Improvement of health-related quality of life in depression after transcranial magnetic stimulation in a naturalistic trial is associated with decreased perfusion in precuneus

Background: Assessing Health-related Quality of life (HRQoL) is necessary to evaluate care and treatments provided to patients with major depressive disorder (MDD), in addition to the traditional assessment of clinical outcomes. However, HRQoL remains under-utilized to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in research or in a routine clinical setting. The primary objective of this exploratory study on MDD was to investigate the impact of low-frequency rTMS on HRQoL using the SF-36 questionnaire. A secondary objective was to study the functional neural substrate underlying HRQoL changes using neuroimaging. Methods: Fifteen right-handed patients who met DSM-IV criteria for MDD participated in the study. HRQoL was assessed using the SF-36, and regional cerebral blood (rCBF) flow using 99mTc-ECD-SPECT. Voxel based correlation was searched between concomitant changes in rCBF and in HRQoL after rTMS. Results: Role-Physical Problems dimension showed a statistical significant improvement of 73.2% (p = 0.001) and an effect size (Cohen's d) of 0.43, indicating moderate effect. Five SF-36 dimension scores and the two composite scores showed effect sizes ranged from 0.28 to 0.43. Improvement of Mental Composite Score (MCS)-SF-36 after rTMS was correlated with a concomitant decrease of precuneus perfusion (p < 0.001). Post-hoc analyses confirmed that decreased perfusion in precuneus was correlated with improvement of HRQoL, especially for MCS (r = -0.71; p < 0.001), Mental Health (r = -0.81; p < 0.001) and Social Functioning (r = -0.57; p = 0.026) dimensions. Conclusions: This study suggests low-frequency rTMS can improve HRQoL, through its role-physical problems dimension, in patients with MDD. This improvement is associated with a decreased perfusion of the precuneus, a brain area involved in self-focus and self-processing, arguing for a neural substrate to the impact of rTMS on HRQoL.