Lived experiences of children and adolescents with obsessive-compulsive disorder: interpretative phenomenological analysis.

BACKGROUND: Childhood obsessive-compulsive disorder (OCD) is distinct from OCD in adults. It can be severely disabling and there is little qualitative research on OCD in children. The present study aims to explore the subjective experiences of diagnosis, treatment processes and meaning of recovery in children and adolescents suffering from OCD and provide a conceptual model of the illness. METHODS: It is a qualitative study of ten children and adolescents selected by purposive sampling. MINI KID 6.0, Children's Yale-Brown Obsessive-Compulsive Scale and Clinical Global Impression-Severity Scale were administered at the time of recruitment of subjects into the study. Interviews were conducted using an in-depth semi-structured interview guide and audio-recorded. The transcribed interviews were analyzed using Interpretative Phenomenological Analysis (IPA). The study sought to explore participants' sense-making of their world, their thoughts, feelings and perceptions through interpretative enquiry. The findings were confirmed by a process called investigator triangulation, member check and peer validation. RESULTS: IPA yielded five major themes-'illness perception changes over time', 'disclosure on a spectrum', 'cascading effects of OCD', 'treatment infuses hope and helps', and 'navigating through OCD'. A summary of these themes and their subthemes is presented as a conceptual model. The essence of this model is to show the inter-relationship between themes and provide a comprehensive understanding of the phenomenon of OCD. CONCLUSIONS: To the best of our knowledge, this is the first study to explore lived experiences of children and adolescents with OCD using interpretative phenomenological analysis (IPA). It was noted that perception of illness and treatment processes evolves over time, and recovery is viewed as a process. Future qualitative research can be carried out with a focus on 'therapist-related barriers' or 'student-teacher dyads' that can inform clinical practice and school policies respectively. Trial registration NIMH/DO/IEC (BEH. Sc. DIV)/2018, l1 April 2018.

Clinical profile of children and adolescents diagnosed with anorexia nervosa in Indian context.

OBJECTIVE: This study was conducted to assess the trends observed in the prevalence pattern, clinical presentation, psychosocial profile and treatment profile of anorexia nervosa in children and adolescents who presented to a tertiary care child and adolescent psychiatry centre over a period of ten years. METHODS: Case records of children and adolescents diagnosed with anorexia nervosa at the department of child and adolescent psychiatry from 1st April 2009-31 st March 2019 were obtained from the medical records department of the National Institute of Mental Health and Neurosciences (NIMHANS). Standardized data abstraction forms were developed and used for the purpose of this study. Pseudo-anonymization was done to ensure confidentiality and clinical characteristics of the sample were studied using frequency analysis and central tendencies. RESULTS: Prevalence of anorexia nervosa in a clinic-based population is estimated to be 0.07% over the 10-year period. The mean age at presentation was 13.96 years (SD-2.3) and the male to female ratio was 1:12. The majority (80.8%) were admitted and only one patient (3.8%) received treatment on an outpatient basis. Two or more psychosocial stressors were associated with the onset of illness in 88.5% (n = 23) of the patients and dysfunctional family dynamics was noted to be a significant issue in the majority of cases. All the patients received pharmacotherapy and CBT-based individual therapy. The overall outcome was favourable based on the CGI-I scores. CONCLUSIONS: Prevalence of anorexia nervosa in the clinic-based setting is rising in the Indian context. Sample characteristics are similar to those seen in the west. There is a huge demand-supply gap that calls for creating a service provider network to ensure community-based care.

Subjective experiences of dissociative and conversion disorders among adolescents in India.

Dissociative/conversion disorders affect almost 31% of children and adolescents in a clinical setting. These children experience significant impairments in their academics, and daily functioning, with high chances of developing other psychiatric comorbidities such as anxiety and depression. However, there are no studies that explore the experiences of suffering from dissociative/conversion disorders from perspective of the sufferer. Therefore, the paper has aimed at exploring the subjective experiences of dissociative and conversion disorders among adolescents in the Indian context by examining their understanding about the illness and the reason they ascribe to the cause of their illness. The study used a qualitative semi-structured interview to understand their illness. In total, 10 adolescents of age group between 12 and 16 years participated. Eight out of the 10 participants were female and the mean age was 12 years. All of them were in-patients in the department of Child and Adolescent Psychiatry, NIMHANS, which is the tertiary mental health care Institute India and pioneer Institute of mental health in Asia. All participants have had at least one or more consultation history either with a traditional healer or/and physician. Thematic analysis identified vital themes such as (1) Adolescents' attributing factors of the illness, (2) Cognitive and emotional appraisal of stressful situation/s, (3) Adolescents' appraisal of different explanatory model, (4) Living with the Impact of the illness. This analysis about dissociative/conversion disorders from adolescents' perspective has a major contribution in enhancing the clinical knowledge and practice in planning and managing children/adolescents diagnosed with dissociative/conversion disorders.

Very early-onset Obsessive-Compulsive Disorder in pre-schoolers: A prospective case series.

Normative Obsessive-compulsive (OC) like behaviors can be common in early childhood. Very young children rarely can present with significantly impairing OC phenomenon associated with severe accommodative behaviors, which may warrant interventions. We describe three pre-schoolers with an onset of impairing OC symptoms at 28-, 21-, and 36-months of ages. An eclectic psychosocial approach based on Behaviorism, Attachment, Sensitive Parenting, Developmental, and Family systems was used. The children were followed-up for one to three years. The cases highlight the pattern of Obsessive-Compulsive Disorders (OCD) in very young children and emphasize the utility of non-pharmacological intervention in this age group.

Shukla-Vernon Syndrome: A Second Family with a Novel Variant in the BCORL1 Gene.

Shukla-Vernon syndrome (SHUVER) is an extremely rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, behavioral anomalies, and dysmorphic features. Pathogenic variants in the BCORL1 gene have been identified as the molecular cause for this disorder. The BCORL1 gene encodes for BCL-6 corepressor-like protein 1, a transcriptional corepressor that is an integral component of protein complexes involved in transcription repression. In this study, we report an Indian family with two male siblings with features of Shukla-Vernon syndrome. The patients exhibited global developmental delay, intellectual disability, kyphosis, seizures, and dysmorphic features including bushy prominent eyebrows with synophrys, sharp beaked prominent nose, protuberant lower jaw, squint, and hypoplastic ears with fused ear lobes. No behavioral abnormalities were observed. Whole exome sequencing revealed a novel potentially pathogenic arginine to cysteine substitution (p.Arg1265Cys) in the BCORL1 protein. This is the second report of Shukla-Vernon syndrome with a novel missense variant in the BCORL1 gene. Our study confirms and expands the phenotypes and genotypes described previously for this syndrome and should aid in diagnosis and genetic counselling of patients and their families.

A novel loss of function mutation in adaptor protein complex 4, subunit mu-1 causing autosomal recessive spastic paraplegia 50.

BACKGROUND: Spastic paraplegia 50 (SPG50) is a rare autosomal recessive inherited disorder characterized by spasticity, severe intellectual disability and delayed or absent speech. Loss-of-function pathogenic mutations in the AP4M1 gene cause SPG50. METHODS: In this study, we investigated the clinical and genetic characteristics of a consanguineous family with two male siblings who had infantile hypotonia that progressed to spasticity, paraplegia in one and quadriplegia in the other patient. In addition, the patients also exhibited neurodevelopmental phenotypes including severe intellectual disability, developmental delay, microcephaly and dysmorphism. RESULTS: In order to identify the genetic cause, we performed cytogenetics, whole-exome sequencing and Sanger sequencing. Whole-exome sequencing of the affected siblings and unaffected parents revealed a novel exonic frameshift insertion of eight nucleotides (c.341_342insTGAAGTGC) on exon 4 of the AP4M1 gene. CONCLUSION: Insertion of these eight nucleotides in the AP4M1 gene is predicted to result in a premature protein product of 132 amino acids. The truncated protein product lacks a signal binding domain which is essential for protein-protein interactions and the transport of cargo proteins to the membrane. Thus, the identified variant is pathogenic and our study expands the knowledge of clinical and genetic features of SPG50.

KIAA1109 gene mutation in surviving patients with Alkuraya-Kucinskas syndrome: a review of literature.

BACKGROUND: Alkuraya-Kucinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot and global developmental delay. KIAA1109, a functionally uncharacterized gene is identified as the molecular cause for Alkuraya-Kucinskas syndrome. Most of the reported mutations in KIAA1109 gene result in premature termination of pregnancies or neonatal deaths while a few mutations have been reported in surviving patients with global developmental delay and intellectual disability. To our knowledge, only three surviving patients from two families have been reported with missense variants in KIAA1109. In this study, we describe four surviving patients from two related families (a multiplex family) with global developmental delay and mild to severe intellectual disability with no other systemic manifestations. There were no miscarriages or neonatal deaths reported in these families. METHODS: X-chromosome exome panel sequencing was carried out in one patient and whole exome sequencing was carried out on the remaining three affected individuals and the unaffected father of the index family. Data analysis was carried out followed by variant filtering and segregation analysis. Sanger sequencing was carried out to validate the segregation of mutation in all four affected siblings and unaffected parents from both families. RESULTS: A novel homozygous missense mutation in a conserved region of KIAA1109 protein was identified. Sanger sequencing confirmed the segregation of mutation in both families in an autosomal recessive fashion. CONCLUSION: Our study is the second study reporting a KIAA1109 variant in surviving patients with Alkuraya-Kucinskas syndrome. Our study expands the spectrum of phenotypic features and mutations associated with Alkuraya-Kucinskas syndrome.

A Novel Missense Variant in PHF6 Gene Causing Börjeson-Forssman-Lehman Syndrome.

Börjeson-Forssman-Lehman Syndrome (BFLS) is a rare X-linked recessive syndrome characterized by intellectual disability, developmental delay, obesity, epilepsy, swelling of the subcutaneous tissues of the face, large but not deformed ears, hypogonadism, and gynecomastia. Pathogenic mutations in PHD finger protein 6 (PHF6) have been reported to cause BFLS. In this study, we describe two male siblings with mild intellectual disability, global developmental delay, short stature, microcephaly, and nyctalopia. Whole exome sequencing of the affected siblings and the parents identified a missense variant (c.413C > G) in the PHF6 gene, which leads to alteration of a serine residue at position 138 to cysteine. This mutation is located in a highly conserved region. Sanger sequencing confirmed the segregation of this mutation in the family in an X-linked recessive fashion. Multiple mass spectrometry-based proteomic studies have reported phosphorylation at serine 138 that describes the possible role of serine 138 in signaling. This novel variant in PHF6 gene helped in establishing a diagnosis of BFLS.

Whole Exome Sequencing Identifies a Novel Homozygous Duplication Mutation in the VPS13B Gene in an Indian Family with Cohen Syndrome.

Cohen syndrome (CS) is an autosomal recessive congenital disorder, characterized by hypotonia, intellectual disability, developmental delay, microcephaly, progressive retinopathy, neutropenia, truncal obesity, joint laxity, characteristic facial, ophthalmic, oral and appendage abnormalities, and an over friendly behavior. It has been linked to mutations in the VPS13B gene. The main purpose of this study was to determine the genetic cause of CS in an Indian family. Whole exome sequencing (WES) was used to identify the genetic cause of CS in the family. The WES analysis identified a homozygous novel duplication mutation c.5272dupG in the VPS13B gene, leading to formation of a truncating protein. The present study will be advantageous in genetic diagnosis and genetic counseling in CS, and increases the mutational spectrum of this gene.

Tolerance of transcranial direct current stimulation in psychiatric disorders: An analysis of 2000+ sessions.

Transcranial direct current stimulation (tDCS), a non-invasive, neuromodulatory technique, is being increasingly applied to several psychiatric disorders. In this study, we describe the side-effect profile of repeated tDCS sessions (N = 2005) that were administered to 171 patients (156 adults and 15 adolescents) with different psychiatric disorders [schizophrenia [N = 109], obsessive-compulsive disorder [N = 28], alcohol dependence syndrome [N = 13], mild cognitive impairment [N = 10], depression [N = 6], dementia [N = 2] and other disorders [N = 3]]. tDCS was administered at a constant current strength of 2 mA with additional ramp-up and ramp-down phase of 20 s each at the beginning and end of the session, respectively. Other tDCS protocol parameters were: schizophrenia and obsessive-compulsive disorder: 5-days of twice-daily 20-min sessions with an inter-session interval of 3-h; Mild cognitive impairment/dementia and alcohol dependence syndrome: at least 5-days of once-daily 20-min session; Depression: 10-days of once-daily 30 min session. At the end of each tDCS session, any adverse event observed by the administrator and/or reported by the patient was systematically assessed using a comprehensive questionnaire. The commonly reported adverse events during tDCS included burning sensations (16.2%), skin redness (12.3%), scalp pain (10.1%), itching (6.7%), and tingling (6.3%). Most of the adverse events were noted to be mild, transient and well-tolerated. In summary, our observations suggest that tDCS is a safe mode for therapeutic non-invasive neuromodulation in psychiatric disorders in adults as well as the adolescent population.

Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome.

Say-Meyer syndrome is a rare and clinically heterogeneous syndrome characterized by trigonocephaly, short stature, developmental delay and hypotelorism. Nine patients with this syndrome have been reported thus far although no causative gene has yet been identified. Here, we report two siblings with clinical phenotypes of Say-Meyer syndrome with moderate to severe intellectual disability and autism spectrum disorder. Cytogenetics and array-based comparative genomic hybridization did not reveal any chromosome abnormalities or copy number alterations. Exome sequencing of the patients revealed a novel X-linked recessive splice acceptor site variant c.145-2A > G in intron 5 of HUWE1 gene in both affected siblings. RT-PCR and sequencing revealed the use of an alternate cryptic splice acceptor site downstream, which led to deletion of six nucleotides resulting loss of two amino acids p.(Cys49-Glu50del) in HUWE1 protein. Deletion of these two amino acids, which are located in a highly conserved region, is predicted to be deleterious and quite likely to affect the function of HUWE1 protein. This is the first report of a potential candidate gene mutation for Say-Meyer syndrome, which was initially described four decades ago.

Interventions for Childhood Anxiety Disorders - What Works Best from a Child's Perspective: A Qualitative Study.

BACKGROUND: Anxiety spectrum disorders are the most prevalent psychopathology among children and adolescents. Qualitative research in childhood anxiety disorders can provide valuable insights regarding interventions. The objectives of this study were to examine the child's perspectives on the subjective experience of concerns, the impact of the symptoms on socioacademic functioning, and the process of recovery with interventions. METHODS: Children and adolescents aged 6-16 years, presenting with any subtype of anxiety spectrum disorder as per International Classification of Diseases and Related Health problems, 10th Revision (ICD-10) Diagnostic Criteria for Research, were included. Convenience sampling was used, and 30 children fulfilling inclusion and exclusion criteria were selected. An interview guide with simple questions to facilitate response was used, at the baseline and 12th week of follow-up, to generate a written narrative account of the experience of concerns, the impact of symptoms, and the treatment process. Children received treatment as usual, which included a workbook-based cognitive behavioral intervention. RESULTS: Content analysis was done using 30 baseline and 20 follow-up narratives. Clustering of themes were done. Themes related to the recovery process reflected perceived improvement in academic performance and competence, apart from the improvement in symptoms. There were more themes in favor of cognitive interventions. CONCLUSION: Children's narratives highlight the importance of cognitive interventions for anxiety disorders.

Eye movement tracking in pediatric obsessive compulsive disorder.

Till date researchers have elucidated the neurobiological substrates in OCD using methods like neuroimaging. However, a potential biomarker is still elusive. The present study is an attempt to identify a potential biomarker in pediatric OCD using eye tracking. The present study measured pro-saccade and anti-saccade parameters in 36 cases of pediatric OCD and 31 healthy controls. There was no significant difference between cases and controls in the error rate, peak velocity, position gain and latency measures in both pro-saccade and anti-saccade eye tracking tasks. With age, anti-saccades become slower in velocity, faster in response and more accurate irrespective of disorder status of the child. Pro-saccades also show a similar effect that is less prominent than anti-saccades. Gain measures more significantly vary with age in children with OCD than the controls, whereas latency measures positively correlated with age in children with OCD as opposed to being negatively correlated in the controls. Findings of this study do not support any of the eye tracking measures as putative diagnostic bio-markers in OCD. However, latency and gain parameters across different age groups in anti-saccade tasks need to be explored in future studies.

Favourable short-term course and outcome of pediatric anxiety spectrum disorders: a prospective study from India.

BACKGROUND: Although anxiety disorders are the most prevalent psychiatric disorders among children and adolescents, there is a paucity of research on the course and outcome of anxiety spectrum disorders in low and middle-income countries. METHODS: 60 children and adolescents aged 6-16 years with anxiety spectrum disorders attending the child and adolescent psychiatry department in a tertiary care center from India were included after taking written informed consent and assent in this prospective study conducted between April 2012 to May 2014. Assessments were done at baseline, 12 weeks and 24 weeks using pediatric anxiety rating scale, clinical global impression-severity, clinical global assessment scale and pediatric quality of life scale; MINI-KID (version 6.0) was used to examine remission status. RESULTS: Mean age of children was 12.68 years and mean duration of illness was 34.52 months. Follow-up rate at 24 weeks was 80% with a remission rate of 64.6%. Socio-demographic factors did not affect the baseline severity or course and outcome measures. Children with greater baseline severity and social phobia had a less favorable outcome at 24 weeks. Improvements made in the initial 12 weeks were maintained at 24 weeks follow up. These findings are in line with earlier studies from high-income countries. LIMITATIONS: Small sample size, attrition, rater bias. CONCLUSION: The study has shown a favorable outcome in children and adolescents with anxiety spectrum disorders receiving treatment-as-usual in a tertiary care setting. Adolescents who present with greater severity, comorbid with other anxiety disorders and depression at baseline require intensive intervention, and long-term follow up. There is a need for interventional research with specific focus on universal preventive programs for anxiety spectrum disorders that are feasible for delivery in low and middle-income countries.

New initiatives: A psychiatric inpatient facility for older adolescents in India.

CONTEXT: Almost 1/5th of the adolescent population suffers from mental morbidity. In older adolescents, clinical challenges are accompanied by unique psychosocial and developmental needs. Recent legislations in India - the Mental Health Care Act, 2017 and the Juvenile Justice Act, 2015 - mandate specific arrangements and provisions for evaluation and treatment of children and adolescents. A separate inpatient Adolescent Psychiatry Center (APC) was started at National Institute of Mental Health and Neurosciences, Bangalore, in 2016. AIMS: (a) The aim of this study is to present the need for, development, infrastructure and workforce at APC; (b) to describe clinical profile of adolescents admitted to APC and (c) to identify clinical and psychosocial challenges in the management of older adolescents. SETTING AND DESIGN: The paper covers consecutive inpatient admissions over the first 7 months of APC. MATERIALS AND METHODS: Data were gathered from a review of hospital records, staff meetings, and case files. STATISTICAL ANALYSIS: Qualitative data, such as clinical management challenges, are summarized under major emergent themes. Quantitative data are summarized as means with standard deviations and frequencies with percentages. RESULTS: Males, from urban, nuclear family background constituted the majority admissions. Family stressors and risk behaviors were prevalent. Unique clinical challenges included - risk behaviors, issues related to autonomy, conflict with family and conflict with the legal system. CONCLUSIONS: Older adolescents need to be treated in an environment appropriate to their age and developmental stage. Restructuring of spaces, routines, and creative inputs to interventions strategies must be made for healing environments for youngsters. APC could be a model for the development of other similar centers.

Early childhood network alterations in severe autism.

OBJECTIVE: To examine the differences in whole brain topology and connectivity in 17 children of the ages 3-8 years across severity of ASD, we performed resting state fMRI using a 3T MRI scanner and graph theoretical analysis of networks. METHOD: Patients were partitioned into two cohorts based on the severity of ASD, determined using the Childhood Autism Rating Scale (CARS) scores (Mild, 30-36; Severe, 37+). Standard preprocessing pipeline was used, followed by independent component analysis (ICA) to identify regions of interest (ROIs) to construct subject-specific Z-correlation matrices representing the whole brain network. Following which, graph theory measures were calculated in the range of sparsity 6%-35% and statistically analyzed, and corrected for significance (FDR corrected, p < 0.05). Regional clustering coefficient that revealed significant between-group (mild vs. severe) differences were correlated against clinical scores (CARS). RESULTS: Children with severe ASD revealed significantly increased clustering coefficient and small-worldness compared to those with mild or moderate ASD. Region of interest analysis revealed altered clustering in the Heschl's gyrus that significantly correlated with CARS scores. CONCLUSION: The findings from the current study provide early stage evidence of aberrant brain connectivity appearing in severe ASD, prior to the effect of environmental bias and pruning mechanisms. The clustering of the Heschl's gyrus correlated to the severity of ASD symptoms and agrees with current literature on ASD-associated cortical changes, reflecting early changes to language processing regions.

National Mental Health Survey of India, 2016 - Rationale, design and methods.

Understanding the burden and pattern of mental disorders as well as mapping the existing resources for delivery of mental health services in India, has been a felt need over decades. Recognizing this necessity, the Ministry of Health and Family Welfare, Government of India, commissioned the National Mental Health Survey (NMHS) in the year 2014-15. The NMHS aimed to estimate the prevalence and burden of mental health disorders in India and identify current treatment gaps, existing patterns of health-care seeking, service utilization patterns, along with an understanding of the impact and disability due to these disorders. This paper describes the design, steps and the methodology adopted for phase 1 of the NMHS conducted in India. The NMHS phase 1 covered a representative population of 39,532 from 12 states across 6 regions of India, namely, the states of Punjab and Uttar Pradesh (North); Tamil Nadu and Kerala (South); Jharkhand and West Bengal (East); Rajasthan and Gujarat (West); Madhya Pradesh and Chhattisgarh (Central) and Assam and Manipur (North East). The NMHS of India (2015-16) is a unique representative survey which adopted a uniform and standardized methodology which sought to overcome limitations of previous surveys. It employed a multi-stage, stratified, random cluster sampling technique, with random selection of clusters based on Probability Proportionate to Size. It was expected that the findings from the NMHS 2015-16 would reveal the burden of mental disorders, the magnitude of the treatment gap, existing challenges and prevailing barriers in the mental-health delivery systems in the country at a single point in time. It is hoped that the results of NMHS will provide the evidence to strengthen and implement mental health policies and programs in the near future and provide the rationale to enhance investment in mental health care in India. It is also hoped that the NMHS will provide a framework for conducting similar population based surveys on mental health and other public health problems in low and middle-income countries.