Director: Jill M. Goldstein, Ph.D.
For more information, please contact Anne Remington at aremington@partners.org

Mission

The Clinical Neuroscience Laboratory of Sex Differences in the Brain, directed by Jill Goldstein, Ph.D., integrates scientists from basic and clinical neuroscience perspectives to address questions of why men and women are at different risks for psychiatric and neurologic disorders.  We take a lifespan approach to our research investigations in that we believe that windows of opportunity for investigation of sex differences in disease occur when the brain and body are differentially exposed to changes in hormonal status, such as during fetal development, puberty, pregnancy, and perimenopause and menopause.   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 co-morbidity of these psychiatric disorders with general medical disorders, such as cardiovascular disease.  We believe that an understanding of these hormonal and genetic pathways will provide knowledge for the development of sex-specific drug discovery and other treatments for these disorders. 

The research team consists of an interdisciplinary team of investigators, integrating structural and functional magnetic resonance and diffusion tensor imaging (i.e., sMRI, fMRI and DTI), psychophysiology [e.g., heart rate, galvanic skin response (GSR)], hormones, genes, and inflammation.  We collaborate with animal investigators of steroid hormones, genes, inflammation, and the brain. Functional domains of interest include the stress response circuitry, long-term memory and working memory circuitries, and reward circuitry implicated in the neural circuitry of obesity.  Current NIH-funded projects investigate these brain circuitries in schizophrenia, affective psychoses, depression and its co-morbidity with cardiovascular disease, and obesity and anorexia.  Included in this work, Goldstein and colleagues have been following a prenatal cohort over the last 20 years (initiated in 1959-1966 following pregnant mothers and their offspring for 7 years), allowing us to re-recruit offspring as 40-year old adults and study in vivo the fetal programming of adult onset diseases.  The work is contributing to understanding the nature of psychiatric disorders, the impact of one’s sex, and normal properties of the male and female brain in the face of disease.

Some examples of scientific contributions: 

  • 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. 
  • Chronic hypoxic exposure and prenatal risk factors producing inflammation during mid-gestation are associated with risk for schizophrenia and major depressive disorder and contribute to explaining sex differences in these disorders in adulthood.
  • Circulating hormones have significant effects on brain activity in stress response circuitry in 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 and associated with hormonal dysregulation in depressed women.