Pharmacogenetics and Pharmacotherapy of Military Personnel Suffering from Post-traumatic Stress Disorder

Abstract

Background:Posttraumatic stress disorder (PTSD) is a severe problem among soldiers with combating experience difficult to treat. The pathogenesis is still not fully understood at the psychological level. Therefore, genetic research became a focus of interest. The identification of single nucleotide polymorphisms (SNPs) may help to predict, which persons are at high risk to develop PTSD as a starting point to develop novel targeted drugs for treatment.Methods:We conducted a systematic review on SNPs in genes related to PTSD pathology and development of targeted pharmacological treatment options based on PubMed database searches. We focused on clinical trials with military personnel.Results:SNPs in 22 human genes have been linked to PTSD. These genes encode proteins acting as neurotransmitters and receptors, downstream signal transducers and metabolizing enzymes. Pharmacological inhibitors may serve as drug candidates for PTSD treatment, e.g. β2 adrenoreceptor antagonists, dopamine antagonists, partial dopamine D2 receptor agonists, dopamine β hydroxylase inhibitors, fatty acid amid hydrolase antagonists, glucocorticoid receptor agonists, tropomyosin receptor kinase B agonists, selective serotonin reuptake inhibitors, catechol-O-methyltransferase inhibitors, gamma-amino butyric acid receptor agonists, glutamate receptor inhibitors, monoaminoxidase B inhibitors, N-methyl-d-aspartate receptor antagonists.Conclusion:The combination of genetic and pharmacological research may lead to novel target-based drug developments with improved specificity and efficacy to treat PTSD. Specific SNPs may be identified as reliable biomarkers to assess individual disease risk. Focusing on soldiers suffering from PTSD will not only help to improve treatment options for this specific group, but for all PTSD patients and the general population.

Vesicular monoamine transporter 2 mediates fear behavior in mice

“…VMAT2 acts in all monoaminergic brain regions, and thus variation in its expression has wide‐ranging effects on neurochemical transmission . It is difficult to attribute any one of the behavioral phenotypes described in this study to a particular monoamine neurotransmitter system or brain region; indeed, genetic variation in multiple monoaminergic systems, including in monoaminergic vesicular packaging itself, has been implicated in risk for PTSD . All three major central monoamine systems (dopamine, norepinephrine and serotonin) interact with each other, and individually to contribute to PTSD outcomes.…”

“…One avenue of research is to examine the genetic differences between trauma‐exposed individuals who develop PTSD and those that do not . Transgenerational and twin studies indicate that genetics, particularly variation in monoamine systems, play a role in the etiology of PTSD . In a recent candidate gene analysis of more than 3000 single nucleotide polymorphisms across more than 300 genes, the gene SLC18A2 , which encodes the vesicular monoamine transporter 2 (VMAT2), was identified as a risk haplotype for PTSD diagnosis in a cohort of 2538 European women and replicated in an independent cohort of 748 male and female African Americans .…”

Effects of pregabalin on neurobehavior in an adult male rat model of PTSD

“…Numerous pharmacological and nutraceutical compounds have been tested in an attempt to alleviate the symptoms of PTSD [18]. One such medication that has shown promise in clinical applications is pregabalin.…”

Expression and functions of adenylyl cyclases in the CNS

“…GWAS studies showed that ADCY8 polymorphism was associated with various neuropsychiatric disorders, including dissociative amnesia, post-traumatic stress disorder, depression and bipolar disorder [ 37 , 112 , 113 ].…”