{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T08:57:18Z","timestamp":1776416238289,"version":"3.51.2"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":77,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Brain Research Center core fund"},{"name":"Department of Biotechnology Ramalingaswami","award":["BT\/RLF\/Re-entry\/36\/2023"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/36\/2023"]}]},{"name":"Indian Council of Medical Research small","award":["IIRPSG-2025-01-00352"],"award-info":[{"award-number":["IIRPSG-2025-01-00352"]}]},{"DOI":"10.13039\/501100007338","name":"All India Institute of Medical Sciences","doi-asserted-by":"crossref","award":["K99\/R00"],"award-info":[{"award-number":["K99\/R00"]}],"id":[{"id":"10.13039\/501100007338","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007338","name":"All India Institute of Medical Sciences","doi-asserted-by":"crossref","award":["K99AG088064"],"award-info":[{"award-number":["K99AG088064"]}],"id":[{"id":"10.13039\/501100007338","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Institutes of"},{"name":"Aging\/National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Alcohol use disorder (AUD) often emerges in adolescence and young adulthood, yet early neural predictors remain scarce. The olfactory system, through its connections with limbic and reward circuits, may provide a novel window into compulsive alcohol use. These brain regions are altered in AUD, but the role of olfactory pathways is poorly understood. Anxiety, a common comorbidity in AUD, may further modulate these circuits. This study investigates whether anxiety moderates the relationship between olfactory\u2013reward brain connectivity and risky alcohol use and dependence. We analysed multimodal data from 1003 participants (22\u201336 years) in the Human Connectome Project. Resting-state functional MRI was used to compute functional connectivity among 41 regions implicated in olfaction, emotion, memory and reward. Odour identification scores were used to isolate connectivity features most correlated with olfactory function. These features served as predictors in ElasticNet and LASSO classification models for three alcohol-related outcomes: (i) lifetime Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV alcohol dependence, (ii) past-year risky drinking and (iii) past-week risky drinking. Models were trained on a Synthetic Minority Over-sampling Technique (SMOTE)-balanced subset (n = 704) and validated on a propensity score-matched holdout dataset (n = 83). Post hoc logistic regression examined anxiety (DSM scores) as a moderator of connectivity\u2013outcome associations. Connectivity between the precuneus\u2013cingulate\u2013accumbens and lateral occipital\u2013hippocampal regions predicted lifetime alcohol dependence (odds ratio = 1.12, P &amp;lt; 0.001). Models showed strong performance (area under the curve &amp;gt; 0.90 training; &amp;gt;0.80 validation). Anxiety moderated key connections: it attenuated the risk effect of memory\u2013reward circuitry and amplified risk via inferior frontal\u2013parietal connectivity. Odour identification scores did not differ across alcohol risk groups. Model performance replicated in a propensity-matched validation set. Our findings reveal a novel olfactory\u2013limbic circuit predictive of alcohol dependence in young adults. Anxiety modulates these pathways, suggesting dynamic brain\u2013behaviour interactions that may underlie individual vulnerability and resilience. This framework supports the integration of sensory, emotional and transdiagnostic features in neurobiological models of addiction.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag096","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:55:55Z","timestamp":1773838555000},"source":"Crossref","is-referenced-by-count":0,"title":["Anxiety modulates odour-linked brain connectivity and alcohol dependence risk"],"prefix":"10.1093","volume":"8","author":[{"given":"Khushbu","family":"Agarwal","sequence":"first","affiliation":[{"name":"Department of Cognitive and Computational Neuroscience, National Brain Research Center , Gurugram, Haryana 122051 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4505-0506","authenticated-orcid":false,"given":"Shefali","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale University School of Medicine , New Haven, CT 06519 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0276-7072","authenticated-orcid":false,"given":"Valentina","family":"Parma","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yatan Pal Singh","family":"Balhara","sequence":"additional","affiliation":[{"name":"National Drug Dependence Treatment Centre, All India Institute of Medical Sciences , New Delhi, Delhi 110029 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-1549","authenticated-orcid":false,"given":"Siddharth","family":"Sarkar","sequence":"additional","affiliation":[{"name":"National Drug Dependence Treatment Centre, All India Institute of Medical Sciences , New Delhi, Delhi 110029 ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"issue":"Supplement_4","key":"2026041703565749300_fcag096-B1","doi-asserted-by":"crossref","first-page":"S290","DOI":"10.1542\/peds.2007-2243D","article-title":"A developmental perspective on alcohol and youths 16 to 20 years of age","volume":"121","author":"Brown","year":"2008","journal-title":"Pediatrics"},{"issue":"4pt2","key":"2026041703565749300_fcag096-B2","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1017\/S0954579413000771","article-title":"The developmental psychopathology of alcohol use and alcohol disorders: Research achievements and future directions","volume":"25","author":"Chassin","year":"2013","journal-title":"Dev Psychopathol"},{"issue":"1","key":"2026041703565749300_fcag096-B3","doi-asserted-by":"crossref","first-page":"21890","DOI":"10.3402\/snp.v3i0.21890","article-title":"Why is adolescence a key period of alcohol initiation and who is prone to develop long-term problem use?: A review of current available data","volume":"3","author":"Petit","year":"2013","journal-title":"Socioaffect Neurosci Psychol"},{"key":"2026041703565749300_fcag096-B4","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.addbeh.2016.08.003","article-title":"Impulsive sensation seeking, binge drinking, and alcohol-related consequences: Do protective behavioral strategies help high risk adolescents?","volume":"64","author":"Doumas","year":"2017","journal-title":"Addict Behav"},{"issue":"7","key":"2026041703565749300_fcag096-B5","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1037\/abn0000191","article-title":"Age at first use and later substance use disorder: Shared genetic and environmental pathways for nicotine, alcohol, and cannabis","volume":"125","author":"Richmond-Rakerd","year":"2016","journal-title":"J Abnorm Psychol"},{"issue":"11","key":"2026041703565749300_fcag096-B6","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1111\/add.12620","article-title":"Early age of alcohol initiation is not the cause of alcohol use disorders in adulthood, but is a major indicator of genetic risk. 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