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Schizophrenia News

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• Bullied Teens' Brains Show Chemical Change
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• AI Clinical Models: Accurate but Study-Specific
• Neonatal Proteins and Adult Health
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Earlier Headlines

Wednesday, august 2, 2023.

• New Neuroimaging Approach Could Improve Diagnosis of Schizophrenia

Thursday, July 6, 2023

• Schizophrenia Is Associated With Somatic Mutations Occurring in Utero

Tuesday, June 6, 2023

• How Does Dopamine Regulate Both Learning and Motivation?

Wednesday, May 31, 2023

• Further Link Identified Between Autoimmunity and Schizophrenia

Wednesday, May 24, 2023

• Vitamin D Alters Developing Neurons in the Brain's Dopamine Circuit

Friday, May 5, 2023

• A Special Omega-3 Fatty Acid Lipid Will Change How We Look at the Developing and Aging Brain

Friday, February 17, 2023

• The Drug Fasudil Is Found to Reverse Key Symptoms of Schizophrenia in Mice

Tuesday, January 24, 2023

• Abnormal 12-Hour Cyclic Gene Activity Found in Schizophrenic Brains

Wednesday, November 30, 2022

• Scientists Link Rare Genetic Phenomenon to Neuron Function, Schizophrenia

Wednesday, November 16, 2022

• ADHD Medication for Amphetamine Addiction Linked to Reduced Risk of Hospitalization and Death, Study Finds

Thursday, November 3, 2022

• Inflammation Amplifies the Effect of Genetic Risk Variants for Schizophrenia

Thursday, October 6, 2022

• Schizophrenia May Increase Dementia Risk by 2.5 Times

Friday, July 15, 2022

• Neuronal Cell Type for Controlling the Flow of Information in the Brain

Tuesday, July 5, 2022

• In Krabbe Disease, Neurons May Bring About Their Own Destruction

Thursday, June 16, 2022

• How the Cerebellum Modulates Our Ability to Socialize

Monday, June 6, 2022

• Body Versus Brain: New Evidence for an Autoimmune Cause of Schizophrenia

Tuesday, May 24, 2022

• 'Happy Hormone' Dopamine Plays Role in Identifying Emotions

Friday, May 20, 2022

• Study Links Thalamus Inhibition in Adolescence to Long-Lasting Cortical Abnormalities

Wednesday, April 27, 2022

• Risk of Psychotic-Like Experiences Can Start in Childhood

Tuesday, April 19, 2022

• Mental Illness Associated With Increased Death from Cardiovascular Disease

Wednesday, April 6, 2022

• Landmark Study Implicates Specific Genes in Schizophrenia

Wednesday, March 30, 2022

• Genetically Determined Levels of Inflammation Linked to Neuropsychiatric Illness

Monday, March 14, 2022

• Novel Cell Survival Mechanisms Through RNA Regulation in the Central Nervous System

Wednesday, March 9, 2022

• People With Serious Mental Illness May Have Increased Heart Disease Risk at Younger Ages

Thursday, March 3, 2022

• Communication Defect in Psychotic Disorders
• Brain Stimulation Shows Promise as Treatment for Cannabis Use Disorder in People With Schizophrenia

Wednesday, January 26, 2022

• Research Reveals New Links Between Brain Over-Activity and Schizophrenia Symptoms

Friday, January 14, 2022

• Risk of Schizophrenia Linked to Brain Cell Development

Tuesday, January 11, 2022

• Sleep Deprivation Increases Serotonin 2a Receptor Response in Brain

Thursday, December 23, 2021

• Clues to Treatment of Schizophrenia and Bipolar Disorder Found in Recently Evolved Region of the ‘dark Genome’

Monday, December 13, 2021

• Identifying Rare Disease-Associated Genetic Variants in Patients With Severe Schizophrenia

Wednesday, December 8, 2021

• Coping With Schizophrenia, When Emotions Can Be Too Much

Thursday, September 9, 2021

• Brain Molecule Helps 'wake Up' Cells That Could Help Tackle MS and Similar Diseases

Monday, September 6, 2021

• Schizophrenia Study Suggests Advanced Genetic Scorecard Cannot Predict a Patient’s Fate

Tuesday, August 3, 2021

• A Machine Learning Approach for Predicting Risk of Schizophrenia Using a Blood Test

Thursday, July 29, 2021

• Amygdala Found to Have Role in Important Pre-Attentive Mechanism in the Brain

Tuesday, July 27, 2021

• Early Signs: Perceptual Distortions in Late-Teens Predict Psychotic Symptoms in Mid-Life

Wednesday, July 21, 2021

• Evidence of Sustained Benefits of Pimavanserin for Dementia-Related Psychosis

Thursday, July 15, 2021

• Hope for Psychosis Sufferers

Tuesday, July 13, 2021

• Impairments Found in Neurons Derived from People With Schizophrenia and Genetic Mutation

Monday, June 14, 2021

• Brain Capillary Structures Show a Correlation With Their Neuron Structures

Tuesday, May 11, 2021

• New Findings Linking Brain Immune System to Psychosis

Tuesday, April 20, 2021

• The Immune Link Between a Leaky Blood-Brain Barrier and Schizophrenia
• Supplement Treats Schizophrenia in Mice, Restores Healthy 'dance' And Structure of Neurons

Tuesday, April 13, 2021

• Genetic Predisposition to Schizophrenia May Increase Risk of Psychosis from Cannabis Use

Thursday, April 1, 2021

• Mice With Hallucination-Like Behaviors Reveal Insight Into Psychotic Illness
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Trending Topics

Potential schizophrenia treatment, discovered at Vanderbilt and being developed by Neumora Therapeutics, entering Phase 1 clinical trial 

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• Vanderbilt University Statement – March 28, 2024

Dec 4, 2023, 12:49 PM

A potential schizophrenia treatment discovered through the Warren Center for Neuroscience Drug Discovery has been cleared by the U.S. Food and Drug Administration for use in phase 1 clinical trials—the third WCNDD therapeutic to reach that benchmark.  

“Vanderbilt is proud that a discovery by our researchers at the Warren Center is now a significant step closer to helping improve the lives of people with schizophrenia,” Chancellor Daniel Diermeier said. “Our work with Neumora is the very definition of translational research and the work we aim to do every day, which is applying innovation and discovery to help address the world’s most complex challenges.”   

The clinical trial has been initiated by Neumora Therapeutics Inc. , a clinical-stage biopharmaceutical company founded to confront the global brain disease crisis by taking a fundamentally different approach to the way treatments are developed. Vanderbilt and Neumora signed an exclusive, worldwide license and a research collaboration agreement for two novel series of M4 receptor modulator compounds, including NMRA-266, in February 2022.  

Vanderbilt’s agreement with Neumora was centered around the M 4 muscarinic receptor, which NMRA-266 targets through positive allosteric modulation. In preclinical studies conducted by Conn and Lindsley, NMRA-266 was found to be highly selective to the M 4 receptor, the area of the brain that regulates neurotransmission of dopamine. Overactive transmission of dopamine is connected to the positive, negative and cognitive symptoms of schizophrenia.   

“The M 4 PAM story has been a Homer-style Odyssey to get to this point and represents almost 20 years of research funded by National Institutes of Health, the William K. Warren Foundation and pharmaceutical companies,” said Lindsley, also a University Professor of pharmacology, biochemistry and chemistry who holds the William K. Warren, Jr. Chair in Medicine. “This mechanism and NMRA-266 represent a potential game-changer for schizophrenic patients and their families. Moreover, this success is a testament to the virtue of academic drug discovery and Vanderbilt’s commitment to supporting the WCNDD, a clinical-stage biotech enterprise within the university.”  

For the WCNDD to have such regular production of clinical assets when up against diverse neuroscience pipeline is unprecedented among academic drug discovery centers, according to Lindsley.  

“NMRA-266 entering phase 1 trials highlights the complementary relationship between university researchers and industry partners,” said Vice Provost for Research and Innovation Padma Raghavan. “By pairing our faculty’s ingenuity with the private sector’s commercialization know-how, we are able to bring life-changing discoveries to patients in need faster.”  

Schizophrenia spectrum disorders affect 3.7 million U.S. adults, a figure up to three times higher than previously understood, according to a recent study . This fundamentally different mechanism that NMRA-266 acts through is very selective for brain circuits involved in schizophrenia, which means in is unlikely to have the adverse effects of current dopamine antagonists—resulting in an improved standard of care for people with schizophrenia.  

“The initiation of this phase 1 study is an important step in the development of NMRA-266. In pre-clinical studies NMRA-266 demonstrated a favorable pharmacologic profile that includes high potency and selectivity for the M 4  receptor subtype, meriting its advancement into the clinic,” Dr. Robert Lenz, executive vice president and head of research and development at Neumora, said in a  release . “With its pre-clinical profile and clinical validation of the M 4  muscarinic receptor class in treating schizophrenia, we believe that NMRA-266 has strong potential as a treatment for neuropsychiatric disorders.”  

Human clinical trials are a significant advancement in a five-step  drug development process . Drug discovery research begins in the lab and is followed by preclinical research to answer basic questions about safety. Then there is clinical research to ensure that the treatment is safe and effective. The FDA then reviews all submitted data. If approved, the therapeutic will be made available for use by the public and be monitored for safety by the FDA for as long as it is available.  

The Vanderbilt-Neumora collaboration was facilitated by the   Center for Technology Transfer and Commercialization . Vanderbilt researchers who contributed to research around NMRA-266 and the power of academic drug discovery include Darren W. Engers , Aaron Bender ,  Olivier Boutaud ,  Thomas Bridges , Julie Engers ,  Alison Gregro , Carrie Jones ,  Colleen Niswender ,  Jerri Rook and Kayla Temple .  

Keep Reading

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Warren Center for Neuroscience Drug Discovery added to Discovery Vanderbilt portfolio; philanthropic matching launched

Vanderbilt scientists make headway in drug development to cure pulmonary arterial hypertension

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Researchers Map the Genetic Landscape of Schizophrenia in the Brain

November 29, 2022 • Research Highlight

Genes are known to play a key role in the risk for schizophrenia, but that genetic contribution is complex. A better understanding of the different genetic factors that contribute to the disorder and how they interact and combine to influence risk could improve treatments for schizophrenia. In an innovative study funded in part by the National Institute of Mental Health, researchers aimed to map the genetic landscape of schizophrenia in the brain. The study sheds light on biological risk factors that may play a role in schizophrenia and suggests potential therapeutic targets.

A multidisciplinary team led by Kynon Jade Benjamin, Ph.D.   , Apuã Paquola, Ph.D.   , Jennifer Erwin, Ph.D.   , and Daniel Weinberger, M.D.   , at the Lieber Institute for Brain Development and the Johns Hopkins University School of Medicine conducted a comprehensive analysis of gene activity in a specific region deep in the brain — the caudate nucleus   . To date, there are no large-scale genetic analyses of the caudate nucleus, despite evidence that it is involved in schizophrenia and a key target of antipsychotic medications used to treat the disorder.

For this study, the research team analyzed postmortem tissue samples from 443 donors, which included adults who had either a schizophrenia or bipolar diagnosis and healthy controls with no known history of mental illnesses. The donors reflected a diverse mix of ancestries.

The researchers performed a comprehensive genetic and transcriptional analysis of the caudate nucleus. To do so, they identified candidate risk genes, gene features, and gene networks associated with schizophrenia and examined how changes in the DNA code translated into changes in the expression of RNA (the instructions copied from DNA and used to create cellular products such as proteins). Moreover, they examined whether a common environmental factor—the use of antipsychotics—influenced the changes in gene expression seen in the brains of people who had schizophrenia. This information was compared with other data, including gene expression in different brain regions and previous genetic risk factors.

This study represents a significant step forward in understanding risk factors for schizophrenia. The analyses showed altered expression in 2,700 genes in the caudate nucleus of people who had schizophrenia—several times more than the number of genes found in previous studies focusing on other brain regions. These included both genes identified in prior studies and new genes linked to schizophrenia for the first time.

To examine the effects of antipsychotics, caudate samples from people with schizophrenia were divided into those with and without exposure to the medication at the time of death. Antipsychotics had an extensive influence on caudate gene expression: 2,692 genes were differentially expressed between people on antipsychotics and controls, as compared to 665 differentially expressed genes between people without antipsychotics and controls. It should be noted that the genes with altered expression in people on antipsychotics overlapped largely with the genes associated with schizophrenia overall, making it difficult to disentangle the effects of antipsychotics from the effects of schizophrenia in general.

In-depth methods for analyzing gene expression data also revealed a role of the dopamine receptor gene, DRD2 , in the genetic risk for schizophrenia. DRD2 is essential for regulating levels of dopamine (a chemical involved in communication between cells) in the brain. The researchers found decreased expression of a form of the receptor that regulates dopamine production and release in the caudate nucleus of people who had schizophrenia, which can lead to elevated dopamine levels. Although excessive dopamine is known to contribute to schizophrenia symptoms, this study is the first to identify a potential causal mechanism—reduced expression of a specific receptor—resulting in diminished control over dopamine activity. This novel finding of a link between a common genetic risk variant and activity of the dopaminergic system highlights a target for further investigation in treating schizophrenia.

Last, the researchers developed a new method for mapping gene networks that allowed them to plot connections between multiple genes with related biological functions that together may influence the risk for schizophrenia. They identified the largest gene expression changes in a network of genes involved in the development of neurons and signaling between neurons. Neurons are basic units of the brain that transmit information between the brain and other parts of the body. This finding suggests that schizophrenia or associated factors, such as medication use, may cause cellular-level changes in the structure and function of the brain. In turn, these biological changes may translate into downstream changes in cognition or behavior that emerge as symptoms of schizophrenia.

By employing a new method for mapping biological networks using gene expression data, the researchers identified “neighborhoods” of interconnected genes in the caudate nucleus. Understanding connections between genes in these networks is critical for developing treatments that target not only one but multiple genes that work together to increase risk. It can also shed light on the broader effects of treatments intended to target a single gene.

Benjamin, K. J. M., Chen, Q., Jaffe, A. E., Stolz, J. M., Collado-Torres, L., Huuki-Myers, L. A., Burke, E. E., Arora, R., Feltrin, A. S., Barbosa, A. R., Radulescu, E., Pergola, G., Shin, J. H., Ulrich, W. S., Deep-Soboslay, A., Tao, R., the BrainSeq Consortium, Hyde, T. M., Kleinman, J. E., … Paquola, A. C. M. Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes. Nature Neuroscience . https://doi.org/10.1038/s41593-022-01182-7  

MH015330  , MH123183 

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Research articles

Visualizing threat and trustworthiness prior beliefs in face perception in high versus low paranoia

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Association of homocysteine with white matter dysconnectivity in schizophrenia

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Polygenic effects on brain functional endophenotype for deficit and non-deficit schizophrenia

• Xiangrong Zhang

Are the results of open randomised controlled trials comparing antipsychotic drugs in schizophrenia biased? Exploratory meta- and subgroup analysis

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