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Only a minority of people exposed to severe trauma develop post-traumatic stress disorder (PTSD), which suggests that certain factors (some of them possibly genetic) may be involved in vulnerability to PTSD. Two studies look at this question.
Mehta and colleagues studied 209 people recruited from an inner-city hospital (90% black; mostly low-income) who had experienced at least one adult trauma; 70% had developed PTSD. The researchers focused on links among PTSD, sensitivity of the glucocorticoid receptor (GR), and a single nucleotide polymorphism (SNP) of FKBP5, a GR co-chaperone involved in negative feedback regulation of the hypothalamic–pituitary–adrenal (HPA) axis. Among PTSD patients, after adjustment for childhood and adult traumas and depression, greater GR receptor sensitivity (measured by dexamethasone suppression) was associated with being an A allele carrier than with GG homozygosity, which was associated with lower baseline serum cortisol levels. Neither PTSD nor genotype alone predicted dexamethasone suppression. However, researchers identified another 41 genes (32 previously unreported) that participate in GR regulation; 19 appeared to form a network related to FKBP5 regulation of HPA axis activation in PTSD.
In Mercer and colleagues' study, 204 undergraduate women (mean age, 20), who had participated in a study of traumatic experiences, social supports, and sexual victimization, were reassessed twice after a lone shooter killed or wounded 26 people on campus (mean follow-ups, 3.2 weeks and 8.4 months). Genotyping of three loci in the serotonin transporter genetic region was performed. Severity of postshooting PTSD symptoms was predicted by the number of exposure events (e.g., hearing gunfire or being hurt), but not by previous traumas or social support. After statistical corrections and adjustment for the shooting exposure, higher PTSD symptom scores (especially avoidance) and acute stress disorder after the shooting were associated with a multimarker genotype that decreases expression of the serotonin transporter.
Mehta D et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies. Arch Gen Psychiatry 2011 Sep; 68:901.
Mercer KB et al. Acute and posttraumatic stress symptoms in a prospective gene × environment study of a university campus shooting. Arch Gen Psychiatry 2011 Sep 5 [e-pub before print]; (http://dx.doi.org/10.1001/archgenpsychiatry.2011.109)
Comment
Studies of gene interactions are subject to false positive results (see JW Psychiatry Sep 12 2011) even after traditional corrections for multiple statistical tests. Still, these studies show that vulnerability to an abnormal stress response is genetically heterogeneous. People with a specific allele in a gene network that regulates the HPA axis may be vulnerable to suppression of cortisol production resulting from burnout of the stress response. Genetic interactions that reduce resilience of serotonergic systems that moderate arousal may increase susceptibility to excessive stress responses. As genotyping becomes cheaper and more reliably tied to clinical phenotypes, clinicians may be able to identify trauma-exposed people who would respond to interventions aimed at a specific dimension of stress response systems.