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Article: Fungal Forces in Mental Health: Microbial Meddlers or Function Fixers?

Severance, Emily G

Current topics in behavioral neurosciences

2022 Volume 61, Page(s) 163–179

Abstract: In the mental health field, the gut-brain axis and associated pathways represent putative mechanisms by which gastrointestinal (GI) microbes and their gene products and metabolites can access and influence the central nervous system (CNS). These GI- ... ...

Abstract	In the mental health field, the gut-brain axis and associated pathways represent putative mechanisms by which gastrointestinal (GI) microbes and their gene products and metabolites can access and influence the central nervous system (CNS). These GI-centered investigations focus on bacteria, with significant information gaps existing for other microbial community members, such as fungi. Fungi are part of a complex and functionally diverse taxonomic kingdom whose interactions with hosts can be conversely deadly and beneficial. As serious sources of morbidity and mortality, fungal pathogens can quickly turn healthy microbiomes into toxic cycles of inflammation, gut permeability, and dysbiosis. Fungal commensals are also important human symbionts that provide a rich source of physiological functions to the host, such as protection against intestinal injuries, maintenance of epithelial structural integrities, and immune system development and regulation. Promising treatment compounds derived from fungi include antibiotics, probiotics, and antidepressants. Here I aim to illuminate the many attributes of fungi as they are applicable to overall improving our understanding of the mechanisms at work in psychiatric disorders. Healing the gut and its complex ecosystem is currently achievable through diet, probiotics, prebiotics, and other strategies, yet it is critical to recognize that the success of these interventions relies on a more precisely defined role of the fungal and other non-bacterial components of the microbiome.
MeSH term(s)	Humans ; Gastrointestinal Microbiome ; Mental Health ; Microbiota ; Inflammation
Language	English
Publishing date	2022-05-10
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2022_364
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Article ; Online: Jumpstarting metabolomics and the next generation of clinically useful gut-brain microbiome research.

Severance, Emily G

Brain, behavior, and immunity

2021 Volume 93, Page(s) 12–13

MeSH term(s)	Brain ; Gastrointestinal Microbiome ; Humans ; Metabolome ; Metabolomics ; Schizophrenia
Language	English
Publishing date	2021-01-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2021.01.019
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Guest Editorial: Binning bugs and beyond: The state of the schizophrenia microbiome.

Severance, Emily G / Yolken, Robert H

Schizophrenia research

2021 Volume 234, Page(s) 1–3

MeSH term(s)	Brain ; Gastrointestinal Microbiome ; Humans ; Microbiota ; Schizophrenia
Language	English
Publishing date	2021-05-15
Publishing country	Netherlands
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639422-x
ISSN	1573-2509 ; 0920-9964
ISSN (online)	1573-2509
ISSN	0920-9964
DOI	10.1016/j.schres.2021.05.002
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Zs.A 2351: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 543: Show issues

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Article: Non-SARS Coronaviruses in Individuals with Psychiatric Disorders.

Dickerson, Faith B / Severance, Emily G / Yolken, Robert H

Current topics in behavioral neurosciences

2022 Volume 61, Page(s) 265–278

Abstract: Background: The pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has highlighted the importance of coronaviruses in human health. Several seasonal, non-SARS Coronaviruses are endemic in most areas of the world. In a ... ...

Abstract	Background: The pandemic caused by severe acute respiratory syndrome-Coronavirus-2 (SARS-CoV-2) has highlighted the importance of coronaviruses in human health. Several seasonal, non-SARS Coronaviruses are endemic in most areas of the world. In a previous study, we found that the level of antibodies to these seasonal Coronaviruses was elevated in persons with a recent onset of psychosis. In the current study, the level of antibodies to seasonal Coronaviruses was compared between individuals with psychiatric disorders and a non-psychiatric comparison group. Methods: Participants (N = 195) were persons with a diagnosis of schizophrenia, bipolar disorder, major depressive disorder, or without a psychiatric disorder. Each participant had a blood sample drawn from which were measured IgG antibodies to the spike proteins in four non-SARS Coronaviruses, 229E, HKU1, NL63, and OC43, using a multiplex electrochemiluminescence assay. Linear regression models were employed to compare the levels of antibodies between each psychiatric group and the comparison group adjusting for demographic variables. Logistic regression models were employed to calculate the odds ratios associated with increased levels of antibodies to each seasonal Coronavirus based on the 50th percentile level of the comparison group. Results: The schizophrenia group had significantly increased levels of antibodies to the seasonal Coronaviruses OC43 and NL63. This group also had increased odds of having elevated antibody levels to OC43. The major depression group showed a significantly lower level of antibodies to Coronavirus 229E. There were no significant differences between any of the psychiatric groups and the comparison group in the levels of antibodies to seasonal Coronaviruses 229E or HKU1. Conclusions: The elevated level of antibodies to OC43 and NL63 in the schizophrenia group indicates increased exposure to these agents and raises the possibility that Coronaviruses may contribute to the etiopathology of this disorder. The cause-and-effect relationship between seasonal Coronaviruses and psychiatric disorders should be the subject of additional investigations focusing on longitudinal cohort studies.
MeSH term(s)	Humans ; Depressive Disorder, Major ; Longitudinal Studies ; COVID-19 ; SARS-CoV-2 ; Coronavirus 229E, Human
Language	English
Publishing date	2022-08-07
Publishing country	Germany
Document type	Journal Article
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2022_386
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Article: From Infection to the Microbiome: An Evolving Role of Microbes in Schizophrenia.

Severance, Emily G / Yolken, Robert H

Current topics in behavioral neurosciences

2019 Volume 44, Page(s) 67–84

Abstract: The study of microorganisms such as bacteria, viruses, archaea, fungi, and protozoa in the context of psychiatric disorders may be surprising to some. This intersection of disciplines, however, has a rich history and is currently revitalized by newfound ... ...

Abstract	The study of microorganisms such as bacteria, viruses, archaea, fungi, and protozoa in the context of psychiatric disorders may be surprising to some. This intersection of disciplines, however, has a rich history and is currently revitalized by newfound functions of the microbiome and the gut-brain axis in human diseases. Schizophrenia, in particular, fits this model as a disorder with gene and environmental roots that may be anchored in the immune system. In this context, the combination of a precisely timed pathogen exposure in a person with genetically encoded altered immunity may have especially destructive consequences for the central nervous system (CNS). Furthermore, significant components of immunity, such as the development of the immune response and the concept of immune tolerance, are largely dictated by the commensal residents of the microbiome. When this community of microbes is imbalanced, perhaps as the result of a pathogen invasion, stress, or immune gene deficiency, a pathological cycle of localized inflammation, endothelial barrier compromise, translocation of gut-derived products, and systemic inflammation may ensue. If these pathologies enable access of gut and microbial metabolites and immune molecules to the CNS across the blood-brain barrier (BBB), and studies of the gut-brain axis support this hypothesis, a worsening of cognitive deficits and psychiatric symptoms is predicted to occur in susceptible individuals with schizophrenia. In this chapter, we review the role of microbes in various stages of this model and how these organisms may contribute to documented phenotypes of schizophrenia. An increased understanding of the role of pathogens and the microbiome in psychiatric disorders will better guide the development of microbial and immune-based therapeutics for disease prevention and treatment.
MeSH term(s)	Brain ; Humans ; Immune System ; Infections/complications ; Microbiota ; Schizophrenia/microbiology
Keywords	covid19
Language	English
Publishing date	2019-04-04
Publishing country	Germany
Document type	Journal Article ; Review
ISSN	1866-3370
ISSN	1866-3370
DOI	10.1007/7854_2018_84
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Article ; Online: Recent anti-infective exposure as a risk factor for first episode of suicidal thoughts and/or behaviors in pediatric patients.

Prichett, Laura M / Severance, Emily G / Yolken, Robert H / Carmichael, Destini / Lu, Yongyi / Zeng, Yong / Young, Andrea S / Kumra, Tina

Brain, behavior, & immunity - health

2024 Volume 36, Page(s) 100738

Abstract: Objectives: We conducted a retrospective cohort study of medical records from a large, Maryland, U.S.-based cohort of pediatric primary care patients for potential associations between antibacterial, antifungal and antiviral prescriptions and subsequent ...

Abstract	Objectives: We conducted a retrospective cohort study of medical records from a large, Maryland, U.S.-based cohort of pediatric primary care patients for potential associations between antibacterial, antifungal and antiviral prescriptions and subsequent suicidal thoughts and/or behaviors. Methods: Using first suicide-related diagnosis as the outcome and prior prescription of antibacterial, antifungal, and/or antiviral use as the exposure, we employed a series of multivariate Cox proportional hazards models. These models examined the hazard of developing newly recognized suicidal thoughts and/or behaviors, controlling for age, sex, race, insurance, number of encounters during the study period, prior mood disorder diagnosis and number of chronic health conditions. We constructed the same series of models stratified by the groups with and without a prior recorded mental or behavioral health diagnosis (MBHD). Results: Suicidal thoughts and/or behaviors were associated with the previous prescription of an antibacterial, antifungal and/or antiviral medication (HR 1.31, 95 %-CI 1.05-1.64) as well as the total number of such medications prescribed (HR 1.04, 95 %-CI 1.01-1.08), with the strongest relationship among patients with three or more medications (HR 1.44, 95 %-CI 1.06-1.96). Among individual medications, the strongest association was with antibacterial medication (HR 1.28, 95 %-CI 1.03-1.60). Correlations were strongest among the subgroup of patients with no previous (MBHD). Interpretation: Infections treated with antimicrobial medications were associated with increased risks of a suicide-related diagnosis among patients who had not had a previous mental or behavioral health diagnosis. This group should be considered for increased levels of vigilance as well as interventions directed at suicide screening and prevention. Funding: National Institutes of Health, Stanley Medical Research Institute.
Language	English
Publishing date	2024-02-17
Publishing country	United States
Document type	Journal Article
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2024.100738
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Article ; Online: COVID-19 and Youth Mental Health Disparities: Intersectional Trends in Depression, Anxiety and Suicide Risk-Related Diagnoses.

Prichett, Laura M / Yolken, Robert H / Severance, Emily G / Carmichael, Destini / Zeng, Yong / Lu, Yongyi / Young, Andrea S / Kumra, Tina

Academic pediatrics

2024

Abstract: Objectives: Mental health disparities were prevalent among racially and ethnically minoritized youth prior to the COVID-19 pandemic. As complete datasets from 2022 become available, we can estimate the extent to which the pandemic further magnified ... ...

Abstract	Objectives: Mental health disparities were prevalent among racially and ethnically minoritized youth prior to the COVID-19 pandemic. As complete datasets from 2022 become available, we can estimate the extent to which the pandemic further magnified existing inequities. Our objective was to quantify disparities in trajectories of depression, anxiety, and suicide risk-related diagnoses in youth before and after the start of the COVID-19 pandemic, using an intersectional lens of race, ethnicity and gender. Methods: Using electronic medical record data from one mid-Atlantic health care system (2015-2022), we evaluated changes in annual rates of depression, anxiety and suicide risk-related diagnoses in 29,117 youths, aged 8-20 years, using graphical analysis, comparison of adjusted mean differences (AMD) and adjusted mixed multilevel logistic regression. Results: Almost all racial and gender subgroups had significantly higher rates of depression and anxiety after the start of COVID-19 compared to the years prior, with the greatest changes observed in Hispanic and Asian females. Suicide risk-related diagnoses significantly increased among all female subgroups, with the largest increase among Asian females (AMD 4.8, 95% CI 0.2-9.3) and Black females (AMD 4.6, 95% CI 2.2-6.9). Conclusions: Rates of depression, anxiety, and suicidal thoughts and/or behaviors in young people continued to increase in the post-pandemic period. Many pre-existing disparities between subgroups, especially females, significantly widened, highlighting the importance of using an intersectional lens. Urgent action is warranted, including universal screening of pediatric patients for suicide risk, broadening effective treatment and support options in minoritized patients, and increasing support services to patients and families.
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2483385-X
ISSN	1876-2867 ; 1876-2859
ISSN (online)	1876-2867
ISSN	1876-2859
DOI	10.1016/j.acap.2024.01.021
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Zs.A 5914: Show issues

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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Deciphering microbiome and neuroactive immune gene interactions in schizophrenia.

Severance, Emily G / Yolken, Robert H

Neurobiology of disease

2018 Volume 135, Page(s) 104331

Abstract: The body's microbiome represents an actively regulated network of novel mechanisms that potentially underlie the etiology and pathophysiology of a wide range of diseases. For complex brain disorders such as schizophrenia, understanding the cellular and ... ...

Abstract	The body's microbiome represents an actively regulated network of novel mechanisms that potentially underlie the etiology and pathophysiology of a wide range of diseases. For complex brain disorders such as schizophrenia, understanding the cellular and molecular pathways that intersect the bidirectional gut-brain axis is anticipated to lead to new methods of treatment. The means by which the microbiome might differ across neuropsychiatric and neurological disorders are not known. Brain disorders as diverse as schizophrenia, major depression, Parkinson's disease and multiple sclerosis appear to share a common pathology of an imbalanced community of commensal microbiota, often measured in terms of a leaky gut phenotype accompanied by low level systemic inflammation. While environmental factors associated with these disease states might contribute to intestinal pathologies, products from a perturbed microbiome may also directly promote specific signs, symptoms and etiologies of individual disorders. We hypothesize that in schizophrenia, it is the putatively unique susceptibility related to genes that modulate the immune system and the gut-brain pleiotropy of these genes which leads to a particularly neuropathological response when challenged by a microbiome in dysbiosis. Consequences from exposure to this dysbiosis may occur during pre- or post-natal time periods and thus may interfere with normal neurodevelopment in those who are genetically predisposed. Here, we review the evidence from the literature which supports the idea that the intersection of the microbiome and immune gene susceptibility in schizophrenia is relevant etiologically and for disease progression. Figuring prominently at both ends of the gut-brain axis and at points in between are proteins encoded by genes found in the major histocompatibility complex (MHC), including select MHC as well as non-MHC complement pathway genes.
MeSH term(s)	Brain/immunology ; Brain/metabolism ; Dysbiosis/immunology ; Dysbiosis/metabolism ; Humans ; Inflammation/immunology ; Inflammation/metabolism ; Microbiota/immunology ; Nervous System Diseases/immunology ; Nervous System Diseases/metabolism ; Schizophrenia/immunology ; Schizophrenia/metabolism
Language	English
Publishing date	2018-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2018.11.016
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ab Jg. 2022: Lesesaal (EG)

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Article: Complex Gastrointestinal and Endocrine Sources of Inflammation in Schizophrenia.

Severance, Emily G / Dickerson, Faith / Yolken, Robert H

Frontiers in psychiatry

2020 Volume 11, Page(s) 549

Abstract: A low level, inflammatory phenotype is prevalent in individuals with schizophrenia, but the source of this inflammation is not known. Studies of the gut-brain axis indicate that this inflammation may be related to the translocation of intestinal microbes ...

Abstract	A low level, inflammatory phenotype is prevalent in individuals with schizophrenia, but the source of this inflammation is not known. Studies of the gut-brain axis indicate that this inflammation may be related to the translocation of intestinal microbes across a permeabilized gut-vasculature barrier. In addition, studies of the endocrine system support that this inflammation may derive from effects of stress hormones and metabolic imbalances. Gastrointestinal (GI) and endocrine conditions are not mutually exclusive, but rather may have additive effects to produce this inflammatory phenotype in schizophrenia. Here, we examined a series of plasma biomarkers used to measure general inflammation and presumably microbial, gut-derived inflammation in 409 individuals with schizophrenia: c-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and IgG antibodies to
Language	English
Publishing date	2020-06-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564218-2
ISSN	1664-0640
ISSN	1664-0640
DOI	10.3389/fpsyt.2020.00549
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Article ; Online: Relationship between antibiotic exposure and subsequent mental health disorders in a primary care health system.

Prichett, Laura M / Yolken, Robert H / Wu, Linxuan / Severance, Emily G / Kumra, Tina

Brain, behavior, & immunity - health

2022 Volume 21, Page(s) 100430

Abstract: Objective: To evaluate the relationship between antibiotic exposure and subsequent psychiatric disorders in a Pediatric primary care setting.: Study design: We conducted a retrospective cohort study using electronic clinical record data for patients ... ...

Abstract	Objective: To evaluate the relationship between antibiotic exposure and subsequent psychiatric disorders in a Pediatric primary care setting. Study design: We conducted a retrospective cohort study using electronic clinical record data for patients ages 8-20 years seen in the outpatient setting of a large urban primary health care practice from 1/1/13 to 12/1/2018. We employed adjusted Cox regression analyses to study the relationship between prescriptions for anti-infective agents and subsequent diagnosis of anxiety or depression. Results: Prescription of anti-infective medication was associated with a hazard rate ratio (HRR) of 1.21 (95%-CI = 1.00-1.45). A first prescription for a broad-spectrum antibiotic (compared to those with no prescription, narrow-spectrum prescription, or topical prescription) was associated with an HRR of 1.27 (95%-CI = 1.04-1.54). The number of anti-infectives prescribed over the course of the study period was associated with an HRR of 1.05 (95%-CI = 1.00-1.10). There was no significant relationship between prescription of topical or narrow-spectrum antibiotics, antifungal, or antiviral medication and subsequent diagnosis of anxiety or depression. Stratified analysis revealed that the association between anti-infective prescription and anxiety and depression was driven by males, among whom prescription of any antibiotic was associated with an HRR of 1.45 (95%-CI = 1.05-1.99). Conclusions: Infections treated with broad-spectrum antibiotics were associated with increased risks of anxiety and/or depression, especially in males. Exploration of the relationship between antibiotic exposure and subsequent mental health disorders is warranted along with continued vigilance in antibiotic prescribing practices in children.
Language	English
Publishing date	2022-02-15
Publishing country	United States
Document type	Journal Article
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2022.100430
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