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

BACKGROUND: So far, little is known about the control of hypothalamic-prolactin axis activity by dopamine (DA) and thyrotropin-releasing hormone (TRH) in depressed patients with suicidal behavior disorder (SBD). METHODS: We evaluated prolactin (PRL) responses to apomorphine (APO; a DA direct receptor agonist) and 0800 h and 2300 h protirelin (TRH) tests in 50 medication-free euthyroid DSM-5 major depressed inpatients with SBD (either current [n = 22], or in early remission [n = 28]); and 18 healthy hospitalized controls (HCs). RESULTS: Baseline (BL) PRL levels were comparable across the three diagnostic groups. SBDs in early remission did not differ from HCs regarding PRL suppression to APO (PRLs), PRL stimulation to 0800 h and 2300 h TRH tests (∆PRL), and ∆∆PRL values (difference between 2300 h-∆PRL and 0800 h-∆PRL values). Current SBDs showed lower PRLs and ∆∆PRL values than HCs and SBDs in early remission. Further analyses revealed that current SBDs with a history of violent and high-lethality suicide attempts were more likely to exhibit co-occurrence of low ∆∆PRL and PRLS values. CONCLUSIONS: Our results suggest that regulation of the hypothalamic-PRL axis is impaired in some depressed patients with current SBD, particularly those who have made serious suicide attempts. Considering the limitations of our study, our findings support the hypothesis that decreased pituitary D2 receptor functionality (possibly adaptive to increased tuberoinfundibular DAergic neuronal activity) together with decreased hypothalamic TRH drive might be a biosignature for high-lethality violent suicide attempts.

Relationship between chronobiological thyrotropin and prolactin responses to protirelin (TRH) and suicidal behavior in depressed patients.

BACKGROUND: So far, investigations of the relationships between suicidality and the activity of the thyrotropic and lactotropic axes are scarce and have yielded conflicting results. METHODS: We studied the thyrotropin (TSH) and prolactin (PRL) responses to 0800h and 2300h protirelin (TRH) stimulation tests, carried out on the same day, in 122 euthyroid DSM-5 major depressed inpatients with suicidal behavior disorder (SBD) (either current [n=71], or in early remission [n=51]); and 50 healthy hospitalized controls. RESULTS: Baseline TSH and PRL measurements did not differ across the 3 groups. In SBDs in early remission, the TSH and PRL responses to TRH tests (expressed as the maximum increment above baseline value after TRH [Δ]) were indistinguishable from controls. Current SBDs showed (1) lower 2300h-ΔTSH and lower ΔΔTSH values (differences between 2300h-ΔTSH and 0800h-ΔTSH) than controls and SBDs in early remission; and (2) lower baseline free thyroxine (FT4B) levels than controls. In the current SBD group, ΔΔPRL values (differences between 2300h-ΔPRL and 0800h-ΔPRL) were correlated negatively with lethality. Moreover, in current SBDs (1) violent suicide attempters (n=15) showed lower FT4B levels, lower TSH-TRH responses (both at 0800h and 2300h), and lower ΔΔTSH and ΔΔPRL values than controls, while (2) non-violent suicide attempters (n=56) showed lower ΔΔTSH values than controls and higher TSH-TRH responses (both at 0800h and 2300h) than violent suicide attempters. CONCLUSIONS: Our results suggest that central TRH secretion is not altered in depressed patients with SBD in early remission. The findings that current SBDs exhibit both decreased FT4B levels and decreased evening TSH responses (and consequently, decreased ΔΔTSH values) support the hypothesis that hypothalamic TRH drive is reduced-leading to an impaired TSH resynthesis in the pituitary during the day after the morning TRH challenge. In violent suicide attempters, the marked abnormalities of TRH test responses might indicate a greatest reduction in hypothalamic TRH drive. These results further strengthen the possibility that a deficit in central TRH function may play a key role in the pathogenesis of suicidal behavior.

Thyroid axis activity and suicidal behavior in depressed patients.

The aim of this study was to investigate the relationship between suicidal behavior and hypothalamic-pituitary thyroid (HPT) axis activity in depressed patients. The serum levels of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were evaluated before and after 0800 and 2300 h thyrotropin-releasing hormone (TRH) challenges, on the same day, in 95 medication-free DSM-IV euthyroid major depressed inpatients and 44 healthy hospitalized controls. Compared to controls: (1) patients with a positive suicide history (PSH; n=53) showed lower basal FT4 (at 0800 h: p<0.005; at 2300 h: p<0.03), but normal FT3 levels, while patients with a negative suicide history (NSH; n=42) showed normal FT4 and FT3 levels; (2) TSH responses to TRH (DeltaTSH) were blunted in NSHs (at 0800 h: p<0.03; at 2300 h: p<0.00001), but not in PSHs; (3) both NSHs and PSHs showed lower DeltaDeltaTSH values (differences between 2300 h-DeltaTSH and 0800 h-DeltaTSH) (p<0.000001 and p<0.003, respectively). Compared to NSHs, basal FT4 levels were reduced in PSHs (at 0800 h: p<0.002; at 2300h: p<0.006). HPT parameters were not significantly different between recent suicide attempters (n=32) and past suicide attempters (n=21). However, compared to controls, recent suicide attempters showed lower 2300 h-DeltaTSH (p<0.04) and DeltaDeltaTSH (p<0.002) values, and lower basal FT4 values (at 0800 h: p<0.006; at 2300 h: p<0.02). Our results, obtained in a large sample of depressed inpatients, indicate that various degrees of HPT axis dysregulation are associated with the history of suicide.