Oxytocin as a Biomarker of Differential Effects to SPACE vs. CBT Treatment of Child Anxiety Disorders.

OBJECTIVE: Two lines of research, on outcome moderators and on novel treatment targets, seek to improve the overall efficacy of child anxiety treatment, with mixed results. We propose that an integration of both lines of research can lead to improved treatment efficacy. In a first proof of concept of this approach, we studied whether the interaction between baseline levels and targeted changes in peripheral oxytocin (OT) can predict differential responses to two childhood anxiety treatments. METHOD: A total of 124 mother-child dyads participated in the study. Children's salivary OT levels were measured at baseline and again, immediately after an experimental dyadic interaction in the lab. Dyads were subsequently randomized to receive one of two treatments, differing in their targets: SPACE (Supportive Parenting for Anxious Childhood Emotions) and CBT (cognitive-behavioral therapy). Treatment outcomes were assessed using the Childhood Anxiety Related Emotional Disorders scale, reported by both mother and child. RESULTS: The findings suggest that in SPACE, where the mother is the main agent of change, higher baseline levels of child OT, coupled with increases in OT following a positive mother-child interaction, predicted greater treatment efficacy. By contrast, in CBT, where the child is the main agent of change, higher baseline levels of child OT, coupled with a decrease in OT following the interaction, predicted greater treatment efficacy. CONCLUSIONS: The findings highlight the importance of the integration between moderators and targets of treatments for progress toward improving treatment efficacy through precision medicine.

Moderators of response to child-based and parent-based child anxiety treatment: a machine learning-based analysis.

BACKGROUND: Identifying moderators of response to treatment for childhood anxiety can inform clinical decision-making and improve overall treatment efficacy. We examined moderators of response to child-based cognitive-behavioral therapy (CBT) and parent-based SPACE (Supportive Parenting for Anxious Childhood Emotions) in a recent randomized clinical trial. METHODS: We applied a machine learning approach to identify moderators of treatment response to CBT versus SPACE, in a clinical trial of 124 children with primary anxiety disorders. We tested the clinical benefit of prescribing treatment based on the identified moderators by comparing outcomes for children randomly assigned to their optimal and nonoptimal treatment conditions. We further applied machine learning to explore relations between moderators and shed light on how they interact to predict outcomes. Potential moderators included demographic, socioemotional, parenting, and biological variables. We examined moderation separately for child-reported, parent-reported, and independent-evaluator-reported outcomes. RESULTS: Parent-reported outcomes were moderated by parent negativity and child oxytocin levels. Child-reported outcomes were moderated by baseline anxiety, parent negativity, and parent oxytocin levels. Independent-evaluator-reported outcomes were moderated by baseline anxiety. Children assigned to their optimal treatment condition had significantly greater reduction in anxiety symptoms, compared with children assigned to their nonoptimal treatment. Significant interactions emerged between the identified moderators. CONCLUSIONS: Our findings represent an important step toward optimizing treatment selection and increasing treatment efficacy.

Gold Nanoparticle Assemblies on Surfaces: Reactivity Tuning through Capping-Layer and Cross-Linker Design.

The immobilization of metal nanoparticles (NPs) with molecular control over their organization is challenging. Herein, we report the formation of molecularly cross-linked AuNP assemblies using a layer-by-layer approach. We observed four types of assemblies: 1) small aggregates of individual AuNPs, 2) large aggregates of individual AuNPs, 3) networks of fused AuNPs, and 4) gold islands. Interestingly, these assemblies with the different cross-linkers and capping layers represent different stages in the complete fusion of AuNPs to afford islands of continuous gold. We demonstrate that the stability toward fusion of the nanoparticles of the on-surface structures can be controlled by the reactivity of the cross-linkers and the hydrophilicity/hydrophobicity of the nanoparticles.

Maternal FGF2 levels associated with child anxiety and depression symptoms through child FGF2 levels.

BACKGROUND: Recent research implicates fibroblast growth factor 2 (FGF2) in anxiety and depressive symptoms of childhood. This study is the first to examine an intergenerational pathway linking FGF2 levels in mothers to FGF2 levels in children, and to the children's anxiety and depressive symptoms. METHODS: We assayed serum FGF2 in 259 mothers and their children, with a range of anxiety and depressive symptoms: 194 were mothers of clinic-referred anxious and depressed children; 65 were mothers of non-referred children. We examined associations between FGF2 levels in mothers and children, and anxiety and depression symptoms. We used structural equation modeling (SEM) to examine associations between maternal and child FGF2 levels, and between maternal and child FGF2 levels and symptoms of anxiety and depression in and children. RESULTS: FGF2 levels in mothers and children were significantly positively correlated. Children's FGF2 levels were significantly negatively correlated with their ratings of anxiety and depression. Results of the SEM model showed that increases in maternal FGF2 levels were significantly associated with increases in child FGF2, which in turn was associated with decreases in child anxiety and child depression, controlling for maternal anxiety and depression. LIMITATIONS: We relied on self-reported ratings of anxiety and depression, and on a single measurement of FGF2 levels for each participant. CONCLUSIONS: Our results point to a role for FGF2 in the intergenerational transmission of risk for, and resilience to, anxiety and depression in youth.

Setting the environmental conditions for controlling gold nanoparticle assemblies.

Fundamental insights into the factors that control the properties and structure of gold nanoparticle (AuNP) based assemblies enable the design and construction of new materials. The dimensions (shape and size) and the optical properties of AuNP assemblies are affected by the electronic properties of the organic cross-linker and the nature of the AuNPs.

Maternal Depression and Mother-Child Oxytocin Synchrony in Youth with Anxiety Disorders.

The neuropeptide oxytocin (OT) plays a central role in the regulation of affiliative bonds and anxiety. However, the degree to which its levels are synchronized between interaction partners has not yet been assessed. Physiological synchrony assessed using other peripheral measures (e.g., heart rate, etc.) has been tied to positive outcomes for the individual and the dyad. The present study examined OT synchrony in the context of child anxiety and maternal depression by examining mother-child dyads. Mothers and their children with anxiety disorders participated in a behavioral interaction task. Changes in OT levels and mother-child OT synchrony before and after the interaction, as well as their moderation by maternal depression, were assessed. Ninety-eight youth with anxiety disorders (ages 10 to 17) and their mothers underwent psychiatric evaluation, and mothers rated their own depressive symptoms and their children's behavior problems. Salivary OT was assayed from mother and child before and after the task. Behavioral coding showed that interactions were characterized by high behavioral synchrony between mothers and their children, and both individuals displayed higher levels of positive vs. negative affect during the interactions. Mothers and their children also showed decreases in OT levels after the interaction. As hypothesized, OT synchrony increased following the task, but only dyads in which mothers showed high levels of depressive symptoms showed this increase. As hypothesized, lower levels of OT-synchrony were associated with higher levels of child internalizing symptoms. The findings suggest that positive interactions may be beneficial for youth with anxiety disorders with mothers with depression.

Fibroblast Growth Factor 2 Implicated in Childhood Anxiety and Depression Symptoms.

BACKGROUND: Research links fibroblast growth factor 2 (FGF2) to anxiety and depression in rodents and human adults. Our study is the first to examine FGF2 levels in a pediatric population. METHODS: We assayed serum FGF2 in 163 children with a broad range of anxiety and depressive symptoms; 111 were clinic-referred anxious and depressed children; 52 were non-referred children. We examined associations between FGF2 and anxiety and depression symptoms, and between each of the three facets of behavioral activation (Reward-Responsiveness, Drive, Fun-Seeking) and behavioral avoidance. We used confirmatory factor analysis (CFA) to determine the relative contribution of anxiety and depression indicators and of FGF2 to a latent variable of Anxiety/Depression. We also examined stability of FGF2 levels. RESULTS: FGF2 levels in clinic-referred children were significantly lower compared with non-referred children. Bivariate correlations and CFA showed negative associations between FGF2 and anxiety, depression and behavioral avoidance. FGF2 levels were positively correlated with the Reward-Responsiveness facet of behavioral activation, implicated in depression. FGF2 levels were stable over six months. LIMITATIONS: We did not have data on behavioral avoidance and stability of FGF2 in the entire sample. CONCLUSIONS: Our results implicate FGF2 in anxiety and depression in children, providing an important first step in showing FGF2 may serve as a stable biomarker for these prevalent and impairing problems.