Of the 5362 individuals selected at birth, 3322 were successfully followed up to the age of 36 years. After exclusion of those who died (n=323), were living abroad (n=644), or had permanently refused to participate (n=520), this represented a follow-up rate of 86%. A total of 3293 of these individuals (99.1%) completed a PSE examination at age 36 years. Two hundred and four (6.2%) demonstrated a likely psychiatric disorder, and 148 (4.5%) scored highly on the fatigue and lack of energy PSE subscale (with 70 individuals suffering from both psychiatric disorder and fatigue). These 282 individuals were excluded to create a sample of 3011 ‘healthy’ individuals without any evidence of fatigue or psychiatric disorder. A total of 2715 (90.2%) of these ‘healthy’ individuals were successfully followed up to age 43, where the presence of new onset fatigue and psychiatric disorder was assessed. A flow diagram demonstrating this and the reasons for any loss to follow-up is provided in . There was no difference between those assessed at age 43 and those lost to follow-up in terms of gender, social class, or personality measures. However, individuals with lower levels of education (P<.001), no family history of psychiatric disorder (P=.003), less negative life events (P=.05), and who were less energetic as children (P=.02) were more likely to be lost to follow-up prior to the age of 43 years.
The characteristics of the 2714 individuals followed up to age 43 years are described in . At age 43 years, 365 (13.4%) of this previously nonfatigued sample reported significant levels of fatigue (fatigue with a duration of >1 month or present for 12 months on at least 2 days each week). Of the 365 fatigued individuals, 164 (44.9%) were suffering from comorbid psychiatric disorder. Two hundred and one participants (55.1% of the fatigued group and 7.4% of the entire sample) had fatigue without any comorbid psychiatric disorder. Despite this group of fatigued individuals not meeting the case definition for psychiatric disorder, they did report significantly increased levels of many associated symptoms including feeling mentally tense, low appetite, difficulty sleeping, low mood, and impaired concentration (P≤.001). However, they did not report increased levels of anxiety symptoms (panic, situational anxiety, or fear of becoming ill) and only 28 (13.9%) reported significant levels of low mood.
Description of the sample followed up to the age of 43 years (n=2714)
demonstrates the associations between the different combinations of fatigue and psychiatric disorder and a number of potential premorbid risk factors. Neuroticism was associated with an increased risk of both fatigue and psychiatric disorder in all possible combinations. The effect size was largest for comorbid fatigue and psychiatric disorder, with an adjusted odds ratio (OR) of 2.13 (95% CI 1.42–3.17, P<.001). Negative life events at age 36 years increased the risk of psychiatric disorder, both with and without fatigue, at age 43 years. Negative life events did not increase the risk of fatigue in the absence of comorbid psychiatric disorder. Both a family history of psychiatric disorder and physical inactivity at age 36 were risk factors for fatigue, but again only when the fatigue was comorbid with psychiatric disorder. Participants whose teachers had reported as being extremely energetic at age 13 years were significantly more likely (adjusted OR 2.20, 95% CI 1.33–3.65, P=.002) to report fatigue without comorbid psychiatric disorder at age 43 years. Energetic children were not at increased risk of fatigue comorbid with psychiatric disorder. Participants who were overweight at age 36 were also at increased risk of fatigue in the absence of psychiatric disorder at age 43 years (adjusted OR 1.56, 95% CI 1.07–2.26, P=.02). While obese individuals did not appear to be at increased risk, there was moderate evidence of a positive linear association between BMI and risk of later fatigue without comorbid psychiatric disorder (P=.05). There was no evidence of any association between chronic illness in childhood or extraversion and the risk of later fatigue or psychiatric disorder.
Premorbid predictors of fatigue and psychiatric disorder
A final multivariable model was created which included all significant premorbid risk factors together with gender, social class, and education. Females were at increased risk for both fatigue and psychiatric disorder. Being described as extremely energetic at age 13 (adjusted OR 2.63, 95% CI 1.55–4.48, P<.001) and being overweight at age 36 (adjusted OR 1.62, 95% CI 1.05–2.49, P=.03) were both independent predictors of fatigue without psychiatric disorder. Neuroticism as a categorical variable was not an independent predictor of fatigue without comorbid psychiatric disorder, although when considered as a continuous variable in a post hoc analysis an independent effect was seen (P=.04). Those with fatigue comorbid with psychiatric disorder were more likely to have a family history of psychiatric disorder (adjusted OR 1.94, 95% CI 1.26–2.98, P=.003), less likely to have been physically active (adjusted OR 0.51, 95% CI 0.31–0.86, P=.01), and more likely to score highly for neuroticism (adjusted OR 1.84, 95% CI 1.18–2.88, P=.07). The impact of increased negative life events on the risk of future comorbid fatigue and depression was reduced to borderline significance (adjusted OR 1.53, 95% CI 0.99–2.37, P=.06).
In order to examine the psychological outcome of fatigue without any comorbid psychiatric disorder, we then focused on the 2445 participants who did not have any evidence of psychiatric disorder at either age 36 or 43 years. The reasons for any exclusions and loss to follow-up are demonstrated in . The selected group of participants without psychiatric disorder contained individuals with a range of fatigue. They were divided into those with no fatigue, those with mild fatigue (up to 1-month duration or once or twice a week for the last 12 months), and those with more severe fatigue (more than 1-month duration or more often than twice a week for the last 12 months). A total of 937 (38.3%) of the participants reported mild fatigue, while 201 (8.2%) individuals described more severe fatigue. As demonstrated in , both mild and severe fatigue (without comorbid psychiatric illness) were associated with increased risk of later psychiatric disorder. There did not appear to be a linear dose–response effect, with the effect size of the increased risk being similar for severe and mild fatigue. Likelihood ratio tests confirmed that a linear model was not appropriate. The increased risk of later psychiatric illness remained after adjustment for social demographics (gender, social class, and education) and other potential confounders (personality, negative life events, family history of psychiatric disorder, childhood illness, energy levels as a child, physical activity as an adult, and BMI).
Multivariable model describing the relationship between preexisting fatigue (without comorbid psychiatric illness) and later psychiatric disorder