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1.
medRxiv ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38712191

ABSTRACT

Genome-wide association studies across diverse populations may help validate and confirm genetic contributions to risk of disease. We estimated the extent of population stratification as well as the predictive accuracy of polygenic scores (PGS) derived from European samples to a data set from India. We analysed 2685 samples from two data sets, a population neurodevelopmental study (cVEDA) and a hospital-based sample of bipolar affective disorder (BD) and obsessive-compulsive disorder (OCD). Genotyping was conducted using Illumina's Global Screening Array. Population structure was examined with principal component analysis (PCA), uniform manifold approximation and projection (UMAP), support vector machine (SVM) ancestry predictions, and admixture analysis. PGS were calculated from the largest available European discovery GWAS summary statistics for BD, OCD, and externalizing traits using two Bayesian methods that incorporate local linkage disequilibrium structures (PGS-CS-auto) and functional genomic annotations (SBayesRC). Our analyses reveal global and continental PCA overlap with other South Asian populations. Admixture analysis revealed a north-south genetic axis within India (FST 1.6%). The UMAP partially reconstructed the contours of the Indian subcontinent. The Bayesian PGS analyses indicates moderate-to-high predictive power for BD. This was despite the cross-ancestry bias of the discovery GWAS dataset, with the currently available data. However, accuracy for OCD and externalizing traits was much lower. The predictive accuracy was perhaps influenced by the sample size of the discovery GWAS and phenotypic heterogeneity across the syndromes and traits studied. Our study results highlight the accuracy and generalizability of newer PGS models across ancestries. Further research, across diverse populations, would help understand causal mechanisms that contribute to psychiatric syndromes and traits.

2.
Psychiatry Res ; 335: 115839, 2024 May.
Article in English | MEDLINE | ID: mdl-38503006

ABSTRACT

Electroconvulsive therapy (ECT) is one of the most effective treatments in psychiatry. However, it has many cognitive and non-cognitive adverse effects (AEs). There are lacunae in the literature on systematic assessment of non-cognitive AEs. There is a need for a standard, comprehensive and specific clinical tool to evaluate this. Hence, a checklist of short-term AEs of ECT (SAVE) with a 2-phase assessment was developed. Content validation was done using 15 experts' ratings and predefined content validity ratio and index (CVR and CVI) in a two-stage modified Delphi method. The checklist had a good CVR and CVI with a final tool of 39 items. The tool was sensitive and identified the non-cognitive AEs after ECT. Cardiovascular and musculoskeletal systems displayed the highest incidence. Many participants exhibited delayed recovery in orientation, gait, and stance, highlighting a necessity for meticulous monitoring. SAVE is the first standardised tool to assess short-term ECT-related AEs systematically. This checklist likely identifies clinically significant incidences of adverse effects. Its regular use may enhance the safety of ECT and patient comfort by supporting early identification and intervention for AEs. However, given the transient nature of AEs, further studies are needed to determine their predictive validity for long-term consequences.


Subject(s)
Drug-Related Side Effects and Adverse Reactions , Electroconvulsive Therapy , Humans , Electroconvulsive Therapy/adverse effects , Electroconvulsive Therapy/methods , Checklist , Treatment Outcome , Forecasting
4.
Mol Psychiatry ; 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38326559

ABSTRACT

White matter pathways, typically studied with diffusion tensor imaging (DTI), have been implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, due to limited sample sizes and the predominance of single-site studies, the generalizability of OCD classification based on diffusion white matter estimates remains unclear. Here, we tested classification accuracy using the largest OCD DTI dataset to date, involving 1336 adult participants (690 OCD patients and 646 healthy controls) and 317 pediatric participants (175 OCD patients and 142 healthy controls) from 18 international sites within the ENIGMA OCD Working Group. We used an automatic machine learning pipeline (with feature engineering and selection, and model optimization) and examined the cross-site generalizability of the OCD classification models using leave-one-site-out cross-validation. Our models showed low-to-moderate accuracy in classifying (1) "OCD vs. healthy controls" (Adults, receiver operator characteristic-area under the curve = 57.19 ± 3.47 in the replication set; Children, 59.8 ± 7.39), (2) "unmedicated OCD vs. healthy controls" (Adults, 62.67 ± 3.84; Children, 48.51 ± 10.14), and (3) "medicated OCD vs. unmedicated OCD" (Adults, 76.72 ± 3.97; Children, 72.45 ± 8.87). There was significant site variability in model performance (cross-validated ROC AUC ranges 51.6-79.1 in adults; 35.9-63.2 in children). Machine learning interpretation showed that diffusivity measures of the corpus callosum, internal capsule, and posterior thalamic radiation contributed to the classification of OCD from HC. The classification performance appeared greater than the model trained on grey matter morphometry in the prior ENIGMA OCD study (our study includes subsamples from the morphometry study). Taken together, this study points to the meaningful multivariate patterns of white matter features relevant to the neurobiology of OCD, but with low-to-moderate classification accuracy. The OCD classification performance may be constrained by site variability and medication effects on the white matter integrity, indicating room for improvement for future research.

5.
Psychiatry Res ; 331: 115625, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38141264

ABSTRACT

There is limited data on the long-term effect of the COVID-19 pandemic on obsessive-compulsive disorder (OCD). We report on the course of a cohort of individuals with OCD followed-up over a period of one year during the first wave of the COVID-19 pandemic in India. A cohort of 240 individuals registered at a specialty OCD clinic was regularly followed-up using standardized rating tools at three months, six months, and one year into the onset of the COVID-19 pandemic in India. These were compared with clinical ratings recorded in a comparable historical cohort of 207 individuals with OCD, followed up during a non-pandemic year. The pandemic and non-pandemic (historical control) cohorts did not differ in illness severity and rate of relapse. It was found that COVID-19-related anxiety declined over time. Among those patients who were treatment responders prior to the pandemic, COVID-19-related anxiety and non-adherence to medication predicted a relapse of symptoms. Contrary to our expectations, the rate of relapse and illness trajectory in the pandemic cohort did not differ from the non-pandemic cohort, suggesting that the pandemic did not impact our largely medication-adherent cohort. Adherence to treatment seemed to have a protective effect during the pandemic.


Subject(s)
COVID-19 , Obsessive-Compulsive Disorder , Humans , Pandemics , Psychiatric Status Rating Scales , Obsessive-Compulsive Disorder/diagnosis , Recurrence
7.
Mol Psychiatry ; 28(10): 4307-4319, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37131072

ABSTRACT

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.


Subject(s)
Connectome , Obsessive-Compulsive Disorder , Humans , Connectome/methods , Brain Mapping/methods , Magnetic Resonance Imaging/methods , Brain , Biomarkers , Neural Pathways
8.
Neuropsychology ; 37(3): 330-343, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36442004

ABSTRACT

OBJECTIVE: To describe the steps of ensuring measurement fidelity of core clinical measures in a five-country study on brain signatures of obsessive-compulsive disorder (OCD). METHOD: We collected data using standardized instruments, which included the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Dimensional YBOCS (DYBOCS), the Brown Assessment of Beliefs Scale (BABS), the 17-item Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), and the Structured Clinical Interview for DSM-5 (SCID). Steps to ensure measurement fidelity included translating instruments, developing a clinical decision manual, and continuing reliability training with 11-13 transcripts of each instrument by 13 independent evaluators across sites over 4 years. We use multigroup confirmatory factor analysis (MGCFA) to report interrater reliability (IRR) among the evaluators and factor structure for each scale in 206 participants with OCD. RESULTS: The overall IRR for most scales was high (ICC > 0.94) and remained good to excellent throughout the study. Consistent factor structures (configural invariance) were found for all instruments across the sites, while similarity in the factor loadings for the items (metric invariance) could be established only for the DYBOCS and the BABS. CONCLUSIONS: It is feasible to achieve measurement fidelity of clinical measures in multisite, multilinguistic global studies, despite the challenges inherent to such endeavors. Future studies should not only report IRR but also consider reporting methods of standardization of data collection and measurement invariance to identify factor structures of core clinical measures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Subject(s)
Obsessive-Compulsive Disorder , Humans , Reproducibility of Results , Obsessive-Compulsive Disorder/diagnosis , Brain , Psychiatric Status Rating Scales
9.
Can J Psychiatry ; 68(6): 407-417, 2023 Jun.
Article in English | MEDLINE | ID: mdl-35989677

ABSTRACT

OBJECTIVE: To systematically evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in reducing comorbid anxiety and depressive symptoms in patients with obsessive-compulsive disorder (OCD). METHODS: Three electronic databases were searched for randomized, sham-controlled clinical trials evaluating rTMS for the treatment of OCD. Hedge's g was calculated as the effect size for anxiety/depression symptom severity (primary outcome) and OCD severity (secondary outcome). Subgroup analyses and meta-regression analyses were carried out to evaluate the most promising target and whether a reduction in OCD severity moderates the change in anxiety or depression scores. RESULTS: Twenty studies (n = 688) were included in the meta-analysis. rTMS had small-medium effect size on OCD (Hedge's g = 0.43; 95% confidence interval [CI]: [0.20, 0.65]; P < 0.001), anxiety (Hedge's g = 0.3; 95% CI: [0.11, 0.48]; P = 0.001) and depression (Hedge's g = 0.24; 95% CI: [0.07, 0.40]; P = 0.003) symptoms. Subgroup analysis showed that protocols targeting dorsolateral prefrontal cortex (DLPFC) were effective for 3 outcome measures. The change in anxiety, but not depression severity, was moderated by a change in OCD symptom scores. However, the findings are uncertain as a majority of the studies had some concerns or a high risk of bias. CONCLUSIONS: Active rTMS protocol targeting DLPFC is effective in reducing the comorbid anxiety/depression symptoms along with OCD severity. The antidepressant effect is not moderated by the anti-obsessive effect of rTMS.


Subject(s)
Obsessive-Compulsive Disorder , Transcranial Magnetic Stimulation , Humans , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/therapy , Obsessive-Compulsive Disorder/diagnosis , Anxiety/epidemiology , Anxiety/therapy , Comorbidity , Treatment Outcome , Prefrontal Cortex , Randomized Controlled Trials as Topic
10.
Dev Psychopathol ; 35(2): 800-808, 2023 05.
Article in English | MEDLINE | ID: mdl-35393927

ABSTRACT

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.


Subject(s)
Mental Disorders , Psychopathology , Infant, Newborn , Humans , Child , Female , Adolescent , Young Adult , Pregnancy , Mental Disorders/psychology , Mental Health , Risk Factors , Surveys and Questionnaires
11.
J Psychiatr Res ; 156: 557-563, 2022 12.
Article in English | MEDLINE | ID: mdl-36368245

ABSTRACT

BACKGROUND: Family studies in obsessive-compulsive disorder (OCD) indicate higher rates of psychosis among their first-degree relatives (FDRs). However, the etiological and clinical relationships between the two disorders remain unclear. We compared the clinical characteristics and pharmacological treatment response in patients diagnosed with OCD with a family history of psychosis (OCD-FHP), with a family history of OCD (OCD-FHO) and those with sporadic OCD (OCD-S). METHODS: A total of 226 patients who met DSM-IV criteria for OCD (OCD-FHP = 59, OCD-FHO = 112, OCD-S = 55) were included for analysis. All patients were evaluated using the Mini International Neuropsychiatric Interview (MINI 6.0.0), Yale-Brown Obsessive-Compulsive Scale (YBOCS), and the Family Interview for Genetic Studies (FIGS). Treatment response was characterized over naturalistic follow-up. RESULTS: The three groups did not differ across any demographic or clinical variables other than treatment response. Patients in the OCD-FHP group were found to have received a greater number of trials with serotonin reuptake inhibitors (SRI) [F (2,223) = 7.99, p < 0.001], were more likely to have failed ≥2 trials of SRIs (χ2 = 8.45, p = 0.014), and less likely to have attained remission (χ2 = 6.57, p = 0.037) CONCLUSIONS: We observed that having a relative with psychosis may predispose to treatment resistance in OCD. Further research on the influence of genetic liability to psychosis on treatment response in OCD may offer novel translational leads.


Subject(s)
Genetic Predisposition to Disease , Obsessive-Compulsive Disorder , Humans , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/epidemiology , Obsessive-Compulsive Disorder/genetics
12.
J Affect Disord ; 318: 204-216, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36041582

ABSTRACT

BACKGROUND: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. METHODS: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6-65) was divided into six successive 6-10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. RESULTS: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6-13 and adults aged 50-65 with OCD taking SRIs (Cohen's d = -0.24 to -0.74). Volumes of putamen, pallidum (d = 0.18-0.40), and ventricles (d = 0.31-0.66) were greater in patients aged 20-29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = -0.27 to -1.31). CONCLUSIONS: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20-29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.


Subject(s)
Antipsychotic Agents , Obsessive-Compulsive Disorder , Aged , Antipsychotic Agents/adverse effects , Benzodiazepines/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Humans , Longevity , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/diagnostic imaging , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/adverse effects
13.
Article in English | MEDLINE | ID: mdl-35995305

ABSTRACT

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p < 0.01), and the interaction had a negative association with global neurocognition (ß = -0.093, p = 0.009), processing speed (ß = -0.109, p = 0.003) and working memory (ß = -0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.


Subject(s)
Adverse Childhood Experiences , Bipolar Disorder , Mental Disorders , Schizophrenia , Bipolar Disorder/epidemiology , Bipolar Disorder/genetics , Bipolar Disorder/psychology , Humans , Mental Disorders/epidemiology , Mental Disorders/genetics , Mental Status and Dementia Tests , Schizophrenia/epidemiology , Schizophrenia/genetics
14.
J Affect Disord ; 305: 179-187, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35247483

ABSTRACT

BACKGROUND: Obsessive-compulsive disorder (OCD) is known to cause significant burden to patients and their caregivers. However, there is limited data on its impact on family functioning, especially from families with an adult member having OCD. METHODS: Four hundred subjects, which included treatment-seeking adult OCD patients (n = 200) and their caregivers (n = 200) were recruited. Patients were evaluated using the Mini International Neuropsychiatric Interview (MINI) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Caregivers were evaluated using the MINI, the Caregiver Strain Index (CSI), the Hamilton Anxiety Rating Scale (HAM-A), the Hamilton Depression Rating Scale (HAM-D), the Socio-Occupational Functioning Assessment Scale (SOFAS), the Family Accommodation Scale (FAS) and the Connor-David Resilience scale (CD-RISC) in a cross-sectional interview. Family functioning was measured using the OCD Family Functioning (OFF) Scale. Structural equation modeling (SEM) was carried out to evaluate the relationships between the patient and caregiver variables to predict family functioning. RESULTS: From the best-fitting path model, we ascertained that OCD symptoms did not have a direct relationship with family dysfunction. Their effects were in turn was mediated by family accommodation, anxiety, caregiver stress/burden and depression. "Contamination & washing" was the only significant symptom dimension within the model. Caregiver resilience was found to predict only their individual functioning, and not family functioning. LIMITATIONS: Study sample included patients from a tertiary care OCD service, only one caregiver from each patient's family was interviewed. CONCLUSIONS: Evaluating family functioning, addressing it as part of interventional modules for patients and caregivers may help improving treatment outcomes.


Subject(s)
Caregivers , Obsessive-Compulsive Disorder , Adult , Anxiety/psychology , Anxiety Disorders , Caregivers/psychology , Cross-Sectional Studies , Humans , Obsessive-Compulsive Disorder/psychology
15.
Transl Psychiatry ; 12(1): 70, 2022 02 21.
Article in English | MEDLINE | ID: mdl-35190533

ABSTRACT

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 T1-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.


Subject(s)
Obsessive-Compulsive Disorder , Thalamus , Adolescent , Adult , Brain/diagnostic imaging , Brain/pathology , Child , Humans , Magnetic Resonance Imaging , Obsessive-Compulsive Disorder/drug therapy , Thalamus/diagnostic imaging , Thalamus/pathology
16.
J Vis Exp ; (180)2022 02 04.
Article in English | MEDLINE | ID: mdl-35188124

ABSTRACT

Multiple lines of research provide compelling evidence for a role of the cerebellum in a wide array of cognitive and affective functions, going far beyond its historical association with motor control. Structural and functional neuroimaging studies have further refined understanding of the functional neuroanatomy of the cerebellum beyond its anatomical divisions, highlighting the need for the examination of individual cerebellar subunits in healthy variability and neurological diseases. This paper presents a standardized pipeline for examining cerebellum grey matter morphometry that combines high-resolution, state-of-the-art approaches for optimized and automated cerebellum parcellation (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization; ACAPULCO) and voxel-based registration of the cerebellum (Spatially Unbiased Infra-tentorial Template; SUIT) for volumetric quantification. The pipeline has broad applicability to a range of neurological diseases and is fully automated, with manual intervention only required for quality control of the outputs. The pipeline is freely available, with substantial accompanying documentation, and can be run on Mac, Windows, and Linux operating systems. The pipeline is applied in a cohort of individuals with Friedreich ataxia (FRDA), and representative results, as well as recommendations on group-level inferential statistical analyses, are provided. This pipeline could facilitate reliability and reproducibility across the field, ultimately providing a powerful methodological approach for characterizing and tracking cerebellar structural changes in neurological diseases.


Subject(s)
Friedreich Ataxia , Gray Matter , Cerebellum/diagnostic imaging , Cerebellum/pathology , Friedreich Ataxia/complications , Friedreich Ataxia/pathology , Gray Matter/diagnostic imaging , Gray Matter/pathology , Humans , Magnetic Resonance Imaging/methods , Reproducibility of Results
17.
Exp Clin Psychopharmacol ; 30(1): 106-112, 2022 Feb.
Article in English | MEDLINE | ID: mdl-32730059

ABSTRACT

Though several SAPAP3 gene knockout studies in mice have implicated its role in compulsivity, human studies have failed to demonstrate its association with obsessive-compulsive disorder (OCD). We examined the association between allelic variants of a single nucleotide polymorphism in the SAPAP3 gene (rs6662980) with specific aspects of the OCD phenotype. A total of 200 individuals with OCD were genotyped using the TaqMan assay. All participants were assessed using the Mini International Neuropsychiatric Interview and the Yale-Brown Obsessive-Compulsive Scale, and their response to serotonin reuptake inhibitors (SRIs) was evaluated over naturalistic treatment and follow-up. After correcting for multiple comparisons, the G allele at rs6662980 was found to be associated with contamination and washing symptoms (p = .003). Logistic regression analysis also showed that presence of the G allele predicted poor response to SRIs (odds ratio [OR] = 2.473, 95% confidence interval [1.157, 5.407], p = .021). Interaction between presence of the G allele and the Contamination and Washing factor score predicted greater SRI resistance (OR = 3.654, [2.761, 4.547], p = .004). We conclude that specific phenotypic manifestations of OCD, which include contamination and washing-related symptoms along with resistance to SRIs, may be affected by variations in the SAPAP3 gene. Limitations of the study are the lack of a dimensional measure for assessing OCD symptoms, the evaluation of treatment response over naturalistic follow-up, and that only a single locus in the SAPAP3 gene was examined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Subject(s)
Nerve Tissue Proteins , Obsessive-Compulsive Disorder , Alleles , Animals , Genotype , Mice , Nerve Tissue Proteins/genetics , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/genetics , Psychiatric Status Rating Scales , Selective Serotonin Reuptake Inhibitors
18.
Front Psychiatry ; 12: 703701, 2021.
Article in English | MEDLINE | ID: mdl-34858219

ABSTRACT

Comorbidities are seen with obsessive-compulsive disorder (OCD) across the lifespan. Neurodevelopmental comorbidities are common in young children, followed by mood, anxiety, and obsessive-compulsive related disorders (OCRDs) in children, adolescents and adults, and neurological and degenerative disorders in the elderly. Understanding comorbidity prevalence and patterns has clinical and research implications. We conducted a systematic review and meta-analysis on comorbidities in OCD across the lifespan, with the objective to, first, estimate age-wise pattern and prevalence of comorbidities with OCD and, second, to examine associations of demographic (age at assessment, gender distribution) and clinical characteristics (age of onset, illness severity) with comorbidities. Four electronic databases (PubMed, EMBASE, SCOPUS, and PsycINFO) were searched using predefined search terms for articles published between 1979 and 2020. Eligible studies, across age, reported original findings on comorbidities and had an OCD sample size of ≥100. We excluded studies that did not use standardised diagnostic assessments, or that excluded patients on the basis of comorbidity. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol has been registered on the International Prospective Register of Systematic Reviews. A comorbidity rate of 69% was found in a pooled sample of more than 15,000 individuals. Mood disorders (major depressive disorder), anxiety disorders (generalised anxiety disorder), neurodevelopmental disorders (NDDs) and OCRDs were the commonest comorbidities. Anxiety disorders prevailed in children, mood disorders in adults, whereas NDDs were similarly prevalent. Higher comorbidity with any psychiatric illness, NDDs, and severe mental disorders was seen in males, vs. females. Illness severity was inversely associated with rates for panic disorder, tic disorders, OCRDs, obsessive compulsive personality disorder, and anorexia nervosa. This systematic review and meta-analysis provides base rates for comorbidities in OCD across the lifespan. This has implications for comprehensive clinical evaluation and management planning. The high variability in comorbidity rates suggests the need for quality, multi-centric, large studies, using prospective designs. Systematic Review Registration: Unique Identifier: CRD42020215904.

19.
Indian J Psychol Med ; 43(1): 81-85, 2021 Jan.
Article in English | MEDLINE | ID: mdl-34349312

ABSTRACT

Reports on behavioral interventions for the treatment of Tourette's disorder (TD) from India are limited. This patient series describes the usefulness and feasibility of conducting behavioral interventions for patients with TD from an Indian general hospital psychiatric unit. Behavioral treatments in these seven consecutively treated adult/adolescent patients with TD included all components of habit reversal treatment, comprehensive behavioral intervention for tics, and exposure with response prevention in some patients. Patients were predominantly male, with adolescent-onset severe TD, typical features and psychiatric comorbidities, and poor response to multiple medications prior to the institution of behavior therapy. In addition to long delays in diagnosis, none of the patients or their caregivers had been informed by the doctors they had consulted earlier about TD or the need for behavioral treatments before attending our center. Institution of behavioral treatments along with medications led to a 75% reduction in the severity of tics and reduction in comorbid symptoms. Patients and caregivers also reported similar rates of improvement as well as reductions in subjective distress and caregiver burden. Five patients have been followed up for seven months to seven years; apart from one patient, all others have had only minor exacerbations of tics during this period. This limited experience suggests that behavior therapies for TD can be successfully implemented in low-resource, non-specialized Indian settings. They are effective, and gains from such treatment are usually enduring.

20.
Curr Opin Psychiatry ; 34(5): 467-476, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34292182

ABSTRACT

PURPOSE OF REVIEW: Cognitive behavioral therapy (CBT) with exposure and response prevention is the first-line treatment for obsessive-compulsive disorder (OCD) and related disorders such as body dysmorphic disorder (BDD). We review here recent developments in CBT and related therapies in treating OCD and related disorders. RECENT FINDINGS: Superiority of CBT over medications in treating OCD is being questioned by some recent meta-analyses, nonetheless CBT continues to be the mainstay of treatment. Web-based therapies have been shown to be beneficial in treating at least mild-to-moderately ill patients. Mindfulness-based CBT, intensive residential treatment and Bergen 4-day concentrated exposure are also proving to be useful in treating OCD. Large well designed studies have demonstrated the efficacy CBT over supportive therapy in treating BDD. Research on the efficacy of CBT in treating hoarding disorder is accumulating. SUMMARY: Efficacy of web-based CBT has a potential public health importance in that CBT may now become accessible to all and benefit at least mild-to-moderately ill patients who form most of the clinically ill sample. Similarly, efficacy of Bergen 4-day concentrated exposure will have a huge public health implication if the findings can be replicated in other centers across the world.


Subject(s)
Cognitive Behavioral Therapy/methods , Mindfulness , Obsessive-Compulsive Disorder/therapy , Cognition/physiology , Humans , Treatment Outcome
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