A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction

L. Elliot Hong, Colin A. Hodgkinson, Yihong Yang, Hemalatha Sampath, Thomas J. Ross, Brittany Buchholz, Betty Jo Salmeron, Vibhuti Srivastava, Gunvant K. Thaker, David Goldman, Elliot A. Stein

Research output: Contribution to journalArticle

Abstract

Whole-genome searches have identified nicotinic acetylcholine receptor α5-α3-β4 subunit gene variants that are associated with smoking. How genes support this addictive and high-risk behavior through their expression in the brain remains poorly understood. Here we show that a key α5 gene variant Asp398Asn is associated with a dorsal anterior cingulate-ventral striatum/extended amygdala circuit, such that the "risk allele" decreases the intrinsic resting functional connectivity strength in this circuit. Importantly, this effect is observed independently in nonsmokers and smokers, although the circuit strength distinguishes smokers from nonsmokers, predicts addiction severity in smokers, and is not secondary to smoking per se, thus representing a trait-like circuitry biomarker. This same circuit is further impaired in people with mental illnesses, who have the highest rate of smoking. Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development.

Original languageEnglish (US)
Pages (from-to)13509-13514
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number30
DOIs
StatePublished - Jul 27 2010
Externally publishedYes

Fingerprint

Nicotine
Smoking
Genes
Gene Regulatory Networks
Gyrus Cinguli
Brain
Nicotinic Receptors
Risk-Taking
Amygdala
Biomarkers
Alleles
Genome

Keywords

  • Functional connectivity
  • Genetics
  • Imaging
  • nAChR
  • Smoking

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. / Hong, L. Elliot; Hodgkinson, Colin A.; Yang, Yihong; Sampath, Hemalatha; Ross, Thomas J.; Buchholz, Brittany; Salmeron, Betty Jo; Srivastava, Vibhuti; Thaker, Gunvant K.; Goldman, David; Stein, Elliot A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 30, 27.07.2010, p. 13509-13514.

Research output: Contribution to journalArticle

Hong, LE, Hodgkinson, CA, Yang, Y, Sampath, H, Ross, TJ, Buchholz, B, Salmeron, BJ, Srivastava, V, Thaker, GK, Goldman, D & Stein, EA 2010, 'A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 30, pp. 13509-13514. https://doi.org/10.1073/pnas.1004745107
Hong, L. Elliot ; Hodgkinson, Colin A. ; Yang, Yihong ; Sampath, Hemalatha ; Ross, Thomas J. ; Buchholz, Brittany ; Salmeron, Betty Jo ; Srivastava, Vibhuti ; Thaker, Gunvant K. ; Goldman, David ; Stein, Elliot A. / A genetically modulated, intrinsic cingulate circuit supports human nicotine addiction. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 30. pp. 13509-13514.
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