Project Summary

Susan L. Andersen, Ph.D. (Young Investigator 2002) of McLean Hospital, is studying the role that an early, adverse experience plays in depression and schizophrenia.  Factors such as stress, viral exposure and hypoxia/anoxia have been associated with depression and schizophrenia, and can influence the expression of an underlying genetic predisposition.  Most of these disorders do not appear until after puberty.  One possible mechanism that can account for this delay in expression is the elimination of synapses and receptors that occurs during the transition between adolescence and adulthood.  Also, reductions in hippocampus size have been reported in depression and have been hypothesized to be a risk factor, and early lesions of the ventral hippocampus produce similar dopaminergic deficits post-pubertally such as those observed in schizophrenia.  Chronic stress induces changes in the hypothalamic-pituitary-adrenal (HPA) axis, monoamine systems and GABA/benzodiazepine systems. Through an animal model, Dr. Andersen has previously shown that the species-relevant stressor of an early maternal separation prevents the overproduction of synapses after the removal of the stressor.  She will now attempt to determine if early maternal stress “kindles” hippocampal atrophy to futureless following additional stress challenges and to determine whether intervention strategies can reinstate synaptic density following stress.  This is a preclinical model of treatment for the enduring effect of early adverse experience on brain development.  Data generated will determine the role of a subsequent “second hit” (i.e., additional social stress) on synaptic density, as well as provide information about treatment with three agents that have been shown to be effective in reducing effects of chronic stress in adult rats. 

Program Area: MULTIPLE FOCUS AREAS\Schizophrenia/Mood Disorders\Child/Adolescent

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