Neuregulin 1-induced AKT phosphorylation in monozygotic twins discordant for schizophrenia.
ABSTRACT Patients with schizophrenia exhibit decreased neuregulin 1 (NRG1)-stimulated AKT phosphorylation in peripheral lymphoblasts. Here, we examined this peripheral marker in monozygotic twins discordant for schizophrenia and in healthy monozygotic twins without psychiatric disorders. B lymphoblasts were stimulated with NRG1a (65 amino-acid residue recombinant protein from the epidermal growth factor [EGF] domain) for 30min. The protein isolated from the cells was analysed by Western blotting. The dependent measure was the ratio of phosphorylated AKT (pAKT) and total AKT at baseline (without NRG1 stimulation) and after NRG1 stimulation (pAKT/AKT). The results revealed that in the case of the unaffected co-twins of patients with schizophrenia, NRG1-stimulated pAKT/AKT ratio was in between the values of their co-twins with schizophrenia and that of the healthy control twin pairs. When the affected twins with schizophrenia were compared with their unaffected co-twins using a Mann-Whitney U-test, we found significantly lower NRG1-induced pAKT/AKT ratios in the patients relative to their unaffected co-twins (p=0.004). However, using a more conservative analysis (Kruskal-Wallis ANOVA followed tests for multiple comparisons), this difference was not significant. The unaffected co-twins of patients with schizophrenia did not differ significantly from the healthy control twins. In the baseline condition, the pAKT/AKT ratios were similar in all groups. These results indicate that impaired AKT-related intracellular signaling is partly related to the developed illness and cannot fully be explained by the genetic background of schizophrenia.