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The search for susceptibility genes for AD with psychosis

The search for susceptibility genes for AD with psychosis. Rebecca Sims Psychological Medicine. Behavioural Symptoms. hallucinations. anxiety. agitation. delusions. dysphoria. non-cognitive symptoms. aberrant motor activities. euphoria. apathy. disinhibition. irritability.

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The search for susceptibility genes for AD with psychosis

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  1. The search for susceptibility genes for AD with psychosis Rebecca Sims Psychological Medicine

  2. Behavioural Symptoms hallucinations anxiety agitation delusions dysphoria non-cognitive symptoms aberrant motor activities euphoria apathy disinhibition irritability

  3. Psychosis • Affects 40–60% of individuals with AD. • Is associated with increased cognitive and functional decline. • Often results in premature institutionalization. • Heritability estimates range from 30% to 61% (Bacanu et al. 2005). • Genes play a specific role; • In the development of psychotic symptoms in AD. • In the development of AD with psychosis as a sub-form of the disease.

  4. Linkage Hollingworth et al. 2007

  5. 6q22

  6. 6q22

  7. 2005) 6q22

  8. Study Design • Explores the hypothesis that susceptibility variants for psychosis are associated with risk of developing psychosis in AD.

  9. Study Markers • Chosen 57 markers from 10 candidate genes for schizophrenia and bipolar disorder. • Markers tested for association in 1205 AD patients (379 with psychotic symptoms; 269 showing no evidence of psychosis) and 1361 controls.

  10. Results

  11. Oligodendrocyte lineage transcription factor 2 3.3 kb • Encodes a basic helix-loop-helix transcription factor which is expressed in oligodendroglial tumours of the brain. • Influences precursor as well as fully matured oligodendrocytes and is both necessary and sufficient for the genesis of oligodendrocytes and myelination.

  12. OLIG2 • Shown association to schizophrenia (Georgieva et al. 2006; Huang et al. 2008). • Several studies report reduced OLIG2 mRNA in the post-mortem schizophrenic brain (Iwamoto et al. 2005; Katsel et al. 2005; Tkachev et al. 2003).

  13. OLIG2 • OLIG2 gene resides on chr21 within the Down syndrome deleted region. • White matter Changes have shown association with psychotic symptoms in AD patients (Lee et al. 2006).

  14. Future Work • Genotyping and analysis of OLIG1 gene

  15. Future Work • MRI – Correlation of white matter changes with psychosis in AD. • GWAS • Myelination. • Psychosis GWAS genes.

  16. Acknowledgements • Professor Julie Williams • Dr Richard Abraham • Professor Mike Owen • Professor Mick O’Donovan • Dr Angharad Morgan • Dr Paul Hollingworth • Kimberley Dowzell • Alexandra Stretton • Laura Jones

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