Abstract

SOCIAL STRESS-RELATED CHANGES IN WHITE MATTER CONNECTIVITY

D.M. Lyons; J.M. Boyett-Anderson; C.L. Buckmaster; R.R. Sood; M.E. Moseley; A.F. Schatzberg
Society for Neuroscience 33rd Annual Meeting. 2003.

Abstract

Studies of stress-related cognitive impairments often tend to focus on the hippocampus despite evidence that complex brain functions depend on distributed networks. Here, we test the hypothesis that stress induces disruptions in white matter tracts that connect prefrontal, thalamic, and limbic forebrain regions. Statistical parametric mapping techniques were used to assess stress-induced changes in magnetic resonance diffusion tensor imaging (DTI) measures of anisotropy in squirrel monkeys randomized to an 18-month protocol of social instability or a stable undisturbed control. A single cluster of contiguous voxels with diminished anisotropy was discerned in monkeys exposed to social instability relative to the undisturbed control. In terms of total size, this cluster of voxels encompassed 2% of all white matter tissue, and extended from prefrontal regions to the anterior limb of the internal capsule. Of particular interest, diminished anisotropy was confined to the right cerebral hemisphere. Right frontal white matter disruptions are of interest because this brain region in humans mediates memory retrieval, emotion regulation, and cognitive response inhibition. Aspects of these functions are impaired in monkeys by exposure to chronic social stress. Chronic stress-levels of glucocorticoids inhibit oligodendrocyte proliferation and suppress myelination in rats. Myelin insulates axons and makes possible saltatory conduction. Diminished myelination reduces conduction velocities, and thereby alters the timing of neurotransmission across neural networks. By disrupting temporal aspects of integration across distributed networks, stress-induced changes in white matter connectivity may contribute to neurocognitive decline. Support Contributed By: NIH grant MH47573 and the Pritzker Neuropsychiatric Disorder Research Consortium Fund.