Schizophrenia

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  • Created by: oaschaaf
  • Created on: 21-04-18 13:04
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  • Schizophrenia
    • Characteristic symptoms - two or more of the following for significant portion of time (1 month):
      • Delusions, hallucinations, disorganised speech, disorganised behaviour, negative symptoms
      • Only one criterion A symptom is required if delusions are bizarre or hallucinations or hearing voices. Not split personality or MPD.
    • History
      • Kraeplin (1919) - described paranoia, grandiose delusions, auditory hallucinations, abnormal emotion regulation and bizarre disturbances of thought.
      • Bleuler (1950) - identified underlying psychological responses: dissociative thinking - major impairment in the logical structure of thought: giving rise to the following symptoms: loosened associations, autism, affective disturbance, delusions and hallucinations.
    • Modern Approaches
      • Andreasan (1991)
        • Described positive symptoms (gained behaviour): hallucinations, delusions of grandeur, disordered thoughts, bizarre behaviours.
        • Negative symptoms (lost): social withdrawal, flat affect, reduced motivation, poor focus on tasks.
    • Genetics
      • Family studies - the closer the biological relatedness the greater the chance that the relative will be schizophrenic (Gottesman, 1991)
      • Genes implicated: neuregulin 1 - participates in glutamate, GABA and Ach receptor regulation. COMT: catecholamine production, G72: glutamatergic activity.
      • Twin studies: concordance rate MZ - 50% and DZ 17%. The symptomatic twin frequently weighs less at birth (differential development in the womb). More physiological distress (affected twin more environmental factors). Twins act differently receiving different parental responses).
    • Brain Abnormalities
      • Schizophrenic population tend to have ventricular abnormalities. Enlargement not related to length of illness or duration of hospitalisation
      • Grey matter loss: shrinkage in the cerebellar vermis, a thicker corpus callosum and frontal abnormalities. Thompson (2001)
      • Cellular disorganisation in the hippocampus in chronic schizophrenia, the most impaired individuals show the greatest disorganisation, (Conrad, 1991)
    • Functional Abnormalities
      • The hypofrontality hypothesis: less activity in the frontal lobes in schizophrenics. Decreased activity in the right middle frontal gyrus during a context processing task, (Holmes, 2005).
      • Holcomb et al., (2000) Hypofrontality - schizophrenics show decreased cerebral blood flow in the anterior cingulate cortex during the performance of an auditory discrimination task.
    • Dopamine hypothesis
      • Schizophrenia is caused by an excess of dopamine. Large doses of amphetamine (a strong DA agonist) can cause psychosis, with similar symptoms to schizophrenia. Parkinson's treatment with L-Dopa (a precursor to dopamine) may induce psychotic symptoms. Dopamine receptor antagonists such as chlorpromazine are effective anti-schizophrenic drugs. These neuroleptic drgus bind to dopamine D2 receptors. Some studies have found an increase in dopamine receptors in schizophrenic persons, including those no longer taking neuroleptic drugs.
        • Too simplistic: some patients show no improvement when treated with DA antagonists. Atypical neuroleptics affect many receptor types, e.g. serotonin as well as D2 receptors. More effective at relieving negative symptoms than typical neuroleptics. Clozapine can also increase dopamine release in the frontal cortex. Studies on D2 receptor levels in schizophrenics are inconsistent.
    • Glutamate hypothesis - NMDA receptor
      • NMDA - postsynaptic glutamate receptor e.g. ketamine. Produce phenomena resembling both positive and negative symptoms. NMDA are agonists that improve both symptoms in schizophrenia but can cause seizures. Probably not just one NT involved.
    • Synthesis: (Rosso, 2000)
      • Genetic influences lead to brain abnormalities - developmental/birth complications may exaggerate such abnormalities - emergence of S is dependent on whether damaged brain is exposed to environmental stressors

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