Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health

Fig. 1. Summary of sympathovagal balance in schizophrenia. Studies of heart rate variability (HRV) use the LF/HF ratio as a proxy for estimating sympathetic activity. HRV studies in schizophrenia have found contradictory findings in terms of the LF/HF ratio. In some instances, autonomic dysfunction in SCZ can be characterized as a decreased parasympathetic functioning while maintaining relatively normal sympathetic activation (~LF/HF ratio). In other cases, the LF/HF ratio is elevated. This may represent two different scenarios: (1) increased sympathetic activation (high LF numerator) or (2) decreased parasympathetic activation (low HF denominator), leading to sympathetic dominance.

Fig. 2. Antipsychotic properties and their effects on autonomic functioning and heart rate variability. The differing effects of antipsychotics (AP) on autonomic dysfunction and heart rate variability (HRV) may be dependent on the pharmacokinetic properties of the APs (i.e. their affinities for cholinergic and adrenergic receptors).

Fig. 3. The Neurovisceral Integration Hypothesis. a Cognitive and emotion processing functions are regulated by brain systems also involved in the regulation of the autonomic nervous system. The Neurovisceral Integration Hypothesis asserts that the prefrontal cortex (PFC) exerts tonic inhibition over limbic brain regions (curved red line) that typically suppress parasympathetic responses (straight red line) and activate sympathetic responses (straight green arrow). b In schizophrenia, deficits in the PFC may lead to disinhibition of the amygdala and medullary regions (orange lines) during situations of emotional or social processing. This results in suppression of parasympathetic activity and stimulation of sympathetic activity, thereby causing increased heart rate and decreased heart rate variability. This may potentially be an explanatory mechanism underlying the correlation between decreased HRV and reduced PFC activity.

Fig. 4. Implications of autonomic nervous system dysfunction in schizophrenia. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, has been implicated in various disease states. Autonomic dysfunction, as assessed through heart rate variability (HRV) and other assessment methods, has been related to various domains of SCZ, including psychopathology, cognitive functioning, cardiometabolic risk, and microbiome changes. The relationship between these domains and autonomic functioning is believed to be bidirectional. SCZ Schizophrenia, HR heart rate, HRV heart rate variability.