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Resting‐state functional connectivity and presynaptic monoamine signaling in Alcohol Dependence
Author(s) -
Zhu Xi,
Dutta Nisha,
Helton Sarah G.,
Schwandt Melanie,
Yan Jia,
Hodgkinson Colin A.,
Cortes Carlos R.,
Kerich Mike,
Hall Samuel,
Sun Hui,
Phillips Monte,
Momenan Reza,
Lohoff Falk W.
Publication year - 2015
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.22951
Subject(s) - monoaminergic , monoamine neurotransmitter , neuroscience , resting state fmri , psychology , dopamine , alcohol dependence , vesicular monoamine transporter , medicine , biology , serotonin , alcohol , receptor , biochemistry
Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting‐state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting‐state FC in 4 networks in alcoholics compared to controls ( P  < 0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants ( P  < 0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles. Hum Brain Mapp 36:4808–4818, 2015 . Published 2015. This article is a U.S. Government work and is in the public domain in the USA

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