Transcript Schizophrenia 精神分裂癥

牛康衛 08301016018
復旦大學上海醫學院 2009.12
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A psychiatric disorder that makes the patient have an
altered sense of reality
Sx must have been present for one month in a period of six
months of dysfunction.
 Anything shorter than this is a schizophrenifom
disorder
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Positive Sx
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paranoid delusions
disorganized speech
Negative Sx
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auditory and visual hallucinations
Flat affect
Alogia (speech poverty)
Anhedonia
Asociality
Avolition
significant social or occupational dysfunction
word salad (incoherent speech)
avolition (apathy)
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In the United States, the APA's DSM-IV-TR is used, while in much of
the rest of the world, the WHO's ICD-10 is used to determind the
criteria. (Although the two mostly overlap)
DSM-IVdiagnosis of schizophrenia must:
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Have 2+ of aforementioned Sx for a the better part of a
month
Have signs of the disturbance for at least
6 months (with at least one month of Sx)
Must have social or occupational
dysfunction (or dysfunction in self-care)
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The DSM-IV and ICD-10 have defined subtypes of
schizophrenia:
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Paranoid type - only with delusions and hallucinations
Disorganized type - thought d/o and flat affect are
present at the same time
Catatonic type - immobile or have purposeless movement
Undifferentiated type - psychotic Sx are present, but
above not met
Residual type - Sx are present, but with low intensity
Post-schizophrenic depression
Simple schizophrenia - progressive development of
negative Sx with no prior psychotic episodes.
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Family history or ties to schizophrenia
Prenatal problems
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Family member has history of psychotic disorder
(such as delusional disorder)
You have problems with drug or alcohol
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e.g., mother was malnourished, had viral infection, took
medications (diuretics, etc)
Shizophrenia causes problems?
Problems cause schizophrenia?
Age of onset:
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Late adolescence and early adulthood
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Dopamine imbalance
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This is the most commonly researched
Genetics (our focus)
Prenatal and early environment
Neurobiology
All factors interact to trigger the manifestation of
schizophrenia.
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Genetics
 must be considered in conjunction with
environmental factors
 Multifactorial (caused by interactions of several genes)
It is still an area that is new and open to much
more further study
 Though it is considered to be a major
contributing cause, studies have only begun to
be performed to determine the genetic effects
with respect to schizophrenia.
Relationship Risk
Monozygotic twins 40-50%
Dizygotic twins 17%
Children 13%
Siblings 10%
Half siblings 6%
Grandchildren 5%
Nieces, Nephews 4%
Aunts, Uncles, Cousins 2%
General Population 1%
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In the upcoming portion we will be talking about
different studies that analyze the genetic factors
behind schizophrenia.
To understand these studies, we have to understand a
few terms.
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Twin studies
 are significant between they allow researches to
separate what is affected by environment and genes.
 especially when twins are separated at birth
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different environment, but same genes
Monozygotic twins share nearly 100% of genetic
polymorphisms
Dizygotic twins share about 50% of polymorphisms
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Phenotype
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Genotype
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"Outward, physical manifestation" of the organism
in other words what we see (either macroscopically
or microscopically)
"Internally coded, inheritable information" carried
within genes of organisms
"Instructions" on all aspects of biological life
in other words what is encoded
Karyotype
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A "map" of the chromosomes in the human body
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Genetics is only a "major" influence
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Twin studies
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There are may schizophrenia patients that do not have a
family history.
Heritability risk at ~80%
Increased risk even when raised apart
Schizophrenic phenotype
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genetically influenced
not genetically determined
Gene variants are usually within normal limits
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A karyotype is a "picture" of all 23 chromosomes and
the X or Y in a human genome.
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In a series of studies published in July 2009 in
Nature, A “hot spot” was found on chromosome
6p22.1
On short arm of chromosome 6, at extended
MHC region
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Has on it a histone gene cluster
Related to control of DNA transcription and repair
Related to antimicrobial defense, immunity
Controls when and how genes turn on/off
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Research by Shi et al show:
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“Schizophrenia is significant associated with
single nucleotide polymorphisms (SNPs) in the
extended major histocompatibility complex
region on chromosome 6”
This region has a histone gene cluster, and also a
some genes related to immunity
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This could imply etiological linkage to:
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Chromatin modification, transcriptional regulation,
autoimmunity, and/or infection.
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Research by the Stefansson et al:
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Based on genome-wide studies of similar
populations as Shi et al
Studied specific Copy Number Variations (CNVs)
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CNVs are areas of DNA where copy-number
differences are found by comparing multiple
genomes
Can be either inherited or caused by de novo
mutations, such as deletions, duplications,
inversions, or translocations.
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Research by Stefansson et al:
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On these MHCs there are a higher than usual
frequency of risk alleles
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Research by the International Schizophrenia
Consortium:
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Shows that there is a linkage between
schizophrenia and bipolar disorder
Also found in sequences on chromosome 6
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Methods by Shi et al:
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Methods by ISC:
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Tested two populations: European-ancestry (2,681
cases), and African-American (1,286 cases).
Appropriate controls were implemented of similar
numbers.
Tested European population (3,322 cases) with 3,587
controls.
Methods by Stefansson et al:
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Tested European population (2,663 cases) 13,498
controls from eight locations
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There is still a lot of room for more research into
the genetic background of schizophrenia
The information presented here was just one tiny
fraction of the research that is already out there