{"id":14887,"date":"2018-10-25T18:53:33","date_gmt":"2018-10-25T18:53:33","guid":{"rendered":"https:\/\/drugprevent.org.uk\/ppp\/?p=14887"},"modified":"2019-03-04T18:13:57","modified_gmt":"2019-03-04T18:13:57","slug":"a-gene-links-impulsivity-and-drug-use-vulnerability","status":"publish","type":"post","link":"https:\/\/drugprevent.org.uk\/ppp\/2018\/10\/a-gene-links-impulsivity-and-drug-use-vulnerability\/","title":{"rendered":"A Gene Links Impulsivity And Drug Use Vulnerability"},"content":{"rendered":"<div class=\"field field-name-field-nn-author field-type-text field-label-hidden\">\n<div class=\"field-items\">\n<div class=\"field-item even\" style=\"text-align: justify\"><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">By William Ross Perlman, Ph.D., CMPP, NIDA Notes Contributing Writer<\/span><\/div>\n<\/div>\n<\/div>\n<div class=\"field field-name-body field-type-text-with-summary field-label-hidden\" style=\"text-align: justify\">\n<div class=\"field-items\">\n<div class=\"field-item even\">\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">This research:<\/span><\/p>\n<ul>\n<li><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Identified a gene variant that promotes impulsive behavior and enhanced responses to heroin in rats.<\/span><\/li>\n<li><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Linked the corresponding human gene variant to increased risk for impulsivity and drug use.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">People who are highly impulsive and those diagnosed with ADHD are at increased risk for substance use disorders (SUD). Recent research implicates a variant of the gene for a protein called cAMP-response element modulator (CREM) in these associations. Drs.\u00a0<span class=\"externalLink\"><a class=\"ext\" style=\"color: #0000ff\" href=\"https:\/\/millem14.u.hpc.mssm.edu\/Site\/Welcome.html\" target=\"_blank\" rel=\"noopener\">Michael L. Miller<\/a><\/span>\u00a0and\u00a0<span class=\"externalLink\"><a class=\"ext\" style=\"color: #0000ff\" href=\"http:\/\/icahn.mssm.edu\/profiles\/yasmin-hurd\" target=\"_blank\" rel=\"noopener\">Yasmin L. Hurd<\/a><\/span>\u00a0from the Icahn School of Medicine at Mount Sinai in New York, with colleagues from several other institutions, showed that the gene variant promotes impulsive and hyperactive behavior in both animals and humans, and can contribute to a person\u2019s risk for developing SUD.<\/span><\/p>\n<h2><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Of Rats\u2026<\/span><\/h2>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">The Icahn researchers began their investigations with a strain of rats that exhibit impulsive behaviors resembling human attention-deficit\/hyperactivity disorder (ADHD). Initial experiments confirmed that, compared with a strain (Western Kyoto) of rats that are not known for impulsivity, these &#8220;spontaneously hypertensive&#8221;\u00a0(SH) rats:<\/span><\/p>\n<ul>\n<li><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Were more impatient to receive rewards, fidgeted more while waiting to receive rewards, ran around more, and were more attracted to novel experiences.<\/span><\/li>\n<li><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Self-administered more heroin and, when it was made unavailable, gave up seeking it less readily. \u00a0<\/span><\/li>\n<li><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Had enhanced elevation of dopamine levels in response to heroin.<\/span><\/li>\n<\/ul>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">The researchers screened the rats\u2019 DNA for genetic differences that might contribute to these behavioral differences. The results revealed that the two strains carried different variants of the gene for CREM. As a result, the SH rats had lower concentrations of CREM in the core of the nucleus accumbens\u2014a key brain region governing reward and movement.<\/span><\/p>\n<h2><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">\u2026And People<\/span><\/h2>\n<h2><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">\u00a0<a style=\"color: #0000ff\" href=\"https:\/\/drugprevent.org.uk\/ppp\/wp-content\/uploads\/2018\/09\/miller_figure_1.gif\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-14890\" src=\"https:\/\/drugprevent.org.uk\/ppp\/wp-content\/uploads\/2018\/09\/miller_figure_1.gif\" alt=\"\" width=\"700\" height=\"404\" \/><\/a><\/span><\/h2>\n<div class=\"border right\"><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\"><span class=\"title\">Figure 1. A\u00a0<em>CREM<\/em>\u00a0Gene Variant Increases Hyperactivity<\/span>Hyperactivity scores were higher in ADHD subjects than in control subjects. In addition, ADHD subjects who carried at least one copy of the less highly expressed A variant (i.e., with the G\/A or A\/A\u00a0<em>CREM<\/em>\u00a0genotype) reported significantly higher hyperactivity than did those carrying only the more highly expressed G variant (i.e., with the G\/G genotype). Genotype had no effect on hyperactivity in non-ADHD control subjects<\/span><\/div>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">The researchers used genetic and behavioral evidence from previous studies conducted by other researchers to demonstrate that the corresponding variant in the human\u00a0<em>CREM<\/em>\u00a0gene similarly predisposes people to impulsivity. This\u00a0variant occupies approximately the same position on the human gene that the rodent variant occupies on the rodent gene. At this site, known as rs12765063, the\u00a0<em>CREM\u00a0<\/em>gene exists in two versions\u2014called A and G\u2014and the A variant dials down CREM production. In one study, preschool children with the A variant were found to be more distractible and to engage in more dangerous activities than peers with only the G variant (Figure 1). In another, among adolescents with ADHD, those who carried the A variant reported more symptomatic hyperactivity than those who did not.<\/span><\/p>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">The researchers further found that by promoting impulsivity, the variant raises the risk of drug use. Thus, in two studies of adolescents, neither the A variant alone nor ADHD alone increased the risk for drug use, but the two together did. The first analysis looked at adolescents with ADHD, and found higher rates of drug use among those with the A variant than among those with only the G variant. The second analysis looked at adolescents who had the A variant of rs12765063 and histories of childhood ADHD. It found that those whose childhood ADHD still persisted reported more use of alcohol, tobacco, marijuana, and prescription stimulants than those who had outgrown their ADHD (Figure 2). Moreover, those who no longer had ADHD reported no more drug use than a comparison group who did not carry the A variant.<\/span><\/p>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\"><a style=\"color: #0000ff\" href=\"https:\/\/drugprevent.org.uk\/ppp\/wp-content\/uploads\/2018\/09\/miller_figure_2.gif\"><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-full wp-image-14891\" src=\"https:\/\/drugprevent.org.uk\/ppp\/wp-content\/uploads\/2018\/09\/miller_figure_2.gif\" alt=\"\" width=\"700\" height=\"404\" \/><\/a><\/span><\/p>\n<p>&nbsp;<\/p>\n<div class=\"border center\">\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\"><span class=\"title\">Figure 2. The A Variant of the\u00a0<em>CREM<\/em>\u00a0Gene Is Associated With Increased Drug Use in People With Persistent ADHD<\/span>\u00a0Among a cohort whose childhood ADHD persisted through adolescence, those with the\u00a0<i>CREM\u00a0<\/i>A variant reported more drug use than those with only the G variant. Genotype was not linked to risk for drug use in people without ADHD (i.e., those who never had ADHD or those with remitted ADHD).<\/span><\/p>\n<\/div>\n<h2><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">A Key to Prevention and Treatment?<\/span><\/h2>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Dr. Hurd suggests that CREM may be a key link between impulsivity and vulnerability to addiction. Understanding these relationships may help identify new ways of treating or preventing SUD. The protein is known to regulate multiple gene networks and their biological functions, and to influence the growth of structures that neurons use to communicate with each other.<\/span><\/p>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Dr. Hurd says, &#8220;These results highlight that CREM is a mediating factor between impulsivity and substance abuse vulnerability. It brings attention to CREM in the nucleus accumbens as a regulator of impulsive action and structural plasticity.&#8221;<\/span><\/p>\n<p><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">The study was supported by NIH grants DA015446, DA030359, DA006470, DA038954, DA031559, and DA007135.<\/span><\/p>\n<\/div>\n<\/div>\n<\/div>\n<p style=\"text-align: left\"><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">Source:\u00a0<a style=\"color: #0000ff\" href=\"https:\/\/www.drugabuse.gov\/news-events\/nida-notes\/2018\/06\/gene-links-impulsivity-drug-use-vulnerability\">https:\/\/www.drugabuse.gov\/news-events\/nida-notes\/2018\/06\/gene-links-impulsivity-drug-use-vulnerability<\/a>\u00a0<\/span><span style=\"font-family: verdana, geneva, sans-serif;font-size: 10pt;color: #0000ff\">June 2018<\/span><\/p>\n","protected":false},"excerpt":{"rendered":"<p>By William Ross Perlman, Ph.D., CMPP, NIDA Notes Contributing Writer This research: Identified a gene variant that promotes impulsive behavior and enhanced responses to heroin in rats. Linked the corresponding human gene variant to increased risk for impulsivity and drug use. People who are highly impulsive and those diagnosed with ADHD are at increased risk [&hellip;]<\/p>\n","protected":false},"author":12,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[73,85,63,22,106],"tags":[],"class_list":["post-14887","post","type-post","status-publish","format-standard","hentry","category-addiction","category-addiction-papers","category-brain-and-behaviour","category-effects-of-drugs-papers","category-medical-studies-papers"],"_links":{"self":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts\/14887","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/users\/12"}],"replies":[{"embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/comments?post=14887"}],"version-history":[{"count":0,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/posts\/14887\/revisions"}],"wp:attachment":[{"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/media?parent=14887"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/categories?post=14887"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/drugprevent.org.uk\/ppp\/wp-json\/wp\/v2\/tags?post=14887"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}