USC Addiction and Violence Research Center Jean C. Shih, Ph.D. School of Pharmacy University of Southern California

The First Structure of MAOB (Nat. Struc. Bol. 2002)

MAO A- inhibitor interaction

MAO B Gene Regulation Stress Inflammatory cytokines growth factors Growth factors mitogens PMA PKC Egr-1c-Jun MAO B Gene cytoplasm nucleus MAPK Pathway CACCC TATA Sp1 / Sp4 Sp3 / BTEB 2 TIEG 2 Sp3

MAO A KO mice MAO B KO mice Wild type mice MAO A/B double KO mice

MAO A KO mice 5-HT, NE, DA  aggression Forebrain-specific transgenic MAO A KO mice 5-HT, NE, DA normal level in forebrain No aggression MAO B KO mice PEA  No aggression MAO A/B double KO mice 5-HT, NE, DA   PEA   Anxiety Disregulation of heart rate The increased 5-HT in forebrain is responsible for aggression Different levels of 5-HT lead to different signaling pathways which lead to different behaviors

USC Addiction and Violence Research Center For Studying the Cause, Treatment and Prevention of Drug Abuse and Violence Addiction: Social Studies Using 10,000 methamphetamine abusers *Demographics (gender, twins, ethnicity, type of substance, criminal justice status) *Social factors (employment and environmental stressors) *Developmental factors (childhood development, maternal smoking and substance use) Y. Hser, UCLA Addiction and Violence: Clinical Studies *Psychological traits *Psychiatric diagnosis (addiction, depression anxiety, aggression) D. Holschneider, J. Victoroff USC Keck School of Medicine DNA, SNP Mutation Discovery (Genes in serotonin and dopamine pathways) J. Shih, K. Chen, USC School of Pharmacy D. Conti, USC Keck School of Medicine L. Baker, USC College of Letters, Arts & Sciences, Psychology Bioinformatics D. Conti USC Keck School of Medicine Animal Models (transgenic mice) Metabolome (correlate brain and urine levels) Behavior K. Chen, USC School of Pharmacy D. Holschneider, USC Keck School of Medicine Education J. Colbert, M. Sundt, USC School of Education R. Aster, USC School of Social Worker Neuro-imaging A. Raine and others USC College of Letters, Arts and Sciences, Psychology