Role of the Allelic Variation in the 5-Hydroxytryptamine Receptor 1a (Htr1a) and the Tryptophan Hydroxylase 2 (Tph2) Genes in the Development of PTSD

Abstract

Background: Post-traumatic stress disorder (PTSD) is a stress related disorder which can occur in an individual after exposure to a traumatic event. It most commonly co-occurs with depression. The two disorders share not only overlapping symptoms, but also genetic diathesis. The aim of this study was to investigate the potential role of single nucleotide polymorphisms (SNPs) of the two serotonergic candidate genes 5-hydroxytryptamine receptor 1A (HTR1A) and tryptophan hydroxylase 2 (TPH2) in the pathogenesis of PTSD and comorbid psychopathology. Subjects and methods: 719 (487 males, 232 females) participants who had experienced war-related trauma between 1991 and 1999 in Bosnia and Herzegovina, Kosovo and Croatia were included in the study. The Sociodemographic questionnaire, Mini International Neuropsychiatric Interview (M.I.N.I.), Clinician Administered PTSD Scale (CAPS) and Brief Symptom Inventory (BSI) were used to collect clinical data. The SNPs rs6295 (HTR1A), rs11178997 and rs1386494 (TPH2) were investigated for their association with PTSD and comorbid psychopathology. Results: A nominal significant association was found between the BSI total score in Lifetime PTSD with the SNP rs6295 of the HTR1A gene. The best result was seen in the dominant model (P=0.018), with the minor allele (C) being the risk allele. Several BSI subscores were also associated with the minor (C) allele in Lifetime PTSD. No association was found for the TPH2 SNPs rs11178997 and rs1386494 in relation to PTSD or comorbid psychopathology. Conclusions: Our findings suggest that rs6295 in the HTR1A gene may contribute to the psychopathology of PTSD.

Quantitative behavioral genetic and molecular genetic foundations of the approach and avoidance strategies

“…All analyzes were performed at the allele level, so that all subjects with risk alleles were classified into one group, relying on the same strategies in previous studies (e.g., Aluja et al, 2019 ; Benko et al, 2010 ; Demetrovics et al, 2010 ; Goçi Uka et al, 2019 ; Light et al, 2007 ; Reuter et al, 2006 ; Smillie et al, 2010 ; Whitmer & Gotlib, 2012 ). There are at least two reasons for this decision.…”

“…On the other hand, increasing in serotonin transmission contributes cognitive flexibility and approaching behaviors, but decreasing could lead to higher sensibility to environments, stress, and avoidance behaviors (e.g., Goçi Uka et al, 2019 ; Kalbitzer et al, 2009 ). Therefore, the main effects of HTR1A and TPH2 on the avoidance strategies, covered by the BIS, Flight and Freeze, are expected.…”

“…HTR1A receptor ( 5-HT1A ) is the major autoreceptor on serotonergic raphe neurons, and its gene HTR1A is located on human chromosome 5q12.3. Several studies have demonstrated that G variant of the HTR1A polymorphism is associated with depression, suicidality, and PTSD (Goçi Uka et al, 2019 ; Lemonde et al, 2003 ), anxiety (Strobel et al, 2003 ), aggression (Witte et al, 2009 ) and general amygdala reactivity (e.g., Kalbitzer et al, 2009 ). Some studies suggested that G carriers are showing higher scores on Neuroticism (Schinka et al, 2004 ) and even impulsivity (e.g., Gray et al, 2018 ), but other studies did not report these connections (e.g., Kalbitzer et al, 2009 ; Koller et al, 2006 ).…”

PTSD as an Endothelial Disease: Insights From COVID-19

“…In addition, tryptophan 5-hydroxylase 2 (TPH2), an enzyme involved in serotonin synthesis, was found to have a strong mimicry with the S protein of SARS-CoV-2, potentially contributing to anxiety and depression (Yapici-Eser et al, 2021). This is significant as TPH2 plays a major role in PTSD, as well as in premature ECs senescence (Goçi Uka et al, 2019;Wu, 2021). Moreover, the molecular mimicry between the SARS-CoV-2 protein S and human anti-inflammatory proteins was associated with inflammation, a pathology demonstrated in PTSD (Kanduc, 2020).…”

Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder

“…There is emerging literature on genetic variations in mechanisms responsible for development and maintenance of PTSD (9)(10)(11). Many studies on detection of candidate genes associated with PTSD have focused on genetic variations of the dopaminergic and serotonergic systems (12)(13)(14)(15), but robust common genetic variants have yet to be identified. Since ubiquitin-proteasome-mediated proteolysis plays a crucial role in synaptic development and long-term synaptic plasticity in neural circuits (16)(17)(18)(19)(20), the ubiquitin-proteasome system is an interesting biological target for the pathophysiology of human neuropsychiatric disorders related to stress-related synaptic plasticity, such as PTSD.…”