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R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
PHI548 - Biomedical Ontology,
Philosophical Aspects of Health and Disease.
Defining Mental Disease.
October 8, 2010; 4.00 PM - 6.00 PM
Department of Philosophy, Buffalo NY
Park Hall 148
Werner CEUSTERS1 and Barry SMITH2
1,2 Ontology
Research Group, Center of Excellence in Bioinformatics and Life Sciences
1 Department of Psychiatry, University at Buffalo, NY, USA
2 Department of Philosophy, University at Buffalo, NY, USA
R T U New York State
Center of Excellence in
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Structure of this presentation
1. Do mental disorders exist and if so, what are
they?
– Overview of relevant positions
2. Foundations of our work
– Methodological
– Representational
3. Towards an ontology for mental health
4. Utility of our work
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Center of Excellence in
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R T U New York State
Center of Excellence in
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Mental disorders
and
‘mental disorders’
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Center of Excellence in
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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
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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.
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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).
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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.
–…
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What is a mental disorder ?
• The social-constructivist position:
– mental disorder is a value-laden social construct with no
counterpart in biomedical reality.
• The objectivist position:
– mental disorders are natural entities that could be understood in
biological terms.
• The hybrid position:
– Mental disorder is harmful dysfunction.
• the social definition of "harm" is counterbalanced by a factual component
of a malfunctioning internal mechanism causing objective dysfunction.
Jablensky A: Does psychiatry need an overarching concept of "mental disorder"? World Psychiatry 2007, 6:157-158.
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A terminological and ontological problem (1)
• WHO: Lexicon of psychiatric and mental health
terms. Second edn. Geneva: WHO; 1994.
– ‘mental disorder’: an imprecise term designating any disorder of
the mind, acquired or congenital
– organic mental disorder: a range of mental disorders grouped
together on the basis of their having in common a demonstrable
etiology in cerebral disease, brain injury, or other insult,
leading to cerebral dysfunction.
• Does WHO rule out the existence of mental
disorders which are not due to brain disorder?
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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
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… 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
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A terminological and ontological problem (2)
• Szasz: ‘mental illness is a myth whose function it
is to disguise and thus render more palatable the
bitter pill of moral conflicts in human relations’
– Szasz TS: The Myth of Mental Illness. American Psychologist
1960, 15:113-118.
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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
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Our interpretation of Szasz (1)
• the group of persons ‘known to manifest various
peculiarities or disorders of thinking and behavior’ and
about which it is therefore said that they have a mental
illness, consists of two subgroups:
– (1) those for which there is an underlying brain
disorder perhaps not yet discoverable by what the state
of the art is able to offer; and
– (2) those who exhibit in their behavior a ‘deviance …
from certain psychosocial, ethical, or legal norms’ as
judged by themselves, by clinicians, or by others.
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Our interpretation of Szasz (2)
• those for which there is an underlying brain disorder
perhaps not yet discoverable by what the state of the art is
able to offer
– would be better described as having a brain disorder,
• those who exhibit in their behavior a ‘deviance … from
certain psychosocial, ethical, or legal norms’ as judged
by themselves, by clinicians, or by others
– while they might indeed have ‘problems of living’, and thus be
suffering, are not suffering because of some disorder of a
special, mental kind.
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Our interpretation of Szasz (3)
• Szasz hereby rejects as fallacious the view which
regards social intercourse ‘as something inherently
harmonious, its disturbance being due solely to
the presence of “mental illness” in many people’.
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A terminological and ontological problem (3)
• Adoption of a generic, presumably universal,
definition of "mental disorder" would be
premature. It may cause more harm than good to
psychiatry.
– Jablensky A: Does psychiatry need an overarching
concept of "mental disorder"? World Psychiatry
2007, 6:157-158.
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Center of Excellence in
Bioinformatics & Life Sciences
Jablensky’s arguments (1)
• A terminological argument
– Neither disease nor health has ever been strictly and
unambiguously defined in terms of finite sets of observable
referential phenomena.
• Arguments of utility:
– the medical person is least concerned with what healthy and
sick mean in general ... we do not need the concept of ‘illness in
general’ at all
• Jaspers K. General psychopathology. Birmingham: Birmingham University Press; 1963.
– doctors do not concern themselves with maximizing the
evolutionary advantages of the human race as a whole, but with
aiding individuals
• Toon PD. Defining "disease" - classification must be distinguished from evaluation. J Med Ethics.
1981;7:197–201.
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Jablensky’s arguments (2)
• Ontological argument:
– we now know that no such general and uniform concept exists.
• Jaspers K. General psychopathology ,Birmingham: Birmingham University Press; 1963..
• Epistemological argument:
– the emergence of molecular genetic classifications of large
groups of diseases, and the concomitant availability of genetic
diagnostic tests, raise the possibility that the entire taxonomy of
human disease may eventually be revised.
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Missing the nail
• A definition of ‘mental disorder’ should be such
– (a) that it ‘can be used as a criterion for assessing potential
candidates for inclusion in the classification, and deletions from
it’ and
– (b) that there should be ‘at least no ambiguity about the reason
that individual candidate diagnoses are included or excluded’.
•
Kupfer D, First M, Regier D (Eds.): A Research Agenda for DSM-V, American Psychiatric Association; 2002.
• This doesn’t address at all what candidate mental
disorders have in common, i.e. what differentiates them
from other, non-mental disorders.
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ICD-10 Mental disease guidelines
• Two distinct ones:
– The ICD-10 Classification of Mental and Behavioural
Disorders: Clinical descriptions and diagnostic
guidelines. Geneva: World Health Organization; 1992.
– The ICD-10 Classification of Mental and Behavioural
Disorders: Diagnostic criteria for research. Geneva:
World Health Organization; 1993.
• Yet, an individual entity, such as a mental disorder
in a specific patient, does not change when looked
at from distinct perspectives.
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Goal of mental disease guidelines
• Goal: to reduce the variability in coding caused by
two sorts of disagreement which can arise when
diagnoses are being made:
– differences in opinion amongst clinicians about what type of
mental disorder a patient with a certain configuration of
symptoms and test results is suffering from;
• in this case the disagreement is about the diagnosis independent of the
diagnostic options offered by the ICD or DSM;
– differences in opinion about what ICD or DSM classification
code should be used in case there is agreement about a
diagnosis.
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Pies’ model
• Introduces a 5-stage account of how our scientific
understanding of a mental disease condition might
evolve over time. The goal is a framework that is
designed to allow us to determine:
whether a condition represents, in the first place, dis-ease and,
secondarily, whether it constitutes a specific disease, on a par with,
say, bipolar I disorder.
For example, how do we decide whether to consider “pathological
bigotry” and “internet addiction” as specific mental disorders?
Pies R: What should count as a mental disorder in DSM-V. Psychiatric Times 2009, 26.
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The basics: existence (in a patient) criterion
• ‘prolonged and severe suffering and incapacity in
the affective, cognitive, or interpersonalbehavioral realms’
– Pies R: What should count as a mental disorder in DSM-V.
Psychiatric Times 2009, 26.
• based on:
– Kendell RE: The concept of disease and its implications for
psychiatry. British Journal of Psychiatry 1975, 127:305-315.
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Pies’ 5-stage model (1)
• Stage 1: patient’s acknowledgement of daily
substantial and prolonged suffering and
incapacity that is ‘specified in terms of social and
vocational impairment, impaired vital functions,
and distortions in the phenomenological realm
(feeling “totally worthless,” “like I’m nothing”)’.
– This must be acknowledged as an intrinsic element of
the condition and not simply as a consequence of
society’s punitive responses to the person’s behavior.
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Pies’ 5-stage model (2)
• Stage 2:
– availability of a general syndromal description of the
condition supported by evidence that the constituent
signs and symptoms reliably ‘hang together’ over long
periods and in geographically distant populations.
• Student: ‘Does it say that the signs and symptoms
endure over time and that they are (or could be)
present regardless of the physical location of the
patient?’
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Pies’ 5-stage model (3)
• Stage 3:
– the syndrome has been characterized by authoritive
sources in terms of usual course, outcome,
comorbidity, familial pattern, and response to
treatment;
– there may also be preliminary data on pathophysiology
and biomarkers, and a more specific understanding of
the afflicted person’s phenomenology
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Pies’ 5-stage model (4)
• Stage 4:
– known pathophysiology, cause, a specific set of
biomarkers, and
– in some cases an inheritance pattern for the condition
(or for multiple conditions that become identified as
separate entities only after Stage 2).
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Pies’ 5-stage model (5)
• Stage 5:
– availability of a precise chromosomal and biomolecular
etiology, and
– a specification of the phenomenology, for all disease
subtypes.
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Foundations for an
Ontology of Mental Health
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Center of Excellence in
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Foundations for our work
• Methodological foundations:
– Ontological Realism
– Open Biomedical Ontologies Foundry
• Representational foundations:
– Basic Formal Ontology
– Relation Ontology
– Ontology of General Medical Science
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Ontology
• In philosophy:
– Ontology (no plural) is the study of what entities exist and how they
relate to each other;
• In computer science and many biomedical informatics
applications:
– An ontology (plural: ontologies) is a shared and agreed upon
conceptualization of a domain;
• The realist view within the Ontology Research Group
combines the two:
– We use Ontological Realism, a specific methodology that uses
ontology as the basis for building high quality ontologies, using
reality as benchmark.
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The basis of Ontological Realism
1. There is an external reality which
is ‘objectively’ the way it is;
2. That reality is accessible to us;
3. We build in our brains cognitive
representations of reality;
4. We communicate with others
about what is there, and what we
believe there is there.
Smith B, Kusnierczyk W, Schober D, Ceusters W. Towards a Reference Terminology for Ontology Research and Development in the
Biomedical Domain. Proceedings of KR-MED 2006, Biomedical Ontology in Action, November 8, 2006, Baltimore MD, USA
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Ontological Realism makes three crucial distinctions
1. Between data and what data are about;
2. Between continuants and occurrents;
3. Between what is generic and what is specific.
Smith B, Ceusters W. Ontological Realism as a Methodology for Coordinated Evolution of Scientific Ontologies.
Applied Ontology, 2010. (forthcoming)
35
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Ontological Realism makes crucial distinctions
• Between data and what data are about:
– Level 1 entities (L1):
• everything what exists or existed
• some are referents
• some are L2, some are L3, none are L2 and L3
(‘are’ used informally)
– Level 2 entities (L2): beliefs
• all are L1
• some are about other L1-entities but none about themselves
– Level 3 entities (L3): expressions
• all are L1, none are L2
• some are about other L1-entities and some about themselves
36
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37
New York State
R
T
U
L3
Center of Excellence in
Bioinformatics & Life Sciences
L2
L1
38
New York State
R
T
U
L3
Center of Excellence in
OBOFoundry
Bioinformatics & Life Sciences
L2
L1
39
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Ontological Realism makes crucial distinctions
• Between data and what data are about;
• Between continuants and occurrents:
– obvious differences:
• a person versus his life
• a disease versus its course
• space versus time
– more subtle differences (inexistent for flawed models e.g. HL7-RIM):
• observation (data-element) versus observing
• diagnosis versus making a diagnosis
• message versus transmitting a message
40
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Is depression considered a continuant or
occurrent?
• What do we mean by ‘depression’ ?
– The name of some disease ?
•  continuant
– A bout of feelings of being worth nothing, sobbing,
appearance of suicidal thoughts, …
•  occurrent
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Three levels of reality in Ontological Realism
Representation and Reference
representational units
(3) Representational units in various
forms about (1), (2) or (3)
cognitive
units
communicative
units
universals
particulars
(2) Cognitive entities which are our
beliefs about (1)
(1) Entities with objective existence
which are not about anything
First Order Reality
42
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No putative negative entities
• DSM-IV criteria for autistic disorder:
– failure to develop peer relationships appropriate to
developmental level
– a lack of spontaneous seeking to share enjoyment,
interests, or achievements with other people
– lack of varied, spontaneous make-believe play or social
imitative play appropriate to developmental level.
• How to represent this ?
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How to represent this ‘negative findings’
• Lack of spontaneous make-believe play in some
child (John) would thus be described in roughly
this way:
– Not (Jim participant_of some instance of MAKEBELIEVE PLAY).
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Basic Formal Ontology
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The representational square
Generic
L3.
Representation
L2. Beliefs
(knowledge)
L1.
First-order
reality
‘person’ ‘drug’
‘insulin’
DIAGNOSIS
INDICATION
PATHOLOGICAL
STRUCTURE
DRUG
MOLECULE
PERSON
DISEASE
PORTION OF
INSULIN
Basic Formal Ontology
Specific
‘W. Ceusters’
‘my sugar’
my doctor’s
work plan
my doctor’s
diagnosis
my doctor’s
computer
my doctor
me
my NIDDM
my blood
glucose level
Referent Tracking
46
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Disposition
• A disposition is a realizable entity which is such
that
(1) if it ceases to exist, then its bearer is physically
changed,
(2) whose realization occurs, in virtue of the
bearer’s physical make-up, when this bearer is in
some special physical circumstances
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The essential pieces
dependent
continuant
material
object
t
history
me
… at t
spatial
region
instanceOf
t
participantOf at t
some
quality
spacetime
region
t
occupies
my
life
my 4D
STR
projectsOn at t
located-in at t
some
spatial
region
temporal
region
projectsOn
some
temporal
region
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OBO Foundry ontologies in BFO-dress
RELATION
TO TIME
GRANULARITY
CONTINUANT
INDEPENDENT
ORGAN AND
ORGANISM
Organism
(NCBI
Taxonomy)
CELL AND
CELLULAR
COMPONENT
Cell
(CL)
MOLECULE
DEPENDENT
Anatomical
Organ
Entity
Function
(FMA,
(FMP, CPRO) Phenotypic
CARO)
Quality
(PaTO)
Cellular
Cellular
Component Function
(FMA, GO)
(GO)
Molecule
(ChEBI, SO,
RnaO, PrO)
OCCURRENT
Molecular Function
(GO)
Biological
Process
(GO)
Molecular Process
(GO)
49
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Ontology of General Medical Science
First ontology in which the
L1/L2/L3 distinction is used
Scheuermann R, Ceusters W, Smith B. Toward an Ontological Treatment of Disease and Diagnosis. 2009
AMIA Summit on Translational Bioinformatics, San Francisco, California, March 15-17, 2009;: 116-120.
Omnipress ISBN:0-9647743-7-2
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Motivation
• Clarity about:
– disease etiology and progression
– disease and the diagnostic process
– phenotype and signs/symptoms
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Big Picture
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Approach
• a disease is a disposition rooted in a physical disorder in the
organism and realized in pathological processes.
produces
etiological process
bears
disorder
realized_in
disposition
pathological process
produces
diagnosis
interpretive process
produces
signs & symptoms
participates_in
abnormal bodily features
recognized_as
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Cirrhosis - environmental exposure
•
•
•
•
•
•
•
Etiological process - phenobarbitolinduced hepatic cell death
– produces
Disorder - necrotic liver
– bears
Disposition (disease) - cirrhosis
– realized_in
Pathological process - abnormal tissue
repair with cell proliferation and
fibrosis that exceed a certain
threshold; hypoxia-induced cell death
– produces
Abnormal bodily features
– recognized_as
Symptoms - fatigue, anorexia
Signs - jaundice, splenomegaly
•
•
•
•
•
•
•
Symptoms & Signs
– used_in
Interpretive process
– produces
Hypothesis - rule out cirrhosis
– suggests
Laboratory tests
– produces
Test results – documentation of
elevated liver enzymes in serum
– used_in
Interpretive process
– produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
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Foundational Terms (1)
• Disorder =def. –
– A causally linked combination of physical components that is
• (a) clinically abnormal and
• (b) maximal, in the sense that it is not a part of some larger such
combination.
• Pathological Process =def. –
– A bodily process that is a manifestation of a disorder and is
clinically abnormal.
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Clinically abnormal
• - something is clinically abnormal if:
– (1) is not part of the life plan for an organism of the
relevant type (unlike aging or pregnancy),
– (2) is causally linked to an elevated risk either of pain
or other feelings of illness, or of death or dysfunction,
and
– (3) is such that the elevated risk exceeds a certain
threshold level.
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Foundational Terms (2)
• Disorder =def. – A causally linked combination of
physical components that is (a) clinically abnormal and
(b) maximal, in the sense that it is not a part of some
larger such combination.
• Pathological Process =def. – A bodily process that is a
manifestation of a disorder and is clinically abnormal.
• Disease =def. –
– A disposition (i) to undergo pathological processes that (ii)
exists in an organism because of one or more disorders in that
organism.
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Disease/disorder in SNOMED-CT
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Disease course
• the totality of all PROCESSES through which a
given DISEASE instance is realized .
• multiple DISEASE COURSES will be associated
with the same DISORDER type, for example in
reflection of the presence or absence of
pharmaceutical or other interventions, of
differences in environmental influence, and so
forth.
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What does “environmental influences” encompass?
• Student: ‘I would say that it includes
psychological and/or physical (external)
influences:
– lead poisoning from exposure to lead-based paint.
– traumatic or particularly “impression-giving” event.
Such events might be a child observing their parents
physically abusing one another.’
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Diagnosis
• Clinical Picture =def. – A representation of a
clinical phenotype that is inferred from the
combination of laboratory, image and clinical
findings about a given patient.
• Diagnosis =def. –
– A conclusion of an interpretive process that has as
input a clinical picture of a given patient and as output
an assertion to the effect that the patient has a disease
of such and such a type.
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Obvious?
• ‘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
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A well-formed diagnosis of ‘pneumococal pneumonia’
• A configuration of
Disease
representational units;
isa
• Believed to mirror the
person’s disease;
Pneumococcal pneumonia
• Believed to mirror the
disease’s cause;
Instance-of at t1
• Refers to the universal
of which the disease is
#78
#56
John’s relevant caused
John’s
believed to be an
portion
by
Pneumonia
of pneumococs
instance.
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Some motivations and consequences (1)
• No use of debatable or ambiguous notions such as
proposition, statement, assertion, fact, ...
• The same diagnosis can be expressed in various
forms.
Disease
isa
Pneumococcal pneumonia
Instance-of at t1
#78
caused
by
#56
Portion of
pneumococs
caused
by
isa
Pneumonia
Instance-of
Instance-of at t1
at t1
#56
caused
by
#78
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Some motivations and consequences (2)
• A diagnosis can be of level 2 or level 3, i.e. either
in the mind of a cognitive agent, or in some
physical form.
• Allows for a clean interpretation of assertions of
the sort ‘these patients have the same diagnosis’:
 The configuration of representational units is such
that the parts which do not refer to the particulars
related to the respective patients, refer to the same
portion of reality.
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Bioinformatics & Life Sciences
Distinct but similar diagnoses
Pneumococcal pneumonia
Instance-of at t1
#78
John’s portion
of pneumococs
caused
by
Instance-of at t2
#56
#956
John’s
Pneumonia
Bob’s
pneumonia
caused
by
#2087
Bob’s portion
of pneumococs
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Some motivations and consequences (3)
• Allows evenly clean interpretations for the wealth
of ‘modified’ diagnoses:
– With respect to the author of the representation:
• ‘nursing diagnosis’, ‘referral diagnosis’
– When created:
• ‘post-operative diagnosis’, ‘admitting diagnosis’, ‘final
diagnosis’
– Degree of belief:
• ‘uncertain diagnosis’, ‘preliminary diagnosis’
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontology for Mental Health
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Ontology for Mental Health V0.0001
Legend
continuant
representation
process
disjunction
MHO
BFO/OGMS
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
MENTAL PROCESS (L1,U)
• =def.
BODILY PROCESS which brings into being,
sustains or modifies a COGNITIVE
REPRESENTATION or a BEHAVIOR INDUCING
STATE
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
BEHAVIOR INDUCING STATE (L1,U)
• =def.
BODILY QUALITY inhering in a MENTAL
FUNCTIONING RELATED ANATOMICAL
STRUCTURE which leads to BEHAVIOR of some
specific sort
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
BEHAVIOR (L1,U)
• =def.
a PROCESS having PROCESSES as parts in which
an ORGANISM participates as agent in response to
external or internal stimuli and following some
pattern which is dependent upon some
combination of that ORGANISM’s internal state
and external conditions. (Derived from the Gene
Ontology)
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
MENTAL FUNCTIONING RELATED ANATOMICAL
STRUCTURE (L1,U)
• =def.
ANATOMICAL STRUCTURE in which there inheres
the DISPOSITION to be the agent of a MENTAL
PROCESS
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Disorder related definitions
• MENTAL DISORDER =def. DISORDER in a MENTAL
FUNCTIONING RELATED ANATOMICAL STRUCTURE
• PATHOLOGICAL MENTAL PROCESS =def.
PATHOLOGICAL PROCESS which is the manifestation of
a MENTAL DISORDER
• MENTAL DISEASE =def. a DISEASE which is a
DISPOSITION to undergo PATHOLOGICAL MENTAL
PROCESSES
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Diagnosis related entities (skip)
• DIAGNOSIS OF MENTAL DISEASE =def.
– DIAGNOSIS asserting the presence of an instance of
MENTAL DISEASE in a given ORGANISM
• MARKER FEATURES FOR DISEASE X =def.
– REPRESENTATION which is a collection of DISEASE
PICTURE COMPONENTS which are characteristic for
DISEASE X (where ‘X’ serves as placeholder for some
disease name)
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Use to improve classification systems
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Future work: a template like this for each mental disease
•
•
•
•
•
•
•
Etiological process - phenobarbitolinduced hepatic cell death
– produces
Disorder - necrotic liver
– bears
Disposition (disease) - cirrhosis
– realized_in
Pathological process - abnormal tissue
repair with cell proliferation and
fibrosis that exceed a certain
threshold; hypoxia-induced cell death
– produces
Abnormal bodily features
– recognized_as
Symptoms - fatigue, anorexia
Signs - jaundice, splenomegaly
•
•
•
•
•
•
•
Symptoms & Signs
– used_in
Interpretive process
– produces
Hypothesis - rule out cirrhosis
– suggests
Laboratory tests
– produces
Test results – documentation of
elevated liver enzymes in serum
– used_in
Interpretive process
– produces
Result - diagnosis that patient X has a
disorder that bears the disease
cirrhosis
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
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
Algorithmic approach (e.g. DSM-IVPC)
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
cross-cultural 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
Use in study design and data collection
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Typical approach (1)
• Building a huge matrix with patient cases in one dimension
and patient characteristics in the other dimension
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Typical approach (2)
• Use statistical correlation techniques to find associations
between characteristics and (dis)similarities between cases
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Fundamental questions
1.
2.
What is a characteristic ?
What (sorts of) characteristics (relevant for psychiatry) go in here ?
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
ch6
...
case1
case2
case3
case4
case5
case6
...
3.
4.
5.
How can we make distinct studies comparable?
Because such matrices tend to become huge, how can we make analysis feasible ?
How can we make results re-usable?
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Q1: what is a characteristic ?
– it is for sure not a category entities can belong to: there
is no natural class of entity for which the name
‘characteristic’ would be appropriate;
– there is also no particular entity that you could point to
and state ‘that over there is the only existing
characteristic’
– thus: there are no characteristics, there is just the term
‘characteristic’ which is used to describe that some
entities are (acknowledged to be) in some way of
interest in some context and for some purpose.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
This requires rephrasing Q2
What (sorts of) characteristics (relevant for
psychiatry) go in here?
What entities described as being characteristic for
psychiatric purposes should be represented here?
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Examples
Universals
• portion of C17H19ClN2S.HCl
Independent • human being
Continuant • gene
Continuant
Dependent
Continuant
Particulars
• portion of chlorpromazine in this tablet
• me
• the HTR2A gene on chromosome 13 of the
most frontal cell in the tip of my nose
• shape
• the shape of my nose
• temperature
• the temperature of the chlorpromazine tablet in
front of me
• length
• the length of that HTR21 gene
• change in shape
• unfolding of a DNA molecule
• motion
• the circulation of a chlorpromazine molecule in
my bloodstream
• rise in temperature
• the rise of my body temperature while teaching
this seminar
Occurrent
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Q3: How can we make distinct studies comparable?
• Map any characteristic used to relevant, standard
and high quality ontologies
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The positive effects of appropriate mappings
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
ch6
...
ch6
...
case1
case2
case3
case4
case5
case6
...
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
Characteristics
Cases
ch6
...
ch1
case1
case1
case2
case2
case3
case3
case4
case4
case5
case5
case6
case6
...
...
ch2
ch3
ch4
ch5
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
The positive effects of appropriate mappings
Characteristics
Cases
ch1 ch2 ch3 ch4 ch5 ch6 ...
case1
case2
–
–
–
–
case3
case4
case5
case6
...
Characteristics
Cases
ch1
ch2
ch3
ch4
ch5
Characteristics
Cases
ch6 ...
ch1
case1
case1
case2
case2
case3
case3
case4
case4
case5
case5
case6
case6
...
...
• identification of ontological
relations prior to statistical
correlation:
ch2
ch3
ch4
ch5
ch6 ...
ch1 and ch4
ch1 and ch5
ch1 and ch2
…
• Contributes to answering
‘Q4: how can we make
analysis feasible’
– this method allows for datareduction without information
loss.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Filling the grid
• We know now that labels from appropriate
ontologies go here
Characteristics
Cases
ch1
case1
case2
case3
case4
case5
case6
...
• But, what goes here?
ch2
ch3
ch4
ch5
ch6
...
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Remember we had this …
Universals
• portion of C17H19ClN2S.HCl
Independent • human being
Continuant • gene
Continuant
Dependent
Continuant
Particulars
• portion of chlorpromazine in this tablet
• me
• the HTR2A gene on chromosome 13 of the
most frontal cell in the tip of my nose
• shape
• the shape of my nose
• temperature
• the temperature of the chlorpromazine tablet in
front of me
• length
• the length of that HTR21 gene
• change in shape
• unfolding of a DNA molecule
• motion
• the circulation of a chlorpromazine molecule in
my bloodstream
• rise in temperature
• the rise of my body temperature while talking
here
Occurrent
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Or after transposition …
Universals
Continuant
Independent
Continuant
portion of
C17H19ClN2
S.HCl
human
being
Occurrent
Dependent
Continuant
gene
shape
temperature
length
change
in shape
motion
rise in temperature
Particulars
• portion of chlorpromazine in
the tablet in front of me
• me
• the HTR2A gene on
chromosome 13 of the most
frontal cell in the tip of my
nose
• the shape of my nose
• unfolding of a DNA molecule
• the temperature of the
chlorpromazine tablet in
front of me
• the circulation of a chlorpromazine molecule in
my bloodstream
• the length of that HTR21
gene
• the rise of my body temperature while teaching
this seminar
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
… and for many patients
Universals
Continuant
Independent
Continuant
portion of
C17H19ClN2S. HCl
case1
Particulars
case2
.
case3
case4
case5
case6
case7
case8
…
.
human
being
..
..
..
.
Occurrent
Dependent
Continuant
gene
shape
..
.
..
temperature
length
change
in shape
motion
. . .
.
.
.
.. .
..
.
.
.
rise in temperature
.
..
..
.
R T U New York State
Center of Excellence in
Bioinformatics & Life Sciences
Referent Tracking
Universals
Continuant
Independent
Continuant
portion of
human gene shape temperature
C19H17ClN2O4 being
case1
Particulars
case2
case3
case4
case5
case6
case7
case8
…
. ..
..
. ..
.
Occurrent
Dependent
Continuant
..
.
..
length
change
in shape
motion
. . .
.
.
.
.. . ..
.
.
.
rise in temperature
.
..
..
.
unique
identification
by means of
‘codes’
unique
identification
by means of
‘instance
unique
identifiers’