This is a request for as supplement to add genetics studies to the funded R01 From Infancy to Adolescence: FMRI and Risk for Anxiety Disorder. This ongoing study centers on adolescence as a critical period of risk for development of mental disorders, and will follow up a well-characterized cohort to 1) test hypotheses regarding the relation between temperamental types observed in infancy and toddlerhood and the subsequent development of adolescent psychiatric disorder, particularly social anxiety disorder (SAD); 2) investigate whether temperamental types predict differences in regional brain activation measured with fMRI, particularly amygdala and RFC, at adolescence; 3) compare within the group of adolescents known to have early temperaments that predispose to the development of SAD, patterns of regional brain activation in adolescents who did and did not develop SAD. This translational study therefore lies at the junction of social neuroscience, psychology. The study population represents an unique resource, having been carefully char- acterized in early infancy and followed though adolescence, using both detailed psychological and biological assessments.Social phobia presents among psychiatric disorders an unusual combination of almost universal early onset in childhood or early adolescence, high prevalence, chronic impairment with a 50% risk of continuing into adulthood for a median duration of 25 years, risk of secondary co-morbidity, and low probability of treatment. Previous research by our group and others has compellingly implicated several genes and biological systems in behavioral and brain phenotypes related to Bl and social anxiety.This cohort provides an opportunity to address the genetic basis for temperamental high reactivity and Bl, and the risk for SAD that is unlikely to be repeated. By examining behavioral and biological intermediate phenotypes (temperament and functional brain imaging) that may be more proximal expressions of gene function, we are in a unique position to examine the influence of genes on the risk for social anxiety disorder. Although previous small studies have examined polymorphisms and candidate genes in fMRI studies of amygdala reactivity, none has included a longitudinal cohort for which early childhood temperament assessments and psychiatric assessments have been collected. Because the phenotypic data has been separately funded, this application will represent a highly cost-effective effort to supplement these efforts with genetic analyses. ? ? ?
| Schwartz, C E; Kunwar, P S; Greve, D N et al. (2012) A phenotype of early infancy predicts reactivity of the amygdala in male adults. Mol Psychiatry 17:1042-50 |
| Schwartz, Carl E; Kunwar, Pratap S; Greve, Douglas N et al. (2010) Structural differences in adult orbital and ventromedial prefrontal cortex predicted by infant temperament at 4 months of age. Arch Gen Psychiatry 67:78-84 |
