Neurological Disorders and Risk of Arrhythmia

Abstract

Neurological disorders including depression, anxiety, post-traumatic stress disorder (PTSD), schizophrenia, autism and epilepsy are associated with an increased incidence of cardiovascular disorders and susceptibility to heart failure. The underlying molecular mechanisms that link neurological disorders and adverse cardiac function are poorly understood. Further, a lack of progress is likely due to a paucity of studies that investigate the relationship between neurological disorders and cardiac electrical activity in health and disease. Therefore, there is an important need to understand the spatiotemporal behavior of neurocardiac mechanisms. This can be advanced through the identification and validation of neurological and cardiac signaling pathways that may be adversely regulated. In this review we highlight how dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, autonomic nervous system (ANS) activity and inflammation, predispose to psychiatric disorders and cardiac dysfunction. Moreover, antipsychotic and antidepressant medications increase the risk for adverse cardiac events, mostly through the block of the human ether-a-go-go-related gene (hERG), which plays a critical role in cardiac repolarization. Therefore, understanding how neurological disorders lead to adverse cardiac ion channel remodeling is likely to have significant implications for the development of effective therapeutic interventions and helps improve the rational development of targeted therapeutics with significant clinical implications.

Keywords: antipsychotic drugs; cardiovascular disease; ion channels; mental illness.

Figure 1

Functional interaction between brain and heart disorders. Scheme of the behavioral, psychosocial and biological risk factors shared among psychiatric disorders that are involved in the increased incidence of cardiovascular diseases. HPA axis = Hypothalamic–Pituitary–Adrenal axis, ANS = Autonomic Nervous System, SNS = Sympathetic Nervous System, PNS = Parasympathetic Nervous System, HR = Heart Rate, BP = Blood Pressure, NE = Norepinephrine, TNF-α = Tumor Necrosis Factor Alpha, PTSD = Post-Traumatic Stress Disorder, I_Kr = Rapid Delayed Rectifier Potassium Current, I_Ks = Slow Delayed Rectifier Potassium Current, I_Ca,L = L-Type Calcium Current, I_Na = Sodium Current, ↑ increased, ↓ decreased.