Sex differences in latent inhibition and their implications for psychotic disorders

Latent inhibition (LI) refers to the reduced ability to learn or express learning about a stimulus following prior exposure to it without consequence. It has been extensively studied to investigate associative learning and memory as well as the aberrant attribution of salience to irrelevant stimuli in both humans and animals, a process which is thought to underpin hallucinations and delusions in psychosis. Despite sex differences observed in numerous aspects of psychosis, few studies have attempted to characterise sex differences in LI. This systematic review outlines the current evidence of sex differences in LI in both human and rodent studies, showing predominantly inconclusive and conflicting evidence for sex differences. However, the majority of cases in which sex differences were found were in studies that assessed the impact of additional factors on LI such as drug administration, juvenile handling, and oestrous phase, and demonstrated interactions between sex and these additional factors. Hence, there is stronger evidence for sex differences in vulnerability to perturbations in LI. Furthermore, we present data demonstrating sex differences in latent inhibition of contextual fear conditioning and associated gene expression in the hippocampus in rodents, suggesting sex differences in hippocampal processing underpinning latent inhibition at both the behavioural and neurobiological levels. Although there have been relatively few studies demonstrating sex differences in LI identified by the systematic review, the data suggest that in hippocampally dependent forms of LI, sex differences may be more apparent, which may be of relevance in relation to sex differences in the presentation of psychosis.