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Psychotic disorders form the core of severe mental illnesses and contribute to substantial disability and health-care costs worldwide. A growing research framework to understand and treat psychotic symptoms using a transdiagnostic paradigm is the social brain perspective of psychoses. The theme of my oration is to highlight how the growing knowledge of evolutionarily preserved social brain networks can help integrate social contextual, psychological, and neurobiological aspects of the genesis of psychotic symptoms and use that knowledge in a translational manner to identify potential therapeutic avenues that extend beyond conventional treatments. The concepts and empirical study of social cognition, social brain (e.g., mirror neuron system), social behaviors (e.g., symptoms and real-world functioning) are illustrated. These give insights into potential newer therapies with brain stimulation, oxytocin, and yoga.

Background: Obsessive-compulsive disorder (OCD) is a heterogeneous and debilitating illness. Symptom dimensions of OCD lend homogeneous avenues for research. Variations in one's appraisal of thoughts and emotions can influence symptom dimensions and impairment. However, little is known about the combined influence of these appraisals in OCD. A clear understanding of these relationships has putative treatment implications. Aim: The aim of the study is to examine the associations among obsessive beliefs, emotional appraisals, and OCD symptom dimensions in adults. Materials and Methods: We examined 50 drug-naïve/drug-free adults with active OCD. Symptom dimensions and impairment were assessed using the Dimensional Yale-Brown Obsessive-Compulsive Severity Scale. Obsessive beliefs and emotional appraisals were studied using the Obsessive Beliefs Questionnaire-44 and Perception of Threat from Emotion Questionnaire. Results: Tobit regression analysis showed the differential association of obsessive beliefs and symptom dimensions - perfectionism/certainty associated with contamination and responsibility/threat estimation associated with aggressive obsessions. Impairment was associated with dimensional symptom severities and with the perception of threat from anger. This association remained even after controlling for depression severity and obsessive beliefs. Conclusions: OCD symptom dimensions are heterogeneous in underlying obsessive beliefs. Emotional appraisals contribute significantly to impairment alongside symptom severity. Emotion-focused interventions must be included in the psychotherapeutic interventions for OCD.

Neuroimaging research in the field of schizophrenia and other psychotic disorders has sought to investigate neuroanatomical markers, relative to healthy control groups. In recent decades, a large number of structural magnetic resonance imaging (MRI) studies have been funded and undertaken, but their small sample sizes and heterogeneous methods have led to inconsistencies across findings. To tackle this, efforts have been made to combine datasets across studies and sites. While notable recent multicentre initiatives and the resulting meta‐ and mega‐analytical outputs have progressed the field, efforts have generally been restricted to MRI scans in one or two illness stages, often overlook patient heterogeneity, and study populations have rarely been globally representative of the diversity of patients who experience psychosis. Furthermore, access to these datasets is often restricted to consortia members who can contribute data, likely from research institutions located in high‐income countries. The Psychosis MRI Shared Data Resource (Psy‐ShareD) is a new open access structural MRI data sharing partnership that will host pre‐existing structural T1‐weighted MRI data collected across multiple sites worldwide, including the Global South. MRI T1 data included in Psy‐ShareD will be available in image and feature‐level formats, having been harmonised using state‐of‐the‐art approaches. All T1 data will be linked to demographic and illness‐related (diagnosis, symptoms, medication status) measures, and in a number of datasets, IQ and cognitive data, and medication history will also be available, allowing subgroup and dimensional analyses. Psy‐ShareD will be free‐to‐access for all researchers. Importantly, comprehensive data catalogues, scientific support and training resources will be available to facilitate use by early career researchers and build capacity in the field. We are actively seeking new collaborators to contribute further T1 data. Collaborators will benefit in terms of authorships, as all publications arising from Psy‐ShareD will include data contributors as authors. The Psy‐ShareD database will host pre‐existing structural MRI data collected at different sites across Europe, North, Central and South America, Asia and Australia that will be suitable for region of interest, voxel‐based morphometry, cortical thickness and surface area analytical approaches.

The current review provides an overview of the existing literature on multimodal transcranial magnetic stimulation, and functional magnetic resonance imaging (TMS/fMRI) studies in individuals with schizophrenia and discusses potential future avenues related to the same. Multimodal studies investigating pathophysiology have explored the role of abnormal thalamic reactivity and have provided further evidence supporting the hypothesis of schizophrenia as a disorder of aberrant connectivity and cortical plasticity. Among studies examining treatment, low-frequency rTMS for the management of persistent auditory verbal hallucinations (AVH) was the most studied. While multimodal TMS/fMRI studies have provided evidence of involvement of local speech-related and distal networks on stimulation of the left temporoparietal cortex, current evidence does not suggest the superiority of fMRI based neuronavigation over conventional methods or of active rTMS over sham for treatment of AVH. Apart from these, preliminary findings suggest a role of rTMS in treating deficits in neurocognition, social cognition, and self-agency. However, most of these studies have only examined medication-resistant symptoms and have methodological concerns arising from small sample sizes and short treatment protocols. That being said, combining TMS with fMRI appears to be a promising approach toward elucidating the pathophysiology of schizophrenia and could also open up a possibility toward developing personalized treatment for its persistent and debilitating symptoms.

Purpose of Review This current review summarizes the investigational and therapeutic applications of transcranial magnetic stimulation (TMS) in schizophrenia. Recent Findings Fairly consistent findings of an impaired cortical excitation-inhibition balance, cortical plasticity, and motor resonance have been reported in schizophrenia. Cortical connectivity impairments have also been demonstrated in motor and prefrontal brain regions. In terms of treatment, the best support is for 1-Hz TMS to the left temporoparietal cortex for the short-term treatment of persistent auditory hallucinations. High-frequency TMS to the left prefrontal cortex improves negative and cognitive symptoms, but with inconsistent and small effects. Summary TMS combined with diverse brain mapping techniques and clinical evaluation can unravel critical brain-behavior relationships relevant to schizophrenia. These provide critical support to the conceptualization of schizophrenia as a connectopathy with anomalous cortical plasticity. Adaptive modulation of these aberrant brain networks in a neuroscience-informed manner drives short-term therapeutic gains in difficult-to-treat symptoms of schizophrenia.

This manuscript introduces a unique program titled \"Clinical Research Center (CRC) for Neuromodulation in Psychiatry\" supported by the prestigious CRC/Public Health Research Center Grant of the DBT Wellcome Trust India Alliance. This multi-institutional research program will be led by NIMHANS (Bengaluru) in collaboration with the Central Institute of Psychiatry (Ranchi), and Kasturba Medical College (Manipal). The goal of this CRC is in alignment with the editorial titled \"Need to Develop \"Interventional Psychiatry\" as a subspecialty in India\" published in the January 2020 issue of the Indian Journal of Psychiatry. The translational research studies and the training programs envisaged through this center will facilitate the development of cost-effective, advanced interventional psychiatry tailored to resource-limited Indian clinical settings and similar other countries as well.

BackgroundDespite significant advancements in healthcare technology, digital health solutions – especially those for serious mental illnesses – continue to fall short of their potential across both clinical practice and efficacy. The utility and impact of medicine, including digital medicine, hinges on relationships, trust, and engagement, particularly in the field of mental health. This paper details results from Phase 1 of a two-part study that seeks to engage people with schizophrenia, their family members, and clinicians in co-designing a digital mental health platform for use across different cultures and contexts in the United States and India.MethodsEach site interviewed a mix of clinicians, patients, and their family members in focus groups (n = 20) of two to six participants. Open-ended questions and discussions inquired about their own smartphone use and, after a demonstration of the mindLAMP platform, specific feedback on the app's utility, design, and functionality.ResultsOur results based on thematic analysis indicate three common themes: increased use and interest in technology during coronavirus disease 2019 (COVID-19), concerns over how data are used and shared, and a desire for concurrent human interaction to support app engagement.ConclusionPeople with schizophrenia, their family members, and clinicians are open to integrating technology into treatment to better understand their condition and help inform treatment. However, app engagement is dependent on technology that is complementary – not substitutive – of therapeutic care from a clinician.

Lithium is an effective, well-established treatment for bipolar disorder (BD). However, the mechanisms of its action, and reasons for variations in clinical response, are unclear. We used neural precursor cells (NPCs) and lymphoblastoid cell lines (LCLs), from BD patients characterized for clinical response to lithium (using the “Alda scale” and “NIMH Retrospective Life chart method”), to interrogate cellular phenotypes related to both disease and clinical lithium response. NPCs from two biologically related BD patients who differed in their clinical response to lithium were compared with healthy controls. RNA-Seq and analysis, mitochondrial membrane potential (MMP), cell viability, and cell proliferation parameters were assessed, with and without in vitro lithium. These parameters were also examined in LCLs from 25 BD patients (16 lithium responders and 9 non-responders), and 12 controls. MMP was lower in both NPCs and LCLs from BD; but it was reversed with in vitro lithium only in LCLs, and this was unrelated to clinical lithium response. The higher cell proliferation observed in BD was unaffected by in vitro lithium. Cell death was greater in BD. However, LCLs from clinical lithium responders could be rescued by addition of in vitro lithium. In vitro lithium also enhanced BCL2 and GSK3B expression in these cells. Our findings indicate cellular phenotypes related to the disease (MMP, cell proliferation) in both NPCs and LCLs; and those related to clinical lithium response (cell viability, BCL2/GSK3B expression) in LCLs.

Objective To examine feasibility and acceptability of smartphone mental health app use for symptom, cognitive, and digital phenotyping monitoring among people with schizophrenia in India and the United States. Methods Participants in Boston, USA and Bhopal and Bangalore, India used a smartphone app to monitor symptoms, play cognitive games, access relaxation and psychoeducation resources and for one month, with an initial clinical and cognitive assessment and a one-month follow-up clinical assessment. Engagement with the app was compared between study sites, by clinical symptom severity and by cognitive functioning. Digital phenotyping data collection was also compared between three sites. Results By Kruskal-Wallis rank-sum test, we found no difference between app activities completed or digital phenotyping data collected across the three study sites. App use also did not correlate to clinical or cognitive assessment scores. When using the app for symptom monitoring, preliminary findings suggest app-based assessment correlate with standard cognitive and clinical assessments. Conclusions Smartphone app for symptom monitoring and digital phenotyping for individuals with schizophrenia appears feasible and acceptable in a global context. Clinical utility of this app for real-time assessments is promising, but further research is necessary to determine the long-term efficacy and generalizability for serious mental illness.

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 74 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimer’s disease and cognitive abilities in genome wide association studies. We then checked whether any of these 74 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 74 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.