Understanding and Altering Prenatal Immune Function and Parenting to Improve Child Mental Health: Investigating Intergenerational Stress Transmission Mechanisms

The Developmental Origins of Health and Disease framework has illuminated that maternal factors during pregnancy, such as exposure to elevated stress, increase children’s risk of mental health problems, via prenatal and postnatal mechanisms. Thus, there is a critical public health imperative to conduct research in this area to understand and ultimately prevent the development of psychopathology. Fetal exposure to elevated maternal inflammation during pregnancy (PMI) increases risk for child psychopathology via placental mechanisms, however, evidence from animal and human models suggests that heightened PMI may also disrupt maternal parenting behaviors. Via a phenomenon called “sickness behaviors,” high levels of inflammation can cause social withdrawal, depression-like feelings, and problems understanding social situations. Although social withdrawal and depressive tendencies may be potentially adaptive, energy- conserving responses that facilitate fighting an infection, affective and social difficulties may impair parents’ ability to recognize and respond optimally to their baby’s signals. Critically, the direct and indirect associations among PMI, parenting, and child mental health have not yet been tested in humans. In this proposal, I will fill critical training gaps in prenatal immune biology, advanced longitudinal statistical modeling, and multidisciplinary intervention research to test 3 Aims. First, I will leverage my primary mentor’s deeply-phenotyped, sociodemographically diverse longitudinal pregnancy cohort of mother-child pairs (n = 1303) to test the novel hypothesis that parenting partially accounts for positive associations between PMI and childhood mental health problems (Aims 1 and 2). Mentored training and findings will inform a pilot intervention study in which I partner with a well-established clinical research program to bridge Aims 1-2 findings with applied solutions (Aim 3). This program delivers an evidence-based intervention targeting traumatic stress exposure (Perinatal Child-Parent Psychotherapy) to pregnant Latina women. In this study, I will collect repeated measures of PMI as well as observations of parenting and infant behavior (n = 20). Preliminary findings from associations among intervention-related changes in PMI, parenting, and infant behavior will validate the mechanism tested in Aims 1 and 2 and lay the groundwork for a follow-on R-34 intervention study testing effects of prenatal psychological intervention on PMI, parenting, and child mental health. Investigating associations between PMI, parenting, and child mental health will elucidate the etiology and maintenance of child psychopathology, as well as mechanisms for targeting prenatal prevention and postnatal intervention. Addressing these potential determinants and solutions are public health and NIMH priorities. Mentored training from this K23 proposal will support my transition to an independent interdisciplinary clinical science career investigating and preventing the intergenerational transmission of stress and psychopathology. Project Number: 1K23MH138756-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Alexandra Sullivan | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $200,376 | Activity Code: K23 | Study Section: Biobehavioral Mechanisms of Emotion, Stress and Health Study Section[MESH] View on NIH RePORTER: https://reporter.nih.gov/project-details/11229684