Gender differences of neurometabolic and neuroendocrine alternations and its lateralization in adolescents with major depressive disorder.

Background: The clinical characteristics of major depressive disorder (MDD) in adolescents show notable gender-related differences, but the cause of these differences is still not understood. The current research concentrates on the changes in neurometabolism and neuroendocrine function, aiming to identify differences in endocrine function and brain metabolism between male and female adolescents with MDD.

Methods: A total of 121 teenagers diagnosed with MDD (43 males and 78 females) were enlisted as participants. Measurement was conducted on levels of endocrine hormones, which included free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), thyroid-stimulating hormone (TSH), cortisol, and adrenocorticotropic hormone (ACTH). Obtained through H-MRS, the N-acetyl aspartate (NAA) and choline containing compounds (Cho) to creatine (Cr) ratios were acquired for the prefrontal whiter matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG), thalamus, and cerebellum.

Result: After adjusting for multiple comparisons, female adolescents with MDD showed lower ACTH levels compared to their male counterparts. An increased lateralization index (LI) was observed in female patients for both the thalamic Cho/Cr ratio and the basal ganglia NAA/Cr ratio. Additionally, an intriguing finding was that in male adolescent patients, TT4 levels were significantly correlated with the Cho/Cr ratio in the left cerebellum. However, no such correlation between hormones and brain metabolism was found in females.

Conclusions: Gender differences in endocrine and neurometabolic abnormalities may contribute to the gender-specific pathophysiology of MDD in adolescent patients. Metabolic abnormalities and lateralization changes are observed in different brain regions for male and female MDD patients.