This presentation is a Work In Progress (WIP) covering experiments examining the molecular correlates of drug abuse in human brains diagnosed with schizophrenia

1. Cellular and Molecular Substrates of Drug Abuse in Schizophrenia by Alan Lesselyong, M.S. (mentor) Carol Tamminga, M.D.

2. Schizophrenia and Drug Abuse Drug Use – Any willful exposure to a psychoactive substance in order to achieve a desired feeling or behavior. Drug Abuse – The repeated use of a substance to the extent that it interferes with adequate social, vocational, or self-care functioning. Drug Dependence (Addiction) – The development of tolerance to a particular substance and the experience of withdrawal symptoms and craving after a period of abstinence. Symptom Domains Of Schizophrenia Positive Hallucinations Delusions Cognitive Attention Working Memory Negative Anhedonia Asociality

7. Prevalence of Drug Abuse (lifetime) A – Kapplan and Sadock, The Comprehensive Textbook on Psychiatry, 8 th ed; B – 2006 National Survey on Drug Abuse; C – Mueser, et al., 1990 2.7% B 14.3% B 1.5% B 3.6% B 5.0% B 5.8% B 14.3% B ? 82.7% B 39.8% B 29.7% B 70.7% B Control PCP Hallucinogens Opiates Sedatives Ecstasy Amphetamine Cocaine Stimulants (any) Ethanol Cannabinoids Nicotine Caffeine Drug 1.40X 20% C ? ? 4.00X 6% C 1.67X 6% C ? ? 4.36X 25.3% C 0.88X 12.6% C ? 29% C 0.60X 50% C 1.08X 43% C 2.86X > 85% A 1.27X >90% A Fold Increase Schizophrenia

13. Systems changes synaptogenesis LTP/LTD Δ in neural excitability Drug Abuse Schizophrenia

14. Neural Circuitry of Schizophrenia

15. Glutamatergic Synapse

19. Cellular changes Reduced NSC proliferation Accelerated neuronal integration, resulting in aberrant morphological developing and mispositioning of new granule cells in a cell-autonomous fashion Reduced neurotrophin expression leads to delays in cell differentiation and maturation Drug Abuse Schizophrenia

21. Preliminary data support methods Lesselyong preliminary data (control only) Harburg Dissertation (control – white; heroin – black)