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seroprevalence in a cohort of Italian psychiatric inpatients with mood or psychotic disorders: a preliminary communication

Claudia Del Grande 1, Elisa Schiavi 1, Isabella Masci 1, Margherita Barbuti 1, Giuseppe Maccariello 1, Barbara Pinto 2, Gabriele Massimetti 1, Fabrizio Bruschi 2, Liliana Dell’Osso 1

1Department of Clinical and Experimental Medicine, Section of Psychiatry and 2Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa,

Background Toxoplasma gondii (T. gondii ) has a strong tropism for the brain tissue, where it induces immunological alterations and establishes a chronic infection. A strong relation has emerged between chronic toxoplasmosis and (SCH) [1,2]. More recently, a significant association of the parasite infection with (BD) and suicidal/aggressive behaviors has also been documented [3,4]. We previously reported a consistent relationship between ocular manifestations of T. gondii infection and the onset and recurrences of psychiatric symptoms in a Brazilian female affected by BD with psychotic features. In this patient, infection reactivation was directly documented through molecular analyses (nested- PCR) and indirectly, by the high level of T. gondii -specific IgG [5].

Objective In the present observational, cross-sectional study we aim to evaluate the possible association of latent toxoplasmosis with several well-defined psychiatric disorders, comparing the seroprevalence for T. gondii in different diagnostic groups. Particularly, we intend to test the hypothesis that Toxoplasma infection may influence illness course and may be associated with a specific pattern of clinical manifestations (e .g. higher prevalence of psychotic and excitatory symptoms, cognitive impairment, and higher risk of suicidal and impulsive/aggressive behaviors).

Figure 1. T. gondii seroprevalence and diagnostic categories of DSM 5 Methods 101 inpatients (54 men; mean age 40,93 ± 12,179 years) with a diagnosis of BD, Major depressive disorder (MDD), or SCH spectrum disorders were Bipolar Disorder 1 (n=47) recruited at the Psychiatric Clinic of the University of Pisa. 40,9 % 40,0 %

The patients, all born in Italy, underwent collection to test serum Bipolar Disorder 2 (n=22) levels of IgG/IgM to T. gondii. Demographic questionnaires and clinical assessments (SCID 5 to 27.7 % Major Depressive Disorder (n=2) establish the diagnosis; CGI, PANSS, HAM-D, YMRS and BPRS to evaluate the severity and the psychopathological manifestations of current episode) were carried out. Schizophrenia (n=5)

The χ2 analysis was used to compare the patient groups. IgG+ % Schizoaffective Disorder (n=23) 13,0 %

Psychotic Disorder due to another medical condition (n=1) Results 0 % 0 % 0 % Substance -induced psychotic • 28 (27,7%) patients had IgG to T. gondii and the seroprevalence was disorder (n=1) higher in patients ≥ 40 years old in comparison with patients 18-39 years of DSM 5 diagnosis age (36,8% vs 15,9%) (p=0,035). • Toxoplasma -IgG titer showed levels between 9 and 159 U/L; only in one case it was ≥ 300 U/L. Figure 2. T. gondii seroprevalence • The IgM antibodies were absent in the whole sample, ruling out acute Schizophrenia spectrum disorders vs Affective disorders infections . Schizophrenia Spectrum Disorder Affective Disorders 78,60% • No statistically significant association was found between toxoplasmic infection and a specific psychiatric diagnosis. However, higher percentages 67,10% of IgG+ were found in patients with BD2 and SCH (Figure 1). • We found that a higher percentage (78,6%) of patients with IgG to T. gondii had a diagnosis of affective disorders (BD, MDD), compared to seropositive patients with SCH spectrum disorders (21,4%), although this result is not statistically significant (p=0,377) (Figure 2). 32,90%

21,40%

Ig- Ig+

Conclusions According to our knowledge, to date this is the first study evaluating the T. gondii seroprevalence in a cohort of Italian psychiatric inpatients. These preliminary data suggest the presence of a major link of toxoplasmic infection with affective disorders. Further investigations are needed to better define the clinical features correlated to seropositive status in BD patients.

References [1] Torrey, E.F., Bartko, J.J., Lun, Z.R., Yolken, R.H., 2007. Antibodies to Toxoplasma gondii in patients with Shizophrenia: a meta-analysis. Schizophr Bull 33, 729-736. [2] Torrey, E.F., Bartko, J.J., Yolken, R.H., 2012. Toxoplasma gondii and other risk factors for schizophrenia: an update. Schizophr Bull 38, 642-647. [3] Del Grande, C., Galli, L., Schiavi, E., et al., 2017. Is Toxoplasma gondii a Trigger of Bipolar Disorder? 6. pii: E3. doi: 10.3390/pathogens6010003. [4] Sutterland, A.L., Fond, G., Kuin, A., et al., 2015. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: and meta-analysis. Acta Psychiatr Scand, 132, 161-179. [5] Del Grande, C., Contini, C., Schiavi, E., et al., 2017. Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite? J Nerv Ment Dis 205, 192-195.