Heart rate variability response to mental arithmetic stress in patients with schizophrenia: Autonomic response to stress in schizophrenia
Introduction
Schizophrenia is characterised by macroscopic and histopathological abnormalities of cortical structures concerned with autonomic control, including the hippocampi, and temporal, cingulate, and prefrontal areas. (McDonald et al., 2004). Although it is well established that schizophrenia is highly heritable (Kendler et al., 1994, Cardno et al., 1999), the syndrome probably requires the concerted effect of several susceptibility genes, in addition to exposure to environmental noxious stimuli (e.g. perinatal damage and psychosocial stressors) in order to be expressed (McDonald and Murray, 2000). Environmental stress influences the time of emergence of symptoms of psychosis (Doering et al., 1998), and according to this “vulnerability-stress model” (Nuechterlein and Dawson, 1984), psychotic symptoms appear whenever stressors exceed the afflicted person's vulnerability level, which is considered a stable, or “trait,” characteristic (Nuechterlein and Dawson, 1984).
The autonomic nervous system is a major bodily mediator of stressful emotions, hence theories of symptom development in schizophrenia have long incorporated the notion of autonomic dysfunction as central to the manifestation of psychosis. Kraepelin (1899) identified extensive autonomic alterations in schizophrenic patients, including pupillary, vasomotor, sweating, heart rate, salivation, and temperature changes, most of them suggesting increased sympathetic output, decreased parasympathetic activity, or both. Later studies on the subject have confirmed and extended those early observations (Lindstrom, 1996). Most available data about autonomic responses to environmental stress in schizophrenia refer to alterations of electrodermal responses (Venables, 1992, Grossberg, 2000). Although skin conductance orienting “hyporesponsiveness” in schizophrenia was suggested to be related to attentional and arousal deficits characteristic of the disorder (Dawson et al., 1994), skin lacks significant parasympathetic innervation.
In the last two decades heart rate variability (HRV) analysis has been developed as a tool to probe the peripheral autonomic output in the cardiovascular territory (Boettger et al., 2006). Most available data obtained with this tool in schizophrenia refer to acute states and show vagal withdrawal or decreased baroreflex sensitivity (Boettger et al., 2006), which support a status of baseline autonomic “hyperarousal” (Williams et al., 2004) in acute schizophrenia. We sought to probe the autonomic reaction to stress in patients with schizophrenia using this tool.
In light of previous observations, we hypothesised that in the patient sample the cardiovascular autonomic status at rest would be characterised by an increased sympathetic/vagal balance and response to stress would be less intense than in controls, paralleling the “hyporesponsiveness” observed in electrodermal studies. Patients with schizophrenia have increased cardiovascular morbidity and cardiac autonomic alterations have been implicated in the increased cardiovascular mortality (Ewing, 1992, Hennekens et al., 2005). Alterations of the cardiac autonomic response to stress may therefore have a cardiovascular prognostic value as well.
Section snippets
Patients
Psychiatry outpatients reaching DSM-IV diagnostic criteria were invited to participate in the study if (a) diagnosis was confirmed with a Composite International Diagnostic Interview (Robins et al., 1988) administered by a psychiatrist participating in the study, (b) aged 18 to 75 years, and (c) on stable medication for at least two weeks. Exclusion criteria were (a) use of illegal substances in the previous 6 months or a history of substance abuse/dependence (b) active symptoms having recently
Results
Table 1 shows the demographic and clinical characteristics of patients and controls. Two women and one man declined to participate in the study. Patients showed a trend towards greater body mass index (BMI), and were less educated than controls. All patients had been on stable doses of antipsychotics for at least two weeks; three were receiving two different antipsychotics simultaneously. Respiratory rate ranged between 13 and 21 cpm (0.22–0.35 Hz) in all participants throughout testing.
Discussion
This study shows that patients with schizophrenia exhibit (a) a decreased baseline HRV and an increased baseline heart rate probably related to impaired parasympathetic input to the heart (as measured by HF-HRV), (b) a normal heart rate response to the standard mental arithmetic stress test of autonomic function, (c) a normal pattern and intensity of the cardiac autonomic response to mental stress in terms of increased sympathetic input (as inferred from increases in LF-HRV) and decreased vagal
Role of the funding source
MNC is a medical student research fellow from the University of Buenos Aires (Project M084). DEV is a fellow from the Argentine National Council on Scientific and Technological Research, CONICET. This study was supported in part by FLENI Foundation, UBACyT (Project M084, SMG), and CONICET (SMG, DPC). These founding sources had no involvement in the study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for
Contributors
SMG and MNC designed the study and wrote the protocol. SMG, MNC, HW, and EC managed the literature searches and analyses. SMG, MNC, HW, RDF, MN, DA, and RCL collected experimental data. DEV, SMG, MNC, DPC, and HW undertook the statistical analysis, and MNC wrote the first draft of the manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest
All authors declare that they have no conflicts of interest.
Acknowledgement
No acknowledgements.
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