The Pharmacological Management of Oppositional Behaviour,Conduct Problems,and Aggression in Children and Adolescents With Attention-Deficit Hyperactivity Disorder,Oppositional Defiant Disorder,and Conduct Disorder: A Systematic Review and Meta-Analysis. Part 1: Psychostimulants,Alpha-2 Agonists,and Atomoxetine

Objective:

Children with attention-deficit hyperactivity disorder (ADHD) may have oppositional behaviour, conduct problems, and aggression. These symptoms vary in severity, and may be related to a comorbid diagnosis of oppositional defiant disorder (ODD) or conduct disorder (CD). Critical evaluation of the efficacy of ADHD medications may guide the clinician regarding the usefulness of medications for these symptoms.

Method:

We performed a systematic review and meta-analysis of psychostimulants, alpha-2 agonists, and atomoxetine for oppositional behaviour, conduct problems, and aggression in youth with ADHD, ODD, and CD. The quality of evidence for medications was rated using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results:

Two systematic reviews and 20 randomized controlled trials were included. There is high-quality evidence that psychostimulants have a moderate-to-large effect on oppositional behaviour, conduct problems, and aggression in youth with ADHD, with and without ODD or CD. There is very-low-quality evidence that clonidine has a small effect on oppositional behaviour and conduct problems in youth with ADHD, with and without ODD or CD. There is moderate-quality evidence that guanfacine has a small-to-moderate effect on oppositional behaviour in youth with ADHD, with and without ODD. There is high-quality evidence that atomoxetine has a small effect on oppositional behaviour in youth with ADHD, with and without ODD or CD.

Conclusions:

Evidence indicates that psychostimulants, alpha-2 agonists, and atomoxetine can be beneficial for disruptive and aggressive behaviours in addition to core ADHD symptoms; however, psychostimulants generally provide the most benefit.     

Introduction to Cognition in Science and Technology

Cognitive studies of science and technology have had a long history of largely independent research projects that have appeared in multiple outlets, but rarely together. The emergence of a new International Society for Psychology of Science and Technology suggests that this is a good time to put some of the latest work in this area into topiCS in a way that will both acquaint readers with the cutting edge in this domain and also give them a hint of its history. One core theme includes how scientists, inventors, and engineers represent and solve problems; another, related theme is the extent to which they distribute and share cognition. Methodologies include fine‐grained studies of historical records, protocols of working scientists, observations and comparisons of engineering science laboratories, and computational simulations designed both to serve as research tools and also to improve scientific problem‐solving. The series of articles will conclude with the Associate Editor’s suggestions for future research.     

Psychopharmacological possibilities in the acute disaster setting.

This article focuses on possible psychopharmacological interventions in the immediate post disaster setting. As there is little evidence for the efficacy or effectiveness of such interventions-given the difficulty in performing randomized, double-blind, placebo controlled studies with these populations-the article will delineate the neurobiological basis for pathological sequelae and theoretical drug interventions targeting putative disease mechanisms.     

FBXO28 causes developmental and epileptic encephalopathy with profound intellectual disability

Chromosome 1q41‐q42 deletion syndrome is a rare cause of intellectual disability, seizures, dysmorphology, and multiple anomalies. Two genes in the 1q41‐q42 microdeletion, WDR26 and FBXO28, have been implicated in monogenic disease. Patients with WDR26 encephalopathy overlap clinically with those with 1q41‐q42 deletion syndrome, whereas only one patient with FBXO28 encephalopathy has been described. Seizures are a prominent feature of 1q41‐q42 deletion syndrome; therefore, we hypothesized that pathogenic FBXO28 variants cause developmental and epileptic encephalopathies (DEEs). We describe nine new patients with FBXO28 pathogenic variants (four missense, including one recurrent, three nonsense, and one frameshift) and analyze all 10 known cases to delineate the phenotypic spectrum. All patients had epilepsy and 9 of 10 had DEE, including infantile spasms (3) and a progressive myoclonic epilepsy (1). Median age at seizure onset was 22.5 months (range 8 months to 5 years). Nine of 10 patients had intellectual disability, which was profound in six of nine and severe in three of nine. Movement disorders occurred in eight of 10 patients, six of 10 had hypotonia, four of 10 had acquired microcephaly, and five of 10 had dysmorphic features, albeit different to those typically seen in 1q41‐q42 deletion syndrome and WDR26 encephalopathy. We distinguish FBXO28 encephalopathy from both of these disorders with more severe intellectual impairment, drug‐resistant epilepsy, and hyperkinetic movement disorders.     

Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates

Male bonnet monkeys (Macaca radiata) were subjected to the variable foraging demand (VFD) early stress paradigm as infants, MRI scans were completed an average of 4 years later, and behavioral assessments of anxiety and ex-vivo corpus callosum (CC) measurements were made when animals were fully matured. VFD rearing was associated with smaller CC size, CC measurements were found to correlate with fearful behavior in adulthood, and ex-vivo CC assessments showed high consistency with earlier MRI measures. Region of interest (ROI) hippocampus and whole brain voxel-based morphometry assessments were also completed and VFD rearing was associated with reduced hippocampus and inferior and middle temporal gyri volumes. The animals were also characterized according to serotonin transporter genotype (5-HTTLPR), and the effect of genotype on imaging parameters was explored. The current findings highlight the importance of future research to better understand the effects of stress on brain development in multiple regions, including the corpus callosum, hippocampus, and other regions involved in emotion processing. Nonhuman primates provide a powerful model to unravel the mechanisms by which early stress and genetic makeup interact to produce long-term changes in brain development, stress reactivity, and risk for psychiatric disorders.     

Developing effective treatments for posttraumatic disorders among people with severe mental illness.

OBJECTIVE: The purpose of the study was to examine strategies for developing effective interventions for clients who have both serious mental illness and posttraumatic symptoms. METHODS: The authors conducted searches for articles published between 1970 and 2000, using MEDLINE, PsycLIT, and PILOTS. They assessed current practices, interviewed consumers and providers, and examined published and unpublished documents from consumer groups and state mental health authorities. RESULTS AND CONCLUSIONS: Exposure to trauma, particularly violent victimization, is endemic among clients with severe mental illness. Multiple psychiatric and behavioral problems are associated with trauma, but posttraumatic stress disorder (PTSD) is the most common and best-defined consequence of trauma. Mental health consumers and providers have expressed concerns about several trauma-related issues, including possible underdiagnosis of PTSD, misdiagnosis of other psychiatric disorders among trauma survivors, incidents of retraumatization in the mental health treatment system, and inadequate treatment for trauma-related disorders. Despite consensus that trauma and PTSD symptoms should be routinely evaluated, valid assessment techniques are not generally used by mental health care providers. PTSD is often untreated among clients with serious mental illness, or it is treated with untested interventions. It is important that policy makers, service system administrators, and providers recognize the prevalence and impact of trauma in the lives of people with severe mental illness. The development of effective treatments for this population requires a rational, orderly process, beginning with the testing of theoretically grounded interventions in controlled clinical trials.     

In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid.

The present study was conducted to compare the in vitro phase I and phase II metabolic profiles of (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30) in human, rat, and dog microsomes and to characterize and identify the associated metabolic kinetics and specific isozymes from human liver microsomes (HLM) responsible for metabolism, respectively. Data from these experiments revealed that nine (M1-M9) phase I metabolites along with a single glucuronide conjugate were observed across the species investigated. With the exception of glucuronidation, no evidence of metabolism was detected for phase II enzymes (data not shown). Significant differences between species with regard to metabolic profile, stability, and gender were noted. For the eight phase I metabolites detected in HLM, the specific isozymes responsible for the biotransformations were CYP2C8, CYP2C9, and CYP2C19, with minor contributions from CYP1A2 and CYP2B6. For the glucuronide conjugate, UGT1A9 was the major catalyzing enzyme, with a minor contribution from UGT1A3. Kinetic analysis of eight of the detected metabolites indicated that four seemed to follow classical hyperbolic kinetics, whereas the remaining four showed evidence of either autoactivation or substrate inhibition.