Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalmic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review resulsts from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73437/1/j.1749-6632.1997.tb52357.x.pd

The Clinical Interview for Depression: A comprehensive review of studies and clinimetric properties.

BACKGROUND: A comprehensive assessment of the wide spectrum of depressive symptomatology, particularly in its subclinical forms, is lacking in standard rating scales. There is also an emerging need for instruments that can detect small differences in therapeutic studies and have good sensitivity. The purpose of this paper is to review the clinimetric characteristics of Paykel's Clinical Interview for Depression (CID) and to examine the results of the studies in which the interview has been used. METHODS: Published reports which involved the use of the CID were identified by searching the following electronic databases: Medline, PsychINFO, EMBASE, and Web of Science. A manual search of the literature was also performed. RESULTS: The initial strategies yielded 169 published reports for potential inclusion in the review: 98 are discussed here. The CID has been used extensively in a variety of studies, including descriptive studies, classification by means of factor analysis and cluster analysis, and predictor variables of response to treatment or relapse. The CID has also been used as an outcome measure in several controlled clinical trials and follow-up studies of pharmacotherapy and psychotherapy of affective disorders. It has been shown to be valid and reliable, to discriminate depressives from controls, or different subgroups of depressed patients, and to reflect changes during the course of treatment, particularly when individual symptoms are considered. CONCLUSIONS: Evidence from these studies highlights the utility of the CID in clinical research and practice. Its clinimetric characteristics, particularly the broad evaluation of affective symptomatology and the sensitivity to change, make it an instrument of choice in therapeutic trials

Alpha-1-acid glycoprotein in major depressive and eating disorders

Plasma alpha 1-acid glycoprotein (AGP) levels were measured in 49 subjects with major depressive disorder, 15 subjects with anorexia nervosa and 18 subjects with bulimia nervosa, together with age- and sex-matched controls. AGP levels were elevated in depression and bulimia compared to controls. They were particularly elevated in depressed subjects who proved unresponsive to treatment with a standard course of antidepressants. In the depressed subjects, elevated AGP levels returned to control levels after treatment whether or not treatment was successful. There was a correlation between AGP and post-dexamethasone plasma cortisol levels in depression but not in bulimia and a correlation with age in depressed subjects only. There was no correlation between AGP values and tritiated imipramine binding parameters. Further studies are suggested to explore the issue of whether variations in AGP level are responsible for the abnormalities in platelet 5HT uptake and tritiated imipramine binding that have been reported in depression or for treatment non-response