Peer-reviewed article

S178. SHOULD SCHIZOAFFECTIVE DISORDER DEPRESSED-TYPE BE DISTINCT FROM SCHIZOPHRENIA? ANALYSIS OF GENETIC LIABILITY AND LIFETIME CLINICAL CHARACTERISTICS

Dennison C, Legge S, Hubbard L, Lynham A, Holmans P et al. · 1 May 2020

Abstract

Abstract Background Schizoaffective disorder depressed type (SAD) has been considered a distinct diagnostic entity since 1987, yet it is rarely recognised in clinical and research settings as it is considered analogous to schizophrenia with comorbid depression. However, these assumptions are often based on anecdotal evidence, as little research has attempted to examine differences between the two disorders. We aimed to establish the validity of SAD as a diagnosis, by investigating phenotypic and genotypic differences between schizophrenia and SAD. Methods Participants were from the Cardiff Cognition study and included if they met ICD-10 criteria for schizophrenia (n=713) or SAD (n=151). Diagnosis was determined via consensus assessment by trained researchers using lifetime symptom data from the SCAN interview alongside patient medical records. Polygenic risk scores were derived for schizophrenia and major depressive disorder using PRSice. Logistic regressions were used to measure the association between diagnosis and lifetime clinical characteristics across five categories: demographics, premorbid functioning, illness progression, psychosis, and depression. Sex and age at interview were included as covariates. Logistic regressions were used to measure the association between diagnosis and polygenic risk scores for schizophrenia and depression at a threshold of p<.05, covarying for sex and principal components. Results Compared to schizophrenia, SAD was significantly associated with female sex (OR= 3.19, 95% CI= 2.23 - 4.59, p=5.0x10-9), lower global assessment score in worst episode of depression (OR= 0.47, 95% CI= 0.37 – 0.59, p=5.0x10-9), higher global assessment score in worst episode of psychosis (OR= 1.44, 95% CI= 1.20 – 1.72, p= 6.8x10-4), a greater likelihood of an admission for depression (OR= 2.24, 95% CI= 1.48 – 3.40, p= 1.2x10-3), greater alcohol abuse or dependence (OR= 2.12, 95% CI= 1.41 – 3.20, p= 2.3x10-3), longer duration of depression (OR= 1.46, 95% CI= 1.19 - 1.84, p= 3.5x10-3), experiencing childhood abuse (OR= 2.07, 95% CI = 1.35 – 3.17, p= 3.9x10-3), a reduced likelihood of an involuntary admission for psychosis (OR= 0.40, 95% CI= 0.22 – 0.75, p= 0.01), depression onset occurring prior to psychosis onset (OR= 2.40, 95% CI= 1.37 – 4.43, p= 0.01), having a higher number of children (OR= 1.34, 95% CI= 1.08 – 1.67, p= 0.03), and better cognitive functioning (OR= 1.20, 95% CI= 1.04 – 1.40, p= 0.05). Depression polygenic risk score was higher in participants with SAD (OR= 1.33, 95% CI= 1.06 – 1.66, R2= 0.015, p= 0.01); schizophrenia polygenic risk score was not associated with diagnosis (OR= 0.94, 95% CI= 0.75 – 1.17, R2= 0.001, p= 0.58). Secondary analyses were conducted to investigate sex-specific effects. A significant difference in schizophrenia polygenic risk was observed between males and females, which indicated that males with SAD have lower schizophrenia polygenic risk scores than females with SAD (OR= 0.46, 95% CI= 0.28 – 0.74, R2= 0.143, p=1.5x10-3). Sex-specific effects were not observed for depression PRS or phenotypes. Discussion Our results indicate a number of differences between individuals with schizophrenia and SAD. Primarily, the results demonstrate a greater burden of depression in those with SAD, both phenotypically and genotypically. Our results also suggest that the genetic contribution to SAD may differ between males and females. The findings indicate that schizophrenia research, particularly genetic research, needs to consider the impacts of sex-specific effects and comorbid depression before combining patient samples for analysis.