Higher levels of AKT-interacting protein in the frontal pole from people with schizophrenia are limited to a sub-group who have a marked deficit in cortical muscarinic M1 receptors

•Compared to controls, AKT-interacting protein (AKTIP) is higher in BA 10, but not BA 9, from people with schizophrenia.•Higher levels of AKTIP protein are specific to a sub-group within schizophrenia defined by markedly low levels of cortical muscarinic M1 receptors.•AKTIP is not changed in BA 10 from people with mood disorders, suggesting regional and diagnostic selectivity to BA 10 in the sub-group within schizophrenia.•AKTIP is a regulator of AKT signalling and therefore our data suggest changes in that signalling pathway could be particularly important in the molecular pathology of BA 10 in a sub-group within schizophrenia. We are studying the molecular pathology of a sub-group within schizophrenia (∼ 25 %: termed Muscarinic Receptor Deficit subgroup of Schizophrenia (MRDS)) who can be separated because they have very low levels of cortical muscarinic M1 receptors (CHRM1). Based on our transcriptomic data from Brodmann's area ((BA) 9, 10 and 33 (controls, schizophrenia and mood disorders) and the cortex of the CHRM1−/− mouse (a molecular model of aberrant CHRM1 signaling), we predicted levels of AKT interacting protein (AKTIP), but not tubulin alpha 1b (TUBA1B) or AKT serine/threonine kinase 1 (AKT1) and pyruvate dehydrogenase kinase 1 (PDK1) (two AKTIP-functionally associated proteins), would be changed in MRDS. Hence, we used Western blotting to measure AKTIP (BA 10: controls, schizophrenia and mood disorders; BA 9: controls and schizophrenia) plus TUBA1B, AKT1 and PDK1 (BA 10: controls and schizophrenia) proteins. The only significant change with diagnosis was higher levels of AKTIP protein in BA 10 (Cohen's d = 0.73; p = 0.02) in schizophrenia compared to controls due to higher levels of AKTIP only in people with MRDS (Cohen's d = 0.80; p = 0.03). As AKTIP is involved in AKT1 signaling, our data suggests that signaling pathway is particularly disturbed in BA 10 in MRDS.