Increased markers of inflammation after cannabis cessation and their association with psychotic symptoms.

INTRODUCTION: A dysbalance of the immune system in psychotic disorders has been well investigated. However, despite a higher prevalence of cannabis (THC) consumption in patients with psychosis, few studies have investigated the impact of this use on inflammatory markers. METHODS: One hundred and two inpatients were included in this retrospective study. Leukocytic formula, hsCRP, fibrinogen levels and urinary THC were measured, and comparisons were performed at baseline and after 4 weeks of cannabis cessation between cannabis users (THC+) and non-users (THC-). RESULTS: After cannabis cessation, we found a greater increase in leucocyte level (p < 0.01), monocyte level (p = 0.05) and a statistical trend to a highest increase of lymphocyte level (p = 0.06) between baseline and 4 weeks in the THC+ group as compared to the THC- group. At 4 weeks, highest leucocyte (p = 0.03), lymphocyte (p = 0.04) and monocyte (p < 0.01) counts were found in the THC+ group, whereas at baseline no difference was found. A positive correlation was found between monocyte count at 4 weeks and baseline Positive and Negative Syndrome Scale (PANSS) negative subscore (p = 0.045) and between the variation of monocyte count between baseline and 4 weeks and the PANSS total score at 4 weeks (p = 0.05). CONCLUSION: THC cessation is associated with an increase in inflammatory markers, including white blood cell, lymphocyte and monocyte levels, which correlates with symptomatology of patients with psychosis.

The Modulated Role of Toxoplasma gondii on Eosinophils in Psychiatric Disorders after Cannabis Cessation.

The aim of our study was to evaluate the impact of T. gondii status on eosinophils count (EOS), the eosinophil-to-lymphocyte ratio (ELR), and the eosinophil-to-neutrophil-to-lymphocytes ratio (ENLR) before and after cannabis cessation in patients with psychiatric disorders. One hundred and eighty-eight patients were included in the study. T. gondii, EOS, ELR, ENLR, and urinary cannabis were measured at baseline and after 4 weeks of cannabis cessation. Highest levels and increase of PNE (p = 0.02), ENLR levels (p = 0.031) and highest level of ELR (p = 0.03) were found in patients after cannabis cessation only in patients positive for T. gondii serology (Toxo+ group). At four weeks, significant interactions between cannabis and T. gondii status for EOS (p = 0.038), and for ENLR (p = 0.043) levels were found, as well as for the evolution between baseline and 4 weeks for ENLR level (p = 0.049). After cannabis cessation, we found a positive correlation between negative symptoms and EOS levels at 4 weeks in the Toxo+ group. This study shows that the increase of inflammation after cannabis cessation might be modulated by T. gondii seropositivity status in patients after cannabis cessation.

White blood cells and patients with psychiatric disorders needing seclusion: A retrospective non-interventional study.

OBJECTIVE: The objective of this retrospective study was to investigate the peripheral immunological markers using leucocyte count, the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and the monocyte to lymphocyte ratio (MLR) in patients with aggressive behavior, during and after seclusion. METHODS: Ninety-nine inpatients were included in this retrospective study. Leucocyte count was measured, and NLR, PLR and MLR were calculated and compared between a group of patients who required seclusion and a group who did not. A multivariate analysis was performed using binary logistic regression, including confounding factors such as age, gender, medication, BMI, smoking status and diagnosis. RESULTS: We found the lowest levels of lymphocytes (P=0.01) and basophils (P<0.01) and the highest NLR (P=0.02) and MLR (P=0.04) in the seclusion group. We also found a restoration of these parameters after the end of the seclusion period. Furthermore, we found a positive correlation between the PANSS negative subscore, and PLR (P=0.05), or MLR (P=0.03) after seclusion, and between the MLR variation across the seclusion period and the PANSS general subscore after the end of seclusion (P=0.04). CONCLUSION: This study shows that NLR and MPR are higher in patients with aggressive symptoms and/or agitation who require seclusion. These immunological markers could be considered as state markers.

Caudate gray matter volumes and risk of relapse in Type A alcohol-dependent patients: A 7-year MRI follow-up study.

Background: Whether alteration in regional brain volumes can be detected in Type A alcoholics both at baseline and after a long follow-up remains to be confirmed. Therefore, we examined volume alterations at baseline, and longitudinal changes in a small follow-up subsample. Methods: In total of 26 patients and 24 healthy controls were assessed at baseline using magnetic resonance imaging and voxel-based morphometry, among which 17 patients and 6 controls were re-evaluated 7 years later. At baseline, regional cerebral volumes of patients were compared to controls. At follow-up, three groups were compared: abstainers (n = 11, more than 2 years of abstinence), relapsers (n = 6, <2 years of abstinence), and controls (n = 6). Results: The cross-sectional analyses detected, at both times, higher caudate nuclei volumes bilaterally in relapsers compared to abstainers. In abstainers, the longitudinal analysis indicated recovery of normal gray matter volumes in the middle and inferior frontal gyrus, and in the middle cingulate, while white matter volumes recovery was detected in the corpus callosum and in anterior and superior white matter specific regions. Conclusions: Overall, the present investigation revealed larger caudate nuclei in the relapser AUD patient group both at baseline and at follow-up in the cross-sectional analyses. This finding suggest that a higher caudate volume could be a candidate risk factor of relapse. In patients with specific type A alcohol-dependence, we showed that long-term recovery in fronto-striato-limbic GM and WM volumes occurs during long-term abstinence. These results support the crucial role of frontal circuitry in AUD.

Impact of cannabis use and its cessation on the dosage and the efficacy of antipsychotic drugs in in- and outpatients with schizophrenia taking medication: A systematic review and meta-analysis.

Compared with the general population, there are more cannabis users among patients suffering from schizophrenia and this consumption seems to impact the course and the treatment of their pathology. The aim of this meta-analysis and systematic review was to assess the impact of cannabis use on the efficacy of treatments, more particularly regarding the antipsychotic dosage, symptoms evolution, therapeutic resistance and the risk of relapse in patients with schizophrenia taking medication. We performed a systematic search of keywords on multiple databases up to August 2020 to identify all studies meeting the following criteria: comparison between cannabis smokers and non-cannabis users in patients with schizophrenia, assessment of antipsychotics doses, information about their efficacy or resistance to treatment and control of the compliance. Standardized mean differences were calculated for antipsychotic dosage and symptoms evolution at discharge, and a systematic review was performed for other outcomes. Twelve studies were included. Cannabis use did not seem to be associated with higher doses of antipsychotics at seven days and at the end of the studies, nor with poorer symptoms evolution, and nor with higher rate of antipsychotic resistance. However, cannabis use seems to be associated with a higher risk of relapse. This meta-analysis provides evidence that previous cannabis use, or occasional use, in patients with schizophrenia taking medication does not impact antipsychotic efficacy as described by antipsychotic dosage or PANSS score.

Cannabis Cessation, Inflammatory Markers and Schizophrenia.

Objective A dysbalance of the immune system in schizophrenia has been largely described but few studies have investigated the impact of cannabis use on inflammatory markers in patients with schizophrenia. The objective of our study was to investigate the impact of cannabis use on high-sensitivity C-reactive protein (hsCRP), fibrinogen levels and leucocytic formula in patients with schizophrenia. Methods: Thirty-eight acutely ill inpatients with schizophrenia were included. Patient hsCRP, fibrinogen levels, leukocytic formula and urinary cannabis were measured at baseline and after four weeks of treatment. Results: After four weeks of cannabis cessation (as confirmed by urinary tests), we found an increase of hsCRP level (p = .016) and lymphocytes (p = .03) in consumers patients whereas no difference was observed in non-consumers patients. As compared to non-consumers patients with schizophrenia, consumers had lower levels of hsCRP (p = .045). Finally, a negative correlation was found between the PANSS score evolution (between baseline and 4 weeks) and baseline hsCRP level. Conclusions: In our study, cannabis cessation raises inflammatory markers though improving clinical symptoms. The investigation and the understanding of interactions between cannabis use and inflammatory markers in patients with schizophrenia is of importance and could in the future be a new target for treatment of psychiatric symptoms linked to inflammation.

Chronic smoking and cognition in patients with schizophrenia: A meta-analysis.

BACKGROUND: Patients with schizophrenia display a very high rate of smoking in comparison with the general population. The aim of the present meta-analysis was to assess the association between cognitive performances and smoking status in patients with schizophrenia. METHODS: This review was registered at PROSPERO, number CRD42019126758. After a systematic search on MEDLINE, PsycINFO, and clinicaltrials.gov databases, all studies measuring neurocognitive performances in both smoking and nonsmoking patients with a diagnosis of schizophrenia were included. Original data were extracted. Standardized mean differences (SMD) were calculated with the means and standard deviations extracted using a random-effect model. Cognitive performances were compared between smoking and nonsmoking patients with schizophrenia. Meta-regressions were performed to explore the influence of sociodemographic and clinical variables on SMD. RESULTS: Eighteen studies were included in this meta-analysis. Chronic smoking in patients with schizophrenia, compared to nonsmoking, was associated with a significant more important impairment in attention (p = 0.02), working memory (p < 0.001), learning (p < 0.001), executive function (EF) reasoning/problem solving (p < 0.001) and speed of processing (p < 0.001), but not in delayed memory, EF abstraction/shifting, EF inhibition and language. The meta-regression analysis found that attention impairment could be influenced by age (p < 0.001) and Positive and Negative Syndrome Scale (PANSS) total score (p = 0.006). CONCLUSIONS: This meta-analysis provides strong evidence that, in patients with schizophrenia, chronic smoking is related to cognitive impairment. This association emphasizes the importance of paying careful attention to both tobacco addiction and cognitive functioning in patients with schizophrenia.

Efficacy of psychedelic treatments on depressive symptoms: A meta-analysis.

BACKGROUND: Psychedelic drugs have shown an efficacy in some psychiatric disorders and have an original mechanism of action with a 5-HT2A agonism. AIM: The aim of this meta-analysis was to assess by a quantitative analysis the putative efficacy of psychedelic drugs on depressive symptoms and to investigate the kinetic of this efficacy. METHODS: We searched the MEDLINE and PsycINFO databases through April 2019, without limits on year of publication. Means and standard deviations were extracted to calculate standardized mean differences (SMD). Scores of depressive symptoms were compared with baseline scores at days 7, 14, and 21; weeks 4-5 and 6-8; and months 3 and 6. RESULTS: Eight studies were included in this meta-analysis. A significant decrease of depressive symptoms was found from day 1 (n = 5 studies; SMD = ‒1.4, 95% confidence interval (CI): ‒2.33 to ‒0.48, p = 0.003) to 6 months (n = 4 studies; SMD = ‒1.07, 95% CI: ‒1.44 to ‒0.7, p < 0.001) after psychedelic sessions. No serious adverse effect was reported in all included studies. A transient increase of the heart rate, blood systolic, and diastolic pressure were found after psychedelics compared with placebo. CONCLUSION: This meta-analysis shows that psychedelic treatments were safe and could contribute to a rapid improvement of depressive symptoms.

Magnetic resonance spectroscopy studies in subjects with high risk for psychosis: A meta-analysis and review.

INTRODUCTION: Even though anomalies on brain metabolites have been found in schizophrenia, researches about subjects with high risk (HR) show heterogeneous results. Thus, this meta-analysis aims to characterize the metabolic profile of HR subjects, first, compared to controls (HC) and then compared to people with schizophrenia. METHODS: After a systematic database search, means and standard deviations were extracted to calculate standardized mean differences (SMD). Cerebral metabolites levels were compared between HR subjects and HC or patients with schizophrenia in all regions of interest investigated in included studies. Meta-regressions were performed to explore the influence of demographic and clinical variables on metabolites level's SMDs. RESULTS: Thirty-nine studies were included in this meta-analysis. A higher level of glutamine + glutamate (Glx) was found in the medial prefrontal cortex (mPFC) (p < 0.01) and potentially in the basal ganglia (p = 0,05) as well as a higher level of myo-inositol (mI) in the dorsolateral prefrontal cortex (DLPFC) (p = 0.04) in HR subjects compared to HC. A higher level of choline (Cho) was found in people with schizophrenia compared to HR subjects in the DLPFC (p < 0.001) and the medial temporal lobe (p = 0.02). Meta-regression analyses showed negative associations between SMD for Cho concentration, the percentage of females or the age (p = 0.01). CONCLUSIONS: The present meta-analysis provides evidence that some brain metabolites concentrations are disrupted before the transition to psychosis and could be considered like a vulnerability.

Kinetics of Cytokine Levels during Antipsychotic Treatment in Schizophrenia: A Meta-Analysis.

Background: Immune system dysfunction is a hypothesis in the psychopathology of schizophrenia, but the impact of antipsychotic treatment within this system is not clear. The aim of this meta-analysis was to investigate the impact of antipsychotic treatment on cytokine levels in in vivo studies on schizophrenia. Methods: After a systematic database search, original data were extracted with the help of certain authors. Means and SDs were extracted to calculate standardized mean differences. Cytokine levels were compared in vivo in schizophrenia patients, before and after antipsychotic treatment. Meta-regressions were performed to explore the influence of demographic and clinical variables on cytokine level standardized mean differences. Stratifications by treatment and diagnosis were also performed. Results: Forty-seven studies were included in this meta-analysis. Proinflammatory cytokine level decreases were found for interleukin-1 ß levels (P<.0001) and interferon-γ (P=.01) and a statistical trend towards a decrease in interleukin-6 (P=.08) and tumor necrosis factor-α (P=.07) levels. An antiinflammatory cytokine level increase was found for soluble tumor necrosis factor-R2 (P<.001) and soluble interleukin 2-R (P=.03) levels. A meta-regression analysis found a correlation between interleukin-6 level standardized mean differences and positive schizophrenia symptom score standardized mean differences before and after treatment (P=.01). Stratification by diagnosis or treatment found a possible impact of the kinetics of cytokine levels. Conclusions: The present meta-analysis provides evidence that antipsychotic treatment has an antiinflammatory effect and could normalize immune balance dysfunction in schizophrenia. Interleukin-6 level normalization could be a marker of illness equilibration and thus used in clinical practice.

Meta-analysis and review of dopamine agonists in acute episodes of mood disorder: Efficacy and safety.

The objective of this meta-analysis is to assess the efficacy and safety of partial and complete dopamine agonists in the treatment of acute mood disorder episodes. Randomized, double-blind and placebo-controlled trials of dopamine agonists in the treatment of acute mood disorder episodes were identified in the MEDLINE and PsycINFO databases and included in the meta-analysis. In monotherapy of mania, improved remission rates were found for cariprazine (odds ratio (OR): 2.08, P < 0.01) and for high-dose aripiprazole (OR: 3.00; P = 0.05), but not for low-dose aripiprazole. In bipolar depression, no improvement of remission and response rates was found for aripiprazole in monotherapy, whereas improved response rate (OR: 10.27, P < 0.01) was found for pramipexole only as an add-on to another mood stabilizer. In major depressive disorder, relatively similar improvements of remission rates were found for high-dose (OR: 1.96, p < 0.01) and low-dose aripiprazole (OR: 1.68, P = 0.01), as well as brexpiprazole (OR: 1.52, P = 0.05) as an add-on to antidepressant medication. Our meta-analysis shows that partial dopamine agonists at high doses are effective in treating acute mania. In major depressive disorder, which is resistant to classical antidepressants, low doses of partial dopamine agonists as adjunct therapy may represent a relatively safe and effective alternative.

Neuropsychological Impairment in Detoxified Alcohol-Dependent Subjects with Preserved Psychosocial Functioning.

BACKGROUND: Chronic alcoholism and its related cognitive impairments are associated with increased social, relational, and professional deficits which have a variable overall impact on social integration. These impairments are known to have varying severities and have rarely been studied among healthy alcohol-dependent subjects with preserved psychosocial functioning. Thus, the objective of this study is to describe neuropsychological performance in this particular population. METHOD: Twenty-nine socially adjusted alcohol-dependent men, hospitalized for a first or second withdrawal and abstinent for 3 weeks minimum, were compared to 29 healthy non-alcoholic controls. All subjects underwent clinical and psychiatric examination, neuropsychological tests of memory (M), working memory (WM), and executive functions (EF). Comparisons were performed using Student's t-tests or Mann-Whitney U tests. RESULTS: No group differences were found on the Self-Reported Social Adjustment Scale (SAS-SR) or in the Mini-Mental State Examination. Compared to controls, patients had greater episodic, spatial, and WM deficits as well as slightly altered executive functions. In contrast, their executive functions (spontaneous flexibility, criteria generation, rule maintenance, and inhibitory control) were relatively preserved. CONCLUSION: Our sample of socially and professionally integrated alcoholic patients shows fewer cognitive deficits than described in previous studies. Our results suggest that early on, alcohol-dependent subjects develop compensatory adaptation processes to preserve social function and adaptation. Minor cognitive impairments should be screened early in the disease to integrate cognitive interventions into the health-care plan to thus eventually prevent further socio-professional marginalization.

Sensitive biomarkers of alcoholism's effect on brain macrostructure: similarities and differences between France and the United States.

Alcohol consumption patterns and recognition of health outcomes related to hazardous drinking vary widely internationally, raising the question whether these national differences are reflected in brain damage observed in alcoholism. This retrospective analysis assessed variability of alcoholism's effects on brain cerebrospinal fluid (CSF) and white matter volumes between France and the United States (U.S.). MRI data from two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) were acquired on 1.5T imaging systems in 287 controls, 165 uncomplicated alcoholics (ALC), and 26 alcoholics with Korsakoff's Syndrome (KS). All data were analyzed at the U.S. site using atlas-based parcellation. Results revealed graded CSF volume enlargement from ALC to KS and white matter volume deficits in KS only. In ALC from France but not the U.S., CSF and white matter volumes correlated with lifetime alcohol consumption, alcoholism duration, and length of sobriety. MRI highlighted CSF volume enlargement in both ALC and KS, serving as a basis for an ex vacuo process to explain correlated gray matter shrinkage. By contrast, MRI provided a sensitive in vivo biomarker of white matter volume shrinkage in KS only, suggesting a specific process sensitive to mechanisms contributing to Wernicke's encephalopathy, the precursor of KS. Identified structural brain abnormalities may provide biomarkers underlying alcoholism's heterogeneity in and among nations and suggest a substrate of gray matter tissue shrinkage. Proposed are hypotheses for national differences in interpreting whether the severity of sequelae observe a graded phenomenon or a continuum from uncomplicated alcoholism to alcoholism complicated by KS.

Chronic alcohol consumption and its effect on nodes of frontocerebellar and limbic circuitry: comparison of effects in France and the United States.

Alcohol use disorders present a significant public health problem in France and the United States (U.S.), but whether the untoward effect of alcohol on the brain results in similar damage in both countries remains unknown. Accordingly, we conducted a retrospective collaborative investigation between two French sites (Caen and Orsay) and a U.S. laboratory (SRI/Stanford University) with T1-weighted, structural MRI data collected on a common imaging platform (1.5T, General Electric) on 288 normal controls (NC), 165 uncomplicated alcoholics (ALC), and 26 patients with alcoholic Korsakoff's syndrome (KS) diagnosed at all sites with a common interview instrument. Data from the two countries were pooled, then preprocessed and analyzed together at the U.S. site using atlas-based parcellation. National differences indicated that thalamic volumes were smaller in ALC in France than the U.S. despite similar alcohol consumption levels in both countries. By contrast, volumes of the hippocampus, amygdala, and cerebellar vermis were smaller in KS in the U.S. than France. Estimated amount of alcohol consumed over a lifetime, duration of alcoholism, and length of sobriety were significant predictors of selective regional brain volumes in France and in the U.S. The common analysis of MRI data enabled identification of discrepancies in brain volume deficits in France and the U.S. that may reflect fundamental differences in the consequences of alcoholism on brain structure between the two countries, possibly related to genetic or environmental differences.

Schizophrenia as a network disease: disruption of emergent brain function in patients with auditory hallucinations.

Schizophrenia is a psychiatric disorder that has eluded characterization in terms of local abnormalities of brain activity, and is hypothesized to affect the collective, "emergent" working of the brain. Indeed, several recent publications have demonstrated that functional networks in the schizophrenic brain display disrupted topological properties. However, is it possible to explain such abnormalities just by alteration of local activation patterns? This work suggests a negative answer to this question, demonstrating that significant disruption of the topological and spatial structure of functional MRI networks in schizophrenia (a) cannot be explained by a disruption to area-based task-dependent responses, i.e. indeed relates to the emergent properties, (b) is global in nature, affecting most dramatically long-distance correlations, and (c) can be leveraged to achieve high classification accuracy (93%) when discriminating between schizophrenic vs control subjects based just on a single fMRI experiment using a simple auditory task. While the prior work on schizophrenia networks has been primarily focused on discovering statistically significant differences in network properties, this work extends the prior art by exploring the generalization (prediction) ability of network models for schizophrenia, which is not necessarily captured by such significance tests.

Episodic memory in detoxified alcoholics: contribution of grey matter microstructure alteration.

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics.Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software.In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant.These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence.

Imaging of language-related brain regions in detoxified alcoholics.

BACKGROUND: Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls. METHODS: Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes. RESULTS: Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls. CONCLUSIONS: These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls.

Diffusion tensor tractography in mesencephalic bundles: relation to mental flexibility in detoxified alcohol-dependent subjects.

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n=20) and a group of healthy men (n=24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning.

The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals.