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Overview

Faculty and trainees are engaged in epidemiological, biological, clinical as well as policy research in diverse areas in psychiatry. Research activities have ranged from community interventions in various psychiatric disorders to fMRI studies in schizophrenia, addiction, obsessive compulsive disorders and other areas. Many collaborations for research exist with academic and research institutions in the country as well as globally.

Memoranda of Understanding: 

International Memoranda of Understandings have been developed with:

1.The Centre for Addiction and Mental Health, Toronto, Canada, 

2.The Royal College of Psychiatrists, UK  

3.The University of British Columbia, Vancouver, Canada.

4.Taipei Medical University, Taipei

Memoranda of understanding have also been developed with:

1.Sri Vivekananda Yoga AnusandhanaSamsthana (SVYASA), Bangalore

2.St Jon’s Medical College and Research Institute, Bangalore

3.Richmond Fellowship Society, India

The Department is also actively involved in institutional MOU’s with the Universities of Liverpool, Glasgow, Dublin, Edinburgh and Maastricht.

Specific Areas of Research

Addiction Medicine 

In the past 5 years the Centre for Addiction Medicine has successfully completed 5 WHO funded projects:  WHO multi-centre study on harms to others from alcohol; Prevalence,  Patterns and Impact of Alcohol use in India – a study in ten states; Naturalistic follow up study of patients with substance use; Assessing Needs and Developing a Community-based Methodology to Reduce Specific Harm from Alcohol; Drug use among street children. The other funded studies include Double Blind-Randomized Control Study of the Efficacy of Baclofen in the Long-Term Treatment of Alcohol Dependence, Study on Efficacy of Homeopathic Remedies in Substance Abuse disorders, Prevalence of substance use disorder in first episode psychosis, ICMR study on genes that predict alcoholism risk, ICMR study on interventions for women partners of men with alcohol dependence, Efficacy of yogic procedure during alcohol rehab are completed. The centre has also created a clinical cohort of patients with early onset ADS and their children. The centre has been doing neurobiological studies to identify the markers that predict high risk for addiction on the same cohort.  There are regular clinical audits on the database of CAM like Substance use disorder in physicians, trends in opioid use disorder and its management, after care follow up outcomes, patent satisfactory audits are done. Faculty from the centre has been guiding MD and PhD students inside and outside the department. 

Schizophrenia

Multimodal Brain Imaging 

The research that is carried out at the Multimodal Brain Image Analysis Laboratory attempts to link the imaging aberrations (structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), electroencephalography (EEG), event-related potential (ERP) and polysomnography (PSG) with neurochemical and molecular genetic aspects for a more comprehensive understanding of brain functioning and its aberrations in schizophrenia, Alzheimer’s dementia and depression. The above research is being carried out in collaboration with other faculty in the Department of Psychiatry (Geriatric Clinic and Services, Molecular Genetics Laboratory) as well as the Departments of Neurophysiology, Neurochemistry, Neuroimaging and Interventional Radiology as well as Clinical Psychology. Collaborations with researchers from other institutes both nationally and internationally have also been established.

Structural MRI studies on schizophrenia have reported interesting findings in corpus callosum as well as rostral prefrontal cortex (Brodmann’s area 10). In addition, a novel landmark-based definition of the rostral prefrontal cortex, having cytoarchitectonic validity has also been proposed. More recent studies have attempted to address the issue of inconsistent regional brain morphometric findings in schizophrenia. The contribution of risk alleles of candidate gene polymorphisms on brain morphometry has been recently reported, which could contribute to the inconsistency of brain morphometric findings in schizophrenia. Functional imaging studies (fMRI, EEG, ERP) have revealed aberrant activations and deactivations during cognitive performance in schizophrenia, which could indirectly support the glutamatergic hypothesis of schizophrenia. The utility of power spectral and fractal dimension analyses in differentiating schizophrenia and its sub-groups from healthy subjects have also been reported. A novel phase synchronization measure reflecting brain connectivity using ERP data has the potential for studying brain connectivity during cognitive tasks in patients with neuropsychiatric disorders.

Current works at MBIAL focuses on study of systems-level connectivity in schizophrenia, dementia and depression using multiple methods of connectivity analyses for linking with neurochemical and molecular genetic parameters as well as possibly with cellular-level connectivity in future studies. The research on schizophrenia at MBIAL have been funded by the Department of Biotechnology and the Department of Science and Technology.

Social Cognition in Schizophrenia: Clinical significance of social cognition in schizophrenia 

A tool to assess social cognition in the Indian sociocultural setting, SOCRATIS- Social Cognition Rating Tools in Indian Setting was first developed and validated to assess the important dimensions of social cognition, viz., theory of mind, attributional bias and social perception. Next, it was demonstrated that patients with schizophrenia had substantial social cognitive deficits across all domains even when they were remitted from their active psychotic symptoms, when compared to matched healthy volunteers. These deficits persisted even after controlling for general cognitive deficits. This supported their possible endophenotype status in schizophrenia. Further, it was evident that theory of mind deficits influenced functional status of these patients and that this relationship was mediated by severity of negative symptoms. These deficits were linked to other important symptom dimensions like insight and empathy, suggesting that we use our ability to know ourselves to know others. The specific influence of cognitive deficits in parenting ability of schizophrenia parents was examined, and found that theory of mind deficits predicted greater parental role dysfunction. 

The work on social cognition also attempts to provide a better understanding of the construct of cognitive deficits in schizophrenia. First, a systematic review demonstrated consistent evidence regarding fairly distinct constructs of social and general cognition in schizophrenia. Further, using transcranial magnetic stimulation, deficits in mirror neuron activation in drug naïve schizophrenia patients has been demonstrated. Interestingly, heightened mirror neuron activity may be associated with catatonic echophenomena and symptom severity in patients with drug naïve mania. On the contrary, reduced mirror neuron activity showed associations with ego-boundary disturbances and social cognitive deficits. This interesting dichotomous role of mirror neuron dysfunction influencing diverse symptom dimensions of schizophrenia is a novel finding, worth further intensive study. It is also shown that GABA-B receptor mediated short interval intracortical inhibition is significantly associated with social cognition deficits in schizophrenia. Lastly, a single case fMRI-experiment showed that putative mirror neuron activity could potentially be enhanced in a healthy individual. This was replicated in a larger randomized controlled parallel group experiment. These findings have important heuristic and therapeutic implications.

Schizophrenia Clinic & Translational Psychiatry Laboratory

The Department of Psychiatry @ NIMHANS runs a special clinic for schizophrenia patients – The Schizophrenia Clinic.  A cohort of about 500 patients attends this clinic; in addition, there has been regular intake of antipsychotic-naïve schizophrenia patients that are recruited through various neurobiological studies of schizophrenia (~ 40 patients per year).  This clinic involves a multidisciplinary team (faculty from psychiatry, psychiatric social work and clinical psychology) that focuses on delivering comprehensive clinical care for patients with schizophrenia through Individualized Schizophrenia Treatment And Re-integration (InSTAR) Program. 

 The patients are offered individualized care through the InSTAR program that comprise of comprehensive clinical assessment, optimizing psychopharmacological treatments, psychosocial interventions including group therapy, cognitive therapy & other psychological interventions.  Yoga-based intervention is one of the unique therapeutic approaches that is offered for suitable patients in this clinic.  Transcranial Direct Current Stimulation (tDCS) is a novel therapeutic technique that is available through the schizophrenia clinic.  In addition, for early course schizophrenia patients, a specialized intervention approach namely - ORACLES – Objective Risk Assessment Care & Liaison for Early Schizophrenia – (ORACLES) is available in the schizophrenia clinic.  ORACLES, which is a component of InSTAR Program, emphasizes on early intervention approaches, comprehensive delineation of course and prognosis, understanding the clinical markers of medication response, identifying the family members at risk for close monitoring and care, identification of prodromal symptoms and interventions to prevent psychosis conversion, initiating early rehabilitation strategies and specific psychological / psychosocial interventions.

Research studies @ Schizophrenia Clinic examining antipsychotic-naïve schizophrenia patients as well as unaffected first-degree relatives are facilitated through the Translational Psychiatry Laboratory in collaboration with departments of Neurovirology, Neuroimaging & Interventional Radiology, Clinical Psychology, Psychiatric Social Work, Human Genetics, Neuropathology and several other departments.  The overarching focus of these studies is to evaluate the clinical implications as well as systems biology interactions in schizophrenia within the translational research paradigm. Current studies at the TransPsych Lab attempt to evaluate composite biomarkers that underlie the neuroimmunological&neurotrophic aberrations reflective of neurodevelopmental pathogenesis in schizophrenia. These studies on Schizophrenia aim at integrating various endophenotypes with neurobiological parameters.  Recent studies from translational psychiatry laboratory as well as schizophrenia clinic have reported several abnormalities in schizophrenia involving clinical / neurocognitive assessments, markers of aberrant neurodevelopment like dermatoglyphics / digit ratio, brain imaging (structural MRI, functional MRI, DTI & MRS), eye tracking, EEG/ERP, tDCS, neurochemical & immunological assays, gene polymorphism & expression studies with specific focus on hippocampus abnormalities and its connectivity with several brain regions.  The figure below demonstrates a recent PLoS One Publication from the Translational Psychiatry Laboratory reporting relationship between hippocampus volume and interleukin-6 gene polymorphism in antipsychotic-naïve schizophrenia patients.

These research studies are supported by Wellcome Trust / DBT India Alliance Senior Fellowship Research Grant, Innovative Young Biotechnologist Award as well as Centre of Excellence & Innovation in Biotechnology (CEIB) Programme Support from the Department of Biotechnology.

Obsessive-compulsive disorder (OCD)

Over the last 5 years considerable progress has been made in pursuing research in the area of OCD. The specialty OCD clinic has been functioning at the institute since 1997. Most of the research published till date on OCD pertains to patients attending the special clinic. The areas of research in OCD are wide ranging from phenomenology to genetics, imaging and treatment response. 

In the area of phenomenology the following aspects were studied: cluster formation in latent class and finite fixture models, age of onset and clinical phenotype, hoarding, gender differences and relationship between symptom dimensions and clinical characteristics and comorbid profile. With respect to comorbidity, the special focus was on comorbid bipolar disorder and effect of anxiety and depressive disorder comorbidity on clinical profile of OCD. The concept of schizo-obsessive disorder was examined by studying the clinical profile of schizophrenia with OCD in a large hospitalized sample in addition to studying their neuropsychological profile in comparison with schizophrenia without OCD and OCD alone.  Role of insight in OCD has attracted much attention in the last decade and the work done at NIMHANS is widely cited in the world literature.  The work on insight includes relationship between symptom dimensions and insight and neuropsychological correlates of poor insight. Much work is done in the area of neuropsychological functioning in OCD. 

Published work in the area of neuroimaging includes deficient cortical thickness of anterior cingulate gyrus (Figure 1) white matter abnormalities in children with OCD and cortical structural abnormalities, and correlates of caudate nucleus, nucleus accumbens and pituitary volume in drug-naive OCD. The work also includes symptom provocation studies and neuroanatomical correlates of naturalistic outcome and treatment non-response in patients treated with drugs. The work in the area of genetics includes studying familial and sporadic forms of OCD and serotonergic, dopaminergic and glutamatergic genes. Molecular markers of SSRI treatment response are also being currently examined using cellular models. 

Study of the long-term course of OCD has been one of the important areas of research: a 5-year naturalistic prospective follow-up of OCD patients demonstrated that patients with OCD generally have an optimistic outcome in the long-run which is contrary to what has been published from other parts of the world. A study also demonstrated that even SSRI non-responsive patients tend to do reasonably well in the long run if they continue to get aggressive treatment, CBT (cognitive-behaviour therapy) in particular. A meta-analysis of all the naturalistic outcome studies in the world demonstrated that outcome of OCD may not be all that bleak and that Indian patients seem to do better than their counterparts in other parts of the world (in press). Research in the area of OCD also included psychotherapy in OCD (CBT, mindfulness based CBT), particularly in those non-responsive to drugs and role of family accommodation and expressed emotions on the naturalistic outcome. A major on-going work in the area of treatment is the role of rTMS in SSRI non-responsive OCD (NIMHANS funded study). 

Bipolar disorder

Genetic research into bipolar disorder has focused on family studies of endophenotypes, case-control studies and linkage studies. We observed deficits in verbal learning and memory and executive functions (planning) in first-degree relatives of subjects who with bipolar disorder, and these could be potential endophenotypes. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. We also observed gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in our population. The DISC1 locus has been investigated in many population samples, and provides an example of both chromosomal rearrangement, as well as allelic variations, being related to risk of psychotic illness. Further work on this model, using cell-based evaluations, opens up several avenues of enquiry. We have continued to identify enriched families for more detailed analyses, and these include a 100-member family with more than 35 individuals affected with bipolar disorder, and many other families with more than 4 affected first-degree relatives. Several linkage regions of interest have been identified, and these are being evaluated in more detail using a combination of genetic tools.  More recently, we have begun using lymphocyte cultures for pharmacogenomics, as well as using cell-based models to study bipolar disease. We have also reported on the preponderance of manic episodes during a 20-year follow-up of bipolar subjects, as well as correlation of risk of bipolar disorder mediated by latitude, as well as exposure to sunshine.

Genetics 

The molecular genetics laboratory of the Dept of Psychiatry has been active in training post-graduates in genetics methods, conducting research, as well as providing diagnostic testing for certain neurodegenerative disorders. More than 20 MD theses (genetics of addiction, OCD, dementia, schizophrenia, bipolar disorder, intra-cranial aneurysms, Parkinson’s disease, Huntington’s disease, DMD) have been carried out. Doctoral work (Psychiatry, Psychology, Clinical Neuroscience) has focussed on the genetics of psychoses and dementia, and correlations with both clinical, and other empirical measurements (MRI and neuro-psychological).The DNA repository now includes several thousand samples with various neuro-psychiatric syndromes, and will be critical to further research. 

Over the past five years, various aspects of genetic correlates in psychiatric and neurological disease have been investigated. Variations in dopamine receptor and metabolizing pathways perhaps mediate the action of anti-psychotics; and we identified variation in these and their relation to drug response. We also compared the distribution of these alleles with diverse populations, and this could help account for some proportion of the differences in drug response across populations. A modest association of both schizophrenia and bipolar disorder, with variations at the DISC1 locus was reported. The effect of genetic variation of clusters of symptoms in obsessive-compulsive disorder, alcohol dependence and complications; and outcomes in schizophrenia was also evaluated. We have continued to identify enriched families for more detailed analyses, and these include a 100-member family with more than 35 individuals affected with bipolar disorder, and many other families with more than 4 affected first-degree relatives. Several linkage regions of interest have been identified, and these are being evaluated in more detail using a combination of genetic tools.  More recently, a Dr Biju V (DST-Inspire) has begun using lymphocyte cultures to for pharmacogenomics, as well as using cell-based models to study bipolar disease. 

A major focus on neurodegenerative disorders has also emerged. We confirmed the association of the ApoE4 allele on risk of dementia in the elderly, and also its effects on depression in the elderly; and possible interaction with co-morbid diabetes. We also evaluated the effect of ApoE4 variation, and other alleles, on brain morphology and activity (MRI based), and cognitive functioning. We were able to confirm the mutations causing ataxia syndromes, and HD, in more than 200 subjects. The correlations of this mutation, with various clinical parameters (EEG, autonomic function, MRI) were reported; as also the patterns of prevalence. These distributions suggest multiple founders for these syndromes, and suggest need for more in-depth studies to describe the genetic correlates in more detail.  

As part of CoE grant (with the NCBS/TIFR), we have developed lymphocyte cultures from individuals with dementia, who have affected first degree relatives, as also those who carry the ApoE4 allele, and those without the risk alleles. These cultures are being further evaluated using both site-directed changes (using CRISPER), and also conversion to induced pluripotent cells and neuronal lineage cells. These approaches will be very useful in understanding the mechanisms by which risk alleles modify cell biology to produce the disease phenotype. 

Gender related issues

Women’s mental health has been a major area of research. The following are major themes of gender-related research works over the past five years. 

•The mental health impact of gender based violence - Study of Health Consequences of domestic violence with special reference to reproductive health(ICMR Taskforce study) and a Canadian Institute of Health Research funded project on  Resilience among vulnerable women facing violence.

•Department of Health Research funded project on Gender and Health- Mental health literacy and the role of Gender Disadvantage among young women from urban slums Developing  low cost, self help based Mental health promotion interventions for young women

•HIV and Gender - A participatory intervention to promote mental health of IDU widows in north east India as a strategy for HIV prevention. DFID research and Learning Fund- in collaboration with Australian International Health institute, Melbourne, Australia

•m Health - Effectiveness of Integrated Mobile Health Intervention by nurses  to improve adherence among HIV positive women with depression – NIH-ICMR funded project in Collaboration with Yale University, Connecticut, USA. Using mobile based text messages for mental health promotion among young women

Perinatal Psychiatry

The dedicated Perinatal psychiatry service and Mother Bbay inpatient unit have provided sevrela research opportunities in Mother Infant psychiatry. 

The ICMR funded study on pathways to care in women with post partum onset psychosis has been completed. The major findings were that patients with no prior history of psychiatric illness often consult faith-healers and general medical practitioners prior to psychiatric consultation and there is delay with associated worsening of symptoms. Patients and family members were found to have several different etiological models ranging from supernatural powers to biological cause. Some of the practices suggested by faith-healers were potentially associated with risk to mother-baby. 

The PRAMMS cohort- Prospective Assessment of Maternal Mental Health Study- This  is an ongoing ICMR funded cohort assessing Anxiety and depression during pregnancy and its impact on antenatal care utilization and pregnancy outcome.  The project is a community based project which also looks at trauma and protective factors in addition to risks in pregnancy and is being done in close collaboration with several obstetricians and antenatal services in Bangalore.

A non funded project on olanzapine exposure in utero and birth weight has been completed.  Prenatal exposure to olanzapine was linked to higher birth weight among infants. There is an ongoing prospective study of course and outcome of bipolar disorders in women during pregnancy and postpartum period. 

Several papers on risk assessment, bonding assessments, breast feeding and ethical issues in Perinatal psychiatry have been published or presented.

Two ongoing research studies are looking at Oxytocin receptor gene expression and its relation to mother infant bonding and SMPs in postpartum psychosis.

An ongoing study in collaboration with Neurovirology is also investigating the relation between postpartum psychosis and immune parameters.

Consultation-Liaison (C-L) Psychiatry

The Consultation-Liaison (C-L) Psychiatry team along with providing clinical services and training for students in the specialty has actively engaged in research. Over last few years, different facets of C-L psychiatry have been addressed. There has been research on communication in medical practice such as breaking bad news and counseling about pain. In the area of psychooncology the research has focused on coping, psychiatric manifestations and palliation. The publications have also focused on hypnotherapy and spiritual factors in healing. The acute events needing liaison with medical team such as self –amputation and catatonia have been studied. Illnesses with public health importance such as influenza have also been focus of the attention. The psychosomatic disorders and pain syndromes that often present to primary care physicians have been extensively studied. Epilepsy and movement disorders are associated with high degree of psychological co-morbidity and the research has focused these issues in different age groups of population. 

Research on Training and Teaching Methods

The department in collaboration with Clinical Psychology and Psychiatric Social work has been conducting systematic research on supervision, learner self ratings and research ethics training. Small Group Teaching methods are also being standardized including- 

Role play and Simulation methods for Skill based teaching; Newer methods of microteaching including adapting the OSCE for teaching using the OSCAF method (Objective Structured Clinical Assessment with Feedback, OSCAF); Objective Structured Video Examination, OSVE; Team Objective Structured Clinical Examination, TOSCE, Professional OSCEs ( for professionalism in psychiatry).

Community psychiatry and rehabilitation

A series of practice-based-research in two rural communities – Thirthahalli and Turuvekere – in Karnataka has been conducted for about a decade now. Close to 600 patients with schizophrenia in these communities are being followed-up. A number of research questions have been answered while following up these cohorts. 

Treatment with antipsychotics goes beyond mere symptom reduction – it reduces disability associated with schizophrenia. Patients receiving treatment had lower disability and even after several years of untreated status, patients’ disability came down significantly when treated with antipsychotics alone. Treatment with antipsychotics went beyond disability limitation. Family burden, which was closely associated with disability, also came down with treatment. That nearly 70% of the patients were able to function well in the occupational domain is a unique finding, which provides meaning to the recovery that patients achieve with treatment. 

Interestingly, patients in these rural communities are able to achieve this improvement with much less adverse effects – the rate of metabolic syndrome was about 12% among patients with schizophrenia in Thirthahalli. In Turuvekere, though the prevalence of metabolic syndrome was higher, it was comparable to that in the general population of the same community. Though prevalence of tardive dyskinesia was observed in about a third of the chronically treated patients, it was disabling / distressing in less than 1% of the patients. Moreover, mortality of patients with schizophrenia, as measured by Standardized Mortality Ratio (SMR) in this rural cohort was much lower than that reported in the developed countries. 

Relatively better outcome and low adverse effects of treatment of schizophrenia in this cohort was not surprising, given that prevalence of substance use was found to be relatively low among patients. This was found not only in the community but also among the first episode psychosis patients attending NIMHANS. These findings, along with similar observations from other parts of the country may be one of the explanations for the relatively better outcome of schizophrenia in India. 

Qualitative and quantitative research has also shown that not accessing treatment even when it is available is a multifactorial issue, with an average of 5 different socioeconomic factors preventing patients from seeking treatment. Similarly, once treatment is initiated, several factors determine whether the individual would continue it. These have provided valuable insights into the complex challenge of reaching treatment to the rural community-dwelling patients. 

The psychiatric rehabilitation service has explored, systematically, the challenges in discharging patients from daycare services. The team has developed a new model of service-cum-training in psychiatric rehabilitation, called the Services for Enhanced Recovery With Intensive and Continued and Engagement (SERWICE). Its empirical utility in improving several aspects of outcome in chronically mentally ill patients has been demonstrated. 

Geriatric Psychiatry

Over the past 5 years the department has been involved in active research in the field of Geriatric Psychiatry on various geriatric neuropsychiatric disorders such as Alzheimer’s dementia, late onset depression, late onset psychosis and Mild Cognitive Impairment (MCI). The focus of research includes wide range of issues such as neurobiology, biomarkers, risk factors, biological and psychosocial intervention studies and outcome evaluation. The research activities include funded and non- funded research projects, MD and Phd Thesis dissertations. The research work has involved collaboration with various departments of NIMHANS such as Neuroimaging, Clinical Psychology, Epidemiology, Neurochemistry, Neurology, Psychiatric Social Work and Speech pathology. There has been active collaboration with external institutes like National Center for Biological Sciences through the Molecular Genetics lab, Department of Psychiatry for the genetics research in geriatric psychiatry.

APOE4 polymorphism is considered as an important risk factor for Alzheimer’s dementia. The positive association of APOE4 polymorphism with Alzheimer’s and vascular dementia has been confirmed in a hospital based study involving 212 patients with dementia and 195 healthy controls (Bharath et al., 2010). There is stronger association of APOE4 in those with alzheimer’s dementia and diabetes mellitus(Kota et al., 2012). APOE4 carriers have been shown to have reduction in the white matter tract integrity at medial temporal and limbic regions in healthy as well as subjects with Alzheimer’s dementia(Bagepally et al., 2012)

Similarly the association of APOE4 polymorphism and Late onset depression has been shown in a pilot study published recently(Sureshkumar et al., 2012). Study on telomere length in neurodegenerative disorders like dementia, Huntington’s disease and ataxia telangiectasia has indicated that the reduction of telomere length might indicate shared biological pathways for cellular senescence across these disorders(Kota LN et al., 2014). In a study evaluating possibility of familial overlap between dementia and other psychiatric disorders, positive association was found for psychosis with early onset dementia(Narayanaswamy et al., 2010). 

Structural brain morphometric abnormalities in patients with Alzheimer’s disease (AD) has been evaluated in a study using Voxel based morphometry (VBM). This study showed diffuse gray matter atrophy in AD. Gray matter volume had significant positive correlation with cognitive scores and negative correlation with functional impairment and dementia severity (Bagepally et al., 2013).

Elderly seeking treatment from clinical services of NIMHANS are screened for cognitive problems and other neuropsychiatric comorbidity. Brief screening instruments have been compiled to constitute the Instruments for Comprehensive Evaluation of the Elderly (ICE-E). This was very useful for identifying neuropsychiatric problems and medical comorbidity in elderly even by trained professionals with non-medical background (Sadanand et al., 2013).

Effects of Yoga therapy on cognitive function, sleep and quality of life in elderly has been evaluated with a randomized controlled study in elderly homes. Yoga module for elderly has been developed and validated(Hariprasad et al., 2013c). Yoga group had significant improvement in verbal, visual and working memory as well as executive function when compared to waitlist control group(Hariprasad et al., 2013a). Yoga therapy also had positive benefits in sleep quality and quality of life of elderly (Hariprasad et al., 2013b). 

Other recently published studies include the profile of elderly with bipolar disorder, group intervention for carers of elderly patients with neuropsychiatric disorders.

Some of the other important areas that have been studied include house hold cost of dementia, association of plasma protein cluster in AD, association of APOE4 in late onset psychosis, quality of life and caregiver burden in dementia, short term efficacy of acetyl cholinesterase inhibitors in AD.

Currently there are ongoing research projects on structural and functional neuroimaging in healthy elderly, Mild Cognitive Impairment, Mild Alzheimer’s dementia and Late onset depression.

Yoga

The main thrust of the work has been the development and validation of disease-specific yoga modules for different neuropsychiatric disorders such as depression, schizophrenia, and mild cognitive impairment, and investigation of the neurobiological processes behind the effects of yoga.  The Centre has successfully developed modules, pilot-tested them, and conducted randomized controlled trials demonstrating the effectiveness of generic yoga modules in these disorders. 

A comparative study demonstrated effectiveness of yoga as a sole intervention in outpatients with major depression, and elucidated the underlying neurobiological changes such as decrease in serum cortisol and increase in BDNF, which is a marker of neuroplasticity. Another study in elderly with subjective memory loss showed significant improvement in memory parameters after 6 months of yoga practice. In small subset of these subjects, MRI revealed an increase in hippocampal volume.  A RCT in 119 patients with schizophrenia using a yoga module as an add-on intervention showed significant decrease in symptoms, improvement in social cognition and real-world functioning in the yoga group. In fact this is the single largest RCT of Yoga in schizophrenia and has been cited by the recent NICE guidelines for treatment of schizophrenia in adults which has included yoga as a complementary treatment in schizophrenia for the first time. Another controlled study demonstrated that yoga can reduce symptomatology in stabilized inpatients with early psychosis. A yoga module for caregivers of outpatients with schizophrenia also showed significant benefits including reduction of burden and improvement in quality of life. The research done under the aegis of the Centre was published as a special supplement of the Indian Journal of Psychiatry in 2013, with 14 original research articles. 

The Advanced Centre’s work is now being continued by the NIMHANS Integrated Centre for Yoga (NICY) instituted in 2014 at the new premises at the AYUSH Block.  Future plans include continuation of work on disease-specific yoga modules for other neuropsychiatric disorders, short-term training courses in yoga applications for mental health professionals, orientation to neuropsychiatric disorders for yoga therapists, and development of a national yoga program for mental hospitals by training and enabling staff in each hospital to reach the benefits of yoga to patients with mental disorders. 

Electro-convulsive therapy (ECT)

In the past 5 years, considerable research has been conducted in the field of ECT. Though schizophrenia is the most common diagnostic indication, research in ECT for schizophrenia is in its infancy world over. The finding of superiority of bifrontal ECT in mania is replicated in a cohort of schizophrenia patients. It has been shown convincingly that bifrontal ECT is cognitively superior to bitemporal ECT. This was not at the cost of any added cardiovascular risks. This research has changed the practice of ECT substantially. 

The ECT team has developed a new tool to quickly assess cognitive adverse effects of ECT. Research has provided useful insights into pertinent clinical aspects of continuing pharmacotherapy (lithium and antiepileptics) with ECT. EEG parameters early in the course of ECT predicts the outcome ECT sessions – maximal fractal dimension of EEG at the 2nd / 3rd ECT predicted outcome at 2 weeks in schizophrenia patients.  Usefulness of briefer and purportedly safer waveforms of electrical stimulus during ECT is being explored. 

Transcranial Direct Current Stimulation

Transcranial direct current stimulation (tDCS), a neuromodulatory plasticity-inducing, non-invasive brain stimulation technique, has recently generated interest as an emerging treatment modality for schizophrenia.  This technique involves the passage of a weak, direct current that flows between electrodes placed over the scalp. This leads to polarity specific changes in neuronal excitability – anodal stimulation causes increase in neuronal excitability while cathodal stimulation causes a decrease, due to subthreshold polarity-specific de- or hyperpolarisation of neuronal membranes. Interestingly, stimulation for some minutes results in after-effects of tDCS, which share some similarities with long-term potentiation and depression.  It has been hypothesized that tDCS can be effective for reducing auditory hallucinations in schizophrenia by decreasing hyperactivity of the temporo-parietal junction (TPJ), and might improve negative symptoms via enhancing prefrontal activation to improve cognitive control. Several first time observations at the department of psychiatry have demonstrated significant clinical improvement with tDCS, with respect to auditory hallucinations, negative symptoms and insight  in schizophrenia.  Moreover, these changes seem to have a large effect size and are likely to be long lasting which makes them potentially clinically relevant. Recently, it has been shown that the improvement in auditory hallucination severity may be due to adaptive modulation of cortical plasticity.

Transcranial Magnetic Stimulation (TMS)

Transcranial Magnetic Stimulation is a non-invasive brain stimulation technique that is used to investigate and treat psychiatric disorders. A magnetic field of about 1.5 Tesla is used to generate electrical currents in the pyramidal cell layers of the cerebral cortex and this could be inhibitory or excitatory, depending on the threshold used. A DST funded research project investigating mirror neuron deficits in schizophrenia demonstrated intra-cortical inhibition deficits in antipsychotic naïve schizophrenia which also had an inverse correlation with social cognition deficits in schizophrenia. Another funded project investigating cortical inhibition deficits in OCD before and after low-frequency rTMS treatment is currently underway. Previously, an intramural funded research has investigated cortical inhibition in individuals at high-risk for alcohol dependence using paired-pulse TMS. Research investigating cortical inhibition and its relationship with mirror neuron function has been conducted in schizophrenia and mania. Evaluation of cortical inhibition in subjects at high-risk for bipolar disorder and remitted first-episode mania is currently ongoing.

History of Psychiatry

Faculty at NIMHANS have been engaged in the study of the history of psychiatry in India and the region in the past two decades. This has included chronicling the history of archival material from international, national and state archives, preservation and digitisation of hospital records and analysis of case notes. In May 2012, a grant from the Wellcome Trust UK (Grant No WT096493MA) has provided impetus to this venture. This grant titled Turning the Pages: History of Psychiatry in India has the broad aim of  examining the growth of institutional psychiatry in India within the socio-historical context and vis-a-vis transnational developments. The objectives have included:

1.  Document the histories of asylum care and explore the growth of ideas guiding care in       various institutions across India. 

2.  Investigate the   patterns   of   use  of   hospital   services  by   patients  in   the  nineteenth   and  twentieth centuries, using clinical records and oral histories. 

3.  Explore ideas about the psychological aspects of social and political change, with a focus on the psychological distress surrounding the India-Pakistan partition. 

4.  Trace the emergence and growth of community care in India, including NGO and government initiatives and incorporating a range of healing models-‘traditional’, ‘cultural’, biomedical, ‘western’ and ‘indigenous’.