Frontal Metabolite Concentration Deficits in Opiate Dependence Relate to Substance Use, Cognition, and Self-Regulation.

Donna E Murray,Donna E Murray,Timothy C Durazzo,Christoph Abé,Dieter J Meyerhoff,Joseph Guydish,Thomas P Schmidt

doi:10.4172/2155-6105.1000286

Abstract

ObjectiveProton magnetic resonance spectroscopy (1H MRS) in opiate dependence showed abnormalities in neuronal viability and glutamate concentration in the anterior cingulate cortex (ACC). Metabolite levels in dorsolateral prefrontal cortex (DLPFC) or orbitofrontal cortex (OFC) and their neuropsychological correlates have not been investigated in opiate dependence.MethodsSingle-volume proton MRS at 4 Tesla and neuropsychological testing were conducted in 21 opiate-dependent individuals (OD) on buprenorphine maintenance therapy. Results were compared to 28 controls (CON) and 35 alcohol-dependent individuals (ALC), commonly investigated treatment-seekers providing context for OD evaluation. Metabolite concentrations were measured from ACC, DLPFC, OFC and parieto-occipital cortical (POC) regions.ResultsCompared to CON, OD had lower concentrations of N-acetylaspartate (NAA), glutamate (Glu), creatine +phosphocreatine (Cr) and myo-Inositol (mI) in the DLPFC and lower NAA, Cr, and mI in the ACC. OD, ALC, and CON were equivalent on metabolite levels in the POC and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region. In OD, prefrontal metabolite deficits in ACC Glu as well as DLPFC NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and Cr correlated with substance use measures. In the OFC of OD, Glu and choline-containing metabolites were elevated and lower Cr concentration related to higher nonplanning impulsivity. Compared to 3 week abstinent ALC, OD had significant DLPFC metabolite deficits.ConclusionThe anterior frontal metabolite profile of OD differed significantly from that of CON and ALC. The frontal lobe metabolite abnormalities in OD and their neuropsychological correlates may play a role in treatment outcome and could be explored as specific targets for improved OD treatment.

Highlights

The misuse of opiates is a serious problem worldwide, is increasing in young adults [1,2,3], and has substantial individual and societal consequences
opiate-dependent individuals (OD), alcohol-dependent individuals (ALC), and CON were equivalent on metabolite levels in the parieto-occipital cortical (POC) and γ-aminobutyric acid (GABA) concentration did not differ between groups in any region
In OD, prefrontal metabolite deficits in anterior cingulate cortex (ACC) Glu as well as dorsolateral prefrontal cortex (DLPFC) NAA and choline containing metabolites (Cho) correlated with poorer working memory, executive and visuospatial functioning; metabolite deficits in DLPFC Glu and ACC GABA and creatine +phosphocreatine (Cr) correlated with substance use measures

Summary

Introduction

The misuse of opiates is a serious problem worldwide, is increasing in young adults [1,2,3], and has substantial individual and societal consequences. In 2014 in the United States alone, approximately 1.9 million people had an opiate use disorder, including 586,000 heroin users [2]. Neuroimaging in opiate dependence indicates both altered brain structure, in the anterior cingulate cortex (ACC; [4,5,6,7]), and brain function involving dorsolateral prefrontal cortex (DLPFC) and ACC [8,9]. The few 1H MRS studies in opiate dependence to date revealed lower concentration of N-acetylaspartate (NAA), a marker of neuronal integrity, in the medial frontal cortex, including the ACC [11,12,13], as well as lower glutamate (Glu), a primary excitatory neurotransmitter, or glutamate+glutamine concentration in some [11,13,14] but not all studies [15]. The discrepant MRS findings may relate to differences among study participants regarding the prevalence and severity of comorbid substance use (i.e., alcohol, tobacco, illicit drugs), the type, dose and duration of replacement therapy for heroin users (buprenorphine, methadone), and/or participant age

Results

Discussion

Conclusion