Relevance of perceived childhood neglect, 5-HTT gene variants and hypothalamus-pituitary-adrenal axis dysregulation to substance abuse susceptibility.

Abstract

The hypotheses of (1) gene x environment interaction in the susceptibility to experiment with drugs and (2) hypothalamus-pituitary-adrenal (HPA) axis involvement in mediating the effects of early adverse experiences and gene variants affecting serotonin function on substance abuse vulnerability were tested by investigating in 187 healthy adolescents the possible relevance of 5-HTT "S" polymorphism, childhood parental neglect reported retrospectively and HPA axis function to the susceptibility to experiment with illicit drugs. Higher frequency of the 5-HTT SS genotype seems to be associated with an increased susceptibility to use illegal psychotropic drugs among the adolescents. At the same time, reduced maternal care perception was found to represent a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors and parental behavior concur to drug use susceptibility. Our results also confirm the relationship between basal plasma levels of cortisol and adrenocorticotropic hormone (ACTH) on the one hand, and retrospective measures of neglect during childhood: the higher the mother and father neglect CECA-Q scores, the higher the plasma levels of the two HPA hormones. Such positive relationship has been proved to be particularly effective and important when associated to the S-allele, both in homozygote and heterozygote individuals. However, when tested together with genotype and parental neglect, the effect of HPA hormones such as cortisol and ACTH was not found to improve significantly the explanatory power of the risk model.

• Authors: G Gerra, A Zaimovic, L Castaldini, L Garofano, M Manfredini, L Somaini, C Leonardi, M L Gerra, C Donnini
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 153B Issue 3 Pg. 715-22 (Apr 05 2010) ISSN: 1552-485X [Electronic] United States
• PMID: 19824018 (Publication Type: Journal Article)

Chemical References

• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins

Topics

• Adolescent
• Child Abuse
• Female
• Genetic Predisposition to Disease
• Humans
• Hypothalamo-Hypophyseal System (physiopathology)
• Logistic Models
• Male
• Pituitary-Adrenal System (physiopathology)
• Polymorphism, Genetic
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Substance-Related Disorders (complications, genetics, physiopathology)
• Young Adult