Letter to the Editor: Insight into the nonlinear association between thyroid-stimulating hormone and suicide risk in first-episode major depressive disorder

Table 1 Hypothalamic-pituitary-thyroid axis dysregulation and suicidal pathogenesis

Biological marker	Neurobiological impact	Contribution to suicidal behavior
Elevated TSH	Reflects “local” brain hypothyroidism and compensatory endocrine strain	Indicates diminished neurochemical resilience and failure of stress-buffering[3,7,9]
Low T3 (active)	Impairs conversion from T4; reduces central serotonin (5-HT) activity	Leads to mood dysregulation and “starves” the brain of cognitive energy[5,10]
5-HT1A receptor	Reduced sensitivity in the prefrontal cortex due to thyroid deficiency	Weakens “top-down” inhibition, increasing the likelihood of impulsive actions[7,9]
5-HT2 receptor	Increased sensitivity as a result of low thyroid levels	Strongly linked to the pathogenesis and progression of suicidal behavior[10]
Blunted TSH response	Failure to respond normally to thyrotropin-releasing hormone	Serves as a physiological indicator for higher risk of violent suicide attempts[11]
Hypercortisolemia	High cortisol (HPA axis) inhibits deiodinase enzymes (HPT axis)	Blocks the production of neuroprotective hormones, leading to treatment resistance[5,6]

TSH: Thyroid-stimulating hormone; HPA: Hypothalamic-pituitary-adrenal; HPT: Hypothalamic-pituitary-thyroid.