ArticlePsychopharmacology2012
Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated with cortisol responsivity to naloxone challenge.
Article in Psychopharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Independent and Interactive Effects of OPRM1 and DAT1 Polymorphisms on Alcohol Consumption and Subjective Responses in Social Drinkers.Alcoholism, clinical and experimental research · 2017Article
- Evaluation of the promoter region polymorphism (5-Experimental and therapeutic medicine · 2015Article
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4 authors.
Funding
Abstract
rationaleThe serotonergic and opioidergic neurotransmitter systems are critical regulators of the hypothalamic-pituitary-adrenal (HPA) axis through their respective excitatory and inhibitory inputs. Serotonin transporter (5-HTT) genotype has been studied as a marker of HPA axis dysregulation and for predicting risk of psychopathology, with mixed findings.
objectivesWe stimulated the HPA axis with naloxone, an opioid receptor antagonist, to examine cortisol reactivity based on 5-HTT-linked polymorphic region (5-HTTLPR) genotypes.
methodsHealthy community volunteers (N = 78) received intravenous (IV) placebo followed by sequential doses of IV naloxone (50, 100, 200, and 400 μg/kg) every 30 min. Plasma cortisol was measured every 15 min. Participants were genotyped for the long (L) and short (S) alleles of the 5-HTT gene and for rs25531 (A/G) in the 5-HTTLPR repetitive element and compared by the 5-HTTLPR/rs25531 genotype (triallele) and by the 5-HTTLPR genotype (biallele) classification.
resultsIn triallele analyses, individuals with one or more L(A) alleles showed higher cortisol response to naloxone compared with individuals with no L(A) alleles. In biallele analyses, less robust effects were found, although individuals with two L alleles showed a higher cortisol response compared with other genotypes.
conclusionsNaloxone blockade leads to a greater activation of the HPA axis among individuals with the L(A) allele. Including rs25531 in the analysis with the 5-HTTLPR genotype appears more sensitive in detecting genetic differences in naloxone-induced cortisol than when using only the 5-HTTLPR genotype. Future research should investigate the interactive effects between the serotonergic and opioidergic systems on HPA axis dysregulation and psychopathophysiology.
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