Neural and neurocognitive markers of vulnerability to gambling disorder: a study of unaffected siblings

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Psychological and neurobiological markers in individuals with gambling disorder (GD) could reflect transdiagnostic vulnerability to addiction or neuroadaptive consequences of long-term gambling. Using an endophenotypic approach to identify vulnerability markers, we tested the biological relatives of cases with GD. Male participants seeking treatment for GD (n = 20) were compared with a male control group (n = 18). Biological siblings of cases with GD (n = 17, unrelated to the current GD group) were compared with a separate control group (n = 19) that overlapped partially with the GD control group. Participants completed a comprehensive assessment of clinical scales, neurocognitive functioning, and fMRI of unexpected financial reward. The GD group displayed elevated levels of self-report impulsivity and delay discounting, and increased risk-taking on the Cambridge Gamble Task. We did not observe impaired motor impulsivity on the stop-signal task. Siblings of GD showed some overlapping effects; namely, elevated impulsivity (negative urgency) and increased risk-taking on the Cambridge Gamble Task. We did not observe any differences in the neural response to win outcomes, either in the GD or sibling analysis compared with their control group. Within the GD group, activity in the thalamus and caudate correlated negatively with gambling severity. Increased impulsivity and risk-taking in GD are present in biological relatives of cases with GD, suggesting these markers may represent pre-existing vulnerability to GD.

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The authors wish to thank the study participants and the clinical team at Imanova, Centre for Imaging Sciences. The research was supported by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.

Funding and disclosure

This study was funded by the Medical Research Council- MRC G1100554 (Clark). E.H.L.O. works as a postdoctoral fellow at the Centre for Gambling Research at UBC which is supported by funding from the Province of British Columbia and the British Columbia Lottery Corporation (BCLC), a Canadian Crown Corporation. She has received a speaker honorarium from the Massachusetts Council on Compulsive Gambling (U.S.A.) and accepted travel/accommodation for speaking engagements from the National Council for Responsible Gambling (U.S.A.), the International Multidisciplinary Symposium on Gambling Addiction (Switzerland) and the Responsible Gambling Council (Canada). She has not received any further direct or indirect payments from the gambling industry or groups substantially funded by gambling. ALH has received Honoraria paid into her Institutional funds for speaking and Chairing engagements from Lundbeck, Lundbeck Institute UK, Janssen-Cilag; received research grants or support from Lundbeck, GSK; consulted by but received no monies from Opiant and Lightlake. HBJ is Director of the NPGC, London, Spokesperson on Behavioural Addictions for Royal College of Psychiatrists, and Board member of International Society of Addictions Medicine. LC is the Director of the Centre for Gambling Research at UBC, which is supported by funding from the Province of British Columbia and the British Columbia Lottery Corporation (BCLC), a Canadian Crown Corporation. LC receives funding from the Natural Sciences and Engineering Research Council (Canada). LC has received a speaker/travel honorarium from the National Association for Gambling Studies (Australia) and reviewing honoraria from the National Center for Responsible Gaming (US) and Gambling Research Exchange Ontario (Canada). He has not received any further direct or indirect payments from the gambling industry or groups substantially funded by gambling. He has provided paid consultancy to, and received royalties from, Cambridge Cognition Ltd. relating to neurocognitive testing. IM, REC, RSAF, ST have no sources of funding or potential conflict of interests to be declared.

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Correspondence to Eve H. Limbrick-Oldfield or Luke Clark.

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