Biology subjects

Miguel, E. C.

Publications and source records attributed to Miguel, E. C..

4 recordsLinked to original sources

bioRxiv2023

Hippocampal and amygdala subfield volumes in obsessive-compulsive disorder differ according to medication status.

IntroAlthough it has been suggested that the hippocampus and amygdala (HA) are involved in the neurobiology of obsessive-compulsive disorder (OCD), volumetric findings have been inconsistent. Furthermore, the HA consist of heterogenous anatomic units with specific functions and cytoarchitecture, and little work has been undertaken on the volumetry of these subfields in OCD. MethodsT1-weighted images from 381 patients with OCD and 338 healthy controls (HCs) from the OCD Brain Imaging Consortium were segmented to produce twelve hippocampal subfields and nine amygdala subfields using FreeSurfer 6.0. We assessed between-group differences in subfield volume using a mixed-effects model adjusted for age, quadratic effects of age, sex, site, and whole HA volume. Given evidence of confounding effects of clinical characteristics on brain volumes in OCD, we also performed subgroup analyses to examine subfield volume in relation to comorbid anxiety and depression, medication status, and symptom severity. ResultsPatients with OCD and HCs did not significantly differ in HA subfield volume. However, medicated patients with OCD had significantly smaller hippocampal dentate gyrus (pFDR=0.042, d=-0.26) and molecular layer (pFDR=0.042, d=-0.29) and larger lateral (pFDR=0.049, d=0.23) and basal (pFDR=0.049, d=0.25) amygdala subfields than HCs. Unmedicated patients had significantly smaller hippocampal CA1 (pFDR=0.016, d=-0.28) than HCs. No association was detected between any subfield volume and OCD severity. ConclusionDifferences in HA subfields between OCD and HCs are dependent on medication status, in line with previous work on other brain volumetric alterations in OCD. This emphasizes the importance of considering psychotropic medication in neuroimaging studies of OCD.

neuroscience↗

bioRxiv2020

Cognitive performance in children and adolescents at high-risk for obsessive-compulsive disorder

BackgroundCognitive performance has been studied in subclinical obsessive-compulsive (OC) adults and in adults relatives of OCD patients. Meanwhile, no study has been conducted with children under the same conditions. Across a sample with 49 participants, we investigated whether children and adolescents at high-risk (HR) for OCD (n=18) would present an impaired performance on neurocognitive domains compared to healthy controls (HC, n=31), especially in visuoconstructive ability, executive functions, and intellectual efficiency, functions previously associated with OCD. MethodsFor the HR group, we considered the first-degree children relatives of patients with OCD that present obsessive-compulsive symptoms (OCS), but do not meet diagnostic criteria for OCD. Child psychiatric diagnoses were assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL) by experienced and trained psychologists and OCS were measured by Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). ResultsAlthough we did not find differences in the domains previously hypothesized, a Multivariate Analysis of Variance (MANOVA) revealed impairments in processing speed in HR group (p =0.019; F=3.115), and a t-test identified a higher IQ discrepancy in HR group when compared to HC (p =0.030; t =-2.239), and a discrepancy in verbal and non-verbal abilities as in the memory and working memory tasks. ConclusionsOur results suggest that differences in motor and processing speed and in IQ discrepancy are already present and were identified in a non-clinical sample of HR subjects. Further studies should investigate neurocognitive domains as possible predictors of pediatric OCD.

neuroscience↗

bioRxiv2020

Cross-sectional and longitudinal associations of threat and deprivation on cognition, emotional processing and psychopathology in children and adolescents

BackgroundExposure to childhood adversity has been consistently associated with poor developmental outcomes, but it is unclear whether these associations vary across different forms of adversity. We examined cross-sectional and longitudinal associations between two types of adversity--threat and deprivation--with cognition, emotional processing, and psychopathology in a middle-income country. MethodsThe sample consisted of 2,511 children and adolescents (6-17 years old) from the Brazilian High-Risk Cohort for Psychiatric Disorders. Parent reports on childhood adversity were used to construct threat and deprivation latent constructs. Psychopathology was measured by the CBCL which generated a measure of general psychopathology (the "p" factor). Executive function (EF) and attention orienting toward angry faces were assessed using cognitive tasks. All measures were acquired at two time-points 3-years apart. Cross-lagged panel models were estimated to evaluate longitudinal associations. ResultsPsychopathology was associated with threat and deprivation cross-sectionally, and higher levels of threat and deprivation predicted increases in general psychopathology at follow-up. For EF, worse performance was more strongly associated with deprivation than threat at baseline, and only with deprivation at follow-up. Deprivation was associated with attention orienting away from angry faces cross-sectionally, but neither form of adversity was associated with changes over time in attention bias. ConclusionBoth types of adversity are associated with current and future psychopathology and with current, but not future, EF. Threat was more strongly linked to higher psychopathology, whereas deprivation was more strongly linked to lower EF. Lack of longitudinal associations between deprivation and EF mean reverse causality cannot be excluded.

neuroscience↗

bioRxiv2017

De novo damaging coding mutations are strongly associated with obsessive-compulsive disorder and overlap with autism

Obsessive-compulsive disorder (OCD) is a debilitating developmental neuropsychiatric disorder with a genetic risk component, yet identification of high-confidence risk genes has been challenging. We performed whole-exome sequencing in 222 OCD parent-child trios (184 trios after quality control), finding strong evidence that de novo likely gene disrupting and predicted damaging missense variants contribute to OCD risk. Together, these de novo damaging variants are enriched in OCD probands (RR 1.52, p=0.0005). We identified two high-confidence risk genes, each containing two de novo damaging variants in unrelated probands: CHD8 (Chromodomain Helicase DNA Binding Protein 8) and SCUBE1 (Signal Peptide, CUB Domain And EGF Like Domain Containing 1). Based on our data, we estimate that 34% of de novo damaging variants seen in OCD contribute to risk, and that de novo damaging variants in approximately 335 genes contribute to risk in 22% of OCD cases. Furthermore, genes harboring de novo damaging variants in OCD are enriched for those reported in neurodevelopmental disorders, particularly autism spectrum disorders. An exploratory network analysis reveals significant functional connectivity and enrichment in canonical pathways related to immune response.\n\nSIGNIFICANCE STATEMENTDecades of genetic studies in obsessive-compulsive disorder (OCD) have yet to provide reproducible, statistically significant findings. Following an approach that has led to tremendous success in gene discovery for several neuropsychiatric disorders, here we report findings from DNA whole-exome sequencing of patients with OCD and their parents. We find strong evidence for the contribution of spontaneous, or de novo, predicted-damaging genetic variants to OCD risk, identify two high-confidence risk genes, and detect significant overlap with genes previously identified in autism. These results change the status quo of OCD genetics by identifying novel OCD risk genes, clarifying the genetic landscape of OCD with respect to de novo variation, and suggesting underlying biological pathways that will improve our understanding of OCD biology.

genetics↗