QT Is Longer in Drug-Free Patients with Schizophrenia Compared with Age-Matched Healthy Subjects

Abstract

The potassium voltage-gated channel KCNH2 is a well-known gene in which mutations induce familial QT interval prolongation. KCNH2 is suggested to be a risk gene for schizophrenia. Additionally, the disturbance of autonomic control, which affects the QT interval, is known in schizophrenia. Therefore, we speculate that schizophrenic patients have characteristic features in terms of the QT interval in addition to the effect of antipsychotic medication. The QT interval of patients with schizophrenia not receiving antipsychotics (n = 85) was compared with that of patients with schizophrenia receiving relatively large doses of antipsychotics (n = 85) and healthy volunteers (n = 85). The QT interval was corrected using four methods (Bazett, Fridericia, Framingham or Hodges method). In ANCOVA with age and heart rate as covariates, patients not receiving antipsychotic treatment had longer QT intervals than did the healthy volunteers, but antipsychotics prolonged the QT interval regardless of the correction method used (P<0.01). Schizophrenic patients with and without medication had a significantly higher mean heart rate than did the healthy volunteers, with no obvious sex-related differences in the QT interval. The QT interval prolongation may be manifestation of a certain biological feature of schizophrenia.

Prolonged QT Interval in Neurodevelopmental Rat Model of Schizophrenia

“…One of the possible mechanisms of QT prolongation in schizophrenia-like rats might be the existence of variant polymorphism or mutation in gene for KCNH2 potassium channel [3] or in other genes (e.g. hERG gene) related to potassium channels and their regulation.…”

“…Moreover, it was reported that also drug-free patients suffering from schizophrenia have an increased QT interval compared to age-matched healthy subjects [3]. It is supposed that the polymorphism in KCNH2 channel might be a possible connection between schizophrenia and QT prolongation.…”

The Prevalence and Significance of Antipsychotic Dosing on QTc Prolongation

“…There had been reports of sudden cardiac deaths associated with antipsychotics, particularly thioridazine, for years before sertindole, but this was the first FDA intervention in the matter. In vitro studies have shown the ability of antipsychotics to block the potassium rectifier channel (I Kr ) that is involved in the repolarization of the ventricles (Berling & Isbister, 2015;Fujii et al, 2014, Polcwiartek et al, 2015, Vieweg et al, 2013. However, in vitro studies have shown that despite risperidone's ability to inhibit this channel by 80% at the highest concentrations, it had minimal effect on cardiac conduction (Berling & Isbister, 2015;Vieweg et al, 2013).…”

“…Additionally, many studies used antipsychotics at higher doses than used in common practice or even used multiple antipsychotics with cumulative doses higher than those on monotherapy (Berling & Isbister, 2015;Fujii et al, 2014;Glassman & Brigger, 2001). In the majority of studies with haloperidol, for example, the agent was administered intravenously and in an acute care or intensive care patients with intubation-related agitation.…”

“…One study demonstrated that the QTc of non-medicated schizophrenics was longer than those of normal healthy subjects. This is potentially related to the variant of potassium channel gene that is responsible for congenital QTc prolongation as some studies have shown that variants in this gene also lead to a risk of developing schizophrenia (Fujii et al, 2014). Also, patients with schizophrenia are at more risk for cardiac disease and sudden death, especially since many are heavy smokers (Glassman & Brigger, 2001).…”