This study focused on identifying risk factors for adolescent post-infectious chronic fatigue syndrome (CFS), utilizing a prospective, nested case–control longitudinal design in which over 300 teenagers with infectious mononucleosis (IM) [aka EBV or glandular fever] were identified through primary care sites and followed. Baseline variables that were gathered several months following IM, included autonomic symptoms, days in bed since IM, perceived stress, stressful life events, family stress, difficulty functioning and attending school, family stress, and psychiatric disorders.

A number of variables were predictors of post-infectious CFS at six months; however, when autonomic symptoma were used as a control variable, only days spent in bed since mono was a significant predictor. Step-wise logistic regression findings indicated that baseline autonomic symptoms as well as days spent in bed since mono, which reflect the severity of illness, were the only significant predictors of those who met CFS criteria at six months.


IM appears to be a predisposing factor for some individuals who develop CFS, especially adolescents (Feder et al., 1994; Smith et al., 1991). Many candidate risk factors have been proposed to explain this phenomenon, but almost all lack prospective data from before IM or CFS. According to this study, significant baseline predictors in the step-wise logistic regression included autonomic symptoms and days spent in bed since the onset of IM. This suggests that indices of illness severity are the best predictors for adolescents destined to develop CFS following IM. It is reasonable to conclude from our study that during the first few months following IM, young people who have more limitations and are more impaired, are subsequently more likely to develop CFS. Our findings are thus comparable to those of Hickie et al. (2006), who followed patients with mononucleosis (glandular fever), Q fever, and Ross River virus who later met criteria for CFS. Development of CFS in their cohort was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors.

Psychological distress has been found to play a significant role in relation to the course of oral and genital herpes virus reactivation, exacerbation of HIV and the development of IM (Carver, Connallon, Flanigan, & Crossley-Miller, 1994; Cohen & Williamson, 1991; Glaser et al., 1991; Imboden, Canter, & Cluff, 1961; Kasl, Evans, & Niederman, 1979; Perry, Fishman, Jacobsberg, & Frances, 1992). However, Hickie, Koschera, Hadzi-Pavlovic, Bennett, and Lloyd (1999) found that chronic fatigue is a persistent diagnosis over time and that longitudinal patterns of comorbidity of fatigue with psychological distress did not suggest a causal relationship or common vulnerability factor. This study also did not find that psychiatric disorders assessed a few months after developing IM were associated with the development of CFS, after controlling for ACS.

Several studies have identified family stress as a precursor to CFS (Carter et al., 1999; Van Middendorp, Geenen, Kuis, Heijnen, & Sinnema, 2001). The studies by van Middendorp and Carter were of children referred to psychologists, in whom one would anticipate a higher rate of behavioral factors. In these studies, along with a potential for referral bias, these adolescents most likely are not representative of the CFS population as a whole. Taylor, Jason, and Jahn (2001) found prevalence rates of sexual and physical abuse among individuals with CFS comparable to those found in individuals with other conditions involving chronic fatigue. Our study also did not show a relationship between familial stress and the development of post-infectious CFS.

Brown, Bell, Jason, Christos, and Bell (2012) examined long-term outcomes of 25 people who were diagnosed with CFS while they were adolescents, approximately 25 years ago. Of the 25 participants, only 5 self-reported maintaining that diagnosis, while 20 reported remission. In spite of their self-reported remission, however, those 20 participants showed significantly more impairment compared with controls, demonstrating that, while adolescents diagnosed with CFS may show improvement over time, they still suffer some level of impairment and may not return to their premorbid level of functioning. Clearly, given the long-term effects of CFS, it is critical to better understand potential risk factors associated with this illness.

It is important to note that the baseline visit occurred within a median of two months of the diagnosis of IM, but the diagnosis of mono itself would have taken some additional time. A reasonable assumption about IM in adolescents is that symptoms are present for up to a month before diagnosis, making the time for administration of the questionnaires up to three months after the onset of illness. Therefore, some of the stressful life events recorded might have occurred in the three months after the onset of IM and might, therefore, have been influenced by the illness severity rather than by prior family stress. Questions on the PSS begin with the wording: “In the last month, how often have you … ” Due to the timing of enrollment, the perceived stress may also be more likely to reflect the stress caused by the illness rather than perceived stress when the individual was healthy. Thus, our study cannot address the issue of whether pre-IM stress is a risk factor for developing CFS following IM in adolescents. While it is true that the Life Events Questionnaire for Adolescents asked about life events in the preceding year, we were not able to specifically tease out those events that occurred prior to the onset of IM. It is also important to differentiate difficulty in school functioning (which infers a behavioral problem) from illness severity as risk factors for the development of CFS following IM, which this study was also unable to accomplish.

This study has several other limitations, including modest sample size and data only at a six-month assessment following IM. In addition, the sample was relatively homogenous in terms of gender and ethnic group. There is a need for more long-term studies with larger community-based samples in order to better identify the predisposing medical and psychological risk factors involved in the development of pediatric CFS. Future studies might examine biological data on symptom severity at onset of IM (such as thromobocytopenia or anemia) in those who develop CFS versus those that do not following IM.

The relationship between IM and CFS needs to be fully understood; not only for comprehending the relationship between the two illnesses, but also for healthcare-provider guidance to adolescents and their parents. The prevention of the progression from IM to CFS not only saves the patient from the potential of lifelong disability, financial dependency, and the potential for ensuing depression, but may save the family from life-altering care-giving and financial responsibilities; the stresses of which alter the family dynamics so drastically and detrimentally that the family unit itself may not survive.

Predictors of post-infectious chronic fatigue syndrome in adolescents by Leonard A. Jasona, Ben Z. Katzb, Yukiko Shiraishic, Cynthia J. Mearsd, Young Ima & Renee R. Taylore in Health Psychology and Behavioral Medicine Volume 2, Issue 1, 2014



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