Cigarette smoking history is associated with poorer recovery in multiple neurocognitive domains following treatment for an alcohol use disorder.

Cigarette smoking is associated with neurocognitive dysfunction in various populations, including those seeking treatment for an alcohol use disorder (AUD). This study compared the rate and extent of recovery on measures of processing speed, executive functions, general intelligence, visuospatial skills and working memory in treatment-seeking alcohol dependent individuals (ALC) who were never-smokers (nvsALC), former-smoker (fsALC), and active smokers (asALC), over approximately 8 months of abstinence from alcohol. Methods: ALC participants were evaluated at approximately 1 month of abstinence (AP1; n = 132) and reassessed after 8 months of sobriety (AP2; n = 54). Never-smoking controls (CON; n = 33) completed a baseline and follow-up (n = 19) assessment approximately 9 months later. Domains evaluated were executive functions, general intelligence, processing speed, visuospatial skills and working memory; a domain composite was formed from the arithmetic average of the foregoing domains. nvsALC showed greater improvement than fsALC, asALC and CON on most domains over the AP1-AP2 interval. fsALC demonstrated greater recovery than asALC on all domains except visuospatial skills; fsALC also showed greater improvements than CON on general intelligence, working memory and domain composite. asALC did not show significant improvement on any domain over the AP1-AP2 interval. At 8 months of abstinence, asALC were inferior to CON and nvsALC on multiple domains, fsALC performed worse than nvsALC on several domains, but nvsALC were not different from CON on any domain. Our results provide robust evidence that smoking status influenced the rate and extent of neurocognitive recovery between 1 and 8 months of abstinence in this ALC cohort. Chronic smoking in AUD likely contributes to the considerable heterogeneity observed in neurocognitive recovery during extended abstinence. The findings provide additional strong support for the benefits of smoking cessation and the increasing clinical movement to offer smoking cessation resources concurrent with treatment for AUD

Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome.

We previously reported that at 1-and-4 weeks of sobriety, those who relapsed after treatment demonstrated significantly smaller total frontal cortical volume than individuals who maintained abstinence for at least 12 months post treatment. The segmentation method employed did not permit examination of frontal subregions that serve as nodes of the executive, salience and emotional regulation networks; structural abnormalities in these circuits are associated with relapse in those seeking treatment for alcohol use disorders (AUD). The primary goal of this study was to determine if frontal cortical subregion volume recovery during early abstinence is associated with long-term abstinence from alcohol. We compared bilateral components of the dorsal prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex and insula volumes, at 1 and 4 weeks of abstinence, between individuals who resumed drinking within 12 months of treatment (Relapsers) those who showed sustained abstinence over 12 months following treatment (Abstainers) and healthy Controls. At 1 and 4 weeks of sobriety, Relapsers demonstrated significantly smaller volumes than Controls in 15 of 20 regions of interest, while Abstainers only had smaller volumes than Controls in 5 of 20 regions. In Relapsers, increasing volumes over 1 month in multiple frontal subregions and the insula were associated with longer duration of abstinence after treatment. The persistent bilateral frontal and insula volume deficits in Relapsers over 4 weeks from last alcohol use may have implications for neurostimulation methods targeting anterior frontal/insula regions, and represent an endophenotype that differentiates those who respond more favorably to available psychosocial and pharmacological interventions

Cigarette smoking is associated with amplified age-related volume loss in subcortical brain regions

BACKGROUND: Magnetic resonance imaging studies of cigarette smoking-related effects on human brain structure have primarily employed voxel-based morphometry, and the most consistently reported finding was smaller volumes or lower density in anterior frontal regions and the insula. Much less is known about the effects of smoking on subcortical regions. We compared smokers and non-smokers on regional subcortical volumes, and predicted that smokers demonstrate greater age-related volume loss across subcortical regions than non-smokers. METHODS: Non-smokers (n=43) and smokers (n=40), 22-70 years of age, completed a 4T MRI study. Bilateral total subcortical lobar white matter (WM) and subcortical nuclei volumes were quantitated via FreeSurfer. In smokers, associations between smoking severity measures and subcortical volumes were examined. RESULTS: Smokers demonstrated greater age-related volume loss than non-smokers in the bilateral subcortical lobar WM, thalamus, and cerebellar cortex, as well as in the corpus callosum and subdivisions. In smokers, higher pack-years were associated with smaller volumes of the bilateral amygdala, nucleus accumbens, total corpus callosum and subcortical WM. CONCLUSIONS: Results provide novel evidence that chronic smoking in adults is associated with accelerated age-related volume loss in subcortical WM and GM nuclei. Greater cigarette quantity/exposure was related to smaller volumes in regions that also showed greater age-related volume loss in smokers. Findings suggest smoking adversely affected the structural integrity of subcortical brain regions with increasing age and exposure. The greater age-related volume loss in smokers may have implications for cortical-subcortical structural and/or functional connectivity, and response to available smoking cessation interventions

Brain GABA and Glutamate Concentrations Following Chronic Gabapentin Administration: A Convenience Sample Studied During Early Abstinence From Alcohol.

Gabapentin (GBP), a GABA analog that may also affect glutamate (Glu) production, can normalize GABA and Glu tone during early abstinence from alcohol, effectively treating withdrawal symptoms and facilitating recovery. Using in vivo magnetic resonance spectroscopy, we tested the degree to which daily GBP alters regional brain GABA and Glu levels in short-term abstinent alcohol-dependent individuals. Regional metabolite levels were compared between 13 recently abstinent alcohol-dependent individuals who had received daily GBP for at least 1 week (GBP+) and 25 matched alcohol-dependent individuals who had not received GBP (GBP-). Magnetic resonance spectra from up to five different brain regions were analyzed to yield absolute GABA and Glu concentrations. GABA and Glu concentrations in the parieto-occipital cortex were not different between GBP- and GBP+. Glu levels in anterior cingulate cortex, dorsolateral prefrontal cortex, and basal ganglia did not differ between GBP- and GBP+. However, in a subgroup of individuals matched on age, sex, and abstinence duration, GBP+ had markedly lower Glu in the frontal white matter (WM) than GBP-, comparable to concentrations found in light/non-drinking controls. Furthermore, lower frontal WM Glu in GBP+ correlated with a higher daily GBP dose. Daily GBP treatment at an average of 1,600 mg/day for at least 1 week was not associated with altered cortical GABA and Glu concentrations during short-term abstinence from alcohol, but with lower Glu in frontal WM. GBP for the treatment of alcohol dependence may work through reducing Glu in WM rather than increasing cortical GABA

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

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

Differences in White Matter Microstructure and Connectivity in Nontreatment‐Seeking Individuals with Alcohol Use Disorder

Background Diffusion‐weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol‐dependent populations. In addition, information on WM deficits in currently drinking, nontreatment‐seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD). Methods Thirty‐eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in‐house preprocessing of the DWI data, FA images were analyzed with tract‐based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption. Results Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family‐wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (ρ = −0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions. Conclusions NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self‐reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol‐dependent individuals, after controlling for the key variable of cigarette smoking

Genetic and behavioral determinants of hippocampal volume recovery during abstinence from alcohol

Alcohol-dependent individuals (ALC) have smaller hippocampi and poorer neurocognition than healthy controls. Results from studies on the association between alcohol consumption and hippocampal volume have been mixed, suggesting that comorbid or premorbid factors (i.e., those present prior to the initiation of alcohol dependence) determine hippocampal volume in ALC. We aimed to characterize the effects of select comorbid (i.e., cigarette smoking) and premorbid factors (brain-derived neurotrophic factor [BDNF] genotype [Val66Met rs6265]) on hippocampal volume in an ALC cohort followed longitudinally into extended abstinence. One hundred twenty-one adult ALC in treatment (76 smokers, 45 non-smokers) and 35 non-smoking light-drinking controls underwent quantitative magnetic resonance imaging, BDNF genotyping, and neurocognitive assessments. Representative subgroups were studied at 1 week, 1 month, and at an average of 7 months of abstinence. ALC had smaller hippocampi than healthy controls at all time points. Hippocampal volume at 1 month of abstinence correlated with lower visuospatial function. Smoking status did not influence hippocampal volume or hippocampal volume recovery during abstinence. However, only BDNF Val homozygotes tended to have hippocampal volume increases over 7 months of abstinence, and Val homozygotes had significantly larger hippocampi than Met carriers at 7 months of abstinence. These findings suggest that BDNF genotype, but not smoking status or measures of drinking severity, regulate functionally relevant hippocampal volume recovery in abstinent ALC. Future studies aimed at exploring genetic determinants of brain morphometry in ALC may need to evaluate individuals during extended abstinence after the acute environmental effects of chronic alcohol consumption have waned