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

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.

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