Brain Bioenergetics and Response to Triiodothyronine Augmentation in Major Depressive Disorder

Background: Low cerebral bioenergetic metabolism has been reported in subjects with major depressive disorder (MDD). Thyroid hormones have been shown to increase brain bioenergetic metabolism. We assessed whether changes in brain bioenergetics measured with phosphorus magnetic resonance spectroscopy (³¹P MRS) correlate with treatment outcome during augmentation treatment with triiodothyronine (T3) in MDD. Methods: Nineteen subjects meeting DSM-IV criteria for MDD who had previously failed to respond to selective serotonin reuptake inhibitor (SSRI) antidepressant drugs received open label and prospective augmentation treatment with T3 for 4 weeks. We obtained ³¹P MRS spectra before and after treatment from all MDD subjects and baseline ³¹P MRS from nine normal control subjects matched for age and gender. Results: At baseline, depressed subjects had lower intracellular Mg²⁺ compared with control subjects. Seven MDD subjects (38.9%) were treatment responders (≥ 50% improvement). Total nucleoside triphosphate (NTP), which primarily represents adenosine triphosphate (ATP), increased significantly in MDD subjects responding to T3 augmentation compared with treatment nonresponders. Phosphocreatine, which has a buffer role for ATP, decreased in treatment responders compared with nonresponders. Conclusions: The antidepressant effect of thyroid hormone (T3) augmentation of SSRIs is correlated with significant changes in the brain bioenergetic metabolism. This seems to be a re-normalization of brain bioenergetics in treatment responders. Further studies will determine whether these findings can be generalized to other antidepressant treatments.