Social support and enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic–pituitary–adrenal function and thyrotropin-releasing hormone tests in patients with major depressive disorder
Introduction
Many published reports described abnormal functioning of the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axis in patients with major depression. Abnormal HPA axis function (hypersecretion of cortisol and of adrenocorticotropic hormone) is reported to occur during relapse in major depression (Holsboer, 1995a).
It has been hypothesized that either increased CRF levels (Nemeroff, 1996), or impaired glucocorticoid negative feedback accounts for HPA overactivity (Young et al., 1991). In major depression a “glucocorticoid cascade” is believed to damage the hippocampus (Sapolsky et al., 1986, O’Brien et al., 1996). According to this hypothesis, stress-induced change in cortisol level helps individuals cope with stressors, but prolonged secretion has toxic effects on the hippocampus. Holsboer-Trachsler et al. (1991) have developed a combined DEX/CRH test. HPA axis dysfunction, which frequently goes unnoticed in 40–60% of depressed patients, is associated with paradoxically increased release of ACTH and cortisol following CRH challenge. This abnormality sometimes persists and constitutes a risk factor for relapse of depression, and normalization of HPA axis function appears to precede full clinical remission (Baghai et al., 2002; Holsboer et al., 2000; Heuser et al., 1994, Holsboer-Trachsler et al., 1991, Holsboer-Trachsler et al., 1994).
Prange et al. (1972) reported that the thyrotropin-releasing hormone (TRH) stimulation test was able to detect blunted TSH responses in patients with depression. Although the feasibility of using TSH response to TRH test as a biological marker of depression has been studied extensively, the results of these studies have not been consistent. Some investigators found a relationship between results of this test and severity of depression and suggested the usefulness of TSH responses to TRH as a state marker (Extein et al., 1982, Gregoire et al., 1977), while others found no relationship between them and suggested the possibility of using TRH as a trait marker (Coppen et al., 1974). Still others were unable to show this response is useful as a marker for predicting treatment outcome (Amsterdam et al., 1996; Loosen et al., 1982).
Iovino et al. (1991) and Samuels and McDaniel (1997) reported that glucocorticoids have a suppressant effect on the TSH response to TRH.
Susceptibility to major depression might be associated with environmental risk factors such as social support status or support levels or perhaps lack of or absence of social supports and genetic risk factors (Kendler et al., 1986). Clinical studies have confirmed the importance of social support status in the development of major depressive disorders (Kendler et al., 1999). Stress induces modification of brain structure and function (Zilles et al., 1992). The hippocampus is a plastic and vulnerable area that controls the HPA activity and is affected by stress hormones (Bremner, 1999).
The Social Support Questionnaire (SSQ) is a 27-item social support inventory developed by Sarason et al., 1983, Sarason et al., 1987 and first reported in 1983. Each item presents a specific scenario and asks respondents to list the people who would be available to give support in that situation. Respondents are also asked to indicate, for each item, the extent to which they are satisfied with the support available to them using a 6-point scale. The SSQ scores are a measure of perceived social support and satisfaction with social support.
The present prospective study tested the hypothesis that social supports influence the results of the TRH test and DEX/CRH test in patients with major depressive disorder at the time of admission. This is presumably the first study about the association between social support status (i.e., availability and satisfaction with social support) and the neuroendocrine response to TRH and DEX/CRH in depression.
Section snippets
Methods
We studied consecutive patients who fulfilled all of the following inclusion criteria: (1) hospitalized at the Neuropsychiatry Clinic of the Oita University Hospital between 24 November 1998 and 31 December 2002; (2) major depressive disorder without psychotic symptoms (not having bipolar disorder) and with a major depressive episode (DSM-IV) diagnosed from a semi-structured interview; and (3) receipt of written informed consent. Exclusion criteria were (1) central nervous system disorders and
Demographic and clinical characteristics
Forty-one patients (19 men, 22 women) were studied. The median age on admission was 54 (range 22–83) years old. Duration of the index episode was 78 (3–452) weeks. The median HRSD score on admission was 25 (range 13–38). The median GAF score on admission was 40 (range 30–55). The median number of episodes was 1.6 (range 1–6). Non-convulsive EST was administered to nine of these patients. There was no in SSQ score between melancholic and non-melancholic patients (U = 173.6, p = 0.48). There was also
Discussion
The present study showed that major depressive disorder is associated with an enhanced suppression of ACTH and cortisol and that the response DEX/CRH and TRH tests are affected by social support status. Our results suggested that social support might attenuate cortisol and TSH stress responses in patients with major depressive disorder. Hypersecretion of CRH is a major factor influencing the HPA axis in major depression (Carroll et al., 1982; Kunugi et al., 2004, Linkowski et al., 1985). Social
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