Abstract
Stress is the response of an organism to demands for change, yet excessive or chronic stress contributes to nearly all psychiatric disorders. The advent of high-throughput transcriptomic methods such as single cell RNA sequencing poses new opportunities to understand the neurobiology of stress, yet substantial barriers to understanding stress remain. Stress adaptation is an organismal survival mechanism conserved across all organisms, yet there is an infinity of potential stressful experiences. Unraveling shared and separate transcriptional programs for adapting to stressful experience remains a challenge, despite methodological and analytic advances. Here we review the state of the field focusing on the technologies used to study the transcriptome for the stress neurobiologist, and also attempt to identify central questions about the heterogeneity of stress for those applying transcriptomic approaches. We further explore how postmortem transcriptome studies aided by preclinical animal models are converging on common molecular pathways for adaptation to aversive experience. Finally, we discuss approaches to integrate large genomic datasets with human neuroimaging and other datasets.
Highlights
Neuropsychiatric disorders cause considerable disability and burden economically and to the health of people around the world
We explore how animal models have contributed to our understanding of the molecular pathology of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD)
While genetic studies have illumi nated the inherited genetic risks for these disorders, transcriptomics has provided a window into understanding the functional output of these risks and of the illness itself
Summary
Neuropsychiatric disorders cause considerable disability and burden economically and to the health of people around the world. Transcriptomic studies of neuropsychiatric disorders in both animal models and human postmortem tissue provide the best strategy for un derstanding how risk variants and stress exposure affect the molecular pathology of the central nervous system (CNS). Postmortem brain tissue provides us with a direct measurement of how risk variants may affect gene expression and perturbation of these genes in animal models pro vides critical functional validation. The transcriptome can be thought of a molecular phenotype of a particular trait or illness state in the same way as neurological disruptions such as plaques and tangles are phenotypic of Alzheimer’s disease This analogy is relevant as there are no macro-neurological features that distinguish patients with psychiatric disorders. Transcriptomic changes of MDD and PTSD and provided comprehensive genomic atlases which can be used to identify clinically relevant changes in animal model comparisons. We describe how postmortem genomics work has revolutionized our understanding of MDD and PTSD and how inte grating these large, rich data sets with other human analyses such as neuroimaging are providing critical information necessary for better biomarker identification and therapeutic design
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