Creatine kinase (CK) and its association with aggressive behavior in patients with schizophrenia☆
Introduction
Aggression is a common symptom in patients with mental illnesses (Daffern et al., 2003; Barzman et al., 2011). It is a body response with an intended infliction of physical harm, including verbal, physical aggression, and aggression against self or others (Glasser, 1998). Aggressive behavior is characterized as sudden, multitude and severe. Larkin reported over 500 violent incidents over a 6-month period at Rampton Hospital, which indicated a rate of more than two incidents per day in that setting (Larkin et al., 1988). A prospective cohort study of 8003 people revealed that the risk of violent crime was significantly increased among people with schizophrenia and co-morbid substance abuse (Fazel et al., 2009; Putkonen, 2010). Hunter reported an annual total 134 serious injuries in a 973 bed forensic psychiatric hospital (Hunter and Carmel, 1992). The average costs per injury were conservatively estimated to be $5719, making the total annual loss of $766,290. The inpatient psychiatric nurses suffered injuries frequently as they deal with the clients at the first line (Cheung et al., 1996; Tamm et al., 1996). The violent and aggressive behaviors have been threatening the health, safety and well-being of patients, staff and others. They caused significant medical consequences and financial burdens.
Clinicians and researchers have been working on how to predict and prevent aggressive behavior. Apart from comprehensive history and symptoms collection, a number of tools were developed to assess the risk of aggression (Singh and Fazel, 2010). Singh did the meta-analyses which identified over 120 structured instruments that were designed to assess and predict violence in psychiatric clients (Singh et al., 2011). However, the analysis did not show effectiveness of these instruments in the evaluation of patients with schizophrenia. And the content of each instrument varied a lot and were not consistent.
Creatine kinase (CK) was noticed to be related to the aggressive behavior in individuals with psychosis (Meltzer et al., 1980; Manor et al., 1998; Hermesh et al., 2002a, Hermesh et al., 2002b). Also known as creatine phosphokinase (CPK), CK consists of three isoenzymes: CK-MM, CK-MB and CK-BB. They were mainly found in specific human tissues: MM in skeletal muscles, MB in heart, and BB in brain. CK-MB was confirmed as a biological marker for heart trauma (Manenti et al., 2006). CK-MM is widely used as a biological marker of skeletal muscle damage, especially in the exercise-induced muscle damage (Clarkson et al., 2006; Gill et al., 2006). Because >95% of CK is stored in skeletal muscle (Walker, 1979), CK is a label of muscle damage and pathology as multiple tissue-specific circulating isoforms. Some studies revealed that increased CK activity was caused by physical trauma, intramuscular injections, neuroleptic malignant syndrome, cardiac disease, seizure, restraint and intense isometric activity (Gabow et al., 1982; Cavanaugh and Finlayson, 1984; Egan et al., 1993). However, the increased CK level found in patents with psychotic manic episodes and schizophrenia might not be exclusively caused by the above nonspecific factors (Meltzer et al., 1980; Manor et al., 1998; Hermesh et al., 2002a, Hermesh et al., 2002b).
Segal reported that increased CK level was found in the manic patients but not in the depressed patients (Segal et al., 2007). Other studies indicated that a large proportion of hospitalized patients with schizophrenia or psychotic mood disorder displayed elevated CK level during the acute stage (Meltzer, 1968; Meltzer, 1969; Meltzer et al., 1969). The increased CK level was also found in the forensic inpatients who had aggressive behaviors (Spitz et al., 1997; Hillbrand et al., 1998). However, the exact relationship between CK level and aggression remains unclear. There is not enough evidence to support the diagnostic and predictive implication of CK level in the evaluation of aggressive behaviors in the psychotic patient. The laboratory test of CK level has not been standardized as different machines produced by different manufacturers have different norms (Grube et al., 2008). The diagnostic criteria for CK level has not been established yet.
Thus, our study aimed to study the relationship between the CK level and aggressive behaviors in the Chinese patients with schizophrenia, and to analyze the risk of aggressive behavior increased in patients with high CK value compared with patients with normal CK value.
Section snippets
Sample
This retrospective study recruited 2780 Chinese patients with schizophrenia who were consecutively admitted to the five psychiatric inpatient units at the Mental Health Center of West China Hospital, Sichuan University from January 2009 to December 2013. The diagnosis of schizophrenia was made according to the DSM-IV criteria (American Psychiatric Association, 2000). The subjects were divided into 2 groups: the patients who had aggressive behavior and those without aggressive behavior before
Demographic data and CK level
A total of 2780 Chinese subjects with schizophrenia were included as they met the inclusion and exclusion criteria. The demographic data and serum CK level results were shown in Table 1. The normal range of CK levels was 19–226 U/L for male and female. The subjects were divided into high CK group (serum level > 226 U/L) and normal CK group (serum level = 19–226 U/L). There were 81.6% (2269/2780) patients who had a normal range of serum CK level (M = 81.29 U/L; SD = 42.85) and 28.4% (511/2780) patients had
Discussion
This retrospective study examined the relationship between the elevated CK level and aggressive behavior in the Chinese inpatients with schizophrenia. There was a statistically significant difference of CK level between the aggressive and non-aggressive group. The increased CK level was positively correlated with the risk of aggression. Risk of aggressive behavior increased in patients with high CK value compared with patients with normal CK value prior to admission (OR = 8.08). The aggressive
Limitations
The limitations of this study need to be addressed. The retrospective case review could have distorted or missed data. Different lab machines may produce different values. We could not differentiate the severity level of the aggression and its association with the CK level. The study was conducted in one hospital in Chengdu, China, and the findings may not be generalized to other populations. Future research should include prospective studies on large samples and other conditions including
Conclusion
In summary, the aggressive patients with schizophrenia displayed increased CK level in our study. We need more future researches to prove that CK elevations related to aggression is a persistent, stable feature. Aggressive behaviors threaten the safety and well-being of both patients and staff members. It would be helpful to take into account of the CK level along with other risk factors when evaluating clients with schizophrenia and history of violence. It may be indicated to order lab test of
Conflict of interest
None to declare.
Author contributions
Study design: Xi Cao, Xian-Dong Meng, Tao-Li, Ji-Ping Li. Data collection and analysis: Xi Cao and Xian-Dong Meng. Manuscript preparation: Xi Cao, Xian-Dong Meng. All authors contributed to and have approved the final manuscript.
Source of funding
Financial support for this research was provided by the Natural Science Foundation of China (key project). The foundation item is schizophrenia molecular genetic mechanisms of brain network connection, and foundation number is 81130024.
Acknowledgement
We would like to express our appreciation to Sherrie Wang, from Williamsville School District, Buffalo, NY for their help in English proofreading.
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Xiandong Meng is the first author, Xi Cao is the co-first author, Tao Li is the first corresponding author, Jiping Li is the second corresponding author.