Director: Jill M. Goldstein, Ph.D.

Mission

The Clinical Neuroscience Laboratory of Sex Differences in the Brain, directed by Jill Goldstein, Ph.D., is located at the Connor's Center for Women's Health and Gender Biology and the Department of Psychiatry at Brigham and Women's Hospital and Harvard Medical School. The lab integrates scientists from clinical and basic neuroscience perspectives to address questions of why men and women are at different risks for disorders of the brain.  The answers to these questions are critical to understanding the nature of these illnesses, given that sex differences in onset, prognosis and treatment of mental disorders are pervasive. We are addressing the current and long-standing gap in psychiatric knowledge regarding the underlying neurobiology of sex differences in these disorders which will provide the basis for the development of sex-specific treatments. 

The work of the lab is investigating the fetal and neonatal programming of sex differences in adult onset psychiatric disorders focusing on the roles of adrenal and gonadal hormones, genes, and inflammatory factors in understanding sex effects in depression, psychoses, aging of the brain and risk for Alzheimer's disease and comorbidity of these neuropsychiatric disorders with general medical disorders, such as cardiovascular disease and metabolic disturbance. We take a lifespan approach to our investigations in that we believe that windows of opportunity for the study of sex differences occur when the brain and body are differentially flooded with hormonal changes, such as during fetal development and puberty, and periods specific to women such as pregnancy and perimenopause/menopause. An understanding of these hormonal and genetic pathways will provide knowledge for the development of sex-specific and sex-dependent drug discovery and other treatments for these disorders.

    Some examples of scientific contributions:
    1. Hormonal and genetic processes that regulate the sexual differentiation of the brain during fetal development have enduring effects on sex differences in structural brain volumes in adulthood in healthy adults. Normal sexual dimorphisms in the brain are disrupted in schizophrenia and major depressive disorder.
    2. Abnormalities in maternal immune response during mid-gestation are significantly associated with sex differences in risk for psychoses and major depressive disorder.
    3. Circulating hormones have significant effects on brain activity in stress response circuitry in healthy women. Hormonal variation in women contributes to explaining sex differences in stress response circuitry in healthy adults. Stress response circuitry activation is disrupted in major depression, schizophrenia, and bipolar psychoses in sex-dependent ways and associated with hormonal dysregulation.