fMRI Studies of Risk for Mood and Anxiety Disorders in Children

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

This work is conducted under protocol 03-M-0186, NCT00060775. In this project, our group is examining biological aspects of risk for mood and anxiety disorders in children. Such work has major public impact. By identifying biological risks in children, information on novel treatments and preventative interventions will emerge. Given the understanding of most chronic mental illnesses as developmental disorders, such information holds the hope of dramatically influencing the mental well-being of many individuals. Our most in-depth studies focus on the temperament, the way children respond to salient stimuli during their first years of life. Specifically, we study a temperament that is known as "behavioral inhibition." Children with this temperament respond with hesitation and wariness when faced with novelty, particularly novelty in social domains. This work is made possible through our strong collaborative relationship with Dr. Nathan Fox at the University of Maryland. Our studies in this area are in the process of ramping down, as we are completing our work performing these follow-up studies. Dr. Fox has followed cohorts of approximately 600 infants as they passed though childhood. These children have received repeated assessments of their temperament. This work establishes the presence of strong, consistent associations between the presence of and risk factors for mental illness in children and the presence of perturbed brain function. This project encompasses work examining the degree to which neurocognitive profiles vary among infants, children, and adolescents stratified with respect to risk factors for mood and anxiety disorders. For these studies, risk is defined based on personal histories of early-childhood temperament, and we are acquiring both fMRI and electrophysiologic data from a subset of these individuals. Our work in these protocols encompasses studies in juveniles across the full span of infancy, childhood, and adolescence. Thus, one set of studies is based among young adults who have been prospectively followed for more than three decades. A second set of studies is based in adolescents transitioning into adulthood. In both sets of studies, as well as the larger series of studies in this project, considerable progress continues to be made. These are the two areas where our work is ramping down. A third set of studies examines infants. This set of studies has grown particularly rapidly in the past five years. Data collection activity during infancy is highly active, and work in this project interfaces closely with studies focused on infants based in extramural settings. Unlike the first two areas of research, activity in this third area continues. Across three sets of cohorts, this project seeks to achieve a developmental perspective throughout the entire period of maturation. Moreover, we lead an international consortium that assembles data from these three cohorts and integrates them with comparable cohorts from around the world. This seeks to maximize the public health impact of insights generated in the research completed at NIH. Studies on temperamental risk are the focus in the protocol. During the past five years, we spent approximately a quarter our efforts on collecting data in a childhood cohort, where the participants are now approximately 30 years old. The most significant component of our effort examined individuals who are in their early 20s. For the last five years, our work in these cohorts consistently replicates findings across cohorts; publishing comparable analyses in the two sets of cohorts has been a priority. This addresses concerns throughout biomedical fields on the replicability of research findings. One of our best replicated sets of findings concerns the nature of risk related to childhood temperament. We demonstrate the persistent influence of temperament on risk into for psychopathology in multiple reports from all three sets of cohorts examined in our research. Moreover, we also have identified important neurocognitive factors that isolate subsets of children with temperaments who face the greatest risk for psychopathology. This has generated a steady stream of brain-imaging papers. Most importantly, as subjects have passed through adolescence into adulthood, our work in this cohort has focused increasingly deeply on mood disorders. Two particularly important papers utilized longitudinal data to document changes in brain function occurring in tandem with changes in symptoms of anxiety and depression. In one paper, appearing in a high-impact journal, spanned more than 20 years of research. We related brain function to anxiety, particularly in children with temperaments associated with anxiety. In the other paper, also appearing in a high-impact journal, we highlighted the risk for depression. This paper focused on reward processing, a known correlate of depression. This stimulated work in our other main project, which also now connects anxiety to depression. In comparing risk factors for behavioral and emotional problems, other questions relate to the identification of factors that differentiate among children who are at high risk yet remain resilient from those who are at risk but manifest problems. Still other questions focus on different psychiatric outcomes from particular temperaments. Work has been particularly active in infants, where we are working with our collaborators at the University of Maryland and at Washington University. To date data have been collected in nearly 300 infants and we have collaborated on four extramural grants. In the past year, our group has continued to transition the focus of our work in this protocol. In terms of our work in the two older cohorts, we continue to finalize data analyses, and we have submitted our findings to multiple journals in the past year. The main findings from the submitted papers that most powerfully shape our future plans involve multi-modal imaging with electrophysiology and functional magnetic resonance imaging. These findings show that the combination of multiple imaging modalities provides greater statistical power when examining risk for anxiety disorders, compared with the use of either imaging modality on its own. We are ending our studies focused on late adolescence and adulthood so that we can devote an increasingly large number of resources to new studies targeting infants and young children. This work has grown particularly swiftly in the past two years, through collaborations on multiple extramurally funded projects. Overall, the results from these studies show that the seeds of temperament continue to be expressed throughout development. Behaviorally, these seeds are expressed in measures of task performance and signs of psychopathology. From a brain-function perspective, these seeds are expressed in measures of electrophysiology and fMRI. Moreover, these measures of brain function mediate and moderate the relationships between temperament and psychopathology. As such, the studies provide important information on understanding risk for psychopathology.