Response

Fine particulate matter (PM_2.5, with an aerodynamic diameter ≤2.5 µm) has been identified as the predominant air pollutant detrimental to human health and is an important risk factor for mortality worldwide.^{Reference Wang, Ma, Ma, Li, Hua and He1} Several studies have also revealed that PM_2.5 could significantly increase the risk of brain diseases, including schizophrenia.^{Reference Sethi, Agarwal, Vora and Gosavi2} With these considerations in mind, we enjoyed reading Liu et al’s recent paper on air pollutants, genetic susceptibility and the risk of schizophrenia.^{Reference Liu, Li, Ma, Tang, Chen and Tian3} Despite agreeing with the authors’ conclusion that long-term exposure to air pollutants was positively related to the risk of schizophrenia, we should not overlook that urban air pollution is a leading problem and can cause serious cardiovascular dysfunction in individuals with schizophrenia.

It is well known that schizophrenia is one of the leading causes of years lived with disability worldwide.^{Reference Zhong, Tan, Chen, Huang, Huang and Li4} Although the burden of schizophrenia is increasing globally, it is mainly driven by the mortality associated with relapsed schizophrenia.^{Reference Zhong, Tan, Chen, Huang, Huang and Li4} Importantly, the mortality rate in people with schizophrenia is higher compared with that in the general population, and sudden unexpected death in schizophrenia is now a widely recognised cause of death in this population.^{Reference Li, Greenstein and Delisi5} In this sense, people with schizophrenia carry a three-fold higher likelihood of experiencing sudden unexpected death, accounting for up to 20% of mortality in this specific population.^{Reference Li, Greenstein and Delisi5} Unfortunately, the occurrence of sudden unexpected death in schizophrenia is extremely difficult to estimate. On the other hand, discovering and carefully evaluating new risk factors that may contribute to the onset of cardiovascular abnormalities in people with schizophrenia might prevent the occurrence of fatal events in these individuals. We should recognise that urban air pollution may have important repercussions in this context. In fact, it is currently determined that certain population subgroups defined by demographic factors, geographical location, their country’s economic status and individuals’ comorbidities may experience the adverse cardiovascular effects of air pollution exposure, and one of these subgroups is people with schizophrenia.^{Reference Wang, Ma, Ma, Li, Hua and He1,Reference Zhong, Tan, Chen, Huang, Huang and Li4,Reference Tibuakuu, Michos, Navas-Acien and Jones6} Furthermore, several studies clearly demonstrate that acute and chronic exposures to particulate matter can promote the onset and aggravation of cardiovascular events in susceptible individuals, including cardiac autonomic nervous system imbalance, increased blood pressure, metabolic disorder, accelerated atherosclerosis and plaque vulnerability, platelet aggregation and thrombosis.^{Reference Feng, Huang, Zhang, Feng, Zhang and Cao7} Importantly, we cannot ignore the fact that long-term exposure to PM_2.5 has the potential to cause disruption to cardiac structure and function, ultimately leading to cardiovascular abnormalities and sudden death.^{Reference Feng, Huang, Zhang, Feng, Zhang and Cao7,Reference Franchini and Mannucci8} Although the mechanisms underlying such effects are not well understood, translational studies suggest that PM_2.5-induced cardiovascular abnormalities may be associated with inflammatory processes or oxidative stress triggered by reactive oxygen species in affected cells, genotoxicity, dysregulation of Ca²⁺ signalling, disturbance of autophagy and induction of apoptosis.^{Reference Feng, Huang, Zhang, Feng, Zhang and Cao7–Reference Thangavel, Park and Lee9}

Based on these data, what lessons do we learn? First, schizophrenia is a multicausal and systemic disease. Second, schizophrenia can be complicated by sudden death. Third, air pollution is a serious public health problem. Finally, the excellent article discussed here^{Reference Liu, Li, Ma, Tang, Chen and Tian3} should stimulate translational research to carefully assess whether environmental exposure to air pollution is an aggravating event for sudden unexpected death in schizophrenia.