Brain Docosahexaenoic Acid [DHA] Incorporation and Blood Flow Are Increased in Chronic Alcoholics: A Positron Emission Tomography Study Corrected for Cerebral Atrophy

John C Umhau,Sharon Majchrzak-Hong,Stephen C Cunnane,James Demar,Joseph R Hibbeln,Nahed Hussein,Weiyin Zhou,Abesh K Bhattacharjee,Abigail Urish,Stanley I Rapoport,Peter Herscovitch,Kaizong Ma,Jussi Hirvonen,Shantalaxmi Thada,Norman Salem,Bernard Le Foll

doi:10.1371/journal.pone.0075333

Abstract

ObjectiveChronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid (DHA, 22∶6n-3), particularly if liver disease is present. In animal models, excessive alcohol consumption is reported to reduce brain DHA concentration, suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA metabolism also is abnormal in chronic alcoholics.MethodsWe compared 15 non-smoking chronic alcoholics, studied within 7 days of their last drink, with 22 non-smoking healthy controls. Using published neuroimaging methods with positron emission tomography (PET), we measured regional coefficients (K*) and rates (Jin) of DHA incorporation from plasma into the brain of each group using [1-11C]DHA, and regional cerebral blood flow (rCBF) using [15O]water. Data were partial volume error corrected for brain atrophy. Plasma unesterified DHA concentration also was quantified.ResultsMean K* for DHA was significantly and widely elevated by 10–20%, and rCBF was elevated by 7%–34%, in alcoholics compared with controls. Unesterified plasma DHA did not differ significantly between groups nor did whole brain Jin, the product of K* and unesterified plasma DHA concentration.DiscussionSignificantly higher values of K* for DHA in alcoholics indicate increased brain avidity for DHA, thus a brain DHA metabolic deficit vis-à-vis plasma DHA availability. Higher rCBF in alcoholics suggests increased energy consumption. These changes may reflect a hypermetabolic state related to early alcohol withdrawal, or a general brain metabolic change in chronic alcoholics.

Highlights

Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA, 22:6n-3), if liver disease is present [1,2]
Reduced dietary n-3 PUFA was reported to promote binge alcohol induced neurodegeneration [3], and a low plasma DHA concentration was associated with relapse vulnerability in substance abusers [4]
Average K* in gray matter regions was not correlated with days of sobriety prior to the positron emission tomography (PET) study (R2 = 0.06, p = 0.363)

Summary

Introduction

Chronic alcohol dependence has been associated with disturbed behavior, cerebral atrophy and a low plasma concentration of the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA, 22:6n-3), if liver disease is present [1,2]. Reduced dietary n-3 PUFA was reported to promote binge alcohol induced neurodegeneration [3], and a low plasma DHA concentration was associated with relapse vulnerability in substance abusers [4]. Excessive chronic alcohol intake was reported to lower DHA concentration in blood and nervous system; the effect was worsened by a low n-3 PUFA diet [5,6]. DHA and its metabolites modulate gene expression, neurotransmission, enzyme activity, membrane channels, receptor activation, inflammation and other cellular processes [12,13,14]

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