The purpose of this K23 application is to support my short-term career objectives of acquiring multimodalneuroimaging, neurocomputational, biostatistical, and theoretical social cognitive knowledge in the study ofanxiety and emotion regulation in youth at high-risk for bipolar disorder (BD). Longitudinal evidence suggeststhat youth at high-risk for BD that develop any mood disorder experience an anxiety disorder as an earlyantecedent. Anxiety is therefore an important symptom in the developmental trajectory of BD.

Saliva performs a number of extremely important biological functions that are instrumental in maintaining oralhealth. It has been estimated that more than 5 million people in the US suffers from salivary gland dysfunction(Sjogren's syndrome). Although no genes mutations have been identified that could explain the pathogenesisof Sjogren's syndrome (SS), recent evidence have suggested that T17-cell infiltration and induction ofapoptosis in salivary gland acinar cells could be the two major events that could lead to salivary glanddestruction.

Phenylalanine hydroxylase (PheH) catalyzes the hydroxylation of dietary phenylalanine to tyrosine. Lack of a functional PheH results in the metabolic disease phenylketonuria (PKU). PheH is one of three aromatic amino acid hydroxylases; the other two are tyrosine hydroxylase and tryptophan hydroxylase. Regulation of PheH is tightly controlled so that only excess phenylalanine is consumed. The enzyme is regulated by activation by phenylalanine, inhibition by tetrahydrobiopterin (BH4), and phosphorylation at Ser16.