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Background Psychiatric diagnosis and treatment have historically taken a symptom-based approach, with less attention on identifying underlying symptom-producing mechanisms. Recent efforts have illuminated the extent to which different underlying circuitry can produce phenotypically similar symptomatology (e.g., psychosis in bipolar disorder vs. schizophrenia). Computational modeling makes it possible to identify and mathematically differentiate behaviorally unobservable, specific reinforcement learning differences in patients with schizophrenia versus other disorders, likely owing to a higher reliance on prediction error–driven learning associated with basal ganglia and underreliance on explicit value representations associated with orbitofrontal cortex. Methods We used a well-established probabilistic reinforcement learning task to replicate those findings in individuals with schizophrenia both on (n = 120) and off (n = 44) antipsychotic medications and included a patient comparison group of bipolar patients with psychosis (n = 60) and healthy control subjects (n = 72). Results Using accuracy, there was a main effect of group (F3,279 = 7.87, p Conclusions Both medicated and unmedicated patients showed overreliance on prediction error–driven learning as well as significantly higher noise and value-related memory decay, compared with the healthy control subjects and the patients with bipolar disorder. Additionally, the computational model parameters capturing these processes can significantly improve patient/control classification, potentially providing useful diagnosis insight.

Background The experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. We aimed to test the efficacy and tolerability of low-dose augmentation with buprenorphine (BPN) for treatment resistant depression, combined with multi-modal assessment of target engagement. Methods In this multi-site, randomized clinical trial, 85 participants ≥ age 50 with a major depressive episode that had not responded to venlafaxine XR were randomized to augmentation with BPN or placebo for 8 weeks. The primary outcome measure was the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, three linked experiments were conducted to test target engagement: 1) functional magnetic resonance imaging (fMRI) using the Monetary Incentive Delay Task; 2) brain positron emission tomography (PET) of healthy participants using a novel kappa opioid receptor (κ-OR) antagonist tracer [11C]LY2795050; 3) transcranial magnetic stimulation (TMS) measure of cortical transmission after daily BPN administration. Results The mean ± SD dosage of BPN was 0.59±0.33 mg/day. There were no significant differences between the BPN and placebo groups in MADRS changes over time or adverse effects. BPN administration had minimal effects on fMRI bold responses in regions involved in reward anticipation and response, no significant displacement of κ-OR radioligand in PET imaging, and no significant changes in TMS measures of inhibitory and excitatory cortical transmission. Conclusions Our findings suggest a lack of clinical effect of low-dose BPN augmentation and lack of target engagement with this dosage and physiological probes.

Early low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood.Children (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures.Lower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20-0.31, p values.003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p.0001) and subcortical gray matter (standardized B = 0.17, p.0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors.These novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

BackgroundChildhood psychotic-like experiences (PLEs) often precede the development of later severe psychopathology. This study examined whether childhood PLEs are associated with several psychopathology-related polygenic scores (PGSs) and additionally examined possible neural and behavioral mechanisms.MethodsAdolescent Brain Cognitive Development Study baseline data from children with European ancestry (n= 4650, ages 9-10 years, 46.8% female) were used to estimate associations between PLEs (i.e., both total and presence of significantly distressing) and PGSs for psychopathology (i.e., schizophrenia, psychiatric cross-disorder risk, PLEs) and related phenotypes (i.e., educational attainment [EDU], birth weight, inflammation). We also assessed whether variability in brain structure indices (i.e., volume, cortical thickness, surface area) and behaviors proximal to PGSs (e.g., cognition for EDU) indirectly linked PGSs to PLEs using mediational models.ResultsTotal and significantly distressing PLEs were associated with EDU and cross-disorder PGSs (all %ΔR2s= 0.202%-0.660%; false discovery rate-corrected ps < .006). Significantly distressing PLEs were also associated with higher schizophrenia and PLE PGSs (both %ΔR2= 0.120%-0.216%; false discovery rate-corrected ps < .03). There was evidence that global brain volume metrics and cognitive performance indirectly linked EDU PGS to PLEs (estimated proportion mediated= 3.33%-32.22%).ConclusionsTotal and significantly distressing PLEs were associated with genomic risk indices of broad-spectrum psychopathology risk (i.e., EDU and cross-disorder PGSs). Significantly distressing PLEs were also associated with genomic risk for psychosis (i.e., schizophrenia, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may indirectly link genomic risk to psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples generalize to indices of psychopathology risk among children.

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting post-traumatic preventive interventions. METHODS: Data come from 1,306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-week, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative-risk=2.6–7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2-week and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2-weeks and 8-weeks could help target early interventions for psychopathological reactions to MVCs.

OBJECTIVE: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental health outcomes to identify neurobiological predictors of risk, resilience, and different symptom presentations. METHODS: A total of 146 participants (discovery cohort: N = 69; internal replication cohort: N = 77) were recruited from emergency departments within 72 hours of a trauma and followed for the next 6 months with a survey, MRI, and physiological assessments. RESULTS: Task-based functional MRI 2 weeks after a motor vehicle collision identified four clusters of individuals based on profiles of neural activity reflecting threat reactivity, reward reactivity, and inhibitory engagement. Three clusters were replicated in an independent sample with a variety of trauma types. The clusters showed different longitudinal patterns of posttrauma symptoms. CONCLUSIONS: These findings provide a novel characterization of heterogeneous stress responses shortly after trauma exposure, identifying potential neuroimaging-based biotypes of trauma resilience and psychopathology.

Objective Callous-unemotional (CU) traits—characterized by low empathy, prosociality, and guilt—predict severe and persistent conduct problems. Although some interventions for conduct problems have been less effective in children with high levels of CU traits, studies have not examined whether CU traits interfere with treatment for other childhood disorders. Moreover, few treatments have demonstrated efficacy in decreasing CU traits themselves in early childhood. This study examined whether Parent–Child Interaction Therapy—Emotion Development (PCIT-ED), a novel PCIT adaptation that promotes emotional competence with demonstrated efficacy in treating preschool-onset major depressive disorder and oppositional defiant disorder, was also effective in treating these disorders in children displaying higher levels of CU traits. The study also examined whether PCIT-ED treatment produced significant and sustained decreases in CU traits. Method This study examined 3- to 5-year-olds (N = 114) with preschool-onset major depressive disorder who completed the PCIT-ED trial. Children were randomly assigned to either immediate PCIT-ED treatment (n = 64) or a waitlist control condition (n = 50) in which they received the active treatment after 18 weeks. Psychiatric diagnoses and severity and CU traits in children were assessed at baseline, immediately after treatment, and 18 weeks after treatment completion. Results Compared with the waitlist, PCIT-ED effectively reduced major depressive disorder and oppositional defiant disorder in preschoolers, regardless of initial levels of CU traits. Moreover, CU traits decreased from before to after treatment, and this treatment effect was sustained 18 weeks after treatment. Conclusion Results support that novel interventions that enhance emotional development display significant promise in treating CU traits—behaviors that left untreated predict severe conduct problems, criminality, and substance use. Clinical trial registration information A Randomized Controlled Trial of PCIT-ED for Preschool Depression; https://clinicaltrials.gov ; NCT02076425.

Loneliness is associated with a myriad of detrimental outcomes in mental and physical health. Previous studies have found that people with schizophrenia report greater loneliness than controls, and that loneliness is related to depressive symptoms. However, research has been limited, particularly regarding contributions of loneliness to social and occupational functioning. Further, few studies have examined associations between loneliness and daily experience in schizophrenia. Thus, we recruited 35 individuals with schizophrenia and 37 controls. All participants completed the UCLA loneliness scale, symptom assessments, and measures of social and occupational functioning. Additionally, participants with schizophrenia completed an ecological momentary assessment (EMA) protocol that indexed daily social and emotional experiences, including loneliness. Similar to previous reports, we found that those with schizophrenia reported greater loneliness than controls. Further, loneliness was positively associated with depressive and negative symptoms, and negatively associated with self-reported social functioning. Interestingly, loneliness remained a significant predictor of functioning even when controlling for other symptoms, suggesting that severity of depressive and negative symptoms cannot fully explain the relationship between loneliness and functioning. In our EMA analyses, loneliness did not significantly differ when individuals were alone versus with others, underscoring the notion that being alone is not the same as feeling lonely. However, self-reported engagement during social interactions was negatively associated with loneliness, at a trend-level, suggesting that quality of social interactions is a potentially important consideration. Taken together, these findings suggest that loneliness is an important treatment target and provide understanding for how loneliness may manifest in daily life in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Monitoring one's performance helps detect errors and adapt to prevent future mistakes. However, elevated performance monitoring is associated with increased checking behaviors and perfectionism and is characteristic of multiple psychiatric disorders. Understanding how heightened performance monitoring in early childhood relates to subsequent brain connectivity may elucidate mechanistic risk factors that influence brain and psychiatric outcomes. The aim of this study was to examine the association between performance monitoring in preschool-aged children and functional connectivity during adolescence. In the current prospective longitudinal study, we performed seed-based functional connectivity analysis using a dorsal anterior cingulate cortex (dACC) seed to assess brain–behavior relationships between observationally coded performance monitoring in preschool-aged children and adolescent functional connectivity (n = 79). We also utilized enrichment analysis to investigate network-level connectome-wide associations. Seed-based analysis revealed negative correlations between preschool performance monitoring and adolescent fc between dACC and orbitofrontal and dorsolateral prefrontal cortex while a positive correlation was observed between dACC-occipital cortex connectivity. Enrichment analysis revealed a negative correlation between preschool performance monitoring and connectivity between motor (MOT) - cingulo-opercular (CO) and salience (SN) - Reward (REW) and a positive correlation with MOT-DMN, and cerebellum (CB) - motor connectivity. Elevated performance monitoring in early childhood is associated with functional connectivity during adolescence in regions and networks associated with cognitive control, sensorimotor processing and cortico-striatal-thalamic-cortico (CTSC) aberrations. These regions and networks are implicated in psychiatric disorders characterized by elevated performance monitoring. Findings shed light on a mechanistic risk factor in early childhood with long-term associations with neural functioning.

Background Pediatric anxiety disorders are linked to dysfunction in multiple functional brain networks, as well as to alterations in the allocation of spatial attention. We used network-level analyses to characterize resting-state functional connectivity (rs-fc) alterations associated with 1) symptoms of anxiety and 2) alterations in stimulus-driven attention associated with pediatric anxiety disorders. We hypothesized that anxiety was related to altered connectivity of the frontoparietal, default mode, cingulo-opercular, and ventral attention networks and that anxiety-related connectivity alterations that include the ventral attention network would simultaneously be related to deviations in stimulus-driven attention. Methods A sample of children (n = 61; mean = 10.6 years of age), approximately half of whom met criteria for a current anxiety disorder, completed a clinical assay, an attention task, and rs-fc magnetic resonance imaging scans. Network-level analyses examined whole-brain rs-fc patterns associated with clinician-rated anxiety and with involuntary capture of attention. Post hoc analyses controlled for comorbid symptoms. Results Elevated clinician-rated anxiety was associated with altered connectivity within the cingulo-opercular network, as well as between the cingulo-opercular network and the ventral attention, default mode, and visual networks. Connectivity between the ventral attention and cingulo-opercular networks was associated with variation in both anxiety and stimulus-driven attention. Conclusions Pediatric anxiety is related to aberrant connectivity patterns among several networks, most of which include the cingulo-opercular network. These results help clarify the within- and between-network interactions associated with pediatric anxiety and its association with altered attention, suggesting that specific network connections could be targeted to improve specific altered processes associated with anxiety.

Background Blunted neural reward responsiveness (RR) is observed in youth depression. However, it is unclear whether symptoms of depression experienced early in development relate to adolescent RR beyond current symptoms and, further, whether such relationships with RR differ during two key components of reward processing: anticipation and outcome. Methods Within a prospective longitudinal study oversampled for early depression, children and caregivers completed semiannual diagnostic assessments beginning in preschool. In later adolescence, mean age = 16.49 years (SD = 0.94), youths’ (N = 100) neurophysiological responses to cues signaling likely win and loss and these outcomes were assessed. Longitudinally assessed dimensional depression and externalizing symptoms (often comorbid with depression as well as associated with RR) experienced at different developmental periods (preschool [age 3–5.11 years], school age [6–9.11 years], early adolescence [10–14.11 years], current) were used as simultaneous predictors of event-related potentials indexing anticipatory cue processing (cue-P3) and outcome processing (reward positivity/feedback negativity and feedback-P3). Results Blunted motivated attention to cues signaling likely win (cue-P3) was specifically predicted by early-adolescent depression symptoms. Blunted initial response to win (reward positivity) and loss (feedback negativity) outcomes was specifically predicted by preschool depression symptoms. Blunted motivational salience of win and loss outcomes (feedback-P3) was predicted by cumulative depression, not specific to any developmental stage. Conclusions Although blunted anticipation and outcome RR is a common finding in depression, specific deficits related to motivated attention to cues and initial outcome processing may map onto the developmental course of these symptoms.

Obesity is a major public health problem and cause of significant burden across the lifespan. Longitudinal samples, beginning in early childhood offer an advantageous approach to studying obesity, given the potential to observe within-individual changes over time. Yet among the many available longitudinal studies of children, particularly those studying psychological disorders, do not assess for overweight/obesity status or related constructs necessary to compute BMI. We offer a unique thin slice approach for assessing obesity/overweight status using previously collected video data. The current study observationally coded overweight/obesity status in a clinically enriched sample of preschoolers oversampled for depression (N = 299). Preschoolers (ages 3–6 years) completed 1–8 structured observational tasks with an experimenter. Overweight/obesity was coded using a “thin slice” technique with 7820 unique ratings available for analysis. Parent-reported physical health problems were assessed throughout the study and BMI percentiles were available from ages 8–19 years. Thin-slice ratings of overweight/obesity were reliably observed in preschoolers’ ages 3–6 years. Thin-slice ratings of overweight/obesity during preschool significantly predicted adolescent BMI percentiles at six separate assessments spanning ages 8–19 years. Further, preschool overweight/obese thin-slice ratings were associated with more physical health problems over time and less sport/activity participation during preschool. Overweight/obesity can be observationally identified in preschool-age children and offers a reliable estimate of future BMI percentile. Study findings highlight how previously collected data could be utilized to study the developmental trajectories of overweight/obesity to inform this critical public health problem.

The Diagnostic and Statistical Manual of Mental Disorders (DSM), used to diagnose psychiatric disorders, was revised to DSM-5 in 2013. Changes were made to the criteria for obsessive-compulsive disorder (OCD), a disorder with a lifetime prevalence of 1% to 3% in children.1 Prior revisions to OCD criteria (from DSM-III to DSM-IV) resulted in lower reported prevalence rates,2 but this is not yet clear with DSM-5. In DSM-5, the definition of obsessions was broadened (Table 1), and the requirement that obsessions cause marked anxiety or distress was removed. Thus we examined rates of OCD within the Adolescent Brain Cognitive Development (ABCD) study3 using both DSM-IV and DSM-5 criteria.

Objective Research implicates environmental risk factors, including correlates of urbanicity, deprivation, and environmental toxins, in psychotic-like experiences (PLEs). The current study examined associations between several types of environmental risk factors and PLEs in school-age children, whether these associations were specific to PLEs or generalized to other psychopathology, and examined possible neural mechanisms for significant associations. Method The current study used cross-sectional data from 10,328 children 9–10 years old from the Adolescent Brain Cognitive Development (ABCD) Study. Hierarchical linear models examined associations between PLEs and geocoded environmental risk factors and whether associations generalized to internalizing/externalizing symptoms. Mediation models examined evidence of structural magnetic resonance imaging abnormalities (eg, intracranial volume) potentially mediating associations between PLEs and environmental risk factors. Results Specific types of environmental risk factors, namely, measures of urbanicity (eg, drug offense exposure, less perception of neighborhood safety), deprivation (eg, overall deprivation, poverty rate), and lead exposure risk, were associated with PLEs. These associations showed evidence of stronger associations with PLEs than internalizing/externalizing symptoms (especially overall deprivation, poverty, drug offense exposure, and lead exposure risk). There was evidence that brain volume mediated between 11% and 25% of associations of poverty, perception of neighborhood safety, and lead exposure risk with PLEs. Conclusion Although in the context of cross-sectional analyses, this evidence is consistent with neural measures partially mediating the association between PLEs and environmental exposures. This study also replicated and extended recent findings of associations between PLEs and environmental exposures, finding evidence for specific associations with correlates of urbanicity, deprivation, and lead exposure risk.

Understanding longitudinal associations between problematic peer relations and psychopathology is needed to inform public health. Three models have been proposed: Poor peer relations (a) lead or are a risk factor for psychopathology, (b) lag or are a consequence of psychopathology, or (c) both lead and lag psychopathology. Another model is that poor peer relations lead or lag psychopathology depending on the developmental period. To test these models, youths’ peer relations and clinical symptoms were assessed up to six times between ages 3 and 11 in 306 children. Bivariate latent-change-score models tested leading and lagging longitudinal relationships between children’s peer relations (peer victimization/rejection, peer-directed aggression, social withdrawal, prosocial behavior) and psychopathology (depression, anxiety, and externalizing symptoms). Peer victimization/rejection was a leading indicator of depression from early childhood into preadolescence. Peer-directed aggression was a leading indicator of externalizing symptoms (in late childhood).

The amygdala has been implicated in processing threat and learning fear. However, the amygdala also responds to motivationally relevant stimuli even in the absence of explicit emotional content. We investigated the relationship among amygdala activation, cognitive and emotional factors, and fMRI task data in participants from the Young Adult Human Connectome Project. We expected to see variation in amygdala activation that corresponded with variation in traits that could affect the salience of task related stimuli (i.e. internalizing symptoms and fearful faces). We found no relationship between amygdala activation during face viewing and emotion related traits. However, amygdala activation under working memory load was negatively correlated with fluid intelligence and reading level. There was also a negative relationship between task performance and activation in the amygdala. The observed relationship suggests that the role of amygdala is not limited to the processing of emotional content of incoming information, but is instead related to salience, which can be influenced by individual differences.

Background Effective emotion regulation (ER) may be supported by 1) accurate emotion identification, encoding, and maintenance of emotional states and related brain activity of regions involved in emotional response (i.e., amygdala, ventral/posterior insula) and 2) cognitive processes that implement reframing, supported by activation in cognitive control brain regions (e.g., frontal, insular, and parietal cortices). The purpose of this project was to examine how emotion labeling ability in early childhood is related to ER concurrently and prospectively. Methods Data from a prospective longitudinal study of youths at risk for depression, including measures of emotion labeling (i.e., Facial Affect Comprehension Evaluation) and ER ability (i.e., Emotion Regulation Checklist) and strategy use (i.e., Cognitive Emotion Regulation Questionnaire, Children’s Response Style Questionnaire), and functional magnetic resonance imaging data during a sadness ER task (N = 139) were examined. Results Findings from multilevel modeling and linear regression suggested that greater emotion labeling ability of more difficult emotions in early childhood was associated with enhanced parent-reported ER in adolescence, but not with a tendency to engage in adaptive or maladaptive ER strategies. Recognition of fear and surprise predicted greater activation in cortical regions involved in cognitive control during an ER of sadness task, including in the insula, anterior cingulate cortex, dorsal medial prefrontal cortex, and inferior frontal gyrus. Conclusions These findings suggest that early ability to identify and label difficult facial emotions in early childhood is associated with better ER in adolescence and enhanced activity of cognitive control regions of the brain.

Background Executive Function Deficits (EFD) accompany depression and are associated with poor outcomes in older adults. We examined whether Intermittent Theta Burst Stimulation (iTBS) could improve depression with EFD. Methods Thirteen geriatric patients with depression and EFD were enrolled. Open label iTBS was delivered bilaterally over the dorso-lateral-prefrontal-cortex for four weeks. Results Montgomery Asberg Depression Scale scores improved significantly from baseline to treatment-end, mean change in score = 11.82 points, 95% CI = 8.3, 15.4. The Flanker Inhibitory control and attention test showed significant improvement in executive function from baseline to treatment-end, mean change in score = −7.73, 95% CI ( −13.54, −1.92). Side effects included twitching in facial muscles (n = 11), headaches (n = 10) and stimulation discomfort (n = 4). Limitations Small sample size and lack of a sham comparator. Conclusion iTBS improved depression with EFD in older adults. Side effects appeared higher than in previous iTBS studies.

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

Prior research has shown that sipping of alcohol begins to emerge during childhood and is potentially etiologically significant for later substance use problems. Using a large, community sample of 9- and 10-year-olds (N = 11,872; 53% female), we examined individual differences in precocious alcohol use in the form of alcohol sipping. We focused explicitly on features that are robust and well-demonstrated correlates of, and antecedents to, alcohol excess and related problems later in the lifespan, including youth- and parent-reported externalizing traits (i.e., impulsivity, behavioral inhibition and activation) and psychopathology. Seventeen percent of the sample reported sipping alcohol outside of a religiously sanctioned activity by age 9 or 10. Several aspects of psychopathology and personality emerged as small but reliable correlates of sipping. Nonreligious sipping was related to youth-reported impulsigenic traits, aspects of behavioral activation, prodromal psychotic-like symptoms, and mood disorder diagnoses, as well as parent-reported externalizing disorder diagnoses. Religious sipping was unexpectedly associated with certain aspects of impulsivity. Together, our findings point to the potential importance of impulsivity and other transdiagnostic indicators of psychopathology (e.g., emotion dysregulation, novelty seeking) in the earliest forms of drinking behavior.

The current study examines the measurement properties and validity of a novel, abbreviated youth version of the UPPS-P Impulsive Behavior Scale that was developed to maintain measurement consistency with the existing adult short form. Specifically, we examined this scale's (a) factor structure; (b) measurement and structural invariance across four demographic characteristics: gender, ethnicity, household income, and parental education; and (c) correlates using a subset of 4,521 preadolescent (9- and 10-year old) children (53% male) from the baseline wave of the Adolescent Brain and Cognitive Development (ABCD) study, a large, community-based sample. Our findings supported a correlated 5-factor model, as well as a hierarchical model that recaptured the covariation among these 5 lower-order factors in three higher-order factors. Both of these models are consistent with the commonly observed structure of the UPPS-P among adults. We established measurement invariance across all demographic characteristics. Finally, our UPPS-P scales evidenced good convergent and discriminant validity with a broad swath of theoretically relevant external criteria, including self- and parent-reported personality and psychopathology, as well as lab-based neurocognitive tasks. Our findings indicate that we can assess multidimensional impulsivity in children reliably and validly by means of self-report, allowing assessment of this critical domain at early stages of development. We hope that this measure will facilitate the study of impulsivity in large-scale samples to begin to understand the evolution and long-term consequences of impulsivity. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background Maladaptive guilt can develop by age three and is associated with severe affective psychopathology in adolescents and adults. Yet, little is known about its prevalence prior to adolescence, or which children are at greatest risk of developing this symptom. This study examined the prevalence and correlates of maladaptive guilt in middle childhood. Methods This study examined a large community sample of 9-to 10-year-old children (N = 4485) from the Adolescent Brain and Cognitive Development (ABCD) study. Maladaptive guilt was assessed through the Kiddie Schedule for Affective Disorders and Schizophrenia for DSM-5. Parental rejection, family conflict, and parental depression were assessed via questionnaires. Results In depressed children, a 1-month prevalence of maladaptive guilt of 18.4% and a lifetime prevalence of 30.8% was found. Lifetime rates ranged from 1.8 to 4.1% in children with other psychiatric disorders. Cross-sectionally, maladaptive guilt was associated with lower family income-to-needs, greater family conflict, a history of maternal depression, and greater parental rejection. These findings held when controlling for children's depressive severity, indicating that these associations are specific to maladaptive guilt. Limitations Maladaptive guilt was assessed through one item, though many studies of maladaptive guilt measure the symptom in this manner. Conclusions Findings suggest that it may be beneficial for clinicians to assess for maladaptive guilt beyond the context of assessment for depression, particularly with children of low socioeconomic status and children of depressed mothers, whom this study suggests are at higher risk. Negative family climates and parenting might also be important targets of preventative interventions.

Long-standing hypotheses about schizophrenia as a "dysconnection" syndrome are consistent with the idea that mental illness arises in part from brain circuit disruptions, with impairments in cognition and behavior occurring because of a failure of coordinated action across multiple brain regions. One such theory, put forth by Andreasen and colleagues, suggested that schizophrenia involves a disruption in the integration of cortical-striatal-thalamic-cerebellar circuits.1 Anatomical work in primates has shown that the thalamus is topographically organized into parallel pathways connecting specific thalamic nuclei to different regions of cortex. The medial dorsal and anterior nuclei of the thalamus project to the dorsolateral prefrontal cortex (dlPFC), whereas the lateral nuclei project more to sensorimotor regions, with similar findings in functional brain connectivity studies in humans. A large body of evidence has shown reduced connectivity from bilateral thalamic regions, medial dorsal, and anterior nuclei in particular, to the bilateral dlPFC, dorsal anterior cingulate, parts of the striatum, and bilateral cerebellum in schizophrenia.2 This is often coupled increased connectivity between the thalamus, lateral nuclei in particular, and motor, visual, and/or auditory sensory regions.2.

ObjectivePrenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression. Potential neural intermediaries remain understudied. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood.MethodsPrenatal SSRI exposure (retrospective caregiver-report), depressive symptoms (caregiver-reported Child Behavior Checklist) and brain structure (MRI-derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns=5,420-7,528; 235 with prenatal SSRI exposure; 9-10 years old) who completed the baseline session of the Adolescent Brain and Cognitive DevelopmentSM Study. Covariates included familial (e.g., 1st degree relative depression density), pregnancy (e.g., planned pregnancy), and child (e.g., birthweight) variables. Matrix spectral decomposition was used to address multiple testing.ResultsThere was no evidence that prenatal SSRI exposure was associated with child depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b=145.3 mm2, p=0.00038) and lateral occipital cortical thickness (b=0.0272 mm, p=0.0000079), neither of which was associated with depressive symptoms.ConclusionsOur findings, combined with adverse associations of prenatal exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for child depression during middle childhood should not discourage SSRI use during pregnancy. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.

The reward positivity (RewP) is a widely studied measure of neural response to rewards, yet little is known about normative developmental characteristics of the RewP during early childhood. The present study utilized a pooled community sample of 309 4- to 6-year-old children who participated in the Doors guessing game to examine the latency and amplitude of the RewP. Peak detection of the gain-loss difference waveform was conducted for electrodes Fz, Cz, Pz, Oz and the mean activity in a 100 ms window centered around this peak was analyzed. There was a significant decrease in RewP latency (RewP was earlier) and increase in RewP amplitude (RewP magnitude was larger) with advancing age in this cross-sectional analysis. Further, these were independent effects, as both RewP latency and RewP amplitude were uniquely associated with children's age. Moreover, our results indicate that the RewP latency in 4- to 6-year-olds falls outside the 250-350 ms window typically used to quantify the RewP (RewP latency in our sample = 381 ms; SD = 60.15). The internal consistency for latency (.64) and amplitude (.27) of the RewP were characterized by moderate to low reliability, consistent with previous work on the reliability of difference scores. Overall, results demonstrate RewP differences in both timing and amplitude across age in early childhood, and suggest that both amplitude and latency of the RewP might function as individual difference measures of reward processing. These findings are discussed in the context of methodological considerations and the development of reward processing across early childhood.

Importance A substantial proportion of the 40 million people in the US who present to emergency departments (EDs) each year after traumatic events develop posttraumatic stress disorder (PTSD) or major depressive episode (MDE). Accurately identifying patients at high risk in the ED would facilitate the targeting of preventive interventions. Objectives To develop and validate a prediction tool based on ED reports after a motor vehicle collision to predict PTSD or MDE 3 months later. Design, Setting, and Participants The Advancing Understanding of Recovery After Trauma (AURORA) study is a longitudinal study that examined adverse posttraumatic neuropsychiatric sequalae among patients who presented to 28 US urban EDs in the immediate aftermath of a traumatic experience. Enrollment began on September 25, 2017. The 1003 patients considered in this diagnostic/prognostic report completed 3-month assessments by January 31, 2020. Each patient received a baseline ED assessment along with follow-up self-report surveys 2 weeks, 8 weeks, and 3 months later. An ensemble machine learning method was used to predict 3-month PTSD or MDE from baseline information. Data analysis was performed from November 1, 2020, to May 31, 2021. Main Outcomes and Measures The PTSD Checklist forDSM-5was used to assess PTSD and the Patient Reported Outcomes Measurement Information System Depression Short-Form 8b to assess MDE. Results A total of 1003 patients (median [interquartile range] age, 34.5 [24-43] years; 715 [weighted 67.9%] female; 100 [weighted 10.7%] Hispanic, 537 [weighted 52.7%] non-Hispanic Black, 324 [weighted 32.2%] non-Hispanic White, and 42 [weighted 4.4%] of non-Hispanic other race or ethnicity were included in this study. A total of 274 patients (weighted 26.6%) met criteria for 3-month PTSD or MDE. An ensemble machine learning model restricted to 30 predictors estimated in a training sample (patients from the Northeast or Midwest) had good prediction accuracy (mean [SE] area under the curve [AUC], 0.815 [0.031]) and calibration (mean [SE] integrated calibration index, 0.040 [0.002]; mean [SE] expected calibration error, 0.039 [0.002]) in an independent test sample (patients from the South). Patients in the top 30% of predicted risk accounted for 65% of all 3-month PTSD or MDE, with a mean (SE) positive predictive value of 58.2% (6.4%) among these patients at high risk. The model had good consistency across regions of the country in terms of both AUC (mean [SE], 0.789 [0.025] using the Northeast as the test sample and 0.809 [0.023] using the Midwest as the test sample) and calibration (mean [SE] integrated calibration index, 0.048 [0.003] using the Northeast as the test sample and 0.024 [0.001] using the Midwest as the test sample; mean [SE] expected calibration error, 0.034 [0.003] using the Northeast as the test sample and 0.025 [0.001] using the Midwest as the test sample). The most important predictors in terms of Shapley Additive Explanations values were symptoms of anxiety sensitivity and depressive disposition, psychological distress in the 30 days before motor vehicle collision, and peritraumatic psychosomatic symptoms. Conclusions and Relevance The results of this study suggest that a short set of questions feasible to administer in an ED can predict 3-month PTSD or MDE with good AUC, calibration, and geographic consistency. Patients at high risk can be identified in the ED for targeting if cost-effective preventive interventions are developed.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, post-concussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging, because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large scale (n = 5,000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for one year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

The ability to identify and label emotions may represent an early-life risk factor that relates to excess weight gain during childhood. The current study investigates the relationships between preschool emotion identification and early adolescent body mass index (BMI), as well as the mediating role of two variables: depressive symptoms and peer relations. In a longitudinal study, preschoolers completed an emotion identification task, and parents completed psychiatric assessments and a peer-relations questionnaire about their child. BMI percentile was measured at later time points in early adolescence. Poor emotion identification during preschool predicted increases in BMI percentile over time, with greater deficits in emotion identification ability relating to steeper increases in BMI percentile across early adolescence. Peer relations in preschool partially mediated the relationship between preschool emotion identification ability and adolescent BMI. This study provides novel information about potential targets for early interventions in the service of obesity prevention.

Reductions in positive affect are a salient feature of preschool-onset major depressive disorder. Yet, little is known about the psychophysiological correlates of this blunted positive affect and whether reduced physiological responding to pleasant stimuli may differentiate depressed and healthy young children. 120 four-to-seven year old children with current depression and 63 psychiatrically healthy 4-to-7 year old children completed a simple picture-viewing task of pleasant and neutral pictures while event-related potentials (ERPs) were recorded. The early-childhood version of the Kiddie Schedule for Affective Disorders and Depression was used to establish psychiatric diagnoses. A one-way ANCOVA was used to test for group differences in response to pleasant and neutral pictures. Young children with depression showed a reduced response to pleasant vs. neutral pictures (LPP), after controlling for children's age (F(1,180) = 4.15, p = 0.04, η2 = 0.02). The LPP for the children with preschool-onset depression (M = 0.99, SE = 0.65) was significantly smaller than the LPP in the healthy group of young children (M = 3.27, SE = 0.90). This difference did not vary as a function of depression or anhedonia severity within the group with depression or the healthy children. Similar to older children and adolescents with depression, young children with depression display reductions in responsivity to pleasant stimuli as indexed by the LPP. These findings extend prior findings indicating a blunted response to pleasant stimuli in preschool- onset depression. Given the greater neuroplasticity of emotional response and regulation, these findings suggest clinical attention to emotional response to pleasure is an important target in preschool-onset depression. Clinical trial registration information: A Randomized Control Trial of PCIT-ED for Preschool Depression; http://clinicaltrials.gov/;NCT02076425.

Clinical depression can occur in young children as early as age three. This very early onset variant of depression shows the same clinical features with developmental adjustments as depression that onsets later in life. One robust neural feature of adult depression is reduced hippocampal volume. We measured hippocampal volume in a sample of 35 children aged 4 to 7 who were either in a clinical trial for preschool onset depression or were recruited from the community. We used T1 MPRAGE acquisitions on a Siemen’s Scanner, with Freesurfer 5.3 used to segment the hippocampus. Depression was measured using the K-SADS early childhood (K-SADS-EC) to create a dimensional depression severity score and the Child Behavior Checklist (CBCL) Depression T-Score. Multilevel models indicated that greater depression severity as measured by either the CBCL Depression Score or the K-SADS-EC was associated with lower hippocampal volume, even controlling for total gray matter, maternal depression, income-to-needs ratio, and stressful life events. These data indicate evidence for reduced hippocampal volume among children with PO-MDD who were more severely depressed. Findings are consistent with the idea that hippocampal volume reductions are an early occurring associated neural marker of MDD, particularly for more severe depression.

Child depression and anxiety have been associated with electronic media use, but the comorbidity between the two has rarely been accounted for in analyses. We examined both child and parent reports of electronic media use in relation to parent-reported child depression and anxiety. Using survey and interview data collected for 9- to 11-year-olds from the 21-site adolescent brain cognitive development study, we conducted generalized linear mixed models. Our results demonstrated that electronic media use was more strongly associated with depression than anxiety, and that accounting for depression significantly reduced the relationship between electronic media use and anxiety. Different categories of electronic media showed differential relationships to anxiety and depression, with video gaming and video chatting related to anxiety, but video watching related to depression. These findings provide important data to ground theories of the mechanisms that contribute to these associations. Electronic supplementary material The online version of this article (10.1007/s10578-019-00892-7) contains supplementary material, which is available to authorized users.

The National Institute of Mental Health (NIMH) plays an enormous role in establishing the agenda for mental health research across the country (its 2016 appropriation was nearly $1.5 billion; NIMH, 2016a). As the primary funder of research that will lead to development of new assessments and interventions to identify and combat mental illness, the priorities set by NIMH have a major impact on the mental health of our nation and training of the next generation of clinical scientists. Joshua Gordon has recently begun his term as the new Director of NIMH and has been meeting with different organizations to understand how they can contribute to the grand challenge of reducing the burden of mental illness. As a group of clinical psychological scientists (most representing the Coalition for the Advancement and Application of Psychological Science), he asked what we saw as key gaps in our understanding of the burden of mental illnesses and psychological disorders that psychosocial research could help fill. In response, we first present data illustrating how funding trends have shifted toward biomedical research over the past 18 years and then consider the objectives NIMH has defined in its recent strategic plan (U.S. Department of Health and Human Services, National Institutes of Health, & National Institute of Mental Health, 2015). We then note ways that advances in psychosocial research can help achieve these objectives. Critically, this involves integrating psychosocial and biomedical approaches to efficiently relieve the suffering of millions of Americans who struggle with mental illnesses and psychological disorders. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

This article has been retracted at the request of John H. Krystal, MD, Editor of Biological Psychiatry, with agreement from all authors. See Elsevier Policy on Article Withdrawal ( https://www.elsevier.com/about/policies/article-withdrawal ). The authors discovered an error in the scoring of the ERP data in this article. Specifically, the ERP in the authors' acquisition and processing stream is live referenced to CZ, and then should be re-referenced in post-processing to TP9 and TP10, as described in the paper. However, the authors discovered that they had accidentally continued to include Cz along with TP9 and TP10 in the template to re-reference the ERP data in post-processing. The authors reprocessed all of the data with only TP9 and TP10 in the referencing, as originally described in the manuscript, and then re-ran all of the analyses. The majority of the key results remained the same in terms of significance and interpretation. The results continue to show that children in PCIT_ED show a greater increase in RewP as a function of treatment than the waitlist group; however, the correlation with the corrected data is in the same direction, but reduced in magnitude and no longer significant. Thus, a greater change in RewP is no longer significantly associated with a greater reduction in MDD symptoms. This error affects the abstract, the results, Table 2, Figures 1-3, discussion, and supplement. The authors voluntarily informed the Journal of this honest error upon its discovery. Because of the extent and nature of the changes to the paper, the editors and authors concluded that, to ensure maximum clarity and transparency, the only course of action was to retract this version of the paper. The authors revised the paper, which the Journal had re-reviewed. The new version was accepted and has been published: 10.1016/j.biopsych.2020.06.032.

Recent studies have found that higher levels of exercise are associated with fewer symptoms of depression among young people. In addition, research suggests that exercise may modify hippocampal volume, a brain region that has been found to show reduced volume in depression. However, it is not clear whether this relationship emerges as early as preadolescence.We examined data from a nationwide sample of 4191 children 9 to 11 years of age from the Adolescent Brain and Cognitive Development Study. The parents of the children completed the Child Behavior Checklist, providing data about the child's depressive symptoms, and the Sports and Activities Questionnaire, which provided data about the child's participation in 23 sports. Children also took part in a structural magnetic resonance imaging scan, providing us with measures of bilateral hippocampal volume.Sports involvement interacted with sex to predict depressive symptoms, with a negative relationship found in boys only (t = -5.257, β = -.115, p.001). Sports involvement was positively correlated with hippocampal volume in both boys and girls (t = 2.810, β = .035, p = .007). Hippocampal volume also interacted with sex to predict depressive symptoms, with a negative relationship in boys (t = -2.562, β = -.070, p = .010), and served as a partial mediator for the relationship between involvement in sports and depressive symptoms in boys.These findings help illuminate a potential neural mechanism for the impact of exercise on the developing brain, and the differential effects in boys versus girls mirror findings in the animal literature. More research is needed to understand the causal relationships between these constructs.

Research examining psychotic disorders typically involves comparison between individuals with a clinical disorder and healthy controls. However, research suggests that psychotic symptoms, such as delusions and hallucinations, may exist on a continuum ranging from variation in healthy individuals to diagnosable psychotic disorders. On this continuum, some individuals endorse occasional psychotic like experiences (PLEs) that do not cause sufficient impairment or distress to warrant a clinical diagnosis. Given this continuum model, one might expect to observe impairments in those with PLEs in the same behavioral domains impaired in schizophrenia. Thus, we examined two domains typically impaired in schizophrenia, effort allocation and reward responsivity, in a large university sample (n = 126). Participants completed tasks assessing effort-based decision-making, reward responsivity, and questionnaires assessing PLEs. Greater PLEs were associated with greater effort expenditure regardless of probability of receiving a reward or reward value. Higher PLEs were related to greater positive feelings when receiving rewards. Importantly, these relationships remained the same when controlling for other symptoms such as depression, anhedonia, and anxiety. These findings suggest that PLEs may be associated with hypersensitivity to reward at the less severe end of the psychotic continuum, with effort to attain a reward expended in a potentially inefficient manner. This pattern is consistent with models of hyperdopaminergic states in psychotic individuals not taking antipsychotic medications, given the role of dopamine in modulating effort allocation and reward anticipation.

Individual differences in child eating self-regulation are associated with excess weight gain and may be explained, in part, by the family feeding environment and a child's general propensity to self-regulate outside of the context of eating (i.e., general self-regulation). Several studies have examined the associations between food parenting behaviors, child eating and general self-regulation, and child weight separately. However, there are a paucity of data on whether and how these factors interact to confer risk for weight gain in early childhood. The current systematic review identified 32 longitudinal studies that examined unidirectional or bidirectional associations among one or more of the following paths: food parenting behaviors and child eating self-regulation (path 1); child eating self-regulation and child weight (path 2); child eating self-regulation and child general self-regulation (path 3); food parenting behaviors and child general self-regulation (path 4); and child general self-regulation and child weight (path 5). Results indicated relationships of food parenting behaviors to child eating self-regulation, child weight to child eating self-regulation, and child general self-regulation to child weight. However, there were scant longitudinal data that examined paths 3 and 4. Further research on the developmental correlates of child eating self-regulation is needed to identify parent and child targets for early childhood obesity prevention.

Background Early-life experiences have profound effects on functioning in adulthood. Altered cortical development may be one mechanism through which early-life experiences, including poverty and psychopathology symptoms, affect outcomes. However, there is little prospective research beginning early in development that combines clinician-rated psychopathology symptoms and multiwave magnetic resonance imaging to examine when these relationships emerge. Methods Children from the Preschool Depression Study who completed diagnostic interviews at three different developmental stages (preschool, school age, early adolescent) and up to three magnetic resonance imaging scans beginning in middle childhood participated in this study (N = 138). Multilevel models were used to calculate intercepts and slopes of cortical thickness within a priori cortical regions of interest. Linear regressions probed how early-life poverty and psychopathology (depression, anxiety, and externalizing symptoms at separate developmental periods) related to intercept/slope. Results Collectively, experiences during the preschool period predicted reduced cortical thickness, via either reduced intercept or accelerated thinning (slope). Early-life poverty predicted intercepts within sensory and sensory-motor integration regions. Beyond poverty, preschool anxiety symptoms predicted intercepts within the insula, subgenual cingulate, and inferior parietal cortex. Preschool externalizing symptoms predicted accelerated thinning within prefrontal and parietal cortices. Depression and anxiety/externalizing symptoms at later ages were not significant predictors. Conclusions Early childhood is a critical period of risk; experiences at this developmental stage specifically have the potential for prolonged influence on brain development. Negative early experiences collectively predicted reduced cortical thickness, but the specific neural systems affected aligned with those typically implicated in these individual disorders/experiences.

Background : Previous work has indicated that differences in neurocognitive functioning may predict the development of adverse post-traumatic neuropsychiatric sequelae (APNS). Such differences may be vulnerability factors or simply correlates of APNS-related symptoms. Longitudinal studies that measure neurocognitive functioning at the time of trauma are needed to determine whether such differences precede the development of APNS. Methods : Here, we present findings from a subsample of 666 ambulatory patients from the AURORA (A dvancing U nderstanding of R ec O very afteR traum A ) study. All patients presented to EDs after a motor vehicle collision (MVC). We examined associations of neurocognitive test performance shortly after MVC with peritraumatic symptoms in the ED and APNS (depression, post-traumatic stress, post-concussive symptoms, and pain) 2 weeks and 8 weeks later. Neurocognitive tests assessed processing speed, attention, verbal reasoning, memory, and social perception. Results : Distress in the ED was associated with poorer processing speed and short-term memory. Poorer short-term memory was also associated with depression at 2 weeks post-MVC, even after controlling for peritraumatic distress. Finally, higher vocabulary scores were associated with pain 2 weeks post-MVC. Limitations : Self-selection biases among those who present to the ED and enroll in the study limit generalizability. Also, it is not clear whether observed neurocognitive differences predate MVC exposure or arise in the immediate aftermath of MVC exposure. Conclusions : Our results suggest that processing speed and short-term memory may be useful predictors of trauma-related characteristics and the development of some APNS, making such measures clinically-relevant for identifying at-risk individuals.

Background Cross-sectional studies have found that individuals with posttraumatic stress disorder (PTSD) exhibit deficits in autonomic functioning. While PTSD rates are twice as high in women compared to men, sex differences in autonomic functioning are relatively unknown among trauma-exposed populations. The current study used a prospective design to examine sex differences in posttraumatic autonomic functioning. Methods 192 participants were recruited from emergency departments following trauma exposure (Mean age = 35.88, 68.2% female). Skin conductance was measured in the emergency department; fear conditioning was completed two weeks later and included measures of blood pressure (BP), heart rate (HR), and high frequency heart rate variability (HF-HRV). PTSD symptoms were assessed 8 weeks after trauma. Results 2-week systolic BP was significantly higher in men, while 2-week HR was significantly higher in women, and a sex by PTSD interaction suggested that women who developed PTSD demonstrated the highest HR levels. Two-week HF-HRV was significantly lower in women, and a sex by PTSD interaction suggested that women with PTSD demonstrated the lowest HF-HRV levels. Skin conductance response in the emergency department was associated with 2-week HR and HF-HRV only among women who developed PTSD. Conclusions Our results indicate that there are notable sex differences in autonomic functioning among trauma-exposed individuals. Differences in sympathetic biomarkers (BP and HR) may have implications for cardiovascular disease risk given that sympathetic arousal is a mechanism implicated in this risk among PTSD populations. Future research examining differential pathways between PTSD and cardiovascular risk among men versus women is warranted.

Excessive response to unexpected or "deviant" stimuli during infancy and early childhood represents an early risk marker for anxiety disorders. However, research has yet to delineate the specific brain regions underlying the neonatal response to deviant stimuli near birth and the relation to risk for anxiety disorders. The authors used task-based functional MRI (fMRI) to delineate the neonatal response to deviant stimuli and its relationship to maternal trait anxiety.The authors used fMRI to measure brain activity evoked by deviant auditory stimuli in 45 sleeping neonates (mean age, 27.8 days; 60% female; 64% African American). In 41 of the infants, neural response to deviant stimuli was examined in relation to maternal trait anxiety on the State-Trait Anxiety Inventory, a familial risk factor for offspring anxiety.Neonates manifested a robust and widespread neural response to deviant stimuli that resembles patterns found previously in adults. Higher maternal trait anxiety was related to higher responses within multiple brain regions, including the left and right anterior insula, the ventrolateral prefrontal cortex, and multiple areas within the anterior cingulate cortex. These areas overlap with brain regions previously linked to anxiety disorders and other psychiatric illnesses in adults.The neural architecture sensitive to deviant stimuli robustly functions in newborns. Excessive responsiveness of some circuitry components at birth may signal risk for anxiety and other psychiatric disorders.

Background Motivational deficits in people with psychosis may be a result of impairments in reinforcement learning (RL). Therefore, behavioral paradigms that can accurately measure these impairments and their change over time are essential. Methods We examined the reliability and replicability of 2 RL paradigms (1 implicit and 1 explicit, each with positive and negative reinforcement components) given at 2 time points to healthy controls (n = 75), and people with bipolar disorder (n = 62), schizoaffective disorder (n = 60), and schizophrenia (n = 68). Results Internal consistency was acceptable (mean α = 0.78 ± 0.15), but test-retest reliability was fair to low (mean intraclass correlation = 0.33 ± 0.25) for both implicit and explicit RL. There were no clear effects of practice for these tasks. Largely, performance on these tasks shows intact implicit and impaired explicit RL in psychosis. Symptom presentation did not relate to performance in any robust way. Conclusions Our findings replicate previous literature showing spared implicit RL and impaired explicit reinforcement in psychosis. This suggests typical basal ganglia dopamine release, but atypical recruitment of the orbitofrontal and dorsolateral prefrontal cortices. However, we found that these tasks have only fair to low test-retest reliability and thus may not be useful for assessing change over time in clinical trials.

Recent research suggests that schizophrenia is associated with reduced effort allocation. We examined the willingness to expend effort, neural correlates of effort allocation, and the relationship of effort to daily motivational experience in individuals with schizophrenia. We recruited 28 individuals with schizophrenia and 30 control participants to perform an effort task during functional MRI. Individuals with schizophrenia also completed a protocol involving ecological momentary assessment (EMA). Individuals with schizophrenia with severe negative symptoms were less willing to expend effort for rewards. Daily EMAs of motivation were positively associated with effort allocation on a trend level. Individuals with schizophrenia and control participants displayed similar increases in blood-oxygen-level-dependent (BOLD) activation in frontal, cingulate, parietal, and insular regions during effort-based decision making. However, negative symptoms were associated with reduced BOLD activation in the bilateral ventral striatum. These results replicate previous reports of reduced effort allocation in patients with severe negative symptoms and provide evidence for the role of the ventral striatum in effort impairments.

Posttraumatic stress disorder (PTSD) is associated with lower gray matter volume (GMV) in brain regions critical for extinction of learned threat. However, relationships among volume, extinction learning, and PTSD symptom development remain unclear. We investigated subcortical brain volumes in regions supporting extinction learning and fear-potentiated startle (FPS) to understand brain-behavior interactions that may impact PTSD symptom development in recently traumatized individuals. Participants (N = 99) completed magnetic resonance imaging and threat conditioning two weeks following trauma exposure as part of a multisite observational study to understand the neuropsychiatric effects of trauma (AURORA Study). Participants completed self-assessments of PTSD (PTSD Checklist for DSM-5; PCL-5), dissociation, and depression symptoms two- and eight-weeks post-trauma. We completed multiple regressions to investigate relationships between FPS during late extinction, GMV, and PTSD symptom development. The interaction between thalamic GMV and FPS during late extinction at two weeks post-trauma predicted PCL-5 scores eight weeks (t (75) = 2.49, β = 0.28, p = 0.015) post-trauma. Higher FPS predicted higher PCL-5 scores in the setting of increased thalamic GMV. Meanwhile, lower FPS also predicted higher PCL-5 scores in the setting of decreased thalamic GMV. Thalamic GMV and FPS interactions also predicted posttraumatic dissociative and depressive symptoms. Amygdala and hippocampus GMV by FPS interactions were not associated with posttraumatic symptom development. Taken together, thalamic GMV and FPS during late extinction interact to contribute to adverse posttraumatic neuropsychiatric outcomes. Multimodal assessments soon after trauma have the potential to distinguish key phenotypes vulnerable to posttraumatic neuropsychiatric outcomes.

Objective Suicidal thoughts and behaviors (STBs) represent a significant and escalating public health concern in youth. Evidence that STBs can emerge in the preschool years suggests that some pathways leading to clinically significant STBs begin early in life. Method This prospective longitudinal study examined the developmental trajectories of STBs in children from ages 3 to 17, oversampled for preschool-onset depression. Results Three unique trajectories of STBs across childhood and adolescence were identified: low class (n = 273) characterized by low rates of STBs, early-persistent class (n = 21) characterized by steadily increasing STBs, and late-onset class (n = 21) characterized by low rates of STBs through age 10 followed by a dramatic increase from ages 11 to 14 years. Preschool measures of depression symptoms, externalizing symptoms, impulsivity, and lower income relative to needs were associated with both high-risk STB classes. Both high-risk STB classes reported greater functional impairment, more externalizing symptoms, and more cumulative stressful life events in adolescence relative to the low class; the late-onset class also reported poorer academic functioning relative to both the early-persistent and low classes. Conclusion A significant minority of this prospectively followed group of preschool children evidenced STBs by and/or after age 10. Although relatively rare before age 10, approximately half of the children who experienced STBs in adolescence first exhibited STBs in early childhood and comprised a trajectory suggesting increasing STBs. In contrast, approximately half of children first exhibited STBs in early adolescence. Early screening and identification of at-risk youth during both preschool and late childhood is important for early intervention regarding STBs.

Post-Traumatic Stress Disorder (PTSD) is a psychiatric condition resulting from threatening or horrifying events. We hypothesized that circadian rhythm changes, measured by a wrist-worn research watch are predictive of post-trauma outcomes. Approach: 1618 post-trauma patients were enrolled after admission to emergency departments (ED). Three standardized questionnaires were administered at week eight to measure post-trauma outcomes related to PTSD, sleep disturbance, and pain interference with daily life. Pulse activity and movement data were captured from a research watch for eight weeks. Standard and novel movement and cardiovascular metrics that reflect circadian rhythms were derived using this data. These features were used to train different classifiers to predict the three outcomes derived from week-eight surveys. Clinical surveys administered at ED were also used as features in the baseline models. Results: The highest cross-validated performance of research watch-based features was achieved for classifying participants with pain interference by a logistic regression model, with an area under the receiver operating characteristic curve (AUC) of 0.70. The ED survey-based model achieved an AUC of 0.77, and the fusion of research watch and ED survey metrics improved the AUC to 0.79. Significance: This work represents the first attempt to predict and classify post-trauma symptoms from passive wearable data using machine learning approaches that leverage the circadian desynchrony in a potential PTSD population.

ObjectiveA potential distinguishing factor between more benign and transient psychotic-like experiences (PLEs) versus PLEs that predict risk for psychiatric disorders is whether the PLEs are sustained and distressing (sustained dPLEs). The current study examined associations of both sustained and transient dPLEs with relevant risk factors (e.g., cognition), use of mental health services, and functional correlates (e.g., school performance) in school-age children.MethodThe current study used three Adolescent Brain Cognitive Development℠ study data waves to create sustained dPLE (n=272), transient dPLE (n=244), and control (n=272) groups. Hierarchical linear models examined whether these groups differed in terms of use of mental health services, functional correlates, family history of mental disorders, other symptoms (e.g., parent-rated psychotic symptoms, internalizing, externalizing symptoms), environmental factors (e.g., adverse childhood events [ACEs]), cognitive functioning, developmental milestone delays, and neuroimaging indices.ResultsSeveral factors were more strongly associated with sustained versus transient dPLEs, including use of mental health services (for sustained vs. controls: d=0.38), drop in grades (d=--.30), other symptoms (i.e., parent-rated psychotic, bipolar, internalizing, externalizing, suicidality; 0.33>dsdsConclusionsThese results have implications for understanding the pathogenesis of dPLEs, including indicating that several factors may distinguish transient from persisting dPLEs in children, including higher symptoms and ACEs, lower executive functioning scores, greater use of mental health services, and worsening school performance.

Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.

BackgroundTo determine whether being raised in a stigmatizing context influences neurodevelopment in children.MethodsWe drew data from one of the first national, multi-site neuroimaging studies with substantial variability in sociopolitical contexts: the Adolescent Brain and Cognitive Development study (N=11,534; M=9.9 years). We measured structural stigma surrounding gender, race, and Latinx ethnicity using objective state-level indicators of social policies and prejudicial attitudes and individual-level experiences of perceived discrimination, and examined associations with two neural markers: hippocampal volume and amygdala reactivity to threat.ResultsIn a pre-registered analysis, we find that Black (B=−57.27, p=0.025) and Latinx (B=−41.02, p=0.037) youths raised in higher-stigma environments have smaller hippocampal volume than youths raised in low-stigma contexts, controlling for demographics and family socioeconomic status. This association was marginal among girls (p=0.082). The magnitude of the observed difference in hippocampal volume between high and low structural stigma contexts was equivalent to a $20,000 difference in annual family income. Stigmatizing environments were unrelated to hippocampal volume in non-stigmatized youth, providing evidence of specificity. Perceived discrimination was unrelated to hippocampal volume among any of the stigmatized groups. No associations between individual or structural forms of stigma and amygdala reactivity to threat were observed in the stigmatized groups.ConclusionsWe provide novel evidence that an objective measure of stigma at the contextual level (structural stigma) may have a stronger influence on neurodevelopment than subjective perceptions of stigma measured at the individual level, suggesting that contextual approaches may yield new insights into neurodevelopment.

Those experiencing psychotic like experiences (PLEs) are at higher risk for suicide ideation and behavior. However, it is unclear if PLEs are related to suicide ideation and behavior in children, and whether other factors such as impulsivity or emotion dysregulation might moderate the relationship. We hypothesize that PLEs are associated with suicide ideation and behavior, with impulsivity and emotion dysregulation moderating this relationship, in middle childhood. History of PLEs, suicide ideation and behavior, depression, emotion dysregulation, and impulsivity were assessed for 10,624 children aged 9 to 10.9 years (47.8% female, 34.4% minority race, 20.0% Hispanic) as part of the Adolescent Brain Cognitive Development℠ study. Hypotheses about associations between variables were assessed using hierarchical linear modeling. PLEs were associated with suicide ideation and suicide behavior even when controlling for depression severity. Emotion dysregulation and impulsivity were also associated with suicide ideation and moderated the relationship between PLEs and suicide ideation. Variation in suicide ideation due to impulsivity and emotion dysregulation appears to be strongest when people are experiencing low levels to no PLEs. Only impulsivity and PLEs were associated with suicide behavior. Depression was associated with suicide ideation, but not suicide behavior. PLEs may be an important risk factor for suicide ideation and behavior in 9 to 10-year-old children, comparable to adult and adolescent populations. When considering prevention of suicidality, these data suggest that considering the relations between PLEs, impulsivity and emotion dysregulation may be important.