Hypothalamic-prolactin axis regulation in major depressed patients with suicidal behavior

Area of Science:

• Neuroendocrinology
• Psychiatry
• Clinical Neuroscience

Background:

• Limited understanding of hypothalamic-prolactin axis regulation by dopamine (DA) and thyrotropin-releasing hormone (TRH) in depressed patients with suicidal behavior disorder (SBD).
• Investigating neuroendocrine markers associated with suicidal behavior in major depressive disorder.

Purpose of the Study:

• To evaluate prolactin (PRL) responses to apomorphine (APO) and protirelin (TRH) in depressed patients with SBD and healthy controls (HCs).
• To identify potential neuroendocrine differences linked to suicidal behavior severity and lethality.

Main Methods:

• Assessed PRL responses to APO (DA agonist) and TRH tests (0800h and 2300h) in 50 medication-free, euthyroid DSM-5 major depressed inpatients with SBD (current or in remission) and 18 HCs.
• Compared baseline PRL, PRL suppression to APO (PRLs), PRL stimulation to TRH (∆PRL), and ∆∆PRL values across groups.

Main Results:

• Baseline PRL levels were similar across groups.
• Depressed patients with current SBD exhibited lower PRLs and ∆∆PRL values compared to HCs and those in remission.
• Current SBD patients with a history of violent, high-lethality suicide attempts were more likely to show co-occurrence of low ∆∆PRL and PRLs.

Conclusions:

• Hypothalamic-prolactin axis regulation is impaired in depressed patients with current SBD, especially those with serious suicide attempts.
• Findings support a hypothesis of decreased pituitary D2 receptor functionality and hypothalamic TRH drive as potential biosignatures for high-lethality suicide attempts.