Opinion The hypothesis of biologically based subtypes of schizophrenia: a 10-year update, 2025, Howes et al

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The hypothesis of biologically based subtypes of schizophrenia: a 10-year update

Oliver D. Howes, Bernard R. Bukala, Sameer Jauhar, Robert A. McCutcheon

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A decade ago we proposed that there are two biological subtypes of schizophrenia: type A, characterized by mesostriatal hyperdopaminergia, and type B, without hyperdopaminergia. One clinical implication was that type A would be associated with good treatment response to antipsychotics, which all act on the dopamine system by blocking dopamine D2 receptors, whereas type B would be associated with poor antipsychotic treatment response. We also proposed that glutamatergic dysfunction would underlie type B, and suggested additional biologically-based subtypes (C, D, etc.), linked to poor treatment response, yet to be discovered.

The hypothesis predicted that biological differences would be present from illness onset. It would be falsified if, for example, there was no response to antipsychotic treatment in schizophrenia despite mesostriatal hyperdopaminergia. Ten years on, we provide here an update on evidence addressing the hypothesis and evaluate the impact it has had.

Link | PDF (World Psychiatry) [Open Access]

 

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Whilst evidence accrued in support of the hypothesis during the past decade, some uncertainty remains. This is partly because not all the studies have been positive, although none have disproven the hypothesis and confounds may explain discrepancies, as discussed above. The hypothesis may also need revision to explain the biological basis of treatment resistance that develops during the illness. Notwithstanding these points, there is encouraging evidence of potential clinical utility and cost-effectiveness of tests based on the subtyping. An important avenue for work over the next decade will be to determine their value in clinical practice.