Evidence Of Differential Changes In Cortical Thickness And Volume Between Ssri And Placebo Treated Patients With Major Depressive Disorder

Bartlett, Elizabeth; DeLorenzo, Christine; Sharma, Priya; Yang, Jie; Zhang, Mengru; Petkova, Eva; Weissman, Myrna M.; McGrath, Patrick; Fava, Maurizio; Ogden, R. Todd; Kurian, Benji; Malchow, Ashley; Cooper, Crystal; Trombello, Joseph; McInnis, Melvin; Adams, Phil; Oquendo, Maria; Pizzagalli, Diego; Trivedi, Madhukar; Parsey, Ramin

Background: Cognitive behavioral therapy (CBT) is effective for a substantial minority of patients with major depressive disorder (MDD), but its mechanism of action is unknown, and predictors of treatment outcome are lacking. As core techniques of CBT seek to enhance emotion regulation, we examined the neural correlates of emotion regulation using functional Magnetic Resonance Imaging (fMRI) before and after a course of CBT for MDD. Methods: 31 unmedicated MDD participants underwent baseline fMRI scanning during tasks in which they engaged in a voluntary emotion regulation strategy during A) recall of negative autobiographical memories and B) presentation of emotionally aversive photographs. 23 participants completed scanning post-treatment. Treatment outcome was assessed using the Beck Depression Inventory and the Hamilton Depression Rating Scale. Image processing and statistical analyses were performed in FSL. Results: While regulating responses to negative autobiographical memories, those with better treatment outcome showed post-treatment suppression of BOLD contrast in subgenual anterior cingulate, medial prefrontal cortex, and lingual gyrus clusters (voxel-wise z>3.1, FWE-corrected p <0.05). From the photographs task, greater pre-treatment BOLD responses to emotionally negative images in a cluster in hippocampus predicted worse treatment outcome (statistical thresholding as above). Conclusions: CBT response may be mediated by enhanced downregulation of neural activity during emotion regulation; regions identified overlap with those found using a similar task in a normative sample, and are implicated in self-referential/ emotion processing. Hippocampal activation during viewing of aversive images may reflect overgeneralization processes predisposing to poor treatment outcome. Future studies should examine the specificity of these effects to CBT.


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Biological Psychiatry

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February 1, 2022