Serotonergic and dopaminergic control of impulsivity in gambling disorder.
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Abstract
Gambling disorder (GD) is major public health issue. The disorder is often characterized by elevated impulsivity with evidence from analogous substance use disorders underlining prominent roles of brain monoamines in addiction susceptibility and outcome. Critically, GD allows the study of addiction mechanisms without the confounder of the effects of chronic substances. Here, we assessed the roles of striatal dopamine transporter binding and extrastriatal serotonin transporter binding in GD as a function of impulsivity using [123 I]FP-CIT SPECT imaging in 20 older adults with GD (DSM-5 criteria; mean age 64 years) and 40 non-GD age- and sex-matched controls. We focused on GD in older individuals because there are prominent age-related changes in neurotransmitter function and because there are no reported neuroimaging studies of GD in older adults. Volume-of-interest-based and voxelwise analyses were performed. GD patients scored clearly higher on impulsivity and had higher tracer binding in the ventromedial prefrontal cortex than controls (p < 0.001), likely reflecting serotonin transporter activity. The binding in the medial prefrontal cortex positively correlated with impulsivity over the whole sample (r = 0.62, p < 0.001) as well as separately in GD patients (r = 0.46, p = 0.04) and controls (r = 0.52, p < 0.001). Striatal tracer binding, reflecting dopamine transporter activity was also positively correlated with impulsivity but showed no group differences. These findings highlight the role of prefrontal serotonergic function in GD and impulsivity. They identify cerebral coordinates of a potential target for neuromodulation for both GD and high impulsivity, a core phenotypic dimensional cognitive marker in addictions.
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Funder: Finnish Foundation for Alcohol Studies; Id: http://dx.doi.org/10.13039/100016238
Funder: Päivikki and Sakari Sohlberg Foundation; Id: http://dx.doi.org/10.13039/501100004212
Funder: Finnish Cultural Foundation; Id: http://dx.doi.org/10.13039/501100003125
Funder: Turku University Foundation; Id: http://dx.doi.org/10.13039/501100022793
Funder: Michael J. Fox Foundation; Id: http://dx.doi.org/10.13039/100000864
Funder: Finnish Parkinson Foundation
Funder: Province of British Columbia
Funder: British Columbia Lottery Corporation (BCLC)
Funder: National Association for Gambling Studies
Funder: National Center for Responsible Gaming; Id: http://dx.doi.org/10.13039/100003977
Funder: GambleAware; Id: http://dx.doi.org/10.13039/501100008625
Funder: Gambling Research Exchange Ontario; Id: http://dx.doi.org/10.13039/501100007553
Funder: Finnish Medical Foundation; Id: http://dx.doi.org/10.13039/100008723
Funder: Instrumentarium Research Foundation
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1369-1600