• obsessive-compulsive disorder
• vitamin D
• vitamin B12
• folic acid
• antibody titers
• neuroinflammation

INTRODUCTION: Obsessive-compulsive disorder (OCD) is a heterogeneous and disabling psychiatric condition. Patients suffering from OCD show a high rate of comorbidity with other psychiatric disorders, relevant suicide risk and a significantly reduced quality of life in several domains, as compared with the general population. Several models have been proposed to understand pathophysiological mechanisms underlying OCD, most of them including the interaction between genetic and environmental factors, and involving a variety of molecular, genetic, epigenetic, cellular, and distinct brain networks. Different vitamins, specifically B12, folic acid, homocysteine, an amino acid related to the functioning of these vitamins, and vitamin D play key roles in several brain functions acting on neurotransmission and brain homeostasis and, not surprisingly, have been associated with some psychopathological disorders/dimensions. High levels of homocysteine, low levels of vitamin B12, folic acid and/or vitamin D have been detected in both adult and adolescent patients suffering from many neuropsychiatric conditions. In particular, accumulating evidence regarding its multifaceted properties has led to define vitamin D as a pleiotropic hormone, due to its regulating effects on different biological processes, including cell differentiation and proliferation, neurotransmission and immunomodulation. Moreover, some alterations in immunological parameters have been found in OCD subgroups, with chronic inflammation and autoimmunity supposed to be responsible for neurotoxic effects triggering long-term neuronal damage.
Given the limited information in OCD, the present study aimed at assessing plasma levels of vitamin B12, D, folic acid, homocysteine and peripheral inflammatory markers or current/past infections, in a group of patients suffering from OCD, in order to better characterize its phenotypic presentations and possibly identify potentially affected symptom clusters or dimensions.
METHOD: A group of 217 adult OCD outpatients were recruited. The diagnoses were carried out according to DSM-5 criteria for OCD and the structured clinical interview for DSM-5 (SCID-5), research version, patient’s edition. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was used to assess the phenotype and the severity of OC symptomatology. Socio-demographic characteristics were recorded together with family, illness and treatment history, comorbid psychiatric and medical conditions, suicidal symptoms and attempts, sleep patterns and metabolic status. Levels of vitamin D, B12, folic acid and homocysteine were measured by common chemical-clinical laboratory tests. In addition, other available serum parameters such as erythrocyte sedimentation rate, C-reactive protein, blood count and antibodies titers for the most common infections (cytomegalovirus (CMV), Epstein Barr virus (EBV), toxoplasma gondii and antistreptolysin titer) were evaluated as possible markers of systemic inflammation. Vitamin D levels were evaluated in 142, vitamin B12 in 98 and folates in 97 patients. EBV Igs were assessed in 99, toxoplasma gondii IgG in 98, CMV IgM in 96 and IgG in 95, antistreptolysin titer in 93 and toxoplasma gondii IgM in 90 patients.
RESULTS: Men showed a younger age at index evaluation and at onset, as well as a higher prevalence of lifetime and current sexual obsessional thoughts, with no significant differences in Y-BOCS scores between the two sexes. An earlier disease onset, a history of perinatal traumas and a chronic course were associated to more severe symptoms. The acute onset, when preceded by stressful life events was related to better clinical characteristics. More than a half of patients (88) showed vitamin D insufficiency, while levels of vitamin B12 and folates were sufficient in most patients (respectively, 84 and 71). Sixty-one patients presented signs of a previous EBV infection, 46 were seropositive for CMV IgG, 24 showed positive anti-streptolysin titers, 14 were seropositive for toxoplasma gondii IgG, four for CMV IgM. Thirty-six patients were seropositive for two, 33 for only one and 12 for three or more antibody titers.
Vitamin D appeared negatively related to all Y-BOCS total and subscales scores, while folic acid only to Y-BOCS total and obsessions subscale scores. In particular, sufficient or optimal levels of vitamin D correlated with lower symptom severity. On the contrary, no significant correlations emerged with the other biological and inflammatory markers. Interestingly, patients with signs of a past EBV infection displayed significantly higher scores in Y-BOCS total and compulsions subscales, and “distress related to obsessions”, “resistance” and “control over compulsive behaviours”, “avoidance”, “indecisiveness”, “overvalued sense of responsibility and “pervasive slowness” items, compared to seronegative patients. No other significant results were noted when the other antibodies titers were considered.
CONCLUSIONS: There is a compelling need of a novel pathophysiological model of OCD, aiming at improving an early detection and effective treatment, while considering the impact on patients’ quality of life and functioning, as well as its direct and indirect community costs. Although the role of vitamins and immune-mediated responses have been established in neuroplasticity and neurotrophic/neurodegenerative processes, their impact on pathophysiology of OCD has only been hypothesized. The findings of our study strongly support the impact of hypovitaminosis and Epstein-Barr infections on the overall severity and specific symptom patterns of OCD. They represent useful, cheap and easy parameters that should be routinely assessed. Further studies are needed to more thoroughly clarify their role on OCD aetiology and outcomes, as well as the potential therapeutic impact of vitamins and antibiotics in some psychiatric conditions.