Sex Differences in Schizophrenia

For over 25 years, Dr. Goldstein has investigated hypotheses regarding the role of one's sex in understanding schizophrenia. She has been identifying mechanisms to explain why men are at higher risk for a more chronic form of the illness than women. Past work characterized sex differences in symptomatology, premorbid history and age at onset, course and treatment responses, genetic transmission and incidence. Her team has also cognitively characterized differences between men and women with schizophrenia and, using structural MRI, identified key brain regions in which men and women differed. Her work suggested that disruption of the hormonal regulation of the normal sexual differentiation of the brain during fetal development contributes to understanding sex differences in schizophrenia in adulthood.

Current work of her team is focused on investigating specific maternal-to-fetal immune pathways that disrupt the normal sexual differentiation of the brain resulting in a differential vulnerability in males and females for risk for schizophrenia, sex-specific brain abnormalities in the stress response circuitry and memory circuitry, and co-morbid neuroendocrine dysfunction. Ongoing studies follow a prenatal cohort 50 years later into adulthood, including structural and functional magnetic resonance brain imaging studies (i.e., sMRI, fMRI, and diffusion tensor imaging - DTI) in tandem with blood collection for hormonal evaluations and genetic analyses. Sex differences in schizophrenia are compared with those in bipolar psychosis.

Other work is investigating sex differences in the emergence of psychosis post-puberty and the vulnerability to illness progression in schizophrenia, focusing on the role of gonadal and adrenal hormonal disruption and memory dysfunction. The team's previous work demonstrated significant sex differences in memory dysfunction and abnormalities in memory circuitry in schizophrenia, with males performing worse than females. Current studies followed first episode patients and those in the prodromal state to investigate the impact of steroid hormonal dysregulation and memory circuitry deficits and dysfunction over time (see www.bostoncidar.org).