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Principal Investigator: Daniel Pine
Organization: NATIONAL INSTITUTE OF MENTAL HEALTH
Fiscal Year: 2024
Award: $1,480,585
Funding agency: National Institute of Mental Health
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 continued to grow and expand this year, as they had done in the immediately prior years. Dr. Fox has followed cohorts of approximately 600 infants as they passed though childhood. These children have received repeated assessments of their temperament. Temperament classifications in the sample during infancy and early childhood have been shown to predict behavior later in life. We have also completed a series of investigations in this sample. Results from these studies support the conclusions generated by other research within our group. Namely, 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. A third set of studies examines infants. This set of studies has grown particularly rapidly in the past five years. Data collection activities during infancy is highly active, and work in this project interfaces closely with studies focused on infants based in extramural settings. 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 four 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 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 has 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. Thus, across the work performed by our group findings could impact thoughts about prevention. Of note, in the current protocol, such investigations of risk have closely examined interactions with exposure to CoVID-19, providing a vital public health message to society. This message integrates understandings of biological, psychological, and social aspects of health. In the final set of studies, we are focusing increasingly deeply on examinations with infants. This occupies a growing level of resources from the group.
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 in St. Louis. 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. 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 year, through collaborations on two 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.
Terms: <0-11 years old><12-20 years old><21+ years old><Address><Adolescence><Adolescent><Adolescent Youth><Adult><Adult Human><Affective Disorders><Amygdala><Amygdaloid Body><Amygdaloid Nucleus><Amygdaloid structure><Anxiety><Anxiety Disorders><Area><Behavioral><Behavioral inhibition><Biological><Brain><Brain Nervous System><Brain imaging><COVID-19 exposure><Child><Child Youth><Childhood><Children (0-21)><Classification><Collaborations><Corpus Striatum><Corpus striatum structure><Data><Data Collection><Development><EXTMR><Electrophysiology><Electrophysiology (science)><Emotional><Emotional Depression><Emotional well being><Encephalon><Exposure to><Extramural><Extramural Activities><Feels well><Functional MRI><Functional Magnetic Resonance Imaging><Funding><Goals><Grant><Health><History><Individual><Infant><International><Investigation><Journals><Lead><Life><Magazine><Maryland><Measures><Mediating><Medical><Mental Depression><Mental disorders><Mental health disorders><Mood Disorders><NIH><National Institutes of Health><Nature><Neurocognitive><Neurophysiology / Electrophysiology><Normal mental condition><Normal mental state><Normal psyche><Outcome><Paper><Participant><Pb element><Prefrontal Cortex><Preventative intervention><Prevention><Protocol><Protocols documentation><Psychiatric Disease><Psychiatric Disorder><Psychological Well Being><Psychopathology><Public Health><Publishing><Recording of previous events><Reporting><Research><Research Resources><Resources><Risk><Risk Factors><SARS-CoV-2 exposure><SARS-CoV2 exposure><Sampling><Sense of well-being><Series><Severe acute respiratory syndrome coronavirus 2 exposure><Societies><Stimulus><Stream><Striate Body><Striatum><Systematics><Task Performances><Temperament><Testing><Thinking><United States National Institutes of Health><Universities><Washington><Well in self><Work><abnormal psychology><adolescence (12-20)><adult youth><adulthood><adulthood transition><amygdaloid nuclear complex><anxiety symptoms><anxious symptom><behavior prediction><behavioral prediction><biologic><brain visualization><chronic mental illness><cohort><coronavirus disease 2019 exposure><depression><depression symptom><depressive><depressive symptoms><developmental><developmental disease><developmental disorder><differentiation factors><early childhood><electrophysiological><emotional wellbeing><emotional wellness><experience><exposure to COVID-19><exposure to SARS-CoV-2><exposure to SARS-CoV2><exposure to Severe acute respiratory syndrome coronavirus 2><exposure to coronavirus disease 2019><fMRI><heavy metal Pb><heavy metal lead><high risk><histories><indexing><infancy><infantile><insight><intervention for prevention><juvenile><juvenile human><kids><mental illness><mental well-being><mental wellbeing><mental wellness><morphogenic factors><morphogens><neural><novel><pediatric><persistent mental illness><prevention intervention><preventional intervention strategy><preventive intervention><programs><prospective><psychiatric illness><psychologic><psychological><psychological disorder><psychological wellbeing><psychological wellness><resilience><resilient><response><reward processing><self wellness><sense of wellbeing><serious mental disorder><serious mental illness><severe mental disorder><severe mental illness><social><striatal><thoughts><transition from adolescence to adulthood><transition into adulthood><transition to adulthood><young adult><young adulthood><youngster>