Early and habitual alcohol use is prodromal to alcohol dependence. Multiple factors including genetics and environment contribute to early and habitual drinking. Numerous studies have suggested cerebral structures and functions as an intermediate phenotype of alcohol misuse and vulnerability to alcohol dependence. On the other hand, while there is abundant information on how cerebral structures and functions are altered as a result of chronic alcohol use, little is known about these influences in non-dependent early and habitual drinking. In particular, what are the neural correlates that would predict increase in problem drinking and the quantity and frequency of alcohol use in non-dependent individuals? To address this question, we propose to recruit a large sample of early alcohol drinkers for magnetic resonance imaging (MRI) studies and clinical follow-up. Volunteers will undergo detailed medical and psychiatric assessments including their drinking behaviors, participate in MRI studies to evaluate cerebral structures (voxel-based morphometry or VBM), white matter integrity (diffusion tensor imaging or DTI), and functions of the component processes of cognitive control and alcohol cue reactivity (functional MRI or fMRI). We will engage all participants in a two-year clinical follow-up with tri-monthly assessments of their drinking behaviors. Head hair ethyl glucuronide will be quantified at baseline and every other follow-up, as a complementary index of alcohol consumption. For each of these neural measures, we will examine how they predict changes in drinking behavior, both independently and synergistically. Our overarching goal is to identify cerebral endophenotypes that best describe non-dependent early, habitual drinking and predict changes in problem drinking as well as the frequency and quantity of drinking. The potential findings would characterize the circuit biomarkers of early habitual drinking at a level of details that are critically needed and yet not currently available. Most importantly, these neural markers would help identify and facilitate early intervention for individuals at risk of developing heavy drinking and alcohol dependence.

Public Health Relevance

Alcohol dependence is often preceded by a period of non-dependent habitual drinking. Current research has provided much information on how brain structures and functions are altered in individuals who are dependent drinkers, but far less is known about these cerebral processes in non-dependent drinkers. Combining brain imaging and prospective clinical assessments, we could identify these neural markers and individuals at risk of developing alcohol dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA021449-01A1
Application #
8503268
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Matochik, John A
Project Start
2013-09-05
Project End
2018-08-31
Budget Start
2013-09-05
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$245,302
Indirect Cost
$69,686
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Cai, Weidong; Chen, Tianwen; Ryali, Srikanth et al. (2016) Causal Interactions Within a Frontal-Cingulate-Parietal Network During Cognitive Control: Convergent Evidence from a Multisite-Multitask Investigation. Cereb Cortex 26:2140-53
Manza, Peter; Hu, Sien; Ide, Jaime S et al. (2016) The effects of methylphenidate on cerebral responses to conflict anticipation and unsigned prediction error in a stop-signal task. J Psychopharmacol 30:283-93
Hu, Jianping; Hu, Sien; Maisano, Julianna R et al. (2016) Novelty Seeking, Harm Avoidance, and Cerebral Responses to Conflict Anticipation: An Exploratory Study. Front Hum Neurosci 10:546
Manza, Peter; Hu, Sien; Chao, Herta H et al. (2016) A dual but asymmetric role of the dorsal anterior cingulate cortex in response inhibition and switching from a non-salient to salient action. Neuroimage 134:466-74
Hu, Sien; Zhang, Sheng; Chao, Herta H et al. (2016) Association of Drinking Problems and Duration of Alcohol Use to Inhibitory Control in Nondependent Young Adult Social Drinkers. Alcohol Clin Exp Res 40:319-28
Rosenberg, Monica D; Zhang, Sheng; Hsu, Wei-Ting et al. (2016) Methylphenidate Modulates Functional Network Connectivity to Enhance Attention. J Neurosci 36:9547-57
Hu, Jianping; Lee, Dianne; Hu, Sien et al. (2016) Individual variation in the neural processes of motor decisions in the stop signal task: the influence of novelty seeking and harm avoidance personality traits. Brain Struct Funct 221:2607-18
Hu, Sien; Ide, Jaime S; Zhang, Sheng et al. (2015) Anticipating conflict: Neural correlates of a Bayesian belief and its motor consequence. Neuroimage 119:286-95
Chang, Andrew; Chen, Chien-Chung; Li, Hsin-Hung et al. (2015) Perigenual anterior cingulate event-related potential precedes stop signal errors. Neuroimage 111:179-85
Manza, Peter; Zhang, Sheng; Hu, Sien et al. (2015) The effects of age on resting state functional connectivity of the basal ganglia from young to middle adulthood. Neuroimage 107:311-22

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