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Background:Vitamin B12 deficiency is a common condition causing neurologic, cognitive, psychiatric, and mood symptoms. With varied religious, ethnic, and socioeconomic heterogeneity among the people in India greatly influencing their dietary habits and with the high prevalence of Helicobacter pylori infection, Vitamin B12 deficiency is not uncommon, but is often under recognized due to the lack of classical symptomatic presentation.Materials and Methods:Retrospective study on Vitamin B12 deficiency with neuropsychiatric symptoms in patients who attended neurology, psychiatry, and geriatric OPDs for a period of 1 year in a specialized neuropsychiatric institute in South India.Results:Out of 259 patients who had Vitamin B12 deficiency (<220 pmol/L), 60 had neuropsychiatric symptoms. Among them the Vitamin B12 levels were <150 (severe), 150-200 (moderate), and 201-220 pmol/L (mild) in 19, 24, 17 patients, respectively. Twenty one were diagnosed with Posterior dementias, 20 with frontotemporal dementia, 7 with Schizophrenia, 4 each with Parkinson's disease and alcohol-dependent syndromes (ADS), 3 with bipolar affective disorder, and 1 with Creutzfeldt-Jakob disease. Eight patients also had hypothyroidism. First symptom of presentation was behavioral disturbances in 30 (50%), memory loss in 20 (33.9%), and sensorimotor and movement disorders in 9 (15.3%), and 56.7% were vegetarians while 43.3% were nonvegetarians. In our study, Vitamin B12 deficiency was more prevalent in elderly males (56.67%) and was associated with increased severity of behavioral disturbances (P = 0.043) which was the most common presentation. Memory loss was present in 16 (84.2%) patients of severe Vitamin B12 deficiency. Hindi mental status examination (HMSE) score was graded as <20, 20-24, 24-31 in 37 (61.7%), 10 (16.7%), and 13 (21.7%) patients, respectively. Cognitive decline in Vitamin B12 deficiency was significantly associated with increased serum cholesterol (P = 0.019) and was significantly prevalent in neurological disorders when compared with primary psychiatric illnesses (P = 0.001). Mean folate and mean homocysteine in our study was 11.7 ± 6.44 ng/ml and 17.77 ± 5.45 μmol/L, respectively. Eighty percent of the population had normal folate levels whereas mean homocysteine values were much higher than that of the western population (10-12 μmol/L).Conclusion:Vitamin B12 deficiency though common in India is often overlooked. It increases the load of cognitive decline and accentuates vascular risk factors in neuropsychiatric illnesses. Vitamin B12 deficiency also increases homocysteine levels contributing to the vascular comorbidity in cerebro and cardiovascular illnesses. So prevention, early detection, and management of this reversible Vitamin B12 deficiency state is of profound importance.

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Idiopathic Parkinson's disease and manganese-induced atypical parkinsonism are characterized by movement disorder and nigrostriatal pathology. Although clinical features, brain region involved and responsiveness to levodopa distinguish both, differences at the neuronal level are largely unknown. We studied the morphological, neurophysiological and molecular differences in dopaminergic neurons exposed to the Parkinson's disease toxin 1-methyl-4-phenylpyridinium ion (MPP ) and manganese (Mn), followed by validation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and Mn mouse models. Morphological analysis highlighted loss of neuronal processes in the MPP and not the Mn model. Cellular network dynamics of dopaminergic neurons characterized by spike frequency and inter-spike intervals indicated major neuronal population (~ 93%) with slow discharge rates (0-5 Hz). While MPP exposure suppressed the firing of these neurons, Mn neither suppressed nor elevated the neuronal activity. High-throughput transcriptomic analysis revealed up-regulation of 694 and 603 genes and down-regulation of 428 and 255 genes in the MPP and Mn models respectively. Many differentially expressed genes were unique to either models and contributed to neuroinflammation, metabolic/mitochondrial function, apoptosis and nuclear function, synaptic plasticity, neurotransmission and cytoskeleton. Analysis of the Janus kinase-signal transducer and activator of transcription pathway with implications for neuritogenesis and neuronal proliferation revealed contrasting profile in both models. Genome-wide DNA methylomics revealed differences between both models and substantiated the epigenetic basis of the difference in the Janus kinase-signal transducer and activator of transcription pathway. We conclude that idiopathic Parkinson's disease and atypical parkinsonism have divergent neurotoxicological manifestation at the dopaminergic neuronal level with implications for pathobiology and evolution of novel therapeutics. Cover Image for this issue: doi. 10.1111/jnc.13821.

Treatment strategies for alcohol use disorder (AUD) aim for abstinence or harm reduction. While deranged biochemical parameters reverse with alcohol abstinence, whether molecular changes at the epigenetic level reverse is not clearly understood.We investigated whether the reduction from high alcohol use reflects DNA methylation at the gene-specific and global level. In subjects seeking treatment for severe AUD, we assessed gene-specific (aldehyde dehydrogenase [ALDH2]/methylene tetrahydrofolate reductase [MTHFR]) and global (long interspersed elements [LINE-1]) methylation across three-time points (baseline, after detoxification and at an early remission period of 3 months), in peripheral blood leukocytes. We observed that both gene-specific and global DNA methylation did not change over time, irrespective of the drinking status at 3 months (52% abstained from alcohol). Further, we also compared DNA methylation in AUD subjects with healthy controls. At baseline, there was a significantly higher gene-specific DNA methylation (ALDH2: p < .001 and MTHFR: p = .001) and a significant lower global methylation (LINE-1: p = .014) in AUD as compared to controls. Our results suggest that epigenetic changes at the DNA methylation level associated with severe AUD persist for at least 3 months of treatment. K E Y W O R D Salcohol abstinence, alcohol use disorder, DNA methylation, long interspersed nucleotide elements, pyrosequencing | INTRODUCTIONAlcohol use accounts for 13.5% of total deaths among young adults worldwide (WHO, 2018). About 29% of men aged 15-54 years consume alcohol in India, with significant numbers using it daily (12%) or weekly (41%) (NFHS-4, 2015(NFHS-4, -2016. alcohol use disorder (AUD) is a chronic relapsing disorder, with only 15-16% of former users in India abstaining from alcohol over the past year (WHO, 2018). With the focus on abstinence and harm reduction approaches in treating AUD, whether molecular adaptations associated with chronic alcohol use reverse with alcohol abstinence poses an intriguing question.Among the molecular adaptations associated with chronic alcohol use, epigenetic changes are significant because of the associated downstream effects on gene expression (Ponomarev, Wang, Zhang, Harris, & Mayfield, 2012). These epigenetic changes are associated with onset, progression to, and persistence of dependence states (Cecil, Walton, & Viding, 2016;Jangra et al., 2016). It is well established that epigenome-wide, global, and gene-specific studies indicate differential methylation related to alcohol consumption

Background:Studying personality profiles allows researchers to generate important hypotheses in risk factors and correlates of alcohol use/misuse. Studies examining the association between personality traits and treatment outcome are limited in India. We studied the correlation between personality and treatment outcome in patients with alcohol dependence.Methods:Adult participants with alcohol dependence were recruited from the inpatient and outpatient wards of de-addiction unit of a tertiary care facility in India using a prospective design and followed up after 3 months. Questionnaires administered were revised NEO personality inventory (NEO-PI-R), alcohol use disorders identification test, and advanced warning of alcohol relapse (AWARE).Results:Out of 99 recruited participants (92% males) with mean age of 37 (±8.36) years, 82 (82.8%) patients were followed up to 3 months. E4 (activity) facet of the extraversion domain in the NEO-PI-R significantly correlated with the baseline drinking scores (r = 0.204, P = 0.042, n = 99) and AWARE scores (r = 0.276, P = 0.043, n = 54). There was a significant negative correlation between the E2 (gregariousness) facet and satisfaction with life scores (r = −0.211, P = 0.036, n = 99). Age at first drink was significantly lower among relapsers (P = 0.021).Conclusion:Our study suggests that factors related to extraversion, specifically, high activity might be associated with higher drinking as well as higher risk of alcohol relapse. Predicting alcohol relapse by studying the personality traits would help clinicians in improving treatment outcomes.

The rapid advancement in information and communication technology has made e‐learning an alternative learning method for many learners. In the last few years, a huge number of learners around the world have registered in massive open online courses (MOOCs) provided by various online learning platforms. However, MOOC platforms have a vital task for the online course provider to provide enhanced students' learning experiences and satisfaction. In this work, we developed a brain–computer interface for gathering data and detecting a learner's mental situation by observing MOOC videos and electroencephalogram (EEG) devices based on John Sweller's Cognitive Load Theory. The acquired EEG signals are preprocessed with two different normalization methods to scale signals. To validate the introduced framework, the system adopted three machine learning algorithms (random forest using non‐Markovian model, support vector machine, and k‐nearest neighbors) to develop a model with preprocessed training data and test the classifiers to validate their ensemble classifiers' performance. Finally, experimental analysis showed that the random forest classifier with the non‐Markovian approach achieved more than the other two techniques in the form of overall accuracy (99.15%) and F‐measures (99.21%).

Sleep disturbances are common among individuals with alcohol use disorder (AUD) and may not resolve completely with short-term abstinence from alcohol, potentially contributing to relapse to drinking. The endocannabinoid system (ECS) is associated with both sleep and alcohol consumption, and genetic variation in the ECS may underlie sleep-related phenotypes among individuals with AUD. In this study, we explored the influence of genetic variants in the ECS (Cannabinoid receptor 1/CNR1: rs806368, rs1049353, rs6454674, rs2180619, and Fatty Acid Amide Hydrolase/FAAH rs324420) on sleep quality in individuals with AUD (N = 497) and controls without AUD (N = 389). We assessed subjective sleep quality (from the Pittsburgh Sleep Quality Index/PSQI) for both groups at baseline and objective sleep efficiency and duration (using actigraphy) in a subset of individuals with AUD at baseline and after 4 weeks of inpatient treatment. We observed a dose-dependent relationship between alcohol consumption and sleep quality in both AUD and control groups. Sleep disturbance, a subscale measure in PSQI, differed significantly among CNR1 rs6454674 genotypes in both AUD (p = 0.015) and controls (p = 0.016). Only among controls, neuroticism personality scores mediated the relationship between genotype and sleep disturbance. Objective sleep measures (sleep efficiency, wake bouts and wake after sleep onset), differed significantly by CNR1 rs806368 genotype, both at baseline (p = 0.023, 0.029, 0.015, respectively) and at follow-up (p = 0.004, p = 0.006, p = 0.007, respectively), and by FAAH genotype for actigraphy recorded sleep duration at follow-up (p = 0.018). These relationships suggest a significant role of the ECS in alcohol-related sleep phenotypes.