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Neuronal Mechanisms in Schizophrenia

Neuronal Mechanisms in Schizophrenia. Robert Freedman, M.D. Department of Psychiatry University of Colorado Denver, Colorado. “He saw the world in a way no one could have imagined.”. Schizophrenia. 1% affected, onset generally late adolescence to early adulthood

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Neuronal Mechanisms in Schizophrenia

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  1. Neuronal Mechanisms in Schizophrenia Robert Freedman, M.D. Department of Psychiatry University of Colorado Denver, Colorado

  2. “He saw the world in a way no one could have imagined.”

  3. Schizophrenia • 1% affected, onset generally late adolescence to early adulthood • Auditory hallucinations and paranoid delusions are the most common forms of thought disorder, the most characteristic chronic symptom • A decrement in psychosocial function, often called “negative symptoms” is part of the illness

  4. Sensory Gating Disturbance • “My mind has to be here, it has to be there, it has to be everywhere. I can’t concentrate on anything.” • “When he gets ill, his sense of hearing seems to increase. He hears the neighbors across street arguing.”

  5. The decrease of nicotinic receptors on nerve cells means that the brain’s own acetylcholine is no longer sufficient to activate the neurons that filter out noises

  6. fMRI indicates increased hemodynamic activity in the hippocampus in schizophrenia during smooth pursuit eye movements

  7. …even though uninterested and autistically encapsulated patients pay little attention to the outside world, they register a remarkable number of events of no concern to them. The selection which attention exercises over normal sensory impressions may be reduced to zero, so that almost everything that meets the senses is registered. Thus both the facilitating and inhibitory propensities of attention are disordered. Bleuler, 1911

  8. Grandfather—Chronically Insane Father—Committed Suicide Proband--- Philosopher Arthur Schopenhauer “The amount of noise which anyone can bear undisturbed stands in inverse proportion to his mental capacity….Noise is a torture to all intellectual people.”

  9. a10 a9

  10. A. 2602 bp -2600 +2 1062 bp -1076 -15 231 bp -15 -245 B.

  11. The decrease of nicotinic receptors on nerve cells means that the brain’s own acetylcholine is no longer sufficient to activate the neurons that filter out noises

  12. A. Control female, -86 C/C T/C= 0.14 P50 B. Control female, -86 C/T T/C= 0.60 C. Schizophrenic female, -86 C/T T/C= 0.54 4mV Conditioning Testing 50 ms

  13. 1-Dopamine adjusts the volume 2-Acetycholine and GABA filter signal from noise 3-Glutamate imprints new memories

  14. Acetycholine and GABA filter signal from noise

  15. Dopamine increases the volume

  16. Glutamate imprints new memories.

  17. 1-Dopamine adjusts the volume—Blockedby antipsychotic 2-Acetycholine and GABA filter signal from noise 3-Glutamate imprints new memories

  18. Nicotine mimics the brain chemical acetylcholine, (but it also poisons acetylcholine receptors!)

  19. First Degree Relative Nicotine can temporarily restore nerve cell inhibition

  20. Decreased hippocampal activity during eye movement in schizophrenics after nicotine treatment

  21. Clozapine, a drug used to treat schizophrenia, increases acetylcholine and normalizes inhibition; cigarette smoking drops by 50%

  22. The University of Colorado with NARSAD, Stanley, and NIMH and VA support, is developing new drugs to treat schizophrenia and bipolar disorder by targeting nicotinic receptors.

  23. 1-Dopamine adjusts the volume 2-Acetycholine and GABA filter signal from noise 3-Glutamate imprints new memories

  24. Memory disorder in schizophrenia • Decreased ability to learn efficiently • Poverty of content • Persistence of paranoid memory • Malfunction of NMDA and other glutamate receptors • Decreased volume of brain regions critical to cognition • Diminished extinction

  25. Veterans without PTSD have enhanced cingulate response to combat stimuli—Shin et al., 2001

  26. Genetics, Neurobiology, and Our Conception of Schizophrenia • Schizophrenia used to be conceptualized as a rare, disastrous malfunction of the mind and/or brain, depending on your view of Cartesian dualism • If three independent factors are involved, then an application of Mendel’s second law suggests that for a population prevalence of schizophrenia = 0.01, the prevalence of any one of these factors is 0.011/3 = 0.22. Calculate the probability that you have at least one factor. What might its effect be on your mental function?

  27. Then came "a miraculous remission." And as happens, for reasons unknown,in the case of some people with schizophrenia,it was not, according to Mrs. Nash, due to any drug or treatment:"It's just a question of living a quiet life."

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