Clinical toxoplasmosis is a rare but often fatal disease that impacts several medical fields, including obstetrics, ophthalmology, transplantation, oncology and the context of the AIDS pandemic. The prognosis for patients with toxoplasmosis largely depends on timely treatment, which makes early diagnosis a priority for clinicians. However, diagnosing toxoplasmosis is a significant challenge due to the lack of specific clinical symptoms. This issue is further complicated by the high seroprevalence of Toxoplasma in the general population, which is far higher than the incidence of the disease. There are currently no clinically useful predictors for toxoplasmosis. Epidemiological studies and host-parasite interactions suggest that the incidence of toxoplasmosis depends on a combination of host and parasite factors. Significant risk factors include immunodeficiency, in utero exposure, genetic predisposition, anti-Toxoplasma antibody levels, older age, virulence of the strain, parasite burden and the infectious form of the parasite. Understanding these risk factors is important for clarifying the uncertainties regarding the incidence of toxoplasmosis and improving patient outcomes. In this review, we discuss the significance of these factors and current measurements for parasite-related factors. Additionally, we discuss potential preventive strategies that focus on screening as well as control of modifiable risk factors.

Abstract Cell-mediated immune responses are crucial for protecting the host against Toxoplasma gondii infection. However, impaired immunity, such as T-cell exhaustion, is a common phenomenon during chronic infection. This may represent a strategy employed by T. gondii to evade host defenses. T-cell immunoglobulin and mucin-domain containing 3 (Tim-3) is an important regulatory molecule involved in cell-mediated immunity. This study examined the expression of Tim-3 and the effects of its blockade in a mouse model of toxoplasmosis. In mice with chronic T. gondii infection, we found that Tim-3 is highly expressed in both cyst-bearing and non-cyst-bearing tissues, and its expression correlates with the parasite burden. Blocking the Tim-3 pathway with an anti-Tim-3 antibody enhances the immune response, resulting in elevated levels of cytokines (IFN-γ, IL-12p70, IL-2, IL-9) and the chemokine CXCL1 in the serum, increased leukocyte infiltration (CD3 + , CD14 + cells) in the brain, and downregulation of Tim-3 expression in microglial cells. As a result, the anti-Tim-3 treatment resulted in a 62% reduction in the number of tissue cysts and a trend towards an increase in the homeostatic signature, P2RY12, in microglia. Our study provides proof of concept for an anti-Tim-3 approach in treating chronic T. gondii infection and potentially other brain-residing pathogens.

Background: Shortages of pediatric mental health (MH) specialty providers have left pediatric primary care providers (PPCP) to care for the influx of youth with MH needs. This study examined trends in prescription of antidepressants and antianxiety medication in pediatric primary care clinics from 2015 to 2023. Methods: Annual rates of prescription of antidepressant and/or antianxiety medication orders were calculated by race/ethnicity, sex, and practice type. Adjusted mean differences (AMD) were calculated and compared for the beginning and end of the study period. Results: Prescription orders for antianxiety and/or antidepressant medications increased between 2015 and 2023 across all patients but was greatest among Hispanic youth (AMD = 50.9, 95% CI = 15.3-86.4) and among females irrespective of race (AMD = 29.3, 95% CI = 16.8-41.7). Despite these increases, non-Hispanic White youth were more likely to receive prescriptions than Hispanic and non-Hispanic Asian or Black youth across time periods. Family practices (treating adults and children) had the highest rates of prescription across time periods. Conclusions: While prescription rates for antidepressant and antianxiety medications have increased overall, treatment gaps between White and ethnoracially minoritized pediatric patients have persisted. Differences in prescribing patterns between practice environments suggest PPCPs may be more comfortable prescribing MH medications in family practices relative to pediatric practices.

This study investigates the role of the gut microbiome in suicidal behavior among individuals with major depressive disorder (MDD). Fecal samples from 50 hospitalized patients with MDD, including 35 with recent suicide attempts (60 % female) and 15 without a history of suicide (73 % female), were analyzed using 16S rRNA and shotgun sequencing to assess microbiome diversity and metabolic potential. Results revealed that suicide attempters exhibited significantly greater microbial richness and distinct beta-diversity patterns. Notably, they had higher levels of Fenollaria timonensis and lower levels of Corynebacterium aurimucosum. Additionally, 25 metabolic pathways differed between groups, with several linked to energy metabolism and amino acid processing-processes previously associated with MDD and suicidal behavior. These findings suggest that microbiome composition may influence suicide risk through gut-brain axis-mediated pathways, although due to the exploratory nature of this study further investigation is needed to validate our findings. Given the microbiome's modifiability, future research should explore microbial-targeted interventions as a potential strategy for suicide prevention in individuals with MDD.

The protozoan parasite, Toxoplasma gondii, has evolved a creative skillset to engage and sustain itself within a diversity of warm-blooded hosts. Progression to adulthood requires residence in the definitive host, Felidae, a taxonomic family encompassing the beloved, sometimes maligned, housecat. Humans are intermediate hosts, primarily infected following ingestion of foodstuffs containing T. gondii tissue cysts or T. gondii oocysts shed by cats. Although most human cases are asymptomatic, acute inflammation and deadly encephalopathies can result if the infection is congenital, or the host is immunocompromised. Increasingly, presumably benign asymptomatic infections are being investigated for behavioral outcomes and complex brain disorders such as schizophrenia. While not typically considered an inflammatory disorder, reports of muted idiopathic inflammation-like comorbidities in schizophrenia persist and cannot be discounted by the usual covariants, medications and metabolic factors. T. gondii's survival success may depend on its ability to regulate host inflammation and satisfy its own life-stage requirements for both motility and quiescence. Within the setting of this fluctuating inflammatory environment putatively controlled by T. gondii, other gene and environmental forces are also at work. We consider a model of schizophrenia centered on complement gene variants and the unique capacity for this set of immune pathways to perpetrate and perpetuate neurobiological dysfunction. We examine T. gondii's connections to the gut, to chronic stress, how its relationship with schizophrenia has matured, and how the boundaries between what qualifies as gene and environment have become blurred as we enter a new era of the microbiome and more personalized medicine.

Background: Zonulin, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14) are frequently used as proxy biomarkers of intestinal permeability in studies involving patients with psychiatric disorders. Although often used interchangeably, these biomarkers reflect distinct biological processes. Objective: This review integrates evidence from basic research on the mechanisms of action of zonulin, LBP, and sCD14 with findings from studies on major depressive disorder, bipolar disorder, and schizophrenia spectrum disorders, aiming to refine their application in gut-brain axis research. Findings: Zonulin is consistently elevated in schizophrenia spectrum disorders and appears most closely linked to gut barrier integrity and systemic immune activation. LBP is consistently elevated in major depressive disorder and may reflect underlying alterations in gut permeability, metabolic status, and psychological stress. sCD14 has been primarily studied in schizophrenia spectrum disorders, where findings are more heterogeneous, and is thought to reflect generalized monocyte activation. These biomarkers were largely unrelated to clinical symptom severity, with the exception of sCD14, which showed associations with positive symptoms, aggression, and the number of manic episodes. Conclusions: Zonulin, LBP, and sCD14 each capture unique aspects of gut and immune system function. Their interchangeable use risks misinterpretation. A more nuanced, context-dependent application-tailored to specific research questions or intervention targets-is essential for advancing gut-brain axis research in psychiatry.

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 suiciderelated 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.

Technological advances in nucleic acid sequencing in recent years effectively launched and propelled a new age of the microbiome. A mechanism known as the gut-brain axis has been adopted by psychiatric and neurological researchers, as another possible way to reconcile gene-by-environmental and other hypotheses of how serious brain disorders develop. Toward this end, the microbiome, may represent an informative biomarker, or series of biomarkers, of cellular, molecular, and metabolic pathways that are altered in disease. As with any field projected to be an enormous influence on the future of medicine, early studies of the microbiome are numerous and sometimes afflicted with study design and data quality issues. Some progress in these areas is underway, and here we provide a brief update of the current state of the microbiome with a focus on clinical studies and the quests to better understand mechanistically what functional outcomes in neuropsychiatric disorders might be mediated by microbes. We also review the concept of the microbiome biomarker as a dynamic and evolving measure that keeps improving as technology flourishes. In vitro gut systems that merge innervation and vascularization of epithelial organoids exemplify next-generation microbiome biomarkers.

Purpose: We examined racial and gender disparities in the underrecognition of mental health disorders in adolescents and young adults as defined by a suicide -related diagnosis without a previous mental or behavioral health diagnosis. Methods: We employed a series of adjusted mixed multilevel logistic regression models to determine the odds of specific mental health diagnoses (anxiety, depression, and suicide -related) in a large, U.S. pediatric ambulatory care group (ages 8-20 years) using Electronic Medical Record Data. Results: Using the reference group of White males, White females had 17% increased odds of having a suicide -related diagnosis (odds ratio (OR) 1.17, 95% confidence intervals (CI) 1.03, 1.34) and Black females had 48% increased odds of suicide -related diagnosis (OR 1.48, 95% CI 1.28, 1.71). Conversely, White females had 75% increased odds of recorded anxiety (OR 1.75, 95% CI 1.62, 1.89), Black males had 62% decreased odds of anxiety (OR 0.38, 95% CI 0.33, 0.42), and Black females had 33% decreased odds of anxiety (OR 0.67, 95% CI 0.60, 0.74). White females had 81% increased odds of having recorded depression (OR 1.81, 95% CI 1.62, 2.04) and Black females had 80% increased odds of underrecognized need for mental or behavioral health diagnosis services (OR 1.80, 95% CI 1.53, 2.13) as defined by a suicide -related diagnosis without a previous mental health diagnosis. Discussion: Black adolescents and young adult patients are either not accessing or identified as needing mental health services at the same rates as their White peers, and Black females are experiencing the most underrecognition of need for mental health services. (c) 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoa in that it can infect the majority of mammalian cell types during the acute phase of infection. Furthermore, it is able to establish a chronic infection for the host’s entire lifespan by developing an encysted parasite form, primarily in the muscles and brain of the host, to avoid the host immune system. The infection affects one third of the world population and poses an increased risk for people with a suppressed immune system. Despite the dormant characteristics of chronic T. gondii infection, there is much evidence suggesting that this infection leads to specific behavior changes in both humans and rodents. Although numerous hypotheses have been put forth, the exact mechanisms underlying these behavior changes have yet to be understood. In recent years, several studies revealed a strong connection between the gut microbiome and the different organ systems that are affected in T. gondii infection. While it is widely studied and accepted that acute T. gondii infection can lead to a dramatic disruption of the host’s normal, well-balanced microbial ecosystem (microbial dysbiosis), changes in the gut microbiome during the chronic stage of infection has not been well characterized. This review is intended to briefly inspect the different hypotheses that attempt to explain the behavior changes during T. gondii infection. Furthermore, this review proposes to consider the potential link between gut microbial dysbiosis, and behavior changes in T. gondii infection as a novel way to describe the underlying mechanism.

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.

Viral infections during childhood can increase susceptibilities to neurodevelopmental and psychiatric disorders. We are currently in the early years following a viral pandemic caused by the rapid evolution of highly transmissible, host-evading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Here we place this virus and the disease it generates, Coronavirus Disease 2019 (COVID-19), in the context of inflammatory host phenotypes and psychosocial factors which exacerbate stress to the developing human nervous system. While exposures to pathogens and inflammation during neurodevelopment are well-studied risk factors in psychiatric research, the subtle effects on a child’s physiology of factors such as social isolation, food insecurity, and other social determinants of health are more difficult to identify and quantify. In this post-pandemic era, we have the unique opportunity to initiate in local community healthcare facilities, inclusive longitudinal studies to measure pandemic-mediated mental health outcomes in children of all races, ethnicities, genders, and other groups shaped by social, cultural, and as yet unidentified determinants. Toward this end, the identification of children in need of prompt psychiatric intervention may be accelerated by the use of biomarkers indicating COVID-19 infection status, inflammation, imbalances of the gut-brain axis, and acute and chronic stress. Especially promising are approaches combining these biomarkers with mental health screening tools such as the Child Behavior Checklist (CBCL) and the Epic Patient Healthcare Questionnaire 9 (PHQ9).

IntroductionHerpesviruses are recognized as major causes of human diseases. Following initial infection, Herpesviruses can undergo cycles of reactivation controlled largely by the immune system. Cigarette smoking is an important modulator of the immune system particularly in individuals with serious mental illness where smoking is associated with increased rates of cardiopulmonary diseases and mortality. However, the effect of smoking on Herpesviruses has not been extensively studied. MethodsIn this nested cohort study, cigarette smoking was assessed in 1323 persons with serious mental illness or without a psychiatric disorder ascertained in a psychiatric health care system and the adjacent community. Participants provided a blood sample from which were measured IgG class antibodies to five human Herpesviruses: Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Herpes Simplex Virus-Type 1 (HSV-1); Varicella Zoster Virus (VZV); and Human Herpes Virus-Type 6 (HHV-6). The associations between smoking variables and antibody levels to the Herpesviruses were analyzed among diagnostic groups in multiple regression models adjusted for age, sex, and race. ResultsCurrent smoking was significantly associated with higher levels of antibodies to CMV (coefficient .183, 95% CI .049, .317, p<.001, q<.007) and the three EBV proteins (EBV NA -(coefficient .088, 95% CI .032, .143, p = .002, q<.014; EBV Virion - coefficient .100, 95% CI .037, .163, p = .002, q<.014; and EBV VCA - coefficient .119, 95% CI .061, .177, p = .00004, q<.0016). The amount of cigarettes smoked was also correlated with higher levels of antibodies to the three EBV proteins. Interaction analyses indicated that the association between cigarette smoking and levels of antibodies to CMV and EBV was independent of diagnostic group. Cigarette smoking was not significantly associated with the level of antibodies to HSV-1, VZV, or HHV-6. ConclusionsIndividuals who smoke cigarettes have increased levels of IgG antibodies to CMV and EBV. Cigarette smoking may be a contributory factor in the relationship between CMV, EBV and chronic somatic disorders associated with these viruses.

Complex brain disorders like schizophrenia may have multifactorial origins related to mis-timed heritable and environmental factors interacting during neurodevelopment. Infections, inflammation, and autoimmune diseases are over-represented in schizophrenia leading to immune system-centered hypotheses. Complement component C4 is genetically and neurobiologically associated with schizophrenia, and its dual activity peripherally and in the brain makes it an exceptional target for biomarker development. Studies to evaluate the biomarker potential of plasma or serum C4 in schizophrenia do so to understand how peripheral C4 might reflect central nervous system-derived neuroinflammation, synapse pruning, and other mechanisms. This effort, however, has produced mostly conflicting results, with peripheral C4 sometimes elevated, reduced, or unchanged between comparison groups. We undertook a pilot biomarker development study to systematically identify sociodemographic, genetic, and immune-related variables (autoimmune, infection-related, gastrointestinal, inflammatory), which may be associated with plasma C4 levels in schizophrenia (SCH; n = 335) and/or in nonpsychiatric comparison subjects (NCs; n = 233). As with previously inconclusive studies, we detected no differences in plasma C4 levels between SCH and NCs. In contrast, levels of general inflammation, C-reactive protein (CRP), were significantly elevated in SCH compared to NCs (ANOVA, F = 20.74, p < 0.0001), suggestive that plasma C4 and CRP may reflect different sources or causes of inflammation. In multivariate regressions of C4 gene copy number variants, plasma C4 levels were correlated only for C4A (not C4B, C4L, C4S) and only in NCs (R Coeff = 0.39, CI = 0.01–0.77, R2 = 0.18, p < 0.01; not SCH). Other variables associated with plasma C4 levels only in NCs included sex, double-stranded DNA IgG, tissue-transglutaminase (TTG) IgG, and cytomegalovirus IgG. Toxoplasma gondii IgG was the only variable significantly correlated with plasma C4 in SCH but not in NCs. Many variables were associated with plasma C4 in both groups (body mass index, race, CRP, N-methyl-D-aspartate receptor (NMDAR) NR2 subunit IgG, TTG IgA, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14). While the direction of most C4 associations was positive, autoimmune markers tended to be inverse, and associated with reduced plasma C4 levels. When NMDAR-NR2 autoantibody-positive individuals were removed, plasma C4 was elevated in SCH versus NCs (ANOVA, F = 5.16, p < 0.02). Our study was exploratory and confirmation of the many variables associated with peripheral C4 requires replication. Our preliminary results point toward autoimmune factors and exposure to the pathogen, T. gondii, as possibly significant contributors to variability of total C4 protein levels in plasma of individuals with schizophrenia.

INTRODUCTION:The combined genetic material of the microorganisms in the human body, known as the microbiome, is being increasingly recognized as a major determinant of human health and disease. Although located predominantly on mucosal surfaces, these microorganisms have profound effects on brain functioning through the gut-brain axis.METHOD:The content of the chapter is based on a study group session at the annual meeting of the American College of Neuropsychopharmacology (ACNP). The objective was to discuss the emerging relationship between the human microbiome and mental health as relevant to ACNP's interests in developing and evaluating novel neuropsychiatric treatment strategies. The focus is on specific brain disorders, such as schizophrenia, substance use, and Alzheimer's disease, as well as on broader clinical issues such as suicidality, loneliness and wisdom in old age, and longevity.RESULTS:Studies of schizophrenia indicate that the microbiome of individuals with this disorder differs from that of non-psychiatric comparison groups in terms of diversity and composition. Differences are also found in microbial metabolic pathways. An early study in substance use disorders found that individuals with this disorder have lower levels of beta diversity in their oral microbiome than a comparison group. This measure, along with others, was used to distinguish individuals with substance use disorders from controls. In terms of suicidality, there is preliminary evidence that persons who have made a suicide attempt differ from psychiatric and non-psychiatric comparison groups in measures of beta diversity. Exploratory studies in Alzheimer's disease indicate that gut microbes may contribute to disease pathogenesis by regulating innate immunity and neuroinflammation and thus influencing brain function. In another study looking at the microbiome in older adults, positive associations were found between wisdom and alpha diversity and negative associations with subjective loneliness. In other studies of older adults, here with a focus on longevity, individuals with healthy aging and unusually long lives had an abundance of specific microorganisms which distinguished them from other individuals.DISCUSSION:Future studies would benefit from standardizing methods of sample collection, processing, and analysis. There is also a need for the standardized collection of relevant demographic and clinical data, including diet, medications, cigarette smoking, and other potentially confounding factors. While still in its infancy, research to date indicates a role for the microbiome in mental health disorders and conditions. Interventions are available which can modulate the microbiome and lead to clinical improvements. These include microbiome-altering medications as well as probiotic microorganisms capable of modulating the inflammation in the brain through the gut-brain axis. This research holds great promise in terms of developing new methods for the prevention and treatment of a range of human brain disorders.

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.

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.