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Network-based approaches to examining stress in the adolescent brain.

ABSTRACT: Exposure to stress, particularly in periods of rapid brain maturation such as adolescence, can profoundly influence developmental processes that undergird the organization of structural and functional brain networks and that may mediate the association between stressful experiences and maladaptive outcomes. While studies in translational developmental neuroscience often focus on how specific brain regions or targeted connections are altered by stress and psychiatric disease, the emerging field of network science may be especially valuable for elucidating the impact of stress on the intricate connectomics of the adolescent brain. Here we review recent studies that use graph theory and other network science approaches to understand normative adolescent brain development, effects of childhood maltreatment on the brain, and disorders characterized by pathological responses to stress in adolescents. Overall, these studies demonstrate that graph theory can be useful in identifying and quantifying developmental processes related to segregation, integration, and localized hub influence that are affected by stress exposure and that may lead to psychopathology. Finally, we discuss limitations in the current application of graph theory in this area and suggest what we believe are important directions for future work.

SUBMITTER: Ho TC

PROVIDER: S-EPMC5991327 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Network-based approaches to examining stress in the adolescent brain.

Ho Tiffany C TC Dennis Emily L EL Thompson Paul M PM Gotlib Ian H IH

Neurobiology of stress 20180201

Exposure to stress, particularly in periods of rapid brain maturation such as adolescence, can profoundly influence developmental processes that undergird the organization of structural and functional brain networks and that may mediate the association between stressful experiences and maladaptive outcomes. While studies in translational developmental neuroscience often focus on how specific brain regions or targeted connections are altered by stress and psychiatric disease, the emerging field o ...[more]

PMID: 29888310

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Project description:Network medicine relies on different types of networks: from the molecular level of protein?protein interactions to gene regulatory network and correlation studies of gene expression. Among network approaches based on the analysis of the topological properties of protein?protein interaction (PPI) networks, we discuss the widespread DIAMOnD (disease module detection) algorithm. Starting from the assumption that PPI networks can be viewed as maps where diseases can be identified with localized perturbation within a specific neighborhood (i.e., disease modules), DIAMOnD performs a systematic analysis of the human PPI network to uncover new disease-associated genes by exploiting the connectivity significance instead of connection density. The past few years have witnessed the increasing interest in understanding the molecular mechanism of post-transcriptional regulation with a special emphasis on non-coding RNAs since they are emerging as key regulators of many cellular processes in both physiological and pathological states. Recent findings show that coding genes are not the only targets that microRNAs interact with. In fact, there is a pool of different RNAs-including long non-coding RNAs (lncRNAs) -competing with each other to attract microRNAs for interactions, thus acting as competing endogenous RNAs (ceRNAs). The framework of regulatory networks provides a powerful tool to gather new insights into ceRNA regulatory mechanisms. Here, we describe a data-driven model recently developed to explore the lncRNA-associated ceRNA activity in breast invasive carcinoma. On the other hand, a very promising example of the co-expression network is the one implemented by the software SWIM (switch miner), which combines topological properties of correlation networks with gene expression data in order to identify a small pool of genes-called switch genes-critically associated with drastic changes in cell phenotype. Here, we describe SWIM tool along with its applications to cancer research and compare its predictions with DIAMOnD disease genes.

Project description:Recent work inspired by graph theory has begun to conceptualize mental disorders as networks of interacting symptoms. Posttraumatic stress disorder (PTSD) symptom networks have been investigated in clinical samples meeting full diagnostic criteria, including military veterans, natural disaster survivors, civilian survivors of war, and child sexual abuse survivors. Despite reliable associations across reported networks, more work is needed to compare central symptoms across trauma types. Additionally, individuals without a diagnosis who still experience symptoms, also referred to as subthreshold cases, have not been explored with network analysis in veterans. A sample of 1,050 Iraq/Afghanistan-era U.S. military veterans (851 males, mean age = 36.3, SD = 9.53) meeting current full-criteria PTSD (n = 912) and subthreshold PTSD (n = 138) were assessed with the Structured Clinical Interview for DSM-IV Disorders (SCID). Combat Exposure Scale (CES) scores were used to group the sample meeting full-criteria into high (n = 639) and low (n = 273) combat exposure subgroups. Networks were estimated using regularized partial correlation models in the R-package qgraph, and robustness tests were performed with bootnet. Frequently co-occurring symptom pairs (strong network connections) emerged between two avoidance symptoms, hypervigilance and startle response, loss of interest and detachment, as well as, detachment and restricted affect. These associations replicate findings reported across PTSD trauma types. A symptom network analysis of PTSD in a veteran population found significantly greater overall connectivity in the full-criteria PTSD group as compared to the subthreshold PTSD group. Additionally, novel findings indicate that the association between intrusive thoughts and irritability is a feature of the symptom network of veterans with high levels of combat exposure. Mean node predictability is high for PTSD symptom networks, averaging 51.5% shared variance. With the tools described here and by others, researchers can help refine diagnostic criteria for PTSD, develop more accurate measures for assessing PTSD, and eventually inform therapies that target symptoms with strong network connections to interrupt interconnected symptom complexes and promote functional recovery.

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Network-based approaches to examining stress in the adolescent brain.

Publications

Network-based approaches to examining stress in the adolescent brain.

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