Abstract
Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear, and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38). We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress associated neural plasticity, and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.
Highlights
Physical and mental threat can induce fear responses, and fear can be associated with objects and places through a process of Pavlovian fear conditioning (Ledoux, 2000)
Using gene expression microarray data from the Online Stanley Genomics Database1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38)
We investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46).The expression levels of CAMK2B, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase 9 (MAPK9), and protein kinase C iota (PRKCI) were increased in the PFC of suicide victims as compared to non-suicide controls
Summary
Physical and mental threat can induce fear responses, and fear can be associated with objects and places through a process of Pavlovian fear conditioning (Ledoux, 2000). Stress is a multi-dimensional challenge to physical and mental homeostasis that can be triggered by fear (Kim and Diamond, 2002; McEwen, 2007), and both acute and chronic stress can alter the properties of fear (Conrad et al, 1999; Rodrigues et al, 2009). A study using a large scale of civilian population (N = 34,653) found that over 70% of the individuals who reported a lifetime history of a suicide attempt had anxiety disorders (Nepon et al, 2010). Individuals with comorbidity of personality disorders such as neuroticism and posttraumatic stress disorder (PTSD) showed a much stronger association with suicide attempts than those who had PTSD alone.
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