The role of stress and anxiety in the onset of familial Creutzfeldt-Jakob Disease (CJD): Review

Abstract

Creutzfeldt-Jakob Disease (CJD) is considered to be a sudden and fatal degenerative brain disorder that leads to death within a few months. In the last decade, we have studied the course of familial CJD (fCJD) among Jews of Libyan descent, one of the largest clusters of fCJD in the world. Recently, we published results that included the identification of abnormal anxiety levels in healthy CJD E200K mutation carriers that were significantly different from those of healthy non-carriers from the same families. All participants were first-degree relatives of patients known to have been carriers of the E200K mutation and had died from CJD, and none of the participants was aware of his/her genetic make-up. In the current review, it is suggested that an abnormality in anxiety levels among the healthy fCJD mutation carriers may reflect the clinical presentation of the disease onset especially during and after any stressful experience. This hypothesis is supported by a summary of relevant literature, dealing with psychological, physiological, and cellular aspects.

The Cost of Stress: A Dilemma With Healthy Mutation Carriers

“…Such thoughts can generate elevated anxiety levels leading to an insufferable life. By considering the recent hypothesis relating the involvement of stressful events in CJD outbursts, we realize that the rendering of such information may ipso facto be fatal (Gigi, 2009). In most cases, the definite knowledge of being a carrier does not improve the person's spiritual state; on the contrary, it serves to induce anxiety, which is detrimental for them.…”

“…Recently, it was argued that theories that focus on stress and coping provide a useful framework for future studies of genetic testing decisions for adultonset disease risk (Gooding, Organista, Burack, Biesecker, 2006). Still, in light of the anxiety hypothesis in CJD (Gigi, 2009) and the absence of available treatment for the disease, the central question remains: Is giving (on request or even demand) individuals information about their genetic status helpful or detrimental to their well-being?…”

“…Because this study was double blind, neither the participants nor the examiner were aware of the participants' genetic status, yet only the carriers perceived the first-degree relative death as highly stressful. Consequently, it was suggested that PRNP mutation carriers are prone to perceive stimuli as more stressful (Gigi, 2009). Additional data also show a relationship between CJD and stressful life events (Brandel & Delasnerie-Laupretre, 1997;Gigi & Babai, 2006;Gigi et al, 2005;Laske et al, 1999).…”

“…However, there is some cumulative animal evidence to support the notion that stress is indeed involved in the cause or triggering of the manifestations of CJD (Kurschner & Morgan, 1996;Matsuki, Shirayama, Hashimoto, Tanaka, & Minabe, 2001;Rieger, Edenhofer, Lasmezas, & Weiss, 1997;Tatzelt, Voellmy, & Welch, 1998). As a result, several research efforts have recently suggested that stress stemming from both psychological (e.g., difficult life events) and/or physical (e.g., due to surgery or anesthesia) events can lead to an almost immediate acceleration of symptom onset in those who are carriers (Gigi, 2009). Individuals from fCJD pedigrees seeking predictive genetic testing are often motivated by traumatic experiences with affected first-degree relatives.…”