Brain GABA+ changes in primary hypothyroidism patients before and after levothyroxine treatment: A longitudinal magnetic resonance spectroscopy study

Objective: Increasing evidence indicates the involvement of the GABAergic system in the pathophysiology of hypothyroidism. We aimed to investigate longitudinal changes of brain GABA in primary hypothyroidism before and after levothyroxine (L-T4) treatment.

Material and methods: In 18 patients with hypothyroidism, we used the MEGA-PRESS (Mescher-Garwood point-resolved spectroscopy) editing sequence to measure brain GABA levels from medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC) at baseline and after 6-months of L-T4 treatment. Sex- and age-matched healthy controls (n = 18) were scanned at baseline. Thyroid function and neuropsychological tests were also performed.

Results: GABA signals were successfully quantified from all participants with fitting errors lower than 15%. GABA signal was labeled as GABA+ due to contamination from co-edited macromoleculars and homocarnosine. In hypothyroid patients, mean GABA+ was significantly lower in the mPFC region compared with controls (p = 0.031), and the mPFC GABA+ measurements were significantly correlated with depressive symptoms and memory function (r = -0.558, p = 0.016; r = 0.522, p = 0.026, respectively). After adequate L-T4 treatment, the mPFC GABA+ in hypothyroid patients increased to normal level, along with relieved neuropsychological impairments.

Conclusion: The study suggested the decrease of GABA+ may be an important neurobiological factor in the pathophysiology of hypothyroidism. Treatment of L-T4 may reverse the abnormal GABA+ and hypothyroidism-induced neuropsychiatric impairments, indicating the action mode of L-T4 in adjunctive treatment of affective disorders.