Abstract

BackgroundRefractory major depressive disorder (MDD) is a severe mental disorder, chronic and difficult to treat. Although generalized anxiety disorder (GAD) is frequently observed as a comorbid diagnosis, little is known on the comorbid neurobiological substrate. Better insights may improve adequate treatment algorithms. ObjectiveTo examine this poorly understood clinical question, we recruited 52 individuals to participate in a [18F] FDG PET brain imaging study. MethodsTwenty-two refractory MDD patients were diagnosed with and 15 refractory MDD patients without comorbid GAD. To compare to the none-depressed state a sample of 15 age and gender matched never-depressed individuals were included. ResultsCompared to healthy control subjects, all patients showed significantly higher metabolic activity in the bilateral parahippocampal areas. Compared to MDD patients, healthy subjects displayed significant higher metabolic activity in distinct (bi)frontotemporal and parietal cortices. Refractory MDD patients without comorbid GAD showed significant higher metabolic activity in the dorsomedial parts of the frontal cortex (dmFC). ConclusionsThe impaired dmFC metabolic activity observed in comorbid GAD within refractory MDD may be indicative of specific emotional dysfunctional top-down processing in this subgroup, conform the anxiety state. Additional psychotherapeutic interventions may be warranted.

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