Effects of ANK3 variation on gray and white matter in bipolar disorder.

The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.

Neural underpinnings of expecting alcohol: Placebo alcohol administration alters nucleus accumbens resting state functional connectivity.

BACKGROUND: Using balanced placebo designs, seminal alcohol administration research has shown individuals' beliefs about whether they have consumed alcohol, irrespective of the actual presence of alcohol, can determine level of alcohol consumption and impact social behavior. Despite the known effect of expecting alcohol on drinking behavior, few studies have used the placebo manipulation to directly investigate the neural underpinnings of the expectancy-related effects that occur following perceived alcohol consumption in humans. The present paper examined placebo responses in the laboratory to better understand the neural basis for the psychological phenomenon of expectancies. METHODS: As part of a larger within-subjects study design, healthy young adults (N = 22, agemean+SD=23 +1) completed resting state fMRI scans and measures of subjective response before and after consuming placebo beverages. Effect of placebo beverage consumption (pre- versus post-beverage consumption) on functional connectivity within prefrontal cortical networks was examined using the CONN Toolbox. Relations between perceived subjective response to alcohol with functional connectivity response following placebo beverage consumption were examined. RESULTS: Compared to pre-beverage scan, placebo beverage consumption was associated with increased positive functional connectivity between right nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex (pFDR<0.05). Subjective ratings of intoxication (i.e., feeling 'drunk') positively correlated with placebo beverage-related increases in nucleus accumbens - subcallosal cingulate cortex functional connectivity. CONCLUSION: Results suggest placebo response to alcohol is associated with increased functional connectivity within a key reward network (nucleus accumbens - ventromedial prefrontal cortex and subcallosal cingulate cortex) and put forth a mechanism by which alcohol expectancies may contribute to the subjective experience of intoxication.