Posterior Cerebellar Resting-State Functional Hypoconnectivity: A Neural Marker of Schizophrenia Across Different Stages of Treatment Response.

BACKGROUND: Identifying stable and consistent resting-state functional connectivity patterns across illness trajectories has the potential to be considered fundamental to the pathophysiology of schizophrenia. We aimed to identify consistent resting-state functional connectivity patterns across heterogeneous schizophrenia groups defined based on treatment response. METHODS: In phase 1, we used a cross-sectional case-control design to characterize and compare stable independent component networks from resting-state functional magnetic resonance imaging scans of antipsychotic-naïve participants with first-episode schizophrenia (n = 54) and healthy participants (n = 43); we also examined associations with symptoms, cognition, and disability. In phase 2, we examined the stability (and replicability) of our phase 1 results in 4 groups (N = 105) representing a cross-sequential gradation of schizophrenia based on treatment response: risperidone responders, clozapine responders, clozapine nonresponders, and clozapine nonresponders following electroconvulsive therapy. Hypothesis-free whole-brain within- and between-network connectivity were examined. RESULTS: Phase 1 identified posterior and anterior cerebellar hypoconnectivity and limbic hyperconnectivity in schizophrenia at a familywise error rate-corrected cluster significance threshold of p < .01. These network aberrations had unique associations with positive symptoms, cognition, and disability. During phase 2, we replicated the phase 1 results while comparing each of the 4 schizophrenia groups to the healthy participants. The participants in 2 longitudinal subdatasets did not demonstrate a significant change in these network aberrations following risperidone or electroconvulsive therapy. Posterior cerebellar hypoconnectivity (with thalamus and cingulate) emerged as the most consistent finding; it was replicated across different stages of treatment response (Cohen's d range -0.95 to -1.44), reproduced using different preprocessing techniques, and not confounded by educational attainment. CONCLUSIONS: Posterior cerebellar-thalamo-cingulate hypoconnectivity is a consistent and stable state-independent neural marker of schizophrenia.

Standards for medical devices: Electroconvulsive therapy machine.

The manuscript calls for establishing a standard for electroconvulsive devices by manufacturers for better regulation in India. This is most relevant in the context of two recent developments, (a) Notification of medical devices rules, 2017 with classification of ECT as Class C and (b) Recent change in classification of ECT devices by US-FDA in 2018. The establishment of standards would help in upregulating the standard of ECT devices as well as ECT practices.

Can yoga practise prevent electro-convulsive therapy induced neurocognitive deficits? - Findings from a pilot randomised controlled trial.

Despite decades of experience with ECT, no single agent has emerged as a suitable strategy to mitigate the associated neuro-cognitive deficits. In this first of its kind pilot randomised controlled trial, we sought to demonstrate the effect of yoga on neurocognitive deficits. We found a favourable effect of Yoga in the domain of verbal fluency, however our study did not reveal significant differences in other cognitive domains. Future studies could look to build on this study while addressing the limitations cited.

Current telepsychiatry practice in India - An online survey of psychiatrists.

Context: Telemedicine Practice Guidelines and Telepsychiatry Operational Guidelines released in 2020 have provided legal backing for telepsychiatry practice. Aims: To understand the current telepsychiatry practices in India. Settings and Design: An online survey was conducted after ethics approval by the IPS Ethics Review Board. All psychiatrists, who are members of the Indian Psychiatric Society and whose email address was available with the society, were sent the survey link by email. Methods and Material: Information about existing telepsychiatry consultation practices in India was collected between June and July 2020. Statistical Analysis Used: Frequency, percentages, mean, and standard deviation were calculated. Results: 340 responses were analyzed. Nearly three-fourths of the responders used smartphones (n = 260, 76.47%) for audio consultations (n = 196, 57.65%). Among those who were using a dedicated software (n = 36), one-third used the Zoom software (n = 12, 33.33%). Nearly three-fourths (n = 218, 73.4%) provided prescriptions with their registration number on a letterhead in the form of an email or text message. Two-thirds of the responders (n = 228, 67.06%) felt that in-person consultation is better. Many preferred a combination of voice, video, and text including emails (n = 134, 42.01%). Conclusions: This online survey showed that the use of technology has caught up with the practicing psychiatrists. Many are practicing telepsychiatry either formally or informally in India and are comfortable and satisfied with the telepractice.

The prescriptions of psychotropic medications in telepsychiatry: An online survey of psychiatrists in India.

Context: Over the years, telepsychiatry services have expanded in many institutes. The Telemedicine Practice Guidelines and Telepsychiatry Operational Guidelines (TPOG) released in 2020 have been received by the fraternity with a mixture of apprehension, relief, and dissatisfaction on the list of drugs provided in Lists O, A, B, and C. Many psychiatrists have raised the issues of having a consensus in the formulation of List A. Aims: To draw consensus on the medications that can be listed in Lists O, A, B, and C in TPOG-2020. Settings and Design: This was an online survey with ethics approval by the Indian Psychiatric Society Ethics Review Board. All psychiatrists, who are members of the Indian Psychiatric Society and whose E-mail address was available with the society, were sent the survey link by E-mail. Methodology: Opinions and suggestions on Lists O, A, B, and C of TPOG-2020 and reasons for the suggestions were collected. Statistical Analysis Used: Frequency, percentages, mean, and standard deviation were calculated. T-test and Chi-square tests were used to see the influence of demographics on the concurrence of the lists. Results: Responses from 340 responders were analyzed. Majority of the responders agreed that List O (277, 85.5%), List B (263, 82.4%), and List C (223, 69%) are apt except for List A (162, 50.3%). Conclusions: This online survey showed that majority of the responders agreed to the lists except for List A. The approach taken to include the medications in List A, which was to include the essential drugs, has various benefits. However, the lists are not final, and the results of this survey may become an impetus to modify the list in the next edition of TPOG.

Perceived advantages and disadvantages of telepsychiatry - An online survey of psychiatrists in India.

Context: Telepsychiatry is being practiced in India for many years but was formalized only in 2020. It has many advantages and disadvantages. Aims: This study aimed to understand the perceived advantages and disadvantages of telepsychiatry practices in India. Settings and Design: An online survey with ethics approval by the Indian Psychiatric Society (IPS) Ethics Review Board. All psychiatrists who are members of the IPS and whose email address was available with the society were sent the survey link by email. Methodology: Information about existing telepsychiatry consultation practices in India and perception of advantages and disadvantages by the practitioners were collected between June and July 2020. Statistical Analysis: Frequency, percentages, mean, and standard deviation were calculated. Results: Responses by 340 responders were analyzed. Majority of the responders felt that telepsychiatry would provide easy accessibility to mental health services (n = 283, 83.24%) and would lead to less exposure to infections (n = 222, 65.29%). Half of the responders (n = 177, 52.06%) felt that there would be an increased doctor shopping resulting in poor care and nearly three-fourth (n = 245, 72.06%) felt that mental health professionals would fall into a problem while dealing with a suicidal or a homicidal patient. Some expressed that the inability to do physical and central nervous system examinations could lead to missing out comorbidities. About one-third (n = 117, 36.56%) felt that the patient recording the consultation would be a legal issue. Conclusions: This online survey showed that psychiatrists perceive many advantages and some disadvantages in practicing telepsychiatry.

Development, validation, and feasibility of a generic yoga-based intervention for Generalized Anxiety Disorder.

CONTEXT: Evidence suggests that yoga effectively manages anxiety, but techniques are derived from different yoga schools. This paper describes the development, validation, and feasibility of a generic yoga-based intervention in patients with Generalized Anxiety Disorder (GAD). METHODS: The first part of the study consisted of designing a generic yoga module from the traditional and contemporary yogic literature and inputs from ten experienced yoga practitioners. The content was validated using a case-vignette method from 28 yoga experts. These yoga experts rated the usefulness of the practices on a scale of 1-5 (5-extremely useful). The second part consisted of testing the feasibility of this validated generic yoga intervention in an open-label clinical trial in patients with GAD. Two weeks of ten supervised yoga sessions (SYS) were offered by a trained yoga therapist to the recruited participants and subsequently advised for home practice. A weekly booster SYS was also provided for three months after 10SYS. RESULTS: Yoga experts (n = 28) opined that the yoga intervention would be helpful in patients with GAD with minimal modifications. All experts opined that the module was easy to teach, learn and practice. The final yoga module retained 97.7% (42 out of 43) items of the initial module. In the feasibility study, (n = 20) patients were recruited, and fifteen followed-up after one month. All patients were able to learn and practice the final yoga module within ten sessions without any significant adverse effects. The severity of anxiety reduced substantially after the ten days of SYS and this improvement was sustained for the next 4 weeks. CONCLUSION: The designed generic yoga intervention was validated by yoga experts and found safe and feasible in patients with GAD. Patients obtained significant symptom reductions which need to be confirmed in randomized controlled trials.

A transdiagnostic evaluation of cortical inhibition in severe mental disorders using Transcranial Magnetic Stimulation.

Multiple lines of investigations suggest the presence of cortical inhibition aberrations as central to the phenotypic manifestations of severe mental disorders. Transcranial Magnetic Stimulation (TMS) combined with electromyography can characterize these inhibitory processes in the motor cortex with satisfactory temporal precision. We examined TMS-evoked short- (SICI) and long-interval intracortical inhibition (LICI) and cortical silent period (CSP) as markers of GABAA- (SICI) and GABAB-mediated (LICI and CSP) cortical neurotransmission in symptomatic individuals with mania (n = 40), schizophrenia (n = 76), unipolar depression (n = 86), and OCD (n = 43), and compared them against similar recordings in healthy subjects (n = 125). We hypothesized transdiagnostic GABAA deficits across all the clinical groups and diagnosis-specific GABAB alterations in mania (increased) and OCD (decreased). After controlling for potential confounder variables (gender, education, benzodiazepine prescription, and motor threshold) using the ANCOVA, we observed no significant group difference in SICI (F = 1.04, P = 0.38), but a significant group effect in LICI (F = 16.29, P < 0.001) and CSP (F = 3.02, P = 0.018). Post-hoc analyses revealed that LICI was significantly reduced in OCD but increased in mania and schizophrenia with reference to the healthy group. Similarly, CSP was significantly reduced in OCD and depression groups as compared to the reference group. We observed that LICI and CSP, both followed similar descending gradients from mania through schizophrenia and depression to OCD; with significant elevation in mania, and reduction in depression and OCD, as compared to the healthy group. This pattern of GABAB-mediated cortical inhibition aberrations needs independent validation as potential state-markers of distinct clinical categories.

Resting-state functional connectivity predictors of treatment response in schizophrenia - A systematic review and meta-analysis.

We aimed to systematically synthesize and quantify the utility of pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI) in predicting antipsychotic response in schizophrenia. We searched the PubMed/MEDLINE database for studies that examined the magnitude of association between baseline rs-fMRI assessment and subsequent response to antipsychotic treatment in persons with schizophrenia. We also performed meta-analyses for quantifying the magnitude and accuracy of predicting response defined continuously and categorically. Data from 22 datasets examining 1280 individuals identified striatal and default mode network functional segregation and integration metrics as consistent determinants of treatment response. The pooled correlation coefficient for predicting improvement in total symptoms measured continuously was ~0.47 (12 datasets; 95% CI: 0.35 to 0.59). The pooled odds ratio of predicting categorically defined treatment response was 12.66 (nine datasets; 95% CI: 7.91-20.29), with 81% sensitivity and 76% specificity. rs-fMRI holds promise as a predictive biomarker of antipsychotic treatment response in schizophrenia. Future efforts need to focus on refining feature characterization to improve prediction accuracy, validate prediction models, and evaluate their implementation in clinical practice.

Parental consanguinity among patients with schizophrenia in a rural community of South India: A clinical and genetic investigation.

BACKGROUND: Studies from certain regions of the world indicate that consanguineous marriages are a risk factor for the development of schizophrenia in offspring. However the evidence is inconsistent partly due to methodological limitation of which hospital based recruitment contributing to significant bias. The studies from the Indian subcontinent, is scarce, where rates of consanguinity is high. METHODS: The schizophrenia patients living in a geographically defined rural south Indian community and randomly selected controls dwelling in the same community sharing sociocultural, economic and lifestyle factors were recruited. They were assessed for parental consanguinity using the clinical interviews as well as DNA-based estimates. The latter was conducted by calculating the coefficient of inbreeding 'f'. A participant was considered to have consanguineous parentage if his/her parents shared a common ancestor no more remote than a great-great-grandparent, corresponding to DNA-based estimates of 'f' ≥ 0.0156. RESULTS: The rates of parental consanguinity assessed by clinical interview were comparable in both groups (Cases: 10.71 %, Controls: 7.25 %; χ2 = 0.493, p = 0.4825). However, DNA-based rates of parental consanguinity showed that 'f' was significantly higher among cases than controls (Mann-Whitney U = 11315.5; p = 0.022). Seventy-five cases (62.5 %) and 108 control participants (48.6 %) had 'f' ≥ 0.0156 (χ2 = 6.008; p = 0.014). The results were consistent across different quality control measures. CONCLUSION: Schizophrenia is associated with higher parental consanguinity, suggesting a role for multiple recessive risk alleles in its etiology. Replication in future studies in diverse settings would add further strength to this.

Development, Validation, and Feasibility Testing of a Yoga Module for Opioid Use Disorder.

CONTEXT: Opioid use disorder (OUD) involves excessive use of opioids-such as heroin, morphine, fentanyl, codeine, oxycodone, and hydrocodone-leading to major health, social, and economic consequences. Yoga lifestyle interventions have been found to be useful as adjunct therapies in management of substance use disorders and chronic pain conditions. OBJECTIVE: The research team intended to develop, validate, and test for feasibility a yoga program for OUD patients that could reduce opiate withdrawal symptoms-such as pain, fatigue, low mood, anxiety and sleep disturbances-and cravings associated with drugs. DESIGN: The research team first performed a literature review of traditional and contemporary yoga texts, such as Hatha Yoga Pradipika and Light on Yoga, as well as modern scientific literature in the following search engines-Google Scholar, PubMed, and PsychInfo, using the keywords yoga, pranayama, hatha yoga, relaxation. meditation, substance use, addiction, impulsivity, craving, sleep quality, and fatigue. Using the information obtained, the team developed a yoga program and designed a pilot study that used the program. SETTING: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bangalore, India. PARTICIPANTS: Participants in the pilot study were 8 inpatients, 6 males and 2 females, who were on opioid agonist treatment (buprenorphine) for OUD. INTERVENTION: The intervention was the yoga program previously validated by the research team. In the pilot study, participants were taught a one-hour, yoga-based intervention, with sessions occurring once per day, for 10 sessions. OUTCOME MEASURES: For validation, 13 experts scored the yoga program that the research team had developed and gave suggestions for each yogic practice for use during the acute phase of withdrawal and the maintenance phase respectively. A content validity ratio (CVR) was calculated from their scoring, and the research team made changes to the program base on the scoring and suggestions. For the pilot study, assessments occurred at baseline and postintervention. The participants' yoga performance was rated by the yoga trainer on a yoga performance assessment scale (YPA). Other measurements included: (1) the Clinical Opiate Withdrawal Scale (COWS), (2) the Hamilton's anxiety rating scale (HAM-A), (3) the Hamilton's depression rating scale (HAM-D), (4) buprenorphine dosage, (5) the Clinical Global Impression Severity (CGI-S) scale, (6) a visual analog scale (VAS) for pain, (7) sleep quality (latency and duration), and (8) the module's safety. RESULTS: Four practices were removed from the program due to CVR scores below the cutoff, and one practice was found not to be feasible (Kapalabhati). Two categories of yoga modules emerged: (1) for the acute symptomatic phase (40 minutes) and (2) for the maintenance phase (one hour). Practices were added or excluded based on the phase. CONCLUSIONS: The yoga module that was developed for reducing withdrawal symptoms and cravings in OUD patients was found to be safe, feasible, and potentially useful as an adjunct therapy to conventional treatment.

Add on yoga treatment for negative symptoms of schizophrenia: A multi-centric, randomized controlled trial.

The efficacy of antipsychotic medications in the treatment of negative symptoms of schizophrenia is modest at best. Preliminary studies suggest the beneficial effects of add on Yoga, a traditional Indian practice, in the treatment of schizophrenia. Hence, in this study, we examined the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia in a randomized, wait-list controlled design from two clinical institutes in south India. 89 patients (age - 34.20 ± 8.06 years; education - 14.22 ± 2.69 years; 28 females) were randomized into the add-on yoga or treatment as usual (TAU - wait-list control) group. Patients had a mean illness duration of 10.97 ± 7.24 years with an age at onset of 23.34 ± 5.81 years. Central block randomization was followed to ensure concealed allocation. Participants randomized to the yoga treatment group attended 12 supervised yoga training sessions over two weeks and practiced yoga sessions at home for the subsequent 10 weeks. 64 patients completed the trial. An intent to treat analysis was conducted with 89 participants using a linear mixed model. Improvement in negative symptoms was our primary outcome measure. The two groups were matched on demographic variables and baseline psychopathology severity. Participants in the add-on yoga group had significantly greater improvement in negative symptoms (SANS baseline: 49.13 ± 2.30; 12-weeks follow up: 31.55 ± 2.53) compared to the TAU group (SANS baseline: 51.22 ± 2.40; 12-weeks follow up: 45.30 ± 2.93; t = 3.36; p = 0.006; Cohen's d-0.65). The current study findings suggest the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia. The effectiveness of yoga practice as a regular clinical intervention for patients needs to be explored in future studies by integrating yoga services along with other clinical services.

Prefrontal cortex activation during working memory task in schizophrenia: A fNIRS study.

Neurocognitive cognitive deficits including working memory (WM) impairment is a key component of schizophrenia (SCZ). Though a prefrontal cortex (PFC) abnormality is recognised to contribute to WM impairment, the exact nature of its neurobiological basis in SCZ is not well established. Functional near infra-red spectroscopy (fNIRS) is an emerging low-cost neuroimaging tool to study neuro-hemodynamics. In this background, we examined the hemodynamic activity during a WM task in schizophrenia using fNIRS. fNIRS was acquired during computerised N-back (zero-, one- & two-back) task in 15 SCZ patients and compared with 22 healthy controls. Performance in N-back test were calculated using signal detection theory alongside the mean reaction times. Concentration and latencies of oxy-, deoxy-, and totalhaemoglobin, and oxygen saturation were computed from 8*8 optodes positioned over bilateral PFC. SCZ performed poorly as measured by most of the WM parameters (p < 0.05). Lesser deoxyhemoglobin concentration (two > zero, at right BA10, p = 0.006) was noted in the right frontopolar cortex in SCZ surviving multiple-comparison correction. In addition, olanzapine equivalent doses correlated negatively with right frontopolar cortex activation (two > zero back, BA10, ρ = 0.70, p = 0.004) and better performance in two back (false alarm rate, ρ = 0.61, p = 0.015). A delayed but compensatory hyperactivation of right frontopolar cortex noted in SCZ may underlie the WM deficit in SCZ. Future studies are recommended to replicate the role of right frontopolar cortex in WM using larger samples and systematically explore the effect of antipsychotics on them.