Washington: According to the researchers at the 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. —ANI

 According to the researchers at the 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.

Researchers Found New Evidence For Autoimmune Cause Of Schizophrenia

Washington: Using state-of-the-art whole-genome sequencing and machine learning techniques, researchers conducted one of the first and the largest investigations of tandem repeats in schizophrenia"&gt;schizophrenia, elucidating their contribution to the development of this devastating disease.
Now, using state-of-the-art whole-genome sequencing and machine learning techniques, the UNC School of Medicine lab of Jin Szatkiewicz, PhD, associate professor of genetics, and colleagues conducted one of the first and the largest investigations of tandem repeats in schizophrenia"&gt;schizophrenia, elucidating their contribution to the development of this devastating disease.
Published in the journal Molecular Psychiatry, the research shows that individuals with schizophrenia"&gt;schizophrenia had a significantly higher rate of rare tandem repeats in their genomes -- 7% more than individuals without schizophrenia"&gt;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"&gt;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"&gt;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"&gt;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"&gt;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"&gt;schizophrenia.
Using gene network analysis, the authors of this study demonstrated that genes with rare tandem repeats found in schizophrenia"&gt;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"&gt;schizophrenia is quite strong. "We think this is an important study," said co-senior author Ryan Yuen, PhD, 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"&gt;schizophrenia." —ANI

Using state-of-the-art whole-genome sequencing and machine learning techniques, researchers conducted one of the first and the largest investigations of tandem repeats in schizophrenia">schizophrenia, elucidating their contribution to the development of this devastating disease.

Scientists Link Rare Genetic Phenomenon To Neuron Function, Schizophrenia

Washington: A recent study headed by the Lieber Institute for Brain Development found that more than 100 genes linked to the risk of schizophrenia appear to induce disease owing to their activity in the placenta rather than the developing brain. For nearly a century, scientists concluded that genes for schizophrenia risk were mostly, if not entirely, concerned with the brain. However, new study published in Nature Communications has discovered that the placenta plays a considerably larger role in the development of sickness than previously thought. "The secret of the genetics of schizophrenia has been hiding in plain sight--the placenta, the critical organ in supporting prenatal development, launches the developmental trajectory of risk," says Daniel Weinberger, M.D., senior author of the paper and Director and CEO of the Lieber Institute for Brain Development, located on the Johns Hopkins medical campus in Baltimore. "The commonly shared view on the causes of schizophrenia is that genetic and environmental risk factors play a role directly and only in the brain, but these latest results show that placenta health is also critical." The researchers discovered that schizophrenia genes alter the placenta's ability to monitor nutrients in the mother's circulation, including oxygen, and exchange nutrients according on what it discovers. The schizophrenia risk genes are more weakly expressed in the placental cells termed trophoblasts, which constitute the core of this maternal-fetal nutrition exchange, adversely compromising the placenta's role in feeding the growing foetus. The paper also identifies several genes in the placenta that are causative factors for diabetes, bipolar disorder, depression, autism and attention deficit hyperactivity disorder, or ADHD. The scientists, however, found far more genetic associations with genes for schizophrenia than for any of these other disorders.  The researchers also discovered that the risk genes for schizophrenia found in the placenta may have a relatively greater effect on heritability, the likelihood of illness inherited from ancestors, than risk genes found in the brain. "Targeting placenta biology is a crucial new potential approach to prevention, which is the holy grail of public health," says Gianluca Ursini, M.D., Ph.D., the lead author on the paper and an investigator at the Lieber Institute. "Scientists could detect changes in placental risk genes decades before the possible onset of a disorder, possibly even in the mother's bloodstream during pregnancy. If doctors knew which children were most at risk of developmental disorders, they could implement early interventions to keep them healthy." The scientists also found interesting sex-based differences in the placenta risk genes. Different genes were associated with schizophrenia risk based on whether the placenta came from a male or female child. In pregnancies with male children, inflammatory processes in the placenta seem to play a central role. Previous research has shown males are more vulnerable than females to prenatal stress. Generally speaking, developmental disorders such as schizophrenia occur more frequently in men and boys. The researchers also uncovered concerning results about COVID-19 pregnancies. The scientists studied a small sample of placentas from mothers who had COVID-19 during pregnancy and found the schizophrenia genes for placenta risk were dramatically activated in these placentas. The finding indicates that COVID-19 infection during pregnancy may be a risk factor for schizophrenia because of how infection affects the placenta. Lieber Institute scientists are pursuing this possibility with NIH-funded research examining COVID-19 placentas to learn more. The Lieber Institute researchers hope their ongoing study of the genes of the placenta will one day lead to new treatment and diagnostic tools, perhaps revolutionizing the field of prenatal medicine. "In the modern era of molecular and genetic medicine, the standard treatment for a complicated pregnancy is still primarily bedrest," said Dr. Weinberger. "These new molecular insights into how genes related to disorders of the brain and other organs play out in the placenta offer new opportunities for improving prenatal health and preventing complications later in life." (ANI)

 A recent study headed by the Lieber Institute for Brain Development found that more than 100 genes linked to the risk of schizophrenia 

Placenta plays an important role in genetic risk of schizophrenia: Study

Tokyo: Autoantibodies, or immune system-produced proteins that may function against one's own body, have been linked to reports of schizophrenia. A minority of schizophrenia patients had autoantibodies that targeted neurexin 1, a "synaptic adhesion protein," according to a study published last month in Brain Behaviour and Immunity. The autoantibodies led to numerous schizophrenia-related alterations when administered to animals. What is a synaptic protein, and why can schizophrenia be related to it? Specialised proteins known as synaptic adhesion proteins bind to form actual connections between brain cells. The cells can exchange molecules through these connections, known as synapses, to communicate. The research team from Tokyo Medical and Dental University (TMDU) opted to look into autoantibodies that target synaptic proteins in patients with schizophrenia because synapses and autoimmunity are both known to be linked to schizophrenia. "In around 2 per cent of our patient population, we identified autoantibodies against the synaptic protein neurexin 1a, which is expressed by one cell in the synapse and binds to proteins known as neuroligins on the other cell in the synapse," says lead author of the study Hiroki Shiwaku. "Once we had identified these autoantibodies, we wanted to see if they were able to cause schizophrenia-related changes." To do this, the researchers isolated autoantibodies from some of the patients with schizophrenia and injected them into the cerebrospinal fluid of mice, so that the autoantibodies would travel into the brain. In these mice, the autoantibodies blocked neurexin 1a and neuroligin binding and altered some related synaptic properties. The administration of these autoantibodies also resulted in fewer synapses in the brains of mice and schizophrenia-related behaviors, such as reduced social behavior toward unfamiliar mice and reduced cognitive function. "Together, our results strongly suggest that autoantibodies against neurexin 1a can cause schizophrenia-related changes, at least in mice," explains Hiroki Shiwaku. "These autoantibodies may therefore represent a therapeutic target for a subset of patients with schizophrenia." Schizophrenia has a wide variety of both symptoms and treatment responses, and many patients have symptoms that are resistant to currently available treatment options. Therefore, the identification of possible disease-causing autoantibodies is important for improving symptom control in patients with schizophrenia. It is hoped that the results of this investigation will allow patients with autoantibodies that target neurexin 1a--all of whom were resistant to antipsychotic treatment in the present study--to better control their symptoms in the future. —ANI

Autoantibodies, or immune system-produced proteins that may function against one's own body

Researchers Give More Insight Into Association Between Autoimmunity, Schizophrenia

Washington: Researchers have investigated overlapping patterns of altered gene activity in two separate models of the 3q29 deletion syndrome, including human brain organoids and mice with the deletion produced via CRIPSR. Mitochondrial activity has declined in each of these systems. When a small portion of chromosome 3 is missing, a disease known as 3q29 deletion syndrome results, which increases the risk of schizophrenia by roughly 40 times. This dysfunction may lead to energy shortages in the brain, which can cause psychiatric symptoms and disorders.   “Our data give strong support to the hypothesis that mitochondrial dysregulation is a contributor to the development of schizophrenia,” said Jennifer Mulle, associate professor of psychiatry, neuroscience and cell biology at Rutgers Robert Wood Johnson Medical School and a co-senior author of the study published in Science Advances. “The interplay between mitochondrial dynamics and neuronal maturation is an important area for additional detailed and rigorous study. Mulle, a member of the Center for Advanced Biotechnology and Medicine at Rutgers, and colleagues first showed that 3q29 deletion was a risk factor for schizophrenia in 2010. The findings converge with work on another genetic risk factor for schizophrenia, 22q11 deletion syndrome (or DiGeorge syndrome), which has also been found to involve disrupted mitochondrial function. “For genetic variants associated with schizophrenia, we want to understand the primary pathology at the cellular level,” said Ryan Purcell, assistant professor of cell biology at Emory University School of Medicine and co-lead author of the study. “This gives us a foothold, which may help cut through schizophrenia’s polygenic complexity and better understand the neurobiology.” About one in 30,000 people are born with 3q29 deletion syndrome. In addition to increasing the risk for schizophrenia, 3q29 deletion can include intellectual disability, autism spectrum disorder and congenital heart defects. The effect of 3q29 deletion on schizophrenia risk is more than any single known gene variant, but the contributions of individual genes within the deletion are still being unravelled. The finding that various schizophrenia-associated chromosomal deletions impair mitochondria runs counter to an expectation in the field that such mutations should alter proteins in the synapses that connect neurons. However, mitochondria are critical for energy-hungry synapses’ function – so these models may not be in conflict. It was also surprising that 3q29 cells have poorly functioning mitochondria because only one of the 22 genes in the deletion appears to encode a protein located in mitochondria. However, that gene or others within the interval may instead regulate the production or importation of mitochondrial proteins, the researchers said. Mitochondria, which are found in every cell, produce energy from sugar or fat. Sometimes this process is aerobic (done with extra oxygen from inhaled air) and sometimes anaerobic (done without oxygen). As a result of altered mitochondrial function, 3q29 cells lack metabolic flexibility, meaning their mitochondria have difficulty adapting to changes in sources of energy. This may interfere with neuronal development because maturing neurons need to switch to relying on aerobic energy production as they differentiate. The results illustrate how 3q29 deletion affects the whole body, not just the brain: The effects on mitochondria are seen in kidney cells as well as in brain cells. Individuals with 3q29 deletion syndrome also tend to be smaller in size, possibly because of altered fat metabolism. “Eventually, we want to understand which cellular changes like these are linked to specific clinical outcomes, which could help in designing more effective therapeutic strategies,” Purcell said. (ANI)

Researchers have investigated overlapping patterns of altered gene activity in two separate models 

Schizophrenia genetic risk factor weakens mitochondrial function: Study

London: People suffering from hospital-treated depression may have a high risk of developing conditions such as substance abuse, bipolar disorder, schizophrenia and anxiety -- depending on their genetic predisposition to the individual disorder, according to a new study. The study, published in the journal Nature Medicine, showed that people with hospital-treated depression and a high genetic predisposition to bipolar disorder are 32 times more likely to develop the disease than the rest of the general population. Similarly, people with hospital-treated depression and a high genetic predisposition to schizophrenia are 14 times more likely to develop schizophrenia compared to the rest of the population. The results can pave the way for offering high-risk people preventative measures and early treatment in the future, said professor Anders Borglum from the Department of Biomedicine at Aarhus University. "For example, targeted efforts that offer more frequent monitoring for the development of bipolar disorder, schizophrenia and anxiety among people with depression who have the highest genetic and clinical risk of being diagnosed with one of these disorders. This would enable early diagnosis and treatment, which we know can have beneficial effects," Borglum said. Likewise, according to Borglum, identifying people with depression and a high genetic risk of developing substance abuse could make the patient and the doctor aware of the issue. Preventative measures could then be initiated to prevent the development of substance abuse. Further, the study shows that people with hospital-treated depression and a high genetic predisposition to substance abuse have a 21 per cent risk of developing a serious substance abuse problem. This is more than five times higher than the group with a low genetic predisposition to substance abuse who have also had depression. And 10 times higher than the general population without hospital-treated depression. This group only has a 2 per cent risk of being diagnosed with substance abuse over the same period of time. Through a detailed genetic scan, the researchers studied the genome of 1.3 million people, where more than 370,000 of them suffered from depression. The researchers found a total of 11,700 genetic risk variants can explain 90 per cent of the heritability of depression, making depression one of the most complex and polygenic mental disorders. The majority of the risk genes still need to be identified. "We found a number of biological systems and cell types that are affected by the genetic risk. The effects are seen in virtually all regions of the brain, but not in other organs. And mainly in the brain's nerve cells -- neurons," said Thomas Als, former associate professor at the Department of Biomedicine. "The genetic risk can affect many different types of neurons. Overall, it can be said that the genetic risk affects the development and communication of brain cells," Als said. —IANS

People suffering from hospital-treated depression may have a high risk of developing conditions such as substance abuse

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Researchers Found New Evidence For Autoimmune Cause Of Schizophrenia

Inam Ansari

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Tag : Schizophrenia

Researchers Found New Evidence For Autoimmune Cause Of Schizophrenia

Inam Ansari

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