Relationship of herpesvirus (HSV1, EBV, CMV, HHV6) seropositivity with depressive disorder and its clinical aspects: The first study in children

Abstract

Infections can lead to the onset of mood disorders in adults, partly through inflammatory mechanisms. However pediatric data are lacking. The aim of this study is to evaluate the relationship between depressive disorder and seropositivity of herpes virus infections in children.The sample group consisted of patients diagnosed with depressive disorder according to DSM-5 diagnostic criteria and healthy volunteers, being between 11 and 18 years with clinically normal mental capacity. All children completed DSM-5-Level-2 Depression Scale, DSM-5-Level-2 Irritability Scale, DSM-5-Level-2 Sleep Scale, DSM-5-Level-2 Somatic Symptoms Scale. The levels of anti-HSV1-IgG, anti-CMV-IgG, anti-EBNA, and anti-HHV6-IgG were examined in all participants.Patients with an antibody value above the cut-off values specified in the test kits were evaluated as seropositive. The mean age was 15.54 ± 1.57 years in the depression group (DG), 14.87 ± 1.76 years in the healthy control group (CG). There were 4 boys (11.2%), 32 girls (88.8%) in the DG, 9 boys (21.9%) and 32 girls (78.04%) in the CG. There was no statistically significant difference between the groups in terms of the presence of seropositivity of HSV1, CMV, EBV, and HHV6. HHV6 antibody levels were significantly higher in the DG (p = 0.000). A significant positive correlation was found between HHV6 antibodies and DSM-5 level-2 somatic symptoms scale score. HHV6 antibody levels were found to be significantly higher in patients with existing suicidal ideation in the DG (n = 13) compared to those without existing suicidal ideation in the DG (p = 0.043). HHV6 persistent infections may be responsible for somatic symptoms and etiology of suicidal ideation in childhood depressive disorder.

Two possible mechanisms of ganciclovir for treatment of major depressive disorder

“…The adult prevalence of HHV in the general population is that HSV-1 infects about 70% of adults, HSV-2 about 30%, VZV more than 90%, EBV also more than 90%, CMV about 70%, and more than 95% of those 2 years and older are infected with either HHV-6A or HHV-6B or both ( 36 ). In contrast, in the depressed population, a study examining serologic testing in Turkish adolescents found HSV-1 in 71.4%, EBV in 82.9%, CMV in 94.2%, and HHV6 in 91.4%, and no statistically significant difference in healthy controls in the same study ( 35 ). No significant differences in HHV morbidity are expected between the general population and the depressed population, and it is likely that some infected individuals are more susceptible to depression than others.…”

“…Cytomegalovirus infection is associated with decreased volume of gray matter in the brain in patients with MDD. This result suggests that cytomegalovirus infection may be a treatable cause of structural brain abnormalities in depressed patients (34). SITH-1-induced olfactory bulb apoptosis may also facilitate HHV-6B or other HHVs invasion into the brain, which is associated with worsening depressive symptoms (31).…”

“…SITH-1-induced olfactory bulb apoptosis may also facilitate HHV-6B or other HHVs invasion into the brain, which is associated with worsening depressive symptoms ( 31 ). In a study of 11- to 18-year-olds in Turkey, depressed patients with suicidal ideation had significantly higher levels of HHV-6 antibodies, suggesting that persistent HHV-6 infection may be a risk factor for suicidal ideation ( 35 ).…”

Identification of a strong genetic risk factor for major depressive disorder in the human virome

“…HHV-6B has been shown to be a risk factor for MDD. 30 , 31 , 32 so we thought it might be possible to obtain evidence for an association of depression and the microbiome by examining whether HHV-6B gene polymorphisms and MDD were related, and thereby solve the problem of missing heritability. Since SITH-1, a latent protein of HHV-6B, is a strong risk factor for MDD, 31 we attempted to identify polymorphisms of HHV-6B genes related to SITH-1.…”