Paediatrics (RCH) - Research Publications
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ItemPolyunsaturated fatty acids metabolism, purine metabolism and inosine as potential independent diagnostic biomarkers for major depressive disorder in children and adolescents(SPRINGERNATURE, 2019-10)Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism-particularly the polyunsaturated fatty acids metabolism, and purine metabolism-that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.
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ItemComparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents: protocol for a network meta-analysis(BMJ PUBLISHING GROUP, 2017-08)INTRODUCTION: Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. METHODS AND ANALYSIS: We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. DISSEMINATION: This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. PROTOCOL REGISTRATION: PROSPERO CRD42015020841.
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ItemPredicting Suicidal Risk in a Cohort of Depressed Children and Adolescents(HOGREFE & HUBER PUBLISHERS, 2012)BACKGROUND: In children and adolescents with a depressive disorder, predicting who will also go on to exhibit suicide-related behaviors (SRBs), including suicide attempt or self-harm, is a key challenge facing clinicians. AIMS: To investigate the relative contributions of depressive disorder severity, hopelessness, family dysfunction, and perceived social support to the risk of suicide-related behaviors. METHODS: This was a cross-sectional study of a group of 10-16-year-olds with major depressive disorders and dysthymic disorder. RESULTS: Child-rated depressive disorder symptom severity emerged as the greatest predictor of risk. Hopelessness and family dysfunction were also significant predictors of SRBs. In combination these variables were strong predictors, accounting for 66% of the variance. This is a cross-sectional study design, rather than longitudinal, therefore risk prediction over time was not possible. CONCLUSIONS: Understanding the child and adolescents depressive disorder symptom severity from their perspective, their level of hopelessness, as well as their family context is critical in understanding the risk of SRBs. These findings may help to provide direction for targeted interventions to address these clinical risk factors.
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ItemThe association of visuospatial working memory with dysthymic disorder in pre-pubertal children(CAMBRIDGE UNIV PRESS, 2010-02)BACKGROUND: Visuospatial working memory (VSWM) deficits have not been investigated specifically in children with dysthymic disorder (DD), although they are associated with impairments in attention that commonly occur in DD. This study investigates VSWM impairment in children with DD. METHOD: A cross-sectional study of VSWM in 6- to 12-year-old children with medication-naive DD (n=26) compared to an age-, gender- and 'performance IQ' (PIQ)-matched healthy control group (n=28) was completed. RESULTS: The DD group demonstrated impairment in VSWM, including impairment in the spatial span and strategy components of VSWM. Furthermore, the VSWM impairment remained after controlling for spatial span. Inattentive symptoms were significantly associated with the VSWM impairment. CONCLUSIONS: This study of children with DD found deficits in performance on VSWM tasks, suggesting that fronto-striatal-parietal neural networks that underlie processes of attention and the executive component of VSWM are dysfunctional in children with DD. These findings further our understanding of DD and suggest more specific interventions that might improve functioning.