title: Nonlinear complexity and spectral analyses of heart rate variability in medicated and unmedicated patients with schizophrenia.
abstract: OBJECTIVE
  Heart rate variability (HRV) reflects functioning of the autonomic nervous system and possibly also regulation by the neural limbic system, abnormalities of which have both figured prominently in various etiological models of schizophrenia, particularly those that address patients' vulnerability to stress in connection to psychosis onset and exacerbation. This study provides data on cardiac functioning in a sample of schizophrenia patients that were either medication free or on atypical antipsychotics, as well as cardiac data on matched healthy controls. We included a medication-free group to investigate whether abnormalities in HRV previously reported in the literature and associated with atypical antipsychotics were solely the effect of medications or whether they might be a feature of the illness (or psychosis) itself.
  
  
  METHODS
  We collected 24-hour ECGs on 19 patients and 24 controls. Of the patients, 9 were medication free and 10 were on atypical antipsychotics. All subject groups were matched for age and gender. Patient groups showed equivalent symptom severity and type, as well as duration of illness. We analyzed the data using nonlinear complexity (symbolic dynamic) HRV analyses as well as standard and relative spectral analyses.
  
  
  RESULTS
  For the medication-free patients as compared to the healthy controls, our data show decreased R-R intervals during sleep, and abnormal suppression of all frequency ranges, but particularly the low frequency range, which persisted even after adjusting the spectral data for the mean R-R interval. This effect was exacerbated for patients on atypical antipsychotics. Likewise, nonlinear complexity analysis showed significantly impaired HRV for medication-free patients that was exacerbated in the patients on atypical antipsychotics.
  
  
  CONCLUSIONS
  Altogether, the data suggest a pattern of significantly decreased cardiac vagal function of patients with schizophrenia as compared to healthy controls, apart from and beyond any differences due to medication side effects. The data additionally confirm earlier reports of a deleterious effect of atypical antipsychotics on HRV, which may exacerbate an underlying vulnerability in patients. These results support previous evidence that autonomic abnormalities may be a core feature of the illness (or psychosis), and that an even more conservative approach to cardiac risk in schizophrenia than previously thought may therefore be clinically appropriate.
authors.affiliation: Department of Biomedical Engineering, School of Medicine at the State University of New York, Stony Brook, NY 11794, USA. lilianne.strey@sunysb.edu
authors.forename: L R
authors.initials: LR
authors.lastname: Mujica-Parodi
authors.forename: Vikram
authors.initials: V
authors.lastname: Yeragani
authors.forename: Dolores
authors.initials: D
authors.lastname: Malaspina
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D003710:Demography; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D013057:Spectrum Analysis
chemical_list: D014150:Antipsychotic Agents