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Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology ('p') factor. Youth aged 8-16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.

Alterations in learning processes and the neural circuitry that supports fear conditioning and extinction represent mechanisms through which trauma exposure might influence risk for psychopathology. Few studies examine how trauma or neural structure relates to fear conditioning in children. Children (n=94) aged 6-18 years, 40.4% (n=38) with exposure to maltreatment (physical abuse, sexual abuse, or domestic violence), completed a fear conditioning paradigm utilizing blue and yellow bells as conditioned stimuli (CS+/CS-) and an aversive alarm noise as the unconditioned stimulus. Skin conductance responses (SCR) and self-reported fear were acquired. Magnetic resonance imaging data were acquired from 60 children. Children without maltreatment exposure exhibited strong differential conditioning to the CS+ vs CS-, based on SCR and self-reported fear. In contrast, maltreated children exhibited blunted SCR to the CS+ and failed to exhibit differential SCR to the CS+ vs CS- during early conditioning. Amygdala and hippocampal volume were reduced among children with maltreatment exposure and were negatively associated with SCR to the CS+ during early conditioning in the total sample, although these associations were negative only among non-maltreated children and were positive among maltreated children. The association of maltreatment with externalizing psychopathology was mediated by this perturbed pattern of fear conditioning. Child maltreatment is associated with failure to discriminate between threat and safety cues during fear conditioning in children. Poor threat-safety discrimination might reflect either enhanced fear generalization or a deficit in associative learning, which may in turn represent a central mechanism underlying the development of maltreatment-related externalizing psychopathology in children.

Childhood adversity is associated with increased risk for psychopathology. Neurodevelopmental pathways underlying this risk remain poorly understood. A recent conceptual model posits that childhood adversity can be deconstructed into at least two underlying dimensions, deprivation and threat, that are associated with distinct neurocognitive consequences. This model argues that deprivation (i.e., a lack of cognitive stimulation and learning opportunities) is associated with poor executive function (EF), whereas threat is not. We examine this hypothesis in two studies measuring EF at multiple levels: performance on EF tasks, neural recruitment during EF, and problems with EF in daily life. In Study 1, deprivation (low parental education and child neglect) was associated with greater parent-reported problems with EF in adolescents ( N = 169; 13–17 years) after adjustment for levels of threat (community violence and abuse), which were unrelated to EF. In Study 2, low parental education was associated with poor working memory (WM) performance and inefficient neural recruitment in the parietal and prefrontal cortex during high WM load among adolescents ( N = 51, 13–20 years) after adjusting for abuse, which was unrelated to WM task performance and neural recruitment during WM. These findings constitute strong preliminary evidence for a novel model of the neurodevelopmental consequences of childhood adversity.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2 , is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1 , GRM8 and CACNA1E ), developmental, axon guidance and transcription factors (for example, FOXP2 , EFNA5 and DCC ), synaptic structure and function genes (for example, PCLO , NCAM1 and PDE4B ) and endocrine or immune regulators (for example, ESR1 , TRAF3 and TANK ). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation. Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d = −0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Adolescents’ ratings of subjective social status within their peer community may represent a useful index of socioeconomic status (SES) which is strongly associated with adolescent psychopathology. However, adolescent subjective social status does not correlate to traditional indicators of SES such as family income. Instead, subjective social status may reflect access to other forms of resources more salient to adolescents such as symbolic capital (behaviors and consumer goods symbolic of social position). I conducted a cultural consensus analysis based on interviews and questionnaire data from 66 students in two high schools in the Pacific Northwest to produce a consensually agreed upon set of symbolic capital markers in those schools. In a separately recruited sample of 80 adolescents, I tested associations between subjective social status, symbolic capital ownership, and psychopathology. Contrary to my hypotheses, subjective social status and symbolic capital were not correlated, although both were associated with parent rated social competence. Subjective social status was associated with psychopathology, but symbolic capital was not. My findings suggest that symbolic capital and subjective social status may convey different information about adolescents’ social competence, and that performing a high-status identity may be less important to socio-emotional functioning than perceiving oneself as well-liked and respected.

Analysis of resting state fMRI (rs‐fMRI) typically excludes images substantially degraded by subject motion. However, data quality, including degree of motion, relates to a broad set of participant characteristics, particularly in pediatric neuroimaging. Consequently, when planning quality control (QC) procedures researchers must balance data quality concerns against the possibility of biasing results by eliminating data. In order to explore how researcher QC decisions might bias rs‐fMRI findings and inform future research design, we investigated how a broad spectrum of participant characteristics in the Adolescent Brain and Cognitive Development (ABCD) study were related to participant inclusion/exclusion across versions of the dataset (the ABCD Community Collection and ABCD Release 4) and QC choices (specifically, motion scrubbing thresholds). Across all these conditions, we found that the odds of a participant's exclusion related to a broad spectrum of behavioral, demographic, and health‐related variables, with the consequence that rs‐fMRI analyses using these variables are likely to produce biased results. Consequently, we recommend that missing data be formally accounted for when analyzing rs‐fMRI data and interpreting results. Our findings demonstrate the urgent need for better data acquisition and analysis techniques which minimize the impact of motion on data quality. Additionally, we strongly recommend including detailed information about quality control in open datasets such as ABCD. This study investigated participant characteristics associated with exclusion of resting state fMRI data across a range of quality control procedures. Many participant characteristics made exclusion more likely across conditions, demonstrating that correction for missing data is necessary for accurate estimates of brain‐behavior relationships when examining functional connectivity.

Fear learning is a core component of conceptual models of how adverse experiences may influence psychopathology. Specifically, existing theories posit that childhood experiences involving childhood trauma are associated with altered fear learning processes, while experiences involving deprivation are not. Several studies have found altered fear acquisition in youth exposed to trauma, but not deprivation, although the specific patterns have varied across studies. The present study utilizes a longitudinal sample of children with variability in adversity experiences to examine associations among childhood trauma, fear learning, and psychopathology in youth. The sample includes 170 youths aged 10-13 years ( 11.56, s.d. = 0.47, 48.24% female). Children completed a fear conditioning task while skin conductance responses (SCR) were obtained, which included both acquisition and extinction. Childhood trauma and deprivation severity were measured using both parent and youth report. Symptoms of anxiety, externalizing problems, and post-traumatic stress disorder (PTSD) were assessed at baseline and again two-years later. Greater trauma-related experiences were associated with greater SCR to the threat cue (CS+) relative to the safety cue (CS-) in early fear acquisition, controlling for deprivation, age, and sex. Deprivation was unrelated to fear learning. Greater SCR to the threat cue during early acquisition was associated with increased PTSD symptoms over time controlling for baseline symptoms and mediated the relationship between trauma and prospective changes in PTSD symptoms. Childhood trauma is associated with altered fear learning in youth, which may be one mechanism linking exposure to violence with the emergence of PTSD symptoms in adolescence.

Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants’ demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LMEINT), (2) LME that models both site-specific random intercepts and age-related random slopes (LMEINT+SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2–81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3–85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (Χ2(3) = 63.704, p < 0.001) as well as case-control differences in age-related cortical thinning (Χ2(3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (Χ2(3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects.