Dataset Information

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

ABSTRACT: Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used voxel-based morphometry to quantify amygdala GMV scores from structural neuroimaging data in a sample of 44 monozygotic twins (i.e., 22 pairs). Dispositional threat sensitivity (THT) was quantified using a biobehavioral cross-domain score that combined neurophysiological indicators with a psychological scale measure. Analyses revealed expected high concordance for amygdala GMV between co-twins. With respect to the major question of the study, a negative correlation was found between biobehavioral THT scores and amygdala volume - with individuals higher in THT showing smaller amygdala GMV scores. More modest associations of amygdala GMV with symptoms of social phobia, and fear disorder symptomology more broadly, were mediated by THT. These results provide insight into prior mixed findings and support the combined use of biological and behavioral measures to quantify characteristics relevant to mental health problems.

SUBMITTER: Foell J

PROVIDER: S-EPMC6338499 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

Foell Jens J Palumbo Isabella M IM Yancey James R JR Vizueta Nathalie N Demirakca Traute T Patrick Christopher J CJ

NeuroImage 20181028

Current literature on the relationship between dispositional fear (or threat sensitivity) and amygdala gray matter volume (GMV) is heterogeneous, with findings including positive, negative, and null correlations. A clearer understanding of this relationship would help to determine the potential utility of amygdala volume as a biomarker of anxious/depressive (internalizing) disorders and contribute to understanding of neural mechanisms for variations in fearfulness. The study reported here used v ...[more]

PMID: 30394325

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Project description:Purpose: Identification the biological response to fear and stress in both brain and blood is vital for investigators performing peripheral studies of psychiatric traits. The goal of this study was to determine genes responsive to fear conditioning (FC), a well-characterized rodent model of threat-exposure, in the presence or absence of prior stress history, providing insight into the physiological processes underlying traumatic memory formation and trauma-related disorders such as PTSD. Methods: RNA sequencing was performed in blood and amygdala from mice that underwent fear conditioning (FC) with and without prior immobilization stress history (Immo+FC), or untreated animals (home cage HC). Libraries were prepared using the Illumina TruSeq™ RNA kit as per manufacturer’s instructions. Libraries were normalized and 8 samples were multiplexed in each lane of the flowcell. PhiX was used as an internal control on each lane to monitor the error statistics. Cluster generation was performed on the V3 flowcell on the Illumina cBot. The clustered flowcell was then sequenced on the Illumina HiSeq1000 system employing a single-end 101 cycles run. Alignment to the mm10 UCSC Mouse Assembly was performed using STAR version 2.3 (Dobin et al, 2013); parameters were set using the annotation as a splice junction reference. Sample reads were assembled into transcript models using cufflinks (v2.1.1) which were then merged and processed with cuffdiff v2.1.1, (Trapnell et al, 2012) to produce per sample FPKM expression levels and estimate differential expression between the sample groups. Results: In the amygdala, 607 genes associated with FC vs. HC (FDR<.05). In the same tissue, 516 genes showed different expression in response of immobilization (Immo+FC) compared to the FC group (FDR<.05). In the blood of the same animals, 468 genes had distinct changes in expression (Immo+FC vs FC; FDR<.05) and were enriched for biological processes such as inflammation and cytokine signaling. Conclusions: This study identified genes and pathways that respond to threat in the amygdala and blood of animals with and without a prior stress history. Future studies will be needed to examine the necessity, function and relevance of these regulated genes in human clinical stress and trauma-related disorders including.

Dataset Information

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

Publications

Biobehavioral threat sensitivity and amygdala volume: A twin neuroimaging study.

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