Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it

Successful Use of Add - On Topiramate for Antipsychotic - Induced Weight Gain

Antipsychotic induced weight gain is the most common and distressing side effect. This also affects the compliance toward the treatment and hence the prognosis. Non - pharmacological interventions such as exercise and diet modifications alone might not be sufficient most of the times; also ensuring compliance toward this is difficult in patients with psychiatric illness. So, the role of weight - reducing drugs become important. In this case report, we describe the use of low - dose topiramate as a weight - reducing agent, in a patient with a bipolar affective disorder - mania with psychotic symptoms, who had significant risperidone - induced weight gain

Transcranial direct current stimulation for mild cognitive impairment

Mild cognitive impairment (MCI) is recognized as a target for early intervention in elderly with high risk for dementia due to Alzheimer's disease (AD) and other related disorders. Transcranial direct current stimulation (tDCS) is reemerging as a novel method of noninvasive brain stimulation in various neuropsychiatric disorders including MCI and dementia based on the potential clinical applications of its utility in modulating neuroplasticity. In this article, we review the neurobiology of aging, AD, and MCI from the perspective of tDCS and summarize the findings from studies applying tDCS in MCI to improve cognitive function. Studies on therapeutic application of tDCS to improve cognitive function in MCI and other related disorders have shown mixed results. Limited studies available in this topic suggest a potential role for tDCS in MCI. Low risk for adverse effects, lower cost, and the possibility of self-administered home-based intervention are important advantages that encourage further research in this field. There is a need for more evidence from large systematic randomized controlled trials regarding the efficacy of tDCS in MCI. Standardization of stimulation protocols, evaluation of long-term outcome with the possibility of maintenance tDCS, and efficacy of combined intervention of tDCS and cognitive training are important areas for future research in this area

Role of Ayurveda in the management of psychotic disorders: A systematic review of clinical evidence

Background: Despite advancements in the treatment of psychosis, many patients continue to experience persistent symptoms and relapses during antipsychotic treatment, particularly when they fail to adhere to prescribed medications. Ayurveda explains psychotic disorders as “Unmada” and describes various treatment protocols. Although these therapies and methods have been in practice for several years, systematic evidence has not been generated for the same. Thus, in the current review an attempt has been made to illustrate currently available clinical trials on Ayurveda management of psychosis. Methods: We identified 23 studies by literature search in PubMed Central, Cochrane Library and AYUSH Research portal. Out of these, 21 were retrieved after systematic deduplication. After excluding nine studies, 12 studies were included for review. Results: Total of 12 articles comprising 10 clinical trials and 2 case reports were reviewed. Most of the studies demonstrated significant improvement in psychopathology assessed through various symptom rating scales. Discussion: The role of Ayurveda, in the treatment of psychosis is least explored. Currently available studies on the effect of Ayurveda treatment on psychosis are very less in number to draw a valuable conclusion. Hence there is a large scope for conducting neurobiologically informed clinical research in the management of psychotic disorders using Ayurvedic approaches

Toxoplasma Antibody Titers in Mania: A Cross Sectional Study

Background: Recent studies have found a role of infectious agents, especially Toxoplasma gondii, in pathology of bipolar disorder - mania. Aim and Objectives: This study was conducted with the aim to find the prevalence of toxoplasma antibody titers in Indian patients with mania and to assess its specificity towards the clinical profile. Material and Methods: Thirty-four patients having mania were recruited who were psychotropic naïve/free, along with 74 healthy controls. Psychopathology was assessed using structured assessment scales. Serum concentration of Toxoplasma IgG was measured using Diesse Enzywell Toxoplasma IgG immunoassay kit. Results: Mann–Whitney U test revealed that the toxoplasma antibody levels were significantly higher in the mania group than healthy controls (U = 766.5, z = 3.25, p = 0.001). Spearman correlation analyses did not reveal any significant correlation between toxoplasma antibody levels and age at onset (ñ = 0.19, p = 0.26) or YMRS scores (ñ = 0.15, p = 0.39). Discussion: The herein reported association could have potential implications in better understanding the pathophysiology of mania and its treatment. This is the first study to evaluate the association between toxoplasma titers and mania in India with only a few studies done elsewhere in the world

Relationship between Brain-Derived Neurotrophic Factor and Schneiderian First Rank Symptoms in Antipsychotic-Naïve Schizophrenia

Neurodevelopmental aberrations influenced by neurotrophic factors are among the important paradigms to understand schizophrenia pathogenesis. Among various neurotrophic factors, Brain-Derived Neurotrophic Factor (BDNF) is strongly implicated by previous research studies. Evaluating co-morbidity free, antipsychotic-naïve schizophrenia patients for BDNF levels and examining the correlates of this factor with symptoms might facilitate elucidation of its pathogenetic role without confounds of potential influencing factors. In this study, 59 co-morbidity free, antipsychotic-naïve schizophrenia patients were compared with 60 healthy controls for serum BDNF levels. In addition, the relationship between Schneiderian First Rank Symptoms (FRS) and BDNF level in patients was examined. As a group, schizophrenia patients (28.8 ± 11.7 ng/mL) had significantly lower serum BDNF than healthy controls (34.9 ± 8.2 ng/mL) after controlling for the potential confounding effects of age and sex (F = 7.8; p = 0.006). Further analyses revealed FRS status to have significant effect on plasma BDNF after controlling for the potential confounding effects of age and sex (F = 4.5; p = 0.01). Follow-up post hoc analyses revealed FRS(+) patients to have significant deficit in plasma BDNF level in comparison with healthy controls (p = 0.002); however, FRS(−) patients did not differ from healthy controls (p = 0.38). Our study observations add further support to the role for BDNF in schizophrenia pathogenesis and suggest a potential novel link between deficient BDNF and FRS

Neural Effects of Transcranial Direct Current Stimulation in Schizophrenia: A Case Study Using Functional Near-Infrared Spectroscopy

Schizophrenia is a severe neuropsychiatric disorder characterized by delusions, hallucinations, behavioral symptoms, and cognitive deficits. Roughly, 70%-80% of schizophrenia patients experience auditory verbal hallucinations (AVHs), with 25%-30% demonstrating resistance to conventional antipsychotic medications. Studies suggest a promising role for add-on transcranial direct current stimulation (tDCS) in the treatment of medication-refractory AVHs. The mechanisms through which tDCS could be therapeutic in such cases are unclear, but possibly involve neuroplastic effects. In recent years, functional near-infrared spectroscopy (fNIRS) has been used successfully to study tDCS-induced neuroplastic changes. In a double-blind, sham-controlled design, we applied fNIRS to measure task-dependent cerebral blood flow (CBF) changes as a surrogate outcome of single session tDCS-induced effects on neuroplasticity in a schizophrenia patient with persistent auditory hallucinations. The observations are discussed in this case report