29,37 It is therefore assumed that activation of the rACC at the acute stage of grief contributes to the promotion of the normal grieving process. It is thought that the low activation of ACC at the

early stage of grief in bereaved with PTSD leads to dysfunction of emotion regulation, resulting in interference with the normal grief process and developing CG. Table II. Comorbidity of post-traumatic stress Inhibitors,research,lifescience,medical disorder (PTSD) and major depressive disorder (MDD) with complicated grief (CG). It was reported the activation of nucleus accumbens, related to the reward system, was associated with CG, which was correlated with strong yearning for the deceased without being able to accept the death.38 Similarly, bereavement with PTSD Inhibitors,research,lifescience,medical is ARN-509 considered to be more difficult to accept the death than those without PTSD, because not only sadness, but also fear, might be evoked when recalling the deceased. In fact, it has been reported that PTSD, or its intrusion symptoms, was responsible for the severity of CG.9,13,39,40 Those reactions work to disrupt the normal grief process and contribute to the onset of CG. The effectiveness of cognitive behavioral therapy for CG, including exposure to death, serves as evidence for the effect of PTSD on CG.31,41-43 Asukai et

al43 modified the CG therapy31 for those bereaved Inhibitors,research,lifescience,medical by violent death, to focus more on an exposure exercises in traumatic situations, and reported that this modified treatment was effective for both symptoms of PTSD and CG. This result suggested that improvement Inhibitors,research,lifescience,medical of PTSD symptoms might act on reducing CG symptoms. Conclusion Violent death is not only sudden and unexpected, but threatens others by intentional power, resulting in significant impact on the mental health of bereaved persons. It was reported that there was 12.5% to 78% prevalence of CG9,13-16 among those bereaved by Inhibitors,research,lifescience,medical violent death. The factors affecting

such high prevalence of CG following violent death are lack of readiness for the death, difficulty in sense-making, a high level of negative appraisal about the self and others, and various social stressors, such as exposure to the mass media, social stigma, and legal procedures. The Metalloexopeptidase comorbidity of PTSD was particularly considered to contribute to the development of CG by suppressing the functioning of the mPFC and the ACC, which facilitates the mourning process when grief distress is activated and interrupts acceptance of death. The DSM-5 working group is currently discussing whether CG as a bereavement-related disorder will be included in axis I mental disorders. However, its symptomatology and the biological basis of its pathology are unclear. It will be helpful to clarify the effect of PTSD on CG among survivors of violent death for understanding the pathogenic mechanism of CG and developing preventive intervention and treatment of CG.