- Schizophrenia Identified in 60 Seconds via Visual Fixation Neuroscience News
- Regulation of synaptic connectivity in schizophrenia spectrum by mutual neuron-microglia interaction | Communications Biology Nature.com
- Study identifies DNA Methylation markers linked to schizophrenia risk in newborns The News International
- Researchers identify DNA methylation markers linked to increased risk of schizophrenia in newborns News-Medical.Net
- Identification of DNA Methylation Markers in Newborns for Increased Schizophrenia Risk Neuroscience News
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Tag Archives: schizophrenia
FDA approves Otsuka and Lundbeck’s schizophrenia, bipolar disorder injection – Endpoints News – Endpoints News
- FDA approves Otsuka and Lundbeck’s schizophrenia, bipolar disorder injection – Endpoints News Endpoints News
- FDA signs off on Otsuka and Lundbeck’s longer-acting Abilify FiercePharma
- FDA Approves Aripiprazole as First Once-Every-2-Months Long-Acting Injectable for Schizophrenia, Bipolar I Disorder Pharmacy Times
- NDA Approved for Long-Acting Injectable for Schizophrenia and Bipolar I Psychiatric Times
- FDA Approves Otsuka and Lundbeck’s ABILIFY ASIMTUFII® (aripiprazole), the First Once-Every-Two-Months Long-acting Injectable (LAI) for the Treatment of Schizophrenia or Maintenance Monotherapy Treatment of Bipolar I Disorder in Adults Business Wire
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A Link Between Schizophrenia and Vascular Alterations in the Brain
Summary: A new study uncovers a link between astrocytes derived from patients with schizophrenia and the formation of narrower blood vessels in the brain. Findings suggest the astrocytes from those with schizophrenia promote less vascularization.
Source: FAPESP
A study conducted in Brazil and reported in an article published in Molecular Psychiatry suggests that schizophrenia may be associated with alterations in the vascularization of certain brain regions.
Researchers at the State University of Campinas (UNICAMP), D’Or Research and Education Institute (IDOR) and the Federal University of Rio de Janeiro (UFRJ) found a link between astrocytes (central nervous system cells) from patients with schizophrenia and formation of narrow blood vessels.
Schizophrenia is a severe multifactorial mental health disorder affecting around 1% of the world population. Common symptoms include loss of contact with reality (psychosis), hallucinations (hearing voices, for example), delusions or delirium, disorganized motor behavior, loss of motivation and cognitive impairment.
In the study, the researchers focused on the role of astrocytes in development of the disease. These glial cells are housekeepers of the central nervous system and important to its defense. They are the central elements of the neurovascular units that integrate neural circuitry with local blood flow and provide neurons with metabolic support.
The study points to novel therapeutic targets and advances scientists’ understanding of the molecular mechanisms behind schizophrenia.
“We show that astrocytes may be involved with an alteration in the thickness of blood vessels in the brain, which in turn may be associated with a reduction in the metabolic flux in certain brain regions, a key factor in schizophrenia.
“Our findings highlight the role of astrocytes as a central element in the disease and suggest they could therefore be a target for novel therapies,” Daniel Martins-de-Souza, penultimate author of the article and a professor at UNICAMP’s Institute of Biology, told Agência FAPESP.
The study was supported by FAPESP via a Thematic Project and a postdoctoral scholarship awarded to Juliana Minardi Nascimento, first author of the artilce, alongside Pablo Trindade, a researcher affiliated with UFRJ and IDOR.
Abnormal vascularization
The researchers compared astrocytes derived from schizophrenic patients’ skin cells with others from people without the disease. This part of the study was conducted at the laboratory of Stevens Rehen, a researcher at IDOR and a professor at UFRJ’s Institute of Biology.
To this end, they reprogrammed epithelial cells from patients with schizophrenia and the control group to become induced pluripotent stem cells (iPSCs). They then induced differentiation of the iPSCs into neural stem cells, which can give rise to both neurons and astrocytes.
“Previous research suggested that both molecular and functional abnormalities of astrocytes could be involved in the pathogenesis of schizophrenia. In our study, we proved this involvement using iPSCs. Without this technique, it would be impossible to study astrocytes the way we did,” Martins-de-Souza said.
The researchers conducted two series of tests with astrocytes derived from patients and healthy controls. The first was a proteomic analysis in which all proteins present in each sample were identified in order to detect differences between the two sets of astrocytes. This part was conducted at UNICAMP’s Laboratory of Neuroproteomics.
“In our analysis of the cells’ proteomes, we observed immune alterations associated with astrocytes. In the case of the cells from patients with schizophrenia, we also found differences in the levels of pro-inflammatory cytokines and several other proteins that indicated angiogenic action in brain vascularization,” Nascimento said.
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels. It is a normal part of growth and healing but can play a role in disease.
After the proteomic analysis, the researchers performed functional trials to show that the inflammatory response in the astrocytes from patients with schizophrenia was altered and that the cells secreted substances that affected vascularization. These tests were part of the postdoctoral research of Pablo Trindade.
The model of the vascular system they used is known as the chicken chorioallantoic membrane (CAM) assay. Derived from chickens’ eggs, the CAM has a dense network of blood vessels and is widely used to study angiogenesis.
The assay was conducted by researchers at the University of Chile in Santiago, Chile. “Put simply, we placed conditioned astrocyte media containing all the substances secreted by these cells in the vascular region of fertilized eggs.
As the vascular cells multiplied, it was possible to see how vessel formation proceeded since egg vascularization could be induced or inhibited by the substances secreted,” Trindade said.
In addition to their effects on vascularization, the astrocytes derived from patients with schizophrenia displayed chronic inflammation.
“Astrocytes are known to regulate the immune response in the central nervous system, so it’s possible that they promote more immature or less efficient vascularization. Our patient-derived astrocytes secreted more interleukin-8 (IL-8) than the controls. IL-8 is pro-inflammatory and suspected to be the main agent of the vascular dysfunction associated with schizophrenia,” he said.
According to the authors, the findings reinforce the role of neurodevelopment in schizophrenia and clearly show that astrocytes are important as mediators.
See also
“The symptoms of the disease usually manifest in young adulthood, but as our study shows, these patients’ glial cells are different from the start, affecting fetal neurodevelopment. Differentiation and brain formation are both altered. It may be the case, therefore, that systematically altered vascularization leads to early brain circuit malformation, and this in turn leads to schizophrenia later on,” Nascimento said.
Another point made in the article is how important astrocytes are to neurological disorders.
“The role of glial cells, including astrocytes, not only in schizophrenia but also in neurological disorders generally has been discovered relatively recently. The predominant view used to be that researchers should focus on neurons. Our vision and understanding of the disease are expanding,” Martins-de-Souza said.
About this schizophrenia and neuroscience research news
Author: Heloisa Reinert
Source: FAPESP
Contact: Heloisa Reinert – FAPESP
Image: The image is in the public domain
Original Research: Closed access.
“Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization” by Daniel Martins-de-Souza et al. Molecular Psychiatry
Abstract
Induced pluripotent stem cell-derived astrocytes from patients with schizophrenia exhibit an inflammatory phenotype that affects vascularization
Molecular and functional abnormalities of astrocytes have been implicated in the etiology and pathogenesis of schizophrenia (SCZ).
In this study, we examined the proteome, inflammatory responses, and secretome effects on vascularization of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with SCZ.
Proteomic analysis revealed alterations in proteins related to immune function and vascularization. Reduced expression of the nuclear factor kappa B (NF-κB) p65 subunit was observed in these astrocytes, with no incremental secretion of cytokines after tumor necrosis factor alpha (TNF-α) stimulation.
Among inflammatory cytokines, secretion of interleukin (IL)-8 was particularly elevated in SCZ-patient-derived-astrocyte-conditioned medium (ASCZCM). In a chicken chorioallantoic membrane (CAM) assay, ASCZCM reduced the diameter of newly grown vessels. This effect could be mimicked with exogenous addition of IL-8.
Taken together, our results suggest that SCZ astrocytes are immunologically dysfunctional and may consequently affect vascularization through secreted factors.
Stem Cells May Help Identify New Schizophrenia Drugs
Summary: Researchers identified 20 drug candidates that reduce C4 immune protein secretion from astrocytes. The discovery could pave the way to treating schizophrenia and other disorders associated with C4 dysregulation in astrocytes.
Source: International Society for Stem Cell Research
Inflammation and overactivation of the immune system in the brain can cause loss of synapses and the death of neurons, leading to neurodegenerative and psychiatric diseases.
In schizophrenia, increased levels of the immune protein C4 have been measured in patients’ brains, and increasing C4 levels due to variations in copy number are associated with an increased risk for developing schizophrenia. Therapies lowering C4 levels in the brain and reducing inflammation may benefit schizophrenia patients but are currently not available.
Brain cells called astrocytes regulate the immune response and inflammatory environment in the brain by secreting immune proteins such as C4. Consequently, astrocytes are a primary target for C4-lowering therapies.
To identify effective drugs, Francesca Rapino, Lee Rubin, and colleagues from Harvard University, U.S., have developed an efficient method to make large numbers of C4-secreting human astrocytes from stem cells.
In a paper recently published in Stem Cell Reports, the researchers followed-up with a screen of 464 drugs and identified a small group of about 20 that reduced C4 secretion from astrocytes. These drugs were effective both in healthy astrocytes and in astrocytes made from schizophrenia patients’ stem cells.
This research opens up new avenues for studying inflammatory responses and their regulation in human astrocytes and serves as a platform to identify therapeutic drugs in large-scale screening approaches.
About this genetics and schizophrenia research news
Author: Press Office
Source: International Society for Stem Cell Research
Contact: Press Office – International Society for Stem Cell Research
Image: The image is credited to Francesca Rapino, Harvard University, USA
Original Research: Open access.
“Small molecule screen reveals pathways that regulate C4 secretion in stem-cell derived astrocytes” by Lee L. Rubin et al. Stem Cell Reports
Abstract
Small molecule screen reveals pathways that regulate C4 secretion in stem-cell derived astrocytes
See also
Highlights
- New method for 3D differentiation of astrocytes from pluripotent stem cells
- Transcriptional profiling identified these cells as dorsal fetal-like astrocytes
- ELISA-based small-molecule screen identified regulators of C4 secretion
- Connectivity map analysis identified additional pathways that regulate C4
Summary
In the brain, the complement system plays a crucial role in the immune response and in synaptic elimination during normal development and disease.
Here, we sought to identify pathways that modulate the production of complement component 4 (C4), recently associated with an increased risk of schizophrenia.
To design a disease-relevant assay, we first developed a rapid and robust 3D protocol capable of producing large numbers of astrocytes from pluripotent cells. Transcriptional profiling of these astrocytes confirmed the homogeneity of this population of dorsal fetal-like astrocytes.
Using a novel ELISA-based small-molecule screen, we identified epigenetic regulators, as well as inhibitors of intracellular signaling pathways, able to modulate C4 secretion from astrocytes. We then built a connectivity map to predict and validate additional key regulatory pathways, including one involving c-Jun-kinase.
This work provides a foundation for developing therapies for CNS diseases involving the complement cascade.
Rare Genetic Phenomenon Linked to Neuron Function and Schizophrenia
Summary: People with schizophrenia have significantly higher rates of tandem repeats in their genome, up to 7% more than in people without the mental health disorder. The genes were primarily found in genes crucial to brain function.
Source: UNC
In our cells, the language of DNA is written, making each of us unique. A tandem repeat occurs in DNA when a pattern of one or more nucleotides—the basic structural unit of DNA coded in the base of chemicals cytosine (C), adenine (A), guanine (G) and thymine (T)—is repeated multiple times in tandem. An example might be: CAG CAG CAG, in which the pattern CAG is repeated three times.
Now, using state-of-the-art whole-genome sequencing and machine learning techniques, the UNC School of Medicine lab of Jin Szatkiewicz, Ph.D., associate professor of genetics, and colleagues conducted one of the first and the largest investigations of tandem repeats in schizophrenia, elucidating their contribution to the development of this devastating disease.
Published in the journal Molecular Psychiatry, the research shows that individuals with schizophrenia had a significantly higher rate of rare tandem repeats in their genomes—7% more than individuals without schizophrenia. And they observed that the tandem repeats were not randomly located throughout the genome; they were primarily found in genes crucial to brain function and known to be important in schizophrenia, according to previous studies.
“We think this discovery opens doors for future functional studies on the precise biological mechanism of such variants,” said Szatkiewicz, who is also adjunct assistant professor of psychiatry.
“Understanding the biological cause of schizophrenia will enable future development of diagnostic tests, effective pharmaceuticals, and personalized treatments.”
Tandem repeats usually don’t have negative health implications. However, based on the location of tandem repeats in the genome and how long they are, they can contribute to disease. For example, Huntington’s disease is caused by a tandem repeat in the HTT gene that has been abnormally expanded. Onset of the disease will happen once the sequence of cytosine-adenine-guanine (CAG) repeats more than 36 times on the HTT gene.
The longer repeat expansions lead to abnormal protein products with an extended track of glutamine that is toxic to brain cells. These repeats are inherited and tend to grow longer and longer in successive generations with increasing disease severity or decreasing age of onset.
In their current study, Szatkiewicz and her team looked at the entire genomes of 2,100 individuals to find tandem repeats that looked abnormally long and were unique or rare. Because all participants provided access to their medical records, the team was able to compare these long and rare repeat DNA sequence samples from people who had schizophrenia versus samples from people in the study who didn’t. This allowed the researchers to determine which of these tandem repeats may be involved with the development of schizophrenia.
Using gene network analysis, the authors of this study demonstrated that genes with rare tandem repeats found in schizophrenia primarily impact synaptic and neuronal signaling functions.
In addition, these genes are highly evolutionarily conserved, indicating important biological functions and therefore the significant impact that tandem repeats might exert.
The UNC School of Medicine researchers then collaborated with scientists from The Hospital for Sick Children in Toronto to see if this increased level of rare tandem variants would also be found in another independently collected group of samples.
The Szatkiewicz findings were replicated in the Canadian investigation, indicating that this newly discovered link between tandem repeats and schizophrenia is quite strong.
“We think this is an important study,” said co-senior author Ryan Yuen, Ph.D., senior scientist at the Hospital for Sick Children and assistant professor of molecular genetics at the University of Toronto. “We’re confident our work sheds significant light on the role of tandem repeat DNA mutations play in the development of schizophrenia.”
About this schizophrenia and genetics research news
Author: Press Office
Source: UNC
Contact: Press Office – UNC
Image: The image is in the public domain
See also
Original Research: Open access.
“Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia” by Jia Wen et al. Molecular Psychiatry
Abstract
Rare tandem repeat expansions associate with genes involved in synaptic and neuronal signaling functions in schizophrenia
Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia.
Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2–20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group.
There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls.
We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions.
These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.
Individuals With Schizophrenia and Social Anhedonia Show Altered Neural Processing for Social Reward Anticipation
Summary: People with schizophrenia and social anhedonia exhibit altered neural processing for social reward processing, leading to impaired social interaction and social dysfunction.
Source: Chinese Academy of Science
Patients with schizophrenia and individuals with social anhedonia have been shown to exhibit impaired social reward processing that ultimately leads to impaired social interaction and social dysfunctions.
However, most of the previous studies on social reward anticipation in schizophrenia spectrum disorders were limited to behavioral design. It remains unclear whether the putative neural processing for social reward anticipation has been altered in both individuals with schizophrenia and individuals with social anhedonia.
Recently, a research team led by Dr. Raymond Chan from the Institute of Psychology (IP) of the Chinese Academy of Sciences (CAS) have conducted a study to specifically examine the underlying neural mechanisms of social reward anticipation in these populations.
The study was published in European Archives of Psychiatry and Clinical Neuroscience on Oct. 28.
The researchers recruited 23 individuals with schizophrenia and 17 healthy controls, as well as 37 individuals with social anhedonia and 50 healthy controls to complete the social incentive delay imaging task while they were undertaking MRI brain scans.
They found that individuals with schizophrenia exhibited hypo-activation of the left medial frontal gyrus and the negative functional connectivities (FCs) with the left parietal regions.
However, individuals with social anhedonia exhibited the hyper-activation of the left middle frontal gyrus when anticipating social reward.
Moreover, individuals with schizophrenia showed strengthened cerebellum-temporal FCs, whilst social anhedonia individuals showed strengthened FCs in left frontal regions.
These findings suggest that both individuals with schizophrenia and with social anhedonia exhibit altered neural processing for social reward anticipation, and such neural activities show a weakened association with real-life social network characteristics.
The study advances our understanding on the neural underpinnings of social motivation in schizophrenia spectrum disorders.
About this mental health research news
Author: Li Yuan
Source: Chinese Academy of Science
Contact: Li Yuan – Chinese Academy of Science
Image: The image is in the public domain
Original Research: Closed access.
“Altered neural mechanism of social reward anticipation in individuals with schizophrenia and social anhedonia” by Yi-jing Zhang et al. European Archives of Psychiatry and Clinical Neuroscience
Abstract
Altered neural mechanism of social reward anticipation in individuals with schizophrenia and social anhedonia
See also
Altered social reward anticipation could be found in schizophrenia (SCZ) patients and individuals with high levels of social anhedonia (SA).
However, few research investigated the putative neural processing for altered social reward anticipation in these populations on the SCZ spectrum.
This study aimed to examine the underlying neural mechanisms of social reward anticipation in these populations.
Twenty-three SCZ patients and 17 healthy controls (HC), 37 SA individuals and 50 respective HCs completed the Social Incentive Delay (SID) imaging task while they were undertaking MRI brain scans.
We used the group contrast to examine the alterations of BOLD activation and functional connectivity (FC, psychophysiological interactions analysis). We then characterized the beta-series social brain network (SBN) based on the meta-analysis results from NeuroSynth and examined their prediction effects on real-life social network (SN) characteristics using the partial least squared regression analysis.
The results showed that SCZ patients exhibited hypo-activation of the left medial frontal gyrus and the negative FCs with the left parietal regions, while individuals with SA showed the hyper-activation of the left middle frontal gyrus when anticipating social reward. For the beta-series SBNs, SCZ patients had strengthened cerebellum-temporal FCs, while SA individuals had strengthened left frontal regions FCs. However, such FCs of the SBN failed to predict the real-life SN characteristics.
These preliminary findings suggested that SCZ patients and SA individuals appear to exhibit altered neural processing for social reward anticipation, and such neural activities showed a weakened association with real-life SN characteristics.
Schizophrenia and Bipolar Disorder May Be Detectable Years Before Illnesses Begin
Summary: Researchers report bipolar depression and schizophrenia may be detectable several years before symptoms appear. A new study reports 50% of patients diagnosed with schizophrenia or bipolar disorder attended specialist child and adolescent mental health services during childhood.
Source: TCD
The risk of schizophrenia and bipolar disorder may be detectable years before the illnesses begin, according to new research.
A University College Dublin led study funded by the Health Research Board has found that 50% of people who developed these mental health disorders had attended specialist child and adolescent mental health services (CAMHS) in childhood.
Published in the journal World Psychiatry, the findings suggest the possibility of earlier intervention and even prevention according to Professor Ian Kelleher, from the UCD School of Medicine, who led the international study which was carried out in conjunction with the Finnish Institute for Health and Welfare (THL).
“Schizophrenia and bipolar disorder typically emerge in early adulthood and can have a devastating impact on the individuals affected, as well as on their families,” he said.
“Our findings show that half of individuals who develop these illnesses had come to CAMHS at some stage in childhood, typically many years before they developed schizophrenia or bipolar disorder.
“We know that early intervention is key to improving outcomes for people with serious mental illness. These findings demonstrate the enormous opportunities to provide far earlier intervention, even while still in childhood, by developing specialist early intervention services within existing child and adolescent mental health services”.
Schizophrenia and bipolar disorder are serious mental illnesses affecting about 65 million people worldwide. Both disorders are usually diagnosed in adulthood and are often associated with high levels of disability, personal and societal cost. Early intervention, however, is known to lead to better outcomes for people affected by these illnesses.
The researchers behind the new study used Finland’s world-leading healthcare registers to trace all individuals born in 1987 throughout childhood and adolescence to see if, between birth and age 17 years, they ever attended CAMHS.
Using unique patient identifiers, the researchers were then able to follow all these individuals up to age 28 years and see who went on to be diagnosed with schizophrenia or bipolar disorder.
They found that the risk of psychosis or bipolar disorder by age 28-years-old was 1.8% for individuals who had not attended CAMHS. For individuals who had attended outpatient CAMHS in adolescence, however, the risk was 15% and for individuals who had been admitted to an inpatient adolescent CAMHS hospital, the risk was 37%.
See also
“This research shows the power of electronic healthcare registers to answer important questions about human health and disease,” said Professor Mika Gissler, THL.
“It demonstrates how healthcare register data can be used to better understand pathways to serious mental illness, from childhood into adulthood, and to identify critical opportunities for early intervention.”
Stressing the importance of early intervention, Professor Ian Kelleher said: “We know it’s crucial to intervene as early as possible to prevent some of the worst effects of these illnesses. But ideally, we would like to be able to intervene even before the onset of illness, to prevent it altogether.
These findings highlight the possibility of intervening far earlier than we do at present, even in childhood and adolescence, to prevent these serious mental illnesses from emerging”.
About this mental health research news
Author: Dominic Martella
Source: TCD
Contact: Dominic Martella – TCD
Image: The image is in the public domain
Original Research: The findings will appear in World Psychiatry
New Model Helps Unravel Complex Psychiatric Disorders Such As Autism and Schizophrenia
The research focuses on mapping cis-regulatory components in human neurons that may be connected to the heredity of psychiatric disorders.
A Mount Sinai stem cell model may be able to shed light on the complex biology behind certain psychiatric disorders.
In order to map disease risk variants in human neurons, researchers from the Icahn School of Medicine at Mount Sinai used a unique stem cell model. This work may help shed light on the biological mechanisms behind neuropsychiatric diseases such as autism and schizophrenia.
Nan Yang, Ph.D., Assistant Professor of Neuroscience. Credit: Mount Sinai Health System
The group’s in vitro cellular model, which was recently published in the journal Cell Reports, was created to make it easier for future researchers to understand the disease mechanisms involving genome-wide association studies (GWAS) that characterize various risk alleles (common genetic variants conferring risk) for psychiatric disorders. This study could help develop better diagnostic methods for spotting mental problems years before patient symptoms manifest.
The research focuses on identifying cis-regulatory elements in human neurons that could be related to the heritability of psychiatric disorders. Cis-regulatory elements, which include enhancers and promoters, are non-coding
In recent years, GWAS have identified hundreds of gene regions associated with psychiatric disease, though understanding disease pathophysiology has been elusive. The functional genomics approach Dr. Yang and her team developed uses stem cell models that can help resolve the impact of patient-specific variants across cell types, genetic backgrounds, and environmental conditions. This unique approach effectively lays a foundation to translate risk variants to genes, genes to pathways, and pathways to circuits that reveal the synergistic relationship between disease risk factors within and between the cell types in the brain.
“Our research attempts to decode and transfer highly complex genetic insights into medically actionable information,” says Dr. Yang, who is a member of the Black Family Stem Cell Institute, The Friedman Brain Institute, and The Ronald M. Loeb Center for
New Evidence for an Autoimmune Cause of Schizophrenia
Summary: Researchers have identified an autoantibody that appears to cause schizophrenia in some individuals. The findings add to the growing body of evidence that schizophrenia could have an autoimmune component.
Source: Tokyo Medical and Dental University
Schizophrenia is a disorder that affects how people act, think, and perceive reality. It is often very difficult to treat because it has many different causes and symptoms.
In a study published last month in Cell Reports Medicine, researchers from Tokyo Medical and Dental University (TMDU) have identified an autoantibody—a protein that is produced by the immune system to attach to a specific substance from the individual’s own body, rather than to a foreign substance like a virus or bacteria—in some patients with schizophrenia.
Notably, they also found that this autoantibody caused schizophrenia-like behaviors and changes in the brain when they injected it into mice.
When considering possible autoantibodies that might cause schizophrenia, the research team had a specific protein in mind. Previous research has suggested that neural cell adhesion molecule (NCAM1), which helps cells in the brain talk to one another via specialized connections known as synapses, may have a role in the development of schizophrenia.
“We decided to look for autoantibodies against NCAM1 in around 200 healthy controls and 200 patients with schizophrenia,” explains lead author of the study Hiroki Shiwaku.
“We only found these autoantibodies in 12 patients, suggesting that they may be associated with the disorder in just a small subset of schizophrenia cases.”
The research team didn’t stop there—they wanted to know whether these autoantibodies could cause any changes that commonly occur in schizophrenia, so they purified autoantibodies from some of the patients and injected them into the brains of mice.
“The results were impressive,” says Hidehiko Takahashi, senior author.
“Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia.”
Specifically, mice with the patient autoantibodies had cognitive impairment and changes in their regulation of the startle reflex, which are both seen in other animal models of schizophrenia.
They also had fewer synapses and dendritic spines, which are structures that are important for the connections between brain cells, and are also affected in schizophrenia.
Given that schizophrenia can present very differently among patients and is often resistant to treatment, the results of this study are promising.
If schizophrenia is indeed caused by autoantibodies against NCAM1 in some patients, this will lead to important improvements in their diagnosis and treatment.
About this schizophrenia research news
Author: Hiroki Shiwaku
Source: Tokyo Medical and Dental University
Contact: Hiroki Shiwaku – Tokyo Medical and Dental University
Image: The image is credited to Department of Psychiatry and Behavioral Sciences, TMDU
Original Research: Open access.
“Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice” by Hidehiko Takahashi et al. Cell Reports Medicine
See also
Abstract
Autoantibodies against NCAM1 from patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice
Highlights
- Some patients with schizophrenia are positive for anti-NCAM1 autoantibodies
- Anti-NCAM1 antibody from schizophrenia patients inhibits NCAM1-NCAM1 interactions
- Anti-NCAM1 antibody from schizophrenia patients reduces spines and synapses in mice
- Anti-NCAM1 antibody from patients induces schizophrenia-related behavior in mice
Summary
From genetic and etiological studies, autoimmune mechanisms underlying schizophrenia are suspected; however, the details remain unclear.
In this study, we describe autoantibodies against neural cell adhesion molecule (NCAM1) in patients with schizophrenia (5.4%, cell-based assay; 6.7%, ELISA) in a Japanese cohort (n = 223). Anti-NCAM1 autoantibody disrupts both NCAM1-NCAM1 and NCAM1-glial cell line-derived neurotrophic factor (GDNF) interactions.
Furthermore, the anti-NCAM1 antibody purified from patients with schizophrenia interrupts NCAM1-Fyn interaction and inhibits phosphorylation of FAK, MEK1, and ERK1 when introduced into the cerebrospinal fluid of mice and also reduces the number of spines and synapses in frontal cortex.
In addition, it induces schizophrenia-related behavior in mice, including deficient pre-pulse inhibition and cognitive impairment. In conclusion, anti-NCAM1 autoantibodies in patients with schizophrenia cause schizophrenia-related behavior and changes in synapses in mice.
These antibodies may be a potential therapeutic target and serve as a biomarker to distinguish a small but treatable subgroup in heterogeneous patients with schizophrenia.
Man Chopped Off Penis Due to Cannabis-Linked Psychosis: Doctors
A man in Thailand’s bong session went disastrously wrong, according to his doctors. In a new case report, they describe how he “completely amputated his penis” using scissors, apparently due to a rare episode of cannabis-induced psychosis. Though the man’s delusional symptoms faded after being admitted to the hospital and his injuries were treated, doctors weren’t able to reattach the lost appendage.
The bizarre injury was detailed in a paper published over the weekend in the Journal of Medical Case Reports by doctors from Chiang Mai University in Thailand.
The 23-year-old man had reportedly been a regular cannabis user for the past two years but had stopped for the preceding three months. He then got back into his habit by smoking two bongs of cannabis, equivalent to two grams worth, according to the paper. Two hours later, he began to experience an unwanted erection, along with a severe and persistent sharp pain in his penis; he also reported that his glans (the tip of the penis) looked “distorted” to him. In an attempt to stop the pain, he decided to grab a pair of scissors and to “trim the penile skin several times.” Eventually, he severed his penis clean off, leaving behind an inch-long stump.
Unsurprisingly, the home surgery caused the man to bleed out. He was admitted to the hospital two hours after the amputation and immediately treated with antibiotics and a tetanus booster. Emergency surgery stopped the man’s bleeding and cleaned his wounds, while he underwent a procedure to create a new opening so he could still urinate through his urethra. Unfortunately, though the penis was recovered, it was deemed too dirty and fragile to be reconstructed and reattached. By the time doctors saw the man, his amputated member had even been left crawling with ants (Yes, there are pictures of the penis and stump in the paper, but I wouldn’t recommend viewing them if you have a weak stomach).
Given the man’s behavior, he was psychologically evaluated as well. Upon admission, he reported experiencing visual and auditory hallucinations, which included seeing moving shadows and hearing birds and insects. But he was otherwise coherent, not suicidal, and denied having a family or personal history of depression, self harm, and any other issues related to his prior drug use. The man was hospitalized for two weeks and given antipsychotics. And by the time he was discharged, he no longer reported any delusional symptoms.
Because the man’s symptoms happened soon after he ingested cannabis and went away after a month of not taking the drug—along with no other likely explanation—the doctors diagnosed him with substance-induced psychotic disorder. Cases of people self-amputating their penis during a drug-induced psychosis aren’t unheard of, though they are rarely reported. Even rarer is a case seemingly brought on by cannabis-induced psychosis, they wrote.
Many studies have shown a link between cannabis use and an increased risk of acute schizophrenia-like symptoms, though it’s less clear whether cannabis actually increases the risk of schizophrenia itself. And while this risk is rare in general, possible factors include being young and ingesting cannabis high in THC, the primary ingredient responsible for making you feel high. The sharp and persistent pain in the man’s penis that prompted his amputation may have been a subjective sensation brought on by his delusion, but it also could have been the result of a genuine unwanted erection caused by the cannabis—it’s simply not possible to tell either way, the doctors concluded.
“In summary, cannabis-induced psychosis is an adverse effect of cannabis, which may lead to impaired judgement and unexpected self-harm,” they wrote.
As for the man himself, the doctors did plan to perform another surgery that would have lengthened and reconstructed his penis further. But the patient apparently relocated and they’ve since lost touch with him.