Faculty Bibliography

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.

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.

Background: Alzheimer"™s disease (AD) is a neurodegenerative illness characterized by progressive accumulation of amyloid beta (Aβ) and neurofibrillary tangles, with cognitive impairment and altered neural activity. Hyperexcitability in the early stages of AD contribute to Aβ accumulation and cognitive impairment, aggravating the progression of AD. However, the hyperexcitability origin is not clear. This study aimed to test whether mossy cells (MCs), an excitatory cell of the hippocampal dentate gyrus, show increased excitability at early stages of AD and contribute to the increased network excitability generation. Indeed, alterations of MCs contribute to hyperexcitability and cognitive impairment in epilepsy. However, the role of MCs in AD has not been substantially explored. Methods: Intrinsic and synaptic properties of MCs and granule cells (GCs) from WT and Tg2576 mice at early ages (1-2 m.o.) were characterized by whole-cell patch-clamp recordings. Synaptic properties included the frequency and amplitude of spontaneous excitatory postsynaptic potentials (EPSPs) and excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs). Deterioration in MCs morphology was evaluated using Nissl staining and GluR2/3 labeling by light- and confocal microscopy. Aβ deposition was evaluated using the McSA1 antibody. Results: Tg2576 GCs did not have any significant difference in their intrinsic properties, as we shown previously in mice ∼3 m.o. However, an enhanced excitatory and inhibitory input to GCs, depicted by augmented IPSC (7.16 vs 14.04 events/s) and NMDA-mediated EPSC frequencies (0.81 vs 1.41 events/s) were found. Interestingly, Tg2576 MCs had an augmented EPSP frequency (5.75 vs 9.44 events/s), and their intrinsic properties showed a depolarized RMP (-72.88 vs -58.36 mV), and reduced rheobase (145.56 vs 47.14 pA), AP amplitude (98.14 vs 76.66 mV), time-to-peak (552.75 vs 266.16 ms) and maximum rise (171.44 vs 88.68 mV/ms) and decay slopes (-61.17 vs -42.38 mV/ms). The correlation between #APs and current injected showed Tg2576 MCs fired significantly more APs (SEZD = 0.34; z = 2.48). Tg2576 MCs showed robust intracellular Aβ aggregation without any significant morphological change. Conclusions: MCs changes in excitability and early accumulation of Aβ suggest that MCs could be the cause of increased excitability occurring later in GCs. In this manner, MCs could be an important contributor to AD.

Beyond detecting brain lesions or tumors, comparatively little success has been attained in identifying brain disorders such as Alzheimer"™s disease (AD), based on magnetic resonance imaging (MRI). Many machine learning algorithms to detect AD have been trained using limited training data, meaning they often generalize poorly when applied to scans from previously unseen scanners/populations. Therefore, we built a practical brain MRI-based AD diagnostic classifier using deep learning/transfer learning on a dataset of unprecedented size and diversity. A retrospective MRI dataset pooled from more than 217 sites/scanners constituted one of the largest brain MRI samples to date (85,721 scans from 50,876 participants) between January 2017 and August 2021. Next, a state-of-the-art deep convolutional neural network, Inception-ResNet-V2, was built as a sex classifier with high generalization capability. The sex classifier achieved 94.9% accuracy and served as a base model in transfer learning for the objective diagnosis of AD. After transfer learning, the model fine-tuned for AD classification achieved 90.9% accuracy in leave-sites-out cross-validation on the Alzheimer"™s Disease Neuroimaging Initiative (ADNI, 6,857 samples) dataset and 94.5%/93.6%/91.1% accuracy for direct tests on three unseen independent datasets (AIBL, 669 samples / MIRIAD, 644 samples / OASIS, 1,123 samples). When this AD classifier was tested on brain images from unseen mild cognitive impairment (MCI) patients, MCI patients who converted to AD were 3 times more likely to be predicted as AD than MCI patients who did not convert (65.2% vs. 20.6%). Predicted scores from the AD classifier showed significant correlations with illness severity. In sum, the proposed AD classifier offers a medical-grade marker that has potential to be integrated into AD diagnostic practice.

The objective of this article is to examine the experiences and challenges faced by Black professionals in the academic psychiatry workforce. The authors used data collected from previous literature to explore experiences faced at each level of the academic psychiatry pipeline. Review of the literature revealed that systemic barriers contribute to burnout, high turnover, and underrepresentation of Black professionals in academic psychiatry. Retention of Black mental health professionals is fostered by institutional support and interventions that address racism and promote growth and development at every level. While there appears to be a growing body of literature in social medical and popular press, peer-reviewed literature on the experiences of Black trainees and professionals in academic psychiatry is still limited. Additional studies, including systematic data collection among Black psychiatrists, psychologists, faculty, and clinical support staff in academic settings, are needed to continue to examine experiences related to race and racism along the educational and professional workforce continuum. [Psychiatr Ann. 2022;52(12):509-513.].

Digital messaging programs have the potential to be a powerful, low-cost, technological tool to support multiple facets of caregivers' knowledge, and implementation of developmentally appropriate caregiver-child activities among diverse immigrant populations. However, involving caregivers and community stakeholders in the cultural and linguistic tailoring of interventions to optimize utilization and engagement may be critical to ensuring messaging programs' usability and acceptability. The purpose of this mixed-method study was to use the dynamic adaptation process (DAP) within an Exploration, Preparation, Implementation, Sustainment (EPIS) framework to examine the implementation of a digital messaging program, developed at the beginning of the COVID-19 pandemic, aimed at providing Spanish-, English-, and Mandarin-speaking immigrant caregivers with caregiver-child activities that supported children's development and caregivers' knowledge. Building upon the EPIS framework, using DAP, we assessed the feasibility and acceptability of a messaging program via short message service or multimedia message service, WeChat, and Remind and webinar program during the COVID-19 pandemic. The study illustrated how a digital messaging program is a feasible mechanism for sharing developmentally and culturally appropriate information with immigrant caregivers. In addition, the use of the DAP and the EPIS framework allowed us to continuously track the process of cultural adaptation, identify barriers and facilitators of the outreach program, and examine how implementation unfolded across all three groups of caregivers.

BACKGROUND/UNASSIGNED:Adolescent parenthood can be associated with a range of adverse outcomes for young mothers such as depression, substance abuse, and posttraumatic stress disorder. Identification of depression and understanding risk factors among pregnant adolescents is important for development of appropriate interventions and programs focused on adolescent mental health. This paper reports on the findings of the prevalence of depression and its associated risk factors among pregnant adolescents in Nairobi, Kenya. METHODS/UNASSIGNED:We recruited 153 pregnant adolescent (14-18 years) who were accessing maternal health services in one of two Nairobi County primary health care facilities in the cross-sectional survey conducted in 2021. The Patient Health Questionnaire 9 was used to screen for depression. Multivariate Stepwise linear regression modelling was used to identify key predictors of depression. RESULTS/UNASSIGNED:Using a cut off of 10 and above on PHQ-9, we found that 43.1% of the respondents were depressed. Depressive symptoms in were independently associated with being in school, experience of intimate partner violence, substance use within the family and having experienced pressure to use substances by family or peers. LIMITATIONS/UNASSIGNED:Cross-sectional by design and the applications of our findings are limited to settings that are similar to our study population. The PHQ-9 used has not been psychometrically validated locally in this sample. CONCLUSION/UNASSIGNED:We found a high prevalence of depressive symptoms among respondents. These risk factors identified merit further investigation. Comprehensive mental health screening needs to be integrated in primary and community health services on the possible presence of depression.

Background: The brain contains interconnected circuits which are neither completed at birth or invariant across life. This neuronal plasticity is essential for life-long adaptive features like continuous learning and memory. However, this plasticity, especially when associated with severe adverse factors during early-life, can lead to the derailment of normative brain development and contribute to the etiology of behavioral deficits and psychiatric disorders. One of the most influential environmental factors during early-life is parental/caregiver care. Childhood adversity has been estimated to account for a significant percentage of adult-onset mental health disorders. In extreme cases of childhood adversity, institutional rearing where the infants were deprived of caregiver contact, cognitive deficits and dysregulated prefrontal cortex (PFC) function were found. In this study we hypothesize that earlylife adversity, in the form of maternal separation, leads to longlasting changes in the transcriptome of specific PFC cell populations leading to a dysregulation of PFC function.
Method(s): Here, we use a mouse model of maternal separation. The brains of pups and adults of normal reared or maternal separated (MS) animals were collected. In one set, we performed single-nucleus RNAseq with hashing to contrast the PFC transcriptome of these groups. In a separate cohort, we recorded whole slice voltage dye (VSD) responses to explore how changes in receptors identified by snRNAseq altered PFC responses.
Result(s): Using snRNAseq, as expected, we observed that the changes between ages were much more accentuated than changes between treatments. We also observed that the proportion of oligodendrocytes in adult-MS animals was similar to infant animals. Furthermore, we found that most of the differential gene expression between MS and standard reared animals was in interneurons, affecting pathways related to GABAergic, glutamatergic, and serotonergic functions. Using VSD we observed that adult-MS responses to GABAergic and serotonergic agonists were similar to the responses of more immature normal-reared animals.
Conclusion(s): This study suggests that MS leads to an immature PFC that may be linked to the behavioral deficits observed in animals and humans exposed to poor early-life care

Maximizing vaccine uptake is critical for the optimal implementation of COVID-19 immunization programs. Indicators of socioeconomic status (SES) have been associated with variations in COVID-19 vaccine uptake in the United States. The present study investigates COVID-19 vaccination behavior in individuals with history of COVID-19 infection, with the specific goal of understanding whether experiences during illness explain socioeconomic disproportionalities in vaccine uptake. We leveraged a large sample of adults (n = 1584) infected with COVID-19 in NYC to examine this question, investigating whether specific experiences during illness explained the association between socioeconomic status and COVID-19 vaccine hesitancy. Data from this study were collected during February and March 2021. Principal component analysis was used to create three composite variables that measure distinct COVID-19 related experiences: infection-related health impacts, pandemic-related psychosocial disruption, and perceived quality of medical care during COVID-19 illness. Neither infection-related impacts nor psychosocial disruption were related to vaccine hesitancy after adjusting for related sociodemographic covariates. However, perceptions of higher quality care received during COVID-19 illness predicted decreased COVID-19 vaccine hesitancy. Furthermore, mediation analysis revealed that perceived care quality during COVID-19 illness mediate the relationship between objective socioeconomic risk and COVID-19 vaccine hesitancy. These findings highlight patient-reported care quality during illness as a novel target that may increase vaccine uptake among socioeconomically vulnerable populations.

Maternal depression negatively impacts child mental health and is a well-known risk factor for child psychopathology. However, maternal depression treatment and child mental health treatment are rarely integrated. The purpose of this review was to assess the impact of maternal depression on child mental health treatment, including (1) how treatment of maternal depression affects child mental health outcomes, (2) the impact of maternal depression on children receiving mental health care, and (3) emerging models that address maternal depression in primary-care pediatrics and child mental health settings. A systematic literature review was conducted using PubMed and PsycInfo. Initial search yielded 224 records, and after exclusion, 29 papers were reviewed. Effective treatment of maternal depression is associated with a significant decrease in child psychiatric symptoms. Maternal depression negatively affects child mental health treatment in that there is a high rate of untreated mental illness among mothers of psychiatrically ill children, and maternal depression impedes effective child mental health treatment. Current models to address maternal depression in child settings include screening in pediatric primary care, psychotherapy for depressed mothers of psychiatrically ill children, and emerging models that integrate maternal and child mental health treatment. Effective treatment of maternal depression significantly improves child mental health and should be better integrated into child treatment. Opportunities to improve care include more robust screening for parental mental illness, supports to refer parents to psychiatric care, and on-site services for parents. Such interventions hold promise, but require significant support from a multidisciplinary team.