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A neurobiological hypothesis for the classification of schizophrenia: type a (hyperdopaminergic) and type B (normodopaminergic)

  • Oliver D. Howes (a1) and Shitij Kapur (a2)
Summary

Schizophrenia is usually classified based on clinical presentation. However, the conventional paranoid–disorganised–residual distinctions have had limited clinical utility. Here we draw on the evidence for differences in pathophysiology underlying treatment response to propose a subclassification based on neurobiology to guide diagnostic testing and treatment.

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Corresponding author
Oliver D. Howes, Box 067, Institute of Psychiatry, De Crespigny Park, Camberwell, London SE5 8AF, UK. Email: oliver.howes@kcl.ac.uk
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Declaration of interest

In the past 3 years O.H. has received investigator-led grants and/or served as a speaker/consultant for Eli Lilly, Roche, Leyden-Delta, Lundbeck, Servier and Janssen-Cilag (J&J). S.K. has received grant support from GlaxoSmithKline, GW and Roche and has served as a one-off consultant and/or speaker for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Envivo, Janssen (J&J), Otsuka, Pfizer and Takeda, and serves on scientific advisory boards for Lundbeck and Roche.

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References
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1 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM-IV). APA, 1994.
2 World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO, 1992.
3 Howes, OD, Kambeitz, J, Kim, E, Stahl, D, Slifstein, M, Abi-Dargham, A, et al. The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 2012; 69: 776–86.
4 Howes, O, Bose, S, Turkheimer, F, Valli, I, Egerton, A, Stahl, D, et al. Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: a PET study. Mol Psychiatry 2011; 16: 885–6.
5 Demjaha, A, Murray, RM, McGuire, PK, Kapur, S, Howes, OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry 2012; 169: 1203–10.
6 Remington, G, Kapur, S, Foussias, G, Agid, O, Mann, S, Borlido, C, et al. Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial. J Clin Psychopharmacol 2012; 32: 95–9.
7 Ottong, SE, Garver, DL. A biomodal distribution of plasma HVA/MHPG in the psychoses. Psychiatr Res 1997; 69: 97103.
8 Yoshimura, R, Ueda, N, Shinkai, K, Nakamura, J. Plasma levels of homovanillic acid and the response to risperidone in first episode untreated acute schizophrenia. Int Clin Psychopharmacol 2003; 18: 107–11.
9 Roberts, RC, Roche, JK, Conley, RR, Lahti, AC. Dopaminergic synapses in the caudate of subjects with schizophrenia: relationship to treatment response. Synapse 2009; 63: 520–30.
10 Abi-Dargham, A, Rodenhiser, J, Printz, D, Zea-Ponce, Y, Gil, R, Kegeles, LS, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 2000; 97: 8104–9.
11 Bose, SK, Turkheimer, FE, Howes, OD, Mehta, MA, Cunliffe, R, Stokes, PR, et al. Classification of schizophrenic patients and healthy controls using [18F] fluorodopa PET imaging. Schizophr Res 2008; 106: 148–55.
12 Howes, OD, Vergunst, F, Gee, S, McGuire, P, Kapur, S, Taylor, D. Adherence to treatment guidelines in clinical practice: study of antipsychotic treatment prior to clozapine initiation. Br J Psychiatry 2012; 201: 481–5.
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  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
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A neurobiological hypothesis for the classification of schizophrenia: type a (hyperdopaminergic) and type B (normodopaminergic)

  • Oliver D. Howes (a1) and Shitij Kapur (a2)
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eLetters

More questions

Prasanna N. de Silva, Consultant Old Age Psychiatrist
09 September 2014

Could the authors address the following questions?

1. How does this hypothesis differ from Crow's Type 1 and 2 division?As you know, there was correlation between imaging and clinical findings for this separation.2. How does your hypothesis fit with presence or otherwise of hypofrontality?3. What are the clinical implications of your hypothesis as to which patients with schizophreniform episodes merit long term continuation of antipsychotics and which might benefit from discontinuation at 6 months?Thank you

References1. Crow, T.O. The two syndrome concept: origin and current status. Schizophrenia Bulletin 1985: Vol 11, pp 471 -4862. Liddle, P.F., Friston, C.D. et.al. Patterns of cerebral blood flow in schizophrenia. Brit. Jour. Psych. 1992: Vol 160, pp 179 - 186

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Conflict of interest: None declared

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Clinical challenges and opportunities: neuroimaging type A and B schizophrenia

Ketan D. Jethwa, Former Academic Clinical Fellow in Psychiatry
12 August 2014

Patients with type B (normodopaminergic) schizophrenia are more likely to be treatment resistant and subsequently have a poorer outcome1. It would be interesting to consider whether there are any phenomenologicaldifferences in the psychotic or cognitive symptoms experienced by patientswith type A or B schizophrenia. Nevertheless, the identification of a potential PET imaging biomarker to assess potential treatment resistance in schizophrenia is certainly good news2. However, it is important to consider how these findings can be translated into clinical practice. There has been a vast amount of neuroimaging research which has significantly increased our understanding of the structural and functionalcorrelates of psychiatric disorders, however this wealth of knowledge has had little impact clinically3. This has been partly related to access, butalso because psychiatric disorders are syndromes that represent the expression of multiple genetic and biological pathways. However with the type A/B distinction there is potential utility of pattern recognition tools in separating patients based on a single molecular target. More research is therefore needed to assess the correlation between striatal dopamine function and treatment response. As the evidence for imaging and other biomarkers becomes stronger they will play a bigger role in aiding diagnosis and assessing outcome. It is therefore important that the links between neuroscience and psychiatry are explicit in training4 and the scientific underpinnings of the specialty are explicit within mental health services and in our interactions with patients and the public in general.

References: 1.Howes OD & Kapur S. A neurobiological hypothesis for the classification of schizophrenia: type A (hyperdopaminergic) and type B (normodopaminergic). Br J Psychiatry 2014; 205: 1-3. 2.Bose SK, Turkheimer FE, Howes OD, Mehta MA, Cunliffe R, Stokes PR, et al. Classification of schizophrenic patients and healthy controls using [18F] fluorodopa PET imaging. Schizophr Res 2008; 106: 148-55.3.Fu CH & Costafreda SG. Neuroimaging-based biomarkers in psychiatry:clinical opportunities of a paradigm shift. Can J Psychiatry 2013; 58 (9):499-508.4.Kendell RE. The next 25 years. Br J Psychiatry 2000; 176: 6-9.

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Conflict of interest: None declared

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