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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 Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences R T U New York State Center of Excellence in Bioinformatics & Life Sciences Mental disorders and ‘mental disorders’ 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 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 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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? 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 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. 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 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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’. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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?’ R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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). R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences Foundations for an Ontology of Mental Health R T U New York State Center of Excellence in Bioinformatics & Life Sciences Foundations for our work • Methodological foundations: – Ontological Realism – Open Biomedical Ontologies Foundry • Representational foundations: – Basic Formal Ontology – Relation Ontology – Ontology of General Medical Science R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 ? R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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). R T U New York State Center of Excellence in Bioinformatics & Life Sciences Basic Formal Ontology R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences Motivation • Clarity about: – disease etiology and progression – disease and the diagnostic process – phenotype and signs/symptoms R T U New York State Center of Excellence in Bioinformatics & Life Sciences Big Picture R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. 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 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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.’ R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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 R T U New York State Center of Excellence in Bioinformatics & Life Sciences 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. R T U New York State Center of Excellence in 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’