Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.
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PMID:Abnormal Barrier Function in Gastrointestinal Disorders. 2799 92

Schizophrenia and bipolar disorder are serious neuropsychiatric disorders of uncertain etiology. Recent studies indicate that immune activation may contribute to the etiopathogenesis of these disorders. Numerous studies in animal models indicate that the mucosal microbiome may influence cognition and behavior by altering the functioning of the immune system. It is thus likely that the microbiome plays a role in human psychiatric disorders. The study of immune alterations and the microbiome in schizophrenia and bipolar disorder is in its infancy. Two recent investigations of the oro-pharyngeal microbiota in schizophrenia found differences between cases and controls. Other studies have found increased gastrointestinal inflammation in schizophrenia and bipolar disorder based on measures of microbial translocation. Several studies have also found an association between the receipt of antibiotics and an increased incidence of psychiatric disorders, perhaps due to alterations in the microbiome. Studies to characterize the intestinal microbiome of individuals with these disorders are in progress. The ultimate test of the role of the microbiome and immune-mediated pathology in schizophrenia and bipolar disorder will come from clinical trials of therapeutic agents which alter gut microbiota or gastrointestinal inflammation. The successful development of such modalities would represent a novel strategy to prevent and treat serious psychiatric disorders.
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PMID:The microbiome, immunity, and schizophrenia and bipolar disorder. 2800 52

The gut microbes, collectively called microbiota, are linked to the brain through a bidirectional system that involves the vagus nerve, the immune system, and various neurotransmitters. Stress response, memory functions, social behavior, and mood are modulated by microbiota. Furthermore, microbiota play a role in the development of the central nervous system. These features, established largely in rodent studies, have informed hypotheses about the role of microbiota in human psychiatric disorders. Microbiota affect phenomena that are known to be parts of the depression phenotype, such as exaggerated response to stress and inflammatory features. Furthermore, the role of microbiota in neurodevelopment and in the modulation of social behavior suggests the possibility of its role in autism spectrum disorder and in schizophrenia. If altered, microbiota play a role in psychiatric disorders, then efforts to normalize the gut microbial population by the ingestion of probiotics (live bacteria) could have antidepresssant or antipsychotic effects. Testing such hypotheses in translational human studies is a matter of future research.
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PMID:Can gut microbes play a role in mental disorders and their treatment? 2829 71

The CCK(1) receptor is a G-protein-coupled receptor activated by the sulfated forms of cholecystokinin (CCK), a gastrin-like peptide released in the gastrointestinal tract and mammal brain. A substantial body of research supports the hypothesis that CCK(1)r stimulates gallbladder contraction and pancreatic secretion in the gut, as well as satiety in brain. However, this receptor may also fulfill relevant roles in behavior, thanks to its widespread distribution in the brain. The strategic location of CCK(1)r in mesolimbic structures and specific hypothalamic and brainstem nuclei lead to complex interactions with neurotransmitters like dopamine, serotonin, and glutamate, as well as hypothalamic hormones and neuropeptides. The activity of CCK(1)r maintains adequate levels of dopamine and regulates the activity of serotonin neurons of raphe nuclei, which makes CCK(1)r an interesting therapeutic target for the development of adjuvant treatments for schizophrenia, drug addiction, and mood disorders. Unexplored functions of CCK(1)r, like the transmission of interoceptive sensitivity in addition to the regulation of hypothalamic hormones and neurotransmitters affecting emotional states, well-being, and attachment behaviors, may open exciting roads of research. The absence of specific ligands for the CCK(1) receptor has complicated the study of its distribution in brain so that research about its impact on behavior has been published sporadically over the last 30 years. The present review reunites all this body of evidence in a comprehensive way to summarize our knowledge about the actual role of CCK in the neurobiology of mental illness.
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PMID:The unappreciated roles of the cholecystokinin receptor CCK(1) in brain functioning. 2834 67

Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might precipitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery. These specific alterations in the genetic and epigenetic make-up of aggressive individuals might determine distinct biochemical signatures detectable through metabolomics. An additional pathophysiological component playing a role in aggressive behavior might be determined by alterations of gut microbiota. Here, we present a selective review of human data on genetic, epigenetic, and metabolomic markers of aggressive behavior in SMI, discussing also the available evidence on the role of microbiome alterations. Clinical implication of these evidences, as well as future perspectives, will be discussed.
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PMID:Targeting aggression in severe mental illness: The predictive role of genetic, epigenetic, and metabolomic markers. 2837 95

Growing interest in gut and digestive processes and their potential link to brain and peripheral based inflammation or biobehavioral phenotypes has led to an increasing number of basic and translational scientific reports focused on the role of gut microbiota within the context of neuropsychiatric disorders. However, the effect of dietary modification on specific gut metabolites, in association with immune, metabolic, and psychopathological functioning in schizophrenia spectrum disorders has not been well characterized. The short chain fatty acids (SCFA) acetate, butyrate, and propionate, major metabolites derived from fermentation of dietary fibers by gut microbes, interact with multiple immune and metabolic pathways. The specific pathways that SCFA are thought to target, are dysregulated in cardiovascular disease, type II diabetes, and systemic inflammation. Most notably, these disorders are consistently linked to an attenuated lifespan in schizophrenia. Although, unhealthy dietary intake patterns and increased prevalence of immune and metabolic dysfunction has been observed in people with schizophrenia; dietary interventions have not been well utilized to target immune or metabolic illness. Prior schizophrenia patient trials primarily focused on the effects of gluten free diets. Findings from these studies indicate that a diet avoiding gluten benefits a limited subset of patients, individuals with celiac disease or non-celiac gluten sensitivity. Therefore, alternative dietary and nutritional modifications such as high-fiber, Mediterranean style, diets that enrich the production of SCFA, while being associated with a minimal likelihood of adverse events, may improve immune and cardiovascular outcomes linked to premature mortality in schizophrenia. With a growing literature demonstrating that SCFA can cross the blood brain barrier and target key inflammatory and metabolic pathways, this article highlights enriching dietary intake for SCFA as a potential adjunctive therapy for people with schizophrenia.
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PMID:Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? 2839 23

With the emergence of knowledge implicating the human gut microbiome in the development and regulation of several physiological systems, evidence has accumulated to suggest a role for the gut microbiome in psychiatric conditions and drug response. A complex relationship between the enteric nervous system, the gut microbiota and the central nervous system has been described which allows for the microbiota to influence and respond to a variety of behaviors and psychiatric conditions. Additionally, the use of pharmaceuticals may interact with and alter the microbiota to potentially contribute to adverse effects of the drug. The gut microbiota has been described in several psychiatric disorders including depression and anxiety, but only a few reports have discussed the role of the microbiome in schizophrenia. The following review examines the evidence surrounding the gut microbiota in behavior and psychiatric illness, the role of the microbiota in schizophrenia and the potential for antipsychotics to alter the gut microbiota and promote adverse metabolic events.
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PMID:The microbiome-gut-brain axis: implications for schizophrenia and antipsychotic induced weight gain. 2862 47

Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis. Much of this interplay may be moderated by epigenetic changes. Similar to genetic mutations, epigenetic modifications such as DNA methylation, histone modifications, and RNA interference can influence gene expression and therefore may cause behavioral and neuronal changes observed in mental disorders. Environmental factors such as diet, gut microbiota, and infections have significant role in these epigenetic modifications. Studies show that bioactive nutrients and gut microbiota can alter either DNA methylation and histone signatures through a variety of mechanisms. Indeed, microbes within the human gut may play a significant role in the regulation of various elements of "gut-brain axis," via their influence on inflammatory cytokines and production of antimicrobial peptides that affect the epigenome through their involvement in generating short chain fatty acids, vitamin synthesis, and nutrient absorption. In addition, they may participate in-gut production of many common neurotransmitters. In this review we will consider the potential interactions of diet, gastrointestinal microbiome, inflammation, and epigenetic alterations in psychiatric disorders.
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PMID:Microbiome, inflammation, epigenetic alterations, and mental diseases. 2869 68

Autoantibodies that bind the N-methyl-D-aspartate receptor (NMDAR) may underlie glutamate receptor hypofunction and related cognitive impairment found in schizophrenia. Exposure to neurotropic pathogens can foster an autoimmune-prone environment and drive systemic inflammation leading to endothelial barrier defects. In mouse model cohorts, we demonstrate that infection with the protozoan parasite, Toxoplasma gondii, caused sustained elevations of IgG class antibodies to the NMDAR in conjunction with compromised blood-gut and blood-brain barriers. In human cohorts, NMDAR IgG and markers of barrier permeability were significantly associated with T. gondii exposure in schizophrenia compared with controls and independently of antipsychotic medication. Combined T. gondii and NMDAR antibody seropositivity in schizophrenia resulted in higher degrees of cognitive impairment as measured by tests of delayed memory. These data underscore the necessity of disentangling the heterogeneous pathophysiology of schizophrenia so that relevant subsets eligible for NMDAR-related treatment can be identified. Our data aid to reconcile conflicting reports regarding a role of pathological NMDAR autoantibodies in this disorder.
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PMID:Pathogen-mediated NMDA receptor autoimmunity and cellular barrier dysfunction in schizophrenia. 2876 62

The focus on the microbiome for the 2017 Named Series in Brain, Behavior, and Immunity reflects the rapidly growing interest in commensal microbes and the effects that they can have on physiological processes often studied in PsychoNeuroImmunology Research. The studies included in this Named Series show that commensal microbes can impact immune system activity, as well as brain and behavioral processes across the lifespan, and are involved in behavioral and immunological responses to social stresses. The studies also show that dietary effects on brain, behavior, and immunity often involve alterations of the gut microbiota. Thus, diet can be used therapeutically for diseases and conditions involving the brain, behavior, and immunity, as can treatment with both pre- and probiotics. While this has been widely tested in animal models, fewer studies have focused on pre- and probiotic treatment in humans. The studies in this Named Series highlight the challenges of probiotic research in human populations, but also highlight the future promise of probiotics for human health. While emotional disorders, such as anxiety and depression have been often been linked to alterations in the gut microbiota, studies in this Named Series identify new domains involving interactions between the microbiota, brain, behavior, and immunity, including schizophrenia, traumatic brain injury, and stroke. As a whole, this collection of work demonstrates the importance of the microbiome in regulating key aspects of immunity, brain, and behavior, and provides important rationale for extending the work so that findings can be translated into clinical practice.
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PMID:The microbiome as a key regulator of brain, behavior and immunity: Commentary on the 2017 named series. 2884 52


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