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 (<1500 g) and low birth weight (1500–2490 g) were associated with higher neuroticism scores assessed in middle age, and lifetime history of either MDD or BD. We controlled for possible confounding factors.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.