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Published online by Cambridge University Press: 26 August 2025
Adverse childhood events have been associated with immune aberrations. Herpes simplex virus 1 (HSV1), a neurotropic pathogen, establishes persistent infection after primary exposure. Elevated HSV1 immunoglobulin (IgG) levels have been found in HSV1-infected patients with severe mental illness (SMI), which likely reflects immune dysregulation.
We assessed childhood maltreatment and HSV1 IgG concentrations in adult patients with SMI and healthy controls. We hypothesized that maltreatment would be associated with elevated HSV1 IgG concentrations reflecting a failure in immune competence, and that such a putative association would be stronger in or even restricted to patients.
We included 448 adult patients with SMI (mean age=31 years, 48% women, 46% HSV1 seropositive), i.e., 259 patients with schizophrenia spectrum and 189 patients with bipolar disorders, and 271 adult healthy controls (mean age=32, 41% women, 46% HSV1 seropositive). We assessed childhood maltreatment with the Childhood Trauma Questionnaire (CTQ), a 28-item retrospective self-report scale. We evaluated circulatory HSV1 IgG concentrations, expressed as continuous and dichotomous measures. In our main analyses, we applied sex- and age-adjusted multiple regressions on HSV1 IgG concentrations.
In patients with SMI (p=0.002) but not in healthy controls (p=0.203), CTQ total score was associated with HSV1 IgG seropositivity. Among seropositive patients (p<0.001) but not healthy controls (p=0.957), CTQ total score was associated with increased HSV1 IgG concentrations. Post-hoc analysis among seropositive patients showed that the five subscale scores for physical (p=0.002), sexual (p=0.019) and emotional abuse (p=0.002), and physical (p=0.012) and emotional neglect (p=0.016) were all associated with increased HSV1 IgG concentrations.
Among patients with SMI, childhood maltreatment is associated with an increased risk of HSV1 infection. Further, among HSV1-infected patients, maltreatment is associated with elevated HSV1 antibody concentrations which may reflect a link between childhood adverse experiences and an immune system dysregulation.
D. Andreou: None Declared, N. E. Steen: None Declared, K. N. Jørgensen: None Declared, T. Ueland: None Declared, I. Drabløs: None Declared, L. Wortinger: None Declared, O. Andreassen Consultant of: HealthLytix, Speakers bureau of: Speaker’s honoraria from Lundbeck and Sunovion, R. Yolken: None Declared, I. Agartz Speakers bureau of: Speaker’s honoraria from Lundbeck
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