Psychologists have discovered a new genetic link between impulsivity and teenage binge-drinking.
Researchers at the University of Sussex, working as part of a team of researchers from across Europe, made the discovery which is published in the journal Frontiers in Genetics.
Professor Dai Stephens from the School of Psychology at the University of Sussex said:
“Alcohol and drug abuse are well documented as being major public health issues in today’s society. By uncovering a particular gene that links impulsive behaviour with binge-drinking we may be an important step closer to understanding why some young people face a struggle to control their urges to engage in risky behaviour like binge drinking.
“We have identified a variant of a specific gene, called KALRN, which is seen in teenagers who act impulsively and also binge-drink. This link is interesting as it suggests that people can be predisposed to impulsive behaviour, and perhaps also to early-life alcohol abuse. If we can understand how these gene variations predispose people to impulsive behaviour, we may be able to help control binge-drinking and other disorders linked to impulsivity, like drug addiction and ADHD.”
Dr Yolanda Peña-Oliver, the postdoctoral researcher who carried out the research under Professor Dai Stephens’ supervision, said:
“These results provide an insight into the possible neurobiological and genetic determinants of impulsivity and alcohol abuse. The KALRN gene codes for a protein called Kalirin. Kalirin is essential to the development of the nervous system, especially the formation of dendritic spines that are important for the ability of nerve cells to communicate with each other. Interestingly, it has also been associated with other impulsivity-related disorders, like ADHD.”
How the research was conducted:
The researchers already knew that there was a link between impulsivity and a lack of control in drug and alcohol abuse, and that genetic factors contribute to addictions. But it is scientifically difficult in human studies to identify which particular genes contribute to impulsive behaviour and binge-drinking. By first studying impulsivity in mice – by measuring how good they were at waiting for a reward – and cross referencing the findings with an international database of genetic information, the team were able to narrow down the search for genes that might have a role to play in human impulsivity.
The study then looked at 1400 teenagers who also took part in a major survey about drinking and drug-taking habits. The teenagers were asked to respond to cues in order to receive a reward, and underwent fMRI scans as they did so. They were scored for their impulsivity, i.e., their inability to wait for the reward. When their results were checked against their DNA profiles, the researchers found that many of the same genes they had identified in mice were also associated with the level of impulsivity in the teenagers.
The brain mechanisms contributing to impulsivity in the teenagers were identified by the degree to which one part of the brain, the ventral striatum, was activated while they were waiting for the reward. Variations in one gene in particular – KALRN – were associated with both impulsivity and with a tendency to binge drink. The gene, KALRN, is involved in efficient connections between nerve cells.
Professor Dai Stephens supervised the research of Yolanda Pena-Oliver while she was at the University of Sussex. Dr Pena-Oliver is now at the University of Cambridge.
About this genetics research
No mice or teenagers were given alcohol as part of this study.
Funding: The research was funded by a European Commission grant. The 1400 teenagers were part of a major European research project, called ‘IMAGEN’, which is investigating mental health and risk-taking behaviour in teenagers.
Source: Anna Ford – University of Sussex Image Credit: The image is credited to Peña-Oliver et al./Frontiers in Genetics. Original Research: Full open access research for “Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse” by Yolanda Peña-Oliver, Fabiana M. Carvalho, Sandra Sanchez-Roige, Erin B. Quinlan, Tianye Jia, Tom Walker-Tilley, Stuart L. Rulten, Frances M. G. Pearl, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Christian Büchel, Patricia J. Conrod, Herta Flor, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Penny Gowland, Marie-Laure Paillere Martinot, Tomáš Paus, Marcella Rietsche, Trevor W. Robbins, Michael N. Smolka, Gunter Schumann, and David N. Stephens for the IMAGEN Consortium in Frontiers in Genetics. Published online April 7 2016 doi:10.3389/fgene.2016.00052
Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse
Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.
“Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse” by Yolanda Peña-Oliver, Fabiana M. Carvalho, Sandra Sanchez-Roige, Erin B. Quinlan, Tianye Jia, Tom Walker-Tilley, Stuart L. Rulten, Frances M. G. Pearl, Tobias Banaschewski, Gareth J. Barker, Arun L. W. Bokde, Christian Büchel, Patricia J. Conrod, Herta Flor, Jürgen Gallinat, Hugh Garavan, Andreas Heinz, Penny Gowland, Marie-Laure Paillere Martinot, Tomáš Paus, Marcella Rietsche, Trevor W. Robbins, Michael N. Smolka, Gunter Schumann, and David N. Stephens for the IMAGEN Consortium in Frontiers in Genetics. Published online April 7 2016 doi:10.3389/fgene.2016.00052