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Serotonergic and dopaminergic control of impulsivity in gambling disorder.

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Honkanen, Emma A 
Lindholm, Kari 
Jaakkola, Elina 
Majuri, Joonas 


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.


Funder: Finnish Foundation for Alcohol Studies; Id:

Funder: Päivikki and Sakari Sohlberg Foundation; Id:

Funder: Finnish Cultural Foundation; Id:

Funder: Turku University Foundation; Id:

Funder: Michael J. Fox Foundation; Id:

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:

Funder: GambleAware; Id:

Funder: Gambling Research Exchange Ontario; Id:

Funder: Finnish Medical Foundation; Id:

Funder: Instrumentarium Research Foundation


SPECT, gambling disorder, impulsivity, Humans, Aged, Middle Aged, Gambling, Dopamine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Impulsive Behavior, Prefrontal Cortex, Dopamine

Journal Title

Addict Biol

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Medical Research Council (MR/P008747/1)