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2.
Mol Psychiatry ; 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326559

RESUMEN

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.

3.
Liver Int ; 43(8): 1822-1836, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37312667

RESUMEN

BACKGROUND & AIMS: Transcription co-activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neurogenesis, including the regulation of fibrogenesis. METHODS: Tcf20 knock-out (Tcf20-/- ) and Tcf20 heterozygous mice were generated by homologous recombination. TCF20 gene genotyping and expression was assessed in patients with pathogenic variants in the TCF20 gene. Neural development was investigated by immufluorescense. Mitochondrial metabolic activity was evaluated with the Seahorse analyser. The proteome analysis was carried out by gas chromatography mass-spectrometry. RESULTS: Characterization of Tcf20-/- newborn mice showed impaired neural development and death after birth. In contrast, heterozygous mice were viable but showed higher CCl4 -induced liver fibrosis and a differential expression of genes involved in extracellular matrix homeostasis compared to wild-type mice, along with abnormal behavioural patterns compatible with autism-like phenotypes. Tcf20-/- embryonic livers and mouse embryonic fibroblast (MEF) cells revealed differential expression of structural proteins involved in the mitochondrial oxidative phosphorylation chain, increased rates of mitochondrial metabolic activity and alterations in metabolites of the citric acid cycle. These results parallel to those found in patients with TCF20 pathogenic variants, including alterations of the fibrosis scores (ELF and APRI) and the elevation of succinate concentration in plasma. CONCLUSIONS: We demonstrated a new role of Tcf20 in fibrogenesis and mitochondria metabolism in mice and showed the association of TCF20 deficiency with fibrosis and metabolic biomarkers in humans.


Asunto(s)
Fibroblastos , Hígado , Humanos , Ratones , Animales , Fibroblastos/patología , Hígado/patología , Cirrosis Hepática/patología , Mitocondrias/patología , Factores de Transcripción/genética
4.
Span J Psychiatry Ment Health ; 16(1): 32-41, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-33901700

RESUMEN

OBJECTIVE: During the COVID-19 pandemic, authorities confined adults, adolescents and children to their homes. Recent articles warn of possible long-term consequences on mental health, especially for those who suffer from underlying psychiatric conditions and for vulnerable sections of the population. The present study explores the psychological impact of the COVID-19 quarantine on outpatients at the Centre of Child and Adolescent Mental Health (CAMHS), which is based in Barcelona. METHODS: A total of 441 caregivers answered an online ad-hoc survey on their sociodemographic and economic situation, perceived stress, and clinical changes and coping strategies observed in their children during lockdown. The Chi-square test was used to compare the response percentages for each behaviour or symptom between age, gender and diagnostic groups. Variance and post-hoc test were also analyzed, as was the Pearson correlation. RESULTS: The use of electronic devices has significantly increased. There has also been an increase in symptoms such as attentional problems, fatigue and irritability, among others. Differences were found between age and gender groups. The diagnostic groups most affected by confinement were Autism Spectrum Disorders and Conduct Disorders. The survey also discovered a relationship between the loss of family income, parental stress and increased symptoms in children. CONCLUSION: Confinement has increased externalizing symptoms and behaviours as well as COVID-19 related concerns, somatic problems and anxieties. It is important to observe the fluctuation of symptoms and how young people adapt to the pandemic in order to reach a better understanding of the situation and devise new strategies to reduce the psychological impact of the pandemic.


Asunto(s)
COVID-19 , Adulto , Humanos , Niño , Adolescente , COVID-19/epidemiología , Salud Mental , Pandemias , SARS-CoV-2 , Control de Enfermedades Transmisibles
5.
Child Psychiatry Hum Dev ; 54(3): 849-856, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-34978642

RESUMEN

Pediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80-0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64-0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65-0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.


Asunto(s)
Trastorno Obsesivo Compulsivo , Adolescente , Humanos , Niño , Psicometría/métodos , Reproducibilidad de los Resultados , Trastorno Obsesivo Compulsivo/diagnóstico , Encuestas y Cuestionarios , Autoinforme
6.
J Psychiatr Res ; 156: 151-158, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36252344

RESUMEN

There is a lack of consensus on whether routine brain magnetic resonance imaging (MRI) should be recommended as part of the initial assessment in patients with psychosis. No study so far has qualitatively assessed brain MRI in patients with early-onset psychosis (EOP), in whom neurodevelopmental factors may play a stronger role. We aimed to determine the prevalence of brain MRI findings in patients with EOP compared to healthy controls, and assess whether these findings were clinically relevant. Retrospective clinical chart review of all patients with EOP in whom a brain MRI scan was acquired during admission to an inpatient child and adolescent psychiatry unit during January 2013-December 2017, compared to age and biologically assigned gender matched healthy controls. Between group analyses tested differences in rates of qualitatively abnormal MRI scans and changes in clinical management as a result of radiological findings. A total of 256 individuals were included (128 patients with EOP and 128 healthy controls). Patients with EOP presented with a significantly higher rate of abnormal MRI scans relative to healthy controls (21.9% vs 11.7%, p = .030; OR = 2.11, [95% CI:1.06-4.17]). Radiological findings in the EOP group triggered clinical referral for further evaluation or management more often than in the healthy control group (7.0% vs 1.6%, p = .030; OR = 4.76, [95% CI:1.01-22.50]). MRI scans in youth with EOP may be characterized by an increased number of radiological abnormalities than in controls. The rates of MRI findings requiring clinical referral suggests that routine MRI acquisition may need to be considered in patients with EOP.


Asunto(s)
Imagen por Resonancia Magnética , Proyectos de Investigación , Niño , Humanos , Adolescente , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen
7.
J Affect Disord ; 318: 204-216, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36041582

RESUMEN

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.


Asunto(s)
Antipsicóticos , Trastorno Obsesivo Compulsivo , Anciano , Antipsicóticos/efectos adversos , Benzodiazepinas/uso terapéutico , Niño , Preescolar , Estudios Transversales , Humanos , Longevidad , Imagen por Resonancia Magnética , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos
8.
Artículo en Inglés | MEDLINE | ID: mdl-35759074

RESUMEN

The Child Obsessive-Compulsive Impact Scale (COIS-R) is a parent- and self-report measure of the impairment related to Obsessive-Compulsive Disorder (OCD) symptoms. Previous research has demonstrated the reliability and validity of the original version of the COIS-R; to date, however, the scale has not been validated for use in Spanish samples of pediatric OCD. The present study aimed to assess the psychometric properties of this in a clinical sample of pediatric OCD (n = 91). Analyses of internal consistency, convergent and divergent validity were conducted. For both the COIS-R report scales estimates similar to those in the original instrument were obtained for internal consistency, test-retest reliability, and convergent validity. Thus, the Spanish version of the COIS-R seems to retain sound psychometric properties of its original version; it appears to be a reliable instrument for the assessment of obsessive-compulsive impairment and the effects of treatment, and can be used in other cultural contexts.

9.
Biol Psychiatry ; 92(4): 299-313, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35489875

RESUMEN

BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Trastorno Bipolar , Trastorno Depresivo Mayor , Nacimiento Prematuro , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Corteza Cerebral , Niño , Trastorno Depresivo Mayor/patología , Femenino , Humanos , Recién Nacido , Imagen por Resonancia Magnética/métodos , Embarazo , Nacimiento Prematuro/patología
10.
Mol Psychiatry ; 27(4): 2114-2125, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35136228

RESUMEN

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.


Asunto(s)
Trastorno del Espectro Autista , Encéfalo , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Vías Nerviosas
11.
Trials ; 23(1): 164, 2022 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-35189937

RESUMEN

BACKGROUND: Obsessive-compulsive disorder (OCD) in children can lead to a huge burden on the concerned patients and their family members. While successful state-of-the art cognitive behavioral interventions exist, there is still a lack of available experts for treatment at home, where most symptoms manifest. Internet-based cognitive behavioral therapy (iCBT) could overcome these restrictions; however, studies about iCBT in children with OCD are rare and mostly target computerized self-help resources and only email contact with the therapist. Therefore, we intended to build up and to evaluate an iCBT approach for children with OCD, replacing successful elements of traditional in-office face-to-face CBT, with face-to-face teleconferences, online materials, and apps. METHODS: With the help of a pilot feasibility study, we developed the iCBT consisting of 14 teleconference sessions with the child and parents. The sessions are supported by an app assessing daily and weekly symptoms and treatment course completed by children and parents. Additionally, we obtain heart rate and activity scores from the child via wristbands during several days and exposure sessions. Using a waiting list randomized control trial design, we aim to treat and analyze 20 children with OCD immediately after a diagnostic session whereas the control group of another set of 20 OCD patients will be treated after waiting period of 16 weeks. We will recruit 30 patients in each group to take account for potential dropouts. Outcomes for the treatment group are evaluated before randomization (baseline, t0), 16 weeks (end of treatment, t1), 32 weeks (follow-up 1, t2), and 48 weeks after randomization (follow-up 2, t3). For the waiting list group, outcomes are measured before the first randomization (baseline), at 16 weeks (waiting list period), 32 weeks (end of treatment), 48 weeks after the first randomization (follow-up I), and 64 weeks after the first randomization (follow-up II). DISCUSSION: Based on our experience of feasibility during the pilot study, we were able to develop the iCBT approach and the current study will investigate treatment effectiveness. Building up an iCBT approach, resembling traditional in-office face-to-face therapy, may ensure the achievement of well-known therapy effect factors, the acceptance in both patients and clinicians, and the wide distribution within the health system. TRIAL REGISTRATION: ClinicalTrials.gov NCT05037344 . Registered May 2019, last release August 13th, 2021.


Asunto(s)
Terapia Cognitivo-Conductual , Trastorno Obsesivo Compulsivo , Niño , Terapia Cognitivo-Conductual/métodos , Humanos , Internet , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/terapia , Proyectos Piloto , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
12.
Hum Brain Mapp ; 43(1): 37-55, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-32420680

RESUMEN

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Encéfalo , Neuroimagen , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Estudios Multicéntricos como Asunto , Neurociencias
14.
J Neural Transm (Vienna) ; 128(9): 1445-1459, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34432173

RESUMEN

Cognitive behavioral therapy (CBT) is the first choice of treatment of obsessive-compulsive disorder (OCD) in children and adolescents. However, there is often a lack of access to appropriate treatment close to the home of the patients. An internet-based CBT via videoconferencing could facilitate access to state-of-the-art treatment even in remote areas. The aim of this study was to investigate feasibility and acceptability of this telemedical approach. A total of nine children received 14 sessions of CBT. The first session took place face-to-face, the remaining 13 sessions via videoconference. OCD symptoms were recorded with a smartphone app and therapy materials were made accessible in a data cloud. We assessed diagnostic data before and after treatment and obtained measures to feasibility, treatment satisfaction and acceptability. Outcomes showed high acceptance and satisfaction on the part of patients with online treatment (89%) and that face-to-face therapy was not preferred over an internet-based approach (67%). The majority of patients and their parents classified the quality of treatment as high. They emphasized the usefulness of exposures with response prevention (E/RP) in triggering situations at home. The app itself was rated as easy to operate and useful. In addition to feasibility, a significant decrease in obsessive-compulsive symptoms was also achieved. Internet-based CBT for pediatric OCD is feasible and well received by the patients and their parents. Furthermore, obsessive-compulsive symptomatology decreased in all patients. The results of this study are encouraging and suggest the significance of further research regarding this technology-supported approach, with a specific focus on efficacy.Trial registration number: Clinical trials AZ53-5400.1-004/44.


Asunto(s)
Terapia Cognitivo-Conductual , Trastorno Obsesivo Compulsivo , Adolescente , Niño , Estudios de Factibilidad , Humanos , Internet , Trastorno Obsesivo Compulsivo/terapia , Padres , Resultado del Tratamiento
15.
Psychiatry Res ; 299: 113858, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33770712

RESUMEN

Evidence based treatments for pediatric Obsessive-Compulsive Disorder (OCD) are delivered with varying levels of expertise. This paper is part of the phase two series by the International OCD Accreditation Task Force (ATF) to advance a standardized high level of care globally. This paper presents specific knowledge and competencies recommended for specialized practice for pediatric psychopharmacologists working with OCD, developed by an international group of clinicians with extensive expertise in assessment and treatment of OCD. Tabulated knowledge and competency standards are operationalized as clinician abilities with specification of evidence for each standard. The distinction between current practice guidelines and ATF standards is discussed. Drug treatment has a solid evidence base. However, it should not be applied isolated, but informed by broad competence in general child and adolescent psychiatry and pediatrics. Other treatment relevant areas such as specialty CBT, family functioning, developmental issues, and neurobiology require consideration. Drug treatment includes several phases with varying degrees of evidence: Starting up medication, titration to maximum tolerated dose, maintenance, termination, and relapse prevention. In complex cases, pharmacotherapy with weak evidence may be needed to target symptoms and/or co-morbidity. The ATF knowledge and competency standards presented will be reviewed and updated commensurate with research.


Asunto(s)
Terapia Cognitivo-Conductual , Trastorno Obsesivo Compulsivo , Pediatría , Preparaciones Farmacéuticas , Adolescente , Niño , Familia , Humanos , Trastorno Obsesivo Compulsivo/tratamiento farmacológico
16.
JAMA Psychiatry ; 78(1): 47-63, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32857118

RESUMEN

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno del Espectro Autista/patología , Trastorno Bipolar/patología , Corteza Cerebral/patología , Trastorno Depresivo Mayor/patología , Desarrollo Fetal/fisiología , Expresión Génica/fisiología , Desarrollo Humano/fisiología , Trastorno Obsesivo Compulsivo/patología , Esquizofrenia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno Bipolar/diagnóstico por imagen , Estudios de Casos y Controles , Corteza Cerebral/citología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/crecimiento & desarrollo , Niño , Preescolar , Estudios de Cohortes , Biología Computacional , Trastorno Depresivo Mayor/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Análisis de Componente Principal , Esquizofrenia/diagnóstico por imagen , Adulto Joven
17.
Transl Psychiatry ; 10(1): 342, 2020 10 08.
Artículo en Inglés | MEDLINE | ID: mdl-33033241

RESUMEN

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.


Asunto(s)
Trastorno Obsesivo Compulsivo , Biomarcadores , Encéfalo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Neuroimagen , Trastorno Obsesivo Compulsivo/diagnóstico por imagen , Trastorno Obsesivo Compulsivo/tratamiento farmacológico
18.
Educ. med. (Ed. impr.) ; 21(5): 328-337, sept.-oct. 2020. tab
Artículo en Español | IBECS | ID: ibc-196877

RESUMEN

El aprendizaje del residente se realiza a través del trabajo que desarrolla en diferentes contextos laborales como: la planta del hospital, el quirófano, el centro de salud, la participación en congresos o en comisiones, etc. Aun así, este desempeño tiene que complementarse con metodologías que conlleven actividades específicas para desarrollar aquellas competencias que no se pueden trabajar de forma planificada y explícita en el día a día como el pensamiento crítico, el trabajo cooperativo, la gestión de las emociones, etc. Más allá de las clásicas sesiones clínicas de casos o bibliográficas, existen otras metodologías activas dirigidas a favorecer estos aprendizajes para alcanzar una formación integral, como el aprendizaje basado en problemas, el método de caso y de proyectos, los incidentes críticos, la gamificación, los juegos de rol o el libro del residente. Destacamos las competencias que cada una de ellas ayudan a adquirir. Dedicamos un apartado a las actividades profesionales confiables (APROC) o entrustable professional activities (EPAs), por tratarse de un enfoque metodológico operativo que facilita la puesta en práctica de la formación y evaluación basada en competencias a través de tareas o actividades complejas. La combinación de metodologías complementarias con las actividades clínicas completa el mapa para adquirir las competencias requeridas en los programas de formación especializada. De este modo, se pretende ayudar al formador a planificar la formación del residente de acuerdo a su perfil competencial


The resident's learning is developed through the work in different settings such as: the hospital ward, the primary health center, the operating room, the participation in congresses or in committees, etc. Even so, this performance has to be complemented with methodologies that involve specific activities to develop those competencies that cannot be worked on a day-to-day basis (critical thinking, cooperative work, emotion management, etc.). We present other methodologies aimed to achieve those competencies, such as problem-based learning, the projects method, the case method, and the critical incidents, gamification, role-playing games or the resident's logbook, highlighting the competencies that each of them help to acquire. We dedicate a section to entrustable professional activities (EPAs), an operational methodological approach that facilitates the implementation of competency-based medical education and evaluation through clinical activities. The combination of complementary methodologies with clinical activities completes the map to acquire the competencies required in specialized training and guide the tutor in order to plan the training of the specialist


Asunto(s)
Humanos , Educación Continua , Aprendizaje , Educación de Postgrado en Medicina/normas , Competencia Profesional/normas , Internado y Residencia , Aprendizaje Basado en Problemas/métodos , Autoaprendizaje como Asunto , Profesionalismo
19.
Am J Psychiatry ; 177(9): 834-843, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32539527

RESUMEN

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Cerebro , Neuroimagen/métodos , Trastorno Obsesivo Compulsivo , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Cerebro/diagnóstico por imagen , Cerebro/patología , Cerebro/fisiopatología , Niño , Femenino , Desarrollo Humano/fisiología , Humanos , Masculino , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/fisiopatología , Trastorno Obsesivo Compulsivo/psicología , Tamaño de los Órganos , Psicopatología , Informe de Investigación , Análisis de Sistemas
20.
Eur Child Adolesc Psychiatry ; 29(12): 1705-1716, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32052174

RESUMEN

We analysed the familial aggregation (familiality) of cognitive dimensions and explored their role as liability markers for early-onset bipolar disorder (EOBD). The sample comprised 99 subjects from 26 families, each with an offspring diagnosed with EOBD. Four cognitive dimensions were assessed: reasoning skills; attention and working memory; memory; and executive functions. Their familiality was investigated in the total sample and in a subset of healthy relatives. The intra-family resemblance score (IRS), a family-based index of the similarity of cognitive performance among family members, was calculated. Familiality was detected for the attention and working memory (AW) dimension in the total sample (ICC = 0.37, p = 0.0004) and in the subsample of healthy relatives (ICC = 0.37, p = 0.016). The IRS reflected that there are families with similar AW mean scores (either high or low) and families with heterogeneous scores. Families with the most common background for the AW dimension (IRS > 0) were selected and dichotomized in two groups according to the mean family AW score. This allowed differentiating families whose members had similar high scores than those with similar low scores: both patients (t = - 4.82, p = 0.0005) and relatives (t = - 5.04, p < 0.0001) of the two groups differed in their AW scores. AW dimension showed familial aggregation, suggesting its putative role as a familial vulnerability marker for EOBD. The IRS estimation allowed the identification of families with homogeneous scores for this dimension. This represents a first step towards the investigation of the underlying mechanisms of AW dimension and the identification of etiological subgroups.


Asunto(s)
Trastorno Bipolar/psicología , Cognición/fisiología , Familia/psicología , Adolescente , Femenino , Humanos , Masculino , Persona de Mediana Edad
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