Effects of Early and Recent Adverse Experiences on Adrenal Response to Psychosocial Stress in Depressed Adolescents

Abstract

Background As observed in depressed adults, there is considerable variability in the degree and direction of hypothalamic-pituitary-adrenal (HPA) dysfunction in depressed adolescents. The variability in HPA findings may be attributed to experiential factors. Methods A modified version of a standard psychosocial stressor used in adults, the Trier Social Stress Test (TSST), was administered to 30 adolescents with major depressive disorder and 25 healthy adolescent volunteers. Cortisol concentrations were measured in saliva samples collected before and after the stressor. Information also was gathered on early and recent adverse experiences with standard interviews. Results Participants from both groups had increased cortisol secretion in response to TSST. Compared with controls, depressed subjects showed more elevated and prolonged cortisol secretion in response to TSST. The combination of early-life adversity and high levels of chronic stress during adolescence was the most powerful predictor of enhanced adrenal response to the TSST. Conclusions These results support previous findings on the role of experiential factors on HPA response to stress and in the development of mood disorders. Dissection of the heterogeneous pathophysiology of adolescent depression will assist in developing more specific interventions for different subgroups of patients.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

“…The cluster analysis identified low (n = 15; mean care 16.33, SD 2.72, range [11][12][13][14][15][16][17][18][19][20], medium (n = 19; mean care 24.74, SD 2.10, range 22-28) and high (n = 29; mean care 32.52, SD 2.21, range 29-36) maternal care groups. Two of the 63 participants (both from the low maternal care group) reported separation of their parents.…”

“…[10][11][12][13] In view of results from animal research 30,31 and our own earlier studies using the MIST, 14 we had expected to find an increased cortisol stress response in participants with low maternal care. The main question arising from the current findings is what an inverted u-shaped relation could mean in terms of stress vulnerability and resistance for each maternal care group, especially since the blunted cortisol stress response in the low care group is clearly incompatible with our hypothesis.…”

“…Rao and colleagues 11 showed that a history of early-life adversity determined increased neuroendocrine stress responses in adolescents and adult women, Carpenter and colleagues 12 and MacMillan and colleagues 13 found attenuated neuroendocrine stress responses in maltreated adolescents and adults. There are only 2 human studies available, from our group, exploring the association between early-life parental care and stress responsivity.…”

Neurobiological Pathways between Chronic Stress and Depression: Dysregulated Adaptive Mechanisms?

“…HPA-axis hyperactivation has also been linked to depression in childhood via dampening of the hippocampal glucocorticoid receptor gene Nr3c1 in infant humans who have had adverse nurturing experiences, [100][101][102] leading to impaired negative feedback to the hypothalamus regarding circulating cortisol. 18 Children whose parents have died have elevated serum cortisol; 103 early and recent aversive experiences predict elevated cortisol responsivity in adolescents; 104 and elevated CRH has also been associated with depression in adults, 105 perhaps via its effect on raphe nuclei that, in turn, influence serotonin activity in the PFC. 106 Depressed suicide victims show elevated CRH in their PFC compared to non-depressed and non-suicide individuals.…”

Assessment of Perigenital Sensitivity and Prostatic Mast Cell Activation in a Mouse Model of Neonatal Maternal Separation

“…These syndromes are often comorbid and share many characteristics in that they have no associated pathology or identified underlying etiology, although dysfunction within the immune system, central nervous system, and peripheral nervous system has been shown to contribute towards the maintenance and progression of these disorders [1][2][3] . Patients with chronic pelvic pain are more likely to present with symptoms of additional, non-pelvic-related functional pain disorders and mood disorders, including anxiety, depression, and panic disorder [4][5][6] , which has been associated with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis [7][8][9][10] . Exposure to early life stress or trauma is a significant risk factor for developing HPA abnormalities and associated chronic pain syndromes 10,11 and, as such, a significant subset of patients with functional pelvic pain disorders report having experienced adverse childhood events such as abuse or neglect [12][13][14] .…”