Faculty Bibliography

Among the many impacts of the Coronavirus disease (COVID-19) pandemic, one of the most dramatic was the immediate closure of in-person schooling in March/April 2020 when parents were faced with much greater responsibility in supporting their children's learning. Despite this, few studies have examined parents' own perspectives of this experience. The aims of this preliminary study were to (a) identify challenges, benefits, and useful strategies related to remote learning and (b) examine differences in findings across two countries, between parents of youth with and without attention-deficit/hyperactivity disorder (ADHD), and between parents of children and adolescents. To address these aims, parent responses to open-ended questions on the Home Adjustment to COVID-19 Scale (HACS; Becker, Breaux, et al., 2020) were examined across three studies conducted in the United States and Australia (N = 606, children: 68.5% male, ages 6-17 years). The challenges most frequently expressed by parents included the child's difficulty staying on task (23.8% of parents), lack of motivation (18.3%), remote learning factors (17.8%), and lack of social interaction (14.4%). The most frequently expressed strategy related to using routines and schedules (58.2%) and the biggest benefit was more family time (20.3%). Findings were largely consistent across countries, ADHD status, and age, with a few notable group differences. Given that the most common challenges involved child- (e.g., difficulties with staying on task and motivation), parent- (e.g., balancing remote learning with work responsibilities), and school- (e.g., remote instruction difficulties) related factors, there is a need for improved support across these systems going forward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

UNLABELLED:Maternal psychopathology given a history of maltreatment and domestic violence exposure increases the risk for child psychopathology. Infant social withdrawal is one warning sign of adverse developmental outcomes including child anxiety and depression. It remains unclear how maternal trauma-related psychopathology might affect infant social withdrawal six-months postpartum. METHODS:One-hundred ninety-five women and their six-month-old infants were studied in an at-risk community sample. Maternal trauma history, posttraumatic stress (PTSD) and major depressive (MDD) disorders were assessed. Maternal and infant behaviors were coded from videotaped interactions. RESULTS:Maternal trauma was correlated with atypical maternal behavior (AMB) and infant social withdrawal (p ≤ .001). PTSD and MDD, and comorbid PTSD/MDD predicted increased AMB (p ≤ .001) but only maternal MDD was predictive of infant social withdrawal (p ≤ .001). Effects of maternal MDD on infant withdrawal were mediated by AMB. CONCLUSIONS:At six-months postpartum, maternal MDD was associated with infant withdrawal. AMB is an important target for early intervention.

BACKGROUND:Children referred for attention-deficit/hyperactivity disorder (ADHD) often present with a broader pattern of conduct problems including oppositionality and defiance. This combination can be extremely stressful to parents, lower parents' self-esteem and negatively impact family life. The National Institute for Health and Care Excellence (NICE) recommends that families receive support as soon as possible after their referral. However, as clinical services are overstretched, and traditional in-person parenting intervention programmes are expensive, families often must wait times a long time prior to receiving this vital input. To address this, we have created a digital parenting programme called STEPS. It is delivered as a mobile phone app providing a set of tools and resources that can be easily accessed at parents' convenience. This study aims to evaluate the clinical and cost-effectiveness of STEPS in supporting parents of children with high levels of hyperactivity/impulsivity, inattention and conduct problems, who are waiting to be assessed by specialist children's clinical services. METHODS:Online Parent Training for The Initial Management of ADHD referrals (OPTIMA) is a two-arm superiority parallel randomised controlled trial with an internal pilot study. We aim to recruit 352 parents and their children, who have been accepted onto a waitlist in Child and Adolescent Mental Health Services or similar child health services. Parents who consent will be randomised 1:1 to either the STEPS or wait-as-usual (WAU) group. The trial will be conducted remotely (online and telephone) with measures taken at baseline and 3, 6, 9 and 12 months post-randomisation. The primary objective is to evaluate whether STEPS reduces the severity of children's oppositional and defiant behaviour, as rated by parents, measured at 3 months post-randomisation compared to WAU. DISCUSSION/CONCLUSIONS:Digital solutions, such as mobile phone apps, have potential for delivering psychological support for parents of children with clinical-level needs in a timely and inexpensive manner. This trial will provide data on the clinical and cost-effectiveness of the STEPS app, which could support the implementation of this scalable parenting intervention programme into standard clinical care and, ultimately, improve the outcomes for families of children referred to specialist child and adolescent health services. TRIAL REGISTRATION/BACKGROUND:ISRCTN 16523503. Prospectively registered on 18 November 2021. https://www.isrctn.com/ISRCTN16523503.

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.

We carried out a systematic review and meta-analysis to investigate the effects of stimulant and non-stimulant medications on autonomic functioning in people with ADHD (PROSPERO: CRD42020212439). We searched (9th August 2021) PsycInfo, MEDLINE, EMBASE, Web of Science and The Cochrane Library, for randomised and non-randomised studies reporting indices of autonomic activity, (electrodermal, pupillometry and cardiac), pre- and post-medication exposure in people meeting DSM/ICD criteria for ADHD. In the narrative syntheses, we included 5 electrodermal studies, 1 pupillometry study and 57 studies investigating heart rate and blood pressure. In the meta-analyses, 29 studies were included on blood pressure and 32 on heart rate. Administration of stimulants, and to a lesser degree, non-stimulants increased heart rate and blood pressure in people with ADHD. Similarly, an upregulation of arousal, reflected in increased electrodermal activity and pupil diameter was observed following stimulant use. Yet, the methodological diversity of studies presented in this review reinforces the need for more standardised and rigorous research to fully understand the relationship between arousal, medication, and behaviour in ADHD.

The British Association for Psychopharmacology course on child and adolescent psychopharmacology has been run for more than 20 years and is currently a very popular course, attracting around 140 delegates/year from across the United Kingdom and abroad. As Faculty of recent sessions of the course, we have selected the most common questions we have been asked in recent years and provided evidence-based and/or expert-informed answers. We have included 27 questions and answers related to attention-deficit/hyperactivity disorder, anxiety and depressive disorders, autism spectrum disorder, bipolar disorder, eating disorders, epilepsy (in differential diagnosis or comorbid with mental health conditions), obsessive-compulsive disorder, personality disorders, psychotic spectrum disorders, and tics/Tourette syndrome in children and young people. We hope that this article will be helpful for prescribers in their daily clinical practice and we look forward to further, high-level evidence informing the answers to these and other questions in child and adolescent psychopharmacology.

IMPORTANCE:Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety. OBJECTIVE:To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs). DATA SOURCES:PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022. STUDY SELECTION:Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD. DATA EXTRACTION AND SYNTHESIS:Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline. MAIN OUTCOMES AND MEASURES:The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest. RESULTS:Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases. CONCLUSIONS AND RELEVANCE:This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

Purpose : Automated segmentation of in-vivo lamina cribrosa (LC) has been challenging, owing to the complex 3D structure and decreased visibility in the lamina depth. Frangi's vesselness filter, which was originally developed for angiogram segmentation, have been successfully demonstrated in segmenting the ex-vivo LC from micro-CT and second harmonic generation microscopy images. In this project we are proposing a new approach of segmenting the in vivo LC from OCT scans, incorporating the Frangi's vesselness principle to facilitate in vivo LC image analysis in much greater detail compared to our previously described 3D analysis method. Methods : In-vivo spectral-domain OCT scans (Leica, Chicago, IL) were acquired from healthy non-human primates. Scans of varying degree of image quality were selected for the analysis and underwent automated brightness and local contrast enhancement. 3D Frangi's vesselness filter was applied using a fixed setting for scans of all qualities. Our previously described segmentation algorithm was then used to quantify the LC microstructure. The measurements generated from the Frangi analysis and from our own conventional method were compared with a standard reference (manually segmented LC by an expert). Paired t tests were performed to compare if the differences between standard reference and conventional method are greater than the differences between standard reference and Frangi analysis. The visibility of analyzable lamina and dice coefficient were also compared to the conventional method using the same test. Results : In vivo scans acquired from 5 rhesus macaques (3 males, 1 female, aged 4.3-10.7 yrs) were used for the analysis. No significant difference was detected for LC microstructure parameters between Frangi's approach and conventional method with respect to the standard reference, except for significantly higher pore count in Frangi's method (p=0.003; Table). Furthermore, visibility (Figure) was significantly higher for the Frangi method compared to the conventional approach (p<0.001) with no difference detected for the semantic segmentation, as reflected by the dice coefficient. Conclusions : The use of Frangi analysis substantially increase the analyzable lamina while providing similar quantification of the LC microstructure compared to our previous 3D analysis method. This improves the potential for automated and thorough volumetric analysis of in vivo OCT LC image

BACKGROUND:Bacterial pneumonia is a major risk factor for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Pseudomonas aeruginosa (PA), an opportunistic pathogen with an increasing resistance acquired against multiple drugs, is one of the main causative agents of ALI and ARDS in diverse clinical settings. Given the anti-inflammatory role of the cannabinoid-2 receptor (CB2R), the effect of CB2R activation in the regulation of PA-induced ALI and inflammation was tested in a mouse model as an alternative to conventional antibiotic therapy. METHODS:In order to activate CB2R, a selective synthetic agonist, JWH133, was administered intraperitoneally (i.p.) to C57BL/6J mice. Furthermore, SR144528 (a selective CB2R antagonist) was administered in combination with JWH133 to test the specificity of the CB2R-mediated effect. PA was administered intratracheally (i.t.) for induction of pneumonia in mice. At 24 h after PA exposure, lung mechanics were measured using the FlexiVent system. The total cell number, protein content, and neutrophil population in the bronchoalveolar lavage fluid (BALF) were determined. The bacterial load in the whole lung was also measured. Lung injury was evaluated by histological examination and PA-induced inflammation was assessed by measuring the levels of BALF cytokines and chemokines. Neutrophil activation (examined by immunofluorescence and immunoblot) and PA-induced inflammatory signaling (analyzed by immunoblot) were also studied. RESULTS:CB2R activation by JWH133 was found to significantly reduce PA-induced ALI and the bacterial burden. CB2R activation also suppressed the PA-induced increase in immune cell infiltration, neutrophil population, and inflammatory cytokines. These effects were abrogated by a CB2R antagonist, SR144528, further confirming the specificity of the CB2R-mediated effects. CB2R-knock out (CB2RKO) mice had a significantly higher level of PA-induced inflammation as compared to that in WT mice. CB2R activation diminished the excess activation of neutrophils, whereas mice lacking CB2R had elevated neutrophil activation. Pharmacological activation of CB2R significantly reduced the PA-induced NF-κB and NLRP3 inflammasome activation, whereas CB2KO mice had elevated NLRP3 inflammasome. CONCLUSION/CONCLUSIONS:Our findings indicate that CB2R activation ameliorates PA-induced lung injury and inflammation, thus paving the path for new therapeutic avenues against PA pneumonia.