Genetic factors involved in depressive behavior and stress reactivity in an amimal model of depression.

摘要

Depression is a complex disorder that is influenced by multiple genetic and environmental factors. Stress is one of the main precipitating factors of this disorder. Whether similar genetic factors underlie the vulnerabilities to depression and to stress reactivity, however, is not known.; The Wistar Kyoto (WKY) rat exhibits depressive behavior in several behavioral tests and is hyper-responsive to stress. In a series of studies described in this dissertation, we demonstrate that the WKY rat also exhibits sleep and hormonal abnormalities similar to human depression. To determine the relationship between the behavioral and hormonal abnormalities of this strain, we have conducted a quantitative trait loci (QTL) analysis using a WKY x Fisher 344 cross. In particular, we have investigated the relationship between depressive behavior in the forced swim test (FST) and abnormalities of the hypothalamic-pituitary-adrenal (BPA) axis, as well as the genetic components involved in these traits, in the segregating F2 population of this cross.; We have shown that in the segregating F2 population of a WKY x F344 cross there is no correlation between depressive behaviors in the FST and three separate measures of the HPA axis, suggesting that these traits are under separate genetic control. We have identified several QTL for immobility and climbing in the FST, some of which have conserved synteny with previously identified QTL for emotionality in the mouse and loci for major depression and bipolar disorder in humans. These results suggest that it is likely that genes involved in depressive disorders may be located in these QTL regions.; Our results suggest that the genetic components involved in the vulnerability to depression and those involved in the vulnerability to stress are separate. While more work is required to confirm this hypothesis, we believe that the findings in this dissertation provide an important step in determining the relationship between and the genetic components involved in depressive behavior and stress reactivity.