Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Work productivity (absenteeism and presenteeism) in persons with common mental disorders: An observational study from South India.

Background: The greatest contributor to the economic impact of common mental disorders (CMDs) is said to be the loss of work productivity. There is a paucity of studies from India that looks at the impact of CMDs on the productivity of work, which costs both patient and society significantly. Aim: To assess and compare work productivity by evaluating both absolute and relative presenteeism and absenteeism, in persons with CMDs. Materials and Methods: This was a cross-sectional observational study on 220 subjects (110, 58, and 52 patients with depressive disorder, anxiety disorders, and somatoform disorders, respectively), recruited through purposive sampling. We evaluated work productivity using the World Health Organization Health and Work Performance Questionnaire. Results: Absolute absenteeism was significantly different before and after treatment for CMDs as a group but not for individual disorders. Relative absenteeism, absolute presenteeism, and relative presenteeism were all significantly different before and after treatment among both CMDs as a group and also among individual disorders. Both presenteeism and absenteeism (absolute as well as relative) did not differ significantly across the diagnostic groups. Work productivity has been linearly associated with illness severity and disability. Conclusion: CMDs are associated with a significant loss of work productivity. Presenteeism is costlier than absenteeism in affecting work productivity. Loss of work productivity appears to be transdiagnostic across all CMDs. Also, the severity of loss of work productivity is associated linearly with the severity of illness and disability.

A close critical look of India's National Mental Health Survey 2016.

The National Mental Health Survey 2016 (NMHS 2016) was a large epidemiological study, one of its kind, conducted by the National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru to overcome the shortcomings of the previous surveys. The detailed report of the study is available in two parts- 'mental health systems' and 'prevalence, pattern and outcomes'. Though done comprehensively, there are some inevitable limitations. The private sector, a substantial health care provider in the country was not a participant in the survey. Though MINI version 6.0 is a standard and structured instrument, it does not cover many commonly encountered mental illnesses like somatoform disorders. Further, the methodology of the survey makes it difficult for an accurate calculation of the prevalence of individual major psychiatric disorders. The survey has been appraised using a standard checklist for prevalence studies. The detailed qualitative data has not been shared in the report. The contribution of the traditional indigenous systems of healthcare and accessibility of services in rural areas have not been elaborated. Thus, the need for a comprehensive and culturally sensitive assessment tool, involvement of the private sector, and enhancing funding provision to improve the infrastructure are emphasized as future directions for the subsequent phases of the survey.

Clinical efficacy and neurobiological correlates of electroconvulsive therapy in patients with clozapine-resistant/intolerant schizophrenia: study protocol of multi-site parallel arm double-blind randomized sham-controlled study.

Background: A substantial proportion of patients with treatment resistant schizophrenia do not respond well or partially to clozapine, with a subset that does not tolerate an adequate trial of clozapine. Electroconvulsive therapy (ECT) is regarded as one of the augmenting options, but there is a lack of high-quality evidence for this practice. This protocol describes a double-blind randomised sham-controlled modified-ECT trial to evaluate its efficacy in patients with clozapine resistant/intolerant schizophrenia. The study also involves multimodal investigations to identify the response predictors and the mechanistic basis of modified ECT in this population. Methods: One hundred consenting schizophrenia patients with resistance/intolerance to clozapine referred by clinicians for ECT would be randomly assigned to receive true ECT or sham ECT at three study centers. Sham ECT would mimic all the procedures of modified ECT including anaesthesia and muscle relaxation, except the electrical stimulation. After a blinded course, non-responders to sham ECT would be offered open-label true ECT. Clinical assessments, neurocognitive assessments and multimodal investigations (magnetic resonance imaging [MRI], electroencephalography, heart rate variability, investigative transcranial magnetic stimulation-transcranial direct current stimulation, gene polymorphism) would be conducted at baseline and repeated after the end of the trial, as well as open-label ECT course. The trial would evaluate the improvement in positive symptoms (scale for assessment of positive symptoms) of schizophrenia as the primary outcome measure with prediction of this change by resting-state functional-MRI based brain-connectivity as the second primary objective. Registration: Clinical Trial Registry of India (Reg no: CTRI/2021/05/033775) on 24 th May 2021.

Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction.

The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impairment (MCI) in T2DM patients in the Indian population and to identify link between cognitive dysfunction in T2DM patients and serum lipid composition through untargeted and targeted lipidomic studies. Using a cross-sectional study, we evaluated 1278 T2DM patients with Montreal cognitive assessment test (MoCA) and digit symbol substitution test (DSST) for cognitive functions. As per MoCA, the prevalences of MCI in T2DM patients in age groups below 40, 41-50, 51-60, 61-70, 71-80 and 81-90 years were 13.7, 20.5, 33.5, 43.7, 57.1 and 75% with DSST scores of 45.8, 41.7, 34.4, 30.5, 24.2 and 18.8% respectively. Binomial logistic regression analysis revealed serum HbA1c ≥ 7.51, duration of T2DM over 20 years, age above 41 years, and females were independent contributors for cognitive dysfunction in T2DM patients. Preliminary studies with untargeted lipidomics of the serum from 20 T2DM patients, including MCI and normal cognition (NC) group, identified a total of 646 lipids. Among the identified lipids, 33 lipids were significantly different between MCI and NC group, which comprised of triglycerides (TGs, 14), sphingolipids (SL, 11), and phosphatidylcholines (PC, 5). Importantly, 10 TGs and 3 PCs containing long-chain polyunsaturated fatty acids (PUFA) were lower, while 8 sphingolipids were increased in the MCI group. Since brain-derived sphingolipids are known to get enriched in the serum, we further quantified sphingolipids from the same 20 serum samples through targeted lipidomic analysis, which identified a total of 173 lipids. Quantitation revealed elevation of 3 species of ceramides, namely Cer (d18:1_24:1), Hex1Cer (d16:0_22:6), and Hex2Cer (d28:1) in the MCI group compared to the NC group of T2DM patients. Overall, this study demonstrated an age-related prevalence of MCI in T2DM patients and highlighted reduced levels of several species of PUFA containing TGs and PCs and increased levels of specific ceramides in T2DM patients exhibiting MCI. Large-scale lipidomic studies in future could help understand the cognitive dysfunction domain in T2DM patients, while studies with preclinical models are required to understand the functional significance of the identified lipids.

Guidelines for TMS/tES clinical services and research through the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has broadly disrupted biomedical treatment and research including non-invasive brain stimulation (NIBS). Moreover, the rapid onset of societal disruption and evolving regulatory restrictions may not have allowed for systematic planning of how clinical and research work may continue throughout the pandemic or be restarted as restrictions are abated. The urgency to provide and develop NIBS as an intervention for diverse neurological and mental health indications, and as a catalyst of fundamental brain research, is not dampened by the parallel efforts to address the most life-threatening aspects of COVID-19; rather in many cases the need for NIBS is heightened including the potential to mitigate mental health consequences related to COVID-19. OBJECTIVE: To facilitate the re-establishment of access to NIBS clinical services and research operations during the current COVID-19 pandemic and possible future outbreaks, we develop and discuss a framework for balancing the importance of NIBS operations with safety considerations, while addressing the needs of all stakeholders. We focus on Transcranial Magnetic Stimulation (TMS) and low intensity transcranial Electrical Stimulation (tES) - including transcranial Direct Current Stimulation (tDCS) and transcranial Alternating Current Stimulation (tACS). METHODS: The present consensus paper provides guidelines and good practices for managing and reopening NIBS clinics and laboratories through the immediate and ongoing stages of COVID-19. The document reflects the analysis of experts with domain-relevant expertise spanning NIBS technology, clinical services, and basic and clinical research - with an international perspective. We outline regulatory aspects, human resources, NIBS optimization, as well as accommodations for specific demographics. RESULTS: A model based on three phases (early COVID-19 impact, current practices, and future preparation) with an 11-step checklist (spanning removing or streamlining in-person protocols, incorporating telemedicine, and addressing COVID-19-associated adverse events) is proposed. Recommendations on implementing social distancing and sterilization of NIBS related equipment, specific considerations of COVID-19 positive populations including mental health comorbidities, as well as considerations regarding regulatory and human resource in the era of COVID-19 are outlined. We discuss COVID-19 considerations specifically for clinical (sub-)populations including pediatric, stroke, addiction, and the elderly. Numerous case-examples across the world are described. CONCLUSION: There is an evident, and in cases urgent, need to maintain NIBS operations through the COVID-19 pandemic, including anticipating future pandemic waves and addressing effects of COVID-19 on brain and mind. The proposed robust and structured strategy aims to address the current and anticipated future challenges while maintaining scientific rigor and managing risk.

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data - emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Auditory P300 event-related potential: Normative data in the Indian population.

OBJECTIVE: To generate the normative data of auditory P300 event-related potential for various age groups in the Indian population. MATERIALS AND METHODS: Auditory P300 event-related potentials, using the oddball paradigm, of healthy control participants in studies carried out at our institute were included to generate normative data in the age range of 10-50 years. The amplitude and latency of P300 for Fz, Cz, and Pz were selected for analysis. RESULTS: For P300 amplitude, overall multivariate analysis of variance (MANOVA) was significant [Pillai's Trace F (9/453) = 3.46, P < 0.001]. Follow-up ANOVA showed significant difference across age groups at Fz, Cz, and Pz. For P300 latency, there was a trend towards significance for overall MANOVA [Pillai's Trace F (9/453) = 1.68, P = 0.09]. Follow-up ANOVA showed a trend towards significant difference across age groups at Fz only. CONCLUSION: Our study generated a P300 amplitude and frequency normative database at Fz, Cz, and Pz, which will serve as a reference for future studies attempting to define P300 abnormalities in various psychiatric disorders in Indian population.

Amisulpride Augmentation in Acute Catatonia.

Benzodiazepines are the first-line treatment of catatonia, but a substantial number of patients do not respond to them. Amisulpride is one of the atypical antipsychotic that has been effective for negative symptoms of schizophrenia. We examined the effect of augmentation of oral low doses of amisulpride with lorazepam on resolution of catatonic symptoms. Fifteen patients with catatonia were treated with a combination of oral lorazepam (2-4 mg) with amisulpride (100 mg). Catatonic symptoms were rated using the Bush Francis Catatonia Rating Scale at the baseline and daily thereafter. There was complete resolution of catatonic symptoms on the third day in all patients. There was significant reduction of the total Bush Francis Catatonia Rating Scale score over time (F = 181.38, P < 0.001) with a strong effect size (partial η = 0.96). Augmentation of lorazepam with low-dose amisulpride can be a reliable strategy for management of catatonia.

Very Low Dose Amitriptyline for Clozapine-Associated Sialorrhea.

Clozapine is an antipsychotic drug recommended for resistant schizophrenia, but its widespread use is limited by adverse effects. Sialorrhea is a common and troublesome adverse effect seen with clozapine which leads to poor compliance. Several treatment strategies are advocated, no single treatment is considered superior. Amitriptyline, a tricyclic antidepressant, has been found to be useful for clozapine-associated sialorrhea at 87-100 mg per day. We report the effect of very low dose amitriptyline (10 mg per day) in a patient with clozapine-associated sialorrhea. There was rapid and complete resolution of sialorrhea after three days without any emergent adverse effect.

Olanzapine-Induced Reversible Pellagroid Skin Lesion.

Adverse cutaneous reactions are frequently reported to occur with the use of psychotropic medications, which may lead to poor drug compliance. As compared to other groups of psychotropic medication, antipsychotics, both typical and atypical, are less likely to cause adverse cutaneous reactions. The most frequent cutaneous adverse reactions associated with antipsychotics include fixed drug eruptions, exanthematous eruptions, photosensitivity reactions and altered skin pigmentation. Most of these commonly seen cutaneous adverse reactions are benign and easily treatable. Rarely, severe cutaneous adverse reactions such as erythema multiforme, Steven-Johnson syndrome are toxic epidermal necrolysis and have also been associated with antipsychotics. Olanzapine is one of the most commonly prescribed atypical antipsychotic with metabolic complications as most common adverse effects. Dermatological reactions are rarely observed with olanzapine. We report occurrence of pellagroid skin lesions over exposed areas of upper limbs with olanzapine that resolved completely after its discontinuation.

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study.

OBJECTIVE: To study the anticraving efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) of the right dorsolateral pre-frontal cortex (DLPFC) in patients with alcohol dependence. METHODS: We performed a prospective, single-blind, sham-controlled study involving 45 patients with alcohol dependence syndrome (according to ICD-10 DCR), with Clinical Institute of Withdrawal Assessment in Alcohol Withdrawal (CIWA-Ar) scores