Sex Differences in Psychosocial and Neurocognitive Outcomes in Adults with Moderate to Complex Congenital Heart Disease - PROJECT ABSTRACT Congenital Heart Disease (CHD) is the number one birth defect worldwide, with 2.4 million people (1.4 million adults) in the United States. Those figures are expected to double in the next decade with more than 90% of CHD patients reaching adulthood. Despite medical and surgical advancements, 50% of adults with CHD have neurocognitive deficits, depression and heart-focused anxiety that can affect their daily life. However, there are no studies that examine sex differences in psychosocial and neurocognitive outcomes in adults with moderate to complex CHD. Only a few studies have examined either neurocognitive function or psychosocial outcomes in adults with CHD. Those studies have shown deficits in neurocognitive domains such as attention, executive function, processing speed, working memory and intelligence. These deficits place the patient at higher risk for lower educational attainment, unemployment, disability, poor self-care, increased mortality and morbidity, lower quality of life and potential loss to medical follow-up. Unfortunately, small sample sizes in these few studies limited further analysis based on sex / gender differences. To address this critical gap, we will recruit 180 CHD participants between 18 to 40 years of age with a diagnosis of moderate-to-complex CHD from the Ahmanson/UCLA Adult CHD Center. An additional sample of 40 healthy controls will be recruited from the Los Angeles community for comparison. This cross-sectional, comparative study will include measurements to assess neurocognition, anxiety/depression, social determinants of health, mental and physical functioning, social support, and quality of life. Clinical data include ventricular ejection fraction (EF), number of cardiac surgeries, CHD severity and menopause status in females. Specific Aim 1) Examine sex /gender differences in psychosocial, physical functioning, social determinants of health (SDoH), and neurocognitive scores in adults with moderate to complex CHD compared to age-, sex-, and ethnicity-matched controls. We hypothesize that males will have worse neurocognitive scores compared to females with CHD and matched controls, while females with CHD will have worse psychosocial scores compared to males with CHD and match controls. Specific Aim 2) Determine the relationship between neurocognitive scores and sex, clinical factors, SDoH, psychosocial, and physical functioning in adults with moderate-to-complex CHD. We hypothesize that greater number of surgeries, lower EF, worse physical function, higher levels of anxiety and depressive symptoms, less social support, negative SDoH, and male sex will be associated with worse neurocognitive scores in adults with moderate to complex CHD. This study will contribute to new knowledge on the association of sex / gender differences related to neurocognition and psychosocial outcomes in aging adults with CHD. The clinical implications are substantial as results will support the development of targeted interventions to improve neurocognitive and psychosocial outcomes in this high-risk, growing population.