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Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study.

ABSTRACT: BACKGROUND:Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder (and other mental disorders), highlighting the importance of identifying neural correlates of childhood PLEs. Three major cortical networks-the cingulo-opercular network (CON), default mode network (DMN), and frontoparietal network-are consistently implicated in psychosis and PLEs in adults. However, it is unclear whether variation in functional connectivity is associated with PLEs in school-aged children. METHODS:Using hierarchical linear models, we examined the relationships between childhood PLEs and resting-state functional connectivity of the CON, DMN, and frontoparietal network, as well as the other networks, using an a priori network parcellation, using data from 9- to 11-year-olds (n = 3434) in the ABCD (Adolescent Brain Cognitive Development) study. We examined within-network, between-network, and subcortical connectivity. RESULTS:Decreased CON and DMN connectivity, as well as cinguloparietal (CPAR) network connectivity, were associated with greater PLEs, even after accounting for family history of psychotic disorders, internalizing symptoms, and cognitive performance. Decreased DMN connectivity was more strongly associated with increased delusional ideation, whereas decreased CON connectivity was more strongly associated with increased perceptual distortions. Increased CON-cerebellar and decreased CPAR-cerebellar connectivity were also associated with increased PLEs, and CPAR-cerebellar connectivity was more strongly associated with increased perceptual distortions. CONCLUSIONS:Consistent with hypotheses about the dimensionality of psychosis, our results provide novel evidence that neural correlates of PLEs, such as reduced functional connectivity of higher-order cognitive networks, are present even in school-aged children. The results provide further validation for continuity of PLEs across the life span.

SUBMITTER: Karcher NR

PROVIDER: S-EPMC6588441 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study.

Karcher Nicole R NR O'Brien Kathleen J KJ Kandala Sridhar S Barch Deanna M DM

Biological psychiatry 20190126 1

<h4>Background</h4>Psychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder (and other mental disorders), highlighting the importance of identifying neural correlates of childhood PLEs. Three major cortical networks-the cingulo-opercular network (CON), default mode network (DMN), and frontoparietal network-are consistently implicated in psychosis and PLEs in adults. However, it is unclear whether variation in functional connectivity i ...[more]

PMID: 30850130

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Project description:The fields of psychology and psychiatry are increasingly recognizing the importance of replication efforts. The current study aimed to replicate previous findings examining the construct validity and psychometric properties of a psychotic-like experiences (PLEs) measure in middle childhood using an independent subset of the baseline Adolescent Brain Cognitive Development (ABCD) sample. Using a remainder baseline sample of 7013 nine- to eleven-year-old children with complete data, we examined measurement invariance across race/ethnicity and sex, and examined the associations between the Prodromal Questionnaire Brief-Child Version (PQ-BC) and other measures of PLEs, internalizing symptoms, neuropsychological test performance, and developmental milestones, to determine whether previously obtained results replicated in this nonoverlapping baseline sample subset. The results replicated measurement invariance across ethnicity and sex, and analyses again found higher PQ-BC scores for African American (β = .364, 95% CI = 0.292, 0.435) and Hispanic (β = .255, 95% CI = 0.185, 0.324) groups. We also replicated that higher PQ-BC scores were associated with psychosis risk measures, higher rates of child-reported internalizing symptoms (Distress: β = .378, 95% CI = 0.357,0.398), neuropsychological test performance deficits (eg, working memory; Distress: β = -.069, 95% CI = -0.096, -0.042), and motor (Distress: β = .026, 95% CI = 0.003, 0.049) and speech (Distress: β = .042, 95% CI = 0.018, 0.065) developmental milestone delays. The current results replicated many findings from the original study examining the PQ-BC. We replicated evidence for mean differences in race/ethnicity, and associations with other PLE measures, greater internalizing symptoms, cognitive impairments, and developmental milestone delays. These findings indicate robust and reliable associations between PLEs and hypothesized correlates can be found in middle childhood nonclinical samples.

Project description:BackgroundChildhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms.MethodsAdolescent Brain Cognitive Development Study baseline data from children with European ancestry (n = 4650, ages 9-10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models.ResultsTotal and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s = 0.202%-0.660%; false discovery rate-corrected ps < .006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2 = 0.120%-0.216%; false discovery rate-corrected ps < .03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated = 3.33%-32.22%).ConclusionsTotal and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.

Project description:IMPORTANCE:Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE:To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS:A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES:Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS:Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R?=?-.523, P?=?.01), dysphoria (R?=?-.455, P?=?.05), and lassitude (R?=?-.449, P?=?.05) and was positively correlated with well-being (R?=?.470, P?=?.03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE:Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

Project description:BackgroundPreviously, a study using a sample of the Adolescent Brain Cognitive Development (ABCD)® study from the earlier 1.0 release found differences in several resting state functional MRI (rsfMRI) brain connectivity measures associated with children reporting anhedonia. Here, we aim to reproduce, replicate, and extend the previous findings using data from the later ABCD study 4.0 release, which includes a significantly larger sample.MethodsTo reproduce and replicate the previous authors' findings, we analyzed data from the ABCD 1.0 release (n = 2437), from an independent subsample from the newer ABCD 4.0 release (excluding individuals from the 1.0 release) (n = 6456), and from the full ABCD 4.0 release sample (n = 8866). Additionally, we assessed whether using a multiple linear regression approach could improve replicability by controlling for the effects of comorbid psychiatric conditions and sociodemographic covariates.ResultsWhile the previously reported associations were reproducible, effect sizes for most rsfMRI measures were drastically reduced in replication analyses (including for both t-tests and multiple linear regressions) using the ABCD 4.0 (excluding 1.0) sample. However, 2 new rsfMRI measures (the Auditory vs. Right Putamen and the Retrosplenial-Temporal vs. Right-Thalamus-Proper measures) exhibited replicable associations with anhedonia and stable, albeit small, effect sizes across the ABCD samples, even after accounting for sociodemographic covariates and comorbid psychiatric conditions using a multiple linear regression approach.ConclusionThe most statistically significant associations between anhedonia and rsfMRI connectivity measures found in the ABCD 1.0 sample tended to be non-replicable and inflated. Contrastingly, replicable associations exhibited smaller effects with less statistical significance in the ABCD 1.0 sample. Multiple linear regressions helped assess the specificity of these findings and control the effects of confounding covariates.

Dataset Information

Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study.

Publications

Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study.

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