Abstract
Major depressive disorder (MDD) and schizophrenia (SZ) are considered two distinct psychiatric disorders. Yet, they have considerable overlap in symptomatology and clinical features, particularly in the initial phases of illness. The amygdala and prefrontal cortex (PFC) appear to have critical roles in these disorders; however, abnormalities appear to manifest differently. In our study forty-nine drug-naïve, first-episode MDD, 45 drug-naïve, first-episode SZ, and 50 healthy control (HC) participants from 13 to 30 years old underwent resting-state functional magnetic resonance imaging. Functional connectivity (FC) between the amygdala and PFC was compared among the three groups. Significant differences in FC were observed between the amygdala and ventral PFC (VPFC), dorsolateral PFC (DLPFC), and dorsal anterior cingulated cortex (dACC) among the three groups. Further analyses demonstrated that MDD showed decreased amygdala-VPFC FC and SZ had reductions in amygdala-dACC FC. Both the diagnostic groups had significantly decreased amygdala-DLPFC FC. These indicate abnormalities in amygdala-PFC FC and further support the importance of the interaction between the amygdala and PFC in adolescents and young adults with these disorders. Additionally, the alterations in amygdala-PFC FC may underlie the initial similarities observed between MDD and SZ and suggest potential markers of differentiation between the disorders at first onset.
Highlights
Treatment approaches toward major depressive disorder (MDD) and SZ differ in targets, pharmacologic agents, use of somatic therapy, and duration of treatment, and accurate diagnosis is important in determining appropriate treatment for individuals with these disorders
Two key brain regions involved in emotional and cognitive processing, the amygdala and prefrontal cortex (PFC), have been strongly implicated in both MDD and SZ. [In this article, the PFC is defined as the dorsal lateral PFC (DLPFC), critically engaged in cognitive regulation of emotion[15] and working memory task[16]; the dorsal medial PFC including the dorsal anterior cingulated cortex and its anterior section of frontal cortices– closely linked with conflict monitoring and reward processing and cognitive-motor functions[17,18,19]; and the ventral PFC (VPFC) including the orbitofrontal cortex (OFC), the inferior and rostral frontal cortices, ventral and rostral components of the ACC, mainly associated with emotional[20] and hedonic processing21]
Consistent with previous magnetic resonance imaging (MRI) studies in MDD or SZ, we hypothesized that (1) amygdala-PFC resting-state FC (rsFC) would be altered in the MDD and SZ groups, compared to the healthy control (HC) group, (2) there would be similarities in amygdala-DLPFC rsFC abnormalities between the MDD and SZ group, (3) there would be differences in amygdala to other regions of PFC rsFC abnormalities between the MDD and SZ group, for example, amygdala-VPFC rsFC abnormalities in MDD and amygdala-dorsal anterior cingulated cortex (dACC) rsFC alterations in SZ
Summary
MDD and SZ participants were recruited from the outpatient clinics at the Department of Psychiatry, First Affiliated Hospital of China Medical University, Shengyang China. Individuals were excluded if any of the following were present: (1) any MRI contraindications; (2) history of head trauma with loss of consciousness 5 or more minutes or any neurological disorder; and (3) any concomitant major medical disorder. The first 10 images were deleted, and the data underwent further preprocessing, including slice timing correction, head motion correction, spatial normalization and smoothing. Functional connectivity analysis was performed using correlation analysis between the seed amygdala ROI and PFC mask in a voxel-wise manner using REST. Z-values were extracted from the PFC regions showing significant differences among the three groups.
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