Interventions for Parental Anxiety in Preparation for Pediatric Surgery: A Narrative Review

The preoperative experience can cause significant anxiety for both pediatric patients and their parents in the lead up to a surgical procedure. Pediatric anxiety in a preoperative setting has been shown to have significant negative downstream effects on the clinical outcomes of children and the healthcare system as a whole. Studies have found that preoperative parental anxiety has significant negative effects on children, regarding anxiety and emotional response. Therefore, interventions for parental preoperative anxiety are important to reduce the child’s anxiety. This review provides a brief overview of a broad range of strategies used to alleviate parental anxiety in a preoperative setting. Preoperative education, play-based interventions, music therapy, the presence of parents at induction of anesthesia, and integrative preoperative preparation programs have all demonstrated some evidence for reducing parental preoperative anxiety. The ultimate goal of using interventions for parental preoperative anxiety is to equip healthcare systems to better support families and optimize the perioperative outcomes of children.

Pharmacogenetically Guided Escitalopram Treatment for Pediatric Anxiety Disorders: Protocol for a Double-Blind Randomized Trial

Current pharmacologic treatments for pediatric anxiety disorders (e.g., selective serotonin reuptake inhibitors (SSRIs)) frequently use “one size fits all” dosing strategies based on average responses in clinical trials. However, for some SSRIs, including escitalopram, variation in CYP2C19 activity produces substantial variation in medication exposure (i.e., blood medication concentrations). This raises an important question: would refining current SSRI dosing strategies based on CYP2C19 phenotypes increase response and reduce side effect burden? To answer this question, we designed a randomized, double-blind trial of adolescents 12–17 years of age with generalized, separation, and/or social anxiety disorders (N = 132). Patients are randomized (1:1) to standard escitalopram dosing or dosing based on validated CYP2C19 phenotypes for escitalopram metabolism. Using this approach, we will determine whether pharmacogenetically-guided treatment—compared to standard dosing—produces faster and greater reduction in anxiety symptoms (i.e., response) and improves tolerability (e.g., decreased risk of treatment-related activation and weight gain). Secondarily, we will examine pharmacodynamic variants associated with treatment outcomes, thus enhancing clinicians’ ability to predict response and tolerability. Ultimately, developing a strategy to optimize dosing for individual patients could accelerate response while decreasing side effects—an immediate benefit to patients and their families. ClinicalTrials.gov Identifier: NCT04623099.

Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety

Excessive expression of threat-anticipatory defensive responses is central in anxiety. Animal research indicates that anticipatory responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from translational work on threat imminence could guide mechanistic research mapping abnormal function in this circuitry to aberrant defensive responses in anxiety. Here, we initiate such research. Fifty pediatric anxiety patients and healthy-comparisons (33 females) completed a threat-anticipation task whereby cues signaled delivery of highly-painful (threat) or non-painful (safety) heat. Temporal changes in skin-conductance indexed defensive responding as function of threat imminence. Resting-state functional connectivity data were used to identify intrinsic-function correlates of anticipatory response within a specific functional network derived from translational research. Results indicate that anxiety was associated with greater increase in anticipatory response as threats became more imminent. Magnitude of increase in threat-anticipatory responses corresponded to intrinsic connectivity within a cortical-subcortical circuit; importantly, more severe anxiety was associated with greater connectivity between ventromedial prefrontal cortex and hippocampus and basolateral amygdala, a circuit implicated in animal models of anxiety. These findings link basic-translational and clinical research, highlighting aberrant intrinsic function in conserved defensive circuitry as potential pathophysiological mechanism in anxiety.