Skip to main content
PMC home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2016 Oct 1.
Published in final edited form as: Psychiatr Genet. 2015 Oct;25(5):213–214. doi: 10.1097/YPG.0000000000000094

Serotonin transporter gene promoter polymorphism predicts relationship between years of cocaine use and impulsivity

Shijing Liu 1,2, Lorena Maili 3, Scott D Lane 4, Joy M Schmitz 4, Catherine J Spellicy 1,2, Kathryn A Cunningham 5, F Gerard Moeller 6, David A Nielsen 1,2
PMCID: PMC4549162  NIHMSID: NIHMS694943  PMID: 26110342

Summary

This study investigated the relationship between the serotonin transporter gene (SLC6A4) 5-HTTLPR genotypes, cocaine-dependence, and impulsivity. Ninety-eight healthy control and 243 treatment-seeking, cocaine-dependent subjects from the greater Houston area were evaluated between February 2007 and April 2012. Subjects signed an informed consent. Medical and drug use histories [ASI (McLellan et al., 19980)], demographics, impulsivity [BIS-11 (Patton et al., 1995)], psychiatric disorders [DSM-IV (SCID-I) (First et al., 1996)], and 10 ml of blood for DNA isolation were collected. This study was approved by the local IRBs at the medical centers of the University of Texas, Baylor College of Medicine, and the Veterans Affairs Research and Development Committee.

DNA was genotyped for the low-expressing S’ and high-expressing L’ triallelic 5-HTTLPR polymorphism (Hu et al., 2006). There were 59, 117, and 67 S’S, L’S’, L’L’ cocaine-dependent subjects, respectively, and 24, 45, and 29 controls, respectively. Cocaine-dependent subjects used cocaine for an average of 14.5 years and 16.1 days in last 30 days. Data analyses were conducted in SAS 9.2 (SAS Institute Inc., Cary, NC) and significance set as P <0.05 (one-tail) for a priori hypotheses (Keppel and Wickens, 2004). We hypothesized that the S’-allele carrier subjects would be more impulsive. Differences were observed in age (P<0.01), sex (P<0.01), population structure (Kosten, et al., 2013 (P<0.05), and educational level (P<0.01) between control and cocaine-dependent groups. Therefore, analyses were adjusted for age, sex, ethnicity, and educational level.

The general linear model revealed a group (cocaine-dependent versus control) × 5-HTTLPR (L’L’ genotype versus S’ allele carriers [L’S’+S’S’ genotypes combined]) interaction (F1,323=4.87, P=0.028), suggesting that the relationship between impulsivity and 5-HTTLPR genotype in cocaine-dependent subjects was different from that in controls. Post hoc analysis showed that S’ allele cocaine-dependent carriers had significantly lower BIS-11 total scores (71.3±1.6) than did those with the L’L’ genotype (74.9±2.0) (P<0.05), while controls showed no difference in BIS-11 total scores as a function of genotype (L’L’: 56.0±2.7; L’S’/S’S’: 59.5±2.0). The cocaine-dependent subjects had higher BIS-11 total scores (73.1±1.7) than did the controls (57.6±2.3; P<0.0001).

There was a group × 5-HTTLPR genotype interaction (F1,323=6.31, P=0.012) for the nonplanning BIS-11 subscore. S’-allele cocaine-dependent carriers had significantly lower BIS-11 nonplanning subscores (28.7±0.7) than those with the L’L’ genotype (31.3±0.9) (P<0.01), a relationship not observed in the controls (S’-allele carriers: 22.5±0.9; L’L’ genotype: 21.2±1.2). For the BIS-11 motor and attentional subscores, the group × 5-HTTLPR genotype interactions were not significant.

A 5-HTTLPR × years of cocaine use interaction (F1,232=4.22, P=0.04) was found for the BIS-11 total scores of the cocaine-dependent subjects. The BIS-11 total score was positively associated with years of cocaine use for S’-allele carriers (r=0.26, P=0.0006, Pearson’s correlation analysis), but not for L’L’ genotype subjects (r=0.02, P=0.87). For the BIS-11 subscores, the 5-HTTLPR × years of cocaine use interactions were not significant. For the BIS-11 total score and subscores, the 5-HTTLPR × days of cocaine use in last 30 days interactions were not significant.

Understanding genotype and dependence in moderating impulsivity may help in the development of effective treatments.

Acknowledgments

We thank Mr. Mark Harding (Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine) for assistance with genotyping. This study was supported by the National Institute on Drug Abuse (NIDA) grants P50 DA009262 (FGM, JMS), P20 DA024157 and K05 DA020087 (KAC), P50 DA018197 (Thomas R. Kosten). SL and DAN were supported by the University of Texas MD Anderson NIDA grant R25 DA026120 (PI Shine Chang). This study was also supported in part by the Toomin Family Fund (DAN) and by resources and the use of facilities at the Michael E. DeBakey VA Medical Center, Houston, TX.

Footnotes

Conflict of Interest

None.

References

  1. First MB, Spitzer RL, Gibbon M, Williams J. Structured Clinical Interview for DSM-IV Axis I Disorders. Patient Edition. New York: Biometrics Research Department, New York State Psychiatric Institute; 1996. [Google Scholar]
  2. McLellan AT, Luborsky L, Woody GE, O’Brien CP. An improved diagnostic evaluation instrument for substance abuse patients. The Addiction Severity Index. J Nerv Ment Dis. 1980;168(1):26–33. doi: 10.1097/00005053-198001000-00006. [DOI] [PubMed] [Google Scholar]
  3. Hu XZ, Lipsky RH, Zhu G, Akhtar LA, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet. 2006;78:815–826. doi: 10.1086/503850. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Keppel G, Wickens TD. Design and Analysis: A Researcher’s Handbook. fourth. Prentice-Hall; Upper Saddle River, NJ: 2004. Planned Comparisons; pp. 115–117. [Google Scholar]
  5. Kosten TR, Wu G, Huang W, Harding MJ, Hamon SC, Lappalainen J, Nielsen DA. Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine beta-hydroxylase. Biol Psychiatry. 2013;73(3):219–224. doi: 10.1016/j.biopsych.2012.07.011. [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES