Trauma and comorbid post-traumatic stress disorder in people with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study.

BACKGROUND: It is estimated that up to 50 % of people with bipolar disorder (BD) also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the presentation and treatment of people with this comorbidity. METHODS: Data from 577 individuals diagnosed with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study of BD were explored at baseline, year two and four. Three trauma groups were created: (i) one trauma (n = 75), (ii) multiple traumas (n = 417), and comorbid PTSD (n = 85). Measures of depression, mania, sleep, number of hospitalisations, suicide attempts, and medication use were analysed using regression modelling to determine differences between the three trauma groups. RESULTS: There was an increase in depression, mania, and sleep scores and a higher number of hospitalisations in participants with comorbid PTSD compared to those experiencing one trauma. Additionally, increased mania and depression scores were reported in participants experiencing multiple traumas compared to those with one trauma. There was no difference in medication use between those who experienced one trauma compared to those with comorbid PTSD. LIMITATIONS: The trauma groups may include confounding with more participants experiencing PTSD than reported in this study due to screening processes. Additionally, the severity of trauma was not recorded, therefore number of traumas was utilised as a proxy. CONCLUSION: Comorbid BD and PTSD is associated with worse symptom scores compared to participants reporting one trauma. Clinical implications include the addition of trauma-informed care to clinical settings to identify PTSD to provide appropriate treatments.

Direct and Indirect Effects of Cannabis Risk Perceptions on Cannabis Use Frequency.

Background: Perceived risk of harm associated with cannabis use has decreased in recent decades, particularly among emerging adults who show the highest prevalence of use. Cannabis-related protective behavioral strategies (PBS) are associated with lower cannabis use and fewer consequences; however, individuals who perceive using cannabis as low risk may use cannabis PBS less often. Therefore, using cross-sectional data, we examined the associations between perceived risk of harm associated with cannabis use, cannabis PBS, and cannabis use frequency. Method: Participants were 146 emerging adults between the ages of 18-25 (56.2% female) who reported consuming cannabis at least 3 times/week and completed measures of past-month cannabis use, past three-month use of cannabis PBS, and perceived risk of harm associated with cannabis use. Path analyses examined direct and indirect effects of perceived risk of cannabis-related harm on cannabis frequency through cannabis PBS. Results: Most (66.4%) participants reported no perceived risk of harm associated with occasional cannabis use, whereas 30.1% reported no perceived risk of harm associated with regular cannabis use. Findings indicated a significant indirect effect between perceived risk of harm and cannabis use frequency through cannabis PBS, b = -10.23, SE = 3.80, 95% CI [-17.67, -2.80], p = .007. Conclusions: Among emerging adults who consume cannabis regularly, findings suggest that a greater perceived risk of cannabis-related harm is associated with decreased cannabis use frequency via increased use of cannabis PBS. Although future analyses evaluating causal mechanisms are needed, these findings have clinical implications for harm reduction interventions focused on cannabis use.

Greater Early Posttrauma Activation in the Right Inferior Frontal Gyrus Predicts Recovery From Posttraumatic Stress Disorder Symptoms.

BACKGROUND: Posttraumatic stress disorder (PTSD) has been associated with altered emotion processing and modulation in specific brain regions, i.e., the amygdala, insula, and medial prefrontal and anterior cingulate cortices. Functional alterations in these regions, recorded shortly after trauma exposure, may predict changes in PTSD symptoms. METHODS: Survivors (N = 104) of a traumatic event, predominantly a motor vehicle accident, were included. Functional magnetic resonance imaging was used to assess brain activation 1, 6, and 14 months after trauma exposure (T1, T2, and T3, respectively). Participants performed the Shifted-attention Emotional Appraisal Task, which probes 3 affective processes: implicit emotional processing (of emotional faces), emotion modulation by attention shifting (away from these faces), and emotion modulation by appraisal (of the participants' own emotional response to these faces). We defined regions of interest based on task-related activations, extracted beta weights from these regions of interest, and submitted them to a series of analyses to examine relationships between neural activation and PTSD severity over the 3 time points. RESULTS: At T1, a regression model containing activations in the left dorsolateral prefrontal cortex, bilateral inferior frontal gyrus (IFG), and medial prefrontal cortex during emotion modulation by appraisal significantly predicted change in PTSD symptoms. More specifically, greater right IFG activation at T1 was associated with greater reduction in symptom severity (T1-T3). Exploratory analysis also found that activation of the right IFG increased from T1 to T3. CONCLUSIONS: The results suggest that greater early posttrauma activation during emotion appraisal in the right IFG, a region previously linked to cognitive control in PTSD, predicts recovery from PTSD symptoms.

A remote brief intervention plus social media messaging for cannabis use among emerging adults: A pilot randomized controlled trial in emergency department patients.

INTRODUCTION: Interventions addressing cannabis use among emerging adults (ages 18-25) are currently needed to prevent negative outcomes. Emergency Department (ED) visits provide an opportunity to initiate interventions. In this pilot study, we created a brief intervention (BI), extended with private social media messaging for emerging adult ED patients who use cannabis regularly. Study aims were to examine intervention feasibility, acceptability, and descriptive outcomes. METHODS: We recruited and randomized N = 58 emerging adults (M age 21.5 years, 65.5% female) who used cannabis from an ED in-person and remotely after their ED visit (given COVID-19 restrictions). Participants randomized to the intervention (N = 30) received a Motivational Interviewing-based BI and 4 weeks of health coaching via private social media; control participants received a resource brochure and entertaining social media messaging. Follow-ups occurred at 1-month and 3-months. RESULTS: Most intervention participants liked the BI (95.8%), found it helpful to discuss cannabis use in the BI (91.7%), and liked interacting with coaches on social media (86.3%). Social media content (e.g., video clips, images/still pictures/memes) were highly rated. Descriptively, the intervention group showed theory-consistent changes in importance of and intentions to change cannabis (increases vs. decrease/stability in control group), whereas findings for cannabis consumption/consequences were mixed. CONCLUSIONS: This BI paired with social media messaging was acceptable in a sample of emerging adults from an ED who used cannabis regularly. Despite feasibility challenges due to COVID-19, this intervention warrants future investigation with a larger sample and longer follow-up period, with attention to the changing cannabis landscape when measuring outcomes.

Investigating gender differences in the co-occurrence of PTSD and food addiction.

OBJECTIVE: Post-traumatic stress disorder (PTSD) commonly co-occurs with substance use disorders (SUDs). Past studies suggest PTSD is also associated with food addiction (compulsive intake of highly processed foods containing refined carbohydrates and/or added fat). However, research investigating gender differences has been limited (e.g., restricted samples) and mixed. We aim to investigate the risk of co-occurring PTSD and food addiction in a community sample for all participants and stratified by gender. Additionally, we conducted risk ratios for problematic substance use and obesity to allow for within-sample comparisons. METHOD: We utilized a sample of 318 participants recruited from Amazon Mechanical Turk (mean age = 41.2, 47.8% men, 78.0% white) to address existing gaps in the literature on PTSD and food addiction. We calculated risk ratios (adjusted for sociodemographic covariates) using modified Poisson regression with 95% confidence intervals. Results were also gender stratified. RESULTS: Risk of food addiction (Risk Ratio (RR) = 6.42, 95% CI [4.10, 10.07], problematic alcohol use (RR) = 3.86, 95% CI [2.25,6.62], problematic smoking (RR) = 3.93, 95% CI [2.22, 6.97], and problematic nicotine vaping (RR) = 5.41, 95% CI [2.41, 11.14] were higher for those meeting criteria for PTSD. Risk of problematic cannabis use, and risk of obesity were not significantly higher for those meeting criteria for PTSD. Gender-stratified results suggest risk of food addiction may be higher for men (RR) = 8.54, 95% CI [4.49, 16.25] compared to women (RR) = 4.32, 95% CI [2.16, 8.62]. DISCUSSION: Food addiction, but not obesity, appears to co-occur with PTSD more strongly than other types of problematic substance use (alcohol, cannabis, cigarettes, nicotine vaping). This risk appears to be particularly high for men compared to women. Assessing for food addiction in those with PTSD, particularly in men, may assist in identifying high-risk groups.

Interpersonal Trauma and Depression Severity Among Individuals With Bipolar Disorder: Findings From the Prechter Longitudinal Study of Bipolar Disorder.

Background: Experiences of interpersonal trauma, both in childhood and in adulthood, can affect the trajectory of bipolar disorder (BD). However, the degree to which childhood and/or adult trauma impacts the longitudinal trajectory of depression severity among individuals with BD actively receiving treatment remains unclear.Methods: The effects of childhood trauma (Childhood Trauma Questionnaire) and adult trauma (Life Events Checklist) on depression severity (Hamilton Depression Rating Scale) were investigated in a treatment-receiving subsample with BD (DSM-IV) of the Prechter Longitudinal Study of Bipolar Disorder (2005-present). A mixed-effects linear regression model was used to assess the trajectory of depression severity over 4 years.Results: Depression severity was evaluated in 360 participants, of whom 267 (74.8%) reported a history of interpersonal trauma. A history of childhood trauma alone (n = 110) and childhood and adult trauma combined (n = 108)-but not adult trauma alone (n = 49) -were associated with greater depression severity at the 2-year and 6-year follow-up assessments. However, the trajectory of depression severity (ie, change over time) was similar between participants with a history of childhood trauma, those with a history of adult trauma, and those with no history of interpersonal trauma. Interestingly, participants with a history of both types of trauma showed more improvement in depression severity (ie, from year 2 to year 4: ß = 1.67, P = .019).Conclusions: Despite actively receiving treatment for BD, participants with a history of interpersonal trauma-particularly childhood trauma-presented with more severe depressive symptoms at several follow-up assessments. Hence, interpersonal trauma may represent an essential treatment target.

Childhood trauma relates to worse memory functioning in bipolar disorder.

BACKGROUND: Childhood trauma is commonly experienced by individuals diagnosed with bipolar disorder (BP). In BP, childhood trauma is related to a more severe clinical course, but its association with cognition remains unclear. METHODS: This study evaluated 405 adult participants diagnosed with BP and 136 controls. Participants completed the Childhood Trauma Questionnaire and a comprehensive neuropsychological battery. High versus low childhood trauma was defined with one standard deviation above the control participant's mean Childhood Trauma Questionnaire score. Neuropsychological data was transformed into eight cognitive factors, including four executive functioning, auditory and visual memory, fine motor, and emotion processing. Multivariate analysis of covariance evaluated group differences in cognition, while adjusting for covariates. RESULTS: There were significant differences among the three groups, F(16, 968) = 4.05, p < .001, Wilks' Λ = 0.88, partial η2 = 0.06. Comparing the high and low trauma BP groups, high trauma was related to lower auditory and visual memory factor scores (p < .05). As compared to controls, the BP high trauma group had lower scores on six of eight factors (all p < .01), while the BP low trauma group had lower scores on four of eight factors (all p < .01). LIMITATIONS: Analyses of factor score do not address which aspect of the memory process is affected and biomarkers may help guide interventions addressing underlying biological process. CONCLUSIONS: Adults diagnosed with BP with higher childhood trauma have worse memory functioning, beyond the lower childhood trauma BP group, highlighting the importance of understanding the long-term cognitive outcomes of childhood trauma.

DNA methylation GrimAge acceleration in US military veterans with PTSD.

Epigenetic alterations in DNA methylation might mediate gene expression effects of trauma underlying PTSD symptoms, or effects of PTSD on related health problems. PTSD is associated with all-cause morbidity and premature mortality, suggesting accelerated biological aging. We measured genome-wide DNA methylation (Illumina MethylationEPIC BeadChip) in whole blood in a treatment study for combat-related PTSD - "PROGrESS", a multisite RCT comparing sertraline plus enhanced medication management (SERT + EMM), prolonged exposure (PE) therapy plus placebo (PE + PLB), and the combination (SERT + PE). DNA methylation was measured in 140 US military veterans who served in Iraq and/or Afghanistan (112 current PTSD cases enrolled in a PTSD treatment study and 28 veterans without PTSD history controls), and also 59 non-trauma exposed controls at baseline posttreatment (24 weeks after baseline). Increased DNA methylation GrimAge acceleration (p = 8.8e-09) was observed in patients with PTSD compared to a pooled control group (trauma exposed and non-trauma exposed), suggesting a higher risk of premature mortality in those with PTSD. There was no difference in GrimAge acceleration between combat trauma and non-trauma exposed controls. No treatment-related changes in GrimAge acceleration were found in within-subject comparisons of PTSD patients pre- to post-treatment.

Childhood trauma and depressive symptoms in bipolar disorder: A network analysis.

BACKGROUND: Childhood trauma is related to an increased number of depressive episodes and more severe depressive symptoms in bipolar disorder. The evaluation of the networks of depressive symptoms-or the patterns of relationships between individual symptoms-among people with bipolar disorder with and without a history of childhood trauma may assist in further clarifying this complex relationship. METHODS: Data from over 500 participants from the Heinz C. Prechter Longitudinal Study of Bipolar Disorder were used to construct a series of regularised Gaussian Graphical Models. The networks of individual depressive symptoms-self-reported (Patient Health Questionnaire-9; n = 543) and clinician-rated (Hamilton Depression Rating Scale-17; n = 529)-among participants with bipolar disorder with and without a history of childhood trauma (Childhood Trauma Questionnaire) were characterised and compared. RESULTS: Across the sets of networks, depressed mood consistently emerged as a central symptom (as indicated by strength centrality and expected influence); regardless of participants' history of childhood trauma. Additionally, feelings of worthlessness emerged as a key symptom in the network of self-reported depressive symptoms among participants with-but not without-a history of childhood trauma. CONCLUSION: The present analyses-although exploratory-provide nuanced insights into the impact of childhood trauma on the presentation of depressive symptoms in bipolar disorder, which have the potential to aid detection and inform targeted intervention development.

Social media interventions addressing physical activity among emerging adults who use cannabis: A pilot trial of feasibility and acceptability.

PURPOSE: Cannabis use is common among emerging adults (ages 18-25), yet few prevention interventions have targeted this unique developmental period. Physical activity (PA) is an under-utilized intervention target for cannabis use, despite research showing its potential utility. Based on prior promising social media-delivered interventions targeting cannabis and PA separately, we developed and piloted, in a randomized controlled feasibility trial (NCT04901910), interventions for emerging adults who use cannabis that focused on PA. PROCEDURES: Using social media, we recruited 60 emerging adults (Mean age=21.7 years; 63.3% female sex) who used cannabis (>=3 times/week for the past month) and could engage in PA. We randomized participants into one of 3 conditions (PA-Only; PA+Cannabis, Attention-Control) that each lasted 8 weeks and were delivered in secret Facebook groups by health coaches. We collected follow-up data at 3- and 6-months post-group start. Outcomes are presented descriptively given the pilot nature and limited sample size. RESULTS: The interventions were rated favorably, with ratings of the content in each condition averaging around 3 on a 5-point scale. Both intervention groups demonstrated larger reductions in cannabis consequences and cannabis-impaired driving over time than the control condition. Findings were mixed regarding patterns of change in cannabis use in the intervention conditions. Proportions of group members reporting increased PA ranged from 38.9% to 80.0% across time. CONCLUSIONS: Interventions targeting PA and delivered via social media to emerging adults who regularly use cannabis offer a novel intervention target. These interventions warrant future investigation in larger trials over a longer follow-up period.

Personality traits as mediators of the relationship between childhood trauma and depression severity in bipolar disorder: A structural equation model.

BACKGROUND: Childhood trauma is negatively associated with depression severity in bipolar disorder; however, the underlying mechanisms remain unclear. We investigated whether personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) mediate the relationship between childhood trauma and the severity of bipolar depression. METHODS: Data from 209 individuals with bipolar disorder recruited for the Prechter Longitudinal Study of Bipolar Disorder were analysed. Using structural equation modelling, we examined the direct and indirect associations between childhood trauma (Childhood Trauma Questionnaire) and depression severity (Hamilton Depression Rating Scale) - with the personality traits (NEO Personality Inventory-Revised) as mediators. RESULTS: The direct effect of childhood trauma on depression severity (standardised ß = 0.32, 95% bootstrap confidence interval [CI] = 0.20-0.45, p < 0.001) and the indirect effect via neuroticism (standardised ß = 0.03, 95% bootstrap CI [0.002, 0.07], p = 0.039) were significant; supporting a partial mediation model. The indirect effect accounted for 9% of the total effect of childhood trauma on depression severity (standardised ß = 0.09, 95% bootstrap CI [0.002, 0.19], p = 0.046). The final model had a good fit with the data (comparative fit index = 0.96; root mean square error of approximation = 0.05, 90% CI = [0.02, 0.07]). CONCLUSION: Personality traits may be relevant psychological mediators that link childhood trauma to a more severe clinical presentation of bipolar depression. Consequently, a person's personality structure may be a crucial operative factor to incorporate in therapeutic plans when treating individuals with bipolar disorder who report a history of childhood trauma.

Social interaction anxiety and depression symptoms are differentially related in men and women.

Social anxiety disorder (SAD) and major depressive disorder (MDD) are highly comorbid with each other, and comorbidity exacerbates distress and impairment. The prevalence of comorbid depression is higher in women with SAD than in men with SAD, but this is based on global depression scores and cannot speak to heterogeneous individual depression symptoms. The current study bridges this gap by examining gender differences in the relationship between social interaction anxiety and individual depression symptoms. 165 community adults (113 women, 52 men) were included in a series of bootstrapped moderation analyses to examine the main and interaction effects of social interaction anxiety and gender on total depression and individual depressive symptom scores while controlling for age and racial/ethnic background. Social interaction anxiety positively predicted total and individual depression scores. Greater social interaction anxiety predicted greater self-dislike and worthlessness in men than in women. Our findings replicate the finding that social anxiety and depression are highly comorbid with respect to total scores and extend this finding to individual symptoms. Our findings also demonstrate that the relationship between social interaction anxiety and depressive symptoms can be modulated by gender identities. Men with social interaction anxiety may be more prone to distress associated with self/identity. These findings elucidate the specific ways in which social interaction anxiety relates to the constellation of depression symptoms in men and women and highlights the need for more tailored assessment and intervention for socially anxious men and women to target individual dimensions of symptom presentations.

Morning light treatment for traumatic stress: The role of amygdala reactivity study protocol.

BACKGROUND: Exposure to trauma can result in various mental health disorders including anxiety, depression, and posttraumatic stress disorder (PTSD). Although psychotherapies and pharmacotherapies exist for the treatment of these disorders, many individuals fail to receive treatment and among those who do, many remain symptomatic. Therefore, it is critical to continue developing new interventions for traumatic stress that target underlying mechanisms of pathology and offer a safe and acceptable alternative to current treatments. Morning light treatment has good potential as a novel non-invasive, low risk treatment for traumatic stress. Evidence suggests that morning light may improve traumatic stress by reducing reactivity in the amygdala, a brain region implicated in the pathophysiology of PTSD and anatomically linked to circadian photoreceptors in the eye. METHODS: In this study, we aim to establish a significant dose-response relationship between duration of morning light treatment and reduction in amygdala reactivity among individuals with traumatic stress symptoms (NCT# 04117347). Using a transdiagnostic approach, sixty-six individuals with a history of a DSM-5 criterion A trauma and traumatic stress symptoms will be recruited to participate in a 5-week study. Participants will be randomized across three treatment arms based on morning light treatment duration: 15-minutes, 30-minutes, or 60-minutes of light treatment per day for four weeks. To evaluate amygdala activity, participants will undergo fMRI at pre-treatment, mid-treatment, and post-treatment. Participants will also complete clinical assessments and self-report measures of PTSD, depression, and anxiety at pre-treatment, mid-treatment, and post-treatment. DISCUSSION: Morning light therapy may be an acceptable, feasible, and effective treatment for individuals suffering from traumatic stress. Identifying mechanistically relevant targets, and the doses needed to impact them, are critical steps in developing this new treatment approach for the sequelae of traumatic stress.

Childhood trauma and food addiction: The role of emotion regulation difficulties and gender differences.

OBJECTIVE: Childhood trauma has been associated with substance use disorders (SUDs), but less research has investigated its association with food addiction (i.e., compulsive intake of highly processed foods containing refined carbohydrates and/or added fat). Existing research on childhood trauma and food addiction has focused primarily on women from restricted samples. Further, emotion dysregulation difficulties are implicated in both childhood trauma and food addiction, but research has not explored whether it may play a mediating role. METHOD: The current study utilizes a sample of 310 participants recruited from Amazon Mechanical Turk (mean age = 41.3 years old, 47.4% men, 78.7% white) to investigate the mediating role of emotion dysregulation in the association between childhood trauma and food addiction. We also conducted exploratory analyses to investigate for gender differences in these associations. Gender-stratified correlational matrixes were conducted to investigate associations between childhood trauma, food addiction, and emotional dysregulation. Moderated mediation models and multilevel regressions were also conducted to identify the role of gender in the association between childhood trauma, food addiction, and emotion dysregulation. RESULTS: Emotion dysregulation was found to partially mediate the associations between food addiction and childhood trauma and gender was found to moderate associations between childhood trauma and emotion dysregulation, as well as childhood trauma and food addiction. Both moderating pathways were significantly stronger for men compared to women. DISCUSSION: Results suggests that emotion dysregulation may be one important mediator in the association between childhood trauma and food addiction, particularly for men. The identification of other potential mechanisms contributing to the association between childhood trauma and food addiction and the use of longitudinal measurement strategies will be important in future research.

Attachment insecurity partially mediates the relationship between childhood trauma and depression severity in bipolar disorder.

BACKGROUND: Childhood trauma is associated with greater depression severity among individuals with bipolar disorder. However, the mechanisms that explain the link between childhood trauma and depression severity in bipolar disorder remain poorly understood. The mediational role of attachment insecurity in childhood and adulthood was assessed in the current study. METHODS: Participants with bipolar disorder (N = 143) completed measures of childhood trauma (Childhood Trauma Questionnaire), attachment insecurity (Experiences in Close Relationships Scale) and depression severity (Hamilton Depression Rating Scale) as part of the Prechter Longitudinal Study of Bipolar Disorder. A sequential mediation model was tested using path analysis: the direct and indirect effects of childhood trauma on depression severity with attachment insecurity (attachment anxiety and avoidance) in childhood (mother and father) and adulthood (partner) as mediators were estimated. RESULTS: The final path model demonstrated an excellent fit to the data (comparative fit index = 0.996; root mean square error of approximation = 0.021 [90% confidence interval = 0.000-0.073]). Supporting the hypothesised sequential mediation model, maternal attachment anxiety in childhood and romantic attachment avoidance in adulthood partially mediated the relationship between childhood trauma and depression severity; this effect accounted for 12% of the total effect of childhood trauma on depression severity. CONCLUSION: Attachment insecurity in childhood and adulthood form part of the complex mechanism informing why people with bipolar disorder who have a history of childhood trauma experience greater depression severity. Addressing attachment insecurity represents a valuable psychotherapeutic treatment target for bipolar disorder.

Charting brain growth and aging at high spatial precision.

Defining reference models for population variation, and the ability to study individual deviations is essential for understanding inter-individual variability and its relation to the onset and progression of medical conditions. In this work, we assembled a reference cohort of neuroimaging data from 82 sites (N=58,836; ages 2-100) and used normative modeling to characterize lifespan trajectories of cortical thickness and subcortical volume. Models are validated against a manually quality checked subset (N=24,354) and we provide an interface for transferring to new data sources. We showcase the clinical value by applying the models to a transdiagnostic psychiatric sample (N=1985), showing they can be used to quantify variability underlying multiple disorders whilst also refining case-control inferences. These models will be augmented with additional samples and imaging modalities as they become available. This provides a common reference platform to bind results from different studies and ultimately paves the way for personalized clinical decision-making.

Differentiated nomological networks of internalizing, externalizing, and the general factor of psychopathology ('p factor') in emerging adolescence in the ABCD study.

BACKGROUND: Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. METHODS: The sample consisted of 10 645 youth aged 9-10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p, INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance. RESULTS: p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. CONCLUSIONS: In this largest study of hierarchical models of psychopathology to date, we found that p, INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p, INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities.

Startle to neutral, not negative stimuli: A neurophysiological correlate of behavioral inhibition in young children.

A putative biomarker of anxiety risk, the startle response is typically enhanced by negative compared to neutral emotion modulation in adults, but remains understudied in children. To determine the extent to which neutral, negative, and positively valenced emotional conditions modulate startle response in early life, a child-friendly film paradigm was used to vary emotion across these conditions during startle induction in sixty-four 4- to 7-year-old children. Association of emotion-modulated startle with parent-reported anxiety symptom severity and child behavioral inhibition, a risk factor for anxiety problems, were assessed. Analyses revealed no difference in startle magnitude during negative compared to neutral film clips. By contrast, startle during both negative and neutral conditions was greater than startle during the positive condition. Larger startle magnitude during the neutral condition associated with higher levels of child behavioral inhibition (BI). These results are consistent with possible immaturity of startle response in young children, and suggest that startle amplitude in more emotionally ambiguous, neutral conditions could serve as an early biomarker for anxiety risk.

Weight-Related Differences in Salience, Default Mode, and Executive Function Network Connectivity in Adolescents.

OBJECTIVE: The current study examined whether adolescents with weight status ranging from lean to obesity showed weight-related differences in the default mode network (DMN), the executive function network (EFN), and the salience network (SN). METHODS: One hundred sixty-four adolescents participated in a resting-state functional connectivity scan. A general linear model was used to examine differences in scan patterns among adolescents with lean weight, overweight, and obesity. RESULTS: Adolescents with obesity compared with those with lean weight showed stronger within-SN connectivity among the medial orbitofrontal cortex, olfactory tubercle, and pallidum; however, they showed lower connectivity between the amygdala and SN regions (nucleus accumbens, thalamus, putamen). Those with obesity also showed lower connectivity between SN (amygdala, caudate) and DMN (parahippocampus, hippocampus, precuneus) regions. Adolescents with obesity compared with those with lean weight showed lower connectivity between SN (medial orbitofrontal cortex) and EFN (ventrolateral prefrontal cortex) regions. CONCLUSIONS: Obesity appears to be related to stronger connectivity within and between regions implicated in determining the salience of stimuli, which may have implications for reward processing. Lower connectivity between SN and EFN regions may suggest that executive-control efforts are going "off-line" when salience and reward-processing regions are engaged in adolescents who have obesity.

Associations between resting-state functional connectivity and treatment response in a randomized clinical trial for posttraumatic stress disorder.

BACKGROUND: Alterations in resting-state functional connectivity (rsFC) have been reported in posttraumatic stress disorder (PTSD). Here, we examined pre- and post-treatment rsFC during a randomized clinical trial to characterize alterations and examine predictors of treatment response. METHODS: Sixty-four combat veterans with PTSD were randomly assigned to prolonged exposure (PE) plus placebo, sertraline plus enhanced medication management, or PE plus sertraline. Symptom assessment and resting-state functional magnetic resonance imaging (fMRI) scans occurred before and after treatment. Twenty-nine trauma-exposed combat veterans without PTSD served as a control group at intake. Seed-based and region of interest (ROI)-to-ROI connectivities, as well as an exploratory connectome-based approach were used to analyze rsFC patterns. Based on previously reported findings, analyses focused on Salience Network (SN) and Default-Mode Network (DMN). RESULTS: At intake, patients with PTSD showed greater DMN-dorsal attention network (DAN) connectivity (between ventromedial prefrontal cortex and superior parietal lobule; family-wise error corrected p = .011), greater SN-DAN connectivity (between insula and middle frontal gyrus; corrected p = .003), and a negative correlation between re-experiencing symptoms and within-DMN connectivity (between posterior cingulate cortex (PCC) and middle temporal gyrus; corrected p < .001). We also found preliminary evidence for associations between rsFC and treatment response. Specifically, high responders (≥50% PTSD symptom improvement), compared with low responders, had greater SN-DMN segregation (i.e., less pre-treatment amygdala-PCC connectivity; p = .011) and lower pre-treatment global centrality (p = .042). CONCLUSIONS: Our findings suggest neural abnormalities in PTSD and may inform future research examining neural biomarkers of PTSD treatment response.