Early infant prefrontal gray matter volume is associated with concurrent and future infant emotionality.

High levels of infant negative emotionality (NE) are associated with emotional and behavioral problems later in childhood. Identifying neural markers of high NE as well as low positive emotionality (PE) in infancy can provide neural markers to aid early identification of vulnerability, and inform interventions to help delay or even prevent psychiatric disorders before the manifestation of symptoms. Prefrontal cortical (PFC) subregions support the regulation of NE and PE, with each PFC subregion differentially specializing in distinct emotional regulation processes. Gray matter (GM) volume measures show good test-retest reliability, and thus have potential use as neural markers of NE and PE. Yet, while studies showed PFC GM structural abnormalities in adolescents and young adults with affective disorders, few studies examined how PFC subregional GM measures are associated with NE and PE in infancy. We aimed to identify relationships among GM in prefrontal cortical subregions at 3 months and caregiver report of infant NE and PE, covarying for infant age and gender and caregiver sociodemographic and clinical variables, in two independent samples at 3 months (Primary: n = 75; Replication sample: n = 40) and at 9 months (Primary: n = 44; Replication sample: n = 40). In the primary sample, greater 3-month medial superior frontal cortical volume was associated with higher infant 3-month NE (p < 0.05); greater 3-month ventrolateral prefrontal cortical volume predicted lower infant 9-month PE (p < 0.05), even after controlling for 3-month NE and PE. GM volume in other PFC subregions also predicted infant 3- and 9-month NE and PE, together with infant demographic factors, caregiver age, and/or caregiver affective instability and anxiety. These findings were replicated in the independent sample. To our knowledge, this is the first study to determine in primary and replication samples associations among infant PFC GM volumes and concurrent and prospective NE and PE, and identify promising, early markers of future psychopathology risk.