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Background: This report concerns long-term mortality risks associated with depression, and the potentially confounding factors of alcoholism and cigarette smoking, as experienced by a general population assessed at a baseline in 1952, followed for re-assessment of survivors in 1968, and for death by 1992.Methods: Self-report and physician-report information was gathered in 1952 and again in 1968 about a sample of 1,079 adults. At the end of follow-up in 1992, the vital status of all subjects was known. Comorbidity among depression, alcoholism, and smoking was investigated. Cox regression models were employed to estimate hazard ratios (HRs) as indicators of mortality risk. Models including age, gender, and depression were fit for the complete sample at baseline as well as for re-assessed survivors. Models simultaneously controlling for the mortality risks associated with depression, alcoholism, and heavy smoking were fit for men.Results: At the baseline in 1952, depression was somewhat more common among women than men (4% compared to 6%) but was found to carry a significant mortality risk only among men (HR 2.7, 95% CI 1.6-4.7). Based on re-assessments made in 1968, depression was associated with mortality risk among both men (HR 2.2, 95% CI 1.0-4.5) and women (HR 2.1, 95% CI 1.2-3.8). In 1952, more than 20% of men smoked cigarettes excessively and 8% abused alcohol, but very few of these groups of men were also depressed. In the original sample and also among the survivors, depression, alcoholism, and heavy smoking were separately associated with mortality among men. Depression and alcoholism carried a more immediate mortality risk while heavy smoking a more delayed one.Conclusions: At the baseline of the Stirling County Study, the mortality risk associated with depression among men was not enhanced or explained by abuse of alcohol or nicotine, mainly because comorbidity was rare at that time. The longitudinal research of the study has pointed to a number of psychiatrically-relevant time-trends such as the fact that an association between depression and cigarette smoking did not appear until the 1990s. It is hypothesized that a similar trend may emerge over time regarding the comorbidity of depression and alcoholism. A trend reported here was that, while depressed women in the original sample did not carry a significant mortality risk, the surviving women who were depressed at the time of re-assessment exhibited a mortality risk that was as significant as that for men. Such information may provide a useful back-drop for future investigations. [ABSTRACT FROM AUTHOR]

This paper by Nobakht, Steinsbekk & Wichstrom (2023) is a model of good science in the study of oppositional defiant disorder and conduct disorder. Their approach illustrates a thoughtful research design, statistical modeling sufficient to empirically evaluate developmental processes, and a full consideration of the theoretical implications of their work. This contrasts with a broad history of research on ODD and CD that far too often has only reified biased assumptions about these phenomena rather than rigorously scrutinizing them. Their demonstration of a unidirectional developmental flow of influence from ODD to interparental aggression, and thence to CD highlights a set of complicated developmental processes involving these disorders and their environment. It expands on evidence of the toll that ODD exerts on parents and provides guidance for more specific intervention. Standards in developmental psychopathology research should include testing bidirectional processes and employing designs that could falsify rather than reify existing beliefs. Examining key mechanisms in such processes will more rapidly generate improvements in assessment and treatment., (© 2024 Association for Child and Adolescent Mental Health.)

Individuals often hold beliefs in religion and in science, but how they mutually function is not well-understood. We examined these conjoint influences by examining their relative contributions to individuals' global meaning systems. We also examined whether subgroups of participants could be identified in terms of relative influence of religious or science beliefs on their meaning systems. A nationally representative sample of 300 American adults completed online surveys. Results suggested that science beliefs and religion beliefs comprise separate but only modestly negatively correlated dimensions. Both contributed similarly to the explanation of world assumptions, but only religious beliefs generally predicted goals, values and sense of meaning in life. Latent profile analysis produced a three-profile solution: one profile of moderate science and religious beliefs represented half the sample while the remainder split evenly between predominantly religious and predominantly science beliefs. In general, across most aspects of global meaning, the religious beliefs group was higher than the science beliefs and moderate beliefs in both groups. Results of this first systematic investigation of the separate effects of beliefs in religion and in science on meaning systems suggest that the balance of these beliefs is a potentially important individual difference warranting further investigation and elaboration., (© 2023 International Union of Psychological Science.)

Objective: The effects of trauma exposure on depression risk and severity are well established, but psychosocial and biological factors that impact or explain those relationships remain poorly understood. This study examined the moderating and mediating effects of perceived control and inflammation in the relationship between trauma and depression., Methods: Moderation analyses and longitudinal mediation analyses were conducted on data from 945 adults who completed all three waves (spanning around 19 years) of the Midlife Development in the United States (MIDUS) study and the MIDUS Biomarker Study. Data were collected during a phone interview, self-report surveys distributed in the mail, and an in-person blood draw. Two dimensions of perceived control-mastery and constraints-were examined separately in all analyses., Results: Perceived control did not significantly moderate the relationship between trauma and depression severity at MIDUS 2 ( b = 0.03, SE = .02, p = .091). Constraints significantly mediated the relationship between trauma and MIDUS 3 depression (indirect effect = 0.03, SE = 0.01, p = .016) but not after accounting for MIDUS 2 depression. Perceived control did not have a significant moderating effect in the relationships between trauma and inflammation or inflammation and depression., Conclusions: Findings from this study revealed that perceived control may be better characterized as an explanatory factor rather than a buffer in trauma-associated depression. Perceived constraints in particular may be a useful treatment target for trauma-associated depression. Further research is needed to examine whether these results generalize to populations other than among mostly non-Hispanic White adults in the United States., (Copyright © 2024 by the American Psychosomatic Society.)

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.

Historically, much of the progress made in youth mental health research can be classified as focusing on externalizing problems , characterized by disruptive behavior (e.g. aggression, defiance), or internalizing problems , characterized by intense negative affect (e.g. depression, anxiety). Until recently, however, less attention has been given to topics that lie somewhere in between these domains, topics that we collectively refer to as the affective side of disruptive behavior . Like the far side of the moon, the affective side of disruptive behavior captures facets of the phenomenon that may be less obvious or commonly overlooked, but are nonetheless critical to understand. This affective side clarifies socially disruptive aspects of traditionally "externalizing" behavior by elucidating proximal causation via intense negative affect (traditionally "internalizing"). Such problems include irritability, frustration, anger, temper loss, emotional outbursts, and reactive aggression. Given a recent explosion of research in these areas, efforts toward integration are now needed. This special issue was developed to help address this need. Beyond the present introductory article, this collection includes 4 empirical articles on developmental psychopathology topics, 4 empirical articles on applied treatment/assessment topics, 1 evidence base update review article on measurement, and 2 future directions review articles concerning outbursts, mood, dispositions, and youth psychopathology more broadly. By deliberatively investigating the affective side of disruptive behavior, we hope these articles will help bring about better understanding, assessment, and treatment of these challenging problems, for the benefit of youth and families.

Clinicians form initial impressions about a child's diagnosis based on behavioral features, but research has not yet identified specific behaviors to guide initial diagnostic impressions. Participants were toddlers (N = 55, mean age 22.9 months) from a multi-site early detection study, referred for concern for ASD due to screening or parent/provider concern. Within 5 min of meeting a child, clinicians noted ASD or non-ASD impression, confidence in impression, and behaviors that informed their impression. These clinicians also determined final diagnoses for each child. When a child's final diagnosis was ASD (n = 35), senior clinicians formed an initial impression of ASD in 22 cases (63%) but missed 13 cases (37%). When final diagnosis was non-ASD (n = 20), senior clinicians made an initial impression of non-ASD in all cases (100%). Results were similar among junior clinicians. Senior and junior clinicians used the same behaviors to form accurate impressions of ASD and non-ASD: social reciprocity, nonverbal communication, and eye contact. Senior clinicians additionally used focus of attention when forming accurate impressions of ASD and non-ASD; junior clinicians used this behavior only when forming accurate non-ASD impressions. Clinicians' initial impressions of ASD are very likely to be consistent with final diagnoses, but initial impressions of non-ASD need follow-up. Toddlers who show all four atypical behaviors (social reciprocity, nonverbal communication, eye contact, and focus of attention) might receive expedited ASD diagnoses. However, presence of apparently typical behaviors should not rule out ASD; for some children a longer evaluation is necessary to allow for more opportunities to observe subtle social behavior., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Objective: The need to understand and treat childhood chronic irritability (CI; i.e. frequent temper loss and angry/irritable mood) is imperative. CI predicts impairment across development and complex comorbidities with both internalizing and externalizing disorders. Research has emphasized frustration reactivity as a key mechanism of CI. However, there are understudied components of frustrative non-reward, particularly regulation-oriented frustration recovery, frustration tolerance, and cognitive control, that may further explain impairments specific to CI beyond comorbid symptoms., Method: Sixty-three community children ( N  = 25 CI/38 non-CI) and a parent completed surveys and the computerized Frustration Go/No-Go (FGNG) and Mirror Tracing Persistence Task (MTPT). Analyses compared task performance and self-rated affect across youth with or without CI, with further comparison based on negative/positive screen for ADHD ( N  = 45-/18+)., Results: In mixed effects models assessing change across task, the CI group did not demonstrate more intense frustration on the MTPT or rigged FGNG block but exhibited persisting frustration and inhibitory control difficulties into the FGNG recovery period; the CI+ADHD subgroup drove recovery effects. In GEE and logistic regression models including dimensional symptom clusters, only internalizing symptoms predicted child frustration intolerance and reactivity across tasks. ADHD severity was also associated with higher MTPT frustration reactivity, while oppositional behavior predicted lower frustration. Better frustration recovery was associated with lower irritability, but higher internalizing symptoms., Conclusions: Co-occurring symptoms may better explain some frustration-related difficulties among youth with CI. Difficulties with postfrustration affect and inhibitory control recovery suggest the importance of characterizing CI by self-regulation impairments.

The assessment of oppositional defiant disorder, conduct disorder, antisocial personality disorder, and intermittent explosive disorder-the Disruptive, Impulse Control and Conduct Disorders-can be affected by biases in clinical judgment, including overestimating concerns about distinguishing symptoms from normative behavior and stigma associated with diagnosing antisocial behavior. Recent nosological changes call for special attention during assessment to symptom dimensions of limited prosocial emotions and chronic irritability. The present review summarizes best practices for evidence-based assessment of these disorders and discusses tools to identify their symptoms. Despite the focus on disruptive behavior disorders, their high degree of overlap with disruptive mood dysregulation disorder can complicate assessment. Thus, the latter disorder is also included for discussion here. Good practice in the assessment of disruptive behavior disorders involves using several means of information gathering (e.g., clinical interview, standardized rating scales or checklists), ideally via multiple informants (e.g., parent-, teacher-, and self-report). A commitment to providing a full and accurate diagnostic assessment, with careful and attentive reference to diagnostic guidelines, will mitigate concerns regarding biases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pragmatic language weaknesses, a core feature of autism spectrum disorder (ASD), are implicated in externalizing behavior disorders (Gremillion & Martel, 2014). Particularly in a clinical setting, these co-occurring externalizing disorders are very common in autism; rates of Attentional Deficit-Hyperactive Disorder (ADHD) and Oppositional Defiant Disorder (ODD) are as high as 83% (ADHD) and 73% (ODD; Joshi et al., 2010). It is possible that pragmatic language weaknesses impact the ability to effectively communicate one's needs, which may lead autistic children to utilize externalizing behaviors in order to achieve a desired outcome (Ketelaars et al., 2010; Rodas et al., 2017)., Methods: The aim of the current study is to investigate the relationship between pragmatic language, assessed via multiple modalities, and externalizing behaviors, assessed by parent interview, in youth with autistic ( n =33) or neurotypical (NT; n =34) developmental histories, along with youth diagnosed with autism, who lost the diagnosis (LAD) by adolescence ( n =31)., Results: The autism group had significantly more pragmatic language difficulties, and more externalizing behaviors and disorders; ADHD symptoms were particularly more prevalent, while LAD and NT groups did not differ. Challenges in pragmatic language abilities were associated with more externalizing symptoms when controlling for other facts that typically influence such symptoms, including nonverbal cognition, structural language, executive functioning, and autistic characteristics, but did not remain when age was included in the model., Conclusions: We discuss the mechanisms underlying difficult-to-manage externalizing behaviors and implications for interventions and long-term outcomes for youth with and without a history of autism., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Oppositional defiant disorder (ODD) is a disruptive behaviour disorder involving an ongoing pattern of angry/irritable mood, argumentative/defiant behaviour and vindictiveness. Onset is typically before 8 years of age, although ODD can be diagnosed in both children and adults. This disorder is associated with substantial social and economic burden, and childhood ODD is one of the most common precursors of other mental health problems that can arise across the lifespan. The population prevalence of ODD is ~3 to 5%. A higher prevalence in males than females has been reported, particularly before adolescence. No single risk factor accounts for ODD. The development of this disorder seems to arise from the interaction of genetic and environmental factors, and mechanisms embedded in social relationships are understood to contribute to its maintenance. The treatment of ODD is often successful, and relatively brief parenting interventions produce large sized treatment effects in early childhood. Accordingly, ODD represents an important focus for research, practice and policy concerning early intervention and prevention in mental health., (© 2023. Springer Nature Limited.)

We conducted secondary analyses of existing data to examine the association between parent scores on the Knowledge of Effective Parenting Test (KEPT) and child symptoms of Conduct Disorder (CD) and Oppositional Defiant Disorder (ODD). Parent knowledge of behavior management skills and child behavior symptoms were assessed in a nationally representative sample of parents/guardians ( N = 1,570) of children aged 5-12 from all 50 states. Results showed consistent and robust correlations between parent knowledge of behavior management skills and CD symptoms but not ODD symptoms. These findings suggest that parent knowledge of behavior management may be a greater risk factor for CD than ODD, with implications for taxonomy and understanding the etiology of these two disorders. We also discuss the implications of these findings for the prevention and treatment of these two disorders which are often grouped together in treatment trials., Competing Interests: Conflict of Interest: The authors declare that they have no conflicts of interest.

Youth exhibiting psychopathic traits are at increased risk for a more severe, persisting, and treatment-resistant course of antisocial behavior. To reflect this diagnostically, the specifier with limited prosocial emotions (LPE) was added to the criteria for conduct disorder (CD). Yet, psychopathic traits often show an earlier onset than CD symptoms and LPE may exclude important dimensions of psychopathy. This study examines grandiose-manipulative (GM) traits both dimensionally and as a diagnostic specifier for behavioral disorders.Data come from a clinic sample of 177 boys aged 7-12 followed up annually through age 17. Annual parent reports of children's GM, and symptoms of CD, oppositional defiant disorder (ODD), and attention-deficit/hyperactivity disorder (ADHD) were tested, controlling for other psychopathology and demographics. A categorical GM specifier for ODD or ADHD was also tested as a predictor of CD or ODD diagnosis.GM and ODD were significantly predictive of increases in CD. Reciprocal associations were observed between GM and ODD symptoms. The GM specifier was most commonly associated with ODD (91.9%), compared to CD (44.1%) or ADHD (67.1%), and was significantly predictive of future CD when applied to ODD. GM as a specifier for ADHD enhanced the prediction from ADHD to ODD, but not to CD. Including GM as a specifier for disorders beyond CD improves the prediction of future behavioral disorders, distinguishing youth with ODD at risk for CD, and youth with ADHD at risk for ODD. Failing to do so may miss a substantial portion of elevated GM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Oppositional defiant disorder (ODD) is a valid mental health disorder, characterized by negativistic defiant behavior and angry, irritable mood. The very low and stable prevalence rate over development from early childhood into adulthood suggests that ODD does not erroneously medicalize normative childhood behavior. ODD is associated with significant impairments across multiple contexts and raises risks for other future psychopathology. Although simplistic tropes often suggest that ODD is merely the product of bad parenting, substantial evidence shows that it is instead influenced by a variety of factors, including genetic and neurobiological factors. Individuals with ODD evoke negative interactions with peers, teachers, coworkers, romantic partners, and parents. ODD is often misunderstood as being a mild form of conduct disorder (CD). Rather, in stark contrast to ODD, CD reflects a pattern of aggressive behaviors, violations of laws or status offenses, and psychopathic features. Mounting evidence for their distinction led to diagnostic changes distinguishing ODD and CD nearly a decade ago. Empirically supported treatments are available and help caregivers to develop specific parenting practices to meet the needs of children with ODD. Minimizing and mischaracterizing ODD increases the likelihood that families who are suffering may not seek the treatment that they need., (© 2022 Association for Child and Adolescent Mental Health.)

Competing Interests: The author declares no conflict of interest.

Oppositional defiant disorder includes distinct but inseparable dimensions of chronic irritability and oppositional behavior. The dimensions have been identified in early childhood to adulthood, and show discriminant associations with internalizing and externalizing psychopathology. The introduction of disruptive mood dysregulation disorders and the requirements that it take precedence over oppositional defiant disorder diagnostically are not supported by evidence and introduce confusion about the structure and linkages of irritability and oppositional behavior, and obscure the importance of the behavioral dimension in explaining and predicting poor outcomes. A dimensional framework with irritability, oppositionality, callous-unemotional traits, and aggression may more fully describe antisocial outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: The author declares no conflict of interest.

Background: Severe irritability has become an important topic in child and adolescent mental health. Based on the available evidence and on public health considerations, WHO classified chronic irritability within oppositional defiant disorder (ODD) in ICD-11, a solution markedly different from DSM-5's (i.e. the new childhood mood diagnosis, disruptive mood dysregulation disorder [DMDD]) and from ICD-10's (i.e. ODD as one of several conduct disorders without attention to irritability). In this study, we tested the accuracy with which a global, multilingual, multidisciplinary sample of clinicians were able to use the ICD-11 classification of chronic irritability and oppositionality as compared to the ICD-10 and DSM-5 approaches., Methods: Clinicians (N = 196) from 48 countries participated in an Internet-based field study in English, Spanish, or Japanese and were randomized to review and use one of the three diagnostic systems. Through experimental manipulation of validated clinical vignettes, we evaluated how well clinicians in each condition could identify chronic irritability versus nonirritable oppositionality, episodic bipolar disorder, dysthymic depression, and normative irritability., Results: Compared to ICD-10 and DSM-5, ICD-11 led to more accurate identification of severe irritability and better differentiation from boundary presentations. Participants using DSM-5 largely failed to apply the DMDD diagnosis when it was appropriate, and they more often applied psychopathological diagnoses to developmentally normative irritability., Conclusions: The formulation of irritability and oppositionality put forth in ICD-11 shows evidence of clinical utility, supporting accurate diagnosis. Global mental health clinicians can readily identify ODD both with and without chronic irritability., (© 2020 The World Health Organization.)

Dimensions of irritability and defiant behavior, though correlated within the structure of ODD, convey separable developmental risks through adolescence and adulthood. Irritability predicts depression and anxiety, whereas defiant behavior is a precursor to antisocial outcomes. Previously we demonstrated that a bifactor model comprising irritability and defiant behavior dimensions, in addition to a general factor, provided the best-fitting structure of ODD symptoms in five large datasets. Herein we extend our previous work by externally validating the bifactor model of ODD using multiple regression and multivariate behavior genetic analyses. We used parent ratings of DSM IV ODD symptoms, and symptom dimensions for ADHD (i.e., inattention and hyperactivity-impulsivity), conduct disorder (CD), depression/dysthymia, and generalized anxiety disorder (GAD) from 846 6-18-year-old twin pairs. We found that the ODD irritability factor was associated only with depression/dysthymia and GAD and the ODD defiant behavior factor was associated only with inattention, hyperactivity-impulsivity, and CD, whereas the ODD general factor was associated with all five symptom dimensions. Multivariate behavior genetic analyses found all five symptom dimensions shared genetic influences in common with the ODD general, irritability, and defiant behavior factors. In contrast, the defiant behavior factor shared genetic influences uniquely with inattention and hyperactivity-impulsivity, whereas the irritability factor shared genetic influences uniquely with depression/dysthymia and GAD, but not vice versa. This suggests that genes that influence irritability in early childhood also predispose to depression and anxiety in adolescence and adulthood. These multivariate genetic findings also support the external validity of the three ODD dimensions at the etiological level. Our study provides additional support for subtyping ODD based on these symptom dimensions, as in the revisions in the ICD-11, and suggests potential mechanisms underlying the development from ODD to behavioral or affective disorders.

In 2013, the American Psychiatric Association (APA) published the 5th edition of its Diagnostic and Statistical Manual of Mental Disorders (DSM-5). In 2019, the World Health Assembly approved the 11th revision of the International Classification of Diseases (ICD-11). It has often been suggested that the field would benefit from a single, unified classification of mental disorders, although the priorities and constituencies of the two sponsoring organizations are quite different. During the development of the ICD-11 and DSM-5, the World Health Organization (WHO) and the APA made efforts toward harmonizing the two systems, including the appointment of an ICD-DSM Harmonization Group. This paper evaluates the success of these harmonization efforts and provides a guide for practitioners, researchers and policy makers describing the differences between the two systems at both the organizational and the disorder level. The organization of the two classifications of mental disorders is substantially similar. There are nineteen ICD-11 disorder categories that do not appear in DSM-5, and seven DSM-5 disorder categories that do not appear in the ICD-11. We compared the Essential Features section of the ICD-11 Clinical Descriptions and Diagnostic Guidelines (CDDG) with the DSM-5 criteria sets for 103 diagnostic entities that appear in both systems. We rated 20 disorders (19.4%) as having major differences, 42 disorders (40.8%) as having minor definitional differences, 10 disorders (9.7%) as having minor differences due to greater degree of specification in DSM-5, and 31 disorders (30.1%) as essentially identical. Detailed descriptions of the major differences and some of the most important minor differences, with their rationale and related evidence, are provided. The ICD and DSM are now closer than at any time since the ICD-8 and DSM-II. Differences are largely based on the differing priorities and uses of the two diagnostic systems and on differing interpretations of the evidence. Substantively divergent approaches allow for empirical comparisons of validity and utility and can contribute to advances in the field., (© 2021 World Psychiatric Association.)

Chronic irritability is a core feature of oppositional defiant disorder (ODD) and disruptive mood dysregulation disorder (DMDD), but few irritability-specific interventions have been tested. Existing evidence-based treatments for disruptive behavior problems offer a strong template. This pilot study was conducted to develop and evaluate a brief irritability-specific module of a validated cognitive-behavioral group intervention for children (Stop Now And Plan (SNAP) Program). Stop now and plan for irritability (I-SNAP) retained core elements of SNAP in a shortened 6-week format. Community families with irritable children ( M  = 8.44 years, SD  = 1.42) were recruited for parent and child emotion regulation skills groups. Of 18 children enrolled (72% male), 14 completed (78%). Half of children attended all six sessions, though homework compliance was lower. All parents reported favorable impressions and would recommend I-SNAP to others. Significant improvements were seen from pre- to post-treatment across parent-reported irritability, ODD symptoms, emotion regulation, and disciplinary effectiveness. This pilot study provides initial support suggesting I-SNAP may be feasible to implement and acceptable to parents. In addition, pilot analyses demonstrated that this brief group intervention was associated with positive outcomes consistent with treatment targets. This preliminary evidence supports the need for further research to assess I-SNAP's effects on irritability relative to control groups.

Questions persist about whether attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder are in fact distinct from one another. When such questions arise, ODD is often suggested to be subsumed under one or the other condition. Modeling approaches that can evaluate whether specific subfactors can be distinguished from general psychopathology are of great interest, and the general bifactor model has been increasingly applied in studies evaluating the structure of psychopathology. However, evidence for bias in the model, the frequency of anomalous indicators, and theoretical concerns about the applicability of the general bifactor model to these questions raise doubts about whether it is reliable or appropriate to do so. Burns and colleagues propose the bifactor S-1 model as a psychometrically sounder alternative. Their systematic examination provides a compelling argument that it is psychometrically sounder, but it is not clear that it is a true alternative. It may not be answering the same questions, cannot test hypotheses regarding the same sets of specific subfactors, and relies on a priori decisions on the part of the researcher that may change the interpretation of the results. The bifactor S-1 model approach appears to be a valuable, psychometrically sound approach to test the structure of psychopathology, particularly in regard to ADHD and ODD.

Parental verbal aggression and corporal punishment are associated with children's conduct problems and oppositional defiant disorder (ODD). The strength of bidirectional relationships among specific disruptive behaviors has been inconsistent across gender, and the direction of influence between parental aggression and girls' ODD symptoms is particularly understudied. This study tested reciprocal effects between aggressive parent behaviors and girls' ODD dimensions of oppositionality, antagonism, and irritability. Data from the Pittsburgh Girls Study ( N = 2,450) were used, including annual child and parent-reported aggressive discipline and girls' parent-reported ODD symptoms between ages 5 and 16. Separate clustered Poisson regression models examined change in parent or child behavior outcomes using predictors lagged by one time point. After controlling for demographic factors, behavior stability, and other disruptive behaviors, parent-reported corporal punishment predicted girls' increasing antagonism and irritability, whereas child-reported corporal punishment was unrelated to ODD symptom change. Both parent- and child-reported verbal aggression predicted increases across ODD dimensions. Girls' oppositionality and antagonism predicted increasing parent-reported verbal aggression over time, but only oppositionality was significantly related to child-reported verbal aggression. Although ODD symptoms were unrelated to change in corporal punishment, attention deficit/hyperactivity disorder (ADHD) predicted increasing parental aggression of both types. Bidirectional associations emerged such that parental verbal aggression escalates reciprocally with girls' behavioral ODD symptoms. Verbal aggression contributed to increasing irritability, but irritability did not influence parenting behavior. "Child effects" may be most salient for behavioral ODD symptoms in transaction with verbal aggression and for ADHD symptoms in predicting worsening corporal punishment and verbal aggression.

Millions of children across the USA have unmet mental health needs. When these include the disruptive behavior disorders (DBDs)-oppositional defiant disorder (ODD), conduct disorder (CD), and attention-deficit/hyperactivity disorder (ADHD)-this can mean significant long-term consequences. Since children rarely seek treatment themselves, parents are central to the help-seeking process. This paper reviews research on the rates of problem recognition and help-seeking for DBDs, and on perceptual barriers that might hinder service engagement. Most children with DBDs are neither identified as such nor engaged in treatment, although this may be less true for ADHD than ODD or CD. Factors associated with DBDs that may reduce service engagement include seeing the behaviors as "normative," interpreting the symptoms as willful, and expecting to be blamed for the child's problems. Implications of these findings are discussed with particular focus on the widespread dissemination of evidence-based information about DBDs.

A doptive c ell t ransfer (ACT) is a powerful experimental approach to directly study T-cell-mediated immunity in vivo In the rhesus macaque AIDS virus model, infusing simian immunodeficiency virus (SIV)-infected animals with CD8 T cells engineered to express anti-SIV T-cell receptor specificities enables direct experimentation to better understand antiviral T-cell immunity in vivo Limiting factors in ACT experiments include suboptimal trafficking to, and poor persistence in, the secondary lymphoid tissues targeted by AIDS viruses. Previously, we redirected CD8 T cells to B-cell follicles by ectopic expression of the CXCR5 homing protein. Here, we modify peripheral blood mononuclear cell (PBMC)-derived CD8 T cells to express the CCR9 chemokine receptor, which induces preferential homing of the engineered cells to the small intestine, a site of intense early AIDS virus replication and pathology in rhesus macaques. Additionally, we increase in vivo persistence and overall systemic distribution of infused CD8 T cells, especially in secondary lymphoid tissues, by minimizing ex vivo culture/manipulation, thereby avoiding the loss of CD28 + /CD95 + central memory T cells by differentiation in culture. These proof-of-principle results establish the feasibility of preferentially localizing PBMC-derived CD8 T cells to the small intestine and enables the direct experimental ACT-based assessment of the potential role of the quality and timing of effective antiviral CD8 T-cell responses to inhibit viral infection and subsequent replication in small intestine CD4 T cells. More broadly, these results support the engineered expression of homing proteins to direct CD8 T cells to target tissues as a means for both experimental and potential therapeutic advances in T-cell immunotherapies, including cancer. IMPORTANCEA doptive c ell t ransfer (ACT) of T cells engineered with antigen-specific effector properties can deliver targeted immune responses against malignancies and infectious diseases. Current T-cell-based therapeutic ACT relies on circulatory distribution to deliver engineered T cells to their targets, an approach which has proven effective for some leukemias but provided only limited efficacy against solid tumors. Here, engineered expression of the CCR9 homing receptor redirected CD8 T cells to the small intestine in rhesus macaque ACT experiments. Targeted homing of engineered T-cell immunotherapies holds promise to increase the effectiveness of adoptively transferred cells in both experimental and clinical settings., (Copyright © 2019 American Society for Microbiology.)

Optimal lysosome function requires maintenance of an acidic pH maintained by proton pumps in combination with a counterion transporter such as the Cl - /H + exchanger, CLCN7 (ClC-7), encoded by CLCN7. The role of ClC-7 in maintaining lysosomal pH has been controversial. In this paper, we performed clinical and genetic evaluations of two children of different ethnicities. Both children had delayed myelination and development, organomegaly, and hypopigmentation, but neither had osteopetrosis. Whole-exome and -genome sequencing revealed a de novo c.2144A>G variant in CLCN7 in both affected children. This p.Tyr715Cys variant, located in the C-terminal domain of ClC-7, resulted in increased outward currents when it was heterologously expressed in Xenopus oocytes. Fibroblasts from probands displayed a lysosomal pH approximately 0.2 units lower than that of control cells, and treatment with chloroquine normalized the pH. Primary fibroblasts from both probands also exhibited markedly enlarged intracellular vacuoles; this finding was recapitulated by the overexpression of human p.Tyr715Cys CLCN7 in control fibroblasts, reflecting the dominant, gain-of-function nature of the variant. A mouse harboring the knock-in Clcn7 variant exhibited hypopigmentation, hepatomegaly resulting from abnormal storage, and enlarged vacuoles in cultured fibroblasts. Our results show that p.Tyr715Cys is a gain-of-function CLCN7 variant associated with developmental delay, organomegaly, and hypopigmentation resulting from lysosomal hyperacidity, abnormal storage, and enlarged intracellular vacuoles. Our data supports the hypothesis that the ClC-7 antiporter plays a critical role in maintaining lysosomal pH., (Published by Elsevier Inc.)

Interferon gamma has long been studied as a critical mediator of tumor immunity. In recent years, the complexity of cellular interactions that take place in the tumor microenvironment has become better appreciated in the context of immunotherapy. While checkpoint inhibitors have dramatically improved remission rates in cancer treatment, IFN-γ and related effectors continue to be identified as strong predictors of treatment success. In this review, we provide an overview of the multiple immunosuppressive barriers that IFN-γ has to overcome to eliminate tumors, and potential avenues for modulating the immune response in favor of tumor rejection., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Parent satisfaction with neurodevelopmental evaluations may influence the pursuit of intervention. Parent satisfaction with a neurodevelopmental evaluation for toddlers at risk for autism (n = 257; 128 with autism) was examined using the Post-Evaluation Satisfaction Questionnaire, which collected quantitative and qualitative information. Fewer ethnic/racial minority than non-minority parents returned the questionnaire. Factor analysis indicated a one-factor model, Total score, which did not differ significantly by diagnosis, autism severity, child's cognitive or adaptive delay, family race/ethnicity, maternal education, family annual income, or parental stress. Examination of 24 individual items showed a race/ethnicity difference for only one item; minority parents scored the evaluation as meeting their needs less. Qualitative data stressed the importance of fully explaining diagnoses/recommendations and providing direct and clear feedback.

Autism Spectrum Disorder (ASD) diagnostic tools are not designed for mental ages (MA) below 12 months. Autism Diagnostic Observation Schedule (ADOS) and Childhood Autism Rating Scale (CARS) were examined in 2-year-olds with ASD-low MA (n = 53), Global Developmental Delay (GDD; n = 175), and ASD-higher MA (n = 425). ADOS and CARS demonstrated similar agreement with clinical diagnosis, but ADOS over-classified ASD in low MA, whereas CARS both over- and under-classified. All ADOS items differentiated GDD from ASD. Elementary social behaviors (e.g., eye contact, social interest) were similar across ASD groups, although advanced skills (e.g., pointing, play) were more impaired in ASD-low MA. ASD-low MA, a severe presentation, may require a modified ADOS algorithm to account for developmental delays.

Research supports the clinical importance of childhood irritability, as well as its developmental implications for later anxiety and depression. Appropriate treatment may prevent this progression; however, little evidence exists to guide clinician decision making regarding treatment for chronic irritability symptoms. Given the empirical support for irritability as a dimension of oppositional defiant disorder (ODD), behavioral interventions that improve ODD symptoms, especially through emotion regulation training, are strong candidates for identifying effective treatment strategies for irritability. Data from a randomized controlled effectiveness trial were used to assess hypotheses regarding irritability. The Stop Now and Plan (SNAP) Program was developed for preadolescent youths demonstrating clinically high rates of conduct problems. Participants (252 boys, ages 6-11) were assigned to participate in either SNAP or standard services; data were collected at 4 time points over 15 months. Although lower irritability scores over time were seen for the SNAP group compared to standard services, the main effect for treatment was small and did not reach statistical significance. However, a significant indirect effect of SNAP treatment on irritability via improved emotion regulation skills was found; improved emotion regulation skills were associated with significant and substantial reductions in irritability. Specific effects of SNAP for the improvement of emotion regulation skills function as a mechanism for subsequent reductions in irritability, supporting the distinction between emotion regulation and irritability symptoms. Enhancing increased emotion regulation skills within existing evidence-based interventions for children with ODD should provide a strong foundation for treatments to target irritability symptoms.

Neurodevelopmental disorders (NDD) are genetically and phenotypically heterogeneous conditions due to defects in genes involved in development and function of the nervous system. Individuals with NDD, in addition to their primary neurodevelopmental phenotype, may also have accompanying syndromic features that can be very helpful diagnostically especially those with recognizable facial appearance. In this study, we describe ten similarly affected individuals from six unrelated families of different ethnic origins having bi-allelic truncating variants in TMEM94, which encodes for an uncharacterized transmembrane nuclear protein that is highly conserved across mammals. The affected individuals manifested with global developmental delay/intellectual disability, and dysmorphic facial features including triangular face, deep set eyes, broad nasal root and tip and anteverted nostrils, thick arched eye brows, hypertrichosis, pointed chin, and hypertelorism. Birthweight in the upper normal range was observed in most, and all but one had congenital heart defects (CHD). Gene expression analysis in available cells from affected individuals showed reduced expression of TMEM94. Global transcriptome profiling using microarray and RNA sequencing revealed several dysregulated genes essential for cell growth, proliferation and survival that are predicted to have an impact on cardiotoxicity hematological system and neurodevelopment. Loss of Tmem94 in mouse model generated by CRISPR/Cas9 was embryonic lethal and led to craniofacial and cardiac abnormalities and abnormal neuronal migration pattern, suggesting that this gene is important in craniofacial, cardiovascular, and nervous system development. Our study suggests the genetic etiology of a recognizable dysmorphic syndrome with NDD and CHD and highlights the role of TMEM94 in early development., (Published by Elsevier Inc.)

Background: Parents and providers are sometimes concerned that exposure to two languages will impair language acquisition in children with autism spectrum disorder (ASD) or other developmental disorders (DD). However, research to date suggests that language milestones and abilities are unaffected by this exposure. The current study explored language abilities in toddlers with ASD or DD exposed to one versus multiple languages, prior to intervention. To our knowledge, this is the largest investigation of language learning in bilingual-exposed (BE) children with ASD., Methods: Participants were 388 children evaluated as part of a larger study on the early detection of ASD. Parents were asked to list all languages that primary caretakers use to communicate with their child. One hundred six BE children (57 ASD, 49 DD) were compared to 282 monolingual-exposed (ME) children (176 ASD, 106 DD). The Mullen Scales of Early Learning assessed nonverbal and verbal abilities. Multiple regression was used to evaluate the relationship of BE to language abilities, beyond the influence of nonverbal cognitive abilities, diagnosis, and socioeconomic status., Results: Results showed greater language impairment in ASD than DD, but no main effect for language exposure group nor any interaction of language group by diagnosis. Results remained consistent after controlling for socioeconomic status., Conclusion: This study suggests that bilingual caregivers can communicate with their children in both languages without adverse effects on their children's language functioning., Competing Interests: Conflicts of Interest Deborah Fein is part owner of M-CHAT-R, LLC, which receives royalties from companies that incorporate the M-CHAT-R into commercial products and charge for its use. Data reported in the current paper is from the freely available paper version of the M-CHAT-R. Yael Dai, Jeffrey Burke, Letitia Naigles, and Inge-Marie Eigsti declare that they have no potential or competing conflicts of interest.

The aim of this study was to determine whether borderline personality disorder (BPD) can be differentiated from other disorders in a clinical sample of adolescent girls. Participants (N = 75) were grouped based on the pattern of BPD symptom endorsement using a latent class analysis. Four latent classes were identified. The most impaired class endorsed seven BPD symptoms and an average of three comorbid disorders. An intermediate class endorsed three BPD symptoms and had the highest prevalence of PTSD (41.7%). A third class reported two BPD symptoms and had a high prevalence of anxiety disorders (62%). The fourth class had no BPD symptoms and, on average, one comorbid disorder. Only a small subset of these teenage girls met criteria for BPD, and they had distinct and severe impairment. The results suggest the modest likelihood of a BPD diagnosis in clinical samples of teenage girls, and to also be vigilant for PTSD.

Progressive microcephaly and neurodegeneration are genetically heterogenous conditions, largely associated with genes that are essential for the survival of neurons. In this study, we interrogate the genetic etiology of two siblings from a non-consanguineous family with severe early onset of neurological manifestations. Whole exome sequencing identified novel compound heterozygous mutations in VARS that segregated with the proband: a missense (c.3192G>A; p.Met1064Ile) and a splice site mutation (c.1577-2A>G). The VARS gene encodes cytoplasmic valyl-tRNA synthetase (ValRS), an enzyme that is essential during eukaryotic translation. cDNA analysis on patient derived fibroblasts revealed that the splice site acceptor variant allele led to nonsense mediated decay, thus resulting in a null allele. Three-dimensional modeling of ValRS predicts that the missense mutation lies in a highly conserved region and could alter side chain packing, thus affecting tRNA binding or destabilizing the interface between the catalytic and tRNA binding domains. Further quantitation of the expression of VARS showed remarkably reduced levels of mRNA and protein in skin derived fibroblasts. Aminoacylation experiments on patient derived cells showed markedly reduced enzyme activity of ValRS suggesting the mutations to be loss of function. Bi-allelic mutations in cytoplasmic amino acyl tRNA synthetases are well-known for their role in neurodegenerative disorders, yet human disorders associated with VARS mutations have not yet been clinically well characterized. Our study describes the phenotype associated with recessive VARS mutations and further functional delineation of the pathogenicity of novel variants identified, which widens the clinical and genetic spectrum of patients with progressive microcephaly.

Abnormalities in reward and punishment processing are implicated in the development of conduct problems (CP), particularly among youth with callous-unemotional (CU) traits. However, no studies have examined whether CP children with high versus low CU traits exhibit differences in the neural response to reward and punishment. A clinic-referred sample of CP boys with high versus low CU traits (ages 8-11; n = 37) and healthy controls (HC; n = 27) completed a fMRI task assessing reward and punishment processing. CP boys also completed a randomized control trial examining the effectiveness of an empirically-supported intervention (i.e., Stop-Now-And-Plan; SNAP). Primary analyses examined pre-treatment differences in neural activation to reward and punishment, and exploratory analyses assessed whether these differences predicted treatment outcome. Results demonstrated associations between CP and reduced amygdala activation to punishment independent of age, race, IQ and co-occurring ADHD and internalizing symptoms. CU traits were not associated with reward or punishment processing after accounting for covariates and no differences were found between CP boys with high versus low CU traits. While boys assigned to SNAP showed a greater reduction in CP, differences in neural activation were not associated with treatment response. Findings suggest that reduced sensitivity to punishment is associated with early-onset CP in boys regardless of the level of CU traits., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In preparation for the World Health Organization's development of the Eleventh Revision of the International Classification of Diseases and Related Health Problems (ICD-11) chapter on Mental and Behavioral Disorders, this article reviews the literature pertaining to severe irritability in child and adolescent psychopathology. First, research on severe mood dysregulation suggests that youth with irritability and temper outbursts, among other features of hyperactivity and arousal, demonstrate cross-sectional correlates and developmental outcomes that distinguish them from youth with bipolar disorder. Second, other evidence points to an irritable dimension of Oppositional Defiant Disorder symptomatology, which is uniquely associated with concurrent and subsequent internalizing problems. In contrast to the Diagnostic and Statistical Manual of Mental Disorders' (5th ed.) Disruptive Mood Dysregulation Disorder, our review of the literature supports a different solution: a subtype, Oppositional Defiant Disorder with chronic irritability/anger (proposal included in Appendix). This solution is more consistent with the available evidence and is a better fit with global public health considerations such as harm/benefit potential, clinical utility, and cross-cultural applicability. Implications for assessment, treatment, and research are discussed., (Copyright © 2017 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Objective: Characterization of academic functioning in children with autism spectrum disorder (ASD), particularly predictors of achievement, may have important implications for intervention. The current study aimed to characterize achievement profiles, confirm associations between academic ability and concurrent intellectual and social skills, and explore preschool predictors of school-age academic achievement in a sample of children with ASD., Method: Children with ASD (n = 26) were evaluated at the approximate ages of two, four, and ten. Multiple regression was used to predict school-age academic achievement in reading and mathematics from both concurrent (i.e. school-age) and preschool variables., Results: Children with ASD demonstrated a weakness in reading comprehension relative to word reading. There was a smaller difference between mathematics skills; math reasoning was lower than numerical operations, but this did not quite reach trend level significance. Concurrent IQ and social skills were associated with school-age academic achievement across domains. Preschool verbal abilities significantly predicted school-age reading comprehension, above and beyond concurrent IQ, and early motor functioning predicted later math skills., Conclusions: Specific developmental features of early ASD predict specific aspects of school-age achievement. Early intervention targeting language and motor skills may improve later achievement in this population.