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Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.

ABSTRACT: Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS) derived polygenic risk scores (PRSs) for relevant psychiatric traits. We hypothesized that the association between PTSD and DMN connectivity would be moderated by genetic risk for one or more psychiatric traits such that individuals with elevated polygenic risk for psychopathology and severe PTSD would exhibit disrupted DMN connectivity.Participants were 156 white, non-Hispanic veterans of the wars in Iraq and Afghanistan who were genotyped and underwent resting state functional magnetic resonance imaging and clinical assessment. PRSs for neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based on five psychiatric disorders) were calculated using summary statistics from published large-scale consortia-based GWASs.Cross-disorder polygenic risk influenced the relationship between DMN connectivity and PTSD symptom severity such that individuals at greater genetic risk showed a significant negative association between PTSD symptom severity and connectivity between the posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for neuroticism, anxiety, and major depressive disorder did not influence DMN connectivity directly or through an interaction with PTSD.Findings illustrate the potential power of genome-wide PRSs to advance understanding of the relationship between PTSD and DMN connectivity, a putative neural endophenotype of the disorder.

SUBMITTER: Miller DR

PROVIDER: S-EPMC5523965 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.

Miller Danielle R DR Logue Mark W MW Wolf Erika J EJ Maniates Hannah H Robinson Meghan E ME Hayes Jasmeet P JP Stone Annjanette A Schichman Steven S McGlinchey Regina E RE Milberg William P WP Miller Mark W MW

Depression and anxiety 20170511 7

<h4>Background</h4>Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS) derived polygenic risk scores (PRSs) for relevant p ...[more]

PMID: 28494120

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Project description:Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized. Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects. Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity. Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics.

Project description:ObjectiveResting-state functional magnetic resonance imaging (rs-fMRI) studies of adult posttraumatic stress disorder (PTSD) have identified default-mode network (DMN) abnormalities, including reduced within-network connectivity and reduced anticorrelation between the DMN and task-positive network (TPN). However, no prior studies have specifically examined DMN connectivity in pediatric PTSD, which may differ due to neurodevelopmental factors.MethodA total of 29 youth with PTSD and 30 nontraumatized healthy youth of comparable age and sex completed rs-fMRI. DMN properties were examined using posterior cingulate cortex (PCC) seed-based connectivity and independent component analysis (ICA).ResultsContrary to findings in adult studies, youth with PTSD displayed increased connectivity within the DMN, including increased PCC-inferior parietal gyrus connectivity, and age-related increases in PCC-ventromedial prefrontal cortex connectivity. Strikingly, youth with PTSD also displayed greater anticorrelation between the PCC and multiple nodes within salience and attentional control networks of the TPN. ICA revealed greater anticorrelation between the entire DMN and TPN networks in youth with PTSD. Furthermore, DMN and TPN connectivity strength were positively and negatively associated, respectively, with re-experiencing symptoms of PTSD.ConclusionPediatric PTSD is characterized by heightened within-DMN connectivity, which may contribute to re-experiencing symptoms of PTSD and is consistent with the role of the DMN in autobiographical memory. At the same time, greater anticorrelation between the DMN and attentional control networks may represent compensatory mechanisms aimed at suppressing trauma-related thought, a notion supported by the inverse relationship between TPN strength and re-experiencing. These findings provide new insights into large-scale network abnormalities underlying pediatric PTSD, which could serve as biomarkers of illness and treatment response.

Dataset Information

Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.

Publications

Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology.

Similar Datasets

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