Hypothalamic-pituitary-adrenal axis hyperactivity is normalized after successful intermittent theta-burst stimulation in resistant depressed patients

Psychoneuroendocrinology. 2024 Jul:165:107037. doi: 10.1016/j.psyneuen.2024.107037. Epub 2024 Mar 30.

Abstract

The present pilot study assessed the effects of multi-session intermittent theta-burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex in 17 treatment resistant depressed inpatients (TRDs) showing cortisol non-suppression to the overnight dexamethasone suppression test (DST) at baseline (i.e., maximum post-DST cortisol [CORmax] level > 130 nmol/L). After 20 iTBS sessions, the DST was repeated in all TRDs. At baseline, post-DST CORmax levels were higher in TRDs compared to healthy control subjects (HCs; n = 17) (p < 0.0001). After 20 iTBS sessions, post-DST CORmax levels decreased from baseline (p < 0.03) and were comparable to HCs. Decreases in post-DST CORmax levels were related to decreases in 17-item Hamilton Depression Rating Scale (HAMD-17) scores (ρ = 0.53; p < 0.03). At endpoint, 10 TRDs showed DST normalization (among them 7 were responders [i.e., HAMD-17 total score > 50% decrease from baseline]), and 7 did not normalize their DST (among them 6 were non-responders) (p < 0.05). Our results suggest that successful iTBS treatment may restore normal glucocorticoid receptor feedback inhibition at the pituitary level.

Keywords: Cortisol; DST; HPA axis; ITBS; RTMS; Resistant depression.

MeSH terms

  • Adult
  • Depressive Disorder, Treatment-Resistant* / metabolism
  • Depressive Disorder, Treatment-Resistant* / physiopathology
  • Depressive Disorder, Treatment-Resistant* / therapy
  • Dexamethasone*
  • Dorsolateral Prefrontal Cortex / metabolism
  • Dorsolateral Prefrontal Cortex / physiology
  • Female
  • Humans
  • Hydrocortisone* / analysis
  • Hydrocortisone* / metabolism
  • Hypothalamo-Hypophyseal System* / metabolism
  • Hypothalamo-Hypophyseal System* / physiopathology
  • Male
  • Middle Aged
  • Pilot Projects
  • Pituitary-Adrenal System* / metabolism
  • Pituitary-Adrenal System* / physiopathology
  • Theta Rhythm / physiology
  • Transcranial Magnetic Stimulation* / methods
  • Treatment Outcome

Substances

  • Hydrocortisone
  • Dexamethasone