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Disease ⇒ Severe Mental Disorders ⇒ Schizophrenia {40000115}

Record Keys
Type:	Disease
Parent:	Severe Mental Disorders
Definition:	Schizophrenia

Details
Initialisation date:	2020-09-06
Other Terms:	SCZ

Links
Wickipedia Merck Manual

Meta Information
MedDra ID:	10039626
MedDra Level:	pt
ICD:	[ ]
Category:	Psychiatry
Zone:	[ ]
Mechanism:	[ ]

Notes:

- Host-genetic-driven increases in Enterobacteriaceae family and Enterobacteriales order were potentially related to a higher risk of SCZ, while Gammaproteobacteria class was related to a lower risk of SCZ
- Gut production of serotonin was potentially associated with a higher risk of SCZ.
- There is a strong relationship of lower platelet serotonin concentrations with depressive symptoms of SCZ.
- According to the principle of brain plasticity, glutamate signals are destroyed by serotonergic overdrive, leading to neuronal hypometabolism, synaptic atrophy, and gray matter loss in the end.
- Enterobacteriaceae family and Enterobacteriales order can produce SCFAs (e.g., acetic acid and formic acid) in carbohydrate fermentation, thus inducing serotonin biosynthesis by enterochromaffin cells which are the major producers of serotonin, and ultimately increasing the risk of SCZ.
- Porphyromonadaceae were associated with poor cognitive performance.
- Gut inflammation can induce activation of microglia and the kynurenine pathway, which activate systemic inflammation-inducing depressive or schizophrenic symptoms (1)

Shared Reference Notes

[1.1]
- The schizophrenia-associated bacterium #Streptococcus vestibularis, which contributed to the microbiota metagenomic-based discrimination of patients with schizophrenia from healthy controls, when transplanted to mice gut induced deficits in social behaviors, altering neurotransmitter levels in peripheral tissues of recipient animals.
[1.2] [#Clostridioides difficile]
- Schizophrenia and autism incidence has been found to be higher in the C. difficile diseased population. - This association was further explained by a #Phenylalanine derivative synthesized and released by the same bacteria in the gut that is known to regulate catecholamine levels in the brain.
- CD14 seropositivity is responsible for three times increase in the risk of having schizophrenia in comparison to control group. The same CD14 seropositivity was associated with #Gluten antibodies in newly diagnosed patients with schizophrenia
- Altered human gut microbiome may have a significant contribution to the NMDA (#N-methyl-D-aspartate) receptor hypoactivity, as observed in patients with schizophrenia.
[1.3] [#Bacteriophage]
- Lactobacillus phiadh infects #Lactobacillus gasseri. - At least 1 match for Lactobacillus phage phiadh was found in 17 of 41 of PWS, as compared to 1 of 33 of controls. - The study also found that the level of Lactobacillus phiadh > correlated with an increased rate of comorbid immunological disorders in PWS. - The phage Lactobacillus phiadh modulates the level of its host bacterium, #Lactobacillus gasseri, which affects the host’s immune system.
[1.4]
- Fecal transplantation from schizophrenia patients to GF mice resulted in elevated levels of glutamine and #GABA in the hippocampus, and led to schizophrenia-related behaviors
[1.5]
- Elevated levels of #Glutamine and γ-aminobutyric acid (#GABA) and reduced #Glutamate were observed in the hippocampus of germ-free mice that received fecal transplants from schizophrenic mice and showed schizophrenia-like behaviors.
[1.6] [#Cancer]
- #Lachnoclostridium depleted in other psychiatric disorders including schizophrenia and #Autism and in patients with gastrointestinal tract neoplasms.
[1.7] [#Bipolar disorder, #Major depressive disorder]
- MDD was often characterized by higher #Alistipes and #Parabacteroides and lower #Prevotella; BD by higher #Bifidobacterium and #Oscillibacter; and SZ by higher #Prevotella and lower #Bacteroides, #Haemophilus, and #Streptococcus
[#Bipolar disorder, #Major depressive disorder] - Gut microbiota in BD, MDD and SZ > increase in #Eggerthella and #Lactobacillus, together with a decrease in #Coprococcus was common for the three conditions in comparison to controls.
[#Bipolar disorder, #Major depressive disorder] - MDD and SZ shared higher levels of #Escherichia/#Shigella and #Veillonella whereas increased #Megasphaera and lower #Roseburia are common for BD and SZ.
[#Bipolar disorder, #Major depressive disorder] [#Quinolinic acid, #kynurenine] - shift in the #Tryptophan metabolism from #Serotonin to the kyn pathway is associated with BD, MDD and SZ, but only in mood disorders (BD and MDD) there was a preferential metabolism of Kyn to the potentially neurotoxic QA.
[#Bipolar disorder] - BD and SZ are characterized by higher serum antibody levels to fungal pathogens #Saccharomyces cerevisiae and #Candida albicans > could be related to cognitive performance or the onset of psychotic symptoms
[1.8]
- Anti-NRXN1α autoantibodies isolated from patients with schizophrenia inhibited the molecular interaction between NRXN1α and Neuroligin 1 (NLGN1) and between NRXN1α and Neuroligin 2 (NLGN2). - Administration of anti-NRXN1α autoantibodies from patients with schizophrenia into the cerebrospinal fluid of mice reduced the number of spines/synapses in the frontal cortex and induced schizophrenia-related behaviors such as reduced cognition, impaired pre-pulse inhibition, and reduced social novelty preference.
[1.9] [#Atopic Dermatitis]
- participants with AD were more likely to have schizophrenia or schizoaffective disorder. - AD was significantly associated with schizophrenia and schizoaffective disorder even after adjusting for demographics and comorbidities.
[#Cognitive impairment] [#Glutamate, #Glutamine] - Disruption within the glutamatergic pathway can lead to cognitive deficits, schizophrenia and frontotemporal #Dementia
[1.11] [#Depression, #Major depressive disorder] [#Candida albicans]
[1.12]
- brain inflammation, as seen in schizophrenia, can be treated with alpha-7 nAChR (α-7nAChR) agonists or by stimulating the vagus nerve
- animal models of schizophrenia had reduced systemic #Dopamine and lower enteric #GABA
[1.13]
[1.14] [#Short Chain Fatty Acid]
- alterations in the #Glutamate-#Glutamine-#GABA cycle and increased SCFAs have been observed in patients with schizophrenia.
[#Short Chain Fatty Acid] - genera #Lactobacillus and #Megasphaera are increased in schizophrenia (SZ), as well as alterations in the #Glutamate-#Glutamine-#GABA cycle, serum levels of #Tryptophan, #kynurenic acid (KYNA), and short-chain fatty acids (SCFAs).
- altered microbiota in psychosis induces lower serum #Tryptophan, higher serum #kynurenic acid (KYNA) levels, and changes in gray matter volume in non-medicated psychotic patients
[1.15] [#Depression] [#Sugar]
- Dietary sugars, like #Fructose and #Glucose, are associated with psychosis-related higher brain dysfunction
[1.16] [#Autism, #Bipolar disorder]
- Increased levels of #Lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. - These changes in #Lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders.
[1.17] [#Bipolar disorder] [#Keto diet, #Mediterranean Ketogen Diet]
[1.18]
- Megasphera, #Akkermansia, #Fusobacterium and #Prevotella were significantly more abundant in SCZ patients, and #Citrobacter, #Blautia, #Coprococcus, #Lachnoclostridium were more abundant in HC controls.
[#Ruminococcus] - #Shigella and #Collinsella were more abundant in SCZ patients, and #Faecalibacterium, #Coprococcus, #Prevotella, #Haemophilus, Ruminococcaceae_Ruminococcus, #Bacteroides, and #Oscillospira are significantly abundant in HC
[#Genome] - #Paraprevotella and #Catabacter were identified to have a strong correlation with the above four SCZ genes
[#Fecal Microbiota Transplantation] - mice transplanted with fecal microbiota of SCZ patients could induce SCZ-like behavior. - mice receiving gut microbiota transfers from patients with SCZ displayed disturbances of transcripts involved in Neuroactive ligand-receptor interaction, inflammation and immunity-related signaling pathways, which has been strongly associated with SCZ pathology.
[#GABA] - SCZ patients and fecal microbiota-recipient mice were mainly enriched in GABAergic synapse and inflammation-related signaling pathways.
[1.19] [#Major depressive disorder, #Parkinson’s Disease]
- #Isoprene is involved in the mevalonate pathway of #Cholesterol synthesis. - decreased exhaled levels of #Isoprene have been detected in patients with #Lung cancer. - #Isoprene > a key role in cell membrane integrity, which has been linked to several neurologic and psychiatric disorders, such as schizophrenia and #Bipolar disorder, as well as Parkinson disease and #Multiple Sclerosis. - A possible neuroprotective function of #Isoprene might explain its absence in the breath of patients with schizophrenia and MDD, indicating a disturbance in neuroprotection in psychiatric disorders.
[#Major depressive disorder] - significant downregulation of TAAR5 in the prefrontal cortex of patients with MDD, but no expression imbalances of TAAR5 for those with #Bipolar disorder or schizophrenia.
- Distinct VOC signatures for schizophrenia were m/z 60 and m/z 74. The first of these was identified as trimethylamine (#TMA). - patients with schizophrenia displayed a significantly lower concentration of #TMA in their breath. - Decreased production of #TMA is found in patients with #Choline-deficient diets, in nonalcoholic #Steatohepatitis and may result in #Obesity and #Hyperglycemia, which are often seen in patients with schizophrenia.
- increased blood levels of #Butyric acid could be associated with a positive treatment response and symptom reduction in patients with schizophrenia. - The neuroprotective features of #Butyric acid stem from its ability to influence histone acetylation and thereby protect neurons from cell death.

References Notes

[1.29]

↥ Microbiota

‐ Actinomyces Stool Human [1.20]

‐ Akkermansia muciniphila Stool Human [1.21]

‐ Alkaliphilus oremlandii Stool Human [1.21]

‐ Anaerococcus Stool Human [1.22]

‐ Anaerotruncus Stool Human [1.20]

‐ Bacteroidaceae Stool Human [1.23]

‐ Bacteroides fragilis Stool Human [1.24]

‐ Bacteroides plebeius Stool Human [1.21]

‐ Bifidobacterium adolescentis Stool Human [1.25]

‐ Bifidobacterium breve Swab throat Human [1.26]

‐ Bifidobacterium dentium Stool Human [1.21]

‐ Bifidobacterium longum Stool Human [1.21]

‐ Bifidobacterium pseudocatenulatum Swab throat Human [1.26]

‐ Bilophila Stool Human [1.20]

‐ Blautia Stool Human [1.20]

‐ Burkholderiaceae Stool Human [1.20]

‐ Catenibacterium mitsuokai Swab throat Human [1.26]

‐ Chaetomium Stool Human [1.20]

‐ Christensenella Stool Human [1.20]

‐ Clostridioides difficile Gut Lumen Human [1.2]

‐ Clostridium innocuum Stool Human [1.20]

‐ Clostridium perfringens Stool Human [1.25]

‐ Clostridium symbiosum Stool Human [1.21]

‐ Clostridium Stool Human [1.24]

‐ Collinsella aerofaciens Stool Human [1.24]

‐ Coriobacteriaceae Stool Human [1.23]

‐ Cronobacter sakazaki Stool Human [1.21]

‐ Deferribacter Stool Human [1.27]

‐ Dialister invisus Stool Human [1.21]

‐ Dorea Stool Human [1.20]

‐ Eggerthella Stool Human [1.20]

‐ Eisenbergiella Stool Human [1.20]

‐ Enterobacteriaceae Deteriorative Gut Lumen Human

‐ Enterobacteriales Deteriorative Gut Lumen Human

‐ Enterococcus faecium Stool Human [1.21]

‐ Escherichia Stool Human [1.28]

‐ Eubacterium hallii Stool Human [1.20]

‐ Eubacterium hallii Swab throat Human [1.26]

‐ Eubacterium siraeum Stool Human [1.21]

‐ Flavonifractor Stool Human [1.20]

‐ Gammaproteobacteria Preventive Gut Lumen Human

‐ Haematonectria Stool Human [1.20]

‐ Halorubrum Stool Human [1.27]

‐ Halothiobacillus Stool Human [1.27]

‐ Holdemania Stool Human [1.20]

‐ Hungatella Stool Human [1.20]

‐ Klebsiella Stool Human [1.24]

‐ Lactobacillus fermentum Stool Human [1.21]

‐ Lactobacillus gasseri Stool Human [1.25]

‐ Lactobacillus gasseri Swab throat Human [1.26]

‐ Lactobacillus oris Stool Human [1.21]

‐ Lactobacillus salivarius Swab throat Human [1.26]

‐ Lactobacillus Stool Human [1.27]

‐ Megasphaera elsdenii Stool Human [1.25]

‐ Megasphaera Stool Human [1.24]

‐ Methanobrevibacter Stool Human [1.24]

‐ Mortierella Stool Human [1.20]

‐ Ochrobactrum Stool Human [1.27]

‐ Oscillibacter Stool Human [1.20]

‐ Parasutterella Stool Human [1.20]

‐ Patescibacteria Stool Human [1.20]

‐ Porphyromonadaceae Deteriorative Gut Lumen Human

‐ Prevotellaceae Stool Human [1.23]

‐ Ruminococcus gnavus Stool Human [1.20]

‐ Saccharophagus Stool Human [1.27]

‐ Shigella Stool Human [1.28]

‐ Sphingomonadaceae Stool Human [1.25]

‐ Streptococcus gordonii Swab throat Human [1.26]

‐ Streptococcus salivarius Stool Human [1.21]

‐ Streptococcus thermophiles Swab throat Human [1.26]

‐ Streptococcus vestibularis Stool Human [1.21]

‐ Succinivibrio Stool Human [1.24]

‐ Synergistetes Stool Human [1.20]

‐ Tropheryma Stool Human [1.27]

‐ Veillonella atypica Stool Human [1.21]

‐ Veillonella dispar Stool Human [1.21]

‐ Veillonella parvula Stool Human [1.21]

‐ Veillonellaceae Stool Human [1.23]

‐ Veillonella Stool Human [1.28]

↧ Microbiota

‐ Actinobacillus Stool Human [1.28]

‐ Agathobacter Stool Human [1.20]

‐ Alcaligenaceae Stool Human [1.25]

‐ Anabaena Stool Human [1.27]

‐ Aspergillaceae Stool Human [1.20]

‐ Bionectriaceae Stool Human [1.20]

‐ Blautia producta Stool Human [1.24]

‐ Butyricicoccus Stool Human [1.20]

‐ Cephalotrichum Stool Human [1.20]

‐ Clostridium Stool Human [1.22]

‐ Coprococcus Stool Human [1.24]

‐ Enterobacteriaceae Stool Human [1.23]

‐ Enterococcus Stool Human [1.25]

‐ Erysipelotrichaceae Gut Lumen Human

‐ Eubacterium ventriosum Stool Human [1.20]

‐ Faecalibacterium Stool Human [1.20]

‐ Fusicatenibacter Stool Human [1.20]

‐ Fusobacterium Stool Human [1.28]

‐ Gallionella Stool Human [1.27]

‐ Glomerellales Stool Human [1.20]

‐ Haemophilus Stool Human [1.22]

‐ Hypocreaceae Stool Human [1.20]

‐ Lachnoclostridium Stool Human [1.6]

‐ Lachnospiraceae Stool Human [1.23]

‐ Leuconostocaceae Stool Human [1.25]

‐ Megasphaera Stool Human [1.28]

‐ Microascaceae Stool Human [1.20]

‐ Nitrosospira Stool Human [1.27]

‐ Ophiostomataceae Stool Human [1.20]

‐ Purpureocillium Stool Human [1.20]

‐ Rhodocyclaceae Stool Human [1.25]

‐ Rikenellaceae Stool Human [1.25]

‐ Roseburia faecis Stool Human [1.24]

‐ Ruminococcaceae Stool Human [1.23]

‐ Ruminococcus gauvreauii Stool Human [1.20]

‐ Scedosporium Stool Human [1.20]

‐ Sutterella Stool Human [1.22]

‐ Trichoderma Stool Human [1.20]

Disease ⇒ Severe Mental Disorders ⇒ Schizophrenia {40000115}

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Notes:

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References Notes

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