L14-2010 - BioNB222 Cornell University Spring 2010 Ronald...

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BioNB222 Spring 2010 Cornell University Ronald Harris-Warrick Lecture 14. Psychiatric Diseases Summary: The major psychoses (schizophrenia, major depression and manic-depressive illness) are psychiatric diseases whose etiologies have a very significant biological and genetic component. Schizophrenia is the more severe of these illnesses, causing fundamental changes in the thought process itself. It is not multiple personality disorder, but rather shows a split between the rational and emotional minds as well as a series of other positive and negative symptoms. Reading Assignment None. Lecture Outline Understanding the defects in neural diseases is important for two reasons. First, we wish to alleviate suffering and come up with new treatments for disease. Second, defects in neural function often give us unique insights into the mechanisms of normal neural function. Today, we will discuss three diseases that affect normal human cognitive function, for which we do not know the underlying defects but we do have relatively good drug treatments: schizophrenia, depression and bipolar (manic-depressive) disorder. A. Schizophrenia Schizophrenia is a debilitating cluster of diseases affecting about 1% of the population. It is characterized by several symptoms, which can be broadly categorized as positive” (because they appear to be an excess of mental activity over normal) and “negative (reflecting a decrease in normal mental activity). The positive signs include: 1) Delusions: bizarre and erroneous beliefs based on a misperception of experiences, typically persecutory or paranoid; 2) Hallucinations, usually auditory; 3) Disorganized thinking and speech patterns. The negative signs include: 1) “Flattened affect”, with reduced or inappropriate aemotional responses to situations; 2) Alogia, or poverty of speech; 3) Avolition, or difficulty in carrying out goal-directed activities; 4) Social isolation and breaking of normal social conventions. Onset is typically in the late teens or early 20's. There is a clear genetic component to the disease, with concordance rates of 48% between monozygotic twins, but only 17% between dizygotic twins. However, no single major gene has been identified as responsible for most cases of schizophrenia. Large-scale single nucleotide polymorphism (SNP) studies of thousands to patients and controls show that thousands of genes may be
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BioNB222 Spring 2010 Cornell University Ronald Harris-Warrick involved, each contributing a small fraction of risk for the disease. Recent microarray studies have detected changes in the level of expression of many genes in schizophrenic brain. These may result from epigenetic changes, which are long term stable modifications (methylation, acetylation, etc) of DNA and the protein histones that make up the chromosomes, and alter gene expression levels without changing the DNA sequence. These could accumulate over time or in response to specific events, eventually leading up to the expression of the
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This note was uploaded on 05/25/2010 for the course BIONB 2220 taught by Professor Hopkins,c.d. during the Spring '10 term at Cornell.

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L14-2010 - BioNB222 Cornell University Spring 2010 Ronald...

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