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Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population.

ABSTRACT: BACKGROUND:Genetic polymorphisms that influence serotonin (5-hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism in the promoter region for the 5HT2A receptor, would be associated with PTSD in a trauma exposed population of adult African-Americans. METHODS:Using a case control design, 118 participants recruited from the primary care clinics and the campus of a historically black university who met inclusion criteria including trauma exposure provided blood samples for genomic DNA. PTSD criteria were determined by the Clinician Assessment of PTSD Scale (CAPS) and criteria for other psychiatric disorders by the Structured Clinical Interview for DSM-IV (SCID). 5HTTLPR and 5HT2A-1438A/G were genotyped using established methods. Associations of genotypes with lifetime PTSD, and models testing associations of allele "dose", were analyzed. RESULTS:Fifty-five (47%) participants met lifetime criteria for PTSD and 26 (22%) met criteria for (mostly comorbid) major depression. The 5HT2A (lower expressing) G allele was significantly associated with PTSD. We did not find significant associations with 5HTTLPR. CONCLUSIONS:Our findings suggest a relationship between genetic variation in the 5HT2A promoter region and PTSD.

SUBMITTER: Mellman TA

PROVIDER: S-EPMC2963151 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population.

Mellman Thomas A TA Alim Tanya T Brown Denver D DD Gorodetsky Elena E Buzas Beata B Lawson William B WB Goldman David D Charney Dennis S DS

Depression and anxiety 20090101 11

<h4>Background</h4>Genetic polymorphisms that influence serotonin (5-hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism in the promoter region for the 5HT2A receptor, would be associated with PTSD in a trauma exposed population of adult African-A ...[more]

PMID: 19842167

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Project description:ImportancePosttraumatic stress disorder (PTSD) is marked by the contrasting symptoms of hyperemotional reactivity and emotional numbing (ie, reduced emotional reactivity). Comprehending the mechanism that governs the transition between neutral and negative emotional states is crucial for developing targeted therapeutic strategies.ObjectivesTo explore whether individuals with PTSD experience a more pronounced shift between neutral and negative emotional states and how the intensity of emotional numbing symptoms impacts this shift.Design, setting, and participantsThis cross-sectional study used hierarchical bayesian modeling to fit a 5-parameter logistic regression to analyze the valence ratings of images. The aim was to compare the curve's slope between groups and explore its association with the severity of emotional numbing symptoms. The study was conducted online, using 35 images with a valence range from highly negative to neutral. The rating of these images was used to assess the emotional responses of the participants. The study recruited trauma-exposed individuals (witnessed or experienced life-threatening incident, violent assault, or someone being killed) between January 17 and March 8, 2023. Participants completed the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (PCL-5).ExposureOn the basis of DSM-5 criteria (endorsing at least 1 symptom from clusters B and C and 2 from D and E), participants were categorized as having probable PTSD (pPTSD) or as trauma-exposed controls (TECs).Main outcomes and measuresThe main outcome was the slope parameter (b) of the logistic curve fitted to the valence rating. The slope parameter indicates the rate at which emotional response intensity changes with stimulus valence, reflecting how quickly the transition occurs between neutral and negatively valenced states. The secondary outcome was the association between emotional numbing (PCL-5 items 12-14) and the slope parameter.ResultsA total of 1440 trauma-exposed individuals were included. The pPTSD group (n = 445) was younger (mean [SD] age, 36.1 [10.9] years) compared with the TEC group (mean [SD] age, 41.5 [13.3] years; P < .001). Sex distribution (427 women in the TEC group vs 230 in the pPTSD group) did not significantly differ between groups (P = .67). The pPTSD group exhibited a steeper slope (mean slope difference, -0.255; 89% highest posterior density [HPD], -0.340 to -0.171) compared with the controls. Across all individuals (n = 1440), a robust association was found between the slope and emotional numbing severity (mean [SD] additive value, 0.100 [0.031]; 89% HPD, 0.051-0.15). Additional analysis controlling for age confirmed the association between emotional numbing and transition sharpness (mean [SD] additive value, 0.108 [0.032]; 89% HPD, 0.056-0.159), without evidence of an age-related association (mean [SD] additive value, 0.031 [0.033]; 89% HPD, -0.022 to 0.083).Conclusions and relevanceThese findings support that individuals with PTSD undergo rapid transitions between neutral and negative emotional states, a phenomenon intensified by the severity of emotional numbing symptoms. Therapeutic interventions aimed at moderating these swift emotional transitions could potentially alleviate PTSD symptoms.

Project description:Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.We investigated whether SLC6A4 promoter polymorphisms (5-HTTLPR, rs25531) and several downstream single nucleotide polymorphisms (SNPs) modulated activity of brain regions involved in the cognitive control of emotion in post-9/11 veterans with PTSD. We used functional MRI to examine neural activity in a PTSD group (n = 22) and a trauma-exposed control group (n = 20) in response to trauma-related images presented as task-irrelevant distractors during the active maintenance period of a delayed-response working memory task. Regions of interest were derived by contrasting activation for the most distracting and least distracting conditions across participants.In patients with PTSD, when compared to trauma-exposed controls, rs16965628 (associated with serotonin transporter gene expression) modulated task-related ventrolateral PFC activation and 5-HTTLPR tended to modulate left amygdala activation. Subsequent to combat-related trauma, these SLC6A4 polymorphisms may bias serotonin signaling and the neural circuitry mediating cognitive control of emotion in patients with PTSD.The SLC6A4 SNP rs16965628 and 5-HTTLPR are associated with a bias in neural responses to traumatic reminders and cognitive control of emotions in patients with PTSD. Functional MRI may help identify intermediate phenotypes and dimensions of PTSD that clarify the functional link between genes and disease phenotype, and also highlight features of PTSD that show more proximal influence of susceptibility genes compared to current clinical categorizations.

Dataset Information

Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population.

Publications

Serotonin polymorphisms and posttraumatic stress disorder in a trauma exposed African American population.

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