How can biological variables truly inform a valid psychiatric nosology

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How can biological variables truly inform a valid
psychiatric nosology?

• Mohammed T. Abou-Saleh,
• WPA Section on Biological Psychiatry,
• St Georges Hospital Medical School,
• University of London

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Scope

• Defining validity
• Validity vs Utility
• Biological markers as diagnostic criteria
• Deconstructing psychiatric disorders
• Turning inventions into discoveries

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Defining Validity

• Robins Guze - includes laboratory studies
• Kendler - antecedent , concurrent and predictive
• Andreasen - Additional validators linking
  symptoms to neural substrates
• molecular genetics
• Cognitive neuroscience

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Disease Entity

• Boundaries point of rarity non-linear
  relationship to outcome or heritability
• Categories ( Axis I ?) and / or dimensions ( Axis
  II ?)
• Not aetiology-based in Huntington, Downs
  aetiology was established later
• Boundary with normality ( Axis I II?)

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Defining utility

• Validity is invariate
• Utility is context-dependent

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Scope

• Defining validity
• Validity vs Utility
• Biological markers as diagnostic criteria
• Deconstructing psychiatric disorders
• Turning inventions into discoveries

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The Dexamethasone Suppression Test and Suicide
Prediction William Coryell, M.D., and Michael
Schlesser, M.D.
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TABLE 1                                         
                                                  
                                        
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Ebrii gignunt ebrios

• Drunkards beget drunkards

Plutarch AD 46 - 120
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Figure 1                                        
                                                  
                                         
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Figure 2                                        
                                                  
                                         
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Comorbidity of depression and drug abuse
biological mechanisms

• Prevalence
• Developmental factors
• Genetic factors
• Environmental factors
• Pharmacological factors

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Videbech
and Ravnkilde perform a systematic review and
meta-analysis of volumetric studies of the
hippocampus in patients with mood disorders.
Results of the study showed that hippocampal
volume is reduced in patients with unipolar
depression, maybe as a consequence of repeated
periods of major depressive disorder.
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MR-based in vivo hippocampal volumetrics 2.
Findings in neuropsychiatric disorders.Review
Geuze, Molecular Psychiatry. 10(2)160-184,
February 2005.
Smaller hippocampal volumes have been reported in
epilepsy, Alzheimer's disease, dementia, mild
cognitive impairment, the aged, traumatic brain
injury, cardiac arrest, Parkinson's disease,
Huntington's disease, Cushing's disease, herpes
simplex encephalitis, Turner's syndrome, Down's
syndrome, survivors of low birth weight,
schizophrenia, major depression, posttraumatic
stress disorder, chronic alcoholism, borderline
personality disorder, obsessive-compulsive
disorder, and antisocial personality disorder.
Significantly larger hippocampal volumes have
been correlated with autism and children with
fragile X syndrome..
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Functional neuroimaging of genetic variation in
serotonergic neurotransmission
Hariri, Weinberger, 2003
. Recently, functional neuroimaging has provided
a dramatic illustration of how a promoter
polymorphism in the human 5-HT transporter
(5-HTT) gene is strongly related to the
engagement of neural systems, namely the
amygdala, subserving emotional processes. We
argue that in time, such knowledge will allow us
to not only transcend phenomenological diagnosis
and represent mechanisms of disease, but also
identify at-risk individuals and biological
pathways for the development of new
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Neurocognitive deficits( NcD )susceptibility
genes

• Discordant twins M Z gt DZ in NcD
• Sibs of patients with Schizophrenia 4 times rate
  NcD than general population
• Unaffected relatives show enlarged
  ventricles,reduced hippocampi and N-acetyl
  aspartate (MRS)
• COMT Val108/158Met genotype less prefrontal
  dopamine function and NcD and excessively
  transmitted to schizophrenic offspring

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Pharmacogenetics in the treatment of depression
pharmacodynamic studies
Serretti et al 2005
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Scope

• Defining validity
• Validity vs Utility
• Biological markers as diagnostic criteria
• Deconstructing psychiatric disorders
• Turning inventions into discoveries
• What value and impact on future nosology

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Nosological tunnel vision in biological
psychiatry. A plea for a functional
psychopathologyVan Praag HM, 1990

• Correlate biological variables with psychological
  dysfunctions, the basic units of classification
  in psychopathology.
• Signs of diminished neurotransmitter metabolism
  are not disorder-specific, but rather are related
  to psychopathological dimensions i.e.,
  hypoactivity/inertia increased
  aggression/anxiety and anhedonia,
• Functional psychopharmacology will be
  dysfunction-oriented and therefore inevitably
  geared towards utilizing drug combinations.
• Nosologomania a disorder of psychiatry.

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Will the Genomics Revolution Revolutionize
Psychiatry?
Merikangas, K R Risch, N. Am J Psychiatry 2003
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How can biological variables truly inform a valid
psychiatric nosology ?

• DSM and ICD are symptom based and ignore
  aetiology
• High reliability, uncertain validity and variable
  utility
• Biological criteria for present diagnostic
  entities are well established?
• Biological variables and established
  endo-phenotypes could validate present diagnostic
  entities
• New nosology could also be aetiology and
  pathogenesis based and include biological
  diagnostic criteria ( Axis )
• New nosology could have in-built utility and
  biological prognostic criteria ( Axis )
• New nosology should provide reliable, valid and
  useful diagnostic entities for a comprehensive
  formulation of diagnosis, treatment and
  prevention

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