This is an exploratory/developmental research proposal which seeks to build on and to enlarge our data into the role of fibroblast growth factor 2 (FGF2) in Fear (Acute Threat) and Approach Motivation, two constructs within the Negative Valence System and Positive Valence System, respectively, in the NIMH Research Domain Criteria (RDoC) project. FGF2 is one of a family of growth factors that impact neural development and that play neuromodulatory roles throughout life, shaping the organism's response to the environment. Disruptions in the Negative Valence and Positive Valence Systems characterize anxiety and depressive disorders, which account for the majority of psychiatric disability over the lifespan. The animal and sparse adult human studies implicating FGF2 in models of anxiety and depression led to FGF2's inclusion in RDoC as a target biological unit of analysis of the Fear construct. We know of no study that has examined FGF2 in humans with anxiety and its disorders, nor do we know of a study that examined FGF2 in clinical and nonclinical pediatric samples, anxious and/or depressed. Our team collected pilot data of FGF2 levels in a clinical sample of 50 anxious and depressed children and their mothers in addition to self-report and behavior data that corresponded with Fear, and Approach Motivation, respectively. We examined the associations between FGF2 levels, self-reports, and behavior in the children and mothers and found significant associations between the measurement units, and in the expected directions. These data, consistent with the animal and human studies, suggest FGF2 may play a role in modulating Fear, and Approach Motivation, which can lead to exciting, new research directions. We have since accumulated serum samples in 150 anxious and/or depressed children and mothers, and self-report and behavior data. We request R21 funds to conduct immunoassay analysis to measure FGF2 concentrations in this sample data. We also propose to broaden our sampling frame by collecting FGF2, self-report, and behavior data on 100 additional children who represent ?normal? controls, and subclinical or subthreshold anxiety and/or depression, and mothers. With these cumulative, dimensional data, we will study these measurement units' associations with Fear, and Approach Motivation in a measurement model using confirmatory factor analysis. Our final, exploratory aim is on the question of stability of FGF2, in relation to self-reports and behavior.
This R21 study aims to build on and enlarge the investigative team's promising data into the role of fibroblast growth factor 2 (FGF2) in Fear (Acute Threat) and Approach Motivation, two constructs within the Negative Valence System and Positive Valence System in the NIMH Research Domain Criteria project. Findings can extend past discoveries mostly with animals implicating FGF2 in these constructs relevant to child anxiety and depression, which can result in advances in behavioral and clinical research, including potential targeting the FGF2 system in treatment.
| Shimshoni, Yaara; Silverman, Wendy K; Byrne, Simon P et al. (2018) Maternal Acceptance Moderates Fear Ratings and Avoidance Behavior in Children. Child Psychiatry Hum Dev 49:460-467 |
| Lebowitz, Eli R; François, Bernard (2018) Using Motion Tracking to Measure Avoidance in Children and Adults: Psychometric Properties, Associations With Clinical Characteristics, and Treatment-Related Change. Behav Ther 49:853-865 |
