• immunoneuropsychiatry
• pathophysiology
• immunoglobulin
• obsessive-compulsive disorder
• neuropsychiatric disorder
• infectious agents

Introduction: Recently, there has been a resurgence of interest in the relationship between infections and psychopathology, given the increasing data on the neurotropism and neurological/psychiatric morbidity of the SARS-COV2 virus, responsible for the current worldwide pandemic. Although much data was obtained for mood and schizophrenic disorders, obsessive-compulsive symptoms precipitated by group A beta-hemolytic streptococcus (GABHS) infections in children are the most robust evidence in this field. In addition, different pathogens, including bacteria, virus, and parasites, such as Toxoplasma Gondii and Herpes Simplex, were associated with primary obsessive-compulsive disorder (OCD) in adults, though only in case reports or single studies, suggesting that the exposure to infectious agents, and related immuno-inflammatory mechanisms, could represent a possible environmental risk factor for primary OCD onset.
Aims: The main objectives of this study were 1) to assess the seropositivity for Cytomegalovirus (CMV), Epstein-Barr (EBV), Toxoplasma Gondii (T. Gondii), and GABHS in a cohort of subjects affected by OCD; 2) to test the possible differences in Y-BOCS total scores, obsessions subscales, and compulsions subscales between three subgroups of subjects represented by patients with one, two, or at least two infectious agent seropositivity. A further aim of this study was to investigate the possible correlations between antibody titers (CMV, EBV, and T. Gondii IgM and IgG, and anti-streptolysin O (ASO) titer) and Y-BOCS total scores.
Material and methods: A cohort of thirty-four outpatients of both sexes, recruited in the period June-November 2021, was enrolled in the present study. All subjects were first assessed by a clinical evaluation with the ensuing diagnoses subsequently supported by the structured clinical interview for DSM-5, research version (SCID-5-RV). The severity of OCD was examined by the Yale-Brown obsessive-compulsive Scale (Y-BOCS). All the information derived from the medical history were collected by the authors. All patients underwent fasting venous blood sampling. Subsequently, common clinical chemical methods were performed to detect the concentrations of antibody titers (IgM and IgG against CMV, EBV, and T. Gondii IgG, and ASO).
Results: The total sample of 34 OCD patients (mean age ± SD: 31.93±10.47 years) included 22 (64.7%) men (mean age ± SD: 30.55±7.42 years), and 12 (35.3%) women (mean age + SD: 34.25±14.30 years). The mean age of onset of OCD was 12.83±1.23 years; 26 (19 men and 7 women) patients referred a slow progressive onset with chronic course, and 8 (3 men and 5 women) an acute onset with episodic course. All patients were free of full-blown psychiatric comorbidities and drug naïve. Nine (26.5%) patients (all men) reported a history of perinatal traumas. The most common obsessions were aggressive (61.76%), followed by symmetry/exactness (52.94%), contamination (47.05%), sexual thoughts/image (20.58%), somatic (17.64%), religious (14.70%). Twenty-six patients (15 men and 11 women) reported miscellaneous obsessions. The most common compulsions were checking rituals (67.64%), repeating compulsions (38.23%), cleaning/washing (41.17%), counting rituals (29.41%), ordering/arranging (14.70%), hoarding/collecting (8.82%), and other types (13 men and 9 women). Sixteen (47.06%) patients were seropositive for CMV IgG, twenty-six (76.47%) were seropositive for EBV IgG, nine (26.47%) were seropositive for T. gondii IgG, and ten (29.41%) were seropositive to ASO. Two (5.88%) patients were seropositive for CMV IgM, one (2.94%) was seropositive to EBV IgM and another (2.94%) for T. Gondii IgM. Thirteen (38,2%) patients were seropositive for one infectious agent, fourteen (41.2%) patients were seropositive for two infectious agents, and seven (20,6%) patients were seropositive for two or more infectious agents. The Y-BOCS total score of the total sample was 25.31±9.56 (indicating severe symptoms), the obsession and compulsion subscales were, respectively, 12.97±4.63 and 12.34±5.10, with no significative differences between the two sexes. The Y-BOCS total score and the obsession and compulsion subscales were, respectively, 25.00±10.60, 12.54±5.26, and 12.45±5.48 in the subgroup of one infectious agents seropositivity, 24.00±8.01, 12.42±3.71, and 11.57±4.56 in the subgroup of two infectious agents seropositivity, and 28.42±11.41, 14.71±5.53, and 13.71±5.96 in the subgroup of at least two infectious agents seropositivity. Statistical analysis (Kruskal Wallis test) showed no significant differences between the three subgroups, although a trend of higher scores of Y-BOCS total score and obsession/compulsion subscales in the subgroups with at least two infectious agents seropositivity emerged (p = 0.593, 0.557, and 0.739 respectively). The correlation analyses showed positive and significant correlation between IgG against CMV and EBV and Y-BOCS total score (Spearman’s coefficient r = 0.377 and 0.468 respectively; p = 0.040 and 0.008 respectively).
Conclusions: The present cross-sectional study would support that infections, reinfections, or reactivation by CMV, EBV, T. Gondii and Streptococcus pyogenes may play a role in the pathophysiology of a subtype of OCD and could be related to the severity of the disorder. Furthermore, our results would indicate a trend of more severe outcomes with co-occurring or-multiple infection than single infection. Although the specificity of these findings requires to be deepened, these preliminary results would suggest novel therapy strategies in a subgroup of OCD patients.