Search

BackgroundStudying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.MethodGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Background: Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method: We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results: Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P =.01), especially when considering emotional abuse (rho = −0.16, P =.001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P =.01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate the associations between recent cannabis use, current symptomatology and age at onset of first manic, depressive and psychotic episodes in a large sample with first-treatment bipolar I disorder ( BD I). Methods One hundred one patients with first-treatment Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ( DSM- IV) bipolar I disorder were included as part of the Thematically Organized Psychosis study. The Structural Clinical Interview for DSM- IV was used for DSM- IV diagnosis and identification of episodes of illness. Earlier suicide attempts were recorded. Manic, depressive and psychotic symptoms were rated using the Young Mania Rating Scale, Inventory of Depressive Symptoms and Positive and Negative Syndrome Scale correspondingly. Cannabis use within the six last months was recorded. Results After controlling for confounders, recent cannabis use was significantly associated with lower age at onset of first manic and psychotic episode, but not with onset of first depressive episode (both P < 0.05). Recent use was also associated with more lifetime suicide attempts ( P < 0.01). No group differences were found on symptom levels. Conclusions The present study confirms earlier findings of an association between cannabis use and a lower age at onset. Recent cannabis use was also associated with more lifetime suicide attempts. The current findings suggest that recent cannabis use is associated with a more severe course of illness in the early phase of BD I. [ABSTRACT FROM AUTHOR]

Abstract: Background: Early onset of bipolar disorder (BD) is an important clinical predictor of a more severe course and poorer outcome. A higher proportion of childhood onset BD has been reported in studies from USA compared to Europe. We investigated age at onset of first affective episode in a Norwegian sample and compared it to previous European and US findings. In addition, we examined whether age at onset influenced on time to first treatment, and if patient characteristics related to illness severity influenced age at onset. Methods: Two hundred and twenty five BD patients were recruited consecutively mainly from psychiatric out-patient units at three major hospitals in Oslo, Norway, diagnosed using SCID-I and divided into four groups based on age at onset. Results: Six percent of the patients had onset in childhood, 32% in adolescence, 43% in young adulthood, and 19% as adults. Average age at onset was 22.8years (SD 9.4). There was a significantly higher age at onset and a significantly shorter time from onset to first treatment in patients with lifetime hospitalization. Limitation: Retrospective information which could be confounded by collection bias. Conclusion: Age at onset in our sample resembled previous European studies, but not US- or Norwegian studies. The difference in age at onset seems more related to different definitions of onset, than to hospitalization history. This highlights the importance of improving the research criteria and of using similar criteria to ascertain age at onset. [Copyright &y& Elsevier]