Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment.

Moral judgments are produced through the coordinated interaction of multiple neural systems, each of which relies on a characteristic set of neurotransmitters. Genes that produce or regulate these neurotransmitters may have distinctive influences on moral judgment. Two studies examined potential genetic influences on moral judgment using dilemmas that reliably elicit competing automatic and controlled responses, generated by dissociable neural systems. Study 1 (N = 228) examined 49 common variants (SNPs) within 10 candidate genes and identified a nominal association between a polymorphism (rs237889) of the oxytocin receptor gene (OXTR) and variation in deontological vs utilitarian moral judgment (that is, judgments favoring individual rights vs the greater good). An association was likewise observed for rs1042615 of the arginine vasopressin receptor gene (AVPR1A). Study 2 (N = 322) aimed to replicate these findings using the aforementioned dilemmas as well as a new set of structurally similar medical dilemmas. Study 2 failed to replicate the association with AVPR1A, but replicated the OXTR finding using both the original and new dilemmas. Together, these findings suggest that moral judgment is influenced by variation in the oxytocin receptor gene and, more generally, that single genetic polymorphisms can have a detectable effect on complex decision processes.

Relationship between genetic variation in the glutaminase gene GLS1 and brain glutamine/glutamate ratio measured in vivo.

BACKGROUND: Abnormalities in glutamatergic neurotransmission are implicated in several psychiatric disorders, but in vivo neurochemical studies of the glutamate (Glu) system have been hampered by a lack of adequate probes. By contrast, glutamine (Gln) and Glu can be quantified separately in proton magnetic resonance spectroscopy studies in vivo. Accumulating evidence suggests that the Gln/Glu ratio is a putative index of glutamatergic neurotransmission but interpretation of changes in the Gln/Glu ratio depends on the conditions of the system, including ammonia levels. METHODS: Here, we explored whether variation in GLS1 (the gene encoding the brain isoform of glutaminase, which catalyzes Gln-to-Glu conversion) is associated with Gln/Glu measured in vivo in two brain regions (anterior cingulate cortex, parieto-occipital cortex). RESULTS: A specific haplotype of four single nucleotide polymorphisms within GLS1 was significantly associated with Gln/Glu in the parieto-occipital cortex in an magnetic resonance spectroscopy-genetics dataset optimized for Gln/Glu detection (n = 42). This finding was replicated in a second magnetic resonance spectroscopy dataset that was optimized for γ-aminobutyric acid detection where Gln and Glu measurements could still be extracted (n = 40). CONCLUSIONS: These findings suggest that genetic variation in a key component of glutamatergic machinery is associated with a putative in vivo index of glutamatergic neurotransmission. Thus, GLS1 genotype might provide insight into normal brain function and into the pathophysiology of many psychiatric conditions where glutamatergic neurotransmission has been implicated. It might also serve as a biomarker for predicting response to existing and novel therapeutic interventions in psychiatry that target glutamatergic neurotransmission.

Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n=103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.