Alterations induced by gestational stress in brain morphology and behaviour of the offspring

Retrospective studies in humans suggest that chronic maternal stress during pregnancy, associated with raised plasma levels of CRH, ACTH and cortisol may increase the likelihood of preterm birth, developmental delays and beba vioural abnormalities in the children. In adulthood, it may contribute to t he significant association between the incidence of schizophrenia, increase d left or mixed handedness, reduction in cerebral asymmetry and anomalies i n brain morphology. Our studies and others have shown that prenatal stress in rats can mimic these developmental and behavioural alterations. These ra ts show a reduced propensity for social interaction, increased anxiety in i ntimidating or novel situations and a reduction in cerebral asymmetry and d opamine turnover, consistent with those in schizophrenic humans. Prenatally -stressed (PS) rats also show behaviour consistent with depression, includi ng a phase-shift in their circadian rhythm for corticosterone, sleep abnorm alities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions. These behavioural abnormalities are associate d with impaired regulation of the hypothalamic-pituitary-adrenal axis respo nse to stress and increased CRH activity. PS males may show demasculinisati on and feminisation of their sexual behaviour. The developmental and behavi oural abnormalities in PS offspring could occur through sensitisation of th e foetal brain by maternal stress hormones to the action of glucocorticoid and CRH and to neurotransmitters affected by them. This may have long-lasti ng consequences and could explain the precipitation of depressive symptoms or schizophrenia by psychosocial stress in later life. The character of the behavioural abnormalities probably depends on the timing of the maternal s tress in relation to development of the particular neuronal systems. (C) 20 01 Elsevier Science Ltd. All rights reserved.