Understanding inequalities in outcomes between demographic groups is a necessary step in addressing them in clinical care. Inequalities in treatment uptake between demographic groups may explain disparities in outcomes in people with first-episode psychosis (FEP).

To investigate disparities between broad demographic groups in symptomatic improvement in patients with FEP and their relationship to treatment uptake.

We used data from 6813 patients from the 2021–2022 National Clinical Audit of Psychosis data-set. Data were grouped by category type to obtain mean outcomes before adjustment to see whether disparities in outcomes remained after differences in treatment uptake had been accounted for. After matching, the average effect of each demographic variable in terms of outcome change was calculated. Moderator effects on specific treatments were investigated using interaction terms in a regression model.

Observational results showed that patients aged 18–24 years were less likely to improve in outcome, unless adjusted for intervention uptake. Patients classified as Black and Black British were less likely to improve in outcome (moderation effect 0.04, 95% CI 0–0.07) after adjusting for treatment take-up and demographic factors. Regression analysis showed the general positive effect of supported employment interventions in improving outcomes (coefficient −0.13, 95% CI −0.07 to −0.18, P < 0.001), and moderator analysis suggested targeting particular groups for interventions.

Inequalities in treatment uptake and psychotic symptom outcome of FEP by social and demographic factors require monitoring over time. Our analysis provides a framework for monitoring health inequalities across national clinical audits in the UK.

Studying 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.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-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.

Earlier 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.

AAO 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.