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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: Seasonal affective disorder (SAD) is considered to be a subtype of depression.AIMS: To compare the clinical picture of SAD to non-seasonal affective disorders (non-SADs).METHOD: Diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) were established in 2185 participants of the Netherlands Study of Depression and Anxiety. The Seasonal Pattern Assessment Questionnaire was administered to diagnose SAD. Symptoms of depression and anxiety were measured with the Inventory of Depressive Symptoms, the Beck Anxiety Inventory and the Fear Questionnaire.RESULTS: Participants with SAD, participants with a lifetime bipolar disorder and participants with a lifetime comorbid anxiety and depressive disorder scored highest in terms of psychopathology in the past year. The seasonal distribution of major depressive episodes was not different for participants with or without SAD.CONCLUSIONS: SAD may be a measure of severity of depression with a subjectively perceived worsening of symptoms in the winter months.DECLARATION OF INTEREST: Y.M. has received research funding and served as a consultant for Royal Philips Electronics NV and The Litebook Company Ltd. W.A.N. has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, Astra Zeneca, Eli Lilly, GlaxoSmithKline and Wyeth; has received honoraria/speaker's fees from Astra Zeneca, Pfizer, Servier and Wyeth; and has served in advisory boards for Astra Zeneca, Pfizer and Servier.COPYRIGHT AND USAGE: © 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.

BackgroundA significantly lower fractional anisotropy (FA) value has been shown in anterior parts of the corpus callosum in patients with bipolar disorder.AimsWe investigated the association between abnormal corpus callosum integrity and interhemispheric functional connectivity (IFC) in patients with bipolar disorder.MethodsWe examined the association between FA values in the corpus callosum (CC-FA) and the IFC between homotopic regions in the anterior cortical structures of bipolar disorder (n=16) and major depressive disorder (n=22) patients with depressed or euthymic states.ResultsWe found a positive correlation between the CC-FA and IFC values between homotopic regions of the ventral prefrontal cortex and insula cortex, and significantly lower IFC between these regions in bipolar disorder patients.ConclusionsThe abnormal corpus callosum integrity in bipolar disorder patients is relevant to the IFC between homotopic regions, possibly disturbing the exchange of emotional information between the cerebral hemispheres resulting in emotional dysregulation.

Background Women with bipolar disorder are at increased risk of having a severe episode of illness associated with childbirth. Aims To explore the factors that influence the decision-making of women with bipolar disorder regarding pregnancy and childbirth. Method Qualitative study with a purposive sample of women with bipolar disorder considering pregnancy, or currently or previously pregnant, supplemented by data from an online forum. Data were analysed using thematic analysis. Results Twenty-one women with bipolar disorder from an NHS organisation were interviewed, and data were used from 50 women's comments via the online forum of the UK's national bipolar charity. The centrality of motherhood, social and economic contextual factors, stigma and fear were major themes. Within these themes, new findings included women considering an elective Caesarian section in an attempt to avoid the deleterious effects of a long labour and loss of sleep, or trying to avoid the risks of pregnancy altogether by means of adoption or surrogacy. Conclusions This study highlights the information needs of women with bipolar disorder, both pre-conception and when childbearing, and the need for improved training for all health professionals working with women with bipolar disorder of childbearing age to reduce stigmatising attitudes and increase knowledge of the evidence base on treatment in the perinatal period.

BackgroundIntellectual ability may be an endophenotypic marker for bipolar disorder.AimsWithin a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood.MethodWe used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 years and lifetime manic features assessed at age 22–23 years using the Hypomania Checklist-32 (HCL-32; n=1881 individuals). An ordinary least squares linear regression model was used, with normal childhood IQ (range 90–109) as the referent group. We adjusted analyses for confounding factors, including gender, ethnicity, handedness, maternal social class at recruitment, maternal age, maternal history of depression and maternal education.ResultsThere was a positive association between IQ at age 8 years and lifetime manic features at age 22–23 years (Pearson's correlation coefficient 0.159 (95% CI 0.120–0.198), P>0.001). Individuals in the lowest decile of manic features had a mean full-scale IQ (FSIQ) which was almost 10 points lower than those in the highest decile of manic features: mean FSIQ 100.71 (95% CI 98.74–102.6) v. 110.14 (95% CI 107.79–112.50), P>0.001. The association between IQ and manic features was present for FSIQ, VIQ and for PIQ but was strongest for VIQ.ConclusionsA higher childhood IQ score, and high VIQ in particular, may represent a marker of risk for the later development of bipolar disorder. This finding has implications for understanding of how liability to bipolar disorder may have been selected through generations. It will also inform future genetic studies at the interface of intelligence, creativity and bipolar disorder and is relevant to the developmental trajectory of bipolar disorder. It may also improve approaches to earlier detection and treatment of bipolar disorder in adolescents and young adults.

BackgroundHypomanic symptoms may be a useful predictor of mood disorder among young people at high risk for bipolar disorder.AimsTo 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.MethodHigh-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.ResultsHCL-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.ConclusionsCSHS are precursors to major mood episodes in high-risk offspring and could identify individuals at ultra-high risk for developing bipolar disorder.

BackgroundLow birth weight has been inconsistently associated with risk of developing affective disorders, including major depressive disorder (MDD). To date, studies investigating possible associations between birth weight and bipolar disorder (BD), or personality traits known to predispose to affective disorders such as neuroticism, have not been conducted in large cohorts.AimsTo assess whether very low birth weight (MethodRetrospective cohort study using baseline data on the 83 545 UK Biobank participants with detailed mental health and birth weight data. Main outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)ResultsReferent to normal birth weight, very low/low birth weight were associated with higher neuroticism scores, increased MDD and BD. The associations between birth weight category and MDD were partially mediated by higher neuroticism.ConclusionsThese findings suggest that intrauterine programming may play a role in lifetime vulnerability to affective disorders.

BackgroundControversy surrounds the diagnosis and prevalence of paediatric bipolar disorder, with estimates varying considerably between countries.AimsTo determine the international hospital discharge rates for paediatric bipolar disorder compared with all other psychiatric diagnoses.MethodWe used national data-sets from 2000 to 2010 from England, Australia, New Zealand, the USA and Germany.ResultsFor those aged under 20 years, the discharge rates for paediatric bipolar disorder per 100 000 population were: USA 95.6, Australia 11.7, New Zealand 6.3, Germany 1.5 and England 0.9. The most marked divergence in discharge rates was in 5- to 9-year-olds: USA 27, New Zealand 0.22, Australia 0.14, Germany 0.03 and England 0.00.ConclusionsThe disparity between US and other discharge rates for paediatric bipolar disorder is markedly greater than the variation for child psychiatric discharge rates overall, and for adult rates of bipolar disorder. This suggests there may be differing diagnostic practices for paediatric bipolar disorder in the USA.

Bipolar disorder is burdensome for the individual and for society; it is associated with significant functional impairment, high comorbidity, lower quality of life and higher rates of suicide. 1 Pharmacotherapy with mood stabilisers and antipsychotics may not lead to sustained remission and more than two-thirds of those treated experience a recurrence within 5 years. 2 Given such poor treatment outcomes, novel approaches to improve therapeutic interventions are an important objective of bipolar disorder research. Mounting, albeit inconsistent, evidence suggests that testosterone may play a role in the pathophysiology of mood disorders. 3 However, the effects of testosterone are complex: the hormonal disorder polycystic ovarian syndrome is characterised by chronically increased testosterone levels and is associated with significantly increased depression, 4 but paradoxically, amelioration of depression has been found following testosterone administration in males 5 and females; 6–8 low testosterone levels have been reported in certain subgroups of men with depression; 9 androgen-induced hypomania has been reported; 10 and high testosterone levels may predict suicidal behaviour in women with bipolar disorder. 3 Further evidence clarifying the relationship between testosterone and bipolar disorder might pave the way for exploring the use of pharmacological strategies that optimise testosterone levels in patients with bipolar disorder. We therefore assessed testosterone levels in bipolar disorder and healthy controls and sought to explore whether this was different between males and females and whether there was a relationship between testosterone, mood and cognition.

Background Data linkage studies find that depression before or after a breast cancer diagnosis predicts reduced survival. This study aimed to determine whether depression or bipolar recorded in routine hospital admission data independently predicts survival in English breast cancer patients and whether onset in relation to cancer diagnosis is significant. Methods Data on 77 173 women diagnosed with breast cancer (ICD‐10 C50) in South East England, 2000–2009, were included. Of these, 131 women had a diagnosis of bipolar affective disorder (ICD‐10 F31) and 955 of depression (either depressive episodes (ICD‐10 F32) or depressive disorder (ICD‐10 F33)) recorded in Hospital Episode Statistics between 3 years before and a year following cancer diagnosis. Kaplan–Meier plots were used to examine overall survival. Cox regression analyses were carried out overall and separately for mood disorder diagnoses before and after the cancer diagnosis and adjusted for confounding variables. Results A record of depression was a predictor of worse overall survival in breast cancer patients (adjusted HR = 1.33, 95% CI: 1.20–1.48, p