Serotonin transporter-linked polymorphic region (5-HTTLPR) genotype is associated with cortisol responsivity to naloxone challenge
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- 作者：Mary Ann C. Stephens (1)
Mary E. McCaul (1) (2)
Elise M. Weerts (1)
Gary Wand (1) (2) - 关键词：Serotonin transporter ; 5 ; HTT ; SLC6A4 ; Naloxone ; Hypothalamic–pituitary–adrenal ; HPA axis ; Cortisol ; Endogenous opioids
- 刊名：Psychopharmacology
- 出版年：2012
- 出版时间：November 2012
- 年：2012
- 卷：224
- 期：2
- 页码：223-230
- 全文大小：203KB
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Mary E. McCaul (1) (2)
Elise M. Weerts (1)
Gary Wand (1) (2)
1. Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, 550 N. Broadway, Ste. 115, Baltimore, MD, 21205, USA
2. Department of Medicine, The Johns Hopkins University School of Medicine, 720 Rutland Ave. Ross Building, Rm 863, Baltimore, MD, 21205, USA - ISSN：1432-2072
文摘
Rationale The 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. Objectives We stimulated the HPA axis with naloxone, an opioid receptor antagonist, to examine cortisol reactivity based on 5-HTT-linked polymorphic region (5-HTTLPR) genotypes. Methods Healthy community volunteers (N--8) 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. Results In triallele analyses, individuals with one or more L A sub> alleles showed higher cortisol response to naloxone compared with individuals with no L A sub> alleles. In biallele analyses, less robust effects were found, although individuals with two L alleles showed a higher cortisol response compared with other genotypes. Conclusions Naloxone blockade leads to a greater activation of the HPA axis among individuals with the L A sub> 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.