DSM IV page 1

1
Classification and genetic background of
psychiatric disorders Judit Lazáry
MD Department of Pharmacology andPharmacotherapy
Semmelweis University 2008.
2
Greek and Roman psychiatry

• Hippocrates (460-370 BC)
• Brain-the seat of life
• Normal functioning the balance of four humours
• Large excess
• phlegm dementia
• Yellow bilemanic rage
• Black bilemelancholia
• Small excess produces phlegmatic, choleric,
  sanguine personalities

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Greek and Roman psychiatry

• Diseases epilepsy, mania, paranoia, organic
  toxic delirium, postpartum psychosis,
  phobias and hysteria
• Treatments Bathing, dieting, elimination of
  excess humours by purgatives,
  chatartics, bleeding
• Galen (AC) Physical disprders can cause
  psychiatric and vica versa

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Middle Ages
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Renaissance
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Historical figures of Psychiatry
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Historical figures of Psychiatry
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Neurobiology and Somatic Treatments
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Epidemiology - Surveys

• 1954 Midtown Survey (1660 Manhattan citizens)
• The prevalence of mental disease is 6 times
  higher in the lowest social class than in the
  highest.
• 1977 ECA Survey (20,000 US citizens)
• Alcohol dependence higher in men
• Drug abuse prevalence is higher under age 30
• Prevalence of depression is 2x higher in women

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Epidemiology - Surveys

• 1991 WHO Collaborative Study ( 27,000 people in
  15 countries)
• - mental disorders occurs in all meassured
  cultures
• - depressive and anxiety symptomes exists in
  same forms but under different classifications
• - psychiatric disorders cause functional
  disorder
• - psychiatric patients give a great charge for
  the general practicions
• - general practicions do not recognize the
  psychiatric disorders

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Classification

• Psychiatric nozology was heterogenous for long
  time
• In same time there was numerous classification
• great professor vs expert consensus
• Aim of united classification adequate
  communication, education, researches for
  clinicians and researchers
• Modern systems
• controllable
• Exact criteria
• Professional reconciliation
• Standardized and validated diagnostic categories
• flexible, corrrectable
• Instead of disease disorder

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Classification of Mental Disorders

• ICD-10
• Since 1900
• International Classification of Disease
• Created by the WHO
• For coding and statistical purposes
• In 1948. (6th edition) mentioned psychiatric
  disorders first time
• In 1968 not only listed psych dis but a few
  sentences about them
• In 1979 (BNO-9) significantly expanded part of
  psychiatric disorders

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ICD-10

• 1992. ICD-10
• Mental disorders expanded very much
• Numerous categories used in the American system
  were involved
• Simplification and multisense
• Principally for statistical purposes

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Classification of Mental Disorders

• Diagnostic and Statistical Manual of Mental
  Disorders
• Created by the American Psychiatric Association
• International clinical standard
• For clinical use and research

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DSM - history

• 1952. DSM-I. (built on codes of BNO-6 but based
  on Meyers phylosophy)
• 1968. DSM-II.(similar to BNO-8)
• 1980. DSM-III. turning point for the modern
  psychiatry!!!
• Revised DSM-III 1987.
• 1994. DSM-IV

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DSM-III

• Diagnoses based on exact criteria
• Descriptive clinical categories (atheorical)
• Comprehensive expert team
• Multiaxial diagnostic system
• Eliminating neurozis
• 18 main categories
• Within 3 years it was translated to 15 languages

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DSM-III-R

• Revised DSM-III1987.
• Use of disorder, correction of criteria
• Instead of hierarchical system multiple
  autonomous disorder side by side
• For Sleep disorders separate chapter was created
• Changes were based on published data

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DSM-IV

• 1994. DSM-IV
• Based on almost only scientific data
• Organic category has disappeared
• New subgroups
• Eating disorders in separate chapter
• 16 major diagnostic classes
• It does not cover all statements which require
  treatment

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DSM IV (page 1)

• Disorders First Diagnosed In Infancy, Childhood,
  Or Adolescence
• Delirium, Dementia, Amnestic And Other Cognitive
  Disorders
• Mental Disorders Due To A General Medical
  Condition Not Elsewhere Classified
• Substance-related Disorders
• Schizophrenia And Other Psychotic Disorders

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DSM IV (page 2)

• Mood Disorders
• Anxiety Disorders
• Somatoform Disorders
• Factitious Disorders
• Dissociative Disorders
• Sexual And Gender Identity Disorders

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DSM IV (page 3)

• Eating Disorders
• Sleep Disorders
• Impulse-control Disorders Not Elsewhere
  Classified
• Adjustment Disorders
• Personality Disorders

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DSM - example

• Affective disorders
• Spec current degree
• 1mild, 2 minimal, 3serious, without psychotic
  characteristics, 4serious, with psychotic
  characteristics , 5partly remissed, 6completly
  remissed, 0 not specified
• bcronicity, cwith kataton characteristics,
  dwith melancholic characteristics, fpostpartum
  beginning
• hseasonal pattern, irapid cycle

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DSM practical points

• Multiaxial evaluation
• I clinical disorders, statments which require
  clinical observation
• II personality disorders, mental retardation
• III somatic disorders
• IV psychosocial and function (GAF 0-100)
• V global estimate of function
• Nonaxial form disorders listed
• main / temporary diagnosis

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ICD and DSM

• The two systems getting closer to each other
• They are interacting with each other
• The aim of DSM-IV was clearly the sincronization
  with ICD-10
• They could be united for one system, BUT
• Both systems insist on its own caracteristics
  which are not evidence based
• standard diagnostic devices were developed for
  DSM classification (DIS, SCID), which absent from
  the European one

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Genetic background of psychiatric disorders

• Genetic studies in majority of psychiatric
  disorders
• Psychiatric disorders are complex diseases thus
  several other factors disturb gentetic
  investigations
• Compared to other type of diseases, measuring
  phenotypes in psychiatric disorders are much more
  difficult
• Most investigated candidates are molecules from
  neurotransmitter systems

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Depression

• Candidates from monoaminergic system
• Serotonin transporter gene (SLC6A4)
• 2A serotonergic receptor gene (5HTR2A)
• Tyrozin-hidroxylase gene (TH)
• Triptophan hidorxylase I. gene (TPH1)
• Catechol-o- metiltransferase gene (COMT)

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Depression

• Several authors found positive association
  between 5-HTTLPR S allel and depression (Lesch
  et al. 1996.,Furlong et al., 1998., Lasky-Su et
  al., 2005.)
• Our data confirm association between S allel
  and subclinical depression (Gonda et al. 2005.),
  and affective temperaments too (Gonda et al.
  2006.)
• Latest data show that effect of S allel not
  directly influence depression, rather cause a
  vulnerabilty to stress life events (Caspi et al.,
  2003., Hariri et al. 2004., Kendler et al. 2005,
  Wilhelm et al 2006.)
• TPH 1 associated with MDD and suicide (Zill et
  al. 2004., Zhou et al.2006.)

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Depression

• Balance of neuroprotectiv and neurotoxic factors
  can damage causing depression
• Significant role of BDNF in this balance
• BDNF gene associated with MDD (Tsai et al. 2003.,
  Kunugi et al. 2004., Strauss et al. 2004.)
• Linkage studies resulted that on 2q chromosome,
  CREB1 gene associated signifanctly with
  depression (Zubenko et al. 2003.)

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Genetics of bipolarity

• Among all depression types, bipolarity is the
  most heritable one
• Several genetic studies provided different
  results but replicated positive findings are
• MAO-A gene (Preisig et al. 2000.)
• COMT gene (Jones et al. 2001.)
• 5-HTT gene (Lasky-Su et al. 2004.)
• Linkage studies on 13q D-amino oxidase aktivator
  DAO (G72) (Schumacher et al. 2004.)
• Same locus is associated with schizophrenia
• New candidate Slynar gene (AZ070435), but the
  product of this gene has unknown function
  (Gursharan et al. 2006.)

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Genetics of Obscessive-compulsive disorder (OCD)

• Serotonin transporter gene majority of authors
  reported significant association between 5-HTTLPR
  l allel and OCD (Seeger et al. 2001., Curran et
  al. 2005, Johann et al. 2003.)
• G861C and T371G polimorphism of 5-HT1Dß receptor
  gene are associated with OCD in family studies
  (Mundo et al. 2000.)
• MAO-A gene was found to be associated with OCD in
  replicated studies (Camarena et al. 2001.,
  Karayiorgou et al. 1999.)
• COMT gene was also significantly associated with
  OCD in multiple studies (Niehaus et al. 2001.,
  Alsobrook et al. 2002.)
• Furthermore, MAO-A and COMT gene enhance each
  others effect
• Several polymorphisms of DRD4 rec. gene showed
  association with OCD (Cruz et al. 1997., Cohen et
  al. 1999.)

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Schizophrenia
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Genetics of addict disordersexample Alcoholism