Stratification of individuals with lifetime depression and low wellbeing in the UK Biobank

BackgroundPrevious studies stratified patients with major depressive disorder (MDD) based on their clinical characteristics. This study used this approach in individuals with lifetime MDD who reported low wellbeing, a group of high clinical relevance.MethodsWe selected participants in the UK Biobank (UKB) with lifetime MDD and a wellbeing score in the lowest 25 %. A wellbeing score was previously created considering happiness, belief that own life is meaningful, health satisfaction and functioning in relevant areas. In the selected group, we applied latent class analysis using mood-spectrum symptoms and personality traits as input variables, then we compared the clinical-demographic and genetic (polygenic risk scores, PRSs) characteristics of the identified classes.ResultsA total of 13,896 individuals were included and a model with five classes showed the best performance. The most common class (31.25 %) was characterised by periods of irritable mood and trait irritability with high neuroticism. A rarer class (16.49 %) showed depressive-manic mood fluctuations and risk-taking personality, higher percentage of males, atypical depressive symptoms, lower socio-economic status, higher PRS for attention-deficit hyperactivity disorder and lower PRS for education. The second most common class (29.79 %) showed worry as main personality trait with low risk of manic/irritable manifestations. The remaining classes showed an anxious-irritable personality profile and a purely depressive profile (4.92 % and 17.55 %, respectively).LimitationsOur results may reflect the characteristics of UKB participants.ConclusionsSubthreshold manic/irritable mood fluctuations and personality traits irritability and neuroticism may distinguish the most common groups with poor wellbeing in lifetime MDD