Next, empirical evidence for the immunologic and neuroimaging aspects of bereavement, and of CG specifically, will be reviewed. Finally, the article ends with a summary of some of the gaps in knowledge of the neurobiological and immunological aspects of CG. Bereavement models and theories Why investigate the immunological and neuroimaging biomarkers of CG? Certainly there is value in the mere evidence of these biomarkers, but in addition, the physiological

components or correlates Inhibitors,research,lifescience,medical of CG may help us to understand how CG arises, predict who it may affect, and CT99021 in vitro provide suggestions for how to treat it. However, these latter reasons are best served when there is a clear theory behind

the study of the biomarkers. Theory points us in the direction for study, and the results of the studies inform and refine Inhibitors,research,lifescience,medical our theories. The following section reviews cognitive stress theory, attachment theory, and the biopsychosocial model of CG. Cognitive stress theory suggests that the death of a loved one is stressful Inhibitors,research,lifescience,medical because it is a disruptive event requiring a great deal of adjustment.2 In addition, at exactly the moment when one must cope with a significant stressor, a primary source of support may be absent (ie, the deceased), reducing one’s emotional and instrumental resources. This is one definition of stress: the perceived demands of the situation tax or exceed the individual’s perceived coping resources.3 Attachment Inhibitors,research,lifescience,medical theory states that the bonds between parent and child, and romantic partners, is a product of behavioral conditioning whereby an association is developed between the attachment figure and: (i) a reduction in distress; and (ii) the generation of pleasure.4 Inhibitors,research,lifescience,medical This conditioning explains a variety of behaviors, such as the maintenance of close proximity between bonded individuals, the development of mental schemas, or working models, that provide comfort during absence of the attachment figure, and distress that is generated upon separation

from the attachment figure. For bereavement, attachment theory has specific predictions. Bereavement Digestive enzyme includes a gradual extinction of this conditioning, in which the regulatory benefits conferred by mental representations of the attachment figure diminish slowly over time. Bowlby4 described the end point of successful mourning as a psychological reorganization of one’s thoughts and feelings about a deceased attachment figure (for review, see ref 5). In a very elegant study comparing cognitive stress theory and attachment theory, Stroebe and colleagues2 examined a prospective dataset of older adults. At the baseline, both members of the couple were alive. At the second time point, one of the spouses had died.