I Gotlib

Background Understanding the prenatal origins of children's psychopathology is a fundamental goal in developmental and clinical science. Recent research suggests that inflammation during pregnancy can trigger a cascade of fetal programming changes that contribute to vulnerability for the emergence of psychopathology. Most studies, however, have focused on a handful of proinflammatory cytokines and have not explored a range of prenatal biological pathways that may be involved in increasing postnatal risk for emotional and behavioral difficulties. Methods Using extreme gradient boosted machine learning models, we explored large‐scale proteomics, considering over 1,000 proteins from first trimester blood samples, to predict behavior in early childhood. Mothers reported on their 3‐ to 5‐year‐old children's (N = 89, 51% female) temperament (Child Behavior Questionnaire) and psychopathology (Child …

BackgroundExposure to environmental pollutants early in life has been associated with increased prevalence and severity of depression in adolescents; the neurobiological mechanisms underlying this association are not well understood. In the current longitudinal study, we investigated whether pollution burden in early adolescence (9-13 years) is associated with altered brain activation and connectivity during implicit emotion regulation and with changes in depressive symptoms across adolescence.Methods145 participants (N=87 females; 9-13 years) provided residential addresses, from which we determined their relative pollution burden at the census-tract level, and performed an implicit affective regulation task in the scanner. Participants also completed questionnaires assessing depressive symptoms at three timepoints, each approximately two years apart, from which we calculated within-person slopes of …

Despite evidence that early life adversity (ELA) affects mental health in adolescence, we know little about sex differences in how distinct dimensions of adversity affect development and their corresponding effects on mental health. In this three-wave longitudinal study, 209 participants (118 females; ages 9–13 years at baseline) provided objective (salivary hormones, BMI, age of menarche) and subjective (perceived gonadal and adrenal status) measures of puberty and physical development, and reported on levels of internalizing and externalizing symptoms at all timepoints. Participants also reported lifetime exposure to three distinct types of ELA: deprivation, threat, and unpredictability. Using generalized additive mixed models, we tested within each sex whether dimensions of adversity were associated with longitudinal changes in measures of pubertal and physical development, and whether these indices of …

BackgroundExposure and sensitivity to early life stress (ELS) are related to increased risk for psychopathology in adolescence. While cross-sectional studies have reported blunted nucleus accumbens (NAcc) activation in the context of these associations, researchers have not yet assessed the effects of ELS on developmental trajectories of activation. We examined whether trajectories are affected by stress and the moderating role of biological sex in predicting vulnerability to symptoms of psychopathology.MethodAdolescents (n=173) completed three assessments at two-year intervals across puberty (ages 9-18 years). At baseline we assessed objective ELS and stress sensitivity using the Traumatic Events Screening Inventory for Children. At all timepoints we assessed NAcc activation using the Monetary Incentive Delay task and externalizing, internalizing, and total problems using the Youth Self-Report. We …

Parenting behaviors and neighborhood environment influence the development of adolescents’ brains and behaviors. Simultaneous trajectories of brain and behavior, however, are understudied, especially in these environmental contexts. In this four-wave study spanning 9–18 years of age (N=224 at baseline, N=138 at final assessment) we used longitudinal k-means clustering to identify clusters of participants with distinct trajectories of uncinate fasciculus (UF) fractional anisotropy (FA) and anxiety symptoms; we examined behavioral outcomes and identified environmental factors that predicted cluster membership. We identified three clusters of participants: 1) high UF FA and low symptoms (“low-risk”); 2) low UF FA and high symptoms (“high-risk”); and 3) low UF FA and low symptoms (“resilient”). Adolescents in disadvantaged neighborhoods were more likely to be in the resilient than high-risk cluster if they also …

We recorded directly from the orbital (oPFC) and ventromedial (vmPFC) subregions of the orbitofrontal cortex (OFC) in 22 (9 female, 13 male) epilepsy patients undergoing intracranial electroencephalography (iEEG) monitoring during an experimental task in which the participants judged the accuracy of self-referential autobiographical statements as well as valenced self-judgments. We found significantly increased high-frequency activity (HFA) in about 13% of oPFC sites (10/18 subjects) and 16% of vmPFC sites (4/12 subjects) during both of these self-referential thought processes, with the HFA power being modulated by the content of self-referential stimuli. The location of these activated sites corresponded with the location of fMRI-identified limbic network. Furthermore, the onset of HFA in the vmPFC was significantly earlier than in the oPFC in all patients with simultaneous recordings in both regions. In 11 …

BackgroundDespite evidence that early life stress (ELS) can influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and increase maladaptive behaviors in adolescence, less attention has been paid to the role of the coordinated effects of the two primary adrenal hormones, cortisol and dehydroepiandrosterone (DHEA), in these associations.Methods138 typically developing adolescents (76 females) reported the stressful events experienced during childhood and early adolescence across 30 domains. Two years later we assessed levels of externalizing problems and obtained salivary levels of cortisol and DHEA. Using causal moderated mediation analyses, we examined whether the ratio of cortisol to DHEA (CD ratio) mediates the association between ELS and subsequent externalizing problems.ResultsWe found that ELS is associated with both a lower CD ratio and more externalizing problems …

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a …

The field of developmental psychopathology has grown exponentially over the past decades, and has become increasingly multifaceted. The initial focus on understanding abnormal child psychology has broadened to the study of the origins of psychopathology, with the goals of preventing and alleviating disorder and promoting healthy development. In this paper, we discuss how technological advances and global events have expanded the questions that researchers in developmental psychopathology can address. We do so by describing a longitudinal study that we have been conducting for the past dozen years. We originally planned to examine the effects of early adversity on trajectories of brain development, endocrine function, and depressive symptoms across puberty; it has since become an interdisciplinary study encompassing diverse domains like inflammation, sleep, biological aging, the environment …

Depression is among the most prevalent mental health problems. Previous research indicates that depressive symptoms and cognitive regulation processes are differentially associated with political attitudes. Here we build and test a model based on cognitive aspects of depression that provides an explanation for those differential associations. We test this formulation using a novel survey dataset that includes measures of worry and stress due to the COVID-19 pandemic, cognitive regulation processes, and depression. We posit that rumination mediates the association between depression and self-related political attitudes, whereas negativity bias mediates the association between depression and government-related attitudes. We find considerable support for these claims. Our findings elucidate how depression may influence people's perceptions of politics.

BackgroundThe prenatal environment plays an important and enduring role in children’s development. Exposure to adversity during the prenatal period is associated with children’s cognitive and emotional difficulties; the neurobiological pathways underlying these associations, however, are not yet clear. Given the central role of the nucleus accumbens (NAcc) in reward processing, we examined here whether NAcc volume at age six mediates the relation between prenatal adversity and subsequent attention problems in offspring.Methods333 pregnant mothers (mean age= 30.14±5.24) were recruited as part of the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study. Data assessing maternal mental health and social stress were obtained at the 26th week of pregnancy. At age six, children underwent structural MRI and, at age seven, their mothers completed the Child Behavior Checklist, reporting …

Elevated levels of systemic inflammation are associated with altered reward-related brain function in ventral striatal areas of the brain like the nucleus accumbens (NAcc). In adolescents, cross-sectional research indicates that exposure to early life stress (ELS) can moderate the relation between inflammation and neural activation, which may contribute to atypical reward function; however, no studies have tested whether this moderation by ELS of neuroimmune associations persists over time. Here, we conducted a cross-sectional analysis and the first exploratory longitudinal analysis testing whether cumulative severity of ELS moderates the association of systemic inflammation with reward-related processing in the NAcc in adolescents (n = 104; 58F/46M; M[SD] age = 16.00[1.45] years; range = 13.07–19.86 years). For the cross-sectional analysis, we modeled a statistical interaction between ELS and levels of …

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in …

BackgroundPanic disorder (PD) and agoraphobia (AG) are prevalent and comorbid anxiety disorders. Studies using functional magnetic resonance imaging (fMRI) have identified different patterns of activation in PD/AG patients and healthy controls. However, these studies have often lacked sufficient statistical power and reported inconsistent results. This meta-analysis seeks to advance our understanding of the neural basis of PD and AG by identifying patterns of neural activation across task-based fMRI activation studies of individuals with PD/AG compared to healthy controls.MethodsTwo teams independently searched PubMed, following PRISMA guidelines and using preregistered inclusion criteria, to identify whole-brain, task-based fMRI activation studies that compared participants with PD/AG and healthy controls. We then conducted a meta-analytic comparison of these groups using multilevel kernel density …

Despite the widespread use of the Research Domain Criteria (RDoC) framework in psychiatry and neuroscience, recent studies suggest that the RDoC is insufficiently specific, or excessively broad, relative to the underlying brain circuitry it seeks to elucidate, leading to potential misrepresentation of circuit-function relations. We used a latent variable approach to address this issue, specifically utilizing bifactor analysis. We examined a total of 84 whole-brain task-based fMRI (tfMRI) activation maps from 19 studies with a total of 6,192 participants. Within this set of 84 maps, a curated subset of 37 maps with a balanced representation of RDoC domains constituted the training set of our analysis, and the remaining held-out maps formed the internal validation set. Furthermore, we externally validated the factor solutions from our curated training dataset using an independent set of 36 coordinate maps sourced through Neurosynth. We used RDoC constructs as seed terms for Neurosynth topic meta-analysis. We hypothesized that if boundaries of RDoC domains warrant refinement, this would be indicated by the presence of overlapping domains or domains lacking specificity. Our findings suggest that a bifactor data-driven structure fits better with the current corpus of tfMRI data, with a general domain representing task-general patterns of brain activation. The data-driven model also proposes a different group of major domains, particularly splitting the RDoC cognitive systems domain into distinct domains. Data-driven models are useful for revising the posited circuit-function relations outlined in the current RDoC framework.

Researchers have begun to examine the psychological toll of the ongoing global COVID-19 pandemic. Data are now emerging indicating that there may be long-term adverse effects of the pandemic on new mothers and on children born during this period. In a longitudinal study of maternal mental health and child emotional development during the pandemic, we conducted online assessments of a cohort of women at two time points: when they were pregnant at the beginning of the surge of the pandemic in the United States (baseline, N = 725), and approximately 1 year postpartum (follow-up, N = 296), examining prenatal and postnatal maternal mental health, prenatal pandemic-related stress, and infant temperament. Pandemic-related stress at baseline was associated with concurrent depressive symptoms and infant negative affect at follow-up. Baseline maternal depressive symptoms were associated with follow …

BackgroundNeighborhood- or area-level socioeconomic disadvantage is associated with neural alterations across the life span. However, few studies have examined the effects of neighborhood disadvantage on white matter microstructure during adolescence, an important period of development that coincides with increased risk for psychopathology.MethodsIn 200 adolescents (ages 13–20 years; 54.5% female, 4% nonbinary) recruited from 2 studies enriched for early adversity and depression, we examined whether neighborhood socioeconomic disadvantage derived from census tract data was related to white matter microstructure in several major white matter tracts. We also examined whether depressive symptoms and sex moderated these associations.ResultsGreater neighborhood socioeconomic disadvantage was associated with lower fractional anisotropy (FA) in the left arcuate fasciculus (β = −0.24, false …

ObjectiveNetwork analysis may identify specific symptoms involved in the maintenance and development of psychopathology. This approach, however, has not been applied to the study of young Black children, a population facing unique challenges and developmental risks. It is also unclear whether network analysis identifies early symptoms in Black children that are linked to their longer-term difficulties and strengths in adolescence.MethodsWe conducted a network analysis of emotional and behavioral difficulties in 1238 Black (non-Hispanic) children from the age-3 assessment in the Future of Families and Child Wellbeing Study (47 % female). We also explored whether early childhood symptoms predict subsequent caregiver-reported internalizing and externalizing problems, and youth-reported social competencies and extracurricular and community involvement, at the age-15 assessment.ResultsWe …

BackgroundMajor depressive disorder (MDD) and generalized anxiety disorder (GAD) are highly prevalent and comorbid mental disorders with many shared genotypic and phenotypic features as well as partially overlapping patterns of neural activation. The present meta-analysis seeks to identify statistically robust common and distinct patterns of neural activation in MDD and GDD reported in the primary literature.MethodsWe conducted a comprehensive literature search in PubMed and independent screening by two coding teams using preregistered inclusion criteria and PRISMA guidelines to identify primary fMRI activation studies comparing participants diagnosed with MDD or GAD to age-matched healthy controls using a voxelwise, whole-brain approach. We then used multilevel kernel density analysis (MKDA) with ensemble thresholding (p<. 05–. 0001; FWE-corrected) and correction for multiple …

IntroductionParenting behaviors are formative to the psychological development of young people; however, parent and adolescent perceptions of parenting are only moderately correlated with each other. Whereas discrepant perceptions may represent a normative process of deindividuation from caregivers in some adolescents, in others a discrepancy might predict psychological maladjustment. The biological sensitivity to context model provides a framework from which individual differences in development can be estimated in adolescents whose perceptions of parenting diverge from those of their parents.MethodsAt baseline we obtained diurnal cortisol samples from US adolescents (M = 13.37 years of age, SD = 1.06) as well as parents' and adolescents’ ratings of parental warmth; we obtained adolescent-reported symptoms of psychopathology at baseline and again at follow-up two years later (N = 108, 57.5 …

Dried blood spots (DBS) are biological samples commonly collected from newborns and in geographic areas distanced from laboratory settings for the purposes of disease testing and identification. MicroRNAs (miRNAs)—small non-coding RNAs that regulate gene activity at the post-transcriptional level—are emerging as critical markers and mediators of disease, including cancer, infectious diseases, and mental disorders. This protocol describes optimized procedural steps for utilizing DBS as a reliable source of biological material for obtaining peripheral miRNA expression profiles. We outline key practices, such as the method of DBS rehydration that maximizes RNA extraction yield, and the use of degenerate oligonucleotide adapters to mitigate ligase-dependent biases that are associated with small RNA sequencing. The standardization of miRNA readout from DBS offers numerous benefits: cost …

IntroductionMeta-analyses of functional magnetic resonance imaging (fMRI) studies have been used to elucidate the most reliable neural features associated with various psychiatric disorders. However, it has not been well-established whether each of these neural features is linked to a specific disorder or is transdiagnostic across multiple disorders and disorder categories, including mood, anxiety, and anxiety-related disorders.ObjectivesThis project aims to advance our understanding of the disorder-specific and transdiagnostic neural features associated with mood, anxiety, and anxiety-related disorders as well as to refine the methodology used to compare multiple disorders.MethodsWe conducted an exhaustive PubMed literature search followed by double-screening, double-extraction, and cross-checking to identify all whole-brain, case-control fMRI activation studies of mood, anxiety, and anxiety-related …

BackgroundPsychosocial stressors characterized by social threat, such as interpersonal loss and social rejection, are associated with depression in adolescents. Few studies, however, have examined whether social threat affects fronto-cingulate-limbic systems implicated in adolescent depression.MethodsWe assessed lifetime stressor severity across several domains using the Stress and Adversity Inventory (STRAIN) in 57 depressed adolescents (16.15 ± 1.32 years, 34 females), and examined whether the severity of social threat and non-social threat stressors was associated with gray matter volumes (GMVs) in the anterior cingulate cortex (ACC), amygdala, hippocampus, and nucleus accumbens (NAcc). We also examined how lifetime social threat severity and GMVs in these regions related to depressive symptoms at baseline and over 9 months.ResultsGeneral stressor severity was related to greater …

Objectives The aim of the study was to: (1) Identify (early in pregnancy) psychosocial and stress-related factors that predict risk of spontaneous preterm birth (PTB, gestational age <37 weeks); (2) Investigate whether “protective” factors (e.g., happiness/social support) decrease risk; (3) Use the Dhabhar Quick-Assessment Questionnaire for Stress and Psychosocial Factors (DQAQ-SPF) to rapidly quantify harmful or protective factors that predict increased or decreased risk respectively, of PTB. Study Design This is a prospective cohort study. Relative risk (RR) analyses investigated association between individual factors and PTB. Machine learning-based interdependency analysis (IDPA) identified factor clusters, strength, and direction of association with PTB. A nonlinear model based on support vector machines was built for predicting PTB and identifying factors that most strongly predicted PTB. Results Higher …

Exposure to early life stress (ELS) has been consistently associated with adverse emotional and neural consequences in youth. The development of brain structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient in the development of psychopathology. Prior work has documented smaller hippocampal volume (HCV) in relation to both ELS exposure and risk for psychopathology. We used longitudinal k-means clustering to identify simultaneous trajectories of HCV and emotional problems in 155 youth across three assessments conducted approximately two years apart (mean baseline age = 11.33 years, 57% female). We also examined depressive symptoms and resilience approximately two years after the third timepoint. We identified three clusters of participants: a cluster with high HCV and low emotional problems; a cluster with low HCV and …

Adolescence is often characterized by sleep disturbances that can affect the development of white matter tracts implicated in affective and cognitive regulation, including the cingulate portion of the cingulum bundle (CGC) and the uncinate fasciculus (UF). These effects may be exacerbated in adolescents exposed to early life adversity (ELA). We examined the longitudinal relations between sleep problems and CGC and UF microstructure during adolescence and their relation to depressive symptoms as a function of exposure to ELA. We assessed self-reported sleep disturbances and depressive symptoms and acquired diffusion-weighted MRI scans twice: in early adolescence (9–13 years) and four years later (13–17 years) (N = 72 complete cases). Independent of ELA, higher initial levels and increases in sleep problems were related to increases in depressive symptoms. Further, increases in right CGC fractional …

BackgroundAltered regulation of diurnal cortisol has been associated with both dimensional symptoms and clinical diagnoses of attention deficit-hyperactivity disorder (ADHD). Indeed, a recent meta-analysis suggests that lower diurnal cortisol output may be a biomarker of attention deficit-hyperactivity disorder (ADHD); importantly, however, the influence of psychiatric comorbidities on this association has not been characterized. Approximately two-thirds of children with ADHD have at least one co-occurring neuropsychiatric condition, and altered HPA-axis function has been implicated in many of these conditions. Using dimensional measures of psychopathology, we examined whether comorbid symptoms influence the association of ADHD symptoms with daily cortisol output.Methods138 adolescents (ages 11–15 years) completed measures of symptoms of psychopathology and provided saliva samples over two …

BackgroundMajor depressive disorder (MDD) frequently originates in early development, yet our understanding of its neural basis in youth is not well established, and existing primary studies on the topic include inconsistent findings. This study aims to advance our understanding of the neural basis of MDD in youth by identifying differential neural activation in youth diagnosed with MDD compared to healthy controls.MethodsWe used multilevel kernel density analysis to perform a meta-analysis of all published whole-brain, task-based, functional magnetic resonance imaging (fMRI) activation studies that compared youth diagnosed with MDD to age-matched healthy controls. Additionally, we used Neurosynth to decode the whole-brain meta-analytic maps to provide a data-driven interpretation of these results.ResultsWe found a statistically significant (p< 0.005; FWE-corrected) pattern of hyperactivation and …

ObjectivesThis meta-analysis aims to advance our understanding of the neural basis of MDD in adults, as measured by fMRI activation studies, and address inconsistencies and discrepancies in the empirical literature.MethodsWe employed multilevel kernel density analysis (MKDA) with ensemble thresholding, a well-established method for voxel-wise, whole-brain meta-analyses, to conduct a quantitative comparison of all relevant primary fMRI activation studies of adult patients with MDD compared to age-matched healthy controls.ResultsWe found that adults with MDD exhibited a reliable pattern of statistically significant (p< 0.05; FWE-corrected) hyperactivation and hypoactivation in several brain regions compared to age-matched healthy controls across a variety of experimental tasks.ConclusionsThis study supports previous findings that there is reliable neural basis of MDD that can be detected across …

The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized …

ObjectiveInvestigators are increasingly studying telomeres given their potential as a transgenerational stress marker and association with longevity. Despite this, little is known about peripartum telomere dynamics. To examine whether leukocyte telomere length (LTL) can be measured reliably postpartum, we evaluated whether LTL is affected by mode of delivery.Study DesignMaternal blood samples were obtained up to 6 months postpartum from a prospectively enrolled cohort of 323 pregnant people at one institution. Term, singleton livebirths between 2012 and 2018 were included. Postpartum LTL was measured using quantitative PCR, reported in basepairs (bp), and compared between people with vaginal versus cesarean births. Multivariable linear regression models were conducted sequentially adjusting for age and delivery leukocyte count. These were stratified into two mutually exclusive groups according …

Depression is a serious and persistent psychiatric disorder that commonly first manifests during childhood. Depression that starts in childhood is increasing in frequency, likely due both to evolutionary trends and to increased recognition of the disorder. In this umbrella review, we systematically searched the extant literature for genetic, epigenetic, and neurobiological factors that contribute to a childhood onset of depression. We searched PubMed, EMBASE, OVID/PsychInfo, and Google Scholar with the following inclusion criteria: (1) systematic review or meta-analysis from a peer-reviewed journal; (2) inclusion of a measure assessing early age of onset of depression; and (3) assessment of neurobiological, genetic, environmental, and epigenetic predictors of early onset depression. Findings from 89 systematic reviews of moderate to high quality suggest that childhood-onset depressive disorders have …

This pandemic has been classified as a “psychological pandemic” that produces anxiety, depression, post-traumatic stress disorder, and sleep disorders. As the mental health effects of the Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continue to unfold, there are still large knowledge gaps about the variables that predispose individuals to, or protect individuals against the disease. However, there are few publications on the effects of the COVID-19 pandemic on the mental health of citizens in Latin American countries. In this study, the effects that COVID-19 had on citizens of Peru have been described. For this, 1699 questionnaires, collected between 2 April and 2 September 2020, were analyzed. Descriptive, bivariate analysis was performed with odds ratio (OR) calculations and a data mining methodology. Sociodemographic variables (from the General Health Questionnaire), health conditions and perception, symptoms, and variables related to contact and preventive measures regarding COVID-19 were analyzed. As compared to other countries, less affectation of mental health and increased use of preventive measures were observed. It has been suggested that the country’s precarious health system and poverty rates prior to the pandemic may justify higher mortality figures in Peru than in other Latin American countries, despite prompt action for its containment and compliance with the protective measures. Psychological distress had a greater incidence in women, young people, people without a partner, and people without university studies. The most significant conditioning variables were self-perceived health status …

Objective A major limitation of current suicide research is the lack of power to identify robust correlates of suicidal thoughts or behavior. Variation in suicide risk assessment instruments used across cohorts may represent a limitation to pooling data in international consortia. Method Here, we examine this issue through two approaches:(a) an extensive literature search on the reliability and concurrent validity of the most commonly used instruments and (b) by pooling data (N∼ 6,000 participants) from cohorts from the Enhancing NeuroImaging Genetics Through Meta-Analysis (ENIGMA) Major Depressive Disorder and ENIGMA–Suicidal Thoughts and Behaviour working groups, to assess the concurrent validity of instruments currently used for assessing suicidal thoughts or behavior. Results We observed moderate-to-high correlations between measures, consistent with the wide range (κ range: 0.15–0.97; r range: 0 …

BackgroundAs the percentage of the population that experiences early life stress (ELS) continues to rise, it is crucial to identify trajectories of both neural and emotional development across adolescence that may contribute to the onset of psychopathology. The development of subcortical structures such as the hippocampus, which plays a significant role in stress and emotion regulation, may be particularly salient.MethodsWe used longitudinal k-means clustering to identify different trajectories of hippocampal volume and emotional problems across three assessments conducted approximately two years apart (mean age at baseline= 11.33 years). Participants with data from at least two assessments were included in analyses (N= 152).ResultsWe identified three clusters of participants: Cluster A, with low hippocampal volume and emotional problems; Cluster B, with high hippocampal volume and low emotional …

Background Pregnant women may be especially susceptible to negative events (i.e. adversity) related to the coronavirus disease 2019 (COVID-19) pandemic and negative affective responses to these events (i.e. stress). We examined the latent structure of stress and adversity related to the COVID-19 pandemic among pregnant women, potential antecedents of COVID-19-related stress and adversity in this population, and associations with prenatal depressive symptoms. Method We surveyed 725 pregnant women residing in the San Francisco Bay Area in March−May 2020, 343 of whom provided addresses that were geocoded and matched by census tract to measures of community-level risk. We compared their self-reported depressive symptoms to women matched on demographic factors and history of mental health difficulties who were pregnant prior to the pandemic. Results Women who were pregnant …

Sleep health tends to worsen during adolescence, partially due to pubertal‐related changes that, in combination with social and psychological factors, can lead to long‐lasting impairments in sleep health and affective functioning. Discrepant findings between subjective and objective measures of sleep in relation to affect have been reported in studies of adults; however, few investigations have assessed both subjective and objective sleep quality in a single sample, and fewer have examined this in the context of pubertal development. We aimed to (1) characterise pubertal associations with subjective sleep satisfaction, objective sleep efficiency, and objective and subjective sleep duration in adolescents; (2) examine the longitudinal association between daily affect and sleep metrics; and (3) test whether pubertal stage moderated this association. Eighty‐nine participants (64% female, ages 13–20) completed an …

ObjectiveAdvancing understanding of how early adversity arises, manifests, and contributes to health difficulties depends on accurate measurement of children’s experiences. In early life, exposure to adversity is often intertwined with that of one’s caregivers. We present preliminary psychometric properties of a novel measure of adversity, the Assessment of Parent and Child Adversity (APCA), which simultaneously characterizes parents’ and children’s adversity.MethodsDuring pregnancy, women reported their past adverse experiences. When their children were ages 3–5 years (47% female), 97 mothers (71% White, 17% Hispanic/Latinx) completed the APCA, the Childhood Trauma Questionnaire, and the Benevolent Childhood Experiences scale. They reported their current symptoms of depression and anxiety and their child’s emotional and behavioral problems. Using the APCA, we distinguished between …

Although the intergenerational transmission of risk for depression is well documented, the mechanisms and moderators involved in this transmission of risk from depressed parents to their offspring are not clear. In this review, we discuss the progress that has been made over the past two decades in studying offspring of depressed parents and describe the maladaptive characteristics of these offspring in a diverse range of domains, including clinical, cognitive, and biological functioning. Despite recent advances in this area, there are unresolved questions that warrant further investigation involving the nature of risk transmission from parent to offspring, the specificity of findings to depression, and the role of factors that often accompany depression. We discuss these issues and offer directions for future research that we believe will move the field forward in gaining a better understanding of the relation between …

BackgroundEfforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.MethodsWe describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level.International datasets are being shared from …

IntroductionMajor depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.ObjectivesThe present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.MethodsWe conducted a meta-analysis of functional magnetic resonance imaging (fMRI …

BackgroundMajor depressive disorder (MDD) is a pervasive mental illness, and treatments often provide limited symptom relief or long-term remission, partly due to our limited understanding of its pathophysiology. This meta-analysis aims to advance our understanding of the neural basis of MDD in adults as well as address inconsistencies and discrepancies among functional magnetic resonance imaging (fMRI) studies.MethodsWe used multilevel kernel density analysis with ensemble thresholding to examine all whole-brain, task-based fMRI activation studies of adults diagnosed with MDD compared to age-matched healthy controls. The Neurosynth decoder was used to provide a data-driven interpretation of our observed meta-analytic results.ResultsWe found reliable patterns of statistically significant (p< 0.005; FWE-corrected) hyperactivation and hypoactivation in several brain regions in the cerebral cortex and …

Exposure to adversity is a well‐documented risk factor for cognitive, behavioral, and mental health problems. In fact, the consequences of adversity may be intergenerational. A growing body of research suggests that maternal exposures to adversity, including those prior to childbirth, are associated with offspring biobehavioral development. In a sample of 36 mothers and their preschool‐age children (mean child age = 4.21 ± 0.92 years), we used functional near‐infrared spectroscopy to replicate and extend this work to include brain activation during inhibitory control in young children. We found that measures of maternal exposure to adversity, including cumulative, childhood, and preconception exposures, were significantly and positively associated with activation in the right frontopolar prefrontal cortex (PFC) and in the left temporal and parietal clusters during inhibitory control. In addition, and consistent with …

Caregivers’ goals influence their interactions with their children. In this preregistered study, we examined whether directing parents to teach their baby versus learn from their baby influenced the extent to which they engaged in intrusive (eg, controlling, adult-centered rather than child-centered), sensitive, warm, or cognitively stimulating caregiving behaviors. Mothers and their 6-month-old infants (N= 66; 32 female infants) from the San Francisco Bay Area participated in a 10-min “free-play” interaction, coded in 2-min epochs for degree of parental intrusiveness. Prior to the final epoch, mothers were randomly assigned to receive instructions to focus on (a) teaching something to their infant or (b) learning something from their infant. A control group of mothers received no instructions. Analyses of within-person changes in intrusive behavior from before to after receiving these instructions indicated that mothers …

Major depressive disorder (MDD) is a complex psychiatric disorder that affects the lives of hundreds of millions of individuals around the globe. Even today, researchers debate if morphological alterations in the brain are linked to MDD, likely due to the heterogeneity of this disorder. The application of deep learning tools to neuroimaging data, capable of capturing complex non-linear patterns, has the potential to provide diagnostic and predictive biomarkers for MDD. However, previous attempts to demarcate MDD patients and healthy controls (HC) based on segmented cortical features via linear machine learning approaches have reported low accuracies. In this study, we used globally representative data from the ENIGMA-MDD working group containing an extensive sample of people with MDD (N=2,772) and HC (N=4,240), which allows a comprehensive analysis with generalizable results. Based on the hypothesis that integration of vertex-wise cortical features can improve classification performance, we evaluated the classification of a DenseNet and a Support Vector Machine (SVM), with the expectation that the former would outperform the latter. As we analyzed a multi-site sample, we additionally applied the ComBat harmonization tool to remove potential nuisance effects of site. We found that both classifiers exhibited close to chance performance (balanced accuracy DenseNet: 51%; SVM: 53%), when estimated on unseen sites. Slightly higher classification performance (balanced accuracy DenseNet: 58%; SVM: 55%) was found when the cross-validation folds contained subjects from all sites, indicating site effect. In conclusion, the …

Internalizing and externalizing problems that emerge during adolescence differentially increase boys’ and girls’ risk for developing psychiatric disorders. It is not clear, however, whether there are sex differences in the intrinsic functional architecture of the brain that underlie changes in the severity of internalizing and externalizing problems in adolescents. Using resting-state fMRI data and self-reports of behavioral problems obtained from 128 adolescents (73 females; 9–14 years old) at two timepoints, we conducted multivoxel pattern analysis to identify resting-state functional connectivity markers at baseline that predict changes in the severity of internalizing and externalizing problems in boys and girls 2 years later. We found sex-differentiated involvement of the default mode network in changes in internalizing and externalizing problems. Whereas changes in internalizing problems were associated with the dorsal …

IntroductionFunctional magnetic resonance imaging (fMRI) has been used to identify the neural activity of both youth and adults diagnosed with major depressive disorder (MDD) in comparison to healthy age-matched controls. Previously reported abnormalities in depressed youth appear to mostly align with those found in depressed adults; however, some of the reported aberrant brain activity in youth has not been consistent with what is observed in adults, and to our knowledge there has not yet been a formal, quantitative comparison of these two groups. In addition, it is not known whether these observed differences between youth and adults with depression are attributable to developmental age or length-of-illness.ObjectivesThe aim of this study is to elucidate the similarities and differences in patterns of abnormal neural activity between adults and youth diagnosed with MDD and to then determine whether these …

BackgroundPrimary studies using functional magnetic resonance imaging (fMRI) have identified abnormal neural activation in adults and youth diagnosed with major depressive disorder (MDD) compared to healthy controls. However, these studies have reported some inconsistencies in neural activation between these age groups. In addition, it is not known whether these neural abnormalities between adults and youth with MDD are attributable to the effects of developmental age or length of illness.MethodsWe conducted a comprehensive PubMed search of whole-brain, task-based fMRI activation studies comparing participants with MDD to age-matched healthy controls and then employed multilevel kernel density analysis with multiple comparisons based on mean developmental age and length of illness. Neurosynth decoding was then used to conduct empirically driven reverse inference.ResultsAdults and …

Background Exposure to adversity early in life (ELA) has been associated with elevated risk for depression during adolescence, particularly for females; the mechanisms underlying this association, however, are poorly understood. One potential mechanism linking ELA and sex differences in depressive symptoms is sleep disturbances, which increase during adolescence and are more common in females. Here, we examined whether sleep disturbances mediate the association between ELA and increases in depressive symptoms during adolescence and whether this mediation differs by sex. Methods 224 (N = 132 females) youth were recruited at age 9–13 years and assessed every 2 years across three timepoints. At the first timepoint, we conducted extensive interviews about stressful events participants experienced; participants provided subjective severity ratings of events and we objectively scored the …

Rumination, or negative repetitive thinking, is a significant risk factor for depression and a common and pervasive habit of thought. Using original data from two online surveys of British adults conducted in March 2021 and February 2022, we examine associations between measures of political engagement and the two types of depressive rumination computed from Nolen-Hoeksema’s Response Styles Theory: brooding (the maladaptive component that assesses negative aspects of self-reflection) and reflective pondering (the adaptive component focused on problem-solving). We show that (1) higher brooding is associated with lower internal political efficacy and voting; (2) higher reflective pondering is associated with higher external political efficacy; and (3) reflective pondering increases voting propensity for nonpartisans but not for partisans. Thus, while maladaptive rumination is detrimental to political …

BackgroundExposure to early adversity has been found to be associated with atypical brain maturation in adolescents; it is unclear, however, whether specific types of adversity are differentially associated with delayed or accelerated brain maturation. We tested this hypothesis in a sample of adolescents with Major Depressive Disorder (MDD) who experienced significant levels of early adversity.Methods59 depressed adolescents (16.25±1.29 years; 37 female) completed a high-resolution T1-weighted MR scan at 3T and the Childhood Trauma Questionnaire (CTQ), which examines severity of emotional, physical, and sexual abuse, and emotional and physical neglect. We used FreeSurfer version 6.0 to estimate cortical and subcortical gray matter morphometry and applied ENIGMA MDD’s BrainAge algorithm to estimate brain age. We examined linear associations between each CTQ subscale and the residualized …

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls …

Women experience dramatic physiological changes during pregnancy, including changes in the production of the “stress hormone,” cortisol. Evidence has been mixed regarding whether hair cortisol concentration (HCC) can be used to accurately capture the trajectory of cortisol during this period and whether factors related to psychosocial stress are related to HCC in pregnant and postpartum women. In the current study, we collected hair samples from 85 individuals during the peripartum period (with collection occasions in pregnancy [12–37 weeks], at 3–8 weeks postpartum, and at 5–8 months postpartum) from which we derived 783 monthly observations of HCC. In addition, at each assessment individuals reported their current depressive symptoms and experiences of recent psychosocial adversity. Using piecewise mixed effects modeling, we identified significant increases in HCC across pregnancy …

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta‐Analysis) Consortium presents the largest‐ever mega‐analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1‐90 years old (47% females). We observed significant patterns of greater male than female between‐subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these …

Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic | Reproductive Sciences; 29(SUPPL 1):191-191, 2022. | Web of Science Conteúdo principal 1 Busca 2 Rodapé 3 +A A -A Alto contraste Base de dados da OMS sobre COVID-19 العربية 中文 (中国) english français Русский español português Notícias/Atualização/Ajuda Busca Avançada Pesquisar 1.Home 2.Pesquisa 3.Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic Cellular Aging and Stress in Pregnant and Non-Pregnant People During the COVID-19 Pandemic Panelli, DM; Diwan, M.; Cruz, GI; Leonard, SA; Chueh, J.; Gotlib, IH; Bianco, K.. Reproductive Sciences ; 29(SUPPL 1):191-191, 2022. Artigo em Inglês | Web of Science | ID: covidwho-1749658 Palavras-chave Obstetrics & Gynecology; Reproductive Biology Buscar no Google Imprimir XML Coleções: Bases de …

To understand how infants become engaged in conversations with their caregivers, we examined who tends to initiate conversations between adults and infants, differences between the features of infant‐ and adult‐initiated conversations, and whether individual differences in how much infants engage in infant‐ or adult‐initiated conversations uniquely predict later language development. We analyzed naturalistic adult–infant conversations captured via passive recording of the daily environment in two samples of 6‐month‐old infants. In Study 1, we found that at age 6 months, infants typically engage in more adult‐ than infant‐initiated conversations and that adult‐initiated conversations are, on average, longer and contain more adult words. In Study 2, we replicated these findings and, further, found that infants who engaged in more adult‐initiated conversations in infancy had better expressive language at age 18 …

Exposure to early life stress (ELS) is common and has been implicated in the development of psychopathology; importantly, however, many individuals who experience ELS do not develop emotional or behavioral difficulties. Prior research implicates stress exposure, negative caregiving behaviors, and patterns of physiological reactivity in predicting psychological well‐being; however, the precise factors that contribute to resilience versus vulnerability to the adverse effects of stress exposures are not well understood. In a longitudinal study of adolescents (N = 120) assessed at three timepoints approximately every 2 years beginning at the ages of 913 years, we examined the roles of autonomic reactivity to social stress (assessed through skin conductance during the Trier Social Stress Task) and negative caregiving behaviors as moderators of the association between exposure to ELS and internalizing and …

BackgroundShort leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.MethodsIn this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time …

Exposure to early life stress (ELS) increases the risk for developing psychopathology; however, the mechanisms underlying this association are not clear. In this study we examined systemic inflammation as a pathway that may link exposure to stress to altered neural correlates of implicit emotion regulation in adolescents with varying levels of exposure to ELS (n = 83; 52 females, 31 males; 15.63 ± 1.10 years). We measured ventrolateral prefrontal cortex (vlPFC) activation and functional connectivity (FC) between the bilateral amygdala and the vlPFC as adolescents completed an affect labeling task in the scanner and assessed concentrations of C-reactive protein (CRP) using a dried blood spot protocol. We found that CRP levels were negatively associated with vlPFC activation during implicit regulation of negatively-valenced stimuli, and that cumulative severity of ELS exposure moderated this neuroimmune …

Internalizing symptoms typically emerge in adolescence and are more prevalent in females than in males; in contrast, externalizing symptoms typically emerge in childhood and are more commonly observed in males. Previous research has implicated aspects of white matter organization, including fractional anisotropy (FA), of cerebral tracts in both internalizing and externalizing symptoms. Although the cerebellum has been posited to integrate limbic and cortical regions, its role in psychopathology is not well understood. In this longitudinal study, we investigated whether FA of the superior (SCP), middle (MCP), and inferior cerebellar peduncles (ICP) predict change in symptoms and whether sex moderates this association. One hundred eleven adolescents completed the Youth Self-Report, assessing symptoms at baseline (ages 9–13 years) and again 2 years later. Participants also underwent diffusion …

BackgroundThalamic structure, function, and connectivity associated with state and trait features of bipolar disorder (BD) before and around newly emergent mania is poorly understood.MethodsYouth with (n= 22) versus without (n= 23) BD underwent structural neuroimaging at baseline and 12 months. Healthy Youth at high and low risk for mood disorders [BD-risk (n= 40), MDD-risk (n= 41), and HC (n= 45)[mean age 13.09+/-2.58, 56.3% female] completed the monetary incentive delay (MID) task at baseline and were followed for behavioral and clinical outcomes over 4.37+/-2.29 years. Region of interest (ROI) and psychophysiological interaction analyses were conducted using an anatomically defined thalamus seed during reward anticipation and feedback (Z> 3.1; FWE-cluster corrected p<. 05). Random Forest was used to predict risk group membership.ResultsAdolescents with BD showed greater reductions in …

The early environment, including maternal characteristics, provides many cues to young organisms that shape their long-term physical and mental health. Identifying the earliest molecular events that precede observable developmental outcomes could help identify children in need of support prior to the onset of physical and mental health difficulties. In this study, we examined whether mothers’ attachment insecurity, maltreatment history, and depressive symptoms were associated with alterations in DNA methylation patterns in their infants, and whether these correlates in the infant epigenome were associated with socioemotional and behavioral functioning in toddlerhood. We recruited 156 women oversampled for histories of depression, who completed psychiatric interviews and depression screening during pregnancy, then provided follow-up behavioral data on their children at 18 months. Buccal cell DNA was …

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD‐related differences in subcortical regions using shape analysis. In this meta‐analysis of subcortical shape from the ENIGMA‐MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by …

BackgroundLeukocyte telomere length (LTL) is a biomarker that is affected by older age, psychosocial stress, and medical comorbidities. Despite the relevance of these factors to obstetric practice, little is known about LTL in pregnancy. Our study explored longitudinal LTL dynamics in pregnant and non-pregnant people.ObjectiveThis pilot study compares changes in LTL between pregnant and non-pregnant people over time, explores potential correlations between LTL and mental health measures, and investigates associations between short first-trimester LTL and adverse pregnancy outcomes.Study designThis was a prospective pilot cohort study of nulliparous pregnant and non-pregnant people between ages 18 and 50 who presented for care at a single institution from January to November 2020. Pregnant people were enrolled between 10 and 14 weeks gestation. Participants had two blood samples drawn for …

Exposure to ozone is a well-documented risk factor for negative physical health outcomes but has been considered less frequently in the context of socioemotional health. We examined whether levels of neighborhood ozone predicted trajectories of depressive symptoms over a four-year period in 213 adolescents (ages 9–13 years at baseline; 57% female; 53% of minority race/ethnicity). Participants self-reported depressive and other types of psychopathology symptoms up to 3 times, and their home addresses were used to compute ozone levels in their census tract. Possible confounding variables, including personal, family, and neighborhood characteristics, were also assessed. We found that higher ozone predicted steeper increases in depressive symptoms across adolescent development, a pattern that was not observed for other forms of psychopathology symptoms. These findings underscore the importance …

BackgroundSeveral studies have evaluated whether depressed persons have older appearing brains than their nondepressed peers. However, the estimated neuroimaging-derived “brain age gap” has varied from study to study, likely driven by differences in training and testing sample (size), age range, and used modality/features. To validate our previously developed ENIGMA brain age model and the identified brain age gap, we aim to replicate the presence and effect size estimate previously found in the largest study in depression to date (N = 2126 controls & N = 2675 cases; +1.08 years [SE 0.22], Cohen's d = 0.14, 95% CI: 0.08–0.20), in independent cohorts that were not part of the original study.MethodsA previously trained brain age model (www.photon-ai.com/enigma_brainage) based on 77 FreeSurfer brain regions of interest was used to obtain unbiased brain age predictions in 751 controls and 766 …

BackgroundEarly life stress (ELS) is associated with long-lasting consequences, including elevated depressive symptoms and attenuated activation in reward circuitry. We know less, however, about the development of these outcomes in adolescence. In this longitudinal study we examined trajectories of depressive symptoms and reward circuitry activation following ELS, hypothesizing that adolescents exposed to more severe ELS will have higher depressive symptoms and altered trajectories of reward circuitry activation.MethodsParticipants (at entry n= 220, age= 9-13 years) were assessed 3 times over 4 years at 2-year intervals, completing the Traumatic Events Screening Inventory and the Children’s Depression Inventory. We assessed activation during anticipation of gain during the monetary incentive delay task. Using a linear mixed effects model, we assessed the main effects and interaction of ELS severity …

Understanding the role of stress in pregnancy and its consequences is important, particularly given documented associations between maternal stress and preterm birth and other pathological outcomes. Physical and psychological stressors can elicit the same biological responses, known as biological strain. Chronic stressors, like poverty and racism (race-based discriminatory treatment), may create a legacy or trajectory of biological strain that no amount of coping can relieve in the absence of larger-scale socio-behavioral or societal changes. An integrative approach that takes into consideration simultaneously social and biological determinants of stress may provide the best insights into the risk of preterm birth. The most successful computational approaches and the most predictive machine-learning models are likely to be those that combine information about the stressors and the biological strain (for example …

The effects of COVID-19 on democracy and mental health are still under investigation. In this article, it is considered that, on average, higher COVID-19 stressors and symptoms of distress are associated with lower political support and that higher COVID-19 stressors are associated with higher symptoms of mental/emotional distress. This formulation was tested by conducting two online surveys in Britain in August 2020 and March 2021. Strong support was found for this hypothesis. Greater worry about COVID-19 life changes is associated with a lower evaluation of government performance on the pandemic and with a lower perceived responsiveness of the political system; higher COVID-19 stress resulting from anti-pandemic measures is associated with a poorer evaluation of government performance and, subsequently, with less trust in government. It was also found that higher COVID-19 worry and stress were …

Childhood adversity and anxiety have been associated with increased risk for internalizing disorders later in life and with a range of brain structural abnormalities. However, few studies have examined the link between harsh parenting practices and brain anatomy, outside of severe maltreatment or psychopathology. Moreover, to our knowledge, there has been no research on parenting and subclinical anxiety symptoms which remain persistent over time during childhood (i.e., between 2.5 and 9 years old). Here, we examined data in 94 youth, divided into four cells based on their levels of coercive parenting (high / low) and of anxiety (high / low) between 2.5 and 9 years old. Anatomical images were analyzed using voxel-based morphometry (VBM) and FreeSurfer. Smaller gray matter volumes in the prefrontal cortex regions and in the amygdala were observed in youth with high versus low levels of harsh parenting …

Adolescent depression is characterized by heightened inflammation and altered connectivity of fronto-cingulate-limbic tracts, including the genu of the corpus callosum (CCG) and the uncinate fasciculus (UF). No studies, however, have yet examined the association between inflammation, measured by peripheral levels of cytokines, and white matter connectivity of fronto-cingulate-limbic tracts in adolescents. Here, 56 depressed adolescents (32 females, 3 non-binary; 16.23 ± 1.28 years) and 19 controls (10 females; 15.72 ± 1.17 years) completed a diffusion-weighted MRI scan at 3 Tesla. We conducted deterministic tractography to segment bilateral corpus callosum (genu and splenium) and UF and computed mean fractional anisotropy (FA) in each tract. A subset of participants (43 depressed and 17 healthy controls) also provided dried blood spot samples from which we assayed interleukin 6 (IL-6) and tumor …

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area …

Suicide is the second leading cause of death among adolescents. While clinicians and researchers have begun to recognize the importance of considering multidimensional factors in understanding risk for suicidal thoughts and behaviors (STBs) during this developmental period, the role of puberty has been largely ignored. In this review, we contend that the hormonal events that occur during puberty have significant effects on the organization and development of brain systems implicated in the regulation of social stressors, including amygdala, hippocampus, striatum, medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex. Guided by previous experimental work in adults, we also propose that the influence of pubertal hormones and social stressors on neural systems related to risk for STBs is especially critical to consider in adolescents with a neurobiological sensitivity to hormonal changes …

BackgroundThe COVID-19 pandemic has led to increased psychological distress on a global scale, particularly for vulnerable people, including new and expecting mothers. We are still determining the magnitude of the toll on parents and their children.Methods516 pregnant people completed online questionnaires during the spring of 2020 (T1); 296 of these people completed additional questionnaires approximately one year postpartum (T2). Participants reported on mental health, coping behaviors, and infant temperament. A principal components analysis (PCA) was conducted to identify coping factors. Linear regression analyses were conducted to evaluate associations among coping factors, maternal depressive symptoms, and infant temperament.ResultsPCA revealed three factors explaining 40.53% of the variance in coping behaviors. The first factor included self-care behaviors (eg, exercise, mediation); the …

BackgroundGiven the high prevalence of depressive symptoms reported by adolescents and associated risk of experiencing psychiatric disorders as adults, differentiating the trajectories of the symptoms related to negative valence at an individual level could be crucial in gaining a better understanding of their effects later in life.MethodsA longitudinal deep learning framework is presented, identifying self-reported and behavioral measurements that detect the depressive symptoms associated with the Negative Valence System domain of the NIMH Research Domain Criteria (RDoC).ResultsApplied to the annual records of 621 participants (age range: 12 to 17 years) of the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA), the deep learning framework identifies predictors of negative valence symptoms, which include lower extraversion, poorer sleep quality, impaired executive …

Different dimensions of adversity may affect mental health through distinct neurobiological mechanisms, though current supporting evidence consists largely of cross-sectional associations between threat or deprivation and fronto-limbic circuitry. In this exploratory three-wave longitudinal study spanning ages 9–19 years, we examined the associations between experiences of unpredictability, threat, and deprivation with the development of functional connectivity within and between three brain networks implicated in psychopathology: the salience (SAL), default mode (DMN), and fronto-parietal (FPN) networks, and tested whether network trajectories moderated associations between adversity and changes in internalizing symptoms. Connectivity decreased with age on average; these changes differed by dimension of adversity. Whereas family-level deprivation was associated with lower initial levels and more …

BackgroundDifferent dimensions of early adversity—including unpredictability, threat, and deprivation—have been posited to affect adolescent psychopathology through distinct neurobiological mechanisms. The majority of research to date, however, has been cross-sectional, making it difficult to evaluate temporal associations.MethodsIn this three-wave longitudinal study of 225 adolescents (ages 9-19 years), we examined the associations between experiences of unpredictability, threat, and deprivation and the development of functional connectivity in three brain networks implicated in psychopathology: the default-mode (DMN), frontoparietal (FPN), and salience (SAL) networks. We tested whether network trajectories moderated associations between adversity exposure and changes in internalizing symptoms.ResultsNetwork connectivity decreased with age (all ßs<-. 05, all ps<. 04); moreover, dimensions of …

BackgroundMental and physical health are affected by family and neighborhood socioeconomic status (SES). Accelerated maturation in the context of lower SES is one mechanism that might contribute to underlying health disparities; few studies, however, have considered neighborhood SES in relation to putative markers of brain maturation in adolescents.MethodsIn 120 adolescents 13 to 18 years of age, we examined family and neighborhood SES in relation to cortical thickness adjusted for age. We also examined whether cortical thickness was related to depressive symptoms and explored regions of interest.ResultsControlling for age, neighborhood socioeconomic disadvantage was associated with a thinner cortex in the left hemisphere (standardized β = −0.20), which was related to more severe depressive symptoms (standardized β = −0.33). Family SES was not significantly associated with age-adjusted …

Caregivers who are higher in dispositional empathy tend to have children with better developmental outcomes; however, few studies have considered the role of child‐directed (i.e., “parental”) empathy, which may be relevant for the caregiver–child relationship. We hypothesized that mothers’ parental empathy during their child's infancy will be a stronger predictor of their child's social‐emotional functioning as a toddler than will mothers’ dispositional empathy. We further explored whether parental and dispositional empathy have shared or distinct patterns of neural activation during a social‐cognitive movie‐watching task. In 118 mother–infant dyads, greater parental empathy assessed when infants were 6 months old was associated with more social‐emotional competencies and fewer problems in the children 1 year later, even after adjusting for dispositional empathy. In contrast, dispositional empathy was not …

Background Females are at higher risk for developing depression during adolescence than are males, particularly during exposure to stressors like the COVID‐19 pandemic. Examining structural connections between brain regions involved in executive functioning may advance our understanding of sex biases in stress and depression. Here, we examined the role of the cingulum bundle in differentiating trajectories of depressive symptoms in males and females across adolescence and during the pandemic. Methods In a longitudinal study of 214 youth (121 females; ages 9–13 years at baseline), we examined whether fixel‐based properties of the cingulum bundle at baseline predict changes in females' and males' severity of depressive symptoms across four timepoints (4–7 years) in adolescence, including during the COVID‐19 pandemic. We also tested whether cingulum properties predict self‐reported …

The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each …

The COVID-19 pandemic is a unique period of stress, uncertainty, and adversity that will have significant implications for adolescent mental health. Nevertheless, stress and adversity related to COVID-19 may be more consequential for some adolescents’ mental health than for others. We examined whether heart rate variability (HRV) indicated differential susceptibility to mental health difficulties associated with COVID-19 stress and COVID-19 family adversity. Approximately 4 years prior to the pandemic, we assessed resting HRV and HRV reactivity to a well-validated stress paradigm in 87 adolescents. During the pandemic, these adolescents (ages 13–19) reported on their health-related stress and concerns about COVID-19, family adversity related to COVID-19, and their recent emotional problems. The association between COVID-19 stress and emotional problems was significantly stronger for adolescents who …

BackgroundFew studies to date have characterized functional connectivity (FC) within emotion and reward networks in relation to family dynamics in youth at high familial risk for bipolar disorder (HR-BD) and major depressive disorder (HR-MDD) relative to low-risk youth (LR). Such characterization may advance our understanding of the neural underpinnings of mood disorders and lead to more effective interventions.MethodsA total of 139 youth (43 HR-BD, 46 HR-MDD, and 50 LR) aged 12.9 ± 2.7 years were longitudinally followed for 4.5 ± 2.4 years. We characterized differences in striatolimbic FC that distinguished between HR-BD, HR-MDD, and LR and between resilience and conversion to psychopathology. We then examined whether risk status moderated FC–family dynamic associations. Finally, we examined whether baseline between-group FC differences predicted resilence versus conversion to …

An alarming high proportion of youth experience at least one kind of stressor in childhood and/or adolescence. Exposure to early life stress is associated with increased risk for psychopathology, accelerated biological aging, and poor physical health; however, it is important to recognize that not all youth who experience such stress go on to develop difficulties. In fact, resilience, or positive adaptation in the face of adversity, is relatively common. Individual differences in vulnerability or resilience to the effects of early stress may be represented in the brain as specific patterns, profiles, or signatures of neural activation, structure, and connectivity (i.e., neurophenotypes). Whereas neurophenotypes of risk that reflect the deleterious effects of early stress on the developing brain are likely to exacerbate negative outcomes in youth, neurophenotypes of resilience may reduce the risk of experiencing these negative outcomes …

Air pollution is a major environmental threat to public health; we know little, however, about its effects on adolescent brain development. Exposure to air pollution co-occurs, and may interact, with social factors that also affect brain development, such as early life stress (ELS). Here, we show that severity of ELS and fine particulate air pollution (PM2.5) are associated with volumetric changes in distinct brain regions, but also uncover regions in which ELS moderates the effects of PM2.5. We interviewed adolescents about ELS events, used satellite-derived estimates of ambient PM2.5 concentrations, and conducted longitudinal tensor-based morphometry to assess regional changes in brain volume over an approximately 2-year period (N = 115, ages 9–13 years at Time 1). For adolescents who had experienced less severe ELS, PM2.5 was associated with volumetric changes across several gray and white …

Our primary objective was to document COVID-19 induced changes to perinatal care across the USA and examine the implication of these changes for maternal mental health. We performed an observational cross-sectional study with convenience sampling using direct patient reports from 1918 postpartum and 3868 pregnant individuals collected between April 2020 and December 2020 from 10 states across the USA. We leverage a subgroup of these participants who gave birth prior to March 2020 to estimate the pre-pandemic prevalence of specific birthing practices as a comparison. Our primary analyses describe the prevalence and timing of perinatal care changes, compare perinatal care changes depending on when and where individuals gave birth, and assess the linkage between perinatal care alterations and maternal anxiety and depressive symptoms. Seventy-eight percent of pregnant participants and …

Background Suicidal ideation (SI) typically emerges during adolescence but is challenging to predict. Given the potentially lethal consequences of SI, it is important to identify neurobiological and psychosocial variables explaining the severity of SI in adolescents. Methods In 106 participants (59 female) recruited from the community, we assessed psychosocial characteristics and obtained resting‐state fMRI data in early adolescence (baseline: aged 9–13 years). Across 250 brain regions, we assessed local graph theory‐based properties of interconnectedness: local efficiency, eigenvector centrality, nodal degree, within‐module z‐score, and participation coefficient. Four years later (follow‐up: ages 13–19 years), participants self‐reported their SI severity. We used least absolute shrinkage and selection operator (LASSO) regressions to identify a linear combination of psychosocial and brain‐based variables that …

BackgroundExpectant mothers are experiencing unprecedented levels of stress throughout the COVID-19 pandemic. It is critical, therefore, that we examine the impact of this stressful perinatal period on infants’ development, growth, and emotional functioning.MethodsWe collected data from women (N= 295) over two time periods: once while they were pregnant (T1), and again at approximately one year postpartum (T2). At T1, participants reported on their levels of stress related to COVID-19, including the overall impact of the COVID-19 outbreak on their daily life, and on their emotion regulation. At T2, participants reported on their infant’s temperament.ResultsWe conducted a hierarchical multiple regression predicting infant negative affect. In the first step, race, education, age, and income explained 6.3% of the variance in infant negative affect (F (10,268)= 1.825, p=. 058). In the second step, maternal emotion …

Brain structural abnormalities and low educational attainment are consistently associated with major depressive disorder (MDD), yet there has been little research investigating the complex interaction of these factors. Brain structural alterations may represent a vulnerability or differential susceptibility marker, and in the context of low educational attainment, predict MDD. We tested this moderation model in a large multisite sample of 1958 adults with MDD and 2921 controls (aged 18 to 86) from the ENIGMA MDD working group. Using generalized linear mixed models and within-sample split-half replication, we tested whether brain structure interacted with educational attainment to predict MDD status. Analyses revealed that cortical thickness in a number of occipital, parietal, and frontal regions significantly interacted with education to predict MDD. For the majority of regions, models suggested a differential …

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and …

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and …

Exposure to environmental pollutants has been associated with cellular aging in children and adolescents. Individuals may vary, however, in their sensitivity or vulnerability to the effects of environmental pollutants. Larger hippocampal volume has emerged as a potential index of increased sensitivity to social contexts. In exploratory analyses (N = 214), we extend work in this area by providing evidence that larger hippocampal volume in early adolescence reflects increased sensitivity to the effect of neighborhood pollution burden on telomere length (standardized β = –0.40, 95% CI[–0.65, –0.15]). In contrast, smaller hippocampal volume appears to buffer this association (standardized β = 0.02). In youth with larger hippocampal volume, pollution burden was indirectly associated with shorter telomere length approximately 2 years later through shorter telomere length at baseline (indirect standardized β = –0.25, 95 …

Psychosocial and stress-related factors (PSFs), defined as internal or external stimuli that induce biological changes, are potentially modifiable factors and accessible targets for interventions that are associated with adverse pregnancy outcomes (APOs). Although individual APOs have been shown to be connected to PSFs, they are biologically interconnected, relatively infrequent, and therefore challenging to model. In this context, multi-task machine learning (MML) is an ideal tool for exploring the interconnectedness of APOs on the one hand and building on joint combinatorial outcomes to increase predictive power on the other hand. Additionally, by integrating single cell immunological profiling of underlying biological processes, the effects of stress-based therapeutics may be measurable, facilitating the development of precision medicine approaches. Objectives The primary objectives were to jointly model multiple APOs and their connection to stress early in pregnancy, and to explore the underlying biology to guide development of accessible and measurable interventions. Materials and Methods In a prospective cohort study, PSFs were assessed during the first trimester with an extensive self-filled questionnaire for 200 women. We used MML to simultaneously model, and predict APOs (severe preeclampsia, superimposed preeclampsia, gestational diabetes and early gestational age) as well as several risk factors (BMI, diabetes, hypertension) for these patients based on PSFs. Strongly interrelated stressors were categorized to identify potential therapeutic targets. Furthermore, for a subset of 14 women, we modeled the connection of PSFs to …

In this paper we provide an overview of the rationale, methods, and preliminary results of the four Connectome Studies Related to Human Disease investigating mood and anxiety disorders. The first study, “Dimensional connectomics of anxious misery” (HCP-DAM), characterizes brain-symptom relations of a transdiagnostic sample of anxious misery disorders. The second study, “Human connectome Project for disordered emotional states” (HCP-DES), tests a hypothesis-driven model of brain circuit dysfunction in a sample of untreated young adults with symptoms of depression and anxiety. The third study, “Perturbation of the treatment resistant depression connectome by fast-acting therapies” (HCP-MDD), quantifies alterations of the structural and functional connectome as a result of three fast-acting interventions: electroconvulsive therapy, serial ketamine therapy, and total sleep deprivation. Finally, the fourth study …

Correction: Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders Page 1 University of Groningen Correction Opel, Nils; Thalamuthu, Anbupalam; Milaneschi, Yuri; Grotegerd, Dominik; Flint, Claas; Leenings, Ramona; Goltermann, Janik; Richter, Maike; Hahn, Tim; Woditsch, Georg Published in: Molecular Psychiatry DOI: 10.1038/s41380-021-01191-1 IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2021 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Opel, N., Thalamuthu, A., Milaneschi, Y., Grotegerd, D., Flint, C., Leenings, R., Goltermann, J., Richter, M., Hahn, T., Woditsch, G., Berger, K., Hermesdorf, M., McIntosh…