Replicability of structural brain alterations associated with general psychopathology: evidence from a population-representative birth cohort.
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ABSTRACT:
SUBMITTER: Romer AL
PROVIDER: S-EPMC7266702 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Network analysis is quickly gaining popularity in psychopathology research as a method that aims to reveal causal relationships among individual symptoms. To date, 4 main types of psychopathology networks have been proposed: (a) association networks, (b) regularized concentration networks, (c) relative importance networks, and (d) directed acyclic graphs. The authors examined the replicability of these analyses based on symptoms of major depression and generalized anxiety between and within 2 highly similar epidemiological samples (i.e., the National Comorbidity Survey-Replication [n = 9282] and the National Survey of Mental Health and Wellbeing [n = 8841]). Although association networks were stable, the 3 other types of network analysis (i.e., the conditional independence networks) had poor replicability between and within methods and samples. The detailed aspects of the models-such as the estimation of specific edges and the centrality of individual nodes-were particularly unstable. For example, 44% of the symptoms were estimated as the "most influential" on at least 1 centrality index across the 6 conditional independence networks in the full samples, and only 13-21% of the edges were consistently estimated across these networks. One of the likely reasons for the instability of the networks is the predominance of measurement error in the assessment of individual symptoms. The authors discuss the implications of these findings for the growing field of psychopathology network research, and conclude that novel results originating from psychopathology networks should be held to higher standards of evidence before they are ready for dissemination or implementation in the field. (PsycINFO Database Record
| S-EPMC5749927 | biostudies-literature
Project description:BackgroundA general psychopathology 'p' factor captures shared variance across mental disorders in diverse samples and may partly reflect executive dysfunction. Higher p factor scores have been related to structural alterations within the visual association cortex (VAC) and a cerebello-thalamo-cerebrocortical circuit (CTCC), both of which are important for executive control. Here, we tested replicability of these direct associations as well as the indirect role of executive functioning in a sample of healthy and cross-diagnostic adult patients.MethodsWe conducted hypothesis-driven (i.e., region-of-interest) and exploratory whole-brain structural neuroimaging analyses using data from the Consortium for Neuropsychiatric Phenomics study of 272 adults who met diagnostic criteria for schizophrenia, bipolar disorder, or attention deficit-hyperactivity disorder or were healthy controls. Using structural equation modeling, we examined direct and indirect relations between structural neural alterations (within regions-of-interest and regions identified from exploratory analyses) and p and executive function factors.ResultsHigher levels of p were associated with decreased executive functioning and VAC grey matter volume, replicating previous research. In contrast, we failed to replicate prior negative relations between the p factor and CTCC structure. A significant indirect relation between VAC grey matter volume and p via executive function also emerged. Whole-brain analyses identified additional structural alterations in supplementary motor area/cingulate cortex, anterior corona radiata, and corpus callosum genu related to the p factor.ConclusionsExecutive dysfunction may be one mechanism underlying relations between brain structure and general psychopathology. Replication of VAC structural alterations related to p encourages further focus on this brain structure.
| S-EPMC8896812 | biostudies-literature
Project description:Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19-20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior corpus callosum/thalamus/fornix and GM volume in temporal gyri bilaterally, accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These results reveal that VPT birth continues to be associated with altered structural brain anatomy in early adult life, although it remains to be ascertained whether these changes reflect neurodevelopmental delays or long lasting structural alterations due to prematurity. GM and WM alterations correlate with length of gestation and mediate cognitive outcome.
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Project description:Toxoplasma gondii (T. gondii) is a protozoan parasite present in around a third of the human population. Infected individuals are commonly asymptomatic, though recent reports have suggested that infection might influence aspects of the host's behavior. In particular, Toxoplasma infection has been linked to schizophrenia, suicide attempt, differences in aspects of personality and poorer neurocognitive performance. However, these studies are often conducted in clinical samples or convenience samples.In a population-representative birth-cohort of individuals tested for presence of antibodies to T. gondii (N = 837) we investigated the association between infection and four facets of human behavior: neuropsychiatric disorder (schizophrenia and major depression), poor impulse control (suicidal behavior and criminality), personality, and neurocognitive performance. Suicide attempt was marginally more frequent among individuals with T. gondii seropositivity (p = .06). Seropositive individuals also performed worse on one out of 14 measures of neuropsychological function.On the whole, there was little evidence that T. gondii was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations or neurocognitive impairment.
| S-EPMC4757034 | biostudies-other
Project description:Pairwise Markov random field networks-including Gaussian graphical models (GGMs) and Ising models-have become the "state-of-the-art" method for psychopathology network analyses. Recent research has focused on the reliability and replicability of these networks. In the present study, we compared the existing suite of methods for maximizing and quantifying the stability and consistency of PMRF networks (i.e., lasso regularization, plus the bootnet and NetworkComparisonTest packages in R) with a set of metrics for directly comparing the detailed network characteristics interpreted in the literature (e.g., the presence, absence, sign, and strength of each individual edge). We compared GGMs of depression and anxiety symptoms in two waves of data from an observational study (n = 403) and reanalyzed four posttraumatic stress disorder GGMs from a recent study of network replicability. Taken on face value, the existing suite of methods indicated that overall the network edges were stable, interpretable, and consistent between networks, but the direct metrics of replication indicated that this was not the case (e.g., 39-49% of the edges in each network were unreplicated across the pairwise comparisons). We discuss reasons for these apparently contradictory results (e.g., relying on global summary statistics versus examining the detailed characteristics interpreted in the literature) and conclude that the limited reliability of the detailed characteristics of networks observed here is likely to be common in practice, but overlooked by current methods. Poor replicability underpins our concern surrounding the use of these methods, given that generalizable conclusions are fundamental to the utility of their results.
| S-EPMC6883148 | biostudies-literature
Project description:BackgroundAn emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging.MethodsThis study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area.ResultsHigher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents.ConclusionsThe current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.
| S-EPMC8885925 | biostudies-literature
Project description:Psychiatric taxonomists have sometimes argued for a unitary psychosis syndrome and sometimes for a pentagonal model, including 5 diagnostic constructs of positive symptoms, negative symptoms, cognitive disorganization, mania, and depression. This continues to be debated in preparation for impending revisions of the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases. We aimed to identify general and specific dimensions underlying psychopathological features of psychosis.The samples comprised 309 patients admitted to psychiatric services in the acute phase of their first or second episode of psychosis and 507 patients with enduring psychosis recruited from community mental health teams. Patients' symptoms were assessed on the Positive and Negative Symptom Scale. Analyses compared unitary, pentagonal, and bifactor models of psychosis.In both samples, a bifactor model including 1 general psychosis factor and, independently, 5 specific factors of positive symptoms, negative symptoms, disorganization, mania, and depression gave the best fit. Scores of general and specific symptom dimensions were differentially associated with phase of illness, diagnosis, social functioning, insight, and neurocognitive functioning.The findings provide strong evidence for a general psychosis dimension in both early and enduring psychosis. Findings further allowed for independent formation of specific symptom dimensions. This may inform the current debate about revised classification systems of psychosis.
| S-EPMC3686436 | biostudies-literature
Project description:BackgroundStudies with behavioural and neuropsychological tests have supported the developmental taxonomy theory of antisocial behaviour, which specifies abnormal brain development as a fundamental aspect of life-course-persistent antisocial behaviour, but no study has characterised features of brain structure associated with life-course-persistent versus adolescence-limited trajectories, as defined by prospective data. We aimed to determine whether life-course-persistent antisocial behaviour is associated with neurocognitive abnormalities by testing the hypothesis that it is also associated with brain structure abnormalities.MethodsWe used structural MRI data collected at 45 years of age from participants in the Dunedin Study, a population-representative longitudinal birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand, who were resident in the province and who participated in the first assessment at 3 years of age. Participants underwent MRI, and mean global cortical surface area and cortical thickness were extracted for each participant. Participants had been previously subtyped as exhibiting life-course-persistent, adolescence-limited, or no history of persistent antisocial behaviour (ie, a low trajectory group) based on informant-reported and self-reported conduct problems from the ages of 7 years to 26 years. Study personnel who processed the MRI images were masked to antisocial group membership. We used linear estimated ordinary least squares regressions to compare each antisocial trajectory group (life-course persistent and adolescence limited) with the low trajectory group to examine whether antisocial behaviour was related to abnormalities in mean global surface area and mean cortical thickness. Next, we used parcel-wise linear regressions to identify antisocial trajectory group differences in surface area and cortical thickness. All results were controlled for sex and false discovery rate corrected.FindingsData from 672 participants were analysed, and 80 (12%) were classified as having life-course-persistent antisocial behaviour, 151 (23%) as having adolescence-limited antisocial behaviour, and 441 (66%) as having low antisocial behaviour. Individuals on the life-course-persistent trajectory had a smaller mean surface area (standardised β=-0·18 [95% CI -0·24 to -0·11]; p<0·0001) and lower mean cortical thickness (standardised β=-0·10 [95% CI -0·19 to -0·02]; p=0·020) than did those in the low group. Compared with the low group, the life-course-persistent group had reduced surface area in 282 of 360 anatomically defined parcels and thinner cortex in 11 of 360 parcels encompassing circumscribed frontal and temporal regions associated with executive function, affect regulation, and motivation. Widespread differences in brain surface morphometry were not observed for the adolescence-limited group compared with either non-antisocial behaviour or life-course-persistent groups.InterpretationThese analyses provide initial evidence that differences in brain surface morphometry are associated with life-course-persistent, but not adolescence-limited, antisocial behaviour. As such, the analyses are consistent with the developmental taxonomy theory of antisocial behaviour and highlight the importance of using prospective longitudinal data to define different patterns of antisocial behaviour development.FundingUS National Institute on Aging, Health Research Council of New Zealand, New Zealand Ministry of Business, Innovation and Employment, UK Medical Research Council, Avielle Foundation, and Wellcome Trust.
| S-EPMC7033555 | biostudies-literature
Project description:Objectives: Although cross-sectional investigations have found a bifactor structure of psychiatric comorbidity that includes a general psychopathology factor plus more specific factors, prospective evidence supporting the bifactor structure is still limited. We evaluated the structural stability (i.e., longitudinal invariance) of the bifactor model in comparison to an alternative structure, a correlated factors model without a general psychopathology factor. We also investigated the models' generalizability to change processes in psychopathology. Methods: The analyses were conducted on 10-year follow-up data from 5,001 respondents in the US National Comorbidity Survey. Invariance was evaluated through a series of nested invariance tests using confirmatory factor analysis, and the models' generalizability to change processes was investigated using change scores of disorder status. Results: The bifactor model and the correlated factors model exhibited an equal degree of strong structural stability over time. Only the bifactor model satisfactorily characterized the structure of temporal changes in psychopathology. Conclusions: The bifactor structure with a general psychopathology factor is stable over time and describes temporal changes in psychopathology. The findings support the notion that the general psychopathology factor describes a transdiagnostic etiology and may therefore provide a useful target for intervention and treatment.
| S-EPMC6728891 | biostudies-literature
Project description:All subjects were recruited at Centennial Women?s Hospital and the Perinatal Research Center in Nashville, TN beginning in 2003. Pregnant women were enrolled during their first clinical visit after obtaining informed consent as described previously. Demographic and clinical data specific to the fetus was collected from clinical records. Gestational age of the neonate was determined by maternal reporting of the last menstrual period and corroboration by ultrasound dating. Accurate knowledge of gestational age (GA) is essential for proper monitoring and care of neonates. However, accurate GA measures are often not available. DNA methylation has previously been shown to associate with GA, and has been used to accurately predict chronological age in adults. In the current study, we examine whether DNA methylation in cord blood can be used to predict gestational age at birth. Results: We found that GA can be accurately predicted from DNA methylation of neonatal cord blood and blood spot samples (DNAm GA), using 148 CpG sites selected through elastic net regression in six training datasets (N=207). We evaluated predictive accuracy in six testing datasets (N=1,202), and found that the accuracy of DNAm GA meets or exceeds accuracy of gestational age estimates based on established methods. We also found an increased DNAm GA, relative to clinical GA, was associated with increased birthweight percentile (p=.00057), adjusting for GA, sex, and ancestry, suggesting that DNAm GA could represent developmental age more accurately than clinical estimates of GA. Conclusions: Further development of this predictor could provide a method of accurate neonatal estimation of GA for use in resource-limited populations, or in cases where GA cannot be estimated clinically. When clinical estimates are available, the predictor can be used to test hypotheses related to developmental age and other early life circumstances, and may provide increased accuracy beyond clinical estimates.
2016-03-11 | GSE79056 | GEO