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

Abstract

Schizophrenia (SCZ) is a psychiatric disorder characterized by a wide range of positive, negative and cognitive symptoms, along with an increased risk of metabolic syndrome and cardiovascular disease that contribute to a 15–20-year reduced life expectancy. Autonomic dysfunction, in the form of increased sympathetic activity and decreased parasympathetic activity, is postulated to be implicated in SCZ and its treatment. The aim of this narrative review is to view SCZ through an autonomic lens and synthesize the evidence relating autonomic dysfunction to different domains of SCZ. Using various methods of assessing autonomic activity, autonomic dysfunction was found to be associated with multiple aspects of SCZ pathophysiology, including symptom severity, cognitive impairment, and the development of cardiometabolic comorbidities, such as metabolic syndrome and high BMI. The strongest association of low heart rate variability was noted among patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine). The review will also suggest ways in which studying autonomic dysfunction can help reduce morbidity and mortality associated with SCZ and its treatment.

A Potential Interface between the Kynurenine Pathway and Autonomic Imbalance in Schizophrenia

“…Furthermore, it contributes to poor medication compliance, worsened quality of life, increased severity of psychotic symptoms and increased mortality (including various causes of death in schizophrenia). The increased risk of premature death in patients with schizophrenia is at two to three times that of the general population, that has a great importance to find a potential therapeutic solutions to improve the autonomic disturbances [ 14 , 42 , 45 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ].…”

“…In antipsychotic treated patients cardiac autonomic dysregulation and reduced complexity of heart rate modulation have been reported, that highly correlated with the pharmacodynamics of the drug applied [ 7 , 46 , 76 , 77 , 78 ]. Thus, the strongest association of low heart rate variability was noted among schizophrenic patients on antipsychotic treatment with high-affinity muscarinic antagonism (i.e., clozapine, olanzapine and quetiapine), that further signify the autonomic dysregulation [ 14 , 79 , 80 , 81 ].…”

“…Pupillography is a non-invasive and cost-effective method to determine autonomic activity, and it is suitable to examine both the sympathetic and parasympathetic functions in the context of schizophrenia, too [ 8 , 14 , 64 ]. The main sympathetically influenced parameter is the resting pupil diameter, which is significantly increased in patients suffering from schizophrenia [ 8 ].…”

“…Besides the behavioral alterations, schizophrenia is commonly associated with autonomic imbalance, that may be related to increased morbidity and mortality [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Thus, the autonomic dysfunction is associated with multiple aspects of schizophrenia pathophysiology, including symptom severity, cognitive impairment and the development of cardiometabolic comorbidities, such as metabolic syndrome and high body mass index [ 8 , 10 , 11 , 14 ].…”

“…Besides the behavioral alterations, schizophrenia is commonly associated with autonomic imbalance, that may be related to increased morbidity and mortality [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Thus, the autonomic dysfunction is associated with multiple aspects of schizophrenia pathophysiology, including symptom severity, cognitive impairment and the development of cardiometabolic comorbidities, such as metabolic syndrome and high body mass index [ 8 , 10 , 11 , 14 ]. The high number of articles (481 in August 2021) found in MEDLINE search using “schizophrenia and autonomic nervous system” (ANS) keywords also suggests that the disturbance of the ANS has a high impact and its treatment is very important in this patient group.…”