Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology

• Sex differences are apparent in almost all aspects of schizophrenia, including age on onset, symptomology and drug response.
• Developmental models of schizophrenia reveal a male-specific vulnerability of the medial prefrontal cortex to early developmental insults.
• Developmental models of schizophrenia show a female bias toward anxiety-related behaviours.
• Genetic models of dopaminergic dysfunction show a male bias toward attentional deficits.
• Cognitive ability is more severely disrupted in male genetic risk models.

Sex differences in schizophrenia are apparent in almost all features of the illness, from incidence and mean age of onset to symptomatology, course of illness and response to pharmacological treatments. Understanding how men and women with schizophrenia differ provides significant clues into the pathophysiology of the disorder. Animal models are powerful tools when dissecting the molecular biology which underlies behavioural disturbances, and allow structured comparisons of biological sex differences without the social environmental gender influence that so often confounds human sex comparison studies. This review will provide a summary of sex differences described in developmental, genetic and drug-induced animal models of schizophrenia and will link sex-specific molecular and behavioural phenotypes of these models in an attempt to unravel the role that sex plays in the pathophysiology of schizophrenia. Both sex and stress hormones interact to shape the developing brain and behaviour and animal models of schizophrenia that include both sexes provide significant insight into the complexities of these interactions and can direct toward novel therapeutic strategies.

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