Neonatal insult to the hippocampal region and schizophrenia: a review and a putative animal model.

Abstract

To review the mounting evidence implicating early hippocampal dysfunction in the pathogenesis and the pathophysiology of schizophrenia. An account is made of recent neurodevelopmental hypotheses indicating how an early dysfunction of the hippocampal region disrupts maturational events in brain systems connected to that structure, thus inducing dysfunctional connectional development. Finally, an animal model is presented. Socioemotional behaviour of monkeys (Macaca mulatta) with selective neonatal hippocampal lesions was assessed by analyzing their interactions with their age-matched controls at 2 months, 6 months, and 5 to 8 years of age and by comparing the social interactions at each age with those of normal controls paired together. At 2 months of age, monkeys with neonatal hippocampal lesions presented minor disturbances in initiation of social interactions. These subtle changes of behaviour were less evident at 6 months, although by that age, the operated monkeys displayed more withdrawals in response to an increase in aggressive responses from their unoperated peers. In adulthood, the amount of time spent by the hippocampectomized monkeys in social contacts with their normal peers decreased markedly. In addition, operated monkeys exhibited more locomotor stereotypies than normal controls. These experimental findings indicate that the time-course and nature of the behavioural disturbances resulting from early trauma to the hippocampal region have some similarities with the clinical symptoms of schizophrenic patients and the typical time-course of the disease.