Background: Substantial heterogeneity exists in both the severity of symptoms experienced as part of the sickness response to naturally-occurring infections, and the time taken for individuals to recover from these symptoms. Although contributing immunological and genetic factors have been previously been explored, less is known about the role of individual psychological and psychosocial factors, which may modulate the host immune response, or contribute independently, to symptom severity and duration.
Methods: Longitudinally-collected data from 484 Caucasian participants (mean age: 33.5 years; 51% women) experiencing a naturally-occurring acute infective illness enrolled in the prospective Dubbo Infection Outcome Study (DIOS) were analysed. At intake and subsequent follow-up assessments, self-report questionnaires were used to ascertain individual psychological and psychosocial characteristics and symptom information. Principal component analysis was applied to symptom data to derive endophenotype severity scores representing discrete symptom domains (fatigue, mood, pain, neurocognitive difficulties) and an overall index of severity. The contribution of individual psychological (trait neuroticism, locus of control, and illness behaviours) and psychosocial factors (relative socioeconomic advantage) to endophenotype severity at baseline were examined using multivariable linear regression models; interval-censored flexible parametric proportional hazards survival models were used to explore time to recovery (defined using within-sample negative threshold values).
Results: After controlling for time since symptom onset, greater levels of trait neuroticism consistently predicted greater symptom severity across all symptom domains (all p's < 0.015). Similarly, greater relative socioeconomic disadvantage was significantly associated with greater severity across all endophenotypes (p's < 0.025) except neurocognitive disturbance. Locus of control and illness behaviours contributed differentially across endophenotypes. Reduced likelihood of recovery was significantly predicted by greater initial symptom severity for all endophenotypes (all p's < 0.001), as well as higher levels of trait neuroticism.
Conclusions: Individual psychological and psychosocial factors contribute to the initial severity and to the prolonged course of symptoms after naturally-occurring infective illnesses. These factors may play an independent role, represent a bias in symptom reporting, or reflect increased stress responsivity and a heightened inflammatory response. Objective metrics for severity and recovery are required to further elucidate their roles.
Keywords: Acute sickness response; Delayed recovery; Fatigue; Mood disturbance; Neurocognitive difficulties; Neuroticism; Pain; Psychosocial factors; Socioeconomic disadvantage; Symptom severity.
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