Genomic Architecture of Functional Brain Networks in PTSD

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ABSTRACT Our overarching goal is to investigate the genetic architecture of canonical functional resting-state networks (RSN) in PTSD. The disruption of several canonical RSNs including the default mode network (DMN), ventral attention network (VAN), and salience network (SN) are strongly implicated in posttraumatic stress disorder (PTSD). These RSN alterations are associated with specific symptom clusters of PTSD (e.g. intrusive re-experiencing symptoms). Canonical RSN connectivity and regional amplitude of BOLD signal, which are associated with PTSD and its symptom dimensions, constitute highly heritable phenotypes (h2 = 0.4 – 0.6) that exceed the heritability of task-based fMRI and the majority of structural neuroimaging phenotypes. A genetic vulnerability to developing PTSD following exposure to trauma has long been hypothesized and is now supported by evidence. Discovery of the genetic factors involved in brain communication and brain connectivity that contribute to PTSD may prove vital to new treatment breakthroughs. The coupling of brain connectivity with its genetic architecture, mapping the neurogenetic pathways of PTSD, and new knowledge of neural and genetic mechanisms will support precision-medicine guided drug discovery for managing mental illnesses that follow psychological trauma. Our aims are to 1: Investigate differences in the genetic architecture of functional connectomics associated with PTSD. 2: Investigate the role of PTSD on the relationship between the genetic architecture of brain structure and functional connectomics. 3: Investigate the effects of PTSD on the link between gene transcription architecture and functional connectomics. The coupling of cortical functional connectomics with its genetic architecture and its transcriptional architecture in relation to known disruptions of functional connectomics in PTSD may offer exciting opportunities to discover targeted therapies. Mapping the neurogenetic pathways of PTSD to the severity of PTSD symptoms will also be critical to the future design, development, and selection of yet undiscovered treatments. Knowledge of their unique neural and genetic mechanisms will be vital to precision-medicine guided drug discovery for managing mental illnesses that may follow psychological trauma.