalistic treatment in individuals at-risk for bipolar disorders: baseline results in the first 180 help-seeking individuals assessed at the Dresden high-risk project.

BACKGROUND: Considering results from the early recognition and intervention in psychosis, identification and treatment of individuals with at-risk states for the development of bipolar disorders (BD) could improve the course and severity of illness and prevent long-term consequences. Different approaches to define risk factors and groups have recently been published, data on treatment options are still missing. METHODS: Help-seeking persons at the early recognition center in Dresden, Germany, were assessed with a standardized diagnostic procedure including following risk factors for BD: familial risk, increasing mood swings, subsyndromal (hypo)manic symptoms, specific sleep and circadian rhythm disturbances, anxiety/fearfulness, affective disorder, decreased psychosocial functioning, increasing periodic substance use, and attention-deficit/hyperactivity disorder. Based on symptomatology and current and/or life-time psychiatric diagnosis, subjects with an at-risk state were offered individual treatment options. RESULTS: Out of 180 referred and screened persons, 29 (16%) met criteria for at-risk state for BD. Altogether, 27 (93%) at-risk individuals fulfilled criteria for a current and/or life-time mental illness other than BD; 14 (48%) had received pharmacological and/or psychotherapeutic treatment in the past. Treatments recommended included psychoeducation (100%), psychotherapy alone (62%), pharmacotherapy alone (17%), and psychotherapy+pharmacotherapy (14%). CONCLUSIONS: To identify at-risk states for BD, a multifactorial approach including all known risk markers should be used. As most at-risk patients meet criteria for other mental disorders, the short- and long-term impact of different treatment strategies on symptomatic, functional and diagnostic outcomes requires detailed investigation. LIMITATIONS: Small sample size of at-risk individuals, lack of sufficient prospective data and control groups.

[Early recognition centers for mental disorders - a complementary supply in the german health system]. / Früherkennungszentren für psychische Erkrankungen - ein Komplementärangebot der psychiatrischen Regelversorgung in Deutschland.

OBJECTIVE: Mental disorders are identified and treated too late, because of stigma, deficient information in the population and lack of specific supply in the public health systems. Another problem is the deficient cooperation between psychiatry and child psychiatry. Therefore early recognition centers were founded, in Germany primarily with focus on psychosis and in research settings. METHODS: The early recognition center in Dresden offers a low-threshold and anonym service for young people independent of diagnosis. The multiprofessional team including psychologists, psychiatrists and child psychiatrists applies defined standards. In addition to standard history taking and formally assessing psychopathology, early recognition instruments for psychosis and bipolar disorders are used as appropriate. RESULTS: In 167 out of 192 individuals a structured diagnostic procedure was recommended, 149 persons (89 %) completed the procedure. Thereof 78 (52 %) persons fulfilled criteria for one, 21 (14 %) persons for two and 10 (7 %) persons for three mental disorders. 49 (33 %) persons fulfilled criteria for (Ultra)high risk for psychosis and/or bipolar disorders. CONCLUSIONS: In the majority of cases diagnostic criteria for at least one mental illness was already fulfilled. All diagnosis and stages from prodromal till chronic were represented. The high percentage of subjects fulfilling criteria for (ultra)high risk-constellations offers the chance for early interventions. The implementation of early detection centers for psychiatric disorders seems reasonable and necessary.

The characteristics of sleep in patients with manifest bipolar disorder, subjects at high risk of developing the disease and healthy controls.

Sleep is highly altered during affective episodes in patients with bipolar disorder. There is accumulating evidence that sleep is also altered in euthymic states. A deficit in sleep regulation may be a vulnerability factor with aetiological relevance in the development of the disease. This study aims to explore the objective, subjective and lifetime sleep characteristics of patients with manifest bipolar disorder and persons with an elevated risk of developing the disease. Twenty-two patients with bipolar I and II disorder, nine persons with an elevated risk of developing the disorder and 28 healthy controls were evaluated with a structured interview to characterize subjective and lifetime sleeping habits. In addition, participants wore an actimeter for six nights. Patients with bipolar disorder had longer sleep latency and duration compared with healthy controls as determined by actigraphy. The subjective and lifetime sleep characteristics of bipolar patients differed significantly from healthy controls. The results of participants with an elevated risk of developing the disorder had subjective and lifetime characteristics that were largely analogous to those of patients with manifest bipolar disorder. In particular, both groups described recurring insomnia and hypersomnia, sensitivity to shifts in circadian rhythm, difficulties awakening and prolonged sleep latency. This study provides further evidence that sleep and circadian timing are profoundly altered in patients with bipolar disorder. It may also tentatively suggest that sleep may be altered prior to the first manic episode in subjects at high risk.