A research team from the Department of Psychiatry at Tohoku University, led by Dr. Zhiqian Yu and Professor Hiroaki Tomita, has uncovered compelling evidence that maternal perinatal depression - psychological distress occurring during pregnancy or postpartum - elevates the risk of autistic-related traits in toddlers, with a particularly strong impact on girls. Their findings are derived from a large-scale Japanese cohort of over 23,000 mother-child pairs (the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study) and supported by mouse experiments. These findings provide important insights into how maternal mental health influences early neurodevelopment, which could help create guidelines to protect the wellbeing of both mother and child.

Using data from the cohort, the team assessed depressive symptoms during early and mid-gestation and at one month postpartum. Higher maternal scores on the Kessler Psychological Distress Scale (K6) or the Edinburgh Postnatal Depression Scale (EPDS) were significantly associated with increased autistic-related traits in toddlers, as measured by the Tokyo Autistic Behavior Scale (TABS). Notably, although autism is generally more common in boys, the risk associated with maternal perinatal depression was especially pronounced in girls. Additionally, girls showed lower birth weights and a stronger association between autistic traits and impaired mother-infant bonding (the Mother-to-Infant Bonding Scale; MIBS).

To explore the biological mechanisms underlying these findings, the researchers established a prenatal stress model in mice "mothers". Stressed mothers displayed depressive-like behaviors and reduced maternal care, while their female offspring exhibited typical autism-like behavioral patterns, including increased self-grooming and impaired recognition of social novelty. Molecular analyses further revealed reduced expression of oxytocin (nicknamed the "love hormone") in prefrontal cortical microglia of stressed mothers and decreased oxytocin receptor expression in the prefrontal cortex of their female offspring. These findings suggest a sex-specific neurobiological pathway through which prenatal stress may disrupt social development. Because oxytocin signaling is essential for maternal bonding and social behavior, disturbances in this system may help explain why daughters appear particularly vulnerable to maternal stress.

This study highlights the societal importance of supporting maternal mental health beginning in pregnancy. Providing appropriate psychological care and monitoring may help reduce adverse developmental outcomes in children, particularly in girls. The findings underscore that maternal well-being is a critical foundation for children's long-term developmental health and provide a scientific basis for sex-sensitive early intervention strategies.

This study was not based on clinical diagnoses of maternal depression or autism spectrum disorder in children. Instead, it focused on the relationship between questionnaire-based measures of maternal depressive symptoms and indicators of autism-related behavioral traits. While the findings do not indicate that maternal perinatal depression directly causes autism spectrum disorder, they underscore the importance of supporting maternal mental health during the perinatal period, particularly in light of potential sex-specific effects on children's emotional and developmental outcomes.

The findings were published in Molecular Psychiatry, a Nature Portfolio journal, on February 4, 2026.