Dataset Information

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity.

ABSTRACT: Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD. Adult females who met formal diagnostic criteria for MDD, SAD or MDD-SAD and psychiatrically healthy participants underwent functional magnetic resonance imaging as they listened to statements directing praise or criticism at them or at another person. MDD groups showed reduced responding to praise across a distributed cortical network, an effect potentially mediated by thalamic nuclei undergirding arousal-mediated attention. SAD groups showed heightened anterior insula and decreased default-mode network response to criticism. The MDD-SAD group uniquely showed reduced responding to praise in the dorsal anterior cingulate cortex. Finally, all groups with psychopathology showed heightened response to criticism in a region of the superior frontal gyrus implicated in attentional gating. The present results suggest novel neural models of anhedonia in MDD, vigilance-withdrawal behaviors in SAD, and poorer outcome in MDD-SAD. Importantly, in identifying unique and common neural substrates of MDD and SAD, these results support a formulation in which common neural components represent general risk factors for psychopathology that, due to factors that are present at illness onset, lead to distinct forms of psychopathology with unique neural signatures.

SUBMITTER: Hamilton JP

PROVIDER: S-EPMC4381237 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity.

Hamilton J Paul JP Chen Michael C MC Waugh Christian E CE Joormann Jutta J Gotlib Ian H IH

Social cognitive and affective neuroscience 20140717 4

Assessing neural commonalities and differences among depression, anxiety and their comorbidity is critical in developing a more integrative clinical neuroscience and in evaluating currently debated categorical vs dimensional approaches to psychiatric classification. Therefore, in this study, we sought to identify patterns of anomalous neural responding to criticism and praise that are specific to and common among major depressive disorder (MDD), social anxiety disorder (SAD) and comorbid MDD-SAD ...[more]

PMID: 25038225

Similar Datasets

Project description:BackgroundSocial anxiety disorder (SAD) and major depressive disorder (MDD) are highly comorbid and share impairments in self-referential and social processing. Many naturalistic judgements activate these processes concurrently, which can be referred to as "self-other referential processing". We sought to examine its neural correlates in young people with SAD and MDD using a novel experimental task.MethodsFifty six young people aged 16 to 25 with diagnoses of SAD and/or MDD (15 with SAD [M = 20.3 years, 60% female], 17 with MDD [M = 19.8 years, 53% female], 24 with comorbid SAD and MDD [M = 19.8 years, 67% female]) and 76 age and gender-matched healthy controls (HCs; M = 20.7 years, 66% female) completed a novel self-other referential processing fMRI task that involved rating how much one related to emotional faces in active conditions and judging how far apart each person's eyes were in control conditions.ResultsParticipants with SAD had more and those with MDD had less activity in social cognitive areas than HCs when processing social information across all conditions and emotion types. Participants with comorbid SAD-MDD exhibited a distinct pattern of neural activity to patients with single diagnoses. Across the whole sample, the activation of reward system areas (the medial orbitofrontal cortex and caudate) in response to increasing relatedness correlated positively with a dimensional measure of social anxiety.ConclusionsYoung people with SAD, MDD and comorbid SAD-MDD showed deficits in social processing, but they were not specifically related to self-other referential processing. Dimensional social anxiety symptoms were correlated with reward system activation, suggesting that such symptoms are associated with an overestimation of the hedonic value of social stimuli. These novel findings have implications for our understanding of the neural correlates of SAD and MDD, suggesting that alterations in social processing and reward functioning underlie the impairments in self and social processing that characterize both disorders.

Project description:The molecular etiology of invididual differences in complex behavior traits and susceptibility to psychiatric illness remains incomplete. Using an unbiased genetic approach in a mouse model, Quantitative Trait Loci (QTL) influencing anxiety-like behaviors and beta-carboline-induced seizure vulnerability have been mapped to the distal portion of mouse chromosome 10 and an interval specific congenic strain (ISCS; A.B6chr10; 66 cM to telomere) was developed. This A.B6chr10 strain facilitated defining the behavioral influences of this region as well as gene expression profiling to identify candidate gene(s) underlying this QTL. By microarray studies, an unsuspected E3 Ubiquitin Ligase, Ring Finger 41 (Rnf41 / Neuregulin Receptor Degrading Protein1; Nrdp1) was differentially expressed in the region of interest, comparing the hippocampi of A/J vs A.B6chr10 mice as well as A/J vs B6 mice. By RT-PCR, Rnf41 expression levels were significantly increased 1.5 and 1.3-fold in the hippocampi of C57BL6/J and A.B6chr10 mice compared to A/J mice, respectively. In addition, protein levels of Rnf41 were increased in hippocampi of B6 mice compared to A/J mice across postnatal development with a 5.5-fold difference at P56. Among LxS recombinant inbred mice (N=33), Rnf41 hippocampal mRNA expression levels were significantly correlated with open field behavior (r= .454, p=.0073). Re-analyzing a microarray database of human post-mortem prefrontal cortex (Brodmannâ??s Area 46/10), RNF41 mRNA expression levels were reduced significantly in patients with major depression and bipolar disorder compared to unaffected controls. Overall, Rnf41 is a pleiotropic candidate gene for anxiety-like behaviors, depression, and vulnerability to seizures. RNF41 and its binding partners provide novel etiological pathways for influencing behavior, highlighting a potential role for the ubiquitin proteasome system in psychiatric illness. Keywords: strain difference, genetic variation Microarray Affymetrix GeneChip: From three independent pools (3 hippocampi /pool) of total RNA for each line, probe was labeled, hybridized as one pool per GeneChip, using a total of six mouse MOE 430 arrays (Affymetrix, Santa Clara, CA). The sequential steps of reverse transcriptions, purification of ds cDNA, in vitro transcription and labeling of cRNA with biotin (Enzo BioArray High Yield RNA Transcript Labeling Kit), fragmentation of cRNA, hybridization to gene chips in a Affymetrix fluidics station 400 system, staining with streptavidin-phycoerythrin, washings, and scannings with a GeneArray Scanner were performed as described in the detailed protocols of the Affymetrix GeneChip Expression Analysis Technical Manual (Affymetrix, Santa Clara, CA) by the UTSW Microarray Core. The Affymetrix two GeneChip MOE 430 A and B set contains more than 45,000 probe sets, interrogating the expression level of 34,000 mouse gene transcripts. Illumina Microarray For the P0.5 microarray study, total RNA from a whole brain was individually used per Sentrix Mouse-6 BeadChip (Illumina, San Diego, CA), allowing individual samples to be evaluated and an increased sample size, namely six P0.5 mouse brains for each of three lines (A/J, B6, A.B6chr10). The Sentrix Mouse-6 BeadChip contains total 47,769 gene-specific, 70-mer oligonucleotide probes. Total RNA from each brain tissue of P0.5 mice was extracted in Trizol as above, reverse transcribed, labeled, and hybridized with a microarray according to the manufacturerâ??s detailed protocol (Illumina, San Diego, Ca.). Briefly, total RNA was reverse transcribed, then in vitro transcribed to cRNA and labeled with biotin-16-UTP. The labeled probe was hybridized to Illumina's Sentrix mouse-6 Expression BeadChips (Illumina, San Diego, CA), washed, and scanned with Illumina's BeadStation 500GX Genetic Analysis System in the UTSW Microarray core.

Dataset Information

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity.

Publications

Distinctive and common neural underpinnings of major depression, social anxiety, and their comorbidity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets