A longer duration of schizophrenic illness has sex-specific associations within the working memory neural network in schizophrenia

An association has previously been demonstrated between prefrontal cortex (PFC) volume decreases and illness progression in schizophrenia. The impact of illness duration on the fronto-parietal working memory neural network, however, remains unexplored. We investigated the effect of ageing and duration of illness, and explored possible sex-specific effects of duration of illness, in working memory-related brain activity in schizophrenia. Fifty individuals (25 stable schizophrenia outpatients, 25 healthy controls) underwent functional magnetic resonance imaging during performance of an ‘n-back’ task. Patients performed significantly worse than controls. Duration of illness correlated with reduced dorsolateral prefrontal cortex activity in males and reduced cerebellum activity in females, regardless of performance and age. Sex-specific effects of illness duration were also evident in the inferior frontal and superior temporal gyri (females) and the inferior parietal cortex (males) which generally show sexually dimorphic activation in healthy people. We detected no significant effect of ageing on neural activation of the working memory network in patients though such an effect was present in healthy controls. In conclusion, our findings demonstrate that a longer duration of schizophrenic illness has sex-specific associations within the working memory neural network, with expected association between illness duration and impaired PFC activation apparent in male, but not in female patients. Additionally, brain regions that exhibit sexually dimorphic activation in healthy people may become compromised in the corresponding sex with illness progression.