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1.
Front Psychiatry ; 15: 1400621, 2024.
Article in English | MEDLINE | ID: mdl-38807685

ABSTRACT

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

2.
Article in English | MEDLINE | ID: mdl-38587680

ABSTRACT

Several studies show great heterogeneity in the type of genetic test requested and in the clinicopathological characteristics of patients with ASD. The following study aims, firstly, to explore the factors that might influence professionals' decisions about the appropriateness of requesting genetic testing for their patients with ASD and, secondly, to determine the prevalence of genetic alterations in a representative sample of children with a diagnosis of ASD. Methods: We studied the clinical factors associated with the request for genetic testing in a sample of 440 children with ASD and the clinical factors of present genetic alterations. Even though the main guidelines recommend genetic testing all children with an ASD diagnosis, only 56% of children with an ASD diagnosis were genetically tested. The prevalence of genetic alterations was 17.5%. These alterations were more often associated with intellectual disability and dysmorphic features. There are no objective data to explicitly justify the request for genetic testing, nor are there objective data to justify requesting one genetic study versus multiple studies. Remarkably, only 28% of males were genetically tested with the recommended tests (fragile X and CMA). Children with dysmorphic features and organic comorbidities were more likely to be genetic tested than those without. Previous diagnosis of ASD (family history of ASD) and attendance at specialist services were also associated with Genetically tested Autism Spectrum Disorder GTASD. Our findings emphasize the importance of establishing algorithms to facilitate targeted genetic consultation for individuals with ASD who are likely to benefit, considering clinical phenotypes, efficiency, ethics, and benefits.

3.
Sci Rep ; 12(1): 1448, 2022 01 27.
Article in English | MEDLINE | ID: mdl-35087123

ABSTRACT

Although the etiology of obsessive-compulsive disorder (OCD) is largely unknown, it is accepted that OCD is a complex disorder. There is a known bi-directional interaction between the gut microbiome and brain activity. Several authors have reported associations between changes in gut microbiota and neuropsychiatric disorders, including depression or autism. Furthermore, a pediatric-onset neuropsychiatric OCD-related syndrome occurs after streptococcal infection, which might indicate that exposure to certain microbes could be involved in OCD susceptibility. However, only one study has investigated the microbiome of OCD patients to date. We performed 16S ribosomal RNA gene-based metagenomic sequencing to analyze the stool and oropharyngeal microbiome composition of 32 OCD cases and 32 age and gender matched controls. We estimated different α- and ß-diversity measures and performed LEfSe and Wilcoxon tests to assess differences in bacterial distribution. OCD stool samples showed a trend towards lower bacterial α-diversity, as well as an increase of the relative abundance of Rikenellaceae, particularly of the genus Alistipes, and lower relative abundance of Prevotellaceae, and two genera within the Lachnospiraceae: Agathobacer and Coprococcus. However, we did not observe a different Bacteroidetes to Firmicutes ratio between OCD cases and controls. Analysis of the oropharyngeal microbiome composition showed a lower Fusobacteria to Actinobacteria ratio in OCD cases. In conclusion, we observed an imbalance in the gut and oropharyngeal microbiomes of OCD cases, including, in stool, an increase of bacteria from the Rikenellaceae family, associated with gut inflammation, and a decrease of bacteria from the Coprococcus genus, associated with DOPAC synthesis.


Subject(s)
Brain-Gut Axis/immunology , Gastrointestinal Microbiome/immunology , Obsessive-Compulsive Disorder/microbiology , Oropharynx/microbiology , Adult , Case-Control Studies , DNA, Bacterial/isolation & purification , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Healthy Volunteers , Humans , Male , Metagenome , Metagenomics , Middle Aged , Obsessive-Compulsive Disorder/immunology , RNA, Ribosomal, 16S/genetics
4.
J Psychiatr Res ; 137: 319-327, 2021 05.
Article in English | MEDLINE | ID: mdl-33744511

ABSTRACT

High doses of antidepressants, particularly clomipramine and selective serotonin reuptake inhibitors (SSRIs), are the well-established treatment for obsessive-compulsive disorder (OCD), but manic/hypomanic episodes are potential adverse events associated with this treatment. A systematic literature review was performed on manic/hypomanic episodes in non-bipolar OCD patients. Clinical, sociodemographic and antidepressant characteristics during the manic/hypomanic switch were extracted using descriptive statistics. Data were obtained from 20 case reports and case series. Switching episodes mostly appeared in the first 12 weeks after antidepressant initiation and took place more frequently during SSRI use (mostly fluoxetine) in 64.3% of cases. Clomipramine and SSRI use differed non-significantly between the switching episodes that appeared during the first 12 weeks of antidepressant treatment and the episodes that appeared beyond 12 weeks. Switching episodes emerging before 12 weeks were associated with a lower defined daily dose of antidepressants than episodes emerging after 12 weeks. These findings suggest that there are two independent characteristics involved in manic/hypomanic switch in OCD: a) they appeared most frequently with SSRI use (fluoxetine) regardless of the time of it use, and b) episodes appeared in the first 12 weeks after SSRI or clomipramine initiation had a lower dose of antidepressant than episodes appeared after 12 weeks.


Subject(s)
Mania , Obsessive-Compulsive Disorder , Antidepressive Agents/adverse effects , Clomipramine/therapeutic use , Humans , Obsessive-Compulsive Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/adverse effects
6.
Transl Psychiatry ; 10(1): 151, 2020 05 18.
Article in English | MEDLINE | ID: mdl-32424139

ABSTRACT

The multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene ontology and biological pathways associated with the presence of aggressive/checking, symmetry/order, contamination/cleaning, hoarding, and sexual/religious symptoms, as assessed via the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) in 399 probands. Logistic regression analyses were performed at the single-nucleotide polymorphism (SNP) level. Gene-based and enrichment analyses were carried out for common (SNPs) and rare variants. No SNP was associated with any dimension at a genome-wide level (p < 5 × 10-8). Gene-based analyses showed one gene to be associated with hoarding (SETD3, p = 1.89 × 10-08); a gene highly expressed in the brain and which plays a role in apoptotic processes and transcriptomic changes, and another gene associated with aggressive symptoms (CPE; p = 4.42 × 10-6), which is involved in neurotrophic functions and the synthesis of peptide hormones and neurotransmitters. Different pathways or biological processes were represented by genes associated with aggressive (zinc ion response and lipid metabolism), order (lipid metabolism), sexual/religious (G protein-mediated processes) and hoarding (metabolic processes and anion transport) symptoms after FDR correction; while no pathway was associated with contamination. Specific genomic bases were found for each dimension assessed, especially in the enrichment analyses. Further research with larger samples and different techniques, such as next-generation sequencing, are needed to better understand the differential genetics of OCD dimensions.


Subject(s)
Genome-Wide Association Study , Obsessive-Compulsive Disorder , Aggression , Histone Methyltransferases , Humans , Obsessive-Compulsive Disorder/genetics , Polymorphism, Single Nucleotide , Sexual Behavior
7.
J Affect Disord ; 267: 23-32, 2020 04 15.
Article in English | MEDLINE | ID: mdl-32063569

ABSTRACT

BACKGROUND: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study explores the genomic bases of OCD severity. METHODS: We administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to 401 patients at their first visit to our clinic to measure their OCD severity. Genotyping data was collected by using the Infinium PsychArray-24 BeadChip kit (Illumina). We analyzed genetic association with OCD severity in a linear regression analysis at single-nucleotide polymorphism (SNP)- and gene-levels, this last also considering rare variants. Enrichment analyses were performed from gene-based analyses' results. RESULTS: No SNP reached significant association (p < 10-8) with the YBOCS. Six markers showed suggestive association (p < 10-5). The top SNP was an intergenic variant in chromosome 2: rs7578149 (p < 1.89 × 10-6), located in a region suggestively associated with MDD. Linkage disequilibrium was found for two clusters of SNPs located between SLC16A14 and SP110 in chromosome 2, all of them forming one peak of association. Enrichment analyses revealed OCD genes to be associated with porin activity (FDR = 0.01) and transmembrane structure (FDR = 0.04). LIMITATIONS: The size of the sample and the transversal nature of the severity measure are limitations of this study. CONCLUSION: This study contributes to better characterize OCD at an individual level, helping to know more about the prognosis of the disorder and develop more individualized treatments.


Subject(s)
Genome-Wide Association Study , Obsessive-Compulsive Disorder , Humans , Linkage Disequilibrium , Minor Histocompatibility Antigens , Nuclear Proteins , Obsessive-Compulsive Disorder/genetics , Polymorphism, Single Nucleotide/genetics
8.
Transl Psychiatry ; 9(1): 70, 2019 02 04.
Article in English | MEDLINE | ID: mdl-30718812

ABSTRACT

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale-Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD.


Subject(s)
Gene-Environment Interaction , Genetic Predisposition to Disease , Obsessive-Compulsive Disorder/drug therapy , Obsessive-Compulsive Disorder/etiology , Obsessive-Compulsive Disorder/genetics , Outcome Assessment, Health Care/methods , Selective Serotonin Reuptake Inhibitors/pharmacology , Stress, Psychological/complications , Adolescent , Adult , Female , Genotype , Humans , Male , Middle Aged , Multifactorial Inheritance , Young Adult
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