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



Single-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.



Compared 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.



The 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.
Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Donna E
DE
Murray
Department of Psychiatry and Behavioural Sciences, Stanford University School of Medicine, Stanford, CA, USA; Mental Illness Research Mental Illness Research and Education Clinical Centers; Sierra-Pacific War Related Illness and Injury Study Center, VA Palo Alto Health Care System, Palo Alto CA, USA.
Timothy C
TC
Durazzo
Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Thomas P
TP
Schmidt
Department of Clinical Neuroscience, Osher Center, Karolinska Institutet, Nobelsväg 9, 17177 Stockholm, Sweden.
Christoph
C
Abé
Philip R. Lee Institute for Health Policy Studies, University of California San Francisco, San Francisco, CA, USA.
Joseph
J
Guydish
Center for Imaging of Neurodegenerative Diseases (CIND), San Francisco VA Medical Center, San Francisco, CA, USA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Dieter J
DJ
Meyerhoff
Alcoholism; Brain; Cognition; Opiate; Proton magnetic resonance spectroscopy; Smoking
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