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path(MESH:Schizophrenia)

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Name
Schizophrenia
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Appears in Networks 8

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer's disease and schizophrenia. v1.0.0

This file encodes the article Activation of M1 and M4 muscarinic receptors as potential treatments for Alzheimer’s disease and schizophrenia by Choi et al, 2014

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System v1.0.0

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses v1.0.0

Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0

Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system v1.0.0

This document contains the curation of the review article Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system by Taly et al. 2009

Chaperoning α7 neuronal nicotinic acetylcholine receptors v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 80

act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Reduced nAChR function/expression in the brain has been associated with the pathophysiology of catastrophic disorders, including AD and schizophrenia (discussed in later sections, and see Refs. 277, 432). PubMed:19126755

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path(MESH:"Sensory Gating") association path(MESH:Schizophrenia) View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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path(MESH:"Sensory Gating") association path(MESH:Schizophrenia) View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

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MeSH
Hippocampus
Text Location
Review

a(CHEBI:xanomeline) decreases path(MESH:Schizophrenia) View Subject | View Object

This study reported that xanomeline treatment produced robust improvements in both the positive and the negative symptoms of patients with SZ PubMed:24511233

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bp(GO:"gamma-aminobutyric acid signaling pathway") association path(MESH:Schizophrenia) View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

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bp(GO:"synaptic transmission, cholinergic") association path(MESH:Schizophrenia) View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

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bp(GO:"synaptic transmission, glutamatergic") association path(MESH:Schizophrenia) View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

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bp(GO:behavior) association path(MESH:Schizophrenia) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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bp(GO:cognition) association path(MESH:Schizophrenia) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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path(MESH:"Cognitive Dysfunction") association path(MESH:Schizophrenia) View Subject | View Object

Schizophrenia (SZ) and Alzheimer’s disease (AD) are two devastating disorders of the central nervous system (CNS) that present clinically with cognitive impairments and psychotic symptoms PubMed:24511233

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MeSH
Central Nervous System

path(MESH:"Executive Function") association path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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path(MESH:"Memory, Short-Term") association path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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path(MESH:"Psychotic Disorders") association path(MESH:Schizophrenia) View Subject | View Object

Schizophrenia (SZ) and Alzheimer’s disease (AD) are two devastating disorders of the central nervous system (CNS) that present clinically with cognitive impairments and psychotic symptoms PubMed:24511233

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MeSH
Central Nervous System

path(MESH:"Social Isolation") biomarkerFor path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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path(MESH:Anhedonia) biomarkerFor path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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path(MESH:Attention) association path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

Appears in Networks:

path(MESH:Delusions) association path(MESH:Schizophrenia) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

Appears in Networks:

path(MESH:Delusions) biomarkerFor path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

Appears in Networks:

path(MESH:Hallucinations) association path(MESH:Schizophrenia) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

Appears in Networks:

path(MESH:Hallucinations) biomarkerFor path(MESH:Schizophrenia) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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p(FPLX:CHRN) association path(MESH:Schizophrenia) View Subject | View Object

Decline, disruption, or alterations of nicotinic cholinergic mechanisms have been implicated in various dysfunctions, such as schizophrenia, epilepsy, autism, Alzheimer’s disease (AD), and addiction (17–23). PubMed:17009926

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p(FPLX:CHRN) association path(MESH:Schizophrenia) View Subject | View Object

Genetic evidence has linked nicotinic receptors to epilepsy and schizophrenia, and studies with mutant mice have implicated nAChRs in pain mechanisms, anxiety, and depression. PubMed:17009926

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a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") association path(MESH:Schizophrenia) View Subject | View Object

Yet some of the other genes identified, such as NRG1, are involved in the assembly of alpha7 nAChRs, further supporting a potential link between alpha7 nAChRs and schizophrenia (Mathew et al., 2007) PubMed:21482353

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MeSH
Schizophrenia

bp(GO:"GABAergic neuron differentiation") association path(MESH:Schizophrenia) View Subject | View Object

Nicotinic receptor control over GABAergic neuronal development and mature activity may represent a point of convergence for diseases such as schizophrenia (see next section), some amblyopias (Bavelier et al., 2010), and some epilepsies (Klaassen et al., 2006), which distort the excitatory-inhibitory balance in general and implicate GABAergic signaling defects in particular PubMed:21482353

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act(p(FPLX:CHRN)) association path(MESH:Schizophrenia) View Subject | View Object

Recent studies provide evidence both that nicotinic signaling partially underlies these schizophrenia-related inhibitory defects and that nicotinic drugs have possible therapeutic roles PubMed:21482353

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g(HGNC:CHRFAM7A, var("?")) association path(MESH:Schizophrenia) View Subject | View Object

Polymorphisms in the alpha7 5' promoter and in a nearby partial duplication of the gene, FAM7A, are associated with both schizophrenia and the defect in inhibition (Leonard et al., 2002) PubMed:21482353

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MeSH
Schizophrenia

p(HGNC:CHRNA7, var("?")) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Mutations in nicotinic receptor subunits are linked to human disease, alpha4 and beta2 in some epilepsies, alpha7 in schizophrenia, and alpha5 in nicotine addiction; and each mutation ultimately manifests itself as an imbalance in the properties of neuronal circuits PubMed:21482353

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p(HGNC:PEMT, var("?")) association path(MESH:Schizophrenia) View Subject | View Object

Variants in the gene for phosphatidylethanolamine methyl transferase, which synthesizes phosphatidylcholine and thus provides a source of choline, are also associated with choline deficiency and with schizophrenia PubMed:21482353

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path(MESH:"Tobacco Use Disorder") positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Third, persons with schizophrenia have the greatest rate and intensity of cigarette smoking of any identifiable subgroup in the population PubMed:21482353

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MeSH
Schizophrenia

a(HBP:"alpha-7-containing nAChR") negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Interestingly, a reduction in the protein level of alpha7 has also been measured in the frontal cortex of patients with schizophrenia (Guan et al 1999), whereas no decrease was measured in the alpha4 nAChR protein level (Guan et al 1999) PubMed:11230871

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MeSH
Frontal Lobe

p(FPLX:CHRN) association path(MESH:Schizophrenia) View Subject | View Object

The nAChRs are found to be involved in a complex range of central nervous system disorders including Alzheimer’s disease (AD), Parkinson’s disease, schizophrenia, Tourette’s syndrome, anxiety, depression, and epilepsy (Newhouse and Kelton 2000; Newhouse et al 1997; Paterson and Nordberg 2000) PubMed:11230871

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a(CHEBI:galanthamine) decreases path(MESH:Schizophrenia) View Subject | View Object

Two compounds that are currently in clinical use might have direct effects on the alpha7 nAChR. The anticholinesterase inhibitor galantamine has modulatory effects on alpha7 nAChR and was reportedly beneficial for patients with schizophrenia in a case study184 PubMed:19721446

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bp(GO:cognition) association path(MESH:Schizophrenia) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

bp(MESH:"Sensory Gating") association path(MESH:Schizophrenia) View Subject | View Object

nAChRs are known to control sensory gating, and studies investigating the role of nAChRs in schizophrenia have focused primarily on alpha7 nAChRs. Sensory-gating deficits in patients with schizophrenia174 have been linked to chromosome 15q14, proximal to the alpha7 locus175,176. PubMed:19721446

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Review

path(MESH:Delusions) association path(MESH:Schizophrenia) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

path(MESH:Hallucinations) association path(MESH:Schizophrenia) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

p(HGNC:CHRNA7) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Decreased expression of α7 AChR has also been associated with schizophrenia [51,195–197]. PubMed:22040696

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MeSH
Hippocampus

r(HGNC:RIC3) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Interestingly, levels of RIC-3 mRNA are elevat- ed in postmortem brains of individuals with bipolar disorder and schizophrenia [181], and a link has been suggested between defi- cient RIC-3 mediated chaperoning of an AChR subunit and individ- uals with bipolar disorder and psychotic symptoms [181]. PubMed:22040696

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MeSH
Brain

a(CHEBI:"lithium(1+)") decreases path(MESH:Schizophrenia) View Subject | View Object

In fact, lithium is able to delay METH-induced sensitization, while being a powerful treatment in schizophrenia PubMed:30061532

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a(CHEBI:"lithium(1+)") decreases path(MESH:Schizophrenia) View Subject | View Object

These pieces of evidence corroborate findings showing that several autophagy inducers, such as lithium, rapamycin, and Food and Drug Administration (FDA) approved antipsychotic drugs are effective to treat psychosis including schizophrenia PubMed:30061532

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a(CHEBI:"reactive oxygen species") association path(MESH:Schizophrenia) View Subject | View Object

Beyond METH, redox-related changes that result from an imbalance between reactive oxygen species (ROS) production and ROS clearance are implicated in schizophrenia PubMed:30061532

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a(CHEBI:dopamine) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Accordingly, clinical evidence points towards an elevation of pre-synaptic DA synthesis and release as a key event for schizophrenia PubMed:30061532

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sec(a(CHEBI:dopamine)) association path(MESH:Schizophrenia) View Subject | View Object

Accordingly, clinical evidence points towards an elevation of pre-synaptic DA synthesis and release as a key event for schizophrenia PubMed:30061532

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a(CHEBI:sirolimus) decreases path(MESH:Schizophrenia) View Subject | View Object

These pieces of evidence corroborate findings showing that several autophagy inducers, such as lithium, rapamycin, and Food and Drug Administration (FDA) approved antipsychotic drugs are effective to treat psychosis including schizophrenia PubMed:30061532

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act(a(GO:microtubule)) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

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MeSH
Brain
MeSH
Schizophrenia

a(MESH:"Antipsychotic Agents") decreases path(MESH:Schizophrenia) View Subject | View Object

These pieces of evidence corroborate findings showing that several autophagy inducers, such as lithium, rapamycin, and Food and Drug Administration (FDA) approved antipsychotic drugs are effective to treat psychosis including schizophrenia PubMed:30061532

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bp(GO:"cytoskeleton organization") negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

In addition, cytoskeletal derangement appears as a prominent feature of the ultrastructural pathology of schizophrenia PubMed:30061532

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bp(GO:"neuron-neuron synaptic transmission") negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Alterations in MAP2 immunoreactivity within the subiculum, entorhinal cortex, hippocampus, and prefrontal cortex have been suggested as the primary array of cytoskeletal abnormalities, which in turn result in impaired neurotransmission observed in schizophrenia PubMed:30061532

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Entorhinal Cortex
MeSH
Hippocampus
MeSH
Prefrontal Cortex

bp(GO:"protein kinase B signaling") association path(MESH:Schizophrenia) View Subject | View Object

Again, an impaired Akt signaling, achieved by neuronal deletion of rictor, a key regulatory subunit of mTORC2, contributes to schizophrenia-like phenotypes in rictor-null (KO) mice PubMed:30061532

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bp(GO:"protein kinase B signaling") association path(MESH:Schizophrenia) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

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bp(GO:autophagy) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

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bp(GO:autophagy) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

A few months later, another transcriptomic study reported a BA 22-specific down-regulation in several autophagy-related genes, thus strengthening the link between impaired autophagy and schizophrenia positive symptoms PubMed:30061532

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bp(GO:autophagy) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Later on, further analysis reported a disruption of the autophagy pathway also in the hippocampus of post-mortem schizophrenic patients PubMed:30061532

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MeSH
Hippocampus

p(HGNC:DISC1) association path(MESH:Schizophrenia) View Subject | View Object

Preliminary in vitro studies demonstrated that two proteins, namely DISC1 and dysbindin-1, which are encoded by two susceptibility genes for schizophrenia, can form insoluble protein aggregates that are reminiscent of those occurring in neurodegenerative disorders PubMed:30061532

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p(HGNC:DISC1) association path(MESH:Schizophrenia) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

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p(HGNC:DPYSL2) association path(MESH:Schizophrenia) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

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p(HGNC:DTNBP1) association path(MESH:Schizophrenia) View Subject | View Object

Preliminary in vitro studies demonstrated that two proteins, namely DISC1 and dysbindin-1, which are encoded by two susceptibility genes for schizophrenia, can form insoluble protein aggregates that are reminiscent of those occurring in neurodegenerative disorders PubMed:30061532

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p(HGNC:DTNBP1) association path(MESH:Schizophrenia) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

Appears in Networks:

p(HGNC:ERBB4) association path(MESH:Schizophrenia) View Subject | View Object

Furthermore, genetic linkage and association studies led to the identification of two additional susceptibility factors related to schizophrenia, such as neuregulin-1 (NRG1) and its receptor ErbB4 PubMed:30061532

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act(p(HGNC:CDK5)) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

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MeSH
Brain

p(HGNC:CDK5R1) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

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MeSH
Brain

g(HGNC:DISC1) association path(MESH:Schizophrenia) View Subject | View Object

This is the case of the disrupted in schizophrenia 1 (DISC1) gene, a schizophrenia-related gene, originally discovered in a large Scottish family with a high incidence of psychiatric symptoms PubMed:30061532

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p(HGNC:NRG1) association path(MESH:Schizophrenia) View Subject | View Object

Furthermore, genetic linkage and association studies led to the identification of two additional susceptibility factors related to schizophrenia, such as neuregulin-1 (NRG1) and its receptor ErbB4 PubMed:30061532

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p(HGNC:NRG1) association path(MESH:Schizophrenia) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

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g(HGNC:DISC1) association path(MESH:Schizophrenia) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

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g(HGNC:DPYSL2) association path(MESH:Schizophrenia) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

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g(HGNC:DPYSL2) association path(MESH:Schizophrenia) View Subject | View Object

Another identified susceptibility gene for schizophrenia is the dihydropyrimidinase-like 2 (DPYSL2) gene PubMed:30061532

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g(HGNC:NRG1) association path(MESH:Schizophrenia) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

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p(HGNC:DISC1, var("?")) increases path(MESH:Schizophrenia) View Subject | View Object

In addition, these findings strongly suggest that DISC1 alterations may increase the risk of schizophrenia by dysregulating DA release PubMed:30061532

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p(HGNC:DISC1, var("?")) increases path(MESH:Schizophrenia) View Subject | View Object

Therefore, disruption of DISC1 activity, due to genetic rearrangements (i.e., balanced (1;11) (q42;q14) chromosomal translocation) or missense mutations, produces schizophrenic-like behavior, which is bound to enhanced Akt activity, over-activation of mTOR signaling, and depressed autophagy PubMed:30061532

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act(p(HGNC:DRD1)) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Increased activity of D1R is considered as a major determinant of neuropsychiatric alterations occurring in both METH models/abusers and in schizophrenia PubMed:30061532

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p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation path(MESH:Schizophrenia) View Subject | View Object

Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532

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act(p(HGNC:MTOR)) association path(MESH:Schizophrenia) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

act(p(HGNC:MTOR)) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

p(HGNC:SLC18A2) negativeCorrelation path(MESH:Schizophrenia) View Subject | View Object

A reduction in VMAT-2 gene expression and protein levels in DA neurons occurs in both METH models and schizophrenic patients, marking quite impressively the overlap between these disorders PubMed:30061532

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Cell Ontology (CL)
dopaminergic neuron

p(HGNC:ULK1, var("?")) association path(MESH:Schizophrenia) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

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path(MESH:"Psychotic Disorders") association path(MESH:Schizophrenia) View Subject | View Object

In humans, the sensitizing effects of prolonged chronic METH intake are considered a major determinant to the occurrence and relapse of psychoses, which mirror those occurring in schizophrenic patients PubMed:30061532

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path(MESH:Catatonia) association path(MESH:Schizophrenia) View Subject | View Object

Remarkably, a very recent neuropathological examination provided evidence for TDP-43-positive cytosolic inclusions and dystrophic neurites in the brain of a patient diagnosed with FTLD presenting brief psychotic episodes and catatonia, which is a syndrome related to schizophrenia PubMed:30061532

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MeSH
Brain

path(MESH:Delusions) association path(MESH:Schizophrenia) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

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path(MESH:Hallucinations) association path(MESH:Schizophrenia) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

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Out-Edges 89

path(MESH:Schizophrenia) negativeCorrelation act(p(HGNCGENEFAMILY:"Cholinergic receptors nicotinic subunits")) View Subject | View Object

Reduced nAChR function/expression in the brain has been associated with the pathophysiology of catastrophic disorders, including AD and schizophrenia (discussed in later sections, and see Refs. 277, 432). PubMed:19126755

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Text Location
Review

path(MESH:Schizophrenia) association path(MESH:"Sensory Gating") View Subject | View Object

In particular, the association of the alpha7 nAChR gene with a sensory gating deficit that is similar to attention deficits in patients with schizophrenia (157), and the degree of alpha4beta2 nAChR loss and altered alpha7 expresson correlate well with the magnitude of progressive cognitive decline in mild-to-moderate AD patients (46). PubMed:19126755

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path(MESH:Schizophrenia) association path(MESH:"Sensory Gating") View Subject | View Object

Chronic alpha7 nAChR inhibition in the hippocampus by elevated levels of KYNA can contribute to auditory gating deficits, which appear to be associated with the development of schizophrenia (156). It is also feasible that KYNAinduced inhibition of alpha7 nAChRs contributes to the cognitive impairment observed in patients with AD and schizophrenia (273). PubMed:19126755

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Hippocampus
Text Location
Review

path(MESH:Schizophrenia) association path(MESH:"Psychotic Disorders") View Subject | View Object

Schizophrenia (SZ) and Alzheimer’s disease (AD) are two devastating disorders of the central nervous system (CNS) that present clinically with cognitive impairments and psychotic symptoms PubMed:24511233

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Central Nervous System

path(MESH:Schizophrenia) association path(MESH:"Cognitive Dysfunction") View Subject | View Object

Schizophrenia (SZ) and Alzheimer’s disease (AD) are two devastating disorders of the central nervous system (CNS) that present clinically with cognitive impairments and psychotic symptoms PubMed:24511233

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Central Nervous System

path(MESH:Schizophrenia) association path(MESH:Hallucinations) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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path(MESH:Schizophrenia) association path(MESH:Delusions) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association bp(GO:cognition) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association bp(GO:behavior) View Subject | View Object

Psychosis is the hallmark symptom of SZ and manifests as hallucinations, disordered thought/speech, and delusions. While these psychotic symptoms are commonly associated with SZ, it has become well documented that these patients also experience cognitive and behavioral disturbances that are not adequately addressed by currently prescribed typical and atypical psychotics. PubMed:24511233

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path(MESH:Schizophrenia) decreases bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Another commonality between AD and SZ is the apparent involvement of dysregulated cholinergic signaling in the brain. PubMed:24511233

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path(MESH:Schizophrenia) association bp(GO:"synaptic transmission, cholinergic") View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

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path(MESH:Schizophrenia) association path(MESH:"Memory, Short-Term") View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

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path(MESH:Schizophrenia) association path(MESH:Attention) View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association path(MESH:"Executive Function") View Subject | View Object

The hallmark psychotic symptoms of SZ are the positive cluster and include auditory hallucinations, delusional beliefs, and disorganized thoughts and speech. SZ patients also exhibit negative symptoms, including anhedonia, dysfunctional social interactions, and poverty of thoughts and speech, as well as cognitive disturbances affecting several behavioral domains, including working memory, attention, and executive function PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association bp(GO:"synaptic transmission, glutamatergic") View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association bp(GO:"gamma-aminobutyric acid signaling pathway") View Subject | View Object

Accumulating evidence suggests that the three clusters of SZ symptoms cannot be ascribed solely to alterations in monoaminergic signaling as dysregulation of glutamatergic, gamma-aminobutyric acid (GABA)-ergic, and cholinergic systems have also been reported PubMed:24511233

Appears in Networks:

path(MESH:Schizophrenia) association p(FPLX:CHRN) View Subject | View Object

Decline, disruption, or alterations of nicotinic cholinergic mechanisms have been implicated in various dysfunctions, such as schizophrenia, epilepsy, autism, Alzheimer’s disease (AD), and addiction (17–23). PubMed:17009926

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path(MESH:Schizophrenia) association p(FPLX:CHRN) View Subject | View Object

Genetic evidence has linked nicotinic receptors to epilepsy and schizophrenia, and studies with mutant mice have implicated nAChRs in pain mechanisms, anxiety, and depression. PubMed:17009926

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path(MESH:Schizophrenia) association act(p(FPLX:CHRN)) View Subject | View Object

Recent studies provide evidence both that nicotinic signaling partially underlies these schizophrenia-related inhibitory defects and that nicotinic drugs have possible therapeutic roles PubMed:21482353

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path(MESH:Schizophrenia) positiveCorrelation p(HGNC:CHRNA7, var("?")) View Subject | View Object

Mutations in nicotinic receptor subunits are linked to human disease, alpha4 and beta2 in some epilepsies, alpha7 in schizophrenia, and alpha5 in nicotine addiction; and each mutation ultimately manifests itself as an imbalance in the properties of neuronal circuits PubMed:21482353

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path(MESH:Schizophrenia) association bp(GO:"GABAergic neuron differentiation") View Subject | View Object

Nicotinic receptor control over GABAergic neuronal development and mature activity may represent a point of convergence for diseases such as schizophrenia (see next section), some amblyopias (Bavelier et al., 2010), and some epilepsies (Klaassen et al., 2006), which distort the excitatory-inhibitory balance in general and implicate GABAergic signaling defects in particular PubMed:21482353

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path(MESH:Schizophrenia) increases act(a(MESH:Hippocampus)) View Subject | View Object

In many persons with schizophrenia, cerebral evoked potential recording shows diminished inhibition of the response to repeated stimuli (Adler et al., 1982) (Figure 2A), and animal models of this phenomenon point to a defect in hippocampal inhibition PubMed:21482353

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path(MESH:Schizophrenia) association g(HGNC:CHRFAM7A, var("?")) View Subject | View Object

Polymorphisms in the alpha7 5' promoter and in a nearby partial duplication of the gene, FAM7A, are associated with both schizophrenia and the defect in inhibition (Leonard et al., 2002) PubMed:21482353

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Schizophrenia

path(MESH:Schizophrenia) association a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") View Subject | View Object

Yet some of the other genes identified, such as NRG1, are involved in the assembly of alpha7 nAChRs, further supporting a potential link between alpha7 nAChRs and schizophrenia (Mathew et al., 2007) PubMed:21482353

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Schizophrenia

path(MESH:Schizophrenia) positiveCorrelation path(MESH:"Tobacco Use Disorder") View Subject | View Object

Third, persons with schizophrenia have the greatest rate and intensity of cigarette smoking of any identifiable subgroup in the population PubMed:21482353

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Schizophrenia

path(MESH:Schizophrenia) association p(HGNC:PEMT, var("?")) View Subject | View Object

Variants in the gene for phosphatidylethanolamine methyl transferase, which synthesizes phosphatidylcholine and thus provides a source of choline, are also associated with choline deficiency and with schizophrenia PubMed:21482353

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path(MESH:Schizophrenia) association p(FPLX:CHRN) View Subject | View Object

The nAChRs are found to be involved in a complex range of central nervous system disorders including Alzheimer’s disease (AD), Parkinson’s disease, schizophrenia, Tourette’s syndrome, anxiety, depression, and epilepsy (Newhouse and Kelton 2000; Newhouse et al 1997; Paterson and Nordberg 2000) PubMed:11230871

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path(MESH:Schizophrenia) negativeCorrelation a(HBP:"alpha-7-containing nAChR") View Subject | View Object

Interestingly, a reduction in the protein level of alpha7 has also been measured in the frontal cortex of patients with schizophrenia (Guan et al 1999), whereas no decrease was measured in the alpha4 nAChR protein level (Guan et al 1999) PubMed:11230871

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Frontal Lobe

path(MESH:Schizophrenia) causesNoChange a(HBP:"alpha-4-containing nAChR") View Subject | View Object

Interestingly, a reduction in the protein level of alpha7 has also been measured in the frontal cortex of patients with schizophrenia (Guan et al 1999), whereas no decrease was measured in the alpha4 nAChR protein level (Guan et al 1999) PubMed:11230871

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Frontal Lobe

path(MESH:Schizophrenia) association bp(GO:cognition) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

path(MESH:Schizophrenia) association path(MESH:Hallucinations) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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path(MESH:Schizophrenia) association path(MESH:Delusions) View Subject | View Object

in addition to the obvious symptoms of hallucinations and delusions, patients with schizophrenia frequently suffer from cognitive symptoms, such as the inability to focus attention173. PubMed:19721446

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Review

path(MESH:Schizophrenia) association bp(MESH:"Sensory Gating") View Subject | View Object

nAChRs are known to control sensory gating, and studies investigating the role of nAChRs in schizophrenia have focused primarily on alpha7 nAChRs. Sensory-gating deficits in patients with schizophrenia174 have been linked to chromosome 15q14, proximal to the alpha7 locus175,176. PubMed:19721446

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Review

path(MESH:Schizophrenia) decreases p(HGNC:CHRNA7) View Subject | View Object

in addition, a decrease in alpha7 nAChR density in the hippocampus of patients with schizophrenia has been reported177. Similarly, a low density of alpha7 nAChRs in inbred strains of mice is associated with poor gating178. Recently, the expression of a novel variant of alpha7 nAChR, CHRNA7-2 (cholinergic receptor, nicotinic, alpha7, variant 2), was found to be reduced below control levels in the prefrontal cortex of patients with schizophrenia179. PubMed:19721446

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Hippocampus
Text Location
Review

path(MESH:Schizophrenia) negativeCorrelation p(HGNC:CHRNA7) View Subject | View Object

Decreased expression of α7 AChR has also been associated with schizophrenia [51,195–197]. PubMed:22040696

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Hippocampus

path(MESH:Schizophrenia) positiveCorrelation r(HGNC:RIC3) View Subject | View Object

Interestingly, levels of RIC-3 mRNA are elevat- ed in postmortem brains of individuals with bipolar disorder and schizophrenia [181], and a link has been suggested between defi- cient RIC-3 mediated chaperoning of an AChR subunit and individ- uals with bipolar disorder and psychotic symptoms [181]. PubMed:22040696

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Brain

path(MESH:Schizophrenia) association path(MESH:Hallucinations) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

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path(MESH:Schizophrenia) association path(MESH:Delusions) View Subject | View Object

As detailed in the following paragraph, METH exerts disruptive effects on DA neurotransmission, which translate into abnormal stimulation of post-synaptic DA receptors, mainly D1-type DA receptors (D1R), thus leading to non-canonical signaling cascades sustaining behavioral alterations that overlap with schizophrenia-like symptoms (i.e., visual and auditory hallucinations and delusions) PubMed:30061532

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path(MESH:Schizophrenia) positiveCorrelation act(p(HGNC:DRD1)) View Subject | View Object

Increased activity of D1R is considered as a major determinant of neuropsychiatric alterations occurring in both METH models/abusers and in schizophrenia PubMed:30061532

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path(MESH:Schizophrenia) association g(HGNC:DISC1) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

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path(MESH:Schizophrenia) association g(HGNC:DISC1) View Subject | View Object

This is the case of the disrupted in schizophrenia 1 (DISC1) gene, a schizophrenia-related gene, originally discovered in a large Scottish family with a high incidence of psychiatric symptoms PubMed:30061532

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path(MESH:Schizophrenia) association g(HGNC:NRG1) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association g(HGNC:DPYSL2) View Subject | View Object

In addition, several susceptibility genes for schizophrenia (e.g., DISC1, NRG1/ErbB4, and CRMP2), which are involved in either pre-synaptic DA release or post-synaptic D1R-related cascades, are similarly dysregulated by METH. Interestingly, they all converge on mTOR signaling (see Section 6, Table 1). PubMed:30061532

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path(MESH:Schizophrenia) association g(HGNC:DPYSL2) View Subject | View Object

Another identified susceptibility gene for schizophrenia is the dihydropyrimidinase-like 2 (DPYSL2) gene PubMed:30061532

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path(MESH:Schizophrenia) association path(MESH:"Psychotic Disorders") View Subject | View Object

In humans, the sensitizing effects of prolonged chronic METH intake are considered a major determinant to the occurrence and relapse of psychoses, which mirror those occurring in schizophrenic patients PubMed:30061532

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path(MESH:Schizophrenia) increases path(MESH:"Psychotic Disorders") View Subject | View Object

In addition, the occurrence of alpha synuclein gene (SNCA) polymorphisms is associated with human METH psychosis [166]. PubMed:30061532

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path(MESH:Schizophrenia) positiveCorrelation a(CHEBI:dopamine) View Subject | View Object

Accordingly, clinical evidence points towards an elevation of pre-synaptic DA synthesis and release as a key event for schizophrenia PubMed:30061532

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path(MESH:Schizophrenia) association sec(a(CHEBI:dopamine)) View Subject | View Object

Accordingly, clinical evidence points towards an elevation of pre-synaptic DA synthesis and release as a key event for schizophrenia PubMed:30061532

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path(MESH:Schizophrenia) increases a(CHEBI:dopamine) View Subject | View Object

Likewise, the psychostimulant effects experienced by METH-addicted patients rely on increased DA synthesis and massive DA release from nerve terminals within limbic areas as occurring in the schizophrenic brain PubMed:30061532

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Brain

path(MESH:Schizophrenia) increases tloc(a(CHEBI:dopamine), fromLoc(MESH:"Nerve Endings"), toLoc(MESH:"Limbic System")) View Subject | View Object

Likewise, the psychostimulant effects experienced by METH-addicted patients rely on increased DA synthesis and massive DA release from nerve terminals within limbic areas as occurring in the schizophrenic brain PubMed:30061532

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Brain

path(MESH:Schizophrenia) decreases p(HGNC:SLC6A3) View Subject | View Object

In line with this, recent studies suggest that DAT expression is significantly reduced in the midbrain of postmortem schizophrenic samples [150], which is reminiscent of the METH-addicted brain [151,152]. PubMed:30061532

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Mesencephalon

path(MESH:Schizophrenia) negativeCorrelation p(HGNC:SLC18A2) View Subject | View Object

A reduction in VMAT-2 gene expression and protein levels in DA neurons occurs in both METH models and schizophrenic patients, marking quite impressively the overlap between these disorders PubMed:30061532

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Cell Ontology (CL)
dopaminergic neuron

path(MESH:Schizophrenia) association a(CHEBI:"reactive oxygen species") View Subject | View Object

Beyond METH, redox-related changes that result from an imbalance between reactive oxygen species (ROS) production and ROS clearance are implicated in schizophrenia PubMed:30061532

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path(MESH:Schizophrenia) negativeCorrelation bp(GO:"cytoskeleton organization") View Subject | View Object

In addition, cytoskeletal derangement appears as a prominent feature of the ultrastructural pathology of schizophrenia PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation bp(GO:"neuron-neuron synaptic transmission") View Subject | View Object

Alterations in MAP2 immunoreactivity within the subiculum, entorhinal cortex, hippocampus, and prefrontal cortex have been suggested as the primary array of cytoskeletal abnormalities, which in turn result in impaired neurotransmission observed in schizophrenia PubMed:30061532

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Entorhinal Cortex
MeSH
Hippocampus
MeSH
Prefrontal Cortex

path(MESH:Schizophrenia) decreases p(HGNC:MAP2) View Subject | View Object

Notably, a marked reduction in MAP2 immunoreactivity, along with a decrease in dendritic arbor, is reported in the primary auditory cortex (BA41) of schizophrenic subjects compared with healthy controls PubMed:30061532

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MeSH
Auditory Cortex

path(MESH:Schizophrenia) decreases a(GO:dendrite) View Subject | View Object

Notably, a marked reduction in MAP2 immunoreactivity, along with a decrease in dendritic arbor, is reported in the primary auditory cortex (BA41) of schizophrenic subjects compared with healthy controls PubMed:30061532

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Auditory Cortex

path(MESH:Schizophrenia) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

Moreover, pathological deposition of hyperphosphorylated MAP-tau (MAPT), which is the hallmark of several neurodegenerative disorders such as AD and frontotemporal dementia (FTD), has been described in elderly subjects with schizophrenia PubMed:30061532

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path(MESH:Schizophrenia) increases p(HGNC:MAPT, loc(MESH:Neurons)) View Subject | View Object

Momeni and colleagues (2010) recently reported two relatives with an early age at onset (27 and 29 years) of schizophrenic symptoms showing a marked neuronal tau deposition, as confirmed at pathological examination PubMed:30061532

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path(MESH:Schizophrenia) decreases bp(GO:"oligodendrocyte development") View Subject | View Object

Notably, post-mortem analysis performed in the prefrontal cortex of schizophrenic patients revealed oligodendrocyte ultrastructural abnormalities PubMed:30061532

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MeSH
Prefrontal Cortex

path(MESH:Schizophrenia) association path(MESH:Catatonia) View Subject | View Object

Remarkably, a very recent neuropathological examination provided evidence for TDP-43-positive cytosolic inclusions and dystrophic neurites in the brain of a patient diagnosed with FTLD presenting brief psychotic episodes and catatonia, which is a syndrome related to schizophrenia PubMed:30061532

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Brain

path(MESH:Schizophrenia) association p(HGNC:DISC1) View Subject | View Object

Preliminary in vitro studies demonstrated that two proteins, namely DISC1 and dysbindin-1, which are encoded by two susceptibility genes for schizophrenia, can form insoluble protein aggregates that are reminiscent of those occurring in neurodegenerative disorders PubMed:30061532

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path(MESH:Schizophrenia) association p(HGNC:DISC1) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association p(HGNC:DTNBP1) View Subject | View Object

Preliminary in vitro studies demonstrated that two proteins, namely DISC1 and dysbindin-1, which are encoded by two susceptibility genes for schizophrenia, can form insoluble protein aggregates that are reminiscent of those occurring in neurodegenerative disorders PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association p(HGNC:DTNBP1) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association p(HGNC:DPYSL2) View Subject | View Object

Intriguingly, the interactome analysis of both DISC1, dysbindin-1, and CRMP2, which is another susceptibility gene for schizophrenia, revealed common protein interactions with microtubules, actin cytoskeleton, and proteins involved in intracellular transport PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation act(a(GO:microtubule)) View Subject | View Object

The biological implication behind an impairment of microtubule dynamics is confirmed in post-mortem schizophrenic brain samples, as well as in mouse models of schizophrenia, where mTOR-dependent autophagy dysfunction is accompanied by an altered gene expression and protein levels of the microtubule-associated protein 6 (MAP6) PubMed:30061532

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MeSH
Brain
MeSH
Schizophrenia

path(MESH:Schizophrenia) association bp(GO:"protein kinase B signaling") View Subject | View Object

Again, an impaired Akt signaling, achieved by neuronal deletion of rictor, a key regulatory subunit of mTORC2, contributes to schizophrenia-like phenotypes in rictor-null (KO) mice PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases bp(GO:"protein kinase B signaling") View Subject | View Object

Dysregulation in Akt signaling and altered Akt protein levels were found in the frontal cortex and hippocampus of post-mortem brain samples from individuals affected by schizophrenia PubMed:30061532

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MeSH
Hippocampus
MeSH
Prefrontal Cortex

path(MESH:Schizophrenia) association bp(GO:"protein kinase B signaling") View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(FPLX:AKT) View Subject | View Object

Dysregulation in Akt signaling and altered Akt protein levels were found in the frontal cortex and hippocampus of post-mortem brain samples from individuals affected by schizophrenia PubMed:30061532

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MeSH
Hippocampus
MeSH
Prefrontal Cortex

path(MESH:Schizophrenia) association p(HGNC:NRG1) View Subject | View Object

Furthermore, genetic linkage and association studies led to the identification of two additional susceptibility factors related to schizophrenia, such as neuregulin-1 (NRG1) and its receptor ErbB4 PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association p(HGNC:NRG1) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association p(HGNC:ERBB4) View Subject | View Object

Furthermore, genetic linkage and association studies led to the identification of two additional susceptibility factors related to schizophrenia, such as neuregulin-1 (NRG1) and its receptor ErbB4 PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) association act(p(HGNC:MTOR)) View Subject | View Object

Moreover, it has been demonstrated that NRG1 also regulates DISC1 expression [230], thus further worsening the aberrancy of the Akt–mTOR pathway and the pathogenesis of schizophrenia and related behaviors. PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation act(p(HGNC:MTOR)) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation p(HGNC:CDK5R1) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

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MeSH
Brain

path(MESH:Schizophrenia) positiveCorrelation act(p(HGNC:CDK5)) View Subject | View Object

Remarkably, the marked reduction of p35 levels in schizophrenic brains, which mirrors enhanced CDK5 activity [247], suggests a role for CDK5-CRMP2-dependent alterations of cytoskeleton architecture and psychiatric behavior PubMed:30061532

Appears in Networks:
Annotations
MeSH
Brain

path(MESH:Schizophrenia) association p(HGNC:ULK1, var("?")) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation bp(GO:autophagy) View Subject | View Object

Remarkably, the identification of rare genetic variants of ULK1 in a cohort of schizophrenic patients by means of exome sequence analysis strengthens the idea of a key role of both disrupted mTOR signaling and autophagy in the pathophysiology and susceptibility to schizophrenia PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation bp(GO:autophagy) View Subject | View Object

A few months later, another transcriptomic study reported a BA 22-specific down-regulation in several autophagy-related genes, thus strengthening the link between impaired autophagy and schizophrenia positive symptoms PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) negativeCorrelation bp(GO:autophagy) View Subject | View Object

Later on, further analysis reported a disruption of the autophagy pathway also in the hippocampus of post-mortem schizophrenic patients PubMed:30061532

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MeSH
Hippocampus

path(MESH:Schizophrenia) decreases p(HGNC:BECN1) View Subject | View Object

In particular, at BA 22, the vast majority of abnormally expressed genes referred to key autophagy genes (i.e., BECN1, ULK2, ATG3), which were significantly down-regulated compared with controls PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(HGNC:BECN1) View Subject | View Object

In detail, the analysis of mRNA expression of a key protein for autophagy initiation, namely beclin1, revealed a significant region-specific reduction in hippocampal samples from 12 schizophrenic patients compared with 12 age-matched healthy controls. PubMed:30061532

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MeSH
Hippocampus

path(MESH:Schizophrenia) decreases p(HGNC:BECN1) View Subject | View Object

Immuno-histochemical analysis showed a three-fold decrease in the number of beclin1-positive cells in Map6+/- mice PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(HGNC:ULK2) View Subject | View Object

In particular, at BA 22, the vast majority of abnormally expressed genes referred to key autophagy genes (i.e., BECN1, ULK2, ATG3), which were significantly down-regulated compared with controls PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(HGNC:ATG3) View Subject | View Object

In particular, at BA 22, the vast majority of abnormally expressed genes referred to key autophagy genes (i.e., BECN1, ULK2, ATG3), which were significantly down-regulated compared with controls PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(HGNC:ADNP) View Subject | View Object

A reduction of ADNP and its homologous protein, ADNP2, is observed in schizophrenic patients [254], and it is recapitulated in Map6-deficient (Map6+/-) mice, another transgenic model of schizophrenia PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(HGNC:ADNP2) View Subject | View Object

A reduction of ADNP and its homologous protein, ADNP2, is observed in schizophrenic patients [254], and it is recapitulated in Map6-deficient (Map6+/-) mice, another transgenic model of schizophrenia PubMed:30061532

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.