Candida albicans exposures, sex specificity and cognitive deficits in schizophrenia and bipolar disorder

Abstract

Immune aberrations in schizophrenia and bipolar disorder have led to the hypotheses that infectious agents or corresponding immune responses might contribute to psychiatric etiopathogeneses. We investigated case–control differences in exposure to the opportunistic fungal pathogen, Candida albicans, and examined associations with cognition, medication, lifestyle, and somatic conditions. We quantified C. albicans IgG antibodies in two cohorts totaling 947 individuals and evaluated odds ratios (OR) of exposure with psychiatric disorder using multivariate regressions. The case–control cohort included 261 with schizophrenia, 270 with bipolar disorder, and 277 non-psychiatric controls; the second included 139 with first-episode schizophrenia, 78 of whom were antipsychotic naive. No differences in C. albicans exposures were found until diagnostic groups were stratified by sex. In males, C. albicans seropositivity conferred increased odds for a schizophrenia diagnosis (OR 2.04–9.53, P⩽0.0001). In females, C. albicans seropositivity conferred increased odds for lower cognitive scores on Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in schizophrenia (OR 1.12, P⩽0.004), with significant decreases on memory modules for both disorders (P⩽0.0007–0.03). C. albicans IgG levels were not impacted by antipsychotic medications. Gastrointestinal (GI) disturbances were associated with elevated C. albicans in males with schizophrenia and females with bipolar disorder (P⩽0.009–0.02). C. albicans exposure was associated with homelessness in bipolar males (P⩽0.0015). In conclusion, sex-specific C. albicans immune responses were evident in psychiatric disorder subsets. Inquiry regarding C. albicans infection or symptoms may expedite amelioration of this treatable comorbid condition. Yeast exposure as a risk factor for schizophrenia and its associated cognitive and GI effects require further investigation including the possible contribution of gut–brain mechanisms.

Probiotic normalization of Candida albicans in schizophrenia: A randomized, placebo-controlled, longitudinal pilot study

“…Each 96-well plate tested contained kit standards as well as study sample replicates for use as internal controls of reproducibility. C. albicans seropositivity designations were assigned according to standards run with the commercial ELISA kit, as previously described [12]. The Limit of Detection (LOD) and Limit of Quantitation (LOQ) were defined as three times and ten times the standard deviation of the blanks, respectively.…”

“…Data analyses were performed at Johns Hopkins and investigators were blinded to treatment groups; data was unblinded by study coordinators at Sheppard Pratt Health System. Because we previously detected significantly different case:control patterns of C. albicans and S. cerevisiae IgG in males versus females with schizophrenia [2, 12], we performed the data analyses separately for both sexes for the present study. We first compared starting mean antibody levels between treatment groups with analyses of variance (ANOVA)s. We then used repeated measures ANOVAs to determine if mean antibody levels differed according to treatment group and to the beginning versus end of the study.…”

“…However, other organisms, including fungi, are also components of the human microbiome and these taxa likely contribute to inter- and intra-kingdom dynamics of resident commensals [10, 11]. We have previously demonstrated that exposure to members of the human mycobiome, the yeast species, Candida albicans and Saccharomyces cerevisiae , was elevated in individuals with schizophrenia compared to non-psychiatric controls [2, 12]. Furthermore, antibody levels against one of these yeast species, C. albicans , were associated with GI disturbances and lower scores on cognitive tests in people with schizophrenia [12].…”

“…We have previously demonstrated that exposure to members of the human mycobiome, the yeast species, Candida albicans and Saccharomyces cerevisiae , was elevated in individuals with schizophrenia compared to non-psychiatric controls [2, 12]. Furthermore, antibody levels against one of these yeast species, C. albicans , were associated with GI disturbances and lower scores on cognitive tests in people with schizophrenia [12]. In immune-competent, healthy individuals, commensal yeast interactions with resident bacteria are stable and balanced; however, during bacterial dysbioses or species depletion, such as following the intake of antibiotics, potentially pathogenic yeast infections can occur [13].…”

Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia?

“…Inflammatory GI diseases, especially colitis, are thought to be highly prevalent (in over 90% of samples) in schizophrenia based on post mortem biopsy (Hemmings, 1990, 2004). Sex specific GI dysfunction may also be present in males with schizophrenia due to Candida albicans exposure (Severance et al, 2016a). …”