The effect of perinatal brain injury on dopaminergic function and hippocampal volume in adult life

Perinatal brain injuries, including hippocampal lesions, cause lasting changes in dopamine function in rodents, but it is not known if this occurs in humans. We compared adults who were born very preterm with perinatal brain injury to those born very preterm without perinatal brain injury, and age-matched controls born at full term using [18F]-DOPA PET and structural MRI. Dopamine synthesis capacity was reduced in the perinatal brain injury group relative to those without brain injury (Cohen's d = 1.36, p=0.02) and the control group (Cohen's d = 1.07, p=0.01). Hippocampal volume was reduced in the perinatal brain injury group relative to controls (Cohen's d = 1.17, p=0.01) and was positively correlated with striatal dopamine synthesis capacity (r = 0.344, p=0.03). This is the first evidence in humans linking neonatal hippocampal injury to adult dopamine dysfunction, and provides a potential mechanism linking early life risk factors to adult mental illness.