ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers

TY - JOUR

T1 - ZNF804A variants confer risk for heroin addiction and affect decision making and gray matter volume in heroin abusers

AU - Sun, Yan

AU - Zhao, Li Yan

AU - Wang, Gui Bin

AU - Yue, Wei Hua

AU - He, Yong

AU - Shu, Ni

AU - Lin, Qi Xiang

AU - Wang, Fan

AU - Li, Jia Li

AU - Chen, Na

AU - Wang, Hui Min

AU - Kosten, Thomas R.

AU - Feng, Jia Jia

AU - Wang, Jun

AU - Tang, Yu De

AU - Liu, Shu Xue

AU - Deng, Gui Fa

AU - Diao, Gan Huan

AU - Tan, Yun Long

AU - Han, Hong Bin

AU - Lin, Lu

AU - Shi, Jie

N1 - Publisher Copyright: © 2015 Society for the Study of Addiction.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.

AB - Drug addiction shares common neurobiological pathways and risk genes with other psychiatric diseases, including psychosis. One of the commonly identified risk genes associated with broad psychosis has been ZNF804A. We sought to test whether psychosis risk variants in ZNF804A increase the risk of heroin addiction by modulating neurocognitive performance and gray matter volume (GMV) in heroin addiction. Using case-control genetic analysis, we compared the distribution of ZNF804A variants (genotype and haplotype) in 1035 heroin abusers and 2887 healthy subjects. We also compared neurocognitive performance (impulsivity, global cognitive ability and decision-making ability) in 224 subjects and GMV in 154 subjects based on the ZNF804A variants. We found significant differences in the distribution of ZNF804A intronic variants (rs1344706 and rs7597593) allele and haplotype frequencies between the heroin and control groups. Decision-making impairment was worse in heroin abusers who carried the ZNF804A risk allele and haplotype. Subjects who carried more risk alleles and haplotypes of ZNF804A had greater GMV in the bilateral insular cortex, right temporal cortex and superior parietal cortex. The interaction between heroin addiction and ZNF804A variants affected GMV in the left sensorimotor cortex. Our findings revealed several ZNF804A variants that were significantly associated with the risk of heroin addiction, and these variants affected decision making and GMV in heroin abusers compared with controls. The precise neural mechanisms that underlie these associations are unknown, which requires future investigations of the effects of ZNF804A on both dopamine neurotransmission and the relative increases in the volume of various brain areas.

KW - Decision making

KW - ZNF804A variants

KW - genotype

KW - gray matter volume

KW - haplotype

KW - heroin addiction

UR - https://www.scopus.com/pages/publications/84924955924

U2 - 10.1111/adb.12233

DO - 10.1111/adb.12233

M3 - Article

C2 - 25708696

SN - 1355-6215

VL - 21

SP - 657

EP - 666

JO - Addiction Biology

JF - Addiction Biology

IS - 3

ER -