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Sophia Frangou  MD PhD FRCPsych Institute of Psychiatry, London Bipolar Disorder
Overview ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Lifetime and 12-month prevalence of bipolar spectrum disorder National Comorbidity Survey Replication Merikangas et al 2007 ,[object Object],[object Object],[object Object],[object Object],n=9282 (aged ≥18 years); US population Prevalence, mean (SD) Any bipolar disorder Bipolar I Bipolar II Bipolar NOS Lifetime 4.4 (24.3) 1.0 (13.2) 1.1 (10.6) 2.4 (23.3) 12-month 2.8 (18.9) 0.6 (9.2) 0.8 (9.9) 1.4 (15.1)
The complexity of symptomatic presentation  Post et al. 2003
Number of DSM-IV Manic Symptoms During  an Index Episode of Bipolar Depression in STEP-BD  (N=1,380) Goldberg et al. 2009
Constant risk of relapse over 40yrs; 0.4episodes/year Angst et al. Eur Arch Psychiatry Clin Neurosci. 2003
Aetiology
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],The Phenotypic Spectrum of Bipolar Disorder
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Susceptibility Genes
Susceptibility Genes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Beyond Symptoms ,[object Object],[object Object],[object Object]
What do these circuits to?   Amygdala Association of stimuli with reward and punishment   Anterior Cingulate  Processing conflicting info  Effortful cognitive processing  Dorsal PFC  Maintenance/ Manipulation of task relevant info  Cognitive set shifting Planning  Ventral PFC  Maintenance/ Manipulation of incentive info  Response modification when contingencies change  Planning
Copyright restrictions may apply. Kempton, M. J. et al. Arch Gen Psychiatry 2008;65:1017-1032. Continuous variables from the bipolar-control meta-analysis Meta-analysis of brain structural changes
RISK  -  Insula Involved emotional recall and self-regulation of affect  Connected to  the cingulate cortex and the brainstem RESILIENCE – Cerebellar Vermis Involved in the homeostatic control of autonomic function Contributes to the adaptive control of complex behaviour DISEASE – Substantia Nigra  Has high concentration of D2 receptors Highest level of expression of the vesicular monoamine transporter gene, which is associated with BD Kempton et al. submitted Brain Structure and Bipolar “Spectrum”
Premorbid Phase  Koenen et al. Am J Psychiatry 2009
Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP)  : Premorbid and Post onset IQ Zanelli et al. Am J Psychiatry 2010 106 44 14 48 41 264
Stefanopoulou at al. 2009 Meta-analytic evidence: IQ decrement in chronic patients
Normal age related gray matter volume changes in BD Sarnicola et al. Bipol Disord. 2009 age from scanned 70.00 60.00 50.00 40.00 30.00 20.00 grey 1.000000 0.900000 0.800000 0.700000 0.600000 0.500000 control patient control patient pat_code1 R Sq Linear = 0.115 R Sq Linear = 0.184 Age (years) 70 60 50 40 30 20 1.00 0.90 0.80 0.70 0.60 0.50 control patient control patient R Sq Linear = 0.115 R Sq Linear = 0.184
Increased risk of dementia in BD Kessing et al.  J Affect Disord 2000 100 97 94 0   10  20 diabetes artritis mania depression
Total white matter volume and IQ predict GAF score in BD patients  Forcada et al. submitted
Lithium decreases the risk of dementia Kessing et al. Arch Gen Psychiatry 2008
Beyond Symptomatic Control? Moore et al Lancet 2000
Germana et al Acta Scan Psychiatrica 2010 Effect of Lithium on regional gray matter volume A B C ,[object Object],[object Object],[object Object],Significant group differences in gray matter volume between BD  patients treated with Lithium and all other treatment groups combined
Genetic  Predisposition
WCST and HSCT  Frangou  et al.  Biol Psychiatry. 2005  9 8 7 6 5 4 3 2 1 0 WCST categories achieved WCST perseverative errors HSCT A error scaled score HSCT B error scaled score BD Patients Offspring Controls
Controls Healthy Relatives MDD Relatives  Bipolar Patients
 

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Updates on Bipolar Disorder

  • 1. Sophia Frangou MD PhD FRCPsych Institute of Psychiatry, London Bipolar Disorder
  • 2.
  • 3.
  • 4. The complexity of symptomatic presentation Post et al. 2003
  • 5. Number of DSM-IV Manic Symptoms During an Index Episode of Bipolar Depression in STEP-BD (N=1,380) Goldberg et al. 2009
  • 6. Constant risk of relapse over 40yrs; 0.4episodes/year Angst et al. Eur Arch Psychiatry Clin Neurosci. 2003
  • 8.
  • 9.
  • 10.
  • 11.
  • 12. What do these circuits to? Amygdala Association of stimuli with reward and punishment Anterior Cingulate Processing conflicting info Effortful cognitive processing Dorsal PFC Maintenance/ Manipulation of task relevant info Cognitive set shifting Planning Ventral PFC Maintenance/ Manipulation of incentive info Response modification when contingencies change Planning
  • 13. Copyright restrictions may apply. Kempton, M. J. et al. Arch Gen Psychiatry 2008;65:1017-1032. Continuous variables from the bipolar-control meta-analysis Meta-analysis of brain structural changes
  • 14. RISK - Insula Involved emotional recall and self-regulation of affect Connected to the cingulate cortex and the brainstem RESILIENCE – Cerebellar Vermis Involved in the homeostatic control of autonomic function Contributes to the adaptive control of complex behaviour DISEASE – Substantia Nigra Has high concentration of D2 receptors Highest level of expression of the vesicular monoamine transporter gene, which is associated with BD Kempton et al. submitted Brain Structure and Bipolar “Spectrum”
  • 15. Premorbid Phase Koenen et al. Am J Psychiatry 2009
  • 16. Aetiology and Ethnicity in Schizophrenia and Other Psychosis (AESOP) : Premorbid and Post onset IQ Zanelli et al. Am J Psychiatry 2010 106 44 14 48 41 264
  • 17. Stefanopoulou at al. 2009 Meta-analytic evidence: IQ decrement in chronic patients
  • 18. Normal age related gray matter volume changes in BD Sarnicola et al. Bipol Disord. 2009 age from scanned 70.00 60.00 50.00 40.00 30.00 20.00 grey 1.000000 0.900000 0.800000 0.700000 0.600000 0.500000 control patient control patient pat_code1 R Sq Linear = 0.115 R Sq Linear = 0.184 Age (years) 70 60 50 40 30 20 1.00 0.90 0.80 0.70 0.60 0.50 control patient control patient R Sq Linear = 0.115 R Sq Linear = 0.184
  • 19. Increased risk of dementia in BD Kessing et al. J Affect Disord 2000 100 97 94 0 10 20 diabetes artritis mania depression
  • 20. Total white matter volume and IQ predict GAF score in BD patients Forcada et al. submitted
  • 21. Lithium decreases the risk of dementia Kessing et al. Arch Gen Psychiatry 2008
  • 22. Beyond Symptomatic Control? Moore et al Lancet 2000
  • 23.
  • 25. WCST and HSCT Frangou et al. Biol Psychiatry. 2005 9 8 7 6 5 4 3 2 1 0 WCST categories achieved WCST perseverative errors HSCT A error scaled score HSCT B error scaled score BD Patients Offspring Controls
  • 26. Controls Healthy Relatives MDD Relatives Bipolar Patients
  • 27.  

Editor's Notes

  1. One off the most common questions asked by patients and relatives is how long the need to stay on medication. Angst and his colleagues estimated the risk of relapse in patients with mood disorders over a 40 year period. Bipolar patients had a higher risk of relapse than unipolar depressives but for both conditions the risk remained constant throughout the 40 year period and averaged a rate of one episode every two years. No gender differences were noted. This evidence suggests that there is no period when the risk of relapse is zero and is therefore safe to discontinue treatment. Patients should be made aware of this but of course the decision of how to manage the risk of relapse rests with them.
  2. I have added this slide to alert you to new evidence regarding the role of lithium and perhaps valproate in other aspects of treatment of bipolar disorder. There is some evidence that lithium may have neuroprotective properties as shown in this study. Here patients treated with lithium for a period of the month showed an increase in the grey matter volume. There is a lot of research currently focusing on exploring further the neuroprotective effects of lithium. At the very least such evidence suggests that recommendations for long-term treatment with lithium are probably unlikely to have adverse effects on the brain.