title: 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.
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Severance
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Gressitt
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Stallings
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Katsafanas
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Schweinfurth
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Savage
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Adamos
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Sweeney
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Origoni
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Khushalani
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University , Mannheim, Germany.
authors.forename: F Markus
authors.initials: FM
authors.lastname: Leweke
authors.affiliation: Sheppard Pratt Health System, Stanley Research Program , Baltimore, MD, USA.
authors.forename: Faith B
authors.initials: FB
authors.lastname: Dickerson
authors.affiliation: Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Yolken