Bipolar disorder is a multifactorial illness with uncertain aetiology. Knowledge of potential risk factors enables clinicians to identify patients who are more likely to develop bipolar disorder, which directs further investigation, follow up and caution when prescribing. Ideally, identifying directly causative factors for bipolar disorder would enable intervention on an individual or population level to prevent the development of the illness, and improve outcomes through earlier treatment. This article reviews the epidemiology of bipolar disorder, along with putative demographic, genetic and environmental risk factors, while assessing the strength of these associations and to what extent they might be said to be 'causative'. While numerous genetic and environmental risk factors have been identified, the attributable risk of individual factors is often small, and most are not specific to bipolar disorder but are associated with several mental illnesses. Therefore, while some genetic and environmental factors have strong evidence supporting their association with bipolar disorder, fewer have sufficient evidence to establish causality. There is increasing interest in the role of specific gene-environment interactions, as well as the mechanisms by which risk factors interact to lead to bipolar disorder.

BackgroundA reliable biomarker signature for bipolar disorder sensitive to illness phase would be of considerable clinical benefit. Among circulating blood-derived markers there has been a significant amount of research into inflammatory markers, neurotrophins and oxidative stress markers.AimsTo synthesise and interpret existing evidence of inflammatory markers, neurotrophins and oxidative stress markers in bipolar disorder focusing on the mood phase of illness.MethodFollowing PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines, a systematic review was conducted for studies investigating peripheral biomarkers in bipolar disorder compared with healthy controls. We searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated studies by bipolar mood phase (mania, depression and euthymia). Extracted data on each biomarker in separate mood phases were synthesised using random-effects model meta-analyses.ResultsIn total, 53 studies were included, comprising 2467 cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses of three or more studies. No biomarker differentiated mood phase in bipolar disorder individually. Biomarker meta-analyses suggest a combination of high-sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic factor/tumour necrosis factor (TNF)-α and soluble TNF-α receptor 1 can differentiate specific mood phase in bipolar disorder. Several other biomarkers of interest were identified.ConclusionsCombining biomarker results could differentiate individuals with bipolar disorder from healthy controls and indicate a specific mood-phase signature. Future research should seek to test these combinations of biomarkers in longitudinal studies.Declaration of interestNone.

Accessible summary Phelan‐McDermid syndrome is an uncommon genetic cause of intellectual disability, but should still be tested for. People with Phelan‐McDermid syndrome may also suffer from bipolar disorder, and doctors should consider this diagnosis. We discuss two patients with both Phelan‐McDermid Syndrome and bipolar disorder. Both patients improved when using a medication called lithium Doctors should consider using lithium in patients with Phelan‐McDermid syndrome and evidence of bipolar disorder. Abstract BackgroundPhelan‐McDermid syndrome is caused by a deletion at chromosome 22q13.3, and results in a phenotype characterised by intellectual disability, features of autism, physical and mental health conditions. It is becoming increasingly recognised that bipolar disorder represents part of this phenotype. Materials and methodsThis case study describes 2 patients with Phelan‐McDermid syndrome presenting with bipolar mania at inpatient unit for adults with intellectual disability. Both patients presented with severe disturbance of their behaviour, at times exhibiting aggression, disinhibition and hypersexuality. ResultsDespite treatment with a number of atypical antipsychotics and anticonvulsant mood stabilising agents, both patients showed the greatest improvement when started on lithium, and were successfully treated with this medication. ConclusionsThis adds further support to the growing evidence of bipolar disorder contributing to the phenotype of Phelan‐McDermid syndrome, and clinicians should have a low threshold for considering the use of lithium in these patients.