Group Richetto
Neurodevelopmental Consequences of Maternal Stress and Depression
Maternal psychological stress and depressive states during pregnancy — and even prior to conception — are increasingly recognized as important etiological factors contributing to neuropsychiatric and neurodevelopmental disorders in offspring. Human epidemiological studies have consistently revealed associations between heightened maternal stress, altered mood, and increased risk for a range of developmental and behavioral outcomes in children, including anxiety, depression, attentional deficits, and socio-emotional dysregulation. Rather than involving direct pathogenic intrusion, these adverse effects are thought to be mediated by complex neuroendocrine, immune, and metabolic processes that shape the intrauterine environment. Dysregulation of the maternal hypothalamic–pituitary–adrenal (HPA) axis, alterations in glucocorticoid signaling, inflammatory cascades, and changes in placental physiology collectively influence fetal brain development by modifying neuronal maturation, circuit formation, and developmental trajectories.
Based on the initial insights provided by human studies, our group has developed several translational animal models to experimentally investigate the pathological consequences of maternal stress and depression on offspring neurodevelopment. One such model centers on maternal preconception stress, which reliably induces depressive-like phenotypes and stress-related physiological alterations in female rodents. When these animals become pregnant, their offspring exhibit a broad spectrum of behavioral and cognitive abnormalities, mirroring key aspects of stress-related neurodevelopmental vulnerability observed in humans. This model provides a unique experimental platform for dissecting how maternal psychological and physiological states prior to and during pregnancy influence fetal development.
We employ a multidisciplinary approach that integrates state-of-the-art behavioral assays, neuroendocrine profiling, immunohistochemical analyses, gene transcriptional and epigenetic interrogation, and targeted pharmacological manipulations. With these tools, we aim to elucidate the developmental and molecular pathways through which maternal stress and depressive symptoms exert their long-term effects on offspring.
Moving forward, a central focus of our research is to mechanistically dissect the role of the placenta in mediating the association between maternal stress exposure and altered offspring outcomes. The placenta is increasingly recognized as a dynamic and responsive interface between maternal and fetal systems, capable of shaping developmental trajectories through regulation of endocrine function, nutrient transport, immune signaling, and epigenetic programming. By integrating placental biology into our experimental framework, we aim to identify specific molecular and cellular processes that drive stress-related neurodevelopmental vulnerability. Ultimately, our goal is to advance the preclinical identification of early interventions that may attenuate—or even prevent—the long-term consequences of maternal stress and depression on the developing brain.
Selected publications:
- Scarborough J, Iachizzi M, Schalbetter SM, Müller FS, Weber-Stadlbauer U, Richetto J: Prenatal and postnatal influences on behavioral development in a mouse model of preconceptional stress. (2024) Neurobiol Stress. 3;29:100614.
- Scarborough J, Mueller FS, Weber-Stadlbauer U, Mattei D, Opitz L, Cattaneo A, Richetto J: A novel murine model to study the impact of maternal depression and antidepressant treatment on biobehavioral functions in the offspring. (2021) Molecular Psychiatry. 26(11):6756-6772.