Early-stage psychotherapy produces elevated frontal white matter integrity in adult major depressive disorder

Abstract

Background: Psychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter.

Methods: Twenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis.

Results: Post-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe.

Conclusions: At an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the "top-down" mechanism of psychotherapy.

Figure 1. Fractional anisotropic (FA) changes in MDD subjects relative to healthy controls, shown through sagittal, transverse, and coronal views (p<0.001, uncorrected).

(A): Decreased FA in the right cuneus gyrus white matter. (B)(C)(D): Increased FA in the right thalamus, right postcentral gyrus, and cerebellar vermis, respectively.

Figure 2. Fractional anisotropic (FA) changes after four weeks of GI therapy, shown through sagittal, transverse, and coronal views using a four-voxel interval (p<0.01, uncorrected).

(A): Increased FA in the left supplementary area. (B): Decreased FA in right angular gyrus.