Publications by authors named "Ganesan Venkatasubramanian"

333 Publications

Domiciliary tDCS in Geriatric Psychiatric Disorders: Opportunities and Challenges.

Indian J Psychol Med 2021 Jul 27;43(4):351-356. Epub 2021 Apr 27.

WISER Neuromodulation Programme, Dept. of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India.

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http://dx.doi.org/10.1177/02537176211003666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327869PMC
July 2021

Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders.

J Psychiatr Res 2021 Oct 20;142:54-62. Epub 2021 Jul 20.

Department of Psychiatry, National Institute for Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address:

Background: Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia).

Methods: Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).

Results: MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.

Conclusion: MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.028DOI Listing
October 2021

Plasma IL-6 levels in unmedicated, comorbidity free obsessive-compulsive disorder.

Int J Psychiatry Clin Pract 2021 Jul 26:1-4. Epub 2021 Jul 26.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India.

Background: Obsessive-compulsive disorder (OCD) is increasingly being evaluated for a neuro-immune basis. Interleukin-6 (IL-6) is the most widely studied cytokine with a potential role in altering neurotransmission. The evidence for plasma IL-6 alterations in OCD has yielded mixed results. Psychotropic medications are known to modulate inflammatory processes and cytokine levels.

Methods: In this study, we recruited unmedicated, co-morbidity-free adult OCD patients ( = 49) and sex-matched healthy controls HC ( = 47) and compared their plasma IL-6 levels and their correlation with age at onset, duration of illness, and severity.

Results: IL-6 plasma level (ng/ml) in unmedicated OCD patients (1.31 ± 0.67) was significantly greater compared to HC (1.03 ± 0.47) [ = 2.33 ( = 0.02)]. The group differences persisted even after controlling for age and sex [(1, 91) = 4.57,  = 0.035, = 0.05]. Plasma IL-6 did not correlate significantly with any clinical variables.

Conclusions: This study adds to the existing literature on immune alterations in OCD. Alterations in plasma IL-6 might have implications in the neurotransmitter alterations and stress-response in OCD. The current study results in unmedicated and comorbidity-free OCD patients give us a better understanding of the immune alterations in OCD. Future studies in such a population will probably help in reducing the heterogeneity of findings.
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http://dx.doi.org/10.1080/13651501.2021.1937657DOI Listing
July 2021

Pars Triangularis Volume Asymmetry and Schneiderian First Rank Symptoms in Antipsychotic-naïve Schizophrenia.

Clin Psychopharmacol Neurosci 2021 Aug;19(3):507-513

Department of Psychiatry, National Institute of Mental Health & NeuroSciences (NIMHANS), Bangalore, India.

Objective: Schizophrenia is a disorder of language and self, with first-rank symptoms (FRS) as one of the predominant features in a subset of patients. Abnormal language lateralization is hypothesized to underlie the neurobiology of FRS in schizophrenia. The role of Broca's area with its right-hemispheric counterpart, consisting of pars triangularis (PTr) and pars opercularis (POp) of the inferior frontal gyrus in FRS is undetermined. We compared the volumes and asymmetries of PTr & POp in anti-psychotic-naive schizophrenia patients with FRS (FRS[+]) with those without FRS (FRS[-]) and healthy-controls (HC) using three dimensional, interactive, semi-automated volumetric morphometry.

Methods: Antipsychotic naïve FRS(+) (n = 27), FRS(-) (n = 24) and HC (n = 51) were carefully assessed with structured and semi-structured clinical tools. T1-weighted images were acquired in a 3T scanner. Volumes of regions of interest were measured independently for both sides using slicer-3D software, and asymmetry indices were calculated.

Results: FRS(+) but not FRS(-) had a significant volume deficit in right PTr after controlling for the potential confounding effects of age, sex, and intracranial volume (p = 0.029). There was a significant leftward asymmetry of PTr in patients with FRS (i.e., leftward asymmetry in patients) (p = 0.026). No significant volume/asymmetry abnormalities were observed in POp.

Conclusion: Study findings suggest reduced right PTr volume with leftward asymmetry to be associated with FRS in schizophrenia. This is consistent with the loss of Yakovlevian torque in schizophrenia. Role of PTr in the neurobiology of schizophrenia as a disorder of self, speech, and social cognition needs further systematic evaluation in future research.
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http://dx.doi.org/10.9758/cpn.2021.19.3.507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316654PMC
August 2021

A proof-of-concept study of maternal immune activation mediated induction of Toll-like receptor (TLR) and inflammasome pathways leading to neuroprogressive changes and schizophrenia-like behaviours in offspring.

Eur Neuropsychopharmacol 2021 Jul 11;52:48-61. Epub 2021 Jul 11.

Department of Human Genetics, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. Electronic address:

Infection, particularly prenatal infection, leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes that drive prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviours through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-6, TNF-α and IL-17A assessed after 24 hours were observed in both the poly (I:C) and LPS-treated rats, while IL-1β was only elevated in LPS-treated rats, indicating MIA. The offspring of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviours, deficits in social behaviours and prepulse inhibition. The hippocampus of offspring rats showed increased expression of Tlr3, Tlr4, Nlrp3, Il1b, and Il18 of poly (I:C) and Tlr4, Nlrp3, Cas1, Il1b, and Il18 of LPS-treated dams. Furthermore, Tlr and inflammasome genes were associated with social deficits and impaired prepulse inhibition in offspring rats. The results suggest that MIA due to prenatal infection can trigger TLR and inflammasome pathways and enhances the risk of schizophrenia-like behaviours in the later stages of life of the offspring.
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http://dx.doi.org/10.1016/j.euroneuro.2021.06.009DOI Listing
July 2021

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

Adv Mind Body Med 2021 Summer;35(3):20-30

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.
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July 2021

Identification of biomarkers that predict response to subthalamic nucleus deep brain stimulation in resistant obsessive-compulsive disorder: protocol for an open-label follow-up study.

BMJ Open 2021 06 22;11(6):e047492. Epub 2021 Jun 22.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.

Introduction: Deep brain stimulation (DBS) of bilateral anteromedial subthalamic nucleus (amSTN) has been found to be helpful in a subset of patients with severe, chronic and treatment-refractory obsessive-compulsive disorder (OCD). Biomarkers may aid in patient selection and optimisation of this invasive treatment. In this trial, we intend to evaluate neurocognitive function related to STN and related biosignatures as potential biomarkers for STN DBS in OCD.

Methods And Analysis: Twenty-four subjects with treatment-refractory OCD will undergo open-label STN DBS. Structural/functional imaging, electrophysiological recording and neurocognitive assessment would be performed at baseline. The subjects would undergo a structured clinical assessment for 12 months postsurgery. A group of 24 healthy volunteers and 24 subjects with treatment-refractory OCD who receive treatment as usual would be recruited for comparison of biomarkers and treatment response, respectively. Baseline biomarkers would be evaluated as predictors of clinical response. Neuroadaptive changes would be studied through a reassessment of neurocognitive functioning, imaging and electrophysiological activity post DBS.

Ethics And Dissemination: The protocol has been approved by the National Institute of Mental Health and Neurosciences Ethics Committee. The study findings will be disseminated through peer-reviewed scientific journals and scientific meetings.
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http://dx.doi.org/10.1136/bmjopen-2020-047492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220486PMC
June 2021

Association between retinal vascular caliber and brain structure in schizophrenia.

Asian J Psychiatr 2021 Jul 27;61:102707. Epub 2021 May 27.

National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Objective: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging.

Method: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis.

Results: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex.

Discussion: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.
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http://dx.doi.org/10.1016/j.ajp.2021.102707DOI Listing
July 2021

Risk mitigation with the use of clozapine - Quo vadimus.

Asian J Psychiatr 2021 Jul 19;61:102693. Epub 2021 May 19.

National Institute of Mental Health and Neurosciences, India.

The risk of neutropenia decreases significantly after the first year of clozapine initiation, and indefinite hematological monitoring is increasingly questioned. Despite comparable risks of neutropenia, the guidelines for antithyroid drugs - carbimazole and propylthiouracil do not recommend routine hematological monitoring. Assuming a similar pathogenic mechanism, data from antithyroid drugs indicate that neutropenia develops rapidly, and indefinite hematological monitoring misses a large majority of cases in the pre-symptomatic phase. Hence, a more pragmatic strategy of intensive hematological monitoring in the first year of clozapine initiation followed by selective haematological monitoring in case of febrile illnesses or pharyngitis needs to be explored.
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http://dx.doi.org/10.1016/j.ajp.2021.102693DOI Listing
July 2021

Comparison of electric field modeling pipelines for transcranial direct current stimulation.

Neurophysiol Clin 2021 Aug 20;51(4):303-318. Epub 2021 May 20.

Department of Psychiatry, National Institute of Mental Health and Neuroscience (NIMHANS), Bengaluru 560029, India.

Objectives: Electric field modeling utilizes structural brain magnetic resonance images (MRI) to model the electric field induced by non-invasive transcranial direct current stimulation (tDCS) in a given individual. Electric field modeling is being integrated with clinical outcomes to improve understanding of inter-individual variability in tDCS effects and to optimize tDCS parameters, thereby enhancing the predictability of clinical effects. The successful integration of modeling in clinical use will primarily be driven by choice of tools and procedures implemented in computational modeling. Thus, the electric field predictions from different modeling pipelines need to be investigated to ensure the validity and reproducibility of tDCS modeling results across clinical or translational studies.

Methods: We used T1w structural MRI from 32 healthy volunteer subjects and modeled the electric field distribution for a fronto-temporal tDCS montage. For five different computational modeling pipelines, we quantitatively compared brain tissue segmentation and electric field predicted in whole-brain, brain tissues and target brain regions between the modeling pipelines.

Results: Our comparisons at various levels did not reveal any systematic trend with regards to similarity or dissimilarity of electric field predicted in brain tissues and target brain regions. The inconsistent trends in the predicted electric field indicate variation in the procedures, routines and algorithms used within and across the modeling pipelines.

Conclusion: Our results suggest that studies integrating electric field modeling and clinical outcomes of tDCS will highly depend upon the choice of the modeling pipelines and procedures. We propose that using these pipelines for further research and clinical applications should be subject to careful consideration, and indicate general recommendations.
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http://dx.doi.org/10.1016/j.neucli.2021.05.002DOI Listing
August 2021

Protocol for magnetic resonance imaging acquisition, quality assurance, and quality check for the Accelerator program for Discovery in Brain disorders using Stem cells.

Int J Methods Psychiatr Res 2021 Sep 7;30(3):e1871. Epub 2021 May 7.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.

Objective: The Accelerator program for Discovery in Brain disorders using Stem cells (ADBS) is a longitudinal study on five cohorts of patients with major psychiatric disorders from genetically high-risk families, their unaffected first-degree relatives, and healthy subjects. We describe the ADBS protocols for acquisition, quality assurance (QA), and quality check (QC) for multimodal magnetic resonance brain imaging studies.

Methods: We describe the acquisition and QC protocols for structural, functional, and diffusion images. For QA, we acquire proton density and functional images on phantoms, along with repeated scans on human volunteer. We describe the analysis of phantom data and test-retest reliability of volumetric and diffusion measures.

Results: Analysis of acquired phantom data shows linearity of proton density signal with increasing proton fraction, and an overall stability of various spatial and temporal QA measures. Examination of dice coefficient and statistical analyses of coefficient of variation in test-retest data on the human volunteer showed consistency of volumetric and diffusivity measures at whole-brain, regional, and voxel-level.

Conclusion: The described acquisition and QA-QC procedures can yield consistent and reliable quantitative measures. It is expected that this longitudinal neuroimaging dataset will, upon its release, serve the scientific community well and pave the way for interesting discoveries.
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http://dx.doi.org/10.1002/mpr.1871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412227PMC
September 2021

Transcranial direct current stimulation for treatment-resistant obsessive-compulsive disorder-A large case series.

Asian J Psychiatr 2021 Jun 5;60:102625. Epub 2021 Apr 5.

Department of Psychiatry, OCD Clinic, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. Electronic address:

Objective: The present study is a large case series evaluating the benefits of transcranial direct current stimulation (tDCS) in treatment-resistant obsessive compulsive disorder (OCD).

Methods: We reviewed the charts of 32 patients with treatment-resistant OCD who received 10-20 sessions of anodal pre-SMA tDCS.

Results: Overall, 9 (28 %) showed at least partial response to tDCS at the end of 10-20 sessions [responders = 8 (25 %), partial responders = 1 (3%)]. Two out of three partial responders at the end of 10 sessions had response at the end of 20 sessions.

Conclusions: tDCS may benefit a proportion of patients with treatment-resistant OCD.
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http://dx.doi.org/10.1016/j.ajp.2021.102625DOI Listing
June 2021

Effect of transcranial direct current stimulation on in-vivo assessed neuro-metabolites through magnetic resonance spectroscopy: a systematic review.

Acta Neuropsychiatr 2021 Oct 30;33(5):242-253. Epub 2021 Apr 30.

Center for Psychophysics, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.

Objectives: Previous studies have examined the effect of transcranial direct current stimulation (tDCS) on the in-vivo concentrations of neuro-metabolites assessed through magnetic resonance spectroscopy (MRS) in neurological and psychiatry disorders. This review aims to systematically evaluate the data on the effect of tDCS on MRS findings and thereby attempt to understand the potential mechanism of tDCS on neuro-metabolites.

Methods: The relevant literature was obtained through PubMed and cross-reference (search till June 2020). Thirty-four studies were reviewed, of which 22 reported results from healthy controls and 12 were from patients with neurological and psychiatric disorders.

Results: The evidence converges to highlight that tDCS modulates the neuro-metabolite levels at the site of stimulation, which, in turn, translates into alterations in the behavioural outcome. It also shows that the baseline level of these neuro-metabolites can, to a certain extent, predict the outcome after tDCS. However, even though tDCS has shown promising effects in alleviating symptoms of various psychiatric disorders, there are limited studies that have reported the effect of tDCS on neuro-metabolite levels.

Conclusions: There is a compelling need for more systematic studies examining patients with psychiatric/neurological disorders with larger samples and harmonised tDCS protocols. More studies will potentially help us to understand the tDCS mechanism of action pertinent to neuro-metabolite levels modulation. Further, studies should be conducted in psychiatric patients to understand the neurological changes in this population and potentially unravel the neuro-metabolite × tDCS interaction effect that can be translated into individualised treatment.
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http://dx.doi.org/10.1017/neu.2021.14DOI Listing
October 2021

Comment on: "Elevated Clozapine Concentrations in Clozapine-Treated Patients with Hypersalivation".

Clin Pharmacokinet 2021 Aug 26;60(8):1073-1075. Epub 2021 Apr 26.

Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.

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http://dx.doi.org/10.1007/s40262-021-01021-1DOI Listing
August 2021

Reduced T cell immunity in unmedicated, comorbidity-free obsessive-compulsive disorder: An immunophenotyping study.

J Psychiatr Res 2021 05 25;137:521-524. Epub 2021 Mar 25.

Translational Psychiatry Laboratory, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru-560029, India; OCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru-560029, India.

Background: Immune system aberrations have been postulated to play a role in the pathophysiology of Obsessive-compulsive disorder (OCD). This study was aimed to examine the profile of immune cell subsets in peripheral blood of un-medicated OCD patients.

Method: Thirteen drug-naïve/free OCD patients and twenty-six age & sex matched healthy controls were recruited. Immunophenotyping was carried out by staining the whole blood specimens with fluorescent monoclonal antibodies against the cell surface markers such as CD45, CD3, CD16, CD56, CD8, CD4, CD28, CD25 and CD127, followed by data acquisition on BD FACSVerse™ flow cytometer. The proportions of CD4 and CD8 T cells; T regulatory (Tregs), Natural Killer (NK) cells and NK-T cells were compared between patients with OCD and healthy control subjects.

Results: Significantly reduced percentage of T regulatory (Treg) cells was observed in individuals with OCD compared to healthy control subjects [1.0 ± 0.7 vs. 1.9 ± 1.4; p = 0.03, r = 0.33].

Conclusion: Treg cells play a crucial role in regulating the immune response, especially by suppressing the functional activities of T cells. In this study, decreased population of Treg cells essentially indicates a dysregulated T cell and/or T cell mediated immune activation in drug-naïve OCD patients. This preliminary observation might form the basis of further studies examining the immuno-inflammatory/autoimmune origin of OCD.
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http://dx.doi.org/10.1016/j.jpsychires.2021.03.035DOI Listing
May 2021

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Transl Psychiatry 2021 03 17;11(1):173. Epub 2021 Mar 17.

Department of Psychiatry, Oxford University, Oxford, UK.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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http://dx.doi.org/10.1038/s41398-021-01276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969744PMC
March 2021

Systematic evaluation of the impact of defacing on quality and volumetric assessments on T1-weighted MR-images.

J Neuroradiol 2021 Mar 13. Epub 2021 Mar 13.

ADBS Neuroimaging Centre, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Multimodal Brain Image Analysis Laboratory, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address:

Background And Purpose: Facial features can be potentially reconstructed from structural magnetic resonance images, thereby compromising the confidentiality of study participants. Defacing methods can be applied to MRI images to ensure privacy of study participants. These methods remove facial features, thereby rendering the image unidentifiable. It is commonly assumed that defacing would not have any impact on quantitative assessments of the brain. In this study, we have assessed the impact of different defacing methods on quality and volumetric estimates.

Materials And Methods: We performed SPM-, Freesurfer-, pydeface, and FSL-based defacing on 30 T1-weighted images. We statistically compared the change in quality measurements (from MRIQC) and volumes (from SPM, CAT, and Freesurfer) between non-defaced and defaced images. We also calculated the Dice coefficient of each tissue class between non-defaced and defaced images.

Results: Almost all quality measurements and tissue volumes changed after defacing, irrespective of the method used. All tissue volumes decreased post-defacing for CAT, but no such consistent trend was seen for SPM and Freesurfer. Dice coefficients indicated that segmentations are relatively robust; however, partial volumes might be affected leading to changed volumetric estimates.

Conclusion: In this study, we demonstrated that volumes and quality measurements get affected differently by defacing methods. It is likely that this will have a significant impact on the reproducibility of experiments. We provide suggestions on ways to minimize the impact of defacing on outcome measurements. Our results warrant the need for robust handling of defaced images at different steps of image processing.
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http://dx.doi.org/10.1016/j.neurad.2021.03.001DOI Listing
March 2021

The dilemma of self vs others' interest: Altruistic behaviour in schizophrenia and the role of vasopressin.

Schizophr Res 2021 04 9;230:77-78. Epub 2021 Mar 9.

National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

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http://dx.doi.org/10.1016/j.schres.2021.02.005DOI Listing
April 2021

Therapeutic drug monitoring of clozapine in Indian patients with schizophrenia - Authors response.

Schizophr Res 2021 03 17;229:25-26. Epub 2021 Feb 17.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore 560029, India. Electronic address:

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http://dx.doi.org/10.1016/j.schres.2021.01.022DOI Listing
March 2021

fNIRS study of prefrontal activation during emotion recognition-A Potential endophenotype for bipolar I disorder?

J Affect Disord 2021 03 30;282:869-875. Epub 2020 Dec 30.

Dept. of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, India. Electronic address:

Background: Facial emotion recognition (FER) deficit is documented in many psychiatric disorders, including bipolar disorder (BD). However, its role as a risk-marker in BD is not well researched. In the present study, we investigated the role of FER and the corresponding prefrontal neurohemodynamic changes (PNHC) with functional near infra-red spectroscopy (fNIRS) in patients with BD and subjects at high risk for BD compared to healthy subject.

Methods: Using a cross-sectional case-control design we compared 14 patients with first episode mania (FEM) in remission (BD group), 14 healthy siblings of BD patients (HR group), and 13 matched healthy subjects (HC group). FER was assessed using a computer-based task called Tool for Recognition of Emotions in Neuropsychiatric Disorders (TRENDS). Simultaneously, the corresponding PNHC was recorded with fNIRS. Kruskal Wallis H test was used to analyze between-group differences and Spearman's rho for correlation analysis.

Results: The three groups were comparable on socio-demographics (all p>0.09) except education (p = 0.03). HR group had the most hyper-activation in the bilateral DLPFC during the TRENDS task (all p<0.05). There was no significant between-group differences in the FER performance and no significant correlation between the FER performance and the PNHC in the HR and BD groups (all p>0.35).

Limitations: The potential confounding effect of medications in the BD group.

Conclusions: The hyper-activation of the DLPCF in HR group during FER could indicate an increased risk for BD. However, the lack of similar findings in the BD group might reflect a possible normalizing effect of medications. It is equally likely that differences in the PNHC are detectable earlier than the differences in FER task performance during the course of the illness. This requires further exploration.
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http://dx.doi.org/10.1016/j.jad.2020.12.153DOI Listing
March 2021

Antisaccade task performance in obsessive-compulsive disorder and its clinical correlates.

Asian J Psychiatr 2021 Mar 7;57:102508. Epub 2021 Jan 7.

Obsessive Compulsive Disorder Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; Translational Psychiatry Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, India.

Objective: Obsessive-Compulsive Disorder (OCD) is characterized by abnormalities in the cortico-striato-thalamo-cortical (CSTC) circuitry of the brain. Antisaccade eye movement tasks measure aspects of the voluntary control of behaviour that are sensitive to CSTC circuitry dysfunction.

Method: In this study, we examined antisaccade eye movement parameters of OCD patients in comparison with healthy controls (HC). In addition, we also examined the relationship between the antisaccade eye movement parameters and the severity of OCD. Antisaccade performance among right handed OCD patients (N = 65) was compared to matched right handed HC (N = 57). Eye tracking data during the task performance were collected using an Eye-Link eye-tracker at 1000-Hz sampling rate. OCD symptom severity was evaluated using Yale-Brown obsessive compulsive scale.

Results: The antisaccade error percentage was significantly greater in OCD patients than HC (p < 0.001). In addition, OCD patients had less accurate final eye position compared to HC (p < 0.001). There were no significant correlation between antisaccade parameters and OCD severity measures.

Conclusion: Deficient performance in antisaccade task supports CSTC abnormality in OCD and this appears to be independent of the illness severity. Examining this in remitted participants with OCD and in unaffected first degree relatives could help ascertaining their endophenotype validity.
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http://dx.doi.org/10.1016/j.ajp.2020.102508DOI Listing
March 2021

High definition transcranial direct current stimulation (HD-tDCS): A systematic review on the treatment of neuropsychiatric disorders.

Asian J Psychiatr 2021 Feb 6;56:102542. Epub 2021 Jan 6.

WISER Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

HD-tDCS (High-definition transcranial direct current stimulation) is a novel non-invasive brain stimulation (NIBS) technique based on the principle that when weak intensity electric currents are targeted on specific areas of the scalp, they cause underlying cortical stimulation. HD-tDCS shares its technical methodology with conventional tDCS (montage comprising of one anode and one cathode) except for a few modifications that are believed to have focal and longer-lasting neuromodulation effects. Although HD-tDCS is a recently available NIBS technique, impactful studies, case reports, and few controlled trials have been conducted in this context, facilitating an understanding of its neurobiological effects and the clinical translation of the same in health care set-up. The current article narratively reviews the mechanism of action of HD-tDCS, and it systematically examines the cognitive, clinical, and neurobiological effects of HD-tDCS in healthy volunteers as well as patients with neuropsychiatric conditions. Thus, this review attempts to explore the role of HD-tDCS in present-day practice and the future in the context of various neurological and psychiatric disorders.
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http://dx.doi.org/10.1016/j.ajp.2020.102542DOI Listing
February 2021

Auditory signal detection in schizophrenia: Correlates with auditory verbal hallucinations & effect of single session transcranial direct current stimulation (tDCS).

Psychiatry Res 2021 03 4;297:113704. Epub 2021 Jan 4.

WISER Neuromodulation Program, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Introduction: Transcranial Direct Current Stimulation (tDCS) has been beneficial for treating auditory verbal hallucinations (AVH) in schizophrenia (SZ). Aberrant auditory signal detection (ASD) is one of the pathogenetic mechanisms for AVH. We investigated the correlates of ASD with AVH and the impact of single-session tDCS on ASD in SZ patients.

Methods: The ASD performance in SZ patients was compared with matched healthy controls (HC) (N = 24). Subsequently, the effect of single-session tDCS on ASD in SZ patients (N = 24) with AVH was examined in a randomized, double-blind, sham-controlled, cross-over design. The true and sham tDCS were administered (anode at the left dorsolateral prefrontal cortex and cathode at the left temporoparietal junction) on two different days. ASD task was performed before and after each session of tDCS.

Results: Auditory hallucination rating scores correlated significantly with false alarm rate, discriminability index, and response bias. SZ patients had a significantly lesser discriminability index in ASD than HC. Single-session tDCS (true versus sham) did not have any significant effect on ASD in SZ patients.

Conclusion: The study findings support the pathogenetic role of ASD in AVH in SZ. Lack of effect on ASD following single-session tDCS suggests the need for multi-session studies in the future.
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http://dx.doi.org/10.1016/j.psychres.2021.113704DOI Listing
March 2021

Estimating the familial risk of psychiatric illnesses: A review of family history scores.

Asian J Psychiatr 2021 Feb 10;56:102551. Epub 2021 Jan 10.

Department of Psychiatry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru.

A history of psychiatric illnesses in family members of those diagnosed to have an illness has been of significant interest both in research and in clinical practice. Almost all of the major psychiatric illnesses have a familial component to them, perhaps influenced by genetics and a shared environment or their combination. Systematic attempts have been made to quantify these familial risks, as obtained from family history (FH) of psychiatric illnesses. The methods range from a simple dichotomous or count scores to those quantifying as weighted risks such as the Family history density (FHD) measures. This article reviews the available literature on such FH methods and discusses their advantages and limitations. Validation studies have shown that FHD measures may be preferred over dichotomous measures as indicators of familial risk. However, the FHD method has certain limitations, like mostly relying on categorical diagnosis and ignoring other familial risk factors. By critically analysing various existing density measures based on 'ideal characteristics', we suggest a modified version of FHD that would benefit psychiatric research.
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http://dx.doi.org/10.1016/j.ajp.2021.102551DOI Listing
February 2021

Psychiatric symptoms and syndromes transcending diagnostic boundaries in Indian multiplex families: The cohort of ADBS study.

Psychiatry Res 2021 02 16;296:113647. Epub 2020 Dec 16.

Department of Psychiatry, National Institute of Mental Health And Neuro Sciences (NIMHANS), Bengaluru, India. Electronic address:

Syndromes of schizophrenia, bipolar disorder, obsessive-compulsive disorder, substance use disorders and Alzheimer's dementia are highly heritable. About 10-20% of subjects have another affected first degree relative (FDR), and thus represent a 'greater' genetic susceptibility. We screened 3583 families to identify 481 families with multiple affected members, assessed 1406 individuals in person, and collected information systematically about other relatives. Within the selected families, a third of all FDRs were affected with serious mental illness. Although similar diagnoses aggregated within families, 62% of the families also had members with other syndromes. Moreover, 15% of affected individuals met criteria for co-occurrence of two or more syndromes, across their lifetime. Using dimensional assessments, we detected a range of symptom clusters in both affected and unaffected individuals, and across diagnostic categories. Our findings suggest that in multiplex families, there is considerable heterogeneity of clinical syndromes, as well as sub-threshold symptoms. These families would help provide an opportunity for further research using both genetic analyses and biomarkers.
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http://dx.doi.org/10.1016/j.psychres.2020.113647DOI Listing
February 2021

Grounded theory of 'lifestyle adaptation' - Perspectives from persons with schizophrenia and their caregivers.

Asian J Psychiatr 2021 Feb 28;56:102511. Epub 2020 Dec 28.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.

Introduction: Available evidence highlights that persons diagnosed with schizophrenia are predisposed to develop physical co-morbidities. Lifestyle modification interventions are identified as appropriate strategies to maintain their physical health. A comprehensive understanding of the facilitators and barriers in adhering to healthy lifestyle interventions is critical to developing individualized interventions that are effective and accessible for these patients.

Aim: To develop and formulate a theory of lifestyle adaptation for the prevention of physical co-morbidities for persons with schizophrenia and their caregivers who are availing mental health services in the psychiatry wards.

Materials And Methods: The qualitative data were collected by semi-structured interviews using topic guides from persons with schizophrenia and their family caregivers from the tertiary level psychiatry center, South India. The interviews explored their perceptions and experiences of the facilitators and barriers in adopting a healthy lifestyle. Final data was analyzed based on grounded theory, and the data was used to formulate the theory of lifestyle adaptation.

Conclusion: The persons with schizophrenia and their family caregivers' perceptions helped in formulating this theory. The present study provides recommendations for physical health services for patients with mental illness. The findings of the study may guide health professionals and mental health advocacy groups, policymakers to plan for appropriate decisions related to incorporating mental health care with physical health care services.
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http://dx.doi.org/10.1016/j.ajp.2020.102511DOI Listing
February 2021

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

Asian J Psychiatr 2021 Feb 20;56:102507. Epub 2020 Dec 20.

InSTAR Program, Schizophrenia Clinic, Department of Psychiatry, National Institute of mental health and neurosciences (NIMHANS), Bengaluru, India.

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.
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http://dx.doi.org/10.1016/j.ajp.2020.102507DOI Listing
February 2021

The frontal pole and cognitive insight in schizophrenia.

Psychiatry Res Neuroimaging 2021 02 13;308:111236. Epub 2020 Dec 13.

Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address:

Absence of insight owing to impaired self-reflection and lack of touch with reality is a hallmark of schizophrenia. Functional imaging studies in healthy individuals have implicated the frontal pole (FP), sub-division of the prefrontal cortex in self-reflective processes. Despite the significance of self-referential processing in the pathogenesis of schizophrenia, the relationship between FP volume and cognitive insight in this disorder is underexplored. We examined the relationship between cognitive insight and volume of FP using precise manual morphometry of high resolution magnetic resonance images in 19 schizophrenia patients (SCZ) and 21 healthy-volunteers (HV). The manual morphometry technique was replicated from a previous study based on a cytoarchitectonically and functionally valid definition of FP and cognitive insight was measured using Beck's cognitive insight scale. Left frontal pole volume was a significant predictor of self-reflection sub-score of Beck's cognitive insight scale (β=0.68; t = 2.86; p = 0.01). A significant inverse relationship between age and bilateral FP volumes was noted in HV (left FP - r=-0.45; p = 0.04; right FP - r=-0.57; p = 0.008) but not in SCZ (p>0.05). Our findings provide anatomical substrates to devise intervention strategies targeting cognitive insight, thereby improving treatment adherence and functional outcomes.
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http://dx.doi.org/10.1016/j.pscychresns.2020.111236DOI Listing
February 2021
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