Short Summary/Abstract:

People with schizophrenia exhibit accelerated biological ageing (1) with fluctuations in symptoms and levels of functioning (2). Older schizophrenia patients (over age 60) experience greater age-associated worsening of cognition (3) compared to controls. Brain-predicted age difference (brain-PAD) is the difference between predicted brain age and chronological age, with plus values indicating a brain older than the chronological age and negative values indicating a brain younger than the chronological age. In people with schizophrenia, the brain-PAD is on average between 3 and 7.7 years, indicating a brain older than their chronological age, which is significantly greater than in matched healthy controls (4.4 years) (4,5). Different brain areas show distinct ageing trajectories in schizophrenia (6,7). Studies have also reported some attenuations in sexual dimorphism in the brain structure in schizophrenia (8). However, existing studies include small samples and lack data regarding outcome-influencing factors, i.e., medication, age at illness onset, or illness duration on brain ageing in chronic schizophrenia samples (5,7). This project aims to comprehensively investigate the sex-specific effects of aging on working memory and associated brain structures in schizophrenia.