Abstract
In adults with major depressive disorder (MDD), a dysfunction between the hypothalamus-pituitary-adrenal (HPA) and the hypothalamus-pituitary-thyroid (HPT) axis has been shown, but the interaction of both axes has not yet been studied in adolescent major depressive disorder (MDD). Data from 273 adolescents diagnosed with MDD from two single center cross-sectional studies were used for analysis. Serum levels of thyrotropin (TSH), free levothyroxine (fT4), and cortisol were determined as indicators of basal HPT and HPA axis functioning and compared to that of adolescent controls by t-tests. Quantile regression was employed in the sample of adolescents with MDD to investigate the relationship between both axes in the normal as well as the pathological range of cortisol levels, considering confounders of both axes. In adolescent MDD, cortisol levels and TSH levels were significantly elevated in comparison to controls (p = <.001, d = 1.35, large effect size, and p = <.001, d = 0.79, moderate effect size, respectively). There was a positive linear relationship between TSH and cortisol (p = .003, d = 0.25, small effect size) at the median of cortisol levels (50th percentile). However, no relationship between TSH and cortisol was found in hypercortisolemia (cortisol levels at the 97.5th percentile). These findings imply that HPT and HPA axis dysfunction is common in adolescents with MDD and that function of both axes is only loosely related. Moreover, the regulation of the HPA and HPT axis are likely subjected to age-related maturational adjustments since findings of this study differ from those reported in adults.
Highlights
The hypothalamus-pituitary-adrenal (HPA) and hypothalamuspituitary-thyroid (HPT) axes are affected in a considerable proportion of patients with major depressive disorder (MDD) (e.g., 1, 2), and endocrine dysfunction of both axes is hypothesized to be closely related (e.g., 3, 4)
Data of the present study were derived from the baseline assessments of a two-armed parallel-group, double-blind RCT which investigated the effect of vitamin D deficiency (25(OH) vitamin D ≤ 12 ng/ml [equivalent to ≤ 30 nmol/l]; DRKS00009758) on depressive symptoms in psychiatric in- or daycare patients treated at the Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy Essen (LVR-Klinikum Essen), Germany [22]
Elevated (z > 1.96) z-TSH scores were observed in 8.1% and elevated z-cortisol scores in 17.6% of patients
Summary
The hypothalamus-pituitary-adrenal (HPA) and hypothalamuspituitary-thyroid (HPT) axes are affected in a considerable proportion of patients with major depressive disorder (MDD) (e.g., 1, 2), and endocrine dysfunction of both axes is hypothesized to be closely related (e.g., 3, 4). While TSH and fT4 levels are mostly within the normal range of thyroid function parameters, TSH is decreased and ft increased when compared to controls [4] These observations have been related to two complementary mechanisms by which the HPA axis affects HPT axis functioning: a) impaired central regulation and b) altered peripheral thyroid hormone homeostasis. The resulting increase in TRH secretion has been shown to prompt TRH receptor downregulation at the level of the pituitary gland due to chronic overstimulation [10], supported by the findings of elevated TRH levels in the cerebrospinal fluid (CSF) of depressed patients [11, 12] and a blunted thyrotropin (TSH) response to TRH [13]. The resulting increase of T4 provides inhibitory feedback to the pituitary gland with a subsequent decrease in TSH secretion
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