The correlation between biochemical abnormalities in frontal white matter, hippocampus and serum thyroid hormone levels in first-episode patients with major depressive disorder

• Lower NAA/Cr ratio in the bilateral WMP indicating reduced neuronal function in MDD patients.
• Lower Cho/Cr ratio in the right WMP indicating decreased membrane turnover, or impaired intracellular signal transduction systems in MDD patients.
• Thyroid dysfunction was found in the MDD patients, which may correlate with the dysfunction of neuronal function in the WMP.

BackgroundPrevious neuroimaging studies found evidence of potential brain biochemical abnormalities in patients with major depressive disorder (MDD). Abnormal serum thyroid hormone levels were also found in MDD patients, which may correlated with the abnormal biochemical metabolism of brain. However, they rarely excluded the compounding effects of medication, and brain degeneration. This study sought to investigate the relationship between the biochemical metabolism and the serum thyroid hormone levels in first-episode, treatment-naive, non-late-life patients with MDD.Methods26 first-episode, treatment-naive, non-late-life patients with MDD and 13 healthy controls were enrolled in this study. Participants underwent two-dimensinal multivoxel proton magnetic resonance spectroscopy (1H MRS) [repetition time (TR)=1000 ms; echo-time (TE)=144 ms] at 1.5 T to obtain bilateral metabolite levels from the white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC), and hippocampus. The ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline containg compounds (Cho)/creatine (Cr) were calculated. Morning serum free triiodothyronine (FT3), free thyroxin (FT4), total triiodothyronine (T3), total thyroxin (T4), and thyroid-stimulating hormone (TSH) were measured before antidepressant treatment.ResultsOn the comparison of brain biochemical changes, MDD patients had a significantly lower NAA/Cr ratio in the left WMP, and lower NAA/Cr and Cho/Cr ratios in the right WMP when compared to the controls. There were no significant differences in the metabolite ratios in the bilateral ACC, and hippocampus. On the comparison of serum thyroid hormone levels, MDD patients had a significantly decreased T3 and TSH levels. On the comparison of correlation of brain biochemical changes and serum thyroid hormone levels in patients with MDD, the NAA/Cr ratio in the right WMP was positively correlated with the level of TSH.ConclusionThese findings suggest that biochemical abnormalities and thyroid dysfunction may emerge early in the course of MDD. Dysfunction of neuronal function in the WMP may correlate with the abnormal TSH in patients with MDD, which may be related to the neuropathology of depression.