Classifications and ‘declassifications’ are not new to schizophrenia. DSm 4 had 5 subtypes, DSm5 removed them all. Icd 10 still has 8 subtypes. Symptom dimensions ( positive, negative , affective and cognitive ) are accepted as the more useful way to subtype this disorder in the new classifications.These classifications do no reflect the clinically valid concept of treatment responsive and treatment refractory schizophrenia. Oliver Howes and Shijit Kapur argue that the biology behind treatment response should be one guiding factor in classification.
Evidence for pre synaptic dopamine dysfunction in schizophrenia is robust. Over 50 in vivo molecular imaging studies support this. Demonstration of substantial D2 blocking by effective antipsychotics provide converging evidence in support of dopamine theory.
Why do not all patients on Dopamine blockers improve? PET imaging show that some patients show little or no response even with high levels of dopamine receptor blockade.
Are there any difference in dopamine system between responders and non responders?
Dopamine metabolite level studies show a bimodal distribution i.e. there is a group with high dopamine and another one with no alteration. Patients who responded show higher dopamine levels in striata in postmortem studies compared with those who did not respond. Amphetamine do not increase psychosis in a subgroup of schizophrenia. Dopamine synthesis capacity was increased in treatment responsive group compared to resistant group.
Based on the above observations, authors argue that may be there are two biological types of schizophrenia: the A- hyper dopaminergic, type B- norm dopaminergic. There are potential advantages to such attempts, as focusing on mechanisms will help open some doors to new treatments. Early identification of Type B patients would perhaps help them to choose clozapine early on. PET imaging of dopamine may help make such decisions.
What underlies type B? probably glutamatergic mechanisms. we don’t know now. Authors are of the view that it is time to move on from descriptive typing.
Summary of the article:
Howes OD, Kapur S. Br J Psychiatry. 2014 Jul;205(1):1-3.