Affirming NIH's commitment to addressing structural racism in the biomedical research enterprise.

NIH has acknowledged and committed to ending structural racism. The framework for NIH's approach, summarized here, includes understanding barriers; developing robust health disparities/equity research; improving its internal culture; being transparent and accountable; and changing the extramural ecosystem so that diversity, equity, and inclusion are reflected in funded research and the biomedical workforce.

Disrupted sensorimotor and social-cognitive networks underlie symptoms in childhood-onset schizophrenia.

Schizophrenia is increasingly recognized as a neurodevelopmental disorder with altered connectivity among brain networks. In the current study we examined large-scale network interactions in childhood-onset schizophrenia, a severe form of the disease with salient genetic and neurobiological abnormalities. Using a data-driven analysis of resting-state functional magnetic resonance imaging fluctuations, we characterized data from 19 patients with schizophrenia and 26 typically developing controls, group matched for age, sex, handedness, and magnitude of head motion during scanning. This approach identified 26 regions with decreased functional correlations in schizophrenia compared to controls. These regions were found to organize into two function-related networks, the first with regions associated with social and higher-level cognitive processing, and the second with regions involved in somatosensory and motor processing. Analyses of across- and within-network regional interactions revealed pronounced across-network decreases in functional connectivity in the schizophrenia group, as well as a set of across-network relationships with overall negative coupling indicating competitive or opponent network dynamics. Critically, across-network decreases in functional connectivity in schizophrenia predicted the severity of positive symptoms in the disorder, such as hallucinations and delusions. By contrast, decreases in functional connectivity within the social-cognitive network of regions predicted the severity of negative symptoms, such as impoverished speech and flattened affect. These results point toward the role that abnormal integration of sensorimotor and social-cognitive processing may play in the pathophysiology and symptomatology of schizophrenia.

Functional and clinical insights from neuroimaging studies in childhood-onset schizophrenia.

Childhood-onset schizophrenia is a rare pediatric onset psychiatric disorder continuous with and typically more severe than its adult counterpart. Neuroimaging research conducted on this population has revealed similarly severe neural abnormalities. When taken as a whole, neuroimaging research in this population shows generally decreased cortical gray matter coupled with white matter connectivity abnormalities, suggesting an anatomical basis for deficits in executive function. Subcortical abnormalities are pronounced in limbic structures, where volumetric deficits are likely related to social skill deficits, and cerebellar deficits that have been correlated to cognitive abnormalities. Structures relevant to motor processing also show a significant alteration, with volumetric increase in basal ganglia structures likely due to antipsychotic administration. Neuroimaging of this disorder shows an important clinical image of exaggerated cortical loss, altered white matter connectivity, and differences in structural development of subcortical areas during the course of development and provides important background to the disease state.

Neuropsychological and dimensional behavioral trait profiles in Costa Rican ADHD sib pairs: Potential intermediate phenotypes for genetic studies.

Attention deficit hyperactivity disorder (ADHD) is associated with substantial functional impairment in children and in adults. Many individuals with ADHD have clear neurocognitive deficits, including problems with visual attention, processing speed, and set shifting. ADHD is etiologically complex, and although genetic factors play a role in its development, much of the genetic contribution to ADHD remains unidentified. We conducted clinical and neuropsychological assessments of 294 individuals (269 with ADHD) from 163 families (48 multigenerational families created using genealogical reconstruction, 78 affected sib pair families, and 37 trios) from the Central Valley of Costa Rica (CVCR). We used principal components analysis (PCA) to group neurocognitive and behavioral variables using the subscales of the Child Behavior Checklist (CBCL) and 15 neuropsychological measures, and created quantitative traits for heritability analyses. We identified seven cognitive and two behavioral domains. Individuals with ADHD were significantly more impaired than their unaffected siblings on most behavioral and cognitive domains. The verbal IQ domain had the highest heritability (92%), followed by auditory attention (87%), visual processing speed and problem solving (85%), and externalizing symptoms (81%). The quantitative traits identified here have high heritabilities, similar to the reported heritability of ADHD (70-90%), and may represent appropriate alternative phenotypes for genetic studies. The use of multigenerational families from a genetically isolated population may facilitate the identification of ADHD risk genes in the face of phenotypic and genetic heterogeneity.

Internally displaced "victims of armed conflict" in Colombia: the trajectory and trauma signature of forced migration.

While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement.

Concordance between two intrapersonal psychological resilience scales: how should we be measuring resilience?

BACKGROUND: While resilience has generated a lot of interest in mental health, operationalizing the construct of resilience remains an important challenge. This study aims to evaluate the concordance of two resilience scales that evaluate intrapersonal aspects of resilience in adolescents. METHODS: Cross-sectional evaluation of internal consistency, concordance, and correlation of the Individual Protective Factors Index Questionnaire (IPFI) and the Adolescent Resilience Scale (ARS) in sixth grade students of three low-income public schools in Colombia. RESULTS: 325 adolescents (41.5% female) participated in the study (72.5% response rate). Mean age was 12.1 years (standard deviation [SD]: 1.04). Of a possible score from 1-4, the mean adjusted IPFI score was 3.3 (SD: 0.3; Cronbach's alpha: 0.87). Of a possible score from 21-105, the total ARS score was 76.4 (SD 13.0; Cronbach's alpha: 0.82); both distributions were non-normal and left-skewed. The Lin's concordance correlation coefficient was 0.34 and the Spearman correlation coefficient was 0.52 (p-value < 0.0001 for both). Notably, 10 adolescents (3.1% of the sample) had a score in the lowest quartile in one of the two instruments, and a score in the highest quartile in the other instrument. CONCLUSIONS: There was low concordance between the scales, with notable lack of overlap in who was identified as having "low" levels of resilience. To better elucidate and operationalize the construct of resilience, studies using resilience scales should consider greater focus in understanding what aspects of the construct are being measured and how they relate to meaningful variables (well-being, risk of illness, etc.).

Consensus Statement on Ethical & Safety Practices for Conducting Digital Monitoring Studies with People at Risk of Suicide and Related Behaviors.

OBJECTIVE: Digital monitoring technologies (e.g., smart-phones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real-time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? METHODS: We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty-four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi-stage survey, and discussion process. RESULTS: Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real-time, and data and safety monitoring. CONCLUSIONS: This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide-with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.

Enhancing mental health research capacity: emerging voices from the National Institute of Mental Health (NIMH) global hubs.

BACKGROUND: Emerging researchers in low- and middle-income countries (LMIC) face many barriers, including inadequacies in funding, international exposure and mentorship. In 2012, the National Institute of Mental Health (NIMH) funded five research hubs aimed at improving the research core for evidence-based mental health interventions, enhancing research skills in global mental health, and providing capacity building (CB) opportunities for early career investigators in LMIC. In this paper emerging researchers contextualize their experiences. CASE PRESENTATION: Each of the five hubs purposively selected an emerging researcher who had experienced more than one hub-related CB opportunity and actively participated in hub-related clinical trial activities. The five 'voices' were invited to contribute narratives on their professional backgrounds, CB experience, challenges and successes as an emerging mental health researcher, and suggestions for future CB activities. These narratives are presented as case studies. CB activities provided broader learning opportunities for emerging researchers. Benefits included the receipt of research funding, hands-on training and mentorship, as well as exposure to networks and collaborative opportunities on a global scale. To overcome ongoing challenges of access to funding, mentoring, networking and global exposure, the emerging voices recommend making mentorship and training opportunities available to a wider range of emerging mental health researchers. CONCLUSIONS: Investing in CB is not enough to ensure sustainability and leave a legacy unless it is accompanied by ongoing mentorship and international exposure. Financial investment in building research capacity, promotion of mentorship and supervision, and international networking are essential to yield well-prepared young investigators in LMIC as experienced by these rising stars. Governments and policymakers should prioritize educational policies to support the continuous development and international engagement of emerging researchers. This can advance strategies to deal with one of most important and costly problems faced by healthcare systems in LMIC: the mental health treatment gap.

Positive adaptations for trauma and healing (PATH), a pilot study of group therapy with Latino youth.

OBJECTIVE: This study examines the acceptability and preliminary efficacy of Positive Adaptations for Trauma and Healing (PATH), a manualized treatment for Latino youth and their caregivers. PATH is a culturally adapted program that incorporates a trauma model, positive psychology, and resilience. METHOD: Latino youth (N = 16) recruited from an urban community clinic participated in PATH with their caregiver. Pre- and postintervention measures on trauma symptoms, resilience, depression, caregiver's view of their youth's well-being, and positive and negative emotions were gathered. Following the intake meetings (1 to 3), the families participated in 10 90-minute weekly group sessions (total of 3 groups). Caregiver groups were conducted in Spanish, and youth in English. RESULTS: At pretest, 56% of the youth endorsed clinically significant symptoms on the UCLA PTSD Index (M = 34.2, SD = 11.2); the percentage dropped to 0% at posttest (M = 17.3, SD = 7.6). Youth reported pre- to posttest reductions on the Child Depression Inventory (mean difference [Mdiff] = 7.3; p = .004) and externalizing (Mdiff = 6.1; p < .001) and internalizing (Mdiff = 9.4; p < .001) behaviors on the caregiver-reported Child Behavior Checklist. Overall, there was high treatment engagement (93% attendance over 10 weeks). CONCLUSION: This novel treatment engaged a community-based Latino sample. The results suggest high acceptability and significant reduction in trauma symptoms and associated symptoms. This study included a small number of participants and results should be interpreted with caution. Future iterations will target larger number of participants to further assess feasibility. (PsycINFO Database Record

Attenuated resting-state functional connectivity in patients with childhood- and adult-onset schizophrenia.

BACKGROUND: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset disorder (AOS). Our previous resting-state fMRI study identified attenuated functional connectivity in COS compared with controls. Here, we ask whether COS and AOS patients and their siblings exhibit similar abnormalities of functional connectivity. METHODS: A whole-brain, data-driven approach was used to assess resting-state functional connectivity differences in COS (patients/siblings/controls, n: 26/28/33) and AOS (n: 19/28/30). There were no significant differences in age, sex, or head motion across groups in each dataset and as designed, the COS dataset has a significantly lower age than the AOS. RESULTS: Both COS and AOS patients showed decreased functional connectivity relative to controls among a wide set of brain regions (P<0.05, corrected), but their siblings did not. Decreased connectivity in COS and AOS patients showed no amplitude differences and was not modulated by age-at-onset or medication doses. Cluster analysis revealed that these regions fell into two large-scale networks: one sensorimotor network and one centered on default-mode network regions, but including higher-order cognitive areas only in COS. Decreased connectivity between these two networks was notable (P<0.05, corrected) for both patient groups. CONCLUSIONS: A shared pattern of attenuated functional connectivity was found in COS and AOS, supporting the continuity of childhood-onset and adult-onset schizophrenia. Connections were altered between sensorimotor areas and default-mode areas in both COS and AOS, suggesting potential abnormalities in processes of self-monitoring and sensory prediction. The absence of substantial dysconnectivity in siblings indicates that attenuation is state-related.

Dynamic mapping of hippocampal development in childhood onset schizophrenia.

Prior cross-sectional anatomic brain imaging studies of the hippocampus in schizophrenia have generally shown loss in total hippocampal volume although the progressive course of these changes remains unknown. We report the first prospective sub-regional maps of hippocampal development in childhood onset schizophrenia (COS), reconstructed from serial brain MRI scans of 29 children with COS scanned every 2 years (87 scans) and compared to 31 controls matched for age, sex, and scan interval (94 scans). As expected, the COS subjects showed significant bilateral deficits (9-10%) in total hippocampal volume which remained consistent between age 9 and 26. However sub-regional maps showed heterogeneous changes with loss of hippocampal volume in both anterior as well as posterior ends while the body of the hippocampus gained in volume suggesting that hippocampal subunits are differentially affected in schizophrenia.

Pharmacological treatment of children and adolescents with depression.

INTRODUCTION: Despite an increasing number of studies, there is debate whether antidepressants have a favorable benefit/risk balance in depressed youth. Areas covered: A systematic search identified 23 systematic reviews and meta-analyses published between 2010-2016. More than 30 controlled clinical trials were conducted in adolescents, but only a few in pre-pubertal patients. About one-third of the trials were severely statistically underpowered. Most studies failed to detect differences from placebo, but a few found fluoxetine effective. Although no suicide occurred in these studies, antidepressants increased suicidality risk (including suicidal ideation and behavior) versus placebo (OR = 2.39). Only two placebo-controlled trials with acceptable statistical power were publicly funded: both showed efficacy of fluoxetine, and one found a higher incidence of suicidality (OR = 3.7, 95% C.I. 1.00-13.7). Expert opinion: In youth, antidepressants have, on average, a small therapeutic effect. The high placebo response is exacerbated by the large number of sites in many industry-funded studies. There is evidence that fluoxetine leads to greater and faster improvement than placebo or psychotherapy in adolescents. Considering both the high response to non-specific interventions and safety concerns, antidepressants should be used cautiously in youth, and limited to patients with moderate-to-severe depression for whom psychosocial interventions are either ineffective or not feasible.

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings.

Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia.

Hazardous drinking among young adults seeking outpatient mental health services.

BACKGROUND: Alcohol use can have a significant negative impact on young adults in mental health treatment. This cross-sectional study examined prevalence and factors associated with hazardous drinking among young adults seeking outpatient mental health services, rate of alcohol use disorders (AUDs), and the relationship between hazardous drinking and other types of substance use. METHODS: Participants were 487 young adults ages 18-25 who completed self-administered computerized screening questions for alcohol and drug use. Alcohol use patterns were assessed and predictors of hazardous drinking (≥5 drinks on one or more occasions in the past year) were identified using logistic regression. RESULTS: Of the 487 participants, 79.8 % endorsed prior-year alcohol use, 52.3 % reported one or more episodes of hazardous drinking in the prior year and 8.2 % were diagnosed with an AUD. Rates of recent and lifetime alcohol, tobacco and marijuana use were significantly greater in those with prior-year hazardous drinking. In logistic regression, prior-year hazardous drinking was associated with lifetime marijuana use (OR 3.30, p < 0.001; 95 % CI 2.05, 5.28), lifetime tobacco use (OR 1.88, p = 0.004; 95 % CI 1.22, 2.90) and older age (OR 1.18 per year, p < 0.001; 95 % CI 1.08, 1.29). CONCLUSIONS: In an outpatient mental health setting, high rates of hazardous drinking were identified, and drinking was associated with history of other substance use. Results highlight patient characteristics associated with hazardous drinking that mental health providers should be aware of in treating young adults, especially older age and greater use of tobacco and marijuana.

Lack of Gender-Related Differences in Childhood-Onset Schizophrenia.

OBJECTIVE: Gender differences, including younger age of onset and greater premorbid deficits in men, have been reported in adult-onset schizophrenia. This study comprehensively evaluated gender differences in childhood-onset schizophrenia (COS), a rare variant of the disorder. METHOD: Demographic, premorbid, clinical, familial, and cognitive characteristics, presence of chromosomal abnormalities, and brain magnetic resonance imaging cortical volumes were evaluated in 133 patients with COS. Cortical analyses included age- and gender-matched healthy volunteers (n = 124). RESULTS: Males with COS (n = 72) had a slightly but significantly younger age of onset than females with COS (mean age 9.51 ± 2.28 versus 10.29 ± 1.63 years, t131 = 2.21, p = .03), higher verbal IQ scores (83.00 ± 15.97 versus 75.58 ± 15.10, t89 = 2.24, p = .03), and higher rates of comorbid pervasive developmental disorder (28.17% versus 6.90%, χ(2)1 = 9.54, p < .01) and attention-deficit/hyperactivity disorder (43.86% versus 21.43%, χ(2)1 = 5.40, p = .02). There were no significant gender differences across other demographic, IQ, or clinical measurements, frequency of chromosomal abnormalities, family clinical measurements, premorbid functioning, or in gender-by-disorder interactions for magnetic resonance imaging brain measurements. CONCLUSION: The present comprehensive examination found few remarkable gender differences in COS. Although less striking than that seen in adult-onset schizophrenia, males with COS had a younger age of onset. Attention-deficit/hyperactivity disorder and pervasive developmental disorder rates were high in COS overall, suggesting greater neurodevelopmental vulnerability in COS. However, the gender ratios of these comorbidities in COS mirror those of the general populations, indicating that these gender differences might be unrelated to COS.

Severity of Cortical Thinning Correlates With Schizophrenia Spectrum Symptoms.

OBJECTIVE: This study investigated the relationship between regional cortical gray matter thinning and symptoms of schizophrenia spectrum personality disorders (PDs) in siblings of patients with childhood-onset schizophrenia (COS). METHOD: A total of 66 siblings of patients with COS were assessed for symptoms of schizophrenia spectrum PDs (avoidant, paranoid, schizoid, schizotypal). Structural magnetic resonance images were obtained at approximately 2-year intervals from the siblings and from 62 healthy volunteers matched for age, sex, ethnicity, and handedness. Cortical thickness measures were extracted. Mixed effect regression models were used to test the relationship between symptoms and cortical gray matter thickness in siblings. Cortical thinning was also tested longitudinally in healthy volunteers and siblings. RESULTS: Cortical thinning was found to correlate with symptoms of schizotypal and, to a lesser extent, schizoid PDs. Thinning was most pronounced in the left temporal and parietal lobes and right frontal and parietal regions. Gray matter loss was found to be continuous with that measured in COS. Longitudinal thinning trajectories were found not to differ between siblings and healthy volunteers. CONCLUSION: The present investigation of cortical thinning in siblings of patients with COS indicates that symptoms of schizophrenia spectrum PDs correlate with regional gray matter loss. This finding supports the idea of cortical thinning as a schizophrenia endophenotype.

Lack of evidence for elevated obstetric complications in childhood onset schizophrenia.

BACKGROUND: Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to "earlier" age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings. METHODS: We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. RESULTS: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. CONCLUSIONS: Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia.

Advancing Research to Action in Global Child Mental Health.

Most mental and substance use disorders begin during childhood and adolescence and are the leading cause of disability in this population. Prenatal and postnatal genetic, familial, social, and environmental exposures interact to influence risk for mental disorders and trajectories of cognitive development. Efforts to advance prevention and implement early interventions to reduce the burden of mental disorders require a global research workforce, intersectoral cooperation, attention to environmental contexts, and the development and testing of evidence-based interventions. The authors describe challenges and resources for building mental health research capacity that stands to influence children's mental health outcomes around the globe.