Serotonergic and dopaminergic control of impulsivity in gambling disorder

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.

Keywords: SPECT; gambling disorder; impulsivity.

FIGURE 1

Increased ventromedial prefrontal cortex and normal striatal [¹²³I]FP‐CIT uptake in patients with gambling disorder compared to healthy controls. (A) Localization and statistical significance of the cluster in the ventromedial prefrontal cortex. Cluster P _FWE = 0.04. (B) Individual [¹²³I]FP‐CIT specific binding ratio values plotted from the ventromedial prefrontal cortex (B), the mean caudate nucleus (C), and the putamen (D). GD, gambling disorder; HC, healthy controls; SBR, specific binding ratio. Note that cluster values in panel (B) are meant to illustrate the magnitude of the effect observed in the voxewise analysis and not to test any hypotheses.

FIGURE 2

Spearman correlations between ventromedial prefrontal cortex tracer uptake and impulsivity in patients with gambling disorder and healthy controls. (A) Tracer uptake versus Barratt Impulsiveness Scale (BIS‐11) total score. (B) Tracer uptake versus BIS‐11 attentional subscore. (C) Tracer uptake versus BIS‐11 motor subscore. (D) Tracer uptake versus BIS‐11 nonplanning subscore. Solid circles = patients with GD, open circles = healthy controls. GD, gambling disorder; HC, healthy controls; SBR, specific binding ratio

FIGURE 3

Spearman correlations between ventromedial prefrontal cortex SERT activity and (A) BMI, (B) BDI, (C) BAI, (D) duration of education and (E) MDS‐UPDRS motor score. No sex‐differences were observed in binding (F). BMI, body mass index; SBR, specific binding ratio

FIGURE 4

Association between impulsivity and [¹²³I]FP‐CIT uptake. Clusters of voxels with a positive association between [¹²³I]FP‐CIT uptake and nonplanning (upper row), attentional (middle row) and motor (bottom row) impulsivity. P _FWE < 0.05 for all clusters. There was no significant group x impulsivity interaction.