BackgroundInfections with different herpes viruses have been associated with cognitive functioning in psychiatric patients and healthy adults. The aim of this study was to find out whether antibodies to different herpes viruses are prospectively associated with cognitive functioning in a general adolescent population.MethodsThis study was performed in TRAILS, a large prospective general population cohort (N = 1084, 54% female, mean age 16.2 years (SD 0.6)). At age 16, immunoglobulin G antibodies against HSV1, HSV2, CMV and EBV were measured next to high sensitive C-Reactive Protein (hsCRP). Two years later, immediate memory and executive functioning were assessed using the 15 words task and the self ordered pointing task. Multiple linear regression analysis with bootstrapping was performed to study the association between viral infections and cognitive function, adjusting for gender, socioeconomic status, ethnicity, and cannabis use.ResultsPresence of HSV1 antibodies was associated with memory function ((B = −0.272, 95% CI = −0.556 to −0.016, p = 0.047)), while the association with executive functioning did not reach statistical significance (B = 0.560, 95% CI is −0.053 to 1.184, p = 0.075). The level of HSV1 antibodies was associated with both memory function (B = −0.160, 95% CI = −0.280 to −0.039, p = 0.014) and executive functioning (B = 0.296, 95% CI = 0.011 to 0.578, p = 0.046). Other herpes viruses and hsCRP were not associated with cognitive functioning.ConclusionsBoth presence and level of HSV1 antibodies are prospectively associated with reduced cognitive performance in a large cohort of adolescents.

The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein–Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hsCRP was not associated with the development of psychiatric disorders at age 19.

BackgroundFSS have been suggested to follow activation of the immune system, triggered by herpes virus infections. The aim of this study was to find out whether herpes virus infections were associated with the experience of FSS in adolescents, and whether this association was mediated by hsCRP, as a general marker of immune activation.MethodsThis study was performed in TRAILS, a large prospective population cohort of 2230 adolescents (mean age: 16.1 years, SD = .66, 53.4% girls). FSS were assessed using the somatic complaints subscale of the Youth Self-Report. FSS were analyzed as total scores and divided in two group clusters based on previous studies in this cohort. Levels of hsCRP and antibody levels to the herpes viruses HSV1, HSV2, CMV, EBV and HHV6 were assessed in blood samples at age 16. Also a value for pathogen burden was created adding the number of viruses the adolescents were seropositive for. Multiple regression analysis with bootstrapping was used to analyze the association between viral antibodies and pathogen burden, hsCRP and FSS scores.ResultsAntibody levels and pathogen burden were not associated with FSS total scores or FSS scores in both symptom groups. hsCRP was associated with the total FSS score (B = .02, 95% CI: .004 to .028, p = .01) and FSS score in the symptom group of headache and gastrointestinal complaints (B = .02, 95% CI: .001 to .039, p = .04).ConclusionOur study showed no association between herpes virus infections and FSS in general or specific FSS symptom clusters. A role for inflammatory processes in FSS development was supported by the significant association we found between hsCRP levels and FSS, especially in the symptom group of headache and gastrointestinal complaints.