Disorder- and Emotional Context-Specific Neurofunctional Alterations During Inhibitory Control in Generalized Anxiety Disorder and Major Depressive Disorder

Background: Major Depressive (MDD) and Generalized Anxiety Disorder (GAD) are highly debilitating and often co-morbid disorders. The disorders exhibit partly overlapping dysregulations on the behavioral and neurofunctional level, and the determination of disorder-specific alterations may promote neuro-mechanistic and diagnostic specificity. Methods: In order to determine disorder-specific alterations in the domain of emotion-cognition interactions the present study examined emotional context-specific inhibitory control in treatment-naive, first-episode MDD (n = 37) and GAD (n = 35) patients and healthy controls (n = 35) by employing a validated affective go/no-go fMRI paradigm. Findings: On the behavioral level MDD but not GAD patients exhibited impaired inhibitory control irrespective of emotional context. On the neural level, no alterations were observed during the positive context, yet specifically MDD patients demonstrated attenuated recruitment of a broad bilateral network encompassing inferior/medial parietal, posterior frontal, and mid-cingulate regions during inhibitory control in the negative context. GAD patients exhibited a stronger engagement of the left dorsolateral prefrontal cortex relative to MDD patients and within the GAD group better inhibitory control in negative contexts was associated with higher recruitment of this region. Interpretation: Findings from the present study suggest disorder- and emotional context-specific behavioral and neurofunctional deficits in inhibitory control in MDD in negative emotional contexts and may point to a depression-specific neuropathological and diagnostic marker. In contrast, GAD patients may maintain intact inhibitory performance via compensatory recruitment of prefrontal regulatory regions. Funding Statement: This study was funded by the National Key Research and Development Program of China (2018YFA0701400) and Science & Technology Department of Sichuan Province, China (2017JY0031, JD). Declaration of Interests: There are no conflicts of interest. Ethics Approval Statement: The study was approved by the local ethics committee at the UESTC and adhered to the latest revision of the Declaration of Helsinki. Written informed consent and agreement to experimental procedures was obtained from all participants before enrollment.