The role of subtypes in understanding disease processes within schizophrenia：a case example of‘Deficit Syndrome’

Lawrence H.YABG,M ing Che TU,Hui Ting LIU,Mark OPLER

1Department of Epidemiology,Columbia University,Bew York,BY 10032,United States

2Department of Psychology,Columbia University,Bew York,BY 10027,United States

3Department of Epidem iology,Bew York University,Bew York,BY 10003,United States

*Correspondence:lhy2001@columbia.edu

The role of subtypes in understanding disease processes within schizophrenia：a case example of‘Deficit Syndrome’

Lawrence H.YABG1*,M ing Che TU2,Hui Ting LIU2,Mark OPLER3

1Department of Epidemiology,Columbia University,Bew York,BY 10032,United States

2Department of Psychology,Columbia University,Bew York,BY 10027,United States

3Department of Epidem iology,Bew York University,Bew York,BY 10003,United States

*Correspondence:lhy2001@columbia.edu

Professor xu［1］provides a thoughtful and eloquent description of the utilization of schizophrenia subtypes,and presents a compelling argument for their continued use in modified form.He notes that subtypes in schizophrenia have a rich history as observable clinical‘phenotypes’and have been used to guide prognosis and treatment for generations. Despite this history,reports from Shanghaiand from Western researchers［2,3］indicate that except for paranoid and undifferentiated schizophrenia most of the other subtypes of schizophrenia defined in the United States and Europe are rarely used；less than 5%of patients with schizophrenia receive these diagnoses.Moreover,the more commonly used subtypes are not stable over time:only a small proportion of those diagnosed with the paranoid subtype and an even a smaller proportion diagnosed as undifferentiated subtype retain the diagnosis over the course of their illness［4］.These issues and the longstanding problem of the varying the number of‘core’subtypes identified by different statistical methods—from two to six［3］—raise serious questions about the validity of subtyping schizophrenia. Consequently,the drafting comm ittee for the proposed DSM-5 has made a deliberate decision to eliminate subtypes of schizophrenia and to em phasize dimensions of psychosis in their stead.

This decision to move towards a dimensional method of assessing the symptom s of schizophrenia raises a fundamental question of whether or not subtypes will be useful in future research about schizophrenia and,if so,how they should be employed.Arguing in favor of the preservation of subtypes,Professor xu believes that subtypes are useful both in practice and in research and recommends the dichotomization of schizophrenia into two main subtypes—‘typical’（i.e.,‘true’）and‘atypical’（i.e.,‘schizophreniform’）.His classification scheme is supported by reports of a different course of illness in acute rem itting psychosis,by reports of different prevalences of acute rem itting psychoses among males versus females,and in developing versus developed countries［5］.

Like Professor xu,we also argue that retaining certain empirically-supported subtypes would powerfully benefit research on the underlying disease pathways of schizophrenia.One well-validated subtype,the‘deficit syndrome’,is an example of a schizophrenic subtype that merits future investigation in biological and genetic studies.The deficit syndrome is characterized by persistent primary negative symptoms.To meet criteria for the deficit syndrome,patients must exhibit symptoms that: 1）include two or more of the following six negative symptom s:restricted affect,diminished emotional range,poverty of speech,lack of interests,diminished sense of purpose,and lack of social drive；2）are clinically stable throughout the past12 months；3）are primary,that is,not secondary due to the effects of medication or psychotic symptoms；and 4）meet DSM criteria for schizophrenia［6］.There is a well-established body of literature summarized in three comprehensive review s［6-8］that support the construct validity of deficit syndrome as a distinct subtype of schizophrenia.Studies in five areas have distinguished deficit syndrome from‘non-deficit syndrome’schizophrenia:1）neurophysiology and neurocognition；2）family history；3）risk factors；4）response to treatment；and 5）illness outcome. These studies report that the primary negative symptom s of deficit syndrome generally show poorer response to medication than other symptoms of schizophrenia and that patients with the deficit syndrome have poorer social and occupational outcomes than other patients with schizophrenia.

Given the remarkable heterogeneity of the syndromes that comprise schizophrenia,continued useof em pirically-validated subtypes such as the deficit syndrome should help assist in the effort to identify underlying disease pathways.Some reports find that phenotypic heterogeneity reflects genetic heterogeneity［9］,so the use of homogeneous phenotypes of schizophrenia by sam pling specific subtypes might facilitate future investigations of etiology and the identification of salient genes and biological markers.In contrast to genetic studies that sample heterogeneous schizophrenia phenotypes and typically report small-effect risk variants and genetic heterogeneity［10］,one seminal study in Taiwan found enhanced genetic linkages within an empirically derived,clinically homogeneous schizophrenia phenotype resembling the deficit syndrome［11］.Hence, the deficit syndrome subtype—that was originally characterized based on clinical traits,neurocognitive functioning,and course characteristics—might be the phenotypic expression of a specific genetic abnormality.What began as clinically-observable phenotypes of schizophrenia in the times of Kraepelin and Bleuler have evolved into em pirically distinct and well-validated subtypes that provide targets for the more sophisticated biological and genetic analyses that are available to us today.It is incumbentupon us to build upon the intellectual legacy of Kraepelin and Bleuler and utilize well-established subtypes such as the deficit syndrome to further our understanding of the etiology of schizophrenia in order to ultimately enable more effective prevention and intervention for this debilitating disease.

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