This presentation is a Work In Progress (WIP) covering experiments examining the molecular correlates of drug abuse in human brains diagnosed with schizophrenia
Molecular Substrates of Drug Abuse in a Schizophrenic Population
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
3.
4.
5.
6.
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
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
20.
21. Preliminary data support methods Lesselyong preliminary data (control only) Harburg Dissertation (control – white; heroin – black)