Biology subjects

Arango, C.

Publications and source records attributed to Arango, C..

5 recordsLinked to original sources

bioRxiv2019

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multicentric EU-GEI Case-Control Study

BackgroundThe \"jumping to conclusions\" (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.\n\nMethods817 FEP patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC (assessed by the number of beads drawn on the probabilistic reasoning \"beads\" task) and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.\n\nResultsThe estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia Polygenic Risk Score (SZ PRS) was non-significantly associated with a higher number of beads drawn (B= 0.47, 95% CI -0.21 to 1.16, p=0.17); whereas IQ PRS (B=0.51, 95% CI 0.25 to 0.76, p<0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with higher level of psychotic-like experiences (PLE) in controls, including after controlling for IQ (B= -1.7, 95% CI -2.8 to -0.5, p=0.006), but did not relate to delusions in patients.\n\nConclusionsthe JTC reasoning bias in psychosis is not a specific cognitive deficit but is rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to psychotic-like experiences, independent of IQ. The work has potential to inform interventions targeting cognitive biases in early psychosis.

neuroscience↗

bioRxiv2019

Analyses of rare and common alleles in parent-proband trios implicate rare missense variants in SLC6A1 in schizophrenia and confirm the involvement of loss of function intolerant and neurodevelopmental disorder genes.

Schizophrenia is a highly polygenic disorder with important contributions coming from both common and rare risk alleles, the latter including CNVs and rare coding variants (RCVs), sometimes occurring as de novo variants (DNVs). We performed DNV analysis in whole exome-sequencing data obtained from a new sample of 613 schizophrenia trios, and combined this with published data for a total of 3,444 trios. Loss-of-function (LoF) DNVs were significantly enriched among 3,488 LoF intolerant genes in our new trio data (rate ratio (RR) (95% CI) = 2.23 (1.31, 3.79); p = 2.2 x 10-3), supporting previous findings. In the full dataset, genes associated with neurodevelopmental disorders (NDD; n=160) were significantly enriched for LoF DNVs (RR (95% CI) = 3.32 (2.0, 5.21); p = 7.4 x 10-6). Within this set of NDD genes, SLC6A1, encoding a gamma-aminobutyric acid transporter, was associated with missense-damaging DNVs (p = 5.2 x 10-5). Using data from a subset of 1,122 trios for which we had genome-wide common variant data, schizophrenia polygenic risk was significantly over-transmitted to probands (p = 2.6 x 10-60), as was bipolar disorder common variant polygenic risk (p = 5.7 x 10-17). We defined carriers of candidate schizophrenia-related DNVs as those with LoF or deletion DNVs in LoF intolerant or NDD genes. These individuals had significantly less over-transmission of common risk alleles than non-carriers (p = 3.5 x 10-4), providing robust support for the hypothesis that this set of DNVs is enriched for those related to schizophrenia.

genetics↗

bioRxiv2019

Different Whole-Brain Functional Connectivity Correlates of Reactive-Proactive Aggression and Callous-Unemotional Traits in Disruptive Children and Adolescents

BackgroundDisruptive behavior in children and adolescents can manifest itself in reactive (RA) and proactive (PA) aggression and is modulated by callous-unemotional (CU) traits and comorbidity. Research on aggression subtype-specific neural correlates is limited and the role of comorbid symptoms largely neglected.\n\nMethodsThe current multi-center study extended previous efforts by investigating unrestricted resting state functional connectivity (rsFC) alterations. The large sample (n = 207) of children and adolescents aged 8 - 18 years (mean age = 13.30 {+/-} 2.60 years) included 118 cases with disruptive behavior (80 diagnosed with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptoms were added as covariates. We measured changes in global and local voxel-to-voxel rsFC using functional magnetic resonance imaging at 3T (mean acquisition time = 8 min 25 sec).\n\nResultsCompared to controls, cases demonstrated altered rsFC including frontal areas when anxiety but not ADHD symptoms were considered. Within cases, RA and PA scores related to changes in global and local rsFC in central gyrus and precuneus previously linked to aggression-related impairments. CU trait severity correlated with global rsFC alterations including inferior and middle temporal gyrus implicated in empathy, emotion, and reward-related activity. Importantly, most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety problems were also accounted for.\n\nConclusionsThe current study clarifies that distinct though overlapping brain connectivity measures can disentangle differing manifestations of aggressive behavior. Moreover, our results highlight the importance of considering comorbid symptoms for detecting aggression-related rsFC alterations.

neuroscience↗

bioRxiv2019

Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

BackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.\n\nMethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.\n\nResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohens d = 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.\n\nConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

neuroscience↗

bioRxiv2018

Reactive/proactive aggression specific cortical and subcortical alterations in children and adolescents with disruptive behavior

ObjectiveMaladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated this association in predefined regions of interest.\n\nMethodT1-weighted magnetic resonance images were acquired from 158 children and adolescents with aggressive behavior (ODD/CD) and 96 controls in a multi-centre study. Aggression subtypes were assessed by questionnaires. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models.\n\nResultsIn cases only proactive aggression was negatively associated with amygdala volume (b=-11.82, p=0.05), while reactive aggression was negatively associated with insula volume (b=-46.41, p=0.01). Classical group comparison showed that children and adolescents with aggressive behavior had smaller volumes than controls in (bilateral) ventral striatum (p=0.003), ACC (p=0.01), and vmPFC (p=0.003) with modest effect sizes.\n\nConclusionsAggression was associated with reduced volume in brain regions involved in decision making. Negative associations were found between reactive aggression and volumes in regions involved in threat responsivity and between proactive aggression and regions linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure.

neuroscience↗