Mental health progress requires causal diagnostic nosology and scalable causal discovery.

Nine hundred and seventy million individuals across the globe are estimated to carry the burden of a mental disorder. Limited progress has been achieved in alleviating this burden over decades of effort, compared to progress achieved for many other medical disorders. Progress on outcome improvement for all medical disorders, including mental disorders, requires research capable of discovering causality at sufficient scale and speed, and a diagnostic nosology capable of encoding the causal knowledge that is discovered. Accordingly, the field's guiding paradigm limits progress by maintaining: (a) a diagnostic nosology (DSM-5) with a profound lack of causality; (b) a misalignment between mental health etiologic research and nosology; (c) an over-reliance on clinical trials beyond their capabilities; and (d) a limited adoption of newer methods capable of discovering the complex etiology of mental disorders. We detail feasible directions forward, to achieve greater levels of progress on improving outcomes for mental disorders, by: (a) the discovery of knowledge on the complex etiology of mental disorders with application of Causal Data Science methods; and (b) the encoding of the etiological knowledge that is discovered within a causal diagnostic system for mental disorders.

Beyond PTSD: Client presentations of developmental trauma disorder from a national survey of clinicians.

OBJECTIVE: The emergence of updated Diagnostic and Statistical Manual of Mental Disorders (5th ed. [DSM-5]; American Psychiatric Association, 2013) criteria for posttraumatic stress disorder (PTSD), which includes modified criteria for young children, raises questions regarding the need for developmentally appropriate standalone psychiatric diagnosis encompassing complex trauma presentations in children. The present study addresses these questions by examining how DSM-5 PTSD and proposed developmental trauma disorder (DTD) diagnoses relate to functional impairment and trauma exposure using clinician-report surveys. METHOD: We surveyed psychotherapists across the United States, and asked them to report on the symptom characteristics, functional impairment, and trauma exposure of children, adolescents, and young adults under their care (n = 210; age range = 2-21). We fit symptom data to the draft criteria for (1) DTD, a proposed trauma diagnosis for children and (2) existing criteria for adult and child/preschool PTSD. RESULTS: Results indicated that comorbidity between DTD and PTSD was high (52.4% and 59.9% for adult and child/preschool criteria, respectively). Comorbid DTD/PTSD and DTD-alone groups had more functional domains impacted and greater exposure to some types of trauma relative to the other groups. CONCLUSIONS: These findings speak to the relationship between trauma complexity and wide-ranging symptom presentations, provide support for research and clinical emphasis on a developmentally informed diagnosis, and may support existing treatment approaches. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neighborhood characteristics and psychiatric disorders in the aftermath of mass trauma: A representative study of New York City public school 4th-12th graders after 9/11.

Studies of the relationship between neighborhood characteristics and childhood/adolescent psychopathology in large samples examined one outcome only, and/or general (e.g., 'psychological distress') or aggregate (e.g., 'any anxiety disorder') measures of psychopathology. Thus, in the only representative sample of New York City public school 4th-12th graders (N = 8202) surveyed after the attacks of 9/11/2001, this study examined whether (1) indices of neighborhood Socioeconomic Status, Quality, and Safety and (2) neighborhood disadvantage (defined as multidimensional combinations of SES, Quality and Safety indicators) are associated with eight psychiatric disorders: posttraumatic stress disorder, separation anxiety disorder (SAD), agoraphobia, generalized anxiety disorder (GAD), panic disorder, major depression, conduct disorder, and alcohol use disorder (AUD). (1) The odds ratios (OR) of psychiatric disorders were between 0.55 (AUD) and 1.55 (agoraphobia), in low and intermediate-low SES neighborhoods, respectively, between 0.50 (AUD) and 2.54 (agoraphobia) in low Quality neighborhoods, and between 0.52 (agoraphobia) and 0.65 (SAD) in low Safety neighborhoods. (2) In neighborhoods characterized by high disadvantage, the OR were between 0.42 (AUD) and 1.36 (SAD). This study suggests that neighborhood factors are important social determinants of childhood/adolescent psychopathology, even in the aftermath of mass trauma. At the community level, interventions on modifiable neighborhood characteristics and targeted resources allocation to high-risk contexts could have a cost-effective broad impact on children's mental health. At the individual-level, increased knowledge of the living environment during psychiatric assessment and treatment could improve mental health outcomes; for example, specific questions about neighborhood factors could be incorporated in DSM-5's Cultural Formulation Interview.

Computational causal discovery for post-traumatic stress in police officers.

This article reports on a study aimed to elucidate the complex etiology of post-traumatic stress (PTS) in a longitudinal cohort of police officers, by applying rigorous computational causal discovery (CCD) methods with observational data. An existing observational data set was used, which comprised a sample of 207 police officers who were recruited upon entry to police academy training. Participants were evaluated on a comprehensive set of clinical, self-report, genetic, neuroendocrine and physiological measures at baseline during academy training and then were re-evaluated at 12 months after training was completed. A data-processing pipeline-the Protocol for Computational Causal Discovery in Psychiatry (PCCDP)-was applied to this data set to determine a causal model for PTS severity. A causal model of 146 variables and 345 bivariate relations was discovered. This model revealed 5 direct causes and 83 causal pathways (of four steps or less) to PTS at 12 months of police service. Direct causes included single-nucleotide polymorphisms (SNPs) for the Histidine Decarboxylase (HDC) and Mineralocorticoid Receptor (MR) genes, acoustic startle in the context of low perceived threat during training, peritraumatic distress to incident exposure during first year of service, and general symptom severity during training at 1 year of service. The application of CCD methods can determine variables and pathways related to the complex etiology of PTS in a cohort of police officers. This knowledge may inform new approaches to treatment and prevention of critical incident related PTS.

Editorial: In the Causal Labyrinth: Finding the Path From Early Trauma to Neurodevelopment.

Exposure to traumatic events early in life has been associated with significant adverse neurodevelopmental consequences.1,2 Ideally, protecting children from trauma would prevent these consequences. Unfortunately, once a child is exposed to early trauma, the only means of prevention requires implementing effective interventions toward the mechanisms known to have caused the consequences. Therefore, it is imperative to carefully define the true mechanistic pathways from which the neurodevelopmental consequences of early trauma result. The process of determining the correct pathway(s) is not a trivial matter, as is made clear from a valiant effort reported in this issue of the Journal titled, "Early Sexual Trauma Exposure and Neural Response Inhibition in Adolescence and Young Adults: Trajectories of Frontal Theta Oscillations During a Go/No-Go Task."3 This editorial reviews the effort to infer causal mechanism in this article, and introduces a literature that can improve the field's capacity to infer causes from observational data.

Brain entropy and human intelligence: A resting-state fMRI study.

Human intelligence comprises comprehension of and reasoning about an infinitely variable external environment. A brain capable of large variability in neural configurations, or states, will more easily understand and predict variable external events. Entropy measures the variety of configurations possible within a system, and recently the concept of brain entropy has been defined as the number of neural states a given brain can access. This study investigates the relationship between human intelligence and brain entropy, to determine whether neural variability as reflected in neuroimaging signals carries information about intellectual ability. We hypothesize that intelligence will be positively associated with entropy in a sample of 892 healthy adults, using resting-state fMRI. Intelligence is measured with the Shipley Vocabulary and WASI Matrix Reasoning tests. Brain entropy was positively associated with intelligence. This relation was most strongly observed in the prefrontal cortex, inferior temporal lobes, and cerebellum. This relationship between high brain entropy and high intelligence indicates an essential role for entropy in brain functioning. It demonstrates that access to variable neural states predicts complex behavioral performance, and specifically shows that entropy derived from neuroimaging signals at rest carries information about intellectual capacity. Future work in this area may elucidate the links between brain entropy in both resting and active states and various forms of intelligence. This insight has the potential to provide predictive information about adaptive behavior and to delineate the subdivisions and nature of intelligence based on entropic patterns.

Machine learning methods to predict child posttraumatic stress: a proof of concept study.

BACKGROUND: The care of traumatized children would benefit significantly from accurate predictive models for Posttraumatic Stress Disorder (PTSD), using information available around the time of trauma. Machine Learning (ML) computational methods have yielded strong results in recent applications across many diseases and data types, yet they have not been previously applied to childhood PTSD. Since these methods have not been applied to this complex and debilitating disorder, there is a great deal that remains to be learned about their application. The first step is to prove the concept: Can ML methods - as applied in other fields - produce predictive classification models for childhood PTSD? Additionally, we seek to determine if specific variables can be identified - from the aforementioned predictive classification models - with putative causal relations to PTSD. METHODS: ML predictive classification methods - with causal discovery feature selection - were applied to a data set of 163 children hospitalized with an injury and PTSD was determined three months after hospital discharge. At the time of hospitalization, 105 risk factor variables were collected spanning a range of biopsychosocial domains. RESULTS: Seven percent of subjects had a high level of PTSD symptoms. A predictive classification model was discovered with significant predictive accuracy. A predictive model constructed based on subsets of potentially causally relevant features achieves similar predictivity compared to the best predictive model constructed with all variables. Causal Discovery feature selection methods identified 58 variables of which 10 were identified as most stable. CONCLUSIONS: In this first proof-of-concept application of ML methods to predict childhood Posttraumatic Stress we were able to determine both predictive classification models for childhood PTSD and identify several causal variables. This set of techniques has great potential for enhancing the methodological toolkit in the field and future studies should seek to replicate, refine, and extend the results produced in this study.

Democratizing Implementation and Innovation in Mental Health Care.

Improvements in the quality of mental health care in the United States depend on the successful implementation of evidence-based treatments (EBT's) in typical settings of care. Unfortunately, there is little evidence that EBT's are used in ways that would approximate their established fidelity standards in such settings. This article describes an approach to more successful implementation of EBT's via a collaborative process between intervention developers and intervention users (e.g. providers, administrators, consumers) called Lead-user Innovation. Lead-user Innovation democratizes the implementation process by integrating the expertise of lead-users in the delivery, adaptation, innovation and evaluation of EBT's.

Posttraumatic Stress Disorder Diagnosis in Young Children With Burns.

The primary aim of this study was to assess the prevalence of posttraumatic stress disorder (PTSD) in young children hospitalized for burns. A secondary aim was to assess partial PTSD in this population. PTSD diagnosis and symptoms were evaluated utilizing both the diagnostic interview for children and adolescents (DICA-P) module and the PTSD semistructured interview and observational report (PTSDSSI). PTSD symptomatology was assessed from parent interviews at 1 month after discharge from a major pediatric burn center. Four of the 42 participants who completed the DICA-P met full criteria for a diagnosis of PTSD (10%).Of the 39 who also completed the PTSDSSI, 1 (3%) met full criteria for PTSD diagnosis on that measure. Twenty-seven percentage of subjects met partial criteria on the DICA-P vs 16% on the PTSDSSI, without impairment. Furthermore, 67% of subjects met DICA-P criteria for the re-experiencing cluster and 54% met the PTSDSSI re-experiencing criteria. Although only a small percentage met full PTSD diagnostic criteria by either measure, a high percentage of young children with burns manifested some posttraumatic symptoms 1 month after discharge. Because PTSDSSI diagnosis is strongly linked to the diagnostic and statistical manual-5 (DSM-5) criteria for "PTSD in children 6 years and younger," these results may offer clues to current diagnoses of PTSD in young children. Future research is needed to improve care by determining the risk factors and course of PTSD to further refine the diagnostic criteria for identifying children most in need of intervention, such as those hospitalized for burn injuries.

A Complex Systems Approach to Causal Discovery in Psychiatry.

Conventional research methodologies and data analytic approaches in psychiatric research are unable to reliably infer causal relations without experimental designs, or to make inferences about the functional properties of the complex systems in which psychiatric disorders are embedded. This article describes a series of studies to validate a novel hybrid computational approach--the Complex Systems-Causal Network (CS-CN) method-designed to integrate causal discovery within a complex systems framework for psychiatric research. The CS-CN method was first applied to an existing dataset on psychopathology in 163 children hospitalized with injuries (validation study). Next, it was applied to a much larger dataset of traumatized children (replication study). Finally, the CS-CN method was applied in a controlled experiment using a 'gold standard' dataset for causal discovery and compared with other methods for accurately detecting causal variables (resimulation controlled experiment). The CS-CN method successfully detected a causal network of 111 variables and 167 bivariate relations in the initial validation study. This causal network had well-defined adaptive properties and a set of variables was found that disproportionally contributed to these properties. Modeling the removal of these variables resulted in significant loss of adaptive properties. The CS-CN method was successfully applied in the replication study and performed better than traditional statistical methods, and similarly to state-of-the-art causal discovery algorithms in the causal detection experiment. The CS-CN method was validated, replicated, and yielded both novel and previously validated findings related to risk factors and potential treatments of psychiatric disorders. The novel approach yields both fine-grain (micro) and high-level (macro) insights and thus represents a promising approach for complex systems-oriented research in psychiatry.

Predicting the Transition From Acute Stress Disorder to Posttraumatic Stress Disorder in Children With Severe Injuries.

INTRODUCTION: The purpose of this study was to examine predictors of risk for and the transition between acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) in a longitudinal sample of youth with severe injuries admitted to the hospital. These data would assist with treatment and discharge planning. METHODS: Youth were assessed for ASD during the initial hospital stay and were followed-up over an 18-month period for PTSD (n = 151). Youth were classified into four groups, including Resilient (ASD-, PTSD-), ASD Only (ASD+, PTSD-), PTSD Only (ASD-, PTSD+), and Chronic (ASD+, PTSD+). Demographic, psychiatric, social context, and injury-related factors were examined as predictors of diagnostic transition. RESULTS: The results of multivariate analysis of variance and pairwise comparisons found that peritraumatic dissociation, gender, and socioeconomic status were significant predictors after controlling for multiple testing. DISCUSSION: Results suggest that both within-child and contextual factors contribute to the longitudinal response to trauma in children. Clinicians should consider early screening and discharge planning, particularly for children most at risk.

Trauma Systems Therapy in Residential Settings: Improving Emotion Regulation and the Social Environment of Traumatized Children and Youth in Congregate Care.

Although abundant evidence exists indicating the prevalence of trauma exposure among youth in residential care, few models exist for creating trauma-informed milieu treatment. This article outlines the problem and describes the implementation of Trauma Systems Therapy (TST) in three residential centers. TST is unique in emphasizing youth emotions and behaviors as well as the role a distressed or threatening social environment may play in keeping a traumatized youth in a dysregulated state. This dual emphasis makes TST specifically appropriate to implementation in congregate care, focusing assessment and intervention strategies on both clinical treatment and the functioning of the therapeutic milieu itself. Data are reported on incidents of the use of physical restraint; numbers of disrupted foster care placements following discharge from residential treatment; and scores on psychometric measures of children's functioning and emotion regulation capacity. Knowledge gained through TST implementation in these three residential centers has important implications for developing a model of trauma-informed congregate care.

Innovations in Practice: Preliminary evidence for effective family engagement in treatment for child traumatic stress-trauma systems therapy approach to preventing dropout.

BACKGROUND: This study aimed to obtain preliminary evidence for the extent to which a novel intervention embedded within a systems-oriented treatment model [trauma systems therapy (TST)] engages and retains traumatized children and their families in treatment. METHOD: Twenty youth who had prominent symptoms of posttraumatic stress were randomly assigned to receive TST or care as usual (CAU). RESULTS: At the 3-month assessment, 90% of TST participants were still in treatment, whereas only 10% of CAU participants remained. Within-group analyses of TST participants demonstrated significant reductions in posttraumatic stress and aggression as well as a slight improvement in home safety. CONCLUSIONS: These preliminary findings point to the need to utilize effective engagement approaches to retain traumatized children and their families in treatment.

A randomized controlled trial of sertraline to prevent posttraumatic stress disorder in burned children.

BACKGROUND: This study evaluated the potential benefits of a centrally acting selective serotonin reuptake inhibitor, sertraline, versus placebo for prevention of symptoms of posttraumatic stress disorder (PTSD) and depression in burned children. This is the first controlled investigation based on our review of the early use of a medication to prevent PTSD in children. METHODS: Twenty-six children aged 6-20 were assessed in a 24-week double-blind placebo-controlled design. Each child received either flexibly dosed sertraline between 25-150 mg/day or placebo. At each reassessment, information was collected in compliance with the study medication, parental assessment of the child's symptomatology and functioning, and the child's self-report of symptomatology. The protocol was approved by the Human Studies Committees of Massachusetts General Hospital and Shriners Hospitals for Children. RESULTS: The final sample was 17 subjects who received sertraline versus 9 placebo control subjects matched for age, severity of injury, and type of hospitalization. There was no significant difference in change from baseline with child-reported symptoms; however, the sertraline group demonstrated a greater decrease in parent-reported symptoms over 8 weeks (-4.1 vs. -0.5, p=0.005), over 12 weeks (-4.4 vs. -1.2, p=.008), and over 24 weeks (-4.0 vs. -0.2, p=0.017). CONCLUSIONS: Sertraline was a safe drug, and it was somewhat more effective in preventing PTSD symptoms than placebo according to parent report but not child report. Based on this study, sertraline may prevent the emergence of PTSD symptoms in children.

Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n=103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

Pretrauma problems, prior stressor exposure, and gender as predictors of change in posttraumatic stress symptoms among physically injured children and adolescents.

OBJECTIVE: This study addressed predictors of change in posttraumatic stress symptoms (PTSS) among youths who had experienced physical injuries. The influences of pretrauma internalizing and externalizing problems, prior stressor exposure, and gender were investigated. Additionally, gender was examined as a moderator of the associations between internalizing problems and PTSS, externalizing problems and PTSS, and prior stressor exposure and PTSS. METHOD: Participants were 157 children and adolescents (75% male; age M = 13.30 years, SD = 3.60; 44% Caucasian, 39% African American, 13% Hispanic, and 4% other) admitted to 2 hospitals for physical injuries. Youths and their parents completed measures of PTSS (Child Posttraumatic Stress Reaction Index), internalizing and externalizing problems (Child Behavior Checklist), and prior stressor exposure (Coddington Life Events Scale, Child) during the hospital stay; youths completed up to 3 additional PTSS assessments targeted at 3, 6, and 12 months postinjury. RESULTS: Multilevel regression analyses revealed a significant average decline in PTSS over time (p < .05) that followed a curvilinear trajectory. Externalizing problems, prior stressor exposure, and female gender predicted higher initial PTSS levels (p < .05). Gender moderated the influence of internalizing problems, externalizing problems, and prior stressor exposure on decline in PTSS over time (p < .05). Patterns of recovery for those with high and low levels of each characteristic differed for girls and boys. CONCLUSIONS: Findings suggest targets for clinical consideration, both with respect to identifying subgroups of children and adolescents that may warrant early assessment and monitoring and timing of more directed PTSS treatment intervention.