Abstract

STRESS, CONNECTIVITY, and COGNITIVE DECLINE

D. Lyons; M. Moseley; A. Schatzberg
42st Annual Meeting of the American College of Neuropsychopharmacology. 2003.

Studies of stress, cortisol, and cognition often focus on the hippocampus despite evidence that complex brain functions depend on distributed networks. Here, we show that hypercortisolism may affect neurocognitive functions by disrupting prefrontal white matter connectivity in monkeys. Adult squirrel monkeys were randomized to either an 18-month social stress (SS) protocol or a no-stress (NS) control condition. Plasma levels of cortisol were 58% greater in SS males relative to NS males after the treatment conditions. SS and NS females did not differ and resembled the NS males. Differences in male monkey cortisol levels were associated with differences in reward-related spatial reversal memory. Males with higher cortisol levels made fewer reach attempts toward the previously baited site after reversals relative to males with normal cortisol levels. Statistical parametric mapping techniques were used to detect group differences in magnetic resonance diffusion tensor imaging (DTI) measures of white matter diffusion anisotropy. A cluster of contiguous voxels was discerned with diminished diffusion anisotropy in SS monkeys relative to the NS monkey controls. In terms of total size, this cluster encompassed 2% of all white matter and extended from prefrontal regions to the anterior limb of the internal capsule. White matter is composed of axons sheath in myelin produced by oligodendrocytes. Chronic exposure to corticosterone in rats decreases adult rates of oligodendrocyte proliferation, and may thereby inhibit the normal regenerative process of myelin repair. Ongoing studies are designed to test the hypothesis that chronic hypercortisolism affects cognitive functions by disrupting proliferation of oligodendrocytes and white matter connectivity. Supported by NIH grant MH47573 and the Pritzker Neuropsychiatric Disorder Research Consortium Fund.