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Background: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features., Methods: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites ( N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPI bipolar )., Results: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPI bipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance., Conclusions: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long‑term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk., Competing Interests: Declaration of Competing Interest JM, KLB, CB, KL, CS, JM, GJ, AJF, ML, AB, AR, SM, TS, TK, IF, AJ, UD, SKÖ, PFP, LMH, PR, SB, PM, BM and AP state to have no conflict of interest. SKS has received author's and advisory honoraria from Takeda/Shire and Medice Arzneimittel Pütter GmbH in the last 3 years. AR serves on advisory boards and receives speaker's honoraria from Medice, Shire/Takeda, Janssen, neuraxpharm, Servier and SAGE. MB has received grant support from the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung, and the European Commission. He served as a consultant to GH Research, Janssen-Cilag, neuraxpharm, Novartis, Shire International, Sunovion, and Takeda, and received fees from Aristo, Hexal, Janssen-Cilag, and Sunovion. CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic., (Copyright © 2023. Published by Elsevier B.V.)

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li + PGS ) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li + PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi + Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li + PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li + PGS was positively associated with lithium treatment response in the ConLi + Gen cohort, in both the categorical (P = 9.8 × 10 - 12 , R 2  = 1.9%) and continuous (P = 6.4 × 10 - 9 , R 2  = 2.6%) outcomes. Compared to bipolar patients in the 1 st decile of the risk distribution, individuals in the 10 th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10 - 4 , R 2  = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li + PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment., (© 2023. The Author(s).)

Background: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD., Methods: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity., Results: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention., Conclusions: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD., (Copyright © 2023. Published by Elsevier Inc.)

Background: In bipolar disorder, impaired affective theory of mind (aToM) performance and aberrant neural activation in the ToM brain network partly explain social functioning impairments. However, it is not yet known whether psychotherapy of bipolar disorder influences neuroimaging markers of aToM., Methods: In this study, conducted within the multicentric randomized controlled trial of the BipoLife consortium, patients with euthymic bipolar disorder underwent 2 group interventions over 6 months (mean = 28.45 weeks): 1) a specific, cognitive behavioral intervention (specific psychotherapeutic intervention [SEKT]) (n = 31) targeting impulse regulation, ToM, and social skills and 2) an emotion-focused intervention (FEST) (n = 28). To compare the effect of SEKT and FEST on neural correlates of aToM, patients performed an aToM task during functional magnetic resonance imaging before and after interventions (final functional magnetic resonance imaging sample of pre- and postcompleters, SEKT: n = 16; FEST: n = 17). Healthy control subjects (n = 32) were scanned twice with the same time interval. Because ToM was trained in SEKT, we expected an increased ToM network activation in SEKT relative to FEST postintervention., Results: Both treatments effectively stabilized patients' euthymic state in terms of affective symptoms, life satisfaction, and global functioning. Confirming our expectations, SEKT patients showed increased neural activation within regions of the ToM network, bilateral temporoparietal junction, posterior cingulate cortex, and precuneus, whereas FEST patients did not., Conclusions: The stabilizing effect of SEKT on clinical outcomes went along with increased neural activation of the ToM network, while FEST possibly exerted its positive effect by other, yet unexplored routes., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Existing guidelines recommend psychopharmacological treatment for the management of schizophrenia and bipolar disorder as part of holistic treatment concepts. About half of the patients do not take their medication regularly, although treatment adherence can prevent exacerbations and re-hospitalizations. To date, the relationship between medication adherence and cognitive performance is understudied. Therefore, this study investigated the relationship between medication adherence and cognitive performance by analyzing the data of 862 participants with schizophrenia-spectrum and bipolar disorders (mean [SD] age, 41.9 [12.48] years; 44.8% female) from a multicenter study (PsyCourse Study). Z-scores for three cognitive domains were calculated, global functioning was measured with the Global Assessment of Functioning Scale, and adherence was assessed by a self-rating questionnaire. We evaluated four multiple linear regression models and built three clusters with hierarchical cluster analyses. Higher adherence behavior (p < 0.001) was associated with better global functioning but showed no impact on the cognitive domains learning and memory, executive function, and psychomotor speed. The hierarchical cluster analysis resulted in three clusters with different cognitive performances, but patients in all clusters showed similar adherence behavior. The study identified cognitive subgroups independent of diagnoses, but no differences were found in the adherence behavior of the patients in these new clusters. In summary, medication adherence was associated with global but not cognitive functioning in patients with schizophrenia-spectrum and bipolar disorders. In both diagnostic groups, cognitive function might be influenced by various factors but not medication adherence., (© 2023. The Author(s).)

Importance: No clinically applicable diagnostic test exists for severe mental disorders. Lipids harbor potential as disease markers., Objective: To define a reproducible profile of lipid alterations in the blood plasma of patients with schizophrenia (SCZ) independent of demographic and environmental variables and to investigate its specificity in association with other psychiatric disorders, ie, major depressive disorder (MDD) and bipolar disorder (BPD)., Design, Setting, and Participants: This was a multicohort case-control diagnostic analysis involving plasma samples from psychiatric patients and control individuals collected between July 17, 2009, and May 18, 2018. Study participants were recruited as consecutive and volunteer samples at multiple inpatient and outpatient mental health hospitals in Western Europe (Germany and Austria [DE-AT]), China (CN), and Russia (RU). Individuals with DSM-IV or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of SCZ, MDD, BPD, or a first psychotic episode, as well as age- and sex-matched healthy controls without a mental health-related diagnosis were included in the study. Samples and data were analyzed from January 2018 to September 2020., Main Outcomes and Measures: Plasma lipidome composition was assessed using liquid chromatography coupled with untargeted mass spectrometry., Results: Blood lipid levels were assessed in 980 individuals (mean [SD] age, 36 [13] years; 510 male individuals [52%]) diagnosed with SCZ, BPD, MDD, or those with a first psychotic episode and in 572 controls (mean [SD] age, 34 [13] years; 323 male individuals [56%]). A total of 77 lipids were found to be significantly altered between those with SCZ (n = 436) and controls (n = 478) in all 3 sample cohorts. Alterations were consistent between cohorts (CN and RU: [Pearson correlation] r = 0.75; DE-AT and CN: r = 0.78; DE-AT and RU: r = 0.82; P < 10-38). A lipid-based predictive model separated patients with SCZ from controls with high diagnostic ability (area under the receiver operating characteristic curve = 0.86-0.95). Lipidome alterations in BPD and MDD, assessed in 184 and 256 individuals, respectively, were found to be similar to those of SCZ (BPD: r = 0.89; MDD: r = 0.92; P < 10-79). Assessment of detected alterations in individuals with a first psychotic episode, as well as patients with SCZ not receiving medication, demonstrated only limited association with medication restricted to particular lipids., Conclusions and Relevance: In this study, SCZ was accompanied by a reproducible profile of plasma lipidome alterations, not associated with symptom severity, medication, and demographic and environmental variables, and largely shared with BPD and MDD. This lipid alteration signature may represent a trait marker of severe psychiatric disorders, indicating its potential to be transformed into a clinically applicable testing procedure.

Biological research and clinical management in psychiatry face two major impediments: the high degree of overlap in psychopathology between diagnoses and the inherent heterogeneity with regard to severity. Here, we aim to stratify cases into homogeneous transdiagnostic subgroups using psychometric information with the ultimate aim of identifying individuals with higher risk for severe illness. 397 participants of the PsyCourse study with schizophrenia- or bipolar-spectrum diagnoses were prospectively phenotyped over 18 months. Factor analysis of mixed data of different rating scales and subsequent longitudinal clustering were used to cluster disease trajectories. Five clusters of longitudinal trajectories were identified in the psychopathologic dimensions. Clusters differed significantly with regard to Global Assessment of Functioning, disease course, and-in some cases-diagnosis while there were no significant differences regarding sex, age at baseline or onset, duration of illness, or polygenic burden for schizophrenia. Longitudinal clustering may aid in identifying transdiagnostic homogeneous subgroups of individuals with severe psychiatric disease., (Copyright © 2022. Published by Elsevier B.V.)

In psychiatry, there has been a growing focus on identifying at-risk populations. For schizophrenia, these efforts have led to the development of early recognition and intervention measures. Despite a similar disease burden, the populations at risk of bipolar disorder have not been sufficiently characterized. Within the BipoLife consortium, we used magnetic resonance imaging (MRI) data from a multicenter study to assess structural gray matter alterations in N = 263 help-seeking individuals from seven study sites. We defined the risk using the EPIbipolar assessment tool as no-risk, low-risk, and high-risk and used a region-of-interest approach (ROI) based on the results of two large-scale multicenter studies of bipolar disorder by the ENIGMA working group. We detected significant differences in the thickness of the left pars opercularis (Cohen's d = 0.47, p = 0.024) between groups. The cortex was significantly thinner in high-risk individuals compared to those in the no-risk group (p = 0.011). We detected no differences in the hippocampal volume. Exploratory analyses revealed no significant differences in other cortical or subcortical regions. The thinner cortex in help-seeking individuals at risk of bipolar disorder is in line with previous findings in patients with the established disorder and corresponds to the region of the highest effect size in the ENIGMA study of cortical alterations. Structural alterations in prefrontal cortex might be a trait marker of bipolar risk. This is the largest structural MRI study of help-seeking individuals at increased risk of bipolar disorder., (© 2021. The Author(s).)

There is increasing evidence from genetic, biochemical, pharmacological, neuroimaging and post-mortem studies that immunological dysregulation plays a crucial role in the pathogenesis of psychoses. The involvement of microglia in schizophrenia and bipolar disorder (BD) has remained controversial, however, since results from various post-mortem studies are still inconclusive. Here, we analyzed the estimated density of microglia of age-matched individuals with schizophrenia (n = 17), BD (n = 13), and non-psychiatric control subjects (n = 17) in the anterior midcingulate cortex (aMCC), a brain area putatively involved in the pathogenesis of psychoses, using ionized calcium binding adaptor molecule 1 (Iba1)-immunohistochemistry. The microglial cells displayed a homogenously distributed Iba1-staining pattern in the aMCC with slightly varying activation states in all three groups. The estimated microglial densities did not differ significantly between individuals with schizophrenia, BD and control subjects. Remarkably, when both hemispheres were investigated separately within the three groups, the density was significantly lateralized towards the right aMCC in schizophrenia (p = 0.01) and-even more evident-in BD subjects (p = 0.008). This left-right lateralization was not observed in the control group (p = 0.52). Of note, microglial density was significantly lower in BD individuals who did not commit suicide compared with BD individuals who died from suicide (p = 0.002). This difference was not observed between individuals with BD who committed suicide and controls. The results, tentatively interpreted, suggest a hitherto unknown increased lateralization of microglial density to the right hemisphere in both psychiatric groups. If confirmed in independent samples, lateralization should be considered in all post-mortem studies on microglia. Density differences between suicide and non-suicide individuals needs further elucidation.

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., (© 2020 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

In this case report, we report an ethical problem that we faced in the course of an interview study on open-door policies in psychiatry with persons under involuntary commitment. One of the interviewees was a young woman with bipolar disorder who was under involuntary commitment at the time of the interview. While the woman had been assessed as competent and gave informed consent to research participation, her manic symptoms increased when the interview became increasingly distressing for her. Because of this, we decided to break off the interview and resume it at a later point of time. Within the research team, we raised the following ethical questions: (1) Was the participant, contrary to the initial assessment, unable to give consent for the study? (2) Was the voluntariness of her research participation compromised by her manic symptoms and involuntary commitment? (3) Should the participant have been excluded from the study against her expressed wish? (4) Should we have refrained from interviewing persons who were still under involuntary commitment?

Objectives: Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients., Methods: A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18 years] vs adulthood [>18 years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models., Results: BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment., Conclusions: The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype., (© 2018 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.)

Characterized by the switch of manic and depressive phases, bipolar disorder was described as early as the fifth century BC. Nevertheless up to date, the underlying neurobiology is still largely unclear, assuming a multifactor genesis with both biological-genetic and psychosocial factors. Significant process has been achieved in recent years in researching the causes of bipolar disorder with modern molecular biological (e.g., genetic and epigenetic studies) and imaging techniques (e.g., positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)). In this chapter we will first summarize our recent knowledge on the etiology of bipolar disorder. We then discuss how several factors observed to contribute to bipolar disorder in human patients can be manipulated to generate rodent models for bipolar disorder. Finally, we will give an overview on behavioral test that can be used to assess bipolar-disorder-like behavior in rodents.

To assess the occurrence and frequency of bipolar at-risk symptoms in a large sample of previously undiagnosed students using the new screening tool Bochumer Screeningbogen Bipolar (BSB). 2329 students of the Ruhr-University Bochum, Germany completed online demographic data as well as various self-rating questionnaires (BSB; Hypomania Checklist 32; Altman Self-Rating Mania Scale; Beck Depression Inventory). Within the student cohort (64.4% female, mean age 24.3 years) every fifth student currently suffered from moderate to severe depressive symptoms; every sixth student had already thought about suicide and every other student reported a history of mood swings. The most frequently reported depressive symptoms included physical exhaustion, depressed mood, and tiredness. The most frequently reported (hypo)manic symptoms included physical agitation, feeling extremely energetic, and lack of concentration. The BSB showed good convergent validity with other established questionnaires capturing depressive or (hypo)manic symptoms, as well as a stable administration of underlying constructs. The BSB correlated significantly with the already established applied questionnaires. The predictive power of the BSB regarding the development of bipolar disorder cannot be correctly quantified at present. The further purpose of this exploratory web-based study should be to examine the validity of the presented measures in a longitudinal design., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Based on many clinical and preclinical findings the 'vigilance regulation model of mania' postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study - a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) - assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20-40mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20-40mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania., Trial Registration: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605)., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

Background: Prodromal symptoms prior to first episode mania/hypomania have been reported. However, the relationship between temperament and manic/hypomanic prodromal symptoms has not been investigated. We hypothesized that subjects scoring higher on cyclothymic and irritable temperament scales show more manic/hypomanic prodromal symptoms., Method: Euthymic patients diagnosed with bipolar-I or -II disorder within 8 years underwent retrospective assessments with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire (TEMPS-A) and the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R)., Results: Among 39 subjects (36.1 ± 9.9 years, females = 59%, bipolar-I = 62%) 100% and 92.3% reported subthreshold mania (mean = 7.4 ± 2.9) or subthreshold depressive symptoms (mean = 2.4 ± 1.5), and 87.2% and 43.6% reported general psychopathology (mean = 3.2 ± 2.0) or subthreshold psychotic symptoms (mean = 0.7 ± 1.0) prior to their first hypo-/manic episode. Subjects with higher cyclothymic and irritable temperament scores showed more subthreshold symptoms prior to the first manic/hypomanic episode, mainly subthreshold hypo-/manic symptoms (cyclothymic temperament r = 0.430; p = 0.006; irritable temperament r = 0.330; p = 0.040), general psychopathology symptoms (cyclothymic temperament r = 0.316; p = 0.05; irritable temperament r = 0.349; p = 0.029) and subthreshold psychotic symptoms (cyclothymic temperament r = 0.413; p = 0.009). In regression analyses, cyclothymic temperament explained 16.1% and 12.5% of the variance of the BPSS-R total score (p = 0.045) and psychosis subscore (p = 0.029)., Limitations: Retrospective study, no control group, small sample size., Conclusion: We present data, which indicate a relationship between cyclothymic and irritable temperament and prodromal symptoms prior to the first manic/hypomanic episode. These findings support the notion that assessing cyclothymic temperament to identify people at-risk of developing bipolar-I and -II disorder may help to increase the predictive validity of applied at-risk criteria., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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.

Objective: Suboptimal availability of circulating thyroid hormones may contribute to the high rate of treatment failures in bipolar disorder. This study tested the efficacy of adjunctive treatment with supraphysiologic doses of levothyroxine in patients with bipolar depression and the hypothesis that women would display a better outcome compared to men., Method: The aims of this multicenter, 6-week, double-blind, randomized, placebo-controlled fixed-dose (300 μg/d) trial conducted from 2004 to 2009 were to assess efficacy and tolerability of levothyroxine adjunctive to continuing treatment with mood stabilizer and/or antidepressant medication for patients with bipolar I or II disorder, currently depressed (DSM-IV), and to investigate gender differences in treatment response. The primary efficacy variable was mean change in Hamilton Depression Rating Scale (HDRS) score., Results: Of 74 patients enrolled in the study, 62 (35 with bipolar I; mean age = 44.9 years) were randomized. Mean change in HDRS score from randomization to week 6 was larger in the levothyroxine group compared to the placebo group, with a 2.7-point difference (decline of -7.8 [38.3%] vs -5.1 [25.5%]; last-observation-carried-forward analysis). The course of HDRS scores over time from randomization to week 6 was significantly different between groups at week 4 (P = .046) but not at the end of the placebo-controlled phase (P = .198). The secondary analysis of women (n = 32) revealed a significant difference between groups in mean change in HDRS score (-16.6% placebo vs -42.4% levothyroxine, P = .018). A mixed-effects model for repeated-measures analysis showed a significant between-group difference in HDRS score (6.8, P = .012) for women. High thyroid-stimulating hormone levels, indicating suboptimal levels of circulating thyroid hormones, were predictive for positive treatment outcome in women treated with levothyroxine in a linear regression model (F3 = 3.47; P = .05)., Discussion: This trial demonstrated that patients treated with levothyroxine did numerically better than those treated with placebo; however, the study failed to detect a statistically significant difference between the 2 groups in the primary outcome measure due to a high placebo response rate. Previous findings that women show better improvement in depression scores with levothyroxine compared to men were confirmed., Trial Registration: ClinicalTrials.gov identifier: NCT01528839., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Objectives: To assess the phenomenology and course of pre-(hypo)manic and pre-depressed prodromal symptoms, including mood swings, as precursors of bipolar disorder (BD) in a German multi-center study., Methods: Semi-structured interviews [Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R); Semi-structured Interview for Mood Swings] were administered to patients within 8 years of BD (BD I, BD II) onset., Results: Forty two outpatients were included (40.5% male, mean age 35.1±10.0 years, illness onset at 30.5±9.5 years). Feeling extremely energetic (85.7%), racing thoughts (78.6%), physical agitation (76.2%), overtalkativeness (71.4%), and low sleep requirement (71.4%) occurred most frequently prior to the first (hypo)manic episode, whereas depressed mood (83.0%), reduced vitality (81.0%), physical exhaustion (78.6%), tiredness (76.2%), and insomnia (66.7%) preceded pre-depressively. Mood lability (p=.006), odd ideas (p=.003) and the psychosis index score (p=.003) differed significantly in prevalence depending on the episodes' mood. Extremely energetic (p=.046), overtalkativeness (p<.001), and racing thoughts (p=.013) lasted significantly longer prior to depression. Neither severity nor frequency of prodromal symptoms differed significantly. Most of the symptoms emerged during the proximal prodromal phase. Links between mood swings and subsequent BD were found., Limitations: Symptoms were evaluated retrospectively with self-reporting tools in bipolar patients from academic treatment settings without comparison to clinical controls., Conclusions: Not only specific depressive or manic but also general symptoms occurred prior to both affective episodes. The pre-depressive prodrome lasted longer than the pre-manic one, but severity and frequency did not differ significantly. Mood swings and disturbed diurnal rhythm occurred prior to both episodes as early signs of BD., (© 2013 Elsevier B.V. All rights reserved.)

Background: Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the 'vigilance regulation model of mania' which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania., Methods/design: A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression-Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-'Vigilance Algorithm Leipzig' (VIGALL)., Discussion: A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives.

Background: In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients., Methods: In the EPOS (European Prediction of Psychosis Study) project, six European outpatient centres in four countries examined 245 young help-seeking patients, who fulfilled the inclusion criteria for clinical risk of psychosis according to the Structured Interview for Prodromal Syndromes (SIPS 3.0) or the Bonn Scale for the Assessment of Basic Symptoms - Prediction List basic symptoms (BASBS-P). Patients who had experienced a psychotic episode lasting more than one week were excluded. Baseline and life-time diagnoses were assessed by the Structured Clinical Interview for DSM-IV (SCID-I). TTP was defined by continuation of BLIPS for more than seven days and predicted in Cox-regression analysis., Results: Altogether, 71% of the CHR patients had one or more life-time and 62% one or more current SCID-I diagnosis; about a half in each category received a diagnosis of life-time depressive and anxiety disorder. Currently, 34% suffered from depressive and 39% from anxiety disorder. Four percent received a current SCID diagnosis of bipolar, and 6.5% of somatoform disorder. During follow-up, 37 (15.1%) patients had developed full-blown psychosis. In bivariate analyses, current non-psychotic bipolar disorder associated significantly with TTP. In multivariate analyses, current bipolar disorder, somatoform and unipolar depressive disorders associated positively, and anxiety disorders negatively, with TTP., Conclusions: Both life-time and current mood and anxiety disorders are highly prevalent among clinical help-seeking CHR patients and need to be carefully evaluated. Among CHR patients, occurrence of bipolar, somatoform and depressive disorders seems to predict TTP, while occurrence of anxiety disorder may predict non-transition to psychosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: The precise characterisation of a high risk status for the development of a psychiatric disorder and the question of how well this predicts disease manifestation is of major importance as negative consequences of late diagnosis and treatment have been well demonstrated. In the absence of well defined and disease specific biological markers for bipolar disorder, the recognition of premature stages must rely on combinations of risk factors that have been associated with later disease manifestation., Methods: A review of the literature and our experience from the Early Recognition Centre led us to identify symptom constellations., Results: Individual categories defined and grouped included: (I) genetic risk, (II) substance use, misuse or dependence, (III) diagnosis/suspected diagnosis of attention deficit hyperactivity disorder, (IV) pronounced creativity, (V) impairment in psychosocial functioning, (VI) subthreshold affective symptoms, and (VII) early symptomatology including (a) changes in sleep and circadian rhythm, (b) changes in mood, mood swings/affective lability, (c) fearfulness/anxiety, and (d) dissociative symptoms. These risk constellations were operationalised and a new risk assessment instrument, the Early Phase Inventory for Bipolar Disorders (EPIbipolar) was developed., Limitations: Challenges regarding the validity of the data on which the instrument is based, specificity of and correlations between risk categories, and ethical considerations were encountered., Conclusions: Further use of EPIbipolar in research should help to refine prodromal features and narrow these down to a less cumbersome core that can be used to develop a shortened tool for use in clinical care. Prospective longitudinal research is needed to establish the predictive validity of this novel bipolar disorder risk assessment tool., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Transcranial brain sonography (TCS) has become a reliable and sensitive diagnostic tool in the evaluation of extrapyramidal movement disorders. Alterations of brainstem raphe (BR) have been depicted by TCS in major depression but not in bipolar disorder. The aim of our study was to evaluate BR echogenicity depending on the different conditions of bipolar patients. Echogenicities of dopaminergic basal ganglia structures were assessed for the first time in bipolar disorder. Thirty-six patients with bipolar I disorder (14 depressed, 8 manic, 14 euthymic) were compared to 35 healthy controls. Echogenicities were investigated according to the examination protocol for extrapyramidal disorders using a Siemens Sonoline® Elegra system. The sonography examiner was blinded for clinical rating scores. Six patients (16.7%) showed hyperechogenicity of the substantia nigra. The raphe was hypoechogenic in 13 (36.1%) of the patients. No significant differences were seen between the subgroups. Compared to the control group, frequency of altered echogenicities did not reach statistical significance. The width of third ventricle was significantly larger in the patient group (3.8±-2.1 mm vs. 2.7±1.2 mm). Depressed bipolar patients with reduced BR echogenicity showed significantly higher scores on the Hamilton Depression Rating Scale as well as the Montgomery-Åsberg Depression Rating Scale. In contrast to unipolar depression, sonographic findings of bipolar patients may generally indicate structural integrity of mesencephalic raphe structures. If bipolar disorder coexists with hypoechogenic raphe structure, depressive symptoms are more severe., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Introduction: There is a lack of data about post-traumatic stress disorder (PTSD) in European bipolar patients compared to the US-population. This study was conducted to ascertain the rates and types of traumatic events and PTSD in bipolar-I disorder., Methods: Euthymic bipolar patients were screened for lifetime diagnosis of PTSD using the Post-Traumatic Stress Diagnostic Scale and the Clinician Administered Post-traumatic Stress Disorder Scale., Results: A total of 74 patients (m = 30, f = 44) with diagnosis of bipolar-I disorder were assessed. 37 patients (50%) reported no trauma, 22 patients (29.7%) experienced traumatic events without diagnosis of PTSD and 15 patients (20.3%) had comorbid PTSD. Bipolar PTSD patients were at higher risk to be exposed to physical violence, parental disregard, alcohol dependence of parents, sexual assault by a family member or acquaintance. The number of siblings was higher and they had higher scores on the Hamilton Depression Rating Scale and the Global Assessment of Functioning Scale., Conclusions: Bipolar patients are more likely to experience traumatic events and PTSD is a relevant comorbid disorder. PTSD is associated with an increased illness severity of bipolar disorder.

Background/aims: Temperament and mood swings are promising indicators for the characterization of mood spectrum vulnerability. The aim of this study was to investigate the relationship between affective temperament and mood swings in bipolar disorder. We explored these clinical features retrospectively., Methods: Patients who met the criteria for bipolar I disorder were enrolled in the study. Exclusion criteria were partial remittance and a full affective or psychotic episode. Data concerning illness and family history, mood swings (semistructured interview for mood swings) and depression (Beck, Depression Inventory) were obtained. We examined premorbid temperament with the validated German version Temps-M of the original version Temps-A. Patients with and without mood swings were compared with respect to the dominant temperament., Results: Out of 20 bipolar patients, 6 subjects reported mood swings prior to the onset of affective disorder. Subjects with mood swings prior to the onset of bipolar disorder significantly correlated with a positive family history of affective disorders. Concerning cyclothymic and irritable temperament, bipolar affective patients with mood swings had higher scores. No differences were found between males and females., Conclusion: Our findings go in line with previous results that mood swings, as represented by the cyclothymic temperament, are present prior to the first onset of bipolar disorder in a subset of patients. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar disorder in order to prevent this illness. Further studies are indicated to clarify the correlation with genetic risk factors.

The combination of a long undetected illness and significant psychosocial impairment renders early identification and intervention a vital role in bipolar disorders. Early detection forms the basis for adequate education and for treatment from the beginning. Several lines of evidence indicate that the characterization of early phases in the development of bipolar disorders is feasible. Risk factors for the development of bipolar disorders have been established and a manic prodrome has been characterized that is sufficiently long to allow recognition and, potentially, intervention. Centers specifically focussing on early detection and prevention of bipolar disorders need to be established. More research in this field is warranted including both groups of symptomatic subjects and symptom-free persons, with and without a positive family history.

Objective: The simple insight in the central serotonergic activity would allow a more specific pharmacotherapy of disorders with serotonergic deficits and could thus serve as a predictive parameter. An antidepressive treatment could be chosen due to the verification or falsification of such a deficit with a serotonergic or noradrenergic substance. In search of predictive parameters we have investigated the loudness dependence of auditory evoked potentials (LDAEP), a parameter that has already been discussed concerning this matter, and serotonin levels in the human blood serum regarding their correlation., Methods: Eight outpatients of a lithium clinics were investigated neurophysiologically after blood samples had been taken., Results: A significant negative correlation between LDAEP and serotonin level in the serum was found, a low serotonin level correlates with a high LDAEP., Conclusions: The result of this pilot study justifies further investigations with larger sample sizes. In case of further and stable evidence the use of serotonin levels in the serum as a predicitve parameter is conceivable.

Rationale: Quetiapine was approved in Germany as an atypical antipsychotic for treatment of schizophrenia in 2000, followed by the approval as an antipsychotic for treatment of bipolar mania in 2003. The approval of quetiapine for treatment of bipolar depression is expected. We hypothesized that the psychogeriatric prescription pattern for quetiapine shifts from the psychotic to the affective spectrum., Methods: Retrospectively we screened discharge reports of all geriatric inpatients of the psychiatric department of the Ruhr-University of Bochum in the period from January 2001 until March 2006 and identified 208 individual patients aged over 60 years, who had received quetiapine as final medication. Age, gender, daily drug dose, year of treatment and diagnosis (according to ICD-10) were recorded and analyzed., Results: Over the six-year time span, the proportion of affective disorders (F3) as indication for quetiapine in the elderly increased, whereas the proportion of dementia (F0) as indication for quetiapine decreased significantly. The proportion of schizophrenic disorders (F2) treated with quetiapine did not change significantly., Discussion: Since the decision of the German Federal Court in 2002 'off label' use goes to the expenses of the prescriber. So the decrease of quetiapine in dementia is probably due to its 'off label' status in dementia. The psychogeriatric indication shift for quetiapine towards affective disorders could be the consequence of good clinical experiences with the drug and growing evidence for its antidepressant effect., Conclusion: In addition to controlled pharmacological trials prospective clinical research is needed to evaluate the prescription attitudes of clinicians., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale.

Mood disorders, including depressive and bipolar disorders, are the group of psychiatric disorders with the highest prevalence and disease burden. However, their pathophysiology remains poorly understood. Animal models are an extremely useful tool for the investigation of molecular mechanisms underlying these disorders. For psychiatric symptom assessment in animals, a meaningful behavioral phenotype is needed. Social behaviors constitute naturally occurring complex behaviors in rodents and can therefore serve as such a phenotype, contributing to insights into disorder related molecular changes. In this narrative review, we give a fundamental overview of social behaviors in laboratory rodents, as well as their underlying neuronal mechanisms and their assessment. Relevant behavioral and molecular changes in models for mood disorders are presented and an outlook on promising future directions is given. [ABSTRACT FROM AUTHOR]

Affective disorders are common, complex disorders representing one of the major challenges to global health in the 21st century. To mitigate the burden of disease, substantial public health efforts need to be undertaken since research on the causes and adequate treatment requires multidisciplinary approaches. These should integrate translational, and clinical research, aided by technological advancements in collecting and analysing comprehensive data. Here we present the rationale, concept, mission and vision of the recently founded National Centre of Affective Disorders (NCAD) in Germany. NCAD founding partners build on their previous successful cooperation within the German Research Network for Mental Disorders funded by the Federal Ministry of Education and Research (BMBF). They form an internationally pre-eminent network of integrative excellence, leading in science and contributing significantly to the improved care of affective disorder patients. The partners will provide complementary structures and innovative methods across the entire translational continuum from bench to clinical and real-world settings. The vision of the NCAD is to foster cross-disciplinary research from basic neuroscience to public mental health by close translational collaboration between academia, non-university research institutions, and international partners, including industry, to deliver cutting-edge research, innovative clinical services and evidence-based training to young clinicians and scientists. The mission is to accomplish research in a highly translational manner, especially with respect to clinical studies in a trans-sectoral way. This approach aims to ensure continuous improvement in the treatment and care provided to patients and an interdisciplinary environment for high-level research and education in affective disorders. [ABSTRACT FROM AUTHOR]

Introduction: According to the World Health Organization, medication adherence is defined as the extent to which a person's behavior corresponds with an agreed recommendation from a healthcare provider. Approximately 50% of patients do not take their medication as prescribed, and non-adherence can contribute to the progress of a disease. For patients suffering from mental diseases non-adherence plays an important role. Various factors have been proposed as contributing to non-adherence, however the literature remains heterogeneous dependent on the analyzed patient subgroups. This study comprehensively evaluates the association of sociodemographic, clinical, personality and quality of life related factors with medication adherence by analyzing data from the PsyCourse study. The PsyCourse study is a large and cross-diagnostic cohort of psychiatric patients from the affective-to-psychotic spectrum. Methods: The study sample comprised 1,062 patients from the PsyCourse study with various psychiatric diagnoses (mean [SD] age, 42.82 [12.98] years; 47.4% female). Data were analyzed to identify specific factors associated with medication adherence, and adherence was measured by a self-rating questionnaire. Odds ratios (OR) were estimated by a logistic regression for binary outcomes. Missing data were imputed using multiple imputation. Results: The following factors showed the strongest association with medication adherence: never having used illicit drugs (OR, 0.71), number of prescribed antipsychotics (OR, 1.40), the personality trait conscientiousness (OR, 1.26), and the environmental domain of quality of life (OR, 1.09). Conclusion: In a large and cross-diagnostic sample, we could show that a higher level of conscientiousness, a higher number of antipsychotic medication, a better quality of life within the environmental domain, and the absence of substance abuse contribute to a better medication adherence independent of the underlying disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Motor impairments of psychiatric patients can be assessed with digital recordings of handwriting tasks. The investigation of patients with bipolar affective disorders differentiates intraindividual changes related to the patient’s fluctuating affective states. An unmedicated 67-year-old male with 48-hour bipolar ultrarapid cycling was investigated during 8 consecutive days of ultrarapid cycling and 4 weeks later, after remission under treatment with valproate. The handwriting skills of the patient followed the same rhythmic changes of the psychopathology in the first part of the study and a steady pattern in the second phase, after remission. Therefore, it can be assumed that the handwriting skills reflect a state marker of the disease. Poorer handwriting skills on the manic days, as compared to the depressive ones, support the hypothesis of a low arousal in manic patients.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]