SPECIFIC NOSOLOGICAL ISSUES: SCHIZOPHRENIA
Wolfgang Gaebel Section on Schizophrenia
Department of Psychiatry and Psychotherapy Heinrich-Heine-University Düsseldorf, Germany
DIAGNOSTIC VALIDITY IN PSYCHIATRIC ILLNESS • Clinical description • Laboratory studies • Delimitation from other disorders
• Follow-up studies
• Family studies
Robins and Guze (1970)
TOWARDS A COMPREHENSIVE DIAGNOSTIC SCHEME IN PSYCHIATRY
Clinical Criteria
1. 2. 3. 4.
Clinical phenomenology Longitudinal course Pedigree study Pharmacological response
Research Criteria
5. Biochemical correlates 6. Neuropsychological/psychophysiological findings
Akiskal (1978)
USE OF MULTIAXIAL ASSESSMENT
• Facilitating comprehensive and systematic evaluation • Organizing and communicating clinical information
• Capturing the complexity of clinical situations
• Describing the heterogeneity of individuals • Promoting the application of the biopsychosocial model
DSM-IV, APA (1994)
CATEGORICAL VS DIMENSIONAL CLASSIFICATION
Dimensional systems . . .
• classify based on quantification of attributes rather than the assignment to categories • work best in describing phenomena that are distributed continuously • increase reliability and communicate more clinical information • are less familiar • lack agreement on the choice of optimal dimensions • may be a research tool for the future
DSM-IV, APA (1994)
The development of taxonomic concepts in the study of mental disorder will probably show two trends: First, a continuation of the shift from systems defined by reference to observable characteristics to systems based on theoretical concepts; and second, a gradual shift from classificatory concepts and methods to ordering concepts and procedures, both of the nonquantitative and of the quantitative varieties.
Hempel (1965)
OUTLINE FOR A POSSIBLE FUTURE MULTIAXIAL SYSTEM (DSM-V)
• Axis I: Genotype • Identification of disease-/symptom-related genes • Identification of resiliency/protective genes • Identification of genes related to therapeutic responses to and side effects of specific psychotropic drugs • Axis II: Neurobiological phenotype • Identification of intermediate phenotypes (neuroimaging, cognitive function, emotional regulation) related to genotype • Relates to targeted pharmacotherapy • Axis III: Behavioral phenotype • Range and frequency of expressed behaviors associated with genotype, neurobiological phenotype, and environment • Relates to targeted therapies • Axis IV: Environmental modifiers or precipitants •Environmental factors that alter the behavioral and neurobiological phenotype
• Axis V: Therapeutic targets and response
Charney et al. (2002)
Endophenotypes
CLINICAL AND PATHOPHYSIOLOGICAL COURSE OF SCHIZOPHRENIA
Lieberman et al. (2001)
SCHIZOPHRENIA: A CONCEPT OF ENDOPHENOTYPE
• Endophenotype = An internal phenotype discoverable by a biochemical test or microscopic examination • First used in schizophrenia genetics by Gottesmann and Shields (Br J Psychiatry 1973;122: 15-30) • Endophenotypes are a tool to study disorders with complex genetics • Endophenotypes represent more elementary phenomena as opposed to behavioral phenomena, the number of genes required to produce such endophenotypes may be fewer than those involved in producing a psychiatric diagnostic entity
ENDOPHENOTYPES IN SCHIZOPHRENIA
Defining categories for Endophenotypes I
(I) The Endophenotype –must be associated with schizophrenia in the population –must be heritable –must be state-independent –must cosegregate with schizophrenia in families –must be found in non-affected family members at a higher rate than in the general population
Gottesman and Gould, Am J Psychiatry 2003; 160:636-645
ENDOPHENOTYPES IN SCHIZOPHRENIA
Defining categories for Endophenotypes II
(II) The Endophenotype –must be an easily measurable neurobiological variable associated with schizophrenia –should be abnormal before disease manifestation –should be stable over time and not influenced by medication or the disease –should show a strong genetic influence –should be associated with a genetically determined disease risk
Zobel and Maier, Nervenarzt 2004;75:205-214
ENDOPHENOTYPES IN SCHIZOPHRENIA
• Sensory-motor gating –Prepulse inhibition of the startle response –P50 suppression • Eye tracking dysfunction –Smooth pursuit eye movements • Working memory –Neuropsychological tests –fMRI (Gottesman and Gould, Am J Psychiatry 2003; 160:636-645) • Structural brain alterations –Ventricular enlargement, regional atrophies (frontal cortex) –Increased gyrification • Late evoked potentials –P300 oddball paradigm (Zobel and Maier, Nervenarzt 2004; 75:205-214)
Behavioral Phenotype
... Überhaupt wird es immer deutlicher, daß der Bezugsrahmen für biologisch-psychiatrische Befunde (...) über die bisher üblichen globalen nosologischen Diagnosen hinausgehen muß, wenn sich die biologische Psychiatrie nicht wesentliche Erkenntnismöglichkeiten selbst verstellen will. ... So müssen in Zukunft die Befunde der biologischen Psychiatrie außer auf nosologisch-diagnostischer Ebene auch im Hinblick auf einen nosologisch neutralen syndromalen Bezugsrahmen, ja womöglich sogar auf Symptom-Ebene ausgewertet werden.
Hippius und Matussek (1978)
Wenn es überhaupt möglich ist, einen Fortschritt der psychopathologischen Diagnostik herbeizuführen, so sind es die Untersuchungsmethoden der experimentellen Psychologie, welche berufen erscheinen, die hier vorhandene Lücke wenigstens teilweise ausfüllen zu helfen.
Kraepelin (1887)
SOURCES OF INFORMATION IN PSYCHOPATHOLOGY • Subjective-verbal • Motor • Physiological
METHODOLOGICAL APPROACHES TO PSYCHOPATHOLOGY • Self-rating • Observer rating • Behavioral observation • Measurement of reaction
CLASSIFICATION OF PSYCHOPATHOLOGICAL SYMPTOMS ACCORDING TO THE METHODOLOGICAL APPROACH
Symptom categories Disorders of consciousness Disturbances of orientation Disturbances of attention and memory Formal disorders of thought Phobias and compulsions Delusions Disorders of perception Disorders of ego Disturbances of affect Disorders of drive and psychomotility Circadian Disturbances Other disturbances Items 4 4 6 12 6 14 6 6 21 9 3 9 S 3 2 6 6 6 1 So 1 1 1 3 3 1 SO 1 2 2 2 2 sO 1 4 4 1 10 8 2 5 O 2 2 8 1 4 4 1
100
24
10
9
35
22
AMDP-Sytem
FUNCTIONAL PSYCHOPATHOLOGY
• Dissection of a psychopathological syndrome in its component parts, i.e. psychological dysfunctions, as a complement to the nosological/categorical approach, to: 1. Shed new light on the non-specificity of biological variables related to psychiatric disorders; 2. Increase the chance of finding meaningful relations between biological and behavioral variables;
3. Explain the uncomprehended non-specificity of certain psychotropic drugs.
Van Praag et al. (1987)
EXPERIMENTAL PSYCHOPATHOLOGY I - Methods and aims • To systematize the assessment of psychopathology: Application of objective assessment methods Experimental variation of assessment
conditions
• To develop a functional psychopathology • To sharpen the phenotype for basic research • To improve diagnosis and treatment
EXPERIMENTAL PSYCHOPATHOLOGY II - Fields of application • Assessment of psychopathology in patients by means of experimental methods • Experimental induction of psychopathology in patients (e.g. pharmacological challenge)
• Experimental induction of psychopathology in healthy probands
• Experimental modelling of psychopathological equivalents in animals
TOWARDS A FUNCTIONAL CLASSIFICATION OF MENTAL DISORDERS
Disrupted life performance
Special case history Clinical psychopathology Operational diagnostic classification Experimental psychopathology
Psychobiological tests of function Functional classification
SYSTEM OF FUNCTIONAL PSYCHOPATHOLOGY
• Taxonomy of normal (basic) functions (BF)
• Formal characteristics of disturbances of BF
Quantitative (hypo-/hyperfunction) Qualitative (dysfunction) Temporal (gradient, rhythm, reversibility) Disturbance of functional/regional brain modules
Loss/increase Inhibition/disinhibition Primary (bio-psycho-social disturbance) Secondary (bio-psycho-social adaptation/compensation/ plasticity)
• Identity of the underlying functional disturbance (FD)
• Formal characteristics of underlying FD
• Determinants of underlying FD
EXPERIMENTAL SETUP FOR THE ASSESSMENT OF PSYCHOPATHOLOGY
Subject
Trackball
Debic 80 (eye movement recording)
Infrared-light camera (eye movements) Camera1 (facial expression) Monitor (scene)
PC (stimulus material)
/ \
\ /
FD
Camera 2 (gestures)
Videorecorder (stimulus material)
Camera 3
Interviewer
Video-Mixer face body
scene
/
\
Videorecorder (recording)
RESEARCH STRATEGIES IN DEVELOPING A TAXONOMY OF PSYCHOBIOLOGICAL BASIC FUNCTIONS Research strategy Example
_____________________________________________________________________ Category Affect • Definition e. g. facial expression • Modelling psychological/cultural En-/Decoding of emotions neurobiological Affect specific modules • Operationalization Facial action units (FACS) • Assessment situation Interview / experiment • Variation of conditions Expressive Spontaneous / voluntary Perceptive Perception of affect • Standardization Normal probands • Deviation from standard Quantitative / qualitative • Nosological specificity Psychiatric controls • Trait-/state specificity Pre- / intra- / postepisode / family • Determinants/treatment response e. g. psychotropic drugs • Biological correlates Specificity of brain modules
MENTAL DISORDERS: OVERLAPPING NETWORK DYSFUNCTIONS
Perception
Psychosis
Cognition
Dementia Function Depression
Parkinson
Social
Emotion
Motor Function
SUMMARY AND CONCLUSIONS
Application of behavior-oriented objective assessment methods and experimental variation of assessment conditions in psychopathology together with the assessment of brain function could provide a more valid starting point for • the differentiation between related/similar syndromes • the investigation of longitudinal stability, illness specificity and effects of various treatment modalities • the identification of meaningful correlations between biological and behavioral variables (brain-behaviorrelationship)
and thus could add a functional reformulation of psychopathology as a new tool for diagnosis and classification.