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.