Transdiagnostic clinical staging for childhood mental health: An adjunctive tool for classifying internalizing and externalizing syndromes that emerge in children aged 5-11 years

Clinical staging is now recognized as a key tool for facilitating innovation in personalized and preventative mental health care. It places a strong emphasis on the salience of indicated prevention, early intervention, and secondary prevention of major mental disorders. By contrast to established models for major mood and psychotic syndromes that emerge after puberty, developments in clinical staging for childhood-onset disorders lags significantly behind. In this article, criteria for a transdiagnostic staging model for those internalizing and externalizing disorders that emerge in childhood is presented. This sits alongside three putative pathophysiological profiles (developmental, circadian, and anxious-arousal) that may underpin these common illness trajectories. Given available evidence, we argue that it is now timely to develop a transdiagnostic staging model for childhood-onset syndromes. It is further argued that a transdiagnostic staging model has the potential to capture more precisely the dimensional, fluctuating developmental patterns of illness progression of childhood psychopathology. Given potential improvements in modelling etiological processes, and delivering more personalized interventions, transdiagnostic clinical staging for childhood holds much promise for assisting to improve outcomes. We finish by presenting an agenda for research in developments of transdiagnostic clinical staging for childhood mental health.

Internalizing–externalizing comorbidity and regional brain volumes in the ABCD study

Despite nonoverlapping diagnostic criteria, internalizing and externalizing disorders show substantial comorbidity. This comorbidity is attributable, at least in part, to transdiagnostic neuroaffective mechanisms. Both unipolar depression and externalizing disorders are characterized by structural and functional compromises in the striatum and its projections to the anterior cingulate cortex (ACC) and other frontal regions. Smaller volumes and dampened reward responding in these regions are associated with anhedonia and irritability – mood states that cut across the internalizing and externalizing spectra. In contrast, smaller amygdala volumes and dampened amygdala function differentiate externalizing disorders from internalizing disorders. Little is known, however, about associations between internalizing–externalizing comorbidity and brain volumes in these regions, or whether such patterns differ by sex. Using a transdiagnostic, research domain criteria (RDoC)-informed approach, we evaluate associations between heterotypic (Internalizing × Externalizing) symptom interactions and striatal, amygdalar, and ACC volumes among participants in the Adolescent Brain Cognitive Development study (N = 6,971, mean age 9.9 years, 51.6% female). Heterotypic symptoms were associated with ACC volumes for both sexes, over and above the main effects of internalizing and externalizing alone. However, heterotypic comorbidity was associated with larger ACC volumes for girls, but with smaller ACC volumes for boys. These findings suggest a need for further studies and transdiagnostic assessment by sex.

Beier Sentence Completion Test Profiles of Adolescents and Emerging Adults With Internalizing and Externalizing Disorders

Background: Understanding adolescents' and emerging adults' psychiatric complaints and their relations with psychiatric disorders can be challenging. Beier Sentence Completion Test (BSCT), as a projective test, can be promising in this respect. However, relations between BSCT profiles and adolescent psychopathology are not well known. Aim: This study aimed to examine and compare BSCT profiles of adolescents and emerging adults with internalizing and externalizing disorders. As well as that, the relation of BSCT profiles with depression and anxiety scores was investigated. Objective: To achieve this aim, we retrospectively collected the hospital records of 300 adolescents and emerging adults (aged. 14-21) admitted to an Adolescent Psychiatry Outpatient Unit. Method: The psychiatric diagnosis of the patients was classified as Internalizing (n =100) and Externalizing (n = 100) disorder groups; the control group (n = 100) consisted of adolescents and young adults without any psychiatric diagnosis. BSCT, the Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were administered on the first admission to all cases before psychiatric evaluation and treatment. BSCT total subfactor (positive, negative, neutral, and non-response) statement scores were compared between groups, and their correlations with BDI and BAI were investigated. Besides, multivariate logistic regression analyses were conducted for estimating any diagnostic group differences, as well as bivariate logistic regression analyses for estimating BDI and BAI cutoff scores with models that included BSCT total subfactor statement scores. Results: It was revealed that lower positive and non-response statements were crucial for distinguishing externalizing and internalizing disorders and that positive and negative statements were correlated with depression and anxiety scores.In the multivariate regression model, these correlations were predictive only for the relationship between internalizing disorders group and low positive statement scores, not higher negative statement scores that can be associated with lack of positive emotional processing in this group. Also, nonresponse statement scores were found to be predictive for externalizing disorder groups. Similarly, BDI cut-off scores were predicted with low positive statement scores. Conclusion: BSCT profiles can be promising for understanding adolescents and emerging adults with internalizing and externalizing disorders. Lack of positive attributions to the self and other domains of life can be important for differentiating adolescent psychopathology.

Anxiety-impulsivity subtypes in adolescent internalizing disorder are characterized by distinguishable neurodevelopmental, neurocognitive and clinical trajectory signatures

Background Anxiety and impulsivity represent transdiagnostic pathology dimensions yet their interaction and contribution to emotional disorders in adolescence and to disease development remain controversial, and previous studies indicate heterogeneity within the broad category of internalizing disorders. Methods A combination of hierarchical and non-hierarchical clustering strategies was employed to determine impulsivity-related subtypes (based on the facets of negative urgency, lack of planning, lack of perseverance, sensation seeking and positive urgency in UPPS-P scales) in a large cohort of adolescents with internalizing disorders (n=2437) from Adolescent Brain Cognitive Development (ABCD) Study. Linear mixed-effect models were employed to determine cortical thickness alterations of the subtypes. Results Data-driven clustering identified two distinct subtypes of internalizing patients (subtype 1/subtype 2) with comparable levels of increased anxiety yet distinguishable levels of impulsivity, i.e., enhanced (subtype 1) or decreased (subtype 2) compared to healthy controls. Subtype 1 was further characterized by thicker prefrontal and temporal cortical regions involved in regulatory control and fear processing, while subtype 2 did not demonstrate significant thickness alterations. The differential neuroanatomical profiles remained stable over the two-year follow-up, while the two subtypes had different neurodevelopmental trajectories. Subtype 1 additionally reported more psychopathology and dysfunctionality including higher suicidal ideation, depressive symptoms and transition rates to externalizing disorders during follow-up as well as impaired neurocognitive and educational performance compared to subtype 2. Moreover, for subtype 1, anxiety at baseline (9-10 years) was significantly positively associated with impulsivity (lack of perseverance) at 2-year follow-up, while in subtype 2, baseline anxiety was significantly negatively associated with impulsivity (sensation seeking) at 2-year follow-up. Conclusions Our results demonstrate an impulsivity-dependent heterogeneity in adolescent internalizing disorders, with high-impulsivity patients being characterized by neurodevelopmental delay at the neural and cognitive levels. Individuals with elevated impulsivity are at a greater risk to develop behavioral dysregulation over the following two years and may thus require specific early interventions.

How different pre-existing mental disorders and their co-occurrence affects clinical outcomes of COVID-19? A study based on real-world data in the Southern United States

Importance: A growing body of research focuses on the impact of pre-existing mental disorders on clinical outcomes of COVID-19 illness. Although a psychiatric history might be an independent risk factor for COVID-19 infection and mortality, no studies have systematically investigated how different clusters of pre-existing mental disorders may affect COVID-19 clinical outcomes or showed how the coexistence of mental disorder clusters is related to COVID-19 clinical outcomes. Objective: To explore how different pre-existing mental disorders and their co-occurrence affects COVID-19-related clinical outcomes based on real-world data. Design, Setting, and Participants: Using a retrospective cohort study design, a total of 476,775 adult patients with lab-confirmed and probable COVID-19 between March 06, 2020 and April 14, 2021 in South Carolina, United States were included in the current study. The electronic health record data of COVID-19 patients were linked to all payer-based claims data through the SC Revenue and Fiscal Affairs Office. Main Outcomes and Measures: Key COVID-19 clinical outcomes included severity, hospitalization, and death. COVID-19 severity was defined as asymptomatic, mild, and moderate/severe. Pre-existing mental disorder diagnoses from Jan 2, 2019 to Jan 14, 2021 were extracted from the patients healthcare utilization data via ICD-10 codes. Mental disorders were categorized into internalizing disorders, externalizing disorders, and thought disorders. Results: Of the 476,775 COVID-19 patients, 55,300 had pre-existing mental disorders. There is an elevated risk of COVID-19-related hospitalization and death among participants with pre-existing mental disorders adjusting for key socio-demographic covariates (i.e., age, gender, race, ethnicity, residence, smoking). Co-occurrence of any two clusters was positively associated with COVID-19-related hospitalization and death. The odds ratio of being hospitalized was 2.50 (95%CI 2.284, 2.728) for patients with internalizing and externalizing disorders, 3.34 (95%CI 2.637, 4.228) for internalizing and thought disorders, 3.29 (95%CI 2.288, 4.733) for externalizing and thought disorders, and 3.35 (95%CI 2.604, 4.310) for three clusters of mental disorders. Conclusions and Relevance: Pre-existing internalizing disorders, externalizing disorders, and thought disorders are positively related to COVID-19 hospitalization and death. Co-occurrence of any two clusters of mental disorders have elevated risk of COVID-19-related hospitalization and death compared to those with a single cluster.

Reward-Related Dysfunctions in Children Developing Attention Deficit Hyperactivity Disorder—Roles of Oppositional and Callous-Unemotional Symptoms

Objectives: Neurocognitive functions might indicate specific pathways in developing attention deficit hyperactivity disorder (ADHD). We focus on reward-related dysfunctions and analyze whether reward-related inhibitory control (RRIC), approach motivation, and autonomic reactivity to reward-related stimuli are linked to developing ADHD, while accounting for comorbid symptoms of oppositional defiant disorder (ODD), and callous-unemotional (CU) traits.Methods: A sample of 198 preschool children (115 boys; age: m = 58, s = 6 months) was re-assessed at age 8 years (m = 101.4, s = 3.6 months). ADHD diagnosis was made by clinical interviews. We measured ODD symptoms and CU traits using a multi-informant approach, RRIC (Snack-Delay task, Gift-Bag task) and approach tendency using neuropsychological tasks, and autonomic reactivity via indices of electrodermal activity (EDA).Results: Low RRIC and low autonomic reactivity were uniquely associated with ADHD, while longitudinal and cross-sectional links between approach motivation and ADHD were completely explained by comorbid ODD and CU symptoms.Conclusion: High approach motivation indicated developing ADHD with ODD and CU problems, while low RRIC and low reward-related autonomic reactivity were linked to developing pure ADHD. The results are in line with models on neurocognitive subtypes in externalizing disorders.

Hypothalamic Hamartomas: Evolving Understanding and Management

Hypothalamic hamartomas (HH) are rare, basilar developmental lesions with widespread comorbidities often associated with refractory epilepsy and encephalopathy. Imaging advances allow for early, even prenatal, detection. Genetic studies suggest mutations in GLI3 and other patterning genes are involved in HH pathogenesis. About 50-80% of children with HH suffer from severe rage and aggression and a majority of cases exhibit externalizing disorders. Behavioral disruption and intellectual disability may predate epilepsy. Neuropsychological, sleep and endocrine disorders are typical. The purpose of this paper is to provide a summary of the current understanding of HH, and to highlight opportunities for future research.

Mental Disorders, Gun Ownership, and Gun Carrying Among Soldiers After Leaving the Army, 2016–2019

Objectives. To examine associations of current mental and substance use disorders with self-reported gun ownership and carrying among recently separated US Army soldiers. Veterans have high rates of both gun ownership and mental disorders, the conjunction of which might contribute to the high suicide rate in this group. Methods. Cross-sectional survey data were collected in 2018–2019 from 5682 recently separated personnel who took part in the Army Study to Assess Risk and Resilience in Servicemembers. Validated measures assessed recent mood, anxiety, substance use, and externalizing disorders. Logistic regression models examined associations of sociodemographic characteristics, service characteristics, and mental disorders with gun ownership and carrying. Results. Of the participants, 50% reported gun ownership. About half of owners reported carrying some or most of the time. Mental disorders were not associated significantly with gun ownership. However, among gun owners, major depressive disorder, panic disorder, posttraumatic stress disorder, and intermittent explosive disorder were associated with significantly elevated odds of carrying at least some of the time. Conclusions. Mental disorders are not associated with gun ownership among recently separated Army personnel, but some mental disorders are associated with carrying among gun owners. (Am J Public Health. 2021;111(10):1855–1864. https://doi.org/10.2105/AJPH.2021.306420 )