Effects of the Fyn kinase inhibitor saracatinib on ventral striatal activity during performance of an fMRI monetary incentive delay task in individuals family history positive or negative for alcohol use disorder. A pilot randomised trial.

Altered striatal regulation of the GluN2B subunit of N-methyl-D-aspartate (NMDA) glutamate receptors by the Fyn/Src family of protein tyrosine kinases has been implicated in animal alcohol consumption. Previously, we have described differences between individuals positive (FHP) and negative (FHN) for familial alcohol use disorder (AUD) in the ventral striatal (VS) activation associated with monetary incentive delay task (MIDT) performance during functional magnetic resonance imaging (fMRI). Here, we used AZD0530 (saracatinib), a centrally active Fyn/Src inhibitor to probe the role of Fyn/Src regulation of NMDA receptors (NMDAR) in VS activation differences between FHP and FHN individuals during fMRI MIDT performance.

The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene.

To identify genetic mechanisms involved in the interplay of risky sexual behaviors (RSBs) and alcohol dependence (AD), we conducted genome-wide gene-by-AD (GW-GxAD) analyses of RSB in 3924 alcohol-exposed and sexually experienced subjects. RSBs were defined as a score based on lifetime experiences of unprotected sex and multiple sexual partners. Diagnosis of lifetime AD was defined by DSM-IV criteria.

Robust changes in reward circuitry during reward loss in current and former cocaine users during performance of a monetary incentive delay task.

Background: Abnormal function in reward circuitry in cocaine addiction could predate drug use as a risk factor, follow drug use as a consequence of substance-induced alterations, or both.

Methods: We used a functional magnetic resonance imaging monetary incentive delay task (MIDT) to investigate reward-loss neural response differences among 42 current cocaine users, 35 former cocaine users, and 47 healthy subjects who also completed psychological measures and tasks related to impulsivity and reward.

Results: We found various reward processing-related group differences in several MIDT phases.

Default mode network activity and white matter integrity in healthy middle-aged ApoE4 carriers.

Alzheimer's disease (AD) is most commonly detected during old age, but the underlying neuropathologic changes likely appear decades earlier, especially among patients possessing genetic risk factors, such as the isoform E4 of the apolipoprotein E (ApoE4). In this study, we used magnetic resonance imaging (MRI) to assess default mode network (DMN) connectivity in 22 ApoE4 non-carriers and 14 matched ApoE4 carriers as well as white matter fractional anisotropy (FA) in 15 ApoE4 non-carriers and 11 demographically matched ApoE4 carriers. Cognitive tests were also administered.