The clinical trajectory of emerging bipolar disorder among the high-risk offspring of bipolar parents: current understanding and future considerations.

Relatively little is known about the onset of bipolar disorder, yet the early illness course is already associated with significant morbidity and mortality. Therefore, characterizing the bipolar illness trajectory is key to risk prediction and early intervention advancement. In this narrative review, we discuss key findings from prospective longitudinal studies of the high-risk offspring of bipolar parents and related meta-analyses that inform us about the clinical trajectory of emerging bipolar disorder. Challenges such as phenotypic and etiologic heterogeneity and the non-specificity of early symptoms and syndromes are highlighted. Implications of the findings for both research and clinical practice are discussed. Bipolar disorder in young people at familial risk does not typically onset with a hypomanic or manic episode. Rather the first activated episode is often preceded by years of impairing psychopathological states that vary over development and across emerging bipolar subtype. Taking heterogeneity into account and adopting a more comprehensive approach to diagnosis seems necessary to advance earlier identification and our understanding of the onset of bipolar disorder

Hypomania Checklist-32 - cross-validation of shorter versions screening for bipolar disorders in an epidemiological study.

Self-reports such as Hypomania Checklist (HCL-32) can be used to enhance recognition of bipolar disorders, but they are often too long and only validated in clinical samples. The objectives of this study are therefore to test whether (i) the HCL-32 can be used for screening in the community and (ii) whether two previously suggested shorter versions would do as well. Data stemmed from the CoLaus|PsyColaus, a prospective cohort study which included randomly selected residents aged 35-66 years from an urban area. Participants underwent semistructured interviews to assess DSM-IV disorders and 1712 of them completed the HCL-32. Forty individuals (2.3%) were diagnosed as having BD. Compared to others, participants with BD scored significantly higher on the HCL-32. The HCL-32 had a sensitivity of 0.78 and specificity of 0.68. Very similar figures were found for two previously proposed shorter versions with 16 and 20 items. The results of confirmatory factor analysis and item response theory (IRT) models supported the postulated two-factor structure for the three HCL versions. Despite the low base rate of BD in this sample, the screening properties of the HCL-32 remained almost as good. Importantly, two previously proposed shorter versions performed as well, suggesting that those could be used without losing essential information

A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10(-6)) and GPC6 showed suggestive evidence for interaction with age (p approximate to 10(-7)). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism

Externalizing disorders and substance use: empirically derived subtypes in a population-based sample of adults.

PURPOSE: Attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are common externalizing disorders of childhood. The common effects of these disorders on substance abuse need further investigation. The current study investigated the joint clusters of childhood/adolescence ADHD, CD, and ODD, and their influence on substance abuse/dependence in a population-based sample of adults. METHODS: The data were drawn from the PsyCoLaus study (n = 3,720) conducted in Lausanne, Switzerland. The population-based sample included 238 subjects meeting criteria for ADHD/ODD/CD diagnoses before the age of 15. Latent class analyses (LCA) were performed to derive comorbidity subtypes, which were subsequently characterized with respect to psychosocial correlates and substance use. RESULTS: The best fit in LCAs was achieved with three latent classes: an ADHD subtype (35.7 %); an externalizing multimorbid subtype (33.6 %) involving ODD, ADHD, and CD; and a third subtype with CD (30.7 %). The CD subtype showed the highest association with substance use. Apart from this, the externalizing multimorbid subtype was also significantly linked to substance use. The ADHD subtype had only elevated frequencies for alcohol dependence in comparison with subjects that had no history of ADHD, ODD, and CD during childhood or adolescence. Finally, important interactions between subtypes and sex were observed with regard to substance use. CONCLUSIONS: This study provides evidence showing that subtyping the externalizing disorders, ADHD, ODD and CD, along their comorbidity patterns leads to important differences regarding substance use. This could have implications for the etiology, prevention, and treatment of substance use disorders

Individuals' quality of life linked to major life events, perceived social support, and personality traits.

PURPOSE: The aim of this study was to investigate the relationship between major recent life events that occurred during the last 5 years, social and personal resources, and subjective quality of life (QoL). METHODS: A total of 1801 participants from the general population (CoLaus/PsyCoLaus study) completed the Life Events Questionnaire, the Social Support Questionnaire, the NEO Five-Factor Inventory Revised, and the Manchester Short Assessment of Quality of Life. RESULTS: Major life events were modestly associated with the QoL (about 5 % of the explained variance). However, QoL was significantly related to perceived social support and personality traits (about 37 % of the explained variance). Particularly, perceived social support, extraversion and conscientiousness personality dimensions were positively linked to life satisfaction, whereas a high level of neuroticism was negatively associated with QoL. CONCLUSION: This study highlights the negative but temporary association between critical events and QoL. However, a combination of high conscientiousness and extraversion, and positive social support may explain better variances for a high-perceived QoL

Childhood adversities as specific contributors to the co-occurrence of posttraumatic stress and alcohol use disorders.

There is much evidence that alcohol use disorders (AUD) often co-occur with posttraumatic stress disorders (PTSD), and that the comorbid condition is associated with a more severe clinical profile than that of PTSD without AUD. However, little is known about the role of childhood adversities as specific risk factors for the development of AUD in individuals presenting with PTSD. The aim of the study was to explore whether specific stressors from the spectrum of trauma and childhood adversities contribute to the development of AUD among subjects with PTSD. From a large community sample, of N=140 individuals with PTSD, N=24 (17.14%) received an additional diagnosis of AUD with an onset after the onset of PTSD. Those with comorbid PTSD/AUD and those with PTSD only were compared regarding type and features of their trauma, childhood adversities and psychiatric comorbidity. Compared to PTSD alone, PTSD/AUD was associated with higher levels of stress in terms of childhood adversities; in particular, sexual abuse below the age of 16, but also with having been brought up in a foster home. PTSD/AUD was also associated with an earlier age of adverse events. Treatment of AUD should include standardized assessments of trauma, especially of trauma experienced during childhood

The association between self-reported and clinically determined hypomanic symptoms and the onset of major mood disorders.

Hypomanic symptoms may be a useful predictor of mood disorder among young people at high risk for bipolar disorder. To determine whether hypomanic symptoms differentiate offspring of parents with bipolar disorder (high risk) and offspring of well parents (control) and predict the development of mood episodes. High-risk and control offspring were prospectively assessed using semi-structured clinical interviews annually and completed the Hypomania Checklist-32 Revised (HCL-32). Clinically significant sub-threshold hypomanic symptoms (CSHS) were coded. HCL-32 total and active or elated scores were higher in control compared with high-risk offspring, whereas 14% of high-risk and 0% of control offspring had CSHS. High-risk offspring with CSHS had a fivefold increased risk of developing recurrent major depression (P=0.0002). The median onset of CSHS in high-risk offspring was 16.4 (6-31) years and was before the onset of major mood episodes. CSHS are precursors to major mood episodes in high-risk offspring and could identify individuals at ultra-high risk for developing bipolar disorder. None. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license

Efficacy of an adjunctive brief psychodynamic psychotherapy to usual inpatient treatment of depression: Results of a randomized controlled trial.

For severe and chronic depression, inpatient treatment may be necessary. Current guidelines recommend combined psychological and pharmacological treatments for moderate to severe depression. Results for positive effects of combined treatment for depressed inpatients are still ambiguous. This randomised controlled trial examined the efficacy of adding an intensive and brief psychodynamic psychotherapy (IBPP) to treatment-as-usual (TAU) for inpatients with DSM-IV major depressive episode. The primary outcomes were reduction in depression severity, and response and remission rates at post-treatment, 3-month and 12-month follow-up points. A linear mixed model analysis (N=149) showed a higher reduction in the observer-rated severity of depressive symptoms at each follow-up point for the IBPP condition compared with the TAU condition (post-treatment ES=0.39, 95%CI 0.06-0.71; 3-month ES=0.46, 95%CI 0.14-0.78; 12-month ES=0.32, 95%CI 0.01-0.64). Response rate was superior in the IBPP group compared with the TAU group at all follow-up points (post-treatment OR =2.69, 95%CI 1.18-6.11; 3-month OR=3.47, 95%CI 1.47-8.25; 12-month OR=2.26, 95%CI 1.02-4.97). IBPP patients were more likely to be remitted 3 months (OR=2.82, 95%CI 1.12-7.10) and 12 months (OR=2.93, 95%CI 1.12-7.68) after discharge than TAU patients. Heterogeneous sample with different subtypes of depression and comorbidity. IBPP decreased observer-rated depression severity up to 12 months after the end of treatment. IBPP demonstrated immediate and distant treatment responses as well as substantial remissions at follow-up. IBPP appears to be a valuable adjunct in the treatment of depressed inpatients