Dopamine mediates a directionally opposite correlation between empathy and the reinforcing effects of amphetamine and gambling in people with gambling disorder vs. healthy controls.

Understanding the relationship between empathy, subjective effects of addictive reinforcers and dopamine function in people with gambling disorder (PGD) vs. healthy controls (HCs) may inform GD treatment. The current investigation addressed this issue via retrospective analysis of data from three studies using amphetamine and a slot machine (SLOTS) as reinforcers in PGD and HCs. The Empathy scale of Eysenck's Impulsiveness Questionnaire assessed trait Empathy. The Gamblers Beliefs Questionnaire assessed cognitive distortions. The Eysenck Lie scale assessed socially desirable responding. PET scans quantified dopamine receptor expression and amphetamine-induced dopamine release in Study 1. Pre-treatment with the D2-receptor (D2R)-preferring antagonist, haloperidol or D1R-D2R antagonist, fluphenazine before SLOTS tested the role of D2 autoreceptors and post-synaptic D2R in Study 2. Pre-treatment with the multi-system indirect dopamine agonist, modafinil before SLOTS assessed the reliability of correlations in PGD. Striatal D2R expression predicted greater Empathy and lower amphetamine 'Liking' in HCs, and predicted greater symptom severity in PGD. Empathy predicted lower 'Exciting' effects of SLOTS under placebo in HCs; no correlation emerged under either antagonist. Relative to placebo, haloperidol decreased, whereas fluphenazine increased, the positive correlation between Empathy and Exciting effects of SLOTS in PGD. Modafinil markedly reduced the positive correlation between Empathy and Exciting effects of SLOTS seen under placebo in PGD. Empathy predicted greater cognitive distortions in PGD in all studies. Lie scale variance influenced several primary effects. Prior research linking the insula with Empathy, reactivity to interoceptive signals for risky rewards (uncertainty), and cognitive distortions, provides a parsimonious account for these results.

Greater monoamine oxidase a binding in alcohol dependence.

BACKGROUND: Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A VT, an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor. METHODS: Sixteen participants with alcohol dependence and 16 healthy control subjects underwent [(11)C]-harmine positron emission tomography. All were nonsmoking, medication- and drug-free, and had no other past or present psychiatric or medical illnesses. RESULTS: MAO-A VT was significantly greater in the PFC (37%, independent samples t test, t30 = 3.93, p < .001), and all brain regions analyzed (mean 32%, multivariate analysis of variance, F7,24 = 3.67, p = .008). Greater duration of heavy drinking correlated positively with greater MAO-A VT in the PFC (r = .67, p = .005) and all brain regions analyzed (r = .73 to .57, p = .001-.02). CONCLUSIONS: This finding represents a new pathological marker present in AD that is therapeutically targetable through direct inhibition or by novel treatments toward oxidative/pro-apoptotic processes implicated by MAO-A overexpression.

Peripheral neuropathic symptoms in celiac disease and inflammatory bowel disease.

OBJECTIVES: An association between celiac disease (CD) and peripheral neuropathy (PN) has been reported. METHODS: Patients with CD and/or inflammatory bowel disease (IBD) were recruited from the gastroenterology clinics at a medical center and local support groups. Control subjects without CD or IBD were recruited from the staff of the medical center as well as relatives and attendees at support groups. Each participant completed a survey that used two validated PN instruments to define and characterize PN. RESULTS: In the CD group, 38.9% met criteria for PN compared with 38.7% in the IBD group (P = 0.97) and 20.5% in the control group (P < 0.001). On multiple logistic regression, the odds of PN after adjusting for age, gender, diabetes, vitamin B12 deficiency, and cancer history were increased for CD (odds ratio, 2.51; 95% confidence interval, 1.82-3.47) and IBD (odds ratio, 2.78; 95% confidence interval, 1.85-4.18). CONCLUSIONS: PN is more often found in patients with CD and/or IBD than in the general population.