Dysregulated Mitochondrial Genes and Networks with Drug Targets in Postmortem Brain of Patients with Posttraumatic Stress Disorder (PTSD) Revealed by Human Mitochondria-Focused cDNA Microarrays
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Posttraumatic stress disorder (PTSD) is associated with decreased activity in the dorsolateral prefrontal cortex (DLPFC), the brain region that regulates working memory and preparation and selection of fear responses. We investigated gene expression profiles in DLPFC Brodmann area (BA) 46 of postmortem patients with (n=6) and without PTSD (n=6) using human mitochondria-focused cDNA microarrays. Our study revealed PTSD-specific expression fingerprints of 800 informative mitochondria-focused genes across all of these 12 BA46 samples, and 119 (+/->1.25, p<0.05) and 42 (+/->1.60, p<0.05) dysregulated genes between the PTSD and control samples. Quantitative RT-PCR validated the microarray results. These fingerprints can essentially distinguish the PTSD DLPFC BA46 brains from controls. Of the 119 dysregulated genes (+/-> or =125%, p<0.05), the highest percentages were associated with mitochondrial dysfunction (4.8%, p=6.61 x 10(-6)), oxidative phosphorylation (3.8%, p=9.04 x 10(-4)), cell survival-apoptosis (25.2%, p<0.05) and neurological diseases (23.5%, p<0.05). Fifty (50) dysregulated genes were present in the molecular networks that are known to be involved in neuronal function-survival and contain 7 targets for neuropsychiatric drugs. Thirty (30) of the dysregulated genes are associated with a number of neuropsychiatric disorders. Our results indicate mitochondrial dysfunction in the PTSD DLPFC BA46 and provide the expression fingerprints that may ultimately serve as biomarkers for PTSD diagnosis and the drugs and molecular targets that may prove useful for development of remedies for prevention and treatment of PTSD.
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Variants of mitochondrial genes and dysregulation of their associated networks have been reported in the postmortem brains of patients with PTSD.
“Variants of mitochondrial genes and dysregulation of their associated networks have been reported in the postmortem brains of patients with PTSD (77).”
From Mechanistic inferences on metabolic dysfunction in posttraumatic stress disorder from an integrated model and multiomic analysis: role of glucocorticoid receptor sensitivity (2019) · cites this paper as [77]
The Abstract and Introduction report dysregulated mitochondria-focused gene expression and associated molecular networks in postmortem PTSD brain tissue. They do not report mitochondrial gene variants: the study measured RNA expression with cDNA microarrays, not genetic variation. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOur findings of defective energy metabolism replicated findings reported by other studies on patients with psychiatric disorders and in PTSD-specific population.
“Our findings of the defective energy metabolism also replicated the findings reported by other studies on patients with psychiatric disorders (91) and in PTSD-specific population (24, 77), implying mitochondrial dysfunction in PTSD.”
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- Authors
- Su, Y. A., Wu, J., Zhang, L., Zhang, Q., Su, D. M., He, P., Wang, B.-D., Li, H., Webster, M. J., Group, T. S. B. S., Rennert, O. M., & Ursano, R. J.
- Affiliations
- George Washington University (US)
- Uniformed Services University of the Health Sciences (US)
- United States Food and Drug Administration (US)
- Stanley Medical Research Institute (US)
- National Institutes of Health (US)
- Venue
- International Journal of Biological Sciences
- Publisher
- Ivyspring International Publisher
- Published
- 2008
- Volume
- 4
- Issue
- 4
- Pages
- 223-235
- ISSN
- 1449-2288 (ISSN-L)
- PMC
- PMC2500154
- OpenAlex
- W2124044398
- Cited by
- 113
- References
- 50
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 10 · 2019: 6 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 9 · 2014: 15 · 2013: 3 · 2012: 9
- FWCI
- 5.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- International Journal of Biological Sciences (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institutes of Health
- Uniformed Services University of the Health Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- post-traumatic stress disorder, dorsolateral prefrontal cortex, Brodmann area 46, mitochondrial dysfunction, gene expression profiling, oxidative phosphorylation, apoptosis, cell survival, biomarkers, postmortem brain
- MeSH terms
- Adult, Brain, Female, Humans, Male, Middle Aged, Postmortem Changes, Stress Disorders, Post-Traumatic, Cluster Analysis, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Genes, Mitochondrial, Gene Regulatory Networks
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