{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:44:30Z","timestamp":1791222270658,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mental Illness Research, Education and Clinical Center at the Crescenz VAMC"},{"name":"Fellowship from the Medical Research Future Fund","award":["1155320"],"award-info":[{"award-number":["1155320"]}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2021\/GNT2009851"],"award-info":[{"award-number":["2021\/GNT2009851"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1104288"],"award-info":[{"award-number":["APP1104288"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Topiramate has been found to be effective in reducing alcohol use and may also attenuate anxiety severity in patients with alcohol use disorder (AUD). This study compared the neural response of treatment-seeking patients with AUD on either topiramate or naltrexone during an anticipatory anxiety task. Participants were 42 patients with AUD who were randomized to receive either topiramate (n\u2009=\u00a023; titrated dose up to 200\u00a0mg\/day) or naltrexone (n\u2009=\u200919; 50\u00a0mg\/day) for 12-weeks as part of a larger randomized controlled trial. Following 6\u00a0weeks of treatment, participants completed an anticipatory anxiety task during a functional magnetic resonance imaging (fMRI) session. The task presented a series of high-threat and low-threat stimuli followed by an unpleasant or pleasant image, respectively. Primary whole-brain analyses revealed no significant differences in neural activation between the topiramate and naltrexone groups. Deactivation for safe cues relative to threat cues was observed within the precuneus, inferior parietal lobule and the cingulate gyrus. In the precentral and middle frontal gyri, threat cues elicited greater activation. Exploratory analyses revealed an effect of change in anxiety from baseline to week 6, with a greater reduction associated with a reduced response to threat cues relative to safe cues in the cuneus and lingual gyrus. The current study is the first to examine and compare neural activation during anticipatory anxiety in treatment-seeking individuals on topiramate and naltrexone. This preliminary research contributes to our understanding of the therapeutic mechanisms of these alcohol pharmacotherapies.<\/jats:p>","DOI":"10.1093\/alcalc\/agae078","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T06:27:03Z","timestamp":1731997623000},"source":"Crossref","is-referenced-by-count":2,"title":["Comparative effects of topiramate and naltrexone on neural activity during anticipatory anxiety in individuals with alcohol use disorder"],"prefix":"10.1093","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-2596","authenticated-orcid":false,"given":"Gezelle","family":"Dali","sequence":"first","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Edith Collins Centre for Translational Research (Alcohol , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Royal Prince Alfred Hospital, Sydney Local Health District , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warren","family":"Logge","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Edith Collins Centre for Translational Research (Alcohol , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Royal Prince Alfred Hospital, Sydney Local Health District , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry R","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, University of Pennsylvania Perelman School of Medicine and Crescenz Veterans Affairs Medical Center , Philadelphia, PA 19104 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristan","family":"Hurzeler","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul S","family":"Haber","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Edith Collins Centre for Translational Research (Alcohol , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Royal Prince Alfred Hospital, Sydney Local Health District , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0868-9928","authenticated-orcid":false,"given":"Kirsten C","family":"Morley","sequence":"additional","affiliation":[{"name":"Specialty of Addiction Medicine, Sydney Medical School, Faculty of Medicine and Health, University of Sydney , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Edith Collins Centre for Translational Research (Alcohol , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]},{"name":"Royal Prince Alfred Hospital, Sydney Local Health District , Drugs & Toxicology), , Sydney, NSW 2050 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"2024111906265215200_ref1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"American Psychiatric Association","year":"2013"},{"key":"2024111906265215200_ref2","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1111\/j.1471-4159.2005.03259.x","article-title":"Topiramate reduces AMPA-induced Ca2+ transients and inhibits GluR1 subunit phosphorylation in astrocytes from primary cultures","volume":"94","author":"\u00c4ngehagen","year":"2005","journal-title":"J Neurochem"},{"key":"2024111906265215200_ref3","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1111\/j.1360-0443.2008.02355.x","article-title":"Comparing topiramate with naltrexone in the treatment of alcohol dependence*","volume":"103","author":"Baltieri","year":"2008","journal-title":"Addiction"},{"key":"2024111906265215200_ref4","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1111\/acer.12411","article-title":"A meta-analysis of Topiramate's effects for individuals with alcohol use disorders","volume":"38","author":"Blodgett","year":"2014","journal-title":"Alc: Clin Experimen Res"},{"key":"2024111906265215200_ref5","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1016\/j.neuropsychologia.2009.01.026","article-title":"A left amygdala mediated network for rapid orienting to masked fearful faces","volume":"47","author":"Carlson","year":"2009","journal-title":"Neuropsychologia"},{"key":"2024111906265215200_ref6","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/S2215-0366(19)30222-6","article-title":"Psychiatric comorbidities in alcohol use disorder","volume":"6","author":"Castillo-Carniglia","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"2024111906265215200_ref7","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1006\/nimg.1999.0407","article-title":"A functional anatomy of anticipatory anxiety","volume":"9","author":"Chua","year":"1999","journal-title":"Neuroimage"},{"key":"2024111906265215200_ref8","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.neuroimage.2010.11.040","article-title":"Experiential, autonomic, and neural responses during threat anticipation vary as a function of threat intensity and neuroticism","volume":"55","author":"Drabant","year":"2011","journal-title":"Neuroimage"},{"key":"2024111906265215200_ref9","doi-asserted-by":"crossref","first-page":"7900","DOI":"10.1073\/pnas.1602413113","article-title":"Cluster failure why fMRI inferences for spatial extent have inflated false-positive rates","volume":"113","author":"Eklund","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024111906265215200_ref10","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1177\/02698811221149643","article-title":"A Bayesian meta-analysis of topiramate\u2019s effectiveness for individuals with alcohol use disorder","volume":"37","author":"Fluyau","year":"2023","journal-title":"J Psychopharmacol"},{"key":"2024111906265215200_ref11","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1111\/acer.14167","article-title":"The use of functional magnetic resonance imaging to test pharmacotherapies for alcohol use disorder: a systematic review","volume":"43","author":"Grodin","year":"2019","journal-title":"Alcohol Clin Exp Res"},{"key":"2024111906265215200_ref12","doi-asserted-by":"publisher","first-page":"1625","DOI":"10.1007\/s00213-018-4843-6","article-title":"Noradrenergic targets for the treatment of alcohol use disorder","volume":"235","author":"Haass-Koffler","year":"2018","journal-title":"Psychopharmacology (Berl)"},{"key":"2024111906265215200_ref13","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1037\/pha0000118","article-title":"Topiramate reduces basal anxiety and relieves ethanol withdrawal-induced anxious behaviors in male rats","volume":"25","author":"Junqueira-Ayres","year":"2017","journal-title":"Exp Clin Psychopharmacol"},{"key":"2024111906265215200_ref14","doi-asserted-by":"publisher","first-page":"231","DOI":"10.3109\/10673229709030550","article-title":"The self-medication hypothesis of substance use disorders: a reconsideration and recent applications","volume":"4","author":"Khantzian","year":"1997","journal-title":"Harv Rev Psychiatry"},{"key":"2024111906265215200_ref15","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.biopsycho.2011.10.010","article-title":"Insula reactivity and connectivity to anterior cingulate cortex when processing threat in generalized social anxiety disorder","volume":"89","author":"Klumpp","year":"2012","journal-title":"Biol Psychol"},{"key":"2024111906265215200_ref16","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0272-7358(99)00027-6","article-title":"The relationship between anxiety disorders and alcohol use disorders: a review of major perspectives and findings","volume":"20","author":"Kushner","year":"2000","journal-title":"Clin Psychol Rev"},{"key":"2024111906265215200_ref17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.drugalcdep.2015.05.031","article-title":"Prevalence of comorbid substance use, anxiety and mood disorders in epidemiological surveys, 1990\u20132014: a systematic review and meta-analysis","volume":"154","author":"Lai","year":"2015","journal-title":"Drug Alcohol Depend"},{"key":"2024111906265215200_ref18","author":"Lovibond","year":"1995","journal-title":"Manual for the Depression Anxiety Stress Scales"},{"key":"2024111906265215200_ref19","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1111\/j.1360-0443.2012.04054.x","article-title":"Meta-analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?","volume":"108","author":"Maisel","year":"2013","journal-title":"Addiction"},{"key":"2024111906265215200_ref20","article-title":"Topiramate pharmacotherapy for alcohol use disorder and other addictions","volume":"13","author":"Manhapra","year":"2019","journal-title":"Narrat Rev J Addict Med"},{"key":"2024111906265215200_ref21","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1097\/JCP.0000000000000228","article-title":"Low-dose Topiramate in alcohol dependence: a single-blind, placebo-controlled study","volume":"34","author":"Martinotti","year":"2014","journal-title":"J Clin Psychopharmacol"},{"key":"2024111906265215200_ref22","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.ijpsycho.2022.07.006","article-title":"Neural responding during uncertain threat anticipation in pediatric anxiety","volume":"183","author":"Michalska","year":"2023","journal-title":"Int J Psychophysiol"},{"key":"2024111906265215200_ref23","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1186\/s13063-018-2824-z","article-title":"Topiramate versus naltrexone for alcohol use disorder: study protocol for a genotype-stratified, double-blind randomised controlled trial (TOP study)","volume":"19","author":"Morley","year":"2018","journal-title":"Trials"},{"key":"2024111906265215200_ref24","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.euroneuro.2021.02.010","article-title":"High-dose baclofen attenuates insula activation during anticipatory anxiety in treatment-seeking alcohol dependant individuals: preliminary findings from a pharmaco-fMRI study","volume":"46","author":"Morley","year":"2021","journal-title":"Eur Neuropsychopharmacol"},{"key":"2024111906265215200_ref25","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1176\/appi.ajp.20230666","article-title":"Topiramate versus naltrexone for alcohol use disorder: a genotype-stratified double-blind randomized controlled trial","volume":"181","author":"Morley","year":"2024","journal-title":"Am J Psychiatry"},{"key":"2024111906265215200_ref26","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1176\/appi.ajp.2008.07101682","article-title":"Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response","volume":"166","author":"Nitschke","year":"2009","journal-title":"Am J Psychiatry"},{"key":"2024111906265215200_ref27","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1038\/npp.2012.77","article-title":"Withdrawal-associated increases and decreases in functional neural connectivity associated with altered emotional regulation in alcoholism","volume":"37","author":"O'daly","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"2024111906265215200_ref28","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1111\/acer.12626","article-title":"Gender effects in alcohol dependence: an fMRI pilot study examining affective processing","volume":"39","author":"Padula","year":"2015","journal-title":"Alcohol Clin Exp Res"},{"key":"2024111906265215200_ref29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1471-244X-11-41","article-title":"Treatment of alcohol dependence with low-dose topiramate: an open-label controlled study","volume":"11","author":"Paparrigopoulos","year":"2011","journal-title":"BMC Psychiatry"},{"key":"2024111906265215200_ref30","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2021"},{"key":"2024111906265215200_ref31","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.eurpsy.2013.08.006","article-title":"Co-morbid anxiety disorders predict early relapse after inpatient alcohol treatment","volume":"30","author":"Schellekens","year":"2015","journal-title":"Eur Psychiatry"},{"key":"2024111906265215200_ref32","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1001\/jamapsychiatry.2013.762","article-title":"Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk","volume":"70","author":"Seo","year":"2013","journal-title":"JAMA Psychiatry"},{"key":"2024111906265215200_ref33","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.biopsych.2006.04.038","article-title":"Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects","volume":"60","author":"Simmons","year":"2006","journal-title":"Biol Psychiatry"},{"key":"2024111906265215200_ref34","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1037\/0021-843X.91.3.199","article-title":"Alcohol dependence syndrome: measurement and validation","volume":"91","author":"Skinner","year":"1982","journal-title":"J Abnorm Psychol"},{"key":"2024111906265215200_ref35","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-0357-5_3","volume-title":"Measuring Alcohol Consumption: Psychosocial and Biochemical Methods","author":"Sobell","year":"1992"},{"key":"2024111906265215200_ref36","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/da.22886","article-title":"Explaining the association between anxiety disorders and alcohol use disorder: a twin study","volume":"36","author":"Torvik","year":"2019","journal-title":"Depress Anxiety"},{"key":"2024111906265215200_ref37","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/bjp.2008.30","article-title":"Neuropharmacology of alcohol addiction","volume":"154","author":"Vengeliene","year":"2008","journal-title":"Br J Pharmacol"},{"key":"2024111906265215200_ref38","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.euroneuro.2019.10.014","article-title":"The effects of nalmefene on emotion processing in alcohol use disorder \u2013 a randomized, controlled fMRI study","volume":"29","author":"Vollst\u00e4dt-Klein","year":"2019","journal-title":"Eur Neuropsychopharmacol"},{"key":"2024111906265215200_ref39","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/j.1528-1157.2000.tb02165.x","article-title":"Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism","volume":"41","author":"White","year":"2000","journal-title":"Epilepsia"},{"key":"2024111906265215200_ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102162","article-title":"Brain activation and subjective anxiety during an anticipatory anxiety task is related to clinical outcome during prazosin treatment for alcohol use disorder","volume":"26","author":"Wilcox","year":"2020","journal-title":"NeuroImage: Clinical"},{"key":"2024111906265215200_ref40a","article-title":"Global status report on alcohol and health","author":"World Health Organization","year":"2014"},{"key":"2024111906265215200_ref41","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1111\/acer.12187","article-title":"Altered neural processing of threat in alcohol-dependent men","volume":"37","author":"Yang","year":"2013","journal-title":"Alcohol: Clin Experiment Res"},{"key":"2024111906265215200_ref42","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.nicl.2016.10.019","article-title":"Cingulate cortex functional connectivity predicts future relapse in alcohol dependent individuals","volume":"13","author":"Zakiniaeiz","year":"2017","journal-title":"NeuroImage: Clinical"},{"key":"2024111906265215200_ref43","doi-asserted-by":"publisher","first-page":"21298","DOI":"10.1038\/srep21298","article-title":"Neural basis of uncertain cue processing in trait anxiety","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci Rep"}],"container-title":["Alcohol and Alcoholism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/alcalc\/article-pdf\/60\/1\/agae078\/60741628\/agae078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/alcalc\/article-pdf\/60\/1\/agae078\/60741628\/agae078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T06:27:12Z","timestamp":1731997632000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/alcalc\/article\/doi\/10.1093\/alcalc\/agae078\/7903160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,11,18]]}},"URL":"https:\/\/doi.org\/10.1093\/alcalc\/agae078","relation":{},"ISSN":["0735-0414","1464-3502"],"issn-type":[{"value":"0735-0414","type":"print"},{"value":"1464-3502","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,1]]},"published":{"date-parts":[[2024,11,18]]},"article-number":"agae078"}}