Werner CEUSTERS 1 and Barry SMITH 2

1. Academic Development SymposiumFoundations for aRealist Ontology of Mental DiseaseAugust 25, 2010; 11.30 AM - 01.00 PMECMC – Department of Psychiatry, Buffalo NYRoom 1108A 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

2. Structure of this presentation • Do mental disorders exist and if so, what are they? • Overview of relevant positions • Foundations of our work • Methodological • Representational • Towards an ontology for mental health • Utility of our work

3. Mental disordersand‘mental disorders’

4. 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.

5. 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?

6. A terminological and ontological problem (2) • Szasz: ‘mental illnessis 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.

7. 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.

8. Our interpretation of Szasz (2) • Those in group (1), according to Szasz, would be better described as having a brain disorder, • those in group (2), while they might indeed have ‘problems of living’, and thus be suffering, are not suffering because of some disorder of a special, mental kind. • 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’.

9. 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.

10. 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.

11. 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. • We believe these arguments are flawed and do not lead to the conclusion

12. 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.

13. 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.

14. 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.

15. 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.

16. The basics: existence (in a patient) criterion • ‘prolonged and severe suffering and incapacity in the affective, cognitive, or interpersonal-behavioral 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.

17. 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.

18. 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.

19. 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

20. 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).

21. 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.

22. Foundations for anOntology of Mental Health

23. Foundations for our work • Methodological foundations: • Ontological Realism • Open Biomedical Ontologies Foundry • Representational foundations: • Basic Formal Ontology • Relation Ontology • Ontology of General Medical Science

24. 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 realism, a specific theory of ontology, as the basis for building high quality ontologies, using reality as benchmark.

25. Ontological realism • There is an external reality which is ‘objectively’ the way it is; • That reality is accessible to us; • We build in our brains cognitive representations of reality; • 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

26. Realism Conceptualism Nominalism Universal Concept Collection of particulars yes: in particulars perhaps: in minds no Realism versus other philosophies • Basic questions: • What does a general term such as ‘disorder’ refer to? • Do generic things exist?

27. Representational units in various • forms about (1), (2) or (3) (2) Cognitive entities which are our beliefs about (1) (1) Entities with objective existence which are not about anything Three levels of reality in Ontological Realism Terminology Realist Ontology Representation and Reference representational units cognitive units communicative units universals particulars First Order Reality

28. Basic Formal Ontology

29. Basic Formal Ontology in a nutshell • The world consists of • entities that are • Either particulars or universals; • Either occurrents or continuants; • Either dependent or independent; and, • relationships between these entities of the form • <particular , universal> e.g. is-instance-of, • <particular , particular> e.g. is-member-of • <universal , universal> e.g. isa (is-subtype-of) 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, November 8, 2006, Baltimore MD, USA

30. process living creature function leg Instance-of at t humanbeing legmoving walking Instance-of at t Instance-of Instance-of at t to make me walk this leg moving Instance-of my left leg me this walking Particulars and Universals 1

31. The importance of temporal indexing malignant tumor benign tumor stomach instanceOf at t2 instanceOf at t1 instanceOf at t2 instanceOf at t1 partOf at t1 this-4 this-1’s stomach partOf at t2

32. process living creature function leg Instance-of at t humanbeing legmoving walking Instance-of at t Instance-of Instance-of at t to make me walk this leg moving Instance-of my left leg me this walking Continuants and Occurrents 2

33. Independent entities Do not require any other entity to exist for their own existence Dependent entities Require the existence of some other entity for their existence Independent versus dependent 3 to make me walk this leg moving Independent continuants Dependent continuants Occurrents (are all dependent) my left leg me this walking

34. continuants occurrents • Realizations • flexing • studying • ordering • breaking Dependent continuants 3 • Realized • Quality: redness (of blood) • Realizable • Function: to flex (of knee joint) • Role: student • Power: boss • Disposition: brittleness (of a bone)

35. 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

36. Relation Ontology universals has_participant Continuant Occurrent process, event isa isa Independent Continuant ~ thing Dependent Continuant inheres_in instance_of (at t) .... ..... ....... particulars

37. The essential pieces dependent continuant material object spacetime region spatial region temporal region history instanceOf t t t participantOf at t occupies some temporal region some quality my 4D STR my life projectsOn me … at t projectsOn at t some spatial region located-in at t

38. The OBO Foundry • a family of interoperable biomedical reference ontologies built around the Gene Ontology (GO) at its core and using the same principles as the GO • a modular annotation catalogue of English phrases • each module created by experts from the corresponding scientific community • http://obofoundry.org

40. OBO Website

41. OBO Foundry ontologies in BFO-dress 41

42. 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

43. Goal of OGMS • To be a consistent, logical and extensible framework (ontology) for the representation of • features of disease • clinical processes • results

44. Motivation • Clarity about: • disease etiology and progression • disease and the diagnostic process • phenotype and signs/symptoms

45. Big Picture

46. Approach • a disease is a disposition rooted in a physical disorder in the organism and realized in pathological processes. produces bears realized_in etiological process disorder disposition pathological process produces diagnosis interpretive process signs & symptoms abnormal bodily features produces participates_in recognized_as

47. Cirrhosis - environmental exposure • 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 • Etiological process - phenobarbitol-induced 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

48. Etiological process - infection of airway epithelial cells with influenza virus produces Disorder - viable cells with influenza virus bears Disposition (disease) - flu realized_in Pathological process - acute inflammation produces Abnormal bodily features recognized_as Symptoms - weakness, dizziness Signs - fever But the disorder also induces normal physiological processes (immune response) that can result in the elimination of the disorder (transient disease course). Influenza - infectious • Symptoms & Signs • used_in • Interpretive process • produces • Hypothesis - rule out influenza • suggests • Laboratory tests • produces • Test results – documentation of elevated serum antibody titers • used_in • Interpretive process • produces • Result - diagnosis that patient X has a disorder that bears the disease flu

49. 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.

50. 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.