Delineating disorder-general and disorder-specific dimensions of psychopathology from functional brain networks in a developmental clinical sample

The interplay between functional brain network maturation and psychopathology during development remains elusive. To establish the structure of psychopathology and its neurobiological mechanisms, mapping of both shared and unique functional connectivity patterns across developmental clinical populations is needed. We investigated shared associations between resting-state functional connectivity and psychopathology in children and adolescents aged 5–21 (n =1689). Specifically, we used partial least squares (PLS) to identify latent variables (LV) between connectivity and both symptom scores and diagnostic information. We also investigated associations between connectivity and each diagnosis specifically, controlling for other diagnosis categories. PLS identified five significant LVs between connectivity and symptoms, mapping onto the psychopathology hierarchy. The first LV resembled a general psychopathology factor, followed by dimensions of internalising- externalising, neurodevelopment, somatic complaints, and thought problems. Another PLS with diagnostic data revealed one significant LV, resembling a cross-diagnostic case-control pattern. The diagnosis-specific PLS identified a unique connectivity pattern for autism spectrum disorder (ASD). All LVs were associated with distinct patterns of functional connectivity. These dimensions largely replicated in an independent sample (n = 420) from the same dataset, as well as to an independent cohort (n =3504). This suggests that covariance in developmental functional brain networks supports transdiagnostic dimensions of psychopathology.publishedVersio

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Shared pattern of impaired social communication and cognitive ability in the youth brain across diagnostic boundaries

Background Abnormalities in brain structure are shared across diagnostic categories. Given the high rate of comorbidity, the interplay of relevant behavioural factors may also cross these classic boundaries. Methods We aimed to detect brain-based dimensions of behavioural factors using canonical correlation and independent component analysis in a clinical youth sample (n = 1732, 64 % male, age: 5–21 years). Results We identified two correlated patterns of brain structure and behavioural factors. The first mode reflected physical and cognitive maturation (r = 0.92, p = .005). The second mode reflected lower cognitive ability, poorer social skills, and psychological difficulties (r = 0.92, p = .006). Elevated scores on the second mode were a common feature across all diagnostic boundaries and linked to the number of comorbid diagnoses independently of age. Critically, this brain pattern predicted normative cognitive deviations in an independent population-based sample (n = 1253, 54 % female, age: 8–21 years), supporting the generalisability and external validity of the reported brain-behaviour relationships. Conclusions These results reveal dimensions of brain-behaviour associations across diagnostic boundaries, highlighting potent disorder-general patterns as the most prominent. In addition to providing biologically informed patterns of relevant behavioural factors for mental illness, this contributes to a growing body of evidence in favour of transdiagnostic approaches to prevention and intervention.publishedVersio

Reaction Time Variability in Children Is Specifically Associated With Attention Problems and Regional White Matter Microstructure

Background Increased intraindividual variability (IIV) in reaction times (RTs) has been suggested as a key cognitive and behavioral marker of attention problems, but findings for other dimensions of psychopathology are less consistent. Moreover, while studies have linked IIV to brain white matter microstructure, large studies testing the robustness of these associations are needed. Methods We used data from the Adolescent Brain Cognitive Development (ABCD) Study baseline assessment to test the associations between IIV and psychopathology (n = 8622, age = 8.9–11.1 years) and IIV and white matter microstructure (n = 7958, age = 8.9–11.1 years). IIV was investigated using an ex-Gaussian distribution analysis of RTs in correct response go trials in the stop signal task. Psychopathology was measured by the Child Behavior Checklist and a bifactor structural equation model was performed to extract a general p factor and specific factors reflecting internalizing, externalizing, and attention problems. To investigate white matter microstructure, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were examined in 23 atlas-based tracts. Results Increased IIV in both short and long RTs was positively associated with the specific attention problems factor (Cohen’s d = 0.13 and d = 0.15, respectively). Increased IIV in long RTs was also positively associated with radial diffusivity in the left and right corticospinal tract (both tracts, d = 0.12). Conclusions Using a large sample and a data-driven dimensional approach to psychopathology, the results provide novel evidence for a small but specific association between IIV and attention problems in children and support previous findings on the relevance of white matter microstructure for IIV.publishedVersio

Recommendations for a better understanding of sex and gender in neuroscience of mental health

There are prominent sex/gender differences in the prevalence, expression and lifespan course of mental health and neurodiverse conditions. Yet the underlying sex and gender related mechanisms and their interactions are still not fully understood. This lack of knowledge has harmful consequences for those suffering from mental health problems. Hence, we set up a co-creation session in a one week workshop with a multidisciplinary team of 25 researchers, clinicians and policy makers, to identify the main barriers in sex and gender research in neuroscience of mental health. Based on this work, we here provide recommendations for methodologies, translational research and stakeholder involvement. These include guidelines for recording, reporting, analysis beyond binary groups, and open science. Improved understanding of sex and gender related mechanisms in neuroscience may benefit public health as this is an important step towards precision medicine and may function as an archetype for studying diversity

Lexical access speed and the development of phonological recoding during immediate serial recall

A recent Registered Replication Report (RRR) of the development of verbal rehearsal during serial recall revealed that children verbalized at younger ages than previously thought, but did not identify sources of individual differences. Here, we use mediation analysis to reanalyze data from the 934 children ranging from 5 to 10 years old from the RRR for that purpose. From ages 5 to 7, the time taken for a child to label pictures (i.e. isolated naming speed) predicted the child’s spontaneous use of labels during a visually presented serial reconstruction task, despite no need for spoken responses. For 6- and 7-year-olds, isolated naming speed also predicted recall. The degree to which verbalization mediated the relation between isolated naming speed and recall changed across development. All relations dissipated by age 10. The same general pattern was observed in an exploratory analysis of delayed recall for which greater demands are placed on rehearsal for item maintenance. Overall, our findings suggest that spontaneous phonological recoding during a standard short-term memory task emerges around age 5, increases in efficiency during the early elementary school years, and is sufficiently automatic by age 10 to support immediate serial recall in most children. Moreover, the findings highlight the need to distinguish between phonological recoding and rehearsal in developmental studies of short-term memory

Lexical access speed and the development of phonological recoding during immediate serial recall

A recent Registered Replication Report (RRR) of the development of verbal rehearsal during serial recall revealed that children verbalized at younger ages than previously thought, but did not identify sources of individual differences. Here, we use mediation analysis to reanalyze data from the 934 children ranging from 5 to 10 years old from the RRR for that purpose. From ages 5 to 7, the time taken for a child to label pictures (i.e. isolated naming speed) predicted the child’s spontaneous use of labels during a visually presented serial reconstruction task, despite no need for spoken responses. For 6- and 7-year-olds, isolated naming speed also predicted recall. The degree to which verbalization mediated the relation between isolated naming speed and recall changed across development. All relations dissipated by age 10. The same general pattern was observed in an exploratory analysis of delayed recall for which greater demands are placed on rehearsal for item maintenance. Overall, our findings suggest that spontaneous phonological recoding during a standard short-term memory task emerges around age 5, increases in efficiency during the early elementary school years, and is sufficiently automatic by age 10 to support immediate serial recall in most children. Moreover, the findings highlight the need to distinguish between phonological recoding and rehearsal in developmental studies of short-term memory

Elevated visual dependency in young adults after chemotherapy in childhood

Chemotherapy in childhood can result in long-term neurophysiological side-effects, which could extend to visual processing, specifically the degree to which a person relies on vision to determine vertical and horizontal (visual dependency). We investigated whether adults treated with chemotherapy in childhood experience elevated visual dependency compared to controls and whether any difference is associated with the age at which subjects were treated. Visual dependency was measured in 23 subjects (mean age 25.3 years) treated in childhood with chemotherapy (CTS) for malignant, solid, non-CNS tumors. We also stratified CTS into two groups: those treated before 12 years of age and those treated from 12 years of age and older. Results were compared to 25 healthy, age-matched controls. The subjective visual horizontal (SVH) and vertical (SVV) orientations was recorded by having subjects position an illuminated rod to their perceived horizontal and vertical with and without a surrounding frame tilted clockwise and counter-clockwise 20° from vertical. There was no significant difference in rod accuracy between any CTS groups and controls without a frame. However, when assessing visual dependency using a frame, CTS in general (p = 0.006) and especially CTS treated before 12 years of age (p = 0.001) tilted the rod significantly further in the direction of the frame compared to controls. Our findings suggest that chemotherapy treatment before 12 years of age is associated with elevated visual dependency compared to controls, implying a visual bias during spatial activities. Clinicians should be aware of symptoms such as visual vertigo in adults treated with chemotherapy in childhood

Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk

Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed psychosis later (CHR-PS+) from healthy controls (HCs) that can differentiate each other. We also evaluated whether we could distinguish CHR-PS+ individuals from those who did not develop psychosis later (CHR-PS-) and those with uncertain follow-up status (CHR-UNK). T1-weighted structural brain MRI scans from 1165 individuals at CHR (CHR-PS+, n = 144; CHR-PS-, n = 793; and CHR-UNK, n = 228), and 1029 HCs, were obtained from 21 sites. We used ComBat to harmonize measures of subcortical volume, cortical thickness and surface area data and corrected for non-linear effects of age and sex using a general additive model. CHR-PS+ (n = 120) and HC (n = 799) data from 20 sites served as a training dataset, which we used to build a classifier. The remaining samples were used external validation datasets to evaluate classifier performance (test, independent confirmatory, and independent group [CHR-PS- and CHR-UNK] datasets). The accuracy of the classifier on the training and independent confirmatory datasets was 85% and 73% respectively. Regional cortical surface area measures-including those from the right superior frontal, right superior temporal, and bilateral insular cortices strongly contributed to classifying CHR-PS+ from HC. CHR-PS- and CHR-UNK individuals were more likely to be classified as HC compared to CHR-PS+ (classification rate to HC: CHR-PS+, 30%; CHR-PS-, 73%; CHR-UNK, 80%). We used multisite sMRI to train a classifier to predict psychosis onset in CHR individuals, and it showed promise predicting CHR-PS+ in an independent sample. The results suggest that when considering adolescent brain development, baseline MRI scans for CHR individuals may be helpful to identify their prognosis. Future prospective studies are required about whether the classifier could be actually helpful in the clinical settings.</p

Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis.

Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation