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One or more keywords matched the following properties of Goldstein, Jill
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overview Introduction: I have had a long-standing interest in sex differences in the brain and the roles of steroid hormones, genes, and markers of immune function in understanding sex differences in psychiatric disorders and their comorbidity with general medicine. I believe that an understanding of these pathways will provide knowledge for the development of novel sex-dependent therapeutic discovery. For >30 years at Harvard, I have been working with colleagues that span Harvard schools and departments and other collaborative institutions that integrate fields of study, methods of analysis, and levels of study from basic to clinical to tackle issues of sex differences in medicine and women's health. Relatively little is known about how sex differences in healthy brain development may or may not deviate in producing pathology and the impact on treatment. Further, clinical decisions based on research are primarily based on data from males that are often inappropriate for females, even for disorders (like depression) in which women predominate. Given the gap between the clinical and scientific importance of studying sex effects in medicine and the relative paucity of studies on these issues, the history of my work has contributed to moving this field forward. History of Research: My laboratory, called the Clinical Neuroscience Laboratory of Sex Differences in the Brain, has been ongoing for >25 years (http://cnl-sd.mgh.harvard.edu). Our team consists of an interdisciplinary group of investigators, integrating structural and functional MRI studies, psychophysiology, steroid hormones, markers of immune function, genetics, and collaborative efforts with preclinical investigators modeling steroid hormones, genes, immune function, and the brain. The first disorder of interest was schizophrenia, a devastating illness for which men have a higher risk than women. Although in the 1980’s, the prevailing ideology was that it was similar in men and women, my team was instrumental in demonstrating that men have a significantly higher risk than women, the causes for which begin during mid-gestation, a key period of the sexual differentiation of the brain. Our studies of sex differences in cognitive functions identified specific domains in which women compared with men had relative preservation of function, i.e. language, executive functions, verbal memory, and olfaction. Using structural and functional MRI, my team identified brain abnormalities in schizophrenia in regions associated with sex differences in cognitive and affective functions. These brain regions, rich in gonadal hormone receptors, led to studies with basic neuroscience colleagues to map out prenatal stress and immune mechanisms associated with the dysregulation of the sexual differentiation of the brain during mid-gestation. We further demonstrated similar causal pathways for understanding sex differences in the risk for major depressive disorder, but for which women have a significantly higher risk than men. Over the last 15 years, the lab has focused on sex differences in major depression and why it is highly comorbid with cardiovascular disease and risk for Alzheimer’s disease later in life. We continue to take a lifespan approach to understanding sex differences in the shared causes of these disorders of the heart and brain. Included in this work, I oversee a unique prenatal cohort study in which subjects have prospective data from pregnancy through their 60’s, including brain imaging, allowing us to investigate in a human population the fetal programming of adult onset disorders, a topic primarily studied in animals. Our work has contributed to identifying fetal stress-immune biomarkers that disrupt the sexual differentiation of the brain and that are retained and expressed in adulthood as sex differences in deficits in stress response circuitry, major depression, and comorbid physiologic and cardiac dysfunction. In 2018, I launched the Innovation Center on Sex Differences in Medicine (ICON), a collaborative effort between Massachusetts General Hospital and the Harvard T. H. Chan School of Public Health, partnering with WomenAgainstAlzheimers (http://icon.mgh.harvard.edu). ICON consists of collaborators across departments, fields and methodologies bringing together psychiatry, OB-GYN, cardiology, neurology, and public health. ICON’s primary mission is to leverage fundamental discoveries “from cells to society” about sex differences in the brain and heart into strategies to develop sex-dependent therapeutics and target them early for prevention. In addition, we are invested in educating the next generation of scientists, clinicians, and the public about sex differences in medicine and advocating for these issues at the national and global levels. In 2020, ICON was designated an NIH Specialized Center of Research Excellence (SCORE) for Sex Differences in Medicine, one of only 8 in the country. Finally, I have spent my career educating the next generation of scientists and clinicians to study sex differences in health and disease across disciplines and methods and providing resources for their careers in women’s health and sex differences in medicine. In the service of this for >15 years, I have been the PI of a Harvard-wide junior faculty training program (ORWH-NICHD K12 HD051959-06) called Building Interdisciplinary Careers in Women's Health (BIRCWH) with ours targeted to "Hormones and Genes in Women's Health: From Bench to Bedside". With a translational focus, BIRCWH is training the next generation to investigate sex differences in medicine, and/or women's health specifically, and incorporate the knowledge into their academic and clinical careers in medicine.
One or more keywords matched the following items that are connected to Goldstein, Jill
Item TypeName
Academic Article Sex differences in stress response circuitry activation dependent on female hormonal cycle.
Academic Article Gender and trauma as predictors of military attrition: a study of Marine Corps recruits.
Academic Article Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry.
Academic Article Stress response circuitry hypoactivation related to hormonal dysfunction in women with major depression.
Concept Stress, Psychological
Concept Stress, Physiological
Concept Stress Disorders, Traumatic
Academic Article Rehospitalization in chronic schizophrenia.
Academic Article The effects of the community environment on chronic psychiatric patients.
Academic Article HPA-axis hormone modulation of stress response circuitry activity in women with remitted major depression.
Academic Article Disruption of fetal hormonal programming (prenatal stress) implicates shared risk for sex differences in depression and cardiovascular disease.
Academic Article 17ß-estradiol differentially regulates stress circuitry activity in healthy and depressed women.
Academic Article Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.
Academic Article Striatal Hypersensitivity During Stress in Remitted Individuals with Recurrent Depression.
Grant Gender and Brain Abnormalities in Schizophrenia
Grant Neural-Physiology Biosignature Shared across Negative Valence and Arousal Domains
Grant Sex, Hormones and GABA in Stress Induced Anhedonia in Depression
Grant Fetal Antecedents to Sex Differences in Depression: A Translational Approach
Grant Prenatal & Adult Immune Biomarkers of the Negative Valence Biosignature
Grant Fetal Hormonal Programming of Sex Differences in Aging of the Memory Circuitry (Phase II)
Academic Article Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome.
Academic Article Socioeconomic disadvantage, gestational immune activity, and neurodevelopment in early childhood.
Academic Article Impact of Prenatal Stress on Offspring Psychopathology and Comorbidity With General Medicine Later in Life.
Academic Article Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures.
Grant Impact of Depression on Alzheimer's disease: Prenatal Immune Origins and Shared Impact of Sex
Grant Sex Differences in Major Depression: Impact of Prenatal Stress-Immune and Autonomic Dysregulation
Academic Article Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later.
Academic Article Reductions in rostral anterior cingulate GABA are associated with stress circuitry in females with major depression: a multimodal imaging investigation.
Academic Article Respiratory-gated auricular vagal afferent nerve stimulation (RAVANS) modulates brain response to stress in major depression.
Academic Article Stress-induced alterations in HPA-axis reactivity and mesolimbic reward activation in individuals with emotional eating.
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  • Stress
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.