Towards an Ontology of Schizophrenia Fumiaki Toyoshima Department of Philosophy University at Buffalo Buffalo, USA fumiakit@buffalo.edu Abstract—The paper presents an Ontology of Schizophrenia signs and symptoms of schizophrenia such as delusions and (OS) that is designed to provide a formal representation of hallucinations. But in the absence of definitions of terms such schizophrenia-related entities crucial to the treatment and study as these, EFO’s characterization of schizophrenia is of schizophrenia. OS is developed in accordance with the OBO uninformative. Additionally, the EFO class ‘schizophrenia’ (Open Biomedical Ontology) Foundry principles and constructed falls under the class ‘mental or behavioural disorder’, which in in compliance with Basic Formal Ontology (BFO) as its upper- turn falls under the class ‘brain disease’. But EFO does not level ontology. It uses mid-level and domain ontologies built in specify what it is that makes a brain disease can qualify as a conformity with BFO such as the Ontology for General Medical mental or behavioral disorder. Science (OGMS) and the Mental Functioning Ontology (MFO). OS is developed using Protégé 4.3 and is implemented in OWL2. Having imported BFO2.0 OWL and the development version of II. PURPOSE AND METHOD OGMS, OS adds approximately 30 schizophrenia-related terms The Ontology of Schizophrenia (OS) aims to provide a and attempts to provide both formal and textual definitions for formal representation of schizophrenia-related entities that are each. The terms in OS are in addition annotated with ontology crucial to the treatment and study of schizophrenia. OS is metadata such as labels, textual definitions, definition sources, developed in accordance with the OBO (Open Biomedical term editors and editor notes. Ontology) Foundry principles and constructed in compliance Keywords—OBO Foundry; Schizophrenia; Ontology with Basic Formal Ontology (BFO) as upper-level ontology and with the mid-level and domain ontologies that are built in conformance with BFO such as the Ontology for General I. INTRODUCTION Medical Science (OGMS) and Mental Functioning Ontology In biomedical ontology research, the ontological analysis of (MFO). OS is developed according to an initial proposal in [4] disease has been much discussed, since disease is of paramount to ontologize mental disease on the basis of BFO, OGMS, and importance for biomedicine. However, little research has been MFO. done on the ontology of mental disease. Consequently, data As the embodiment of the realist methodology, BFO has and information about mental disease have not yet been been widely used in various domains, specifically in exploited using ontology-based approaches. biomedical fields [2]. OGMS is intended to be used primarily Among mental diseases, schizophrenia has been a focus of in the development of clinical application ontologies, and attention because of its unique features. A rigorous focuses on the main types of entities involved in a clinical representation of the entities relevant to the study of encounter such as ‘disease’, ‘disorder’, and ‘disease course’ [6]. schizophrenia would provide a new avenue for its prevention MFO aims to represent all the aspects of mental functioning, and cure [9]. However, the definitions or general descriptions including mental processes such as cognition and perception of schizophrenia vary greatly from one domain expert to and qualities such as intelligence [8]. another [1, 7, 12]. For instance: “Schizophrenia is a chronic OS is developed using Protégé 4.3 and is implemented in and severe disorder that affects how a person thinks, feels, and OWL2. Having imported BFO2.0 OWL and the development acts.” (National Institute of Mental Health); “Schizophrenia is version of OGMS, OS adds approximately 30 schizophrenia- a mental disorder that makes it hard to tell the difference related terms such as ‘schizophrenia’, ‘pathological between what is real and not real.” (Medical Encyclopedia); schizophrenia process’, ‘schizophrenia disorder’ and and “Schizophrenia is a serious brain illness.” (National ‘schizophrenia course’ (Figure 1). Library of Science). An attempt to create an ontology of schizophrenia is therefore a challenging but potentially valuable task. Furthermore, efforts to deal with schizophrenia in existing ontologies are not fully adequate. For instance, schizophrenia is textually defined in the Experimental Factor Ontology (EFO) [5] as follows: “A major psychotic disorder characterized by abnormalities in the perception or expression of reality.” We assume that the phrases ‘abnormalities in the perception or expression of reality’ is an attempt to refer to common clinical Fig. 1. Core OS terms and relations between them Further development of OS includes: continued enlargement, especially adding terms relating to the treatment of schizophrenia; the specification of OS’s relation with ND; and a quantitative assessment such as to what extent schizophrenia-related data can be mapped onto OS. With further bottom-up approaches, OS is highly expected to assist medical practitioners and researchers. For instance, OS has the potential to promote the treatment of schizophrenia patients by enhancing the International Psychopharmacology Algorithm Project (IPAP) Schizophrenia Algorithm [10], given that the BFO framework is able to capture, in a rigorous and computationally tractable way, all the types of entities represented in the IPAP Schizophrenia Algorithm [3]. Fig. 2. Screenshot from Protégé showing the formal definition for the OS class ‘schizophrenia’ REFERENCES [1] APA (2013). Diagnostic and Statistical Manual of Mental Disorders, OS attempts to provide both formal and textual definitions Fifth Edition - Text Revision. American Psychiatric Association, Washington, DC. for each of these terms. Currently, some OS terms cannot be [2] Arp, R., Smith, B., and Spear, A. D. (2015). Building Ontologies with defined by providing a statement of necessary and sufficient Basic Formal Ontology. Cambridge, Massachusetts: The MIT Press. conditions. For instance, given OS’s framework, the class [3] Ceusters, W. & Smith, B. (2006). Referent tracking for treatment ‘schizophrenia’ cannot currently be defined in this way due to optimisation in schizophrenic patients: A case study in applying a lack of scientific consensus. The class is however specified philosophical ontology to diagnostic algorithms. Web Semantics via a formal definition through a set of subclass axioms (Online) 4 (3): 229-236. http://doi.org/10.1016/j.websem.2006.05.002 (Figure 2). The classes ‘gray matter volume reduction process’, [4] Ceusters, W. and Smith, B. (2010). Foundations for a realist ontology of mental disease. Journal of Biomedical Semantics 1 (10). ‘white matter volume reduction process’, and ‘synapse [5] Experimetal Factor Ontology. http://www.ebi.ac.uk/efo/ Last visited on quantity reduction process’ are created to represent excessive June 25. 2016. loss of gray and white matter and reduced numbers of synaptic [6] Goldfain, A. et al. (2014). OGMS: The Ontology for General Medical structures on neurons, which have been repeatedly observed Science. In Proceedings of International Conference on Biomedical traits with schizophrenia [12, 13]. Ontologies (ICBO2014). The classes ‘delusion’ and ‘hallucination’ fall into the [7] Green, M. F., Horan, W. P., and Lee, J. (2015). Social cognition in class ‘non-referring cognitive representation’. OS’s way of schizophrenia. Nature Reviews Neuroscience 16: 620-631. handling cognitive representation and non-referentiality draws [8] Hastings, J., Ceusters, W., Jensen, M., Mulligan, K., and Smith, B. (2012). Representing Mental Functioning: Ontologies for Mental Health on recent discussions on the realist approach to aboutness [14]. and Disease. In Towards an Ontology of Mental Functioning (ICBO OS terms are in addition annotated with ontology metadata Workshop), Proceeedings of the Third International Conference on such as labels, textual definitions, definition sources, term Biomedical Ontology (ICBO2012). editors and editor notes. For instance, the class ‘hallucination’ [9] Insel, T. R. (2010). Rethinking schizophrenia. Nature 468 (7321): 187- 193. doi:10.1038/nature09552 is textually defined as follows: “A non-referring cognitive [10] IPAP Schizophrenia Algorithm Project. representation that is experienced without an external stimulus http://www.ipap.org/schiz/index.php Last visited on June 25, 2016. as if there were something perceived.” [11] Jensen, M. et al. (2013). The neurological disease ontology. Journal of The current version of OS focuses exclusively on Biomedical Semantics 4 (42). schizophrenia in part because many related kinds of mental [12] Kahn, R. S. et al. (2015). Schizophrenia. Nature Reviews Disease disease – for instance schizoaffective disorders – cannot be Primers 1: Article Number 15067. specified in the ontology until schizophrenia itself has [13] Sekar, A. et al. (2016). Schizophrenia risk from complex variation of received an adequate treatment. However, many of the classes complement component 4. Nature 530: 177-183. discussed so far are applicable to schizoaffective disorders. [14] Smith, B. and Ceusters, W. (2015). Aboutness: Towards Foundations for the Information Artifact Ontology. In Proceedings of International III. CONCLUSION Conference on Biomedical Ontologies (ICBO2015). A qualitative assessment of work on OS thus far might read as follows: OS unifies different existing definitions of schizophrenia into a set of manifestations of schizophrenia. In addition, the ontological characterization of schizophrenia in OS is more coherently aligned with BFO than is the case with other BFO-based ontologies, such as EFO. As an extension of BFO and OGMS, OS also fits well with the Neurological Disease Ontology (ND) [11]. More generally, OS has made a positive contribution to biomedical ontologies in the sense of being one of the few ontologies of mental disease.