Beginning in the 1980’s, Dr. Goldstein led the way in rethinking the importance of sex in the risk for schizophrenia even though the prevailing view was that it was similar in men and women. Studies demonstrated that men have a significantly higher risk than women, the causes for which began during mid-gestation, a key period of the sexual differentiation of the brain. She published the first MRI study of sex differences across the entire healthy brain >20 years ago, laying the groundwork for how the development of these differences was disrupted prenatally by sex in both schizophrenia and major depression.

Her team went on to uncover how prenatal maternal stress was transmitted to offspring brain development in a sex-dependent way, providing critical insights into understanding early antecedents to the risk for sex differences in psychoses and depression and abnormalities in brain circuitries (stress, mood/anxiety, memory) and physiology (hormonal, autonomic function, and immune) that are shared across disorders of the brain and heart. Her team discovered some of the same early antecedents implicated in depression were shared with risk for cardiovascular disease. In 2021, in the largest psychiatric genetics consortium (PGC) dataset to date, her team uncovered sex differences in genes (shared and non-shared) between depression, schizophrenia, and bipolar psychosis.

Together, this work has contributed to understanding shared pathophysiology that cross disorders of the brain as well as with the heart.

Using a sex differences lens, studies have taken a lifespan approach from fetal development to aging, focusing on periods of reproductive changes. Since 2014, work in the lab has expanded to identify developmental risks for sex differences in memory decline and risk for Alzheimer’s disease in early midlife and the impact of reproductive age as distinct from chronologic age.

Dr Goldstein has published >200 articles, chapters and other original and peer-reviewed work in these areas (+ Info)

Dr Goldstein spent her career at Harvard training, mentoring, and sponsoring the next generation in women’s health/sex differences in medicine, including leading for almost 20 years an ORWH Harvard-wide K12 junior faculty training program on building interdisciplinary careers in women’s health.

In 2018, she launched the Innovation Center on Sex Differences in Medicine (ICON-✘) at MGH across departments and divisions, whose mission is to enhance discoveries of sex differences in medicine and translate them into the development of sex-dependent therapeutics to address the need for precision medicine.