Markers of muscarinic deficit for individualized treatment in schizophrenia

Recent clinical studies have shown that agonists at muscarinic acetylcholine receptors effectively reduce schizophrenia symptoms. It is thus conceivable that, for the first time, a second substance class of procholinergic antipsychotics could become established alongside the usual antidopaminergic antipsychotics. In addition, various basic science studies suggest that there may be a subgroup of schizophrenia in which hypofunction of muscarinic acetylcholine receptors is of etiological importance. This could represent a major opportunity for individualized treatment of schizophrenia if markers can be identified that predict response to procholinergic vs. antidopaminergic interventions. In this perspective, non-response to antidopaminergic antipsychotics, specific symptom patterns like visual hallucinations and strong disorganization, the presence of antimuscarinic antibodies, ERP markers such as mismatch negativity, and radiotracers are presented as possible in vivo markers of muscarinic deficit and thus potentially of response to procholinergic therapeutics. Finally, open questions and further research steps are outlined.

Automated summary

Recent clinical studies have found that muscarinic acetylcholine receptor agonists effectively alleviate schizophrenia symptoms, indicating the potential establishment of procholinergic antipsychotics as a second class of drugs alongside the usual antidopaminergic antipsychotics. Basic science studies also suggest that muscarinic acetylcholine receptor hypofunction may play a role in a subgroup of schizophrenia, offering an opportunity for personalized treatment if markers predictive of response to procholinergic vs. antidopaminergic interventions can be identified. Possible in vivo markers of muscarinic deficit and response to procholinergic therapeutics such as non-response to antidopaminergic antipsychotics, specific symptom patterns, presence of antimuscarinic antibodies, ERP markers, and radiotracers are presented. Open questions and further research steps are also discussed.