Abstract
In animals and humans, behavior can be influenced by irrelevant stimuli, a phenomenon called Pavlovian-to-instrumental transfer (PIT). In subjects with substance use disorder, PIT is even enhanced with functional activation in the nucleus accumbens (NAcc) and amygdala. While we observed enhanced behavioral and neural PIT effects in alcohol-dependent subjects, we here aimed to determine whether behavioral PIT is enhanced in young men with high-risk compared to low-risk drinking and subsequently related functional activation in an a-priori region of interest encompassing the NAcc and amygdala and related to polygenic risk for alcohol consumption. A representative sample of 18-year old men (n = 1937) was contacted: 445 were screened, 209 assessed: resulting in 191 valid behavioral, 139 imaging and 157 genetic datasets. None of the subjects fulfilled criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders-IV-TextRevision (DSM-IV-TR). We measured how instrumental responding for rewards was influenced by background Pavlovian conditioned stimuli predicting action-independent rewards and losses. Behavioral PIT was enhanced in high-compared to low-risk drinkers (b = 0.09, SE = 0.03, z = 2.7, p < 0.009). Across all subjects, we observed PIT-related neural blood oxygen level-dependent (BOLD) signal in the right amygdala (t = 3.25, pSVC = 0.04, x = 26, y = −6, z = −12), but not in NAcc. The strength of the behavioral PIT effect was positively correlated with polygenic risk for alcohol consumption (rs = 0.17, p = 0.032). We conclude that behavioral PIT and polygenic risk for alcohol consumption might be a biomarker for a subclinical phenotype of risky alcohol consumption, even if no drug-related stimulus is present. The association between behavioral PIT effects and the amygdala might point to habitual processes related to out PIT task. In non-dependent young social drinkers, the amygdala rather than the NAcc is activated during PIT; possible different involvement in association with disease trajectory should be investigated in future studies.
Highlights
Problematic alcohol drinking patterns like bingeing or heavy drinking during adolescence and early adulthood are associated with severe psychological, social and health problems [1]
1974 males were randomly drawn from local registration offices in two sites (Berlin & Dresden, Germany [34]) shortly after their 18th birthday representing their local legal adult age
To present the full picture, we report results at other p-levels
Summary
Problematic alcohol drinking patterns like bingeing or heavy drinking during adolescence and early adulthood are associated with severe psychological, social and health problems [1]. Previous studies have examined alcohol-specific behavioral PIT effects in social drinkers but did not assess the association between behavioral PIT effects and individual drinking patterns [14], nor did they find an association with subclinical alcohol dependence [15,16] or neural PIT correlates using electroencephalography (EEG) [16]. In contrast to these studies, we investigate nondrug-related PIT effects in young high-versus low-risk [17] social drinkers on a behavioral and neural level using functional magnetic resonance imaging (fMRI)
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