Cortical Inhibition in Alcohol Dependence

Perceived Effectiveness of Medications Among Mental Health Service Users With and Without Alcohol Dependence

Treatment of Psychiatric Symptoms Associated With a Frontal Lobe Tumor Through Surgical Resection

The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.

The inability to inhibit certain behaviors is a key feature of impulsivity, which is often present in people with a substance use disorder. However, the findings on impulsivity in people with alcohol dependence (AD) are inconsistent, possibly because of the frequent co-occurrence of depression/anxiety (D/A) and its influence on impulsivity. In the current study, we aimed to distinguish response inhibition impairments in AD from possible response inhibition effects associated with D/A. AD patients (n = 31) with high D/A co-morbidity were compared to patients with D/A only (n = 18) and healthy controls (HCs; n = 16) using the Stop Signal Task (SST) during functional magnetic resonance imaging (fMRI). Correlation analyses were performed between activated brain areas, behavioral data and addiction and D/A characteristics. The three groups did not differ on response inhibition performance. However, AD severity, but not D/A severity, was positively associated with decreased response inhibition. During the SST, AD patients showed hyperactivity in the putamen and thalamus compared with D/A patients and HCs. Thalamus activation was negatively associated with AD duration. In addition, AD patients showed hypoactivity in the supplementary motor area (SMA) compared with HCs. SMA activity within HCs was negatively correlated with depressive symptom severity. Discussion In general, AD patients were not more impulsive than D/A patients or HCs but they did reveal inhibition impairments with increasing AD severity. A shift from cortical to subcortical engagement in AD patients during response inhibition may represent an alternative strategy, which decreased with longer drinking history, suggesting the presence of an AD-specific endophenotype.

Addolorato et al. [1] recently published a welcome review article in CNS Drugs, entitled ‘‘Management of alcohol dependence in patients with liver disease’’. Alcoholic liver disease (ALD) is too often forgotten within the numerous review articles that are regularly published on alcoholdependence medications, whereas cirrhosis is one of the most dramatic consequences of alcohol dependence and can deeply affect the safe use of numerous medications. Addolorato and colleagues [2] state that the gamma amino-butyric acid type B (GABAB) receptor agonist baclofen should be currently preferred in ALD because baclofen was the sole drug that had a good efficacy/safety profile in ALD patients with alcohol dependence in a study whose results were published in The Lancet. Albeit relevant, this conclusion is relatively ironic in the sense that an off-label treatment for alcohol dependence has exhibited higher evidence in ALD than any of the currently approved medications. This indicates to what extent this field of research has been neglected until now. Although baclofen is definitely one of the most promising drugs for treating alcohol dependence in ALD patients, several important safety concerns remain in using this drug in ALD. The findings of the study in The Lancet were obtained from patients with no psychiatric history and who had undergone permanent monitoring by close relatives throughout the trial period. Moreover, as baclofen was particularly effective in maintaining abstinence, only nine patients within the baclofen group experienced relapse, and the amounts of alcohol drinking were not detailed. Thus, possible interactions between baclofen and alcohol intoxication were difficult to identify. Additionally, no patient presented with hepatic encephalopathy, although this condition has been hypothesized to result from GABArelated mechanisms [3]. For all of these reasons, despite the important advances provided by this study, several safety concerns still persist for baclofen because the patient profiles and monitoring conditions in this study were not comparable to those of real-life patients, in whom significant psychiatric co-morbidities; persisting or recurrent alcohol abuse; or ALD complications, such as encephalopathy, may be found. We believe that the question of dose is even more crucial. In the aforementioned study, baclofen was tested at 30 mg/day. Addolorato’s Roman team has published many articles using this dose, which has thus made the dose the most studied and most supported by evidence in the offlabel use of baclofen for abstinence maintenance. However, a dose–response effect of baclofen has been suspected in alcohol dependence [4], and this drug has recently been used in clinical practice at very high doses, i.e., up to 300 mg/day or more, and notably more with a purpose of temperance than of abstinence [5–8]. Although several of these uses have been limited to last-resort situations by hospital teams that could provide enhanced patient monitoring [9, 10], there also exists certain spreading, albeit less visible, practices of prescribing of high-dose baclofen, notably in France [10]. The possible hepatic toxicity of B. Rolland (&) A. Louvet O. Cottencin R. Bordet University of Lille Nord de France, 59045, Lille, France e-mail: benjrolland@gmail.com; benjamin.rolland@chrulille.fr

EPA-1807 – Internet intervention for people with insomnia and alcohol-dependence in ukraine

Dopamine receptors are associated with reward and dependence towards alcohol. The polymorphisms of dopamine D2 receptor (DRD2) genes have been reported to be involved in susceptibility to alcoholism. Therefore, we investigated the association of three single-nucleotide polymorphisms (SNPs) in DRD2 and ankyrin repeat and kinase domain containing one (ANKK1) genes with alcohol dependence in Korean subjects, who were classified by the criteria of the Lesch typology. The DRD2 -141C (Insertion (Ins)/Deletion (Del)), exon8 (A/G) and the ANKK1 TaqIA (A1/A2) polymorphisms were genotyped in a case-control sample consisting of 245 alcohol-dependent (AD) patients and 110 healthy controls. AD patients were classified into four subtypes by the Lesch typology. The majority of them (77.1%) were Lesch type 1. Differences in genotype and allele frequencies were examined between the AD patients and the controls. Also those analyses were done between the Lesch type 1 group and the controls. There were significant differences in the genotype and allele frequencies of -141C Ins/Del and TaqIA A1/A2 between the AD patients and the controls. However, there were no significant differences in genotype or allele frequencies of exon8 A/G between the AD patients and the controls. The -141C Ins/Ins and TaqIA A1+ variants were associated with Lesch type 1 AD patients. When analysing haplotypes of three SNPs, the odds ratio of -141C Ins-A-A1 was 2.286, while the odds ratio of -141C Del-G-A2 was 0.323. The present study showed a significant difference in DRD2 -141C and ANKK1 TaqIA polymorphisms between the AD patients and the controls. Our findings suggest that -141C Ins and TaqIA A1 alleles can be a predisposing factor for alcohol dependence in the Korean population.

Commitment strength, alcohol dependence and HealthCall participation: Effects on drinking reduction in HIV patients

DIAGNOSIS AND MANAGEMENT OF ALCOHOL PROBLEMS

The human orbitofrontal cortex, ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex are involved in reward processing and thereby in emotion but are also implicated in episodic memory. To understand these regions better, the effective connectivity between 360 cortical regions and 24 subcortical regions was measured in 172 humans from the Human Connectome Project and complemented with functional connectivity and diffusion tractography. The orbitofrontal cortex has effective connectivity from gustatory, olfactory, and temporal visual, auditory, and pole cortical areas. The orbitofrontal cortex has connectivity to the pregenual anterior and posterior cingulate cortex and hippocampal system and provides for rewards to be used in memory and navigation to goals. The orbitofrontal and pregenual anterior cortex have connectivity to the supracallosal anterior cingulate cortex, which projects to midcingulate and other premotor cortical areas and provides for action-outcome learning including limb withdrawal or flight or fight to aversive and nonreward stimuli. The lateral orbitofrontal cortex has outputs to language systems in the inferior frontal gyrus. The medial orbitofrontal cortex connects to the nucleus basalis of Meynert and the pregenual cingulate to the septum, and damage to these cortical regions may contribute to memory impairments by disrupting cholinergic influences on the neocortex and hippocampus.

BACKGROUND: Alcohol dependence syndrome (ADS) has become a global public health challenge because of its high prevalence and the concomitant increase in risk of liver disease, cardiovascular disease and premature death. Influence of alcohol use on lipid metabolism is well recognized. Investigations had been carried out in the earlier period on abnormal lipid profile as a risk factor for Coronary Heart disease (CHD). Patients of alcohol dependence usually have a consumption pattern of more heavy use. Therefore it is useful to study the lipid profile in patients of alcohol dependence, to understand the effects of increasing levels of consumption. METHODS: This cross-sectional study was conducted in TU Teaching Hospital. ADS patients were screened by the consultant psychiatrist using the Alcohol Use Disorder Identification Test (AUDIT) questionnaire. A total of 89 patients scored positive on the AUDIT as having alcohol-related problems and were included in the study. 89 ADS patients and 89 healthy controls both male and female were enrolled as participants. Blood Pressure and other anthropometric parameters were measured while fasting blood samples were analyzed for serum lipid profile. SPSS program was used to analyze data, t-test & Spearman's correlation coefficient was used to find correlation. RESULTS: Among the ADS cases 95% were current smokers. Mean age of cases and controls was 35.42±5.6 & 34.53±3.5 years respectively. The mean total cholesterol levels were found to be higher in cases (5.41±0.70) than controls (3.79±0.74) with a strong statistical significance (p<0.001). Also, Mean triglyceride (TG) levels (2.09±0.72), along with the mean HDL-cholesterol (1.66±0.40) and LDL-cholesterol levels (2.79±0.81) were also elevated in cases when compared to the control samples (p<0.001). CONCLUSION: This study has demonstrated definitive lipid profile changes in patients of alcohol dependence, with some correlation to the liver dysfunction. Alcohol causes alteration in various parameters of lipid metabolism including those which predispose to CHD. Low to moderate alcohol use over prolonged periods has been linked to have protective influence for development of coronary heart disease (CHD), through increase in high density lipoprotein cholesterol (HDL-C) levels. DOI: http://dx.doi.org/10.3126/acclm.v1i1.12312 Ann. Clin. Chem. & Lab. Med. 1(1) 2015: 29-32

Long-term use of methamphetamine could induce psychosis, but consequences with regards to intelligence have seldom been investigated. Long-term use of alcohol could also result in intellectual deterioration. The IQ of 34 methamphetamine-induced psychosis (MIP) patients (age, 28.7 +/- 6.1 years) and 34 alcohol-dependent (AD) patients (age, 40.7 +/- 7.3 years) was compared using the Chinese version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III). The average full-scale IQ, verbal IQ, performance IQ, verbal comprehension index, working memory index, perceptual organization index, and processing speed index was 82.3 +/- 10.8, 84.3 +/- 11.9, 81.9 +/- 12.1, 85.5 +/- 11.9, 84.7 +/- 12.5, 85.4 +/- 13.6, and 78.5 +/- 12.7 in MIP patients and 90.5 +/- 12.0, 95.2 +/- 11.3, 86.0 +/- 13.7, 95.5 +/- 11.0, 87.1 +/- 14.5, 96.2 +/- 13.1, and 84.5 +/- 15.0 in AD patients, respectively. There were six MIP patients (17.6%) whose full-scale IQ was <70 and 13 (38.2%) whose full-scale IQ was <85 and >70, while one AD patient had a full-scale IQ <70 (2.9%) and 10 (22%) had full-scale IQ <85 and >70. Long-term use of methamphetamine can result not only in psychosis, but also in mentality deterioration. Intelligence deterioration is more severe in clinical MIP patients than AD patients. Assessment of the mentality of MIP patients is suggested to help with the implementation of rehabilitative programs for these patients.

Changes in brain morphometry have been extensively reported in various studies examining the effects of chronic alcohol use in alcohol-dependent patients. Such studies were able to confirm the association between chronic alcohol use and volumetric reductions in subcortical structures using FSL (FMRIB software library). However, each study that utilized FSL had different sets of subcortical structures that showed significant volumetric reduction. First, we aimed to investigate the reproducibility of using FSL to assess volumetric differences of subcortical structures between alcohol-dependent patients and control subjects. Second, we aimed to use Vertex analysis, a less utilized program, to visually inspect 3D meshes of subcortical structures and observe significant shape abnormalities that occurred in each subcortical structure. Vertex analysis results from the hippocampus and thalamus were overlaid on top of their respective subregional atlases to further pinpoint the subregional locations where shape abnormalities occurred. We analyzed the volumes of 14 subcortical structures (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens) in 21 alcohol-dependent subjects and 21 healthy controls using images acquired with 3T MRI. The images were run through various programs found in FSL, such as SIENAX, FIRST, and Vertex analysis. We found that in alcohol-dependent patients, the bilateral thalamus (left: p < 0.01, right: p = 0.01), bilateral putamen (left: p = 0.02, right: p < 0.01), right globus pallidus (p < 0.01), bilateral hippocampus (left: p = 0.05, right: p = 0.03) and bilateral nucleus accumbens (left: p = 0.05, right: p = 0.03) were significantly reduced compared to the corresponding subcortical structures of healthy controls. With vertex analysis, we observed surface reductions of the following hippocampal subfields: Presubiculum, hippocampal tail, hippocampal molecular layer, hippocampal fissure, fimbria, and CA3. We reproduced the assessment made in previous studies that reductions in subcortical volume were negatively associated with alcohol dependence by using the FMRIB Software Library. In addition, we identified the subfields of the thalamus and hippocampus that showed volumetric reduction.

BackgroundAccording to the reward deficiency syndrome and allostatic hypotheses, hyposensitivity of mesocorticolimbic regions to non–alcohol-related stimuli predisposes to dependence or is long-lastingly enhanced by chronic substance use. To date, no study has directly compared mesocorticolimbic brain activity during non–drug reward anticipation between alcohol-dependent, at risk, and healthy subjects. MethodsSeventy-five abstinent alcohol-dependent human subjects (mean abstinence duration 957.66 days), 62 healthy first-degree relatives of alcohol-dependent individuals, and 76 healthy control subjects without family history of alcohol dependence performed a monetary incentive delay task. Functional magnetic resonance imaging data of the anticipation phase were analyzed, during which visual cues predicted that fast response to a target would result in monetary gain, avoidance of monetary loss, or a neutral outcome. ResultsDuring gain anticipation, there were no significant group differences. During loss anticipation, abstinent alcohol-dependent subjects showed lower activity in the left anterior insula compared with healthy control subjects without family history of alcohol dependence only (Montreal Neurological Institute [MNI] −25 19 –5; t206 = 4.17, familywise error corrected p = .009). However, this effect was no longer significant when age was included as a covariate. There were no group differences between abstinent alcohol-dependent subjects and healthy first-degree relatives or between healthy first-degree relatives and healthy control subjects during loss anticipation, respectively. ConclusionsNeither the neural reward deficiency syndrome nor the allostatic hypotheses are supported by the results. Future studies should investigate whether the incentive salience hypothesis allows for more accurate predictions regarding mesocorticolimbic brain activity of subjects with alcohol dependence and healthy individuals during reward and loss anticipation and further examine the neural substrates underlying a predisposition to dependence.

Aim:To assess personality disorder (PD), emotional intelligence (EI), and locus of control of alcohol dependent (AD) patients and its comparison with normal controls.Materials and Methods:Based on purposive sampling technique, 33 AD patients were selected from the De-Addiction Ward of Ranchi Institute of Neuro-Psychiatry and Allied Sciences (RINPAS) and 33 matched normal subjects were selected from Ranchi and nearby places. Both the groups were matched on various sociodemographic parameters, that is, age, gender, and socioeconomic level. All participants were assessed with Millon Clinical Multiaxial Inventory-III, Mangal EI Inventory, and Locus of Control scale. Obtained responses were scored by using standard scoring procedures and subsequently statistically analyzed by using Chi-square test.Results:AD patients have more comorbid pathological personality traits and disorders in comparison to their normal counterparts. Depressive, narcissistic, and paranoid PDs were prominent among AD group; followed by schizotypal, antisocial, negativistic, dependent, schizoid, sadistic, masochistic, and borderline PD. In comparison to normal participants, AD patients were significantly deficient in almost all the areas of EI and their locus of control was externally oriented.Conclusion:Patients with AD have significantly higher PDs, low EI, and an external orientation on the locus of control. Identification and management of these comorbid conditions are likely to improve the management and outcome of AD.