Fig. 1.

In brains of patients with SCZ compared with those of unaffected age-matched controls, CRMP2 levels are elevated and dendritic spine densities and basilar dendrite lengths are reduced. (A and B) Representative brightfield photomicrographs of the basilar dendrites of Golgi-stained pyramidal neurons in the DLPFC from a representative control subject (A) compared with a representative patient with SCZ (B). Red arrows point to dendritic spines, which are markedly reduced in the SCZ patient. (Scale bar, 5 µm.) (C) Graph depicting the relative protein expression of CRMP2 in control and SCZ patients (whose representative neuropathology is illustrated in B). The SCZ values were normalized to control values (percent control) collected in parallel from the same gel. CRMP2 was significantly increased by 10% in SCZ patients relative to controls (*P = 0.05) and CRMP2 protein expression was inversely correlated with basilar dendrite length (r = –0.37, P = 0.04). However, as indicated in SI Appendix, Table S1, this cohort of brain donors tended to be older (a mean age of ∼60 y old). Focusing on the few patients <40 y-old (among the SCZ patients, indicated by the blue arrow and green square, and among the unaffected controls, indicated by the pink arrow and green dot) suggested that we should explore additional CRMP2 parameters—such as diminished p-CRMP2:CRMP2 ratios—as we did in SI Appendix, Fig. S1, and found to be distinctively low in SCZ patients. It also prompted us to focus on young patients (defined as <40 y old) in our second prospective clinical study (Fig. 2) where, in this more highly powered cohort 2, the differences were significantly greater. Please see the Introduction for a summary of the relationship between CRMP2 and dendritogenesis.