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Biological aspects of schizophrenia

Biological aspects,schizophrenia

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Biological aspects of schizophrenia

  1. 1. BIOLOGICAL ASPECTS OF SCHIZOPHRENIA - BY Dr.SRIRAM.R
  2. 2. Genetic factors Dopamine hypothesis and other biochemical factors Brain structure Associated factors – Birth complications/Viral
  3. 3. Prevalence of schizophrenia is the same all over the world (about 1%) Supports a biological view as prevalence does not vary with environment There are variations within broad geographical areas (e.g. Torrey 2002 – found high rates of Sz in Ireland (4%) Incidence is also high in Croatia and Scandinavian countries, but low in Spain and Italy and very low in some parts of Africa
  4. 4. Twin studies Share the same genes and the same environment However one is usually born bigger than the other Share as many genes as siblings but share the same environment However they might be treated differently
  5. 5. Gottesman and Shields reviewed the results of 5 twin studies looking for concordance rates for schizophrenia. These studies looked at 210 MZ twins and 319 DZ twins. It was found that in MZ twins there was a concordance rate of 35-58% compared with dizygotic (DZ) twin rates that ranged from 9-26%. They also found a concordance rate in MZ twins of 75- 91% when the sample was restricted to the most severe form of schizophrenia. Cardno (2002) – showed concordance rate of 26.5% MZ and 0% for DZ
  6. 6. Twins are not representative of the wider population (gestational environment differs) It is a very small sample. There are very few MZ twins in the population and only 1% are Sz. Are these diagnosis made using the same criteria?
  7. 7. This seems to indicate an influence of genetic factors but also the importance of environmental/ social factors
  8. 8. Milder forms of schizophrenia CR is 17-33% (greater genetic loading with severe Sz) The twin studies have all assumed that the shared environmental effects for MZ and DZ twins are equal which may be incorrect The finding of a higher rate of schizophrenia among the biological relatives of an adopted-away person who develops schizophrenia, as compared to the adoptive, nonbiological relatives who rear the patient, provides further support to the genetic contribution in the etiology of schizophrenia
  9. 9. GENETICS - ADOPTION STUDIES Tienari – 155 adopted children – whose biological mothers had schizophrenia –they had a concordance of 10% compared to 1% in adopted children without schizophrenic parents. This is very strong evidence that genetics are a risk factor for schizophrenia
  10. 10. Age of the father has a direct correlation with the development of schizophrenia. In studies of schizophrenic patients with no history of illness in either the maternal or paternal line, it was found that those born from fathers >60 years old were vulnerable to developing the disorder All the evidence also suggests environmental triggers: Epigenetics could explain that the concordance rate is less than 100% in MZ twins
  11. 11. Several genes appear to make a contribution nine linkage sites: 1q, 5q, 6p, 6q, 8p, 10p, 13q, 15q, and 22q Further analyses of these chromosomal sites have led to the identification of specific candidate genes, and the best current candidates are alpha-7 nicotinic receptor, DISC 1, GRM 3, COMT, NRG 1, RGS 4, and G 72 Dystrobrevin (DTNBP1) and neureglin 1 NEGATIVE SYMPTOMS
  12. 12. DOPAMINE HYPOTHESIS
  13. 13. The theory evolved from two observations. First, the efficacy and the potency of DRAs are due to antagonism of D2 receptors Second, cocaine and amphetamine (increase dopamine) are psychotomimetic The basic theory does not elaborate on whether the dopaminergic hyperactivity is due to too much release of dopamine, too many dopamine receptors, hypersensitivity of the dopamine receptors to dopamine, or a combination of these mechanisms Mesocortical and Mesolimbic tracts are most often implicated
  14. 14. Normal Level of Dopamine In The Human Brain Elevated Level of Dopamine In The Brain of a Schizophrenic Patient (specifically the D2 receptor)  Neurons that use the transmitter ‘dopamine’ fire too often and transmit too many messages or too often.  Certain D2 receptors are known to play a key role in guiding attention.  Lowering DA activity helps remove the symptoms of schizophrenia
  15. 15. Parkinson’s sufferers have low levels of dopamine L-dopa raises DA activity People with Parkinson's develop schizophrenic symptoms if they take too much L-dopa
  16. 16. • Evidence comes from – studies with drugs – post mortems – pet scans Brain of schizophrenic patients produces more dopamine than normal brains
  17. 17. • Amphetamines and cocaine lead to increase in DA levels • Large quantities lead to delusions and hallucinations • If drugs are given to schizophrenic patients their symptoms get worse • Drugs which block dopamine (Phenothiazines) also seem to reduce the symptoms of schizophrenia
  18. 18. • Falkai et al 1988 Autopsies have found that people with schizophrenia have a larger than usual number of dopamine receptors. Increase of DA in brain structures and receptor density (left amygdala and caudate nucleus, putamen) Concluded that DA production is abnormal for schizophrenia
  19. 19. • Lindstroem et al (1999) Radioactively labelled a chemical L-Dopa Administered to 10 patients with schizophrenia and 10 with no diagnosis L-Dopa taken up quicker with schizophrenic patients vs controls Suggests they were producing more DA than the control group • Increase in D2 receptors in the caudate nucleus of drug-free patients with schizophrenia
  20. 20. Serotonin: Causes both +ve and –ve symptoms in Sz. Clozapine dec. +ve symptoms and has robust Serotonin antagonist activity NE : Neuronal degeneration in NE system may account for anhedonia. Akathisia in Schizoaffective disorder was found to be associated with increased levels of norepinephrine (Agronin and Maletta, 2006) GABA : loss of GABAergic neurons in hippocampus- >dec. GABA->inc. dopaminergic activity Substance P and neurotensin causing altered neuropeptide mechanisms
  21. 21. Decreased muscarinic and nicotinic receptors in the caudate- putamen, hippocampus, and selected regions of the prefrontal cortex may directly impact cognition. There is also decreased muscarinic receptor in the STG responsible for auditory hallucinations in Sz (up to 48 per cent less muscarinic receptors in the STG of schizophrenia brains than in healthy brains) Source - http://www.schizophreniaresearch.org.au/category/research-news/2006-research-news/
  22. 22. Glutamate has been implicated because ingestion of phencyclidine, a glutamate antagonist, produces an acute syndrome similar to schizophrenia The hypotheses proposed about glutamate include those of hyperactivity, hypoactivity, and glutamate-induced neuro- toxicity Abnormally low levels of glutamate receptors are found in postmortem brains of people previously diagnosed with schizophrenia (Konradi and Heckers, 2003)
  23. 23. The main problem with previous studies is that it is not found in all schizophrenics. This has lead to further research done by Crow in 1985. He suggested two types of schizophrenia with two biological causes.
  24. 24. TwoSyndromeHypothesis -Crow1985 Type one - genetically inherited associated with dopamine – characterised by positive symptoms. Type Two – Neurodevelopmenal disorder – to do with Brain structure – characterised by negative symptoms.
  25. 25. The loss of brain volume widely reported in schizophrenic brains appears to result from reduced density of the axons, dendrites, and synapses that mediate associative functions of the brain One theory, based in part on the observation that patients often develop schizophrenic symptoms during adolescence, holds that schizophrenia results from excessive pruning of synapses during this phase of development.
  26. 26. Swayze (1990) reviewed 50 studies of schizophrenics and found that many had abnormally large amounts of liquid in the cavities of the brain. Suddath, who supports this found the same enlarged cavities when using MRI scans on schizophrenic twins. Beng-Choon Ho (2010) in a longitudinal correlational study of 211 schizophrenics found that antipsychotic drugs have measurable influence on brain tissue loss over time. This was supported by Lewis (2009) who administered antipsychotic drugs to primates and found a brain volume loss of 10% .
  27. 27. Whether an active pathological process is continuing to evolve in schizophrenia patients is still uncertain. Some studies indicate progression, while others do not.
  28. 28.  Andreasen et 1990 – conducted a very well controlled CAT scan study and found significant enlargement of the ventricles in schizophrenics compared to controls.  However this was only the case for men and not for women. Therefore CANNOT generalise the findings to women.
  29. 29. • There is a reduced symmetry in several brain areas in schizophrenia, including the temporal, frontal, and occipital lobes. • This reduced symmetry is believed by some investigators to originate during fetal life and to be indicative of a disruption in brain lateralization during neurodevelopment. • High density of white matter in the right frontal and parietal lobe. • Small amount of grey matter in the temporal lobes.
  30. 30. PM findings and MRI -> decrease in the size of the limbic system including the amygdala, the hippocampus, and the parahippocampal gyrus Hippocampus is small, functionally abnormal and has disorganised neurons Hippocampal pyramidal cell disarray in schizophrenia as a bilateral phenomenon. Arch Gen Psychiatric. 1991;48:415
  31. 31. PM studies show anatomical abnormalities in the PFC. Functional deficits have also been demonstrated. It has long been noted that several symptoms of schizophrenia mimic those found in persons with prefrontal lobotomies or frontal lobe syndromes.
  32. 32. Volume shrinkage or neuronal loss, in particular subnuclei The medial dorsal nucleus of the thalamus, which has reciprocal connections with the prefrontal cortex, has been reported to contain a reduced number of neurons Number of neurons, oligodendrocytes, and astrocytes is reduced by 30 to 45 percent in schizophrenic patients Photomicrographs of Nissl-stained frontal sections through the anterior (A), middle (B), and posterior (C) levels of the mediodorsal nucleus
  33. 33. Many patients with schizophrenia show odd movements, even in the absence of medication- induced movement disorders Examples are akathisia, facial grimacing, stereotypies The movement disorders involving the basal ganglia (e.g., Huntington's disease, Parkinson's disease) are the ones most commonly associated with psychosis Increase in the number of D2 receptors in the caudate, the putamen, and the nucleus accumbens
  34. 34. Decreased rate of blinking Staring Lack of the blink reflex in response to a tap on the forehead Poor visual pursuit movements Poor pupil reactions to light Abnormal eye movements in 50 to 85 percent of patients with schizophrenia
  35. 35. In recent years, there has been a build up of evidence supporting the role of viral infections in the development of schizophrenia, including the poliovirus, the flu virus and encephalitis lethargica virus Data supporting a viral hypothesis increased number of physical anomalies at birth, an increased rate of pregnancy and birth complications, seasonality of birth consistent with viral infection, geographical clusters of adult cases, and seasonality of hospitalizations
  36. 36. Complications during pregnancy, abnormal foetal growth and complications during delivery are significant risk factors in the development of schizophrenia. Those that play a significant role in the development of schizophrenia include: bleeding, diabetes and pre-eclampsia.
  37. 37. Summary Biological explanations do account for schizophrenia, however the fact that there is no conclusive explanation that accounts for all schizophrenics – psychological explanations need to be considered.
  38. 38. KAPLAN AND SADOCK SYNOPSIS OF PSYCHIATRY www.schizophrenia.com Various sources from the internet

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Biological aspects,schizophrenia

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