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Corticotropin-releasing hormone challenge in prepubertal major depression
B Birmaher1, R E Dahl, J Perel
1Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, PA 15213, USA.
Insights
Cortisol and ACTH responses to corticotropin-releasing hormone were similar in children with major depressive disorder (MDD) and controls. However, melancholic and inpatient MDD subgroups showed distinct hormonal patterns, suggesting potential continuities with adult depression studies.
Area of Science:
- Endocrinology
- Neuroscience
- Child Psychiatry
Background:
- The hypothalamic-pituitary-adrenal (HPA) axis is implicated in major depressive disorder (MDD).
- Previous research suggests HPA axis abnormalities are less common in early-onset depression compared to adult-onset depression.
Purpose of the Study:
- To investigate cortisol and adrenocorticotropic hormone (ACTH) responses to human corticotropin-releasing hormone (CRH) in prepubertal children with MDD.
- To compare these responses between children with MDD and healthy controls.
- To explore differences within MDD subgroups (melancholic vs. non-melancholic, inpatient vs. outpatient).
Main Methods:
- 34 prepubertal children with MDD and 22 healthy controls underwent a CRH stimulation test.
- Participants received an infusion of 1 microgram/kg human CRH.
- Blood samples were collected for cortisol and ACTH measurements at baseline and post-CRH stimulation.
Main Results:
- No significant differences in overall cortisol or ACTH levels were found between children with MDD and healthy controls.
- Children with melancholic depression exhibited significantly higher baseline cortisol levels than non-melancholic children.
- Inpatient and melancholic MDD subgroups showed significantly lower total ACTH secretion post-CRH compared to outpatients and non-melancholic children, respectively.
Conclusions:
- Overall HPA axis function, as measured by CRH stimulation, appears largely intact in prepubertal MDD.
- Specific subgroups, particularly melancholic and inpatient children, display altered ACTH secretion patterns.
- These subgroup findings suggest potential HPA axis continuities between early-onset and adult-onset depression.
Abstract:
This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.