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R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Showcase Lecture Series:
"Ontology, Bioinformatics and the Life Sciences"
Ontology and the Future of
Psychiatric Diagnosis
Buffalo, NY, USA, Thursday October 19th, 2006
Werner CEUSTERS
Center of Excellence in Bioinformatics and Life Sciences
Department of Psychiatry
National Center for Biomedical Ontology
University at Buffalo, NY, USA
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontology and Psychiatry
• Ontology:
– (roughly) the branch of philosophy that deals with what exists
and with how the entities that exist relate to each other.
– representing reality in IT systems
• Psychiatry:
– (roughly) the branch of medicine that deals with the diagnosis,
treatment, and prevention of mental and emotional disorders.
• Ontology applied to psychiatry:
– Studying the nature of mental disorders and their place in
pathological anatomy and pathophysiology;
– Finding better ways to build IT systems to support the practice
of psychiatry.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
This could then be a very short presentation
• Their question:
Does Mental Illness Exist?
• Their answer:
The
Antipsychiatry
Coalition
–‘there are no biological abnormalities
responsible for so-called mental illness, mental
disease, or mental disorder, therefore mental
illness has no biological existence.
– Perhaps more importantly, however, mental
illness also has no non-biological existence,
– except in the sense that the term is used to
indicate disapproval of some aspect of a
person's mentality.’
Lawrence Stevens, J.D, 1999
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Their argument is based on the (narrow ?)
definitions for disease.
• Most attempts refer to bodily issues:
– STEDMAN (27th edition):
• An interruption, cessation, or disorder of body function, system, or organ.
Syn: illness, morbus, sickness
• A morbid entity characterized usually by at least two of these criteria:
recognized etiologic agent(s), identifiable group of signs and symptoms,
or consistent anatomic alterations.
– DORLAND
• any deviation from or interruption of the normal structure or function of a
part, organ, or system of the body as manifested by characteristic
symptoms and signs; the etiology, pathology, and prognosis may be
known or unknown.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
‘Ontology inspired’ definition
• An organism (or part of an organism) is diseased if and
only if
– it includes among its parts pathological anatomical structures which
compromise the organism’s physiological processes to the degree that
they give rise to symptoms and signs.
• An anatomical structure is pathological whenever:
– it has come into being as a result of changes in some pre-existing
canonical anatomical structure
– through processes other than the expression of the normal complement
of genes of an organism of the given type, and
– is predisposed to have health-related consequences for the organism in
question manifested by symptoms and signs.
Smith B, Kumar A, Ceusters W, Rosse C. On carcinomas and other pathological entities. Comparative
and Functional Genomics, Volume 6, Issue 7-8 (October - December 2005), p 379-387.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Latest WHO definition
• A disease is:
– an interconnected set of one or more dysfunctions in one or
more body systems including:
• a pattern of signs, symptoms and findings (symptomatology manifestations)
• a pattern or patterns of development over time (course and outcome)
• a common underlying causal mechanism (etiology)
– linking to underling genetic factors (genotypes, phenotypes and
endophenotypes) and to interacting environmental factors
– and possibly: to a pattern or patterns of response to
interventions (treatment response).
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
WHO constitution
• The State Parties to this Constitution declare, in
conformity with the Charter of the United Nations,
that the following principles are basic to the
happiness, harmonious relations and security of
all peoples:
– Health is a state of complete physical, mental and
social well-being and not merely the absence of
disease or infirmity.
–…
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The “Myth of Mental Illness”
• “I maintain
– that the mind is not the brain,
– that mental functions are not reducible to brain functions, and
– that mental diseases are not brain diseases,
– indeed, that mental diseases are not diseases at all.
• When I assert the latter, I do not imply that distressing personal
experiences and deviant behaviors do not exist. Anxiety, depression,
and conflict do exist--in fact, are intrinsic to the human condition-but they are not diseases in the pathological sense.”
Thomas S. Szasz (MD), Mental Disorders Are Not Diseases.
USA Today (Magazine) January 2000
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The old debate on the “body-mind problem”…
• Dualistic views in Philosophy of Mind:
– asserts the separate existence of mind and body
– comes in various flavours:
• Ontological dualism
– Substance dualism
– Property dualism
– Predicate dualism
• Interaction dualism
• Monistic views in Philosophy of Mind:
•
•
•
•
• …
Behaviourism
Identity theory
Functionalism
Non-reductive physicalism
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
… and its impact on Psychiatry
• Mental health professionals continue to employ a mind-brain dichotomy when
reasoning about clinical cases.
• The more a behavioral problem is seen as originating in “psychological”
processes, the more a patient tends to be viewed as responsible and blameworthy
for his or her symptoms;
• conversely, the more behaviors are attributed to neurobiological causes, the less
likely patients are to be viewed as responsible and blameworthy.
Miresco MJ, Kirmayer LJ.
The Persistence of Mind-Brain Dualism in Psychiatric Reasoning About Clinical Scenarios.
Am J Psychiatry 2006; 163:913–918
• But:
• Conducted in one institution
• Based on a questionnaire with voluntary submission
• Thus risk for major bias
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
A parallel: the ‘categorical – dimensional’ debate
on the classification of mental disorders
• Rough distinction:
– “Categorical”: ‘mental disorders’ can be classified as single,
discrete and mutually exclusive types, of which a particular
patient does or does not exhibit an instance.
– “Dimensional”: any particular ‘mental disorder’ in a patient is
an instance of just one single type and differences between cases
are a matter of ‘scale’.
• ‘Rough’, because
– the literature is huge and vague
– descriptions are (philosophically) very incoherent
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The categorical view
• Recognizes various mental
disorder types
• Accepts that disorders are
manifested through signs and
symptoms, either ‘marker’ or
‘constitutional’
• Provides diagnostic criteria to
guide the clinician in making a
diagnosis.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Evolution of the DSM (1)
• Psychodynamic period: I and II, 1952-1980
– no sharp distinction between normal and abnormal.
– psychosis / neurosis scale
– all disorders viewed as reactions (leading to behavior)
to environmental events,
– everyone is more or less abnormal,
– inclusion in the manual presumes abnormality.
• DSM-II contained “homosexuality” as mental
disorder which was removed in 1973 by vote.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Evolution of the DSM (2)
• Adoption of biomedical model: III, IV 1980 – Clear distinction between normal/abnormal
– Introduction of diagnostic criteria
– Latest version is from 2000
• DSM-V: foreseen for 2011
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
An example: Anxiety Disorders
•
•
•
•
•
•
•
•
Acute Stress Disorder
Agoraphobia
Generalized Anxiety Disorder
Obsessive-Compulsive Disorder
Panic Disorder
Posttraumatic Stress Disorder
Separation Anxiety Disorder
Social Phobia Specific Phobia
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Example of diagnostic criteria
Asperger Syndrome
• Severe and sustained impairment in social interaction
• The development of restricted, repetitive patterns of behaviour, interests, and
activities.
• The disturbance must cause clinically significant impairment in social,
occupational, or other important areas of functioning.
• In contrast to Autistic Disorder, there are no clinically significant delays in
language (eg: single words are used by age 2 years, communicative phrases are
used by age 3 years).
• There are no clinically significant delays in cognitive development or in the
development of age-appropriate self-help skills, adaptive behaviour (other than in
social interaction), and curiosity about the environment in childhood.
• The diagnosis is not given if the criteria are met for any other specific Pervasive
Developmental Disorder or for Schizophrenia.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
‘Making’ a DSM diagnosis
• Axis I:
major mental disorders, developmental
disorders and learning disabilities
• Axis II: underlying pervasive or personality conditions,
as well as mental retardation
• Axis III: any nonpsychiatric medical condition
("somatic")
• Axis IV: social functioning and impact of symptoms
• Axis V: Global Assessment of Functioning (on a scale
from 100 to 0)
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
By the way: frequent terminological confusions
• ‘Diseases and diagnoses are the principal ways in
which illnesses are classified and quantified, and
are vital in determining how clinicians organize
health care.’
Ann Fam Med 1(1):44-51, 2003.
• ‘MedDRA […] is a standardized dictionary of
medical terminology [ … which …] includes
terminology for symptoms, signs, diseases and
diagnoses.’
Medical Dictionary for Regulatory Activities
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Disease/disorder in SNOMED-CT
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Algorithmic approach (e.g. DSM-IVPC)
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Sometimes not really useful
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
DSM under fire (1)
• severely ill inpatients often meet criteria for more than
one DSM-IV personality disorder
 suggests a high rate of co-morbidity, however in absence of any
medical or etiologic reason for such a situation
• many outpatients do not meet the criteria for any of the
specific categories identified in DSM-IV;
• patients with the same categorical diagnosis often vary
substantially with respect to which diagnostic criteria
were used to make the diagnosis, so that two patients with
the same diagnosis can manifest very different signs and
symptoms;
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
DSM under fire (2)
• frequent revision of the diagnostic thresholds
separating what is normal from what is disordered
 it is as if given disorders would appear and disappear
in course of time;
• a number of the diagnostic categories mentioned
in DSM-IV lack any developing scientific base for
an understanding of the corresponding disorder
types
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The Dimensional Approach (1)
• Mental processes and behavior follow
traits/phenomena which are to be seen as
continuous variables along continua on which all
members of the population can be located. These
continua extend to both normal and pathological
phenotypes.
• These traits are on a par with properties such as
temperature, weight, …
 Homo sapiens is not further subdivided in subspecies
according to weight, temperature, …
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The Dimensional Approach (2)
• “Diagnostic categories defined by their syndromes should
be regarded as valid only if they have been shown to be
discrete entities with natural boundaries that separate
them from other disorders.”
Kendell R, Jablensky A. Distinguishing between the validity and
utility of psychiatric diagnoses. Am J Psychiatry 2003; 160:4–12.
• “there is no empirical evidence for natural boundaries
between major syndromes” … “the categorical approach
is fundamentally flawed”
Cloninger CR: A new conceptual paradigm from genetics and psychobiology
for the science of mental health. Aust N Z J Psychiatry 33:174–186, 1999.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Is there empirical evidence for this boundary ?
And if not, do these mountains exist ?
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Then also these guys would be from the same species
W.N. Kellogg, L.A. Kellogg. The Ape and The Child; A Comparative Study of the Environmental
Influence Upon Early Behavior. Hafner Publishing Company, New York and London, 1967.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Attempts to resolve the problem (1)
• Mental disorders as ‘practical kinds’
– ‘stable patterns that can be identified with varying
levels of reliability and validity’ and which are justified
by their usefulness for specific purposes – such as
giving an appropriate treatment
Zachar, P. 2000b. Psychiatric disorders are not natural kinds.
Philosophy, Psychiatry and Psychology 7:167–94.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Basis: ‘epistemic value commitments’
• ‘values involved in making and advancing
epistemologically-relevant claims, such as
scientific ones’:
Coherence
Instrumental efficacy
Consistency
Originality
Comprehensiveness Relevance
Fecundity
Precision
Simplicity
JZ. Sadler. Epistemic Value Commitments in the Debate over Categorical vs. Dimensional
Personality Diagnosis. Philosophy, Psychiatry, & Psychology 3.3 (1996) 203-222
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Attempts to resolve the problem (2)
Non-arbitrary basis for drawing a categorical distinction
No
Yes
Non-kind
‘severity’
‘neuroticism’
This basis is an objective discontinuity
No
Yes
Practical kind
‘essential hypertension’
‘depression’
Haslam N. Kinds of Kinds: A
Conceptual Taxonomy of
Psychiatric Categories.
Philosophy, Psychiatry, &
Psychology, 9 (2002), 203-218
The discontinuity is sharp and binary
No
Yes
Fuzzy kind
‘borderline personality’
The discontinuity is constituted by an ‘essence’
No
Yes
Discrete kind
‘melancholia’
Natural kind
‘Williams syndrome’
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Williams Syndrome
www.thefencingpost.com/mary/
www.williams.ngo.hu/
medgen.genetics.utah.ed
u/.../pages/williams.htm
http://www.williams-syndrome.org/
Williams Syndrome (WS) is a rare genetic disorder characterized by
mild to moderate mental retardation or learning difficulties, a distinctive
facial appearance, and a unique personality that combines
overfriendliness and high levels of empathy with anxiety.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
DSM-IV-TR currently plays it both ways
• “In DSM-IV, there is no assumption that each
category of mental disorder is a completely
discrete entity with absolute boundaries dividing it
from other mental disorders or from no mental
disorder”
• “DSM-IV is a categorical classification that
divides mental disorders into types based on
criterion sets with defining features”
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text
Revision [DSM-IV-TR]; AmericanPsychiatric Association [APA], 2000, p. xxxi).
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
… but asks for research in preparation of DSM-V
• Some desiderata:
1. generate acceptable definitions for mental disorder; disease and
illness;
2. provide a framework for validating the correctness of
assignments of instances to disorder categories;
3. provide assessment of the arguments to the effect that a
dimensional view is needed in addition to the categorical view;
4. reduce the discrepancies between DSM-V and ICD-11;
5. ensure that DSM-V can be used cross-culturally;
6. ensure that DSM-V can be used in non-psychiatric settings.
Kupfer DJ, First MB, Regier DA (eds.) A Research Agenda for DSM-V.
American Psychiatric Association 2002.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
… but asks for research in preparation of DSM-V
• to establish, among many other things,
– under which circumstances one or the other of the two views
should be adopted,
– the categories which will then need to be recognized, and
– the thresholds for associated criteria.
• The proposed research is to be based on large scale crosscultural clinical, genetic, pathophysiologic, etiologic and
outcome assessments,
and thus requires the collection of vast
amounts of data of diverse sorts.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Our proposal
1. Address the theoretical issues in the research
agenda within the framework of
1. Basic Formal Ontology
2. Granular Partition Theory
3. as they are applied in the Ontology of Biomedical
Reality.
2. Use Referent Tracking for keeping track of the
instance data that will be generated when
carrying out the field studies.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Applicability criteria
• give mental health patients the best possible care in spite of ongoing
changes and controversies in psychiatry,
• allow health care workers to remain faithful to their existing beliefs as
concerns mental disorders as long as these beliefs do not stand in
conflict with accumulated evidence,
• minimize the burden of carrying out the data collection, especially
when the data are to be collected by clinicians not directly involved in
the studies,
• ensure that the data remain useful even when research questions
change, and
• satisfy privacy and security issues as expressed in HIPAA rules and
other provisions.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Basic Formal Ontology (BFO)
• Based on philosophical realism
– acknowledge only those entities which exist in biological reality,
– reject all those types of putative negative entities – absences, non-existents,
possibilia, and the like – which are postulated merely as artifacts of specific
logical or computational frameworks.
– BFO can accept the existence of processes such as ‘developing peer
relationships’ or ‘seeking to share enjoyment’, but not the ‘existence’ of
absences thereof which are two criteria for autistic disorder.
• Fundamental distinctions:
–
–
–
–
Particulars (p) / universals (u)
Continuants / occurrents
Dependent / independent entities
3 major sorts of relations: <p,p> <p,u> <u,u>
Grenon P, Smith B, Goldberg L. Biodynamic ontology: applying BFO in the biomedical domain.
In DM Pisanelli (ed.), Ontologies in Medicine, Amsterdam: IOS Press, 2004, p. 20-38.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Granular Partition Theory
• A highly general framework for understanding the ways in which,
when cataloguing, classifying, mapping or diagnosing a certain
portion of reality, we divide up or partition this reality at one or
more levels of granularity.
Bittner T, Smith, B. A taxonomy of granular partitions, in D Montello (ed.),
Spatial Information Theory. (Lecture Notes in Computer Science 2205), 28–43.
• Applied in a calculus for quality assurance in evolving ontologies
and data-repositories by distinguishing:
• (1) the level of reality
• (2) the cognitive representations of this reality
• (3) the publicly accessible concretizations of these cognitive
representations in artifacts of various sorts.
Ceusters W, Smith B. A Realism-Based Approach to the Evolution of Biomedical Ontologies.
Forthcoming in Proceedings of AMIA 2006, Washington DC, November 11-15, 2006.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Referent Tracking
• Purpose:
– explicit reference to the concrete individual entities
relevant to the accurate description of each patient’s
condition, therapies, outcomes, ...
• Method:
– Introduce an Instance Unique Identifier (IUI) for each
relevant particular (individual) entity
Ceusters W, Smith B. Strategies for Referent Tracking in Electronic Health Records.
J Biomed Inform. 2006 Jun;39(3):362-78.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Essentials of Referent Tracking
• Generation of universally unique identifiers;
• deciding what particulars should receive a IUI;
• finding out whether or not a particular has already been
assigned a IUI (each particular should receive maximally
one IUI);
• using IUIs in the EHR, i.e. issues concerning the syntax
and semantics of statements containing IUIs;
• determining the truth values of statements in which IUIs
are used;
• correcting errors in the assignment of IUIs.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Work in progress
• Required (core) ontological entities
– For sure:
• normal anatomical structure, pathological anatomical
structure, pathological formation, organismal process,
pathological process, disease, course of disease, clinical
picture
– Probably:
• behavioural process, behavioural quality, cognitive process,
sign, symptom
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Some temptative definitions (1)
• ‘pathological process’:
– an organismal process that contributes to the
dysfunctioning of an anatomical structure within the
same organism.
• ‘disease’:
– a disposition which, when realized, affects the wellbeing of the organism or any of its parts.
• this entity is NOT what usually is referred to by the term
‘disease’ in general medical language.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Some temptative definitions (2)
• ‘course of disease’:
– the process composed of pathological processes that
realize the disease.
• ‘clinical picture’:
– the unit, comparable to physical-behavioural units in
which organisms behave, formed by the course of the
disease and the anatomical structures and pathological
formations that participate in the pathological
processes, and, by its nature, has both temporal and
spatial parts.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Beliefs about the relevant portion of reality (1)
• P1. A particular person may exhibit parts of a clinical
picture.
– Most relevant in the domain of psychiatry are pathological
behavioural or cognitive processes such as tics, confabulations,
perseverations and abnormal thought formations.
• P2. A particular clinical picture
– starts to exist at the time the first pathological process that is a
realization of a particular disease starts to exist.
– ceases to exist when the last pathological process that is a
realization of a particular disease comes to an end, and when
there are no more pathological formations or pathological
anatomical structures that were formed by the course of the
disease.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Beliefs about the relevant portion of reality (2)
• P3.A particular disease exists in a particular
person before a particular clinical picture is
present in that person.
• P4.There can be no clinical picture without a
disease.
• P5.A person may exhibit different particular
diseases during his lifetime, some or all of them of
the same disease type, and some or all of them at
the same time or during overlapping time spans.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Beliefs about the relevant portion of reality (3)
• P6.The course of some particular disease may lead
to other particular diseases of the same or different
disease types in a particular person.
• P7.A particular disease of type A in one person
may lead to a particular clinical picture of type B,
while a particular disease of that same type A in
another person may lead to a clinical picture of a
totally different type.
• …
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Application in preparation of DSM-V (1)
• For each ‘mental disorder’
– Express the criteria in terms of the core ontological
entities and their possible co-occurrence in concrete
cases
• For each particular case (‘disorder in patient’)
– Describe the case using the core ontological entities
and their actual co-occurrence, i.e.
• Assign IUIs
• Express in RT-formalism
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Application in preparation of DSM-V (2)
• Create an adequate IT infrastructure:
– For case registration: RTU-based electronic patient
record
– For data collection: RTU back-end
• Use the DSM-criteria as hypotheses that need to
be validated on the basis of the data collected, and
adjust when needed.