Prenatal stress: role in psychotic and depressive diseases

The birth of neurons, their migration to appropriate positions in the brain, and their establishment of the proper synaptic contacts happen predominately during the prenatal period. Environmental stressors during gestation can exert a major impact on brain development and thereby contribute to the pathogenesis of neuropsychiatric illnesses, such as depression and psychotic disorders including schizophrenia.

The objectives here are to present recent preclinical studies of the impact of prenatal exposure to gestational stressors on the developing fetal brain and discuss their relevance to the neurobiological basis of mental illness. The focus is on maternal immune activation, psychological stresses, and malnutrition, due to the abundant clinical literature supporting their role in the etiology of neuropsychiatric illnesses.

Prenatal maternal immune activation, viral infection, unpredictable psychological stress, and malnutrition all appear to foster the development of behavioral abnormalities in exposed offspring that may be relevant to the symptom domains of schizophrenia and psychosis, including sensorimotor gating, information processing, cognition, social function, and subcortical hyperdopaminergia. Depression-related phenotypes, such as learned helplessness or anxiety, are also observed in some model systems. These changes appear to be mediated by the presence of proinflammatory cytokines and/or corticosteroids in the fetal compartment that alter the development the neuroanatomical substrates involved in these behaviors.

Prenatal exposure to environmental stressors alters the trajectory of brain development and can be used to generate animal preparations that may be informative in understanding the pathophysiological processes involved in several human neuropsychiatric disorders.