The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD

High leptin levels are associated with migraine with aura.

Background Migraine is a prevalent disorder characterised by recurrent headache attacks preceded or accompanied by aura in a subgroup of patients. Migraine often occurs together with major depressive disorder (MDD). Alterations of adipokine levels have been reported both in migraine and in MDD. In this cross-sectional study, we aimed to assess the associations between serum leptin and adiponectin levels and migraine or migraine subtypes. Analyses were adjusted for a lifetime history of MDD in order to investigate the association between adipokines and migraine under consideration of depression status. Methods We included 3025 participants from the CoLaus/PsyCoLaus study. The impact of leptin and adiponectin levels on a diagnosis of migraine was analysed by binary regression analyses, adjusting for variables known to influence adipokine levels. Subgroup analyses were conducted based on the presence of aura. Results Crude leptin levels were significantly higher in subjects with migraine than controls (Mann-Whitney U = 515,102, p = 6 × 10-7). When performing adjusted analyses, leptin levels were found to be significantly higher in subjects with migraine (odds ratio = 1.22, p = 0.024) and migraine with aura (odds ratio = 1.34, p = 0.004). Conclusion High leptin levels might play a role in the pathogenesis of migraine and migraine with aura

Annual Research Review: interparental conflict and youth psychopathology: an evidence review and practice focused update

The quality of the interparental relationship is recognized as an important influence on child and adolescent psychopathology. Historically, clinically-oriented research on this topic has focused on the impacts of parental divorce and domestic violence as primary interparental relationship influences on child outcomes, to the relative neglect of dimensional or qualitative features of the couple/interparental relationship for youth (child and adolescent) psychopathology. Recent research has highlighted that children are affected by attributes of interparental conflict, specifically how parents express and manage conflicts in their relationship, across a continuum of expressed severity and negativity – ranging from silence to violence. Further, new evidence highlights that children’s emotional, behavioral, social, academic outcomes and future interpersonal relationships are adversely affected by conflict between parents/carers whether adults are living together or not (i.e. married or separated), or where children are or are not genetically related to their rearing parents (e.g. adoption). We review evidence and present an integrated theoretical model, highlighting how children are affected by interparental conflict and what this evidence base means for effective intervention and prevention program development, as well as the development of possible cost-benefit models. Additionally, we review policy implications of this research and highlight some very recent examples of UK-based policy focusing on addressing the interparental relationship and its impact on youth psychopathology

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. Current combined MDD [β = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (β = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated

Differences between unipolar mania and bipolar-I disorder: Evidence from nine epidemiological studies.

Although clinical evidence suggests important differences between unipolar mania and bipolar-I disorder (BP-I), epidemiological data are limited. Combining data from nine population-based studies, we compared subjects with mania (M) or mania with mild depression (Md) to those with BP-I with both manic and depressive episodes with respect to demographic and clinical characteristics in order to highlight differences. Participants were compared for gender, age, age at onset of mania, psychiatric comorbidity, temperament, and family history of mental disorders. Generalized linear mixed models with adjustment for sex and age as well as for each study source were applied. Analyses were performed for the pooled adult and adolescent samples, separately. Within the included cohorts, 109 adults and 195 adolescents were diagnosed with M/Md and 323 adults and 182 adolescents with BP-I. In both adult and adolescent samples, there was a male preponderance in M/Md, whereas lifetime generalized anxiety and/panic disorders and suicide attempts were less common in M/Md than in BP-I. Furthermore, adults with mania revealed bulimia/binge eating and drug use disorders less frequently than those with BP-I. The significant differences found in gender and comorbidity between mania and BP-I suggest that unipolar mania, despite its low prevalence, should be established as a separate diagnosis both for clinical and research purposes. In clinical settings, the rarer occurrence of suicide attempts, anxiety, and drug use disorders among individuals with unipolar mania may facilitate successful treatment of the disorder and lead to a more favorable course than that of BP-I disorder

Examining parent and child agreement in the diagnosis of adolescent depression

Background: The diagnosis of depression in adolescents relies on identifying the presence of specific core and additional symptoms. Symptoms can be identified using structured or unstructured interviews and a range of questionnaire measures, which are completed by the young person and by a parent or carer. The aim of this research was to examine the inter- and intra-rater reliability of parent report and adolescent self-report of depression symptoms. Method: In a sample of parent-child dyads, where young people aged 13-17 were referred to a mental health service for depression, we examined adolescents’ (n = 46) and parents’ (n = 46) independent responses to the Schedule for Affective Disorders and Schizophrenia in School-Age Children (Kaufman et al., 1997) and the Mood and Feelings Questionnaire (Costello & Angold, 1988). Results: In the clinical interview, diagnostic criteria were more often met based on the adolescent’s report, and adolescents endorsed more symptoms of depression than their parents. Tentative results also suggest that parent-child agreement about specific symptoms was low. Comparing different measures of depression revealed that adolescent report on the questionnaire and interview was significantly correlated. However, there was no significant correlation between parent questionnaire and interview report. Conclusion: These results suggest that relying solely on parents to identify depression in their children may result in young people with depression being missed and therefore untreated. Young people themselves should be encouraged and enabled to recognise the symptoms of depression, and have an established pathway to services that offer assessment and treatment

Prevalence and correlates of prolonged fatigue in a U.S. sample of adolescents

Objective: Prolonged fatigue in adolescents has a major impact on social functioning and school attendance. In adults, prolonged fatigue substantially overlaps with mood and anxiety disorders. Extending the data to adolescents, the authors studied the prevalence and correlates of fatigue in a representative U.S. sample. Method: The participants were 10,123 adolescents ages 13-18 years from the National Comorbidity Survey Adolescent Supplement. They were interviewed about prolonged fatigue, defined as extreme fatigue with at least one associated symptom (pains, dizziness, headache, sleep disturbance, inability to relax, irritability) that does not resolve by resting or relaxing and lasting at least 3 months. Results: The prevalence of prolonged fatigue was 3.0% (SE=0.3), with 1.4% (SE=0.2) for prolonged fatigue only and 1.6% (SE=0.2) for prolonged fatigue concomitant with a depressive or anxiety disorder. Nearly 60% of the adolescents with prolonged fatigue only had severe or very severe disability, and their rates of poor physical and mental health were comparable to those of adolescents with mood or anxiety disorders only. Adolescents with prolonged fatigue and comorbid mood or anxiety disorders had significantly greater disability, poorer mental health, and more health service use than those with either condition alone. Conclusions: These findings suggest that prolonged fatigue is associated with disability and is an important clinical entity independent of mood and anxiety disorders in adolescents. Persistent fatigue with a comorbid mood or anxiety state is related to even more functional impairment, suggesting that prolonged fatigue may reflect greater severity of mood and anxiety disorders in adolescents