 |
|
Interaction between gene variants may alter brain function in schizophrenia
November 10, 2008Imaging study is 1 of the first to analyze influence of multiple genes
A collaborative study led by investigators from Massachusetts General Hospital (MGH) is giving what may be the first look at how interactions between genes underlie a key symptom of schizophrenia, impaired working memory. Functional imaging studies reveal how a combination of common variants in two genes is associated with reduced activity of important brain structures in schizophrenia patients but not in normal controls. The report has been released online in the Early Edition of the Proceedings of the National Academy of Sciences.
"Schizophrenia is a highly genetic disorder, but we are learning that its genetics are not straightforward. In most cases potential risk genes appear to have very small effects on symptoms, making it difficult to attribute clinical findings to particular genes," says Joshua Roffman, MD, of the MGH Department of Psychiatry, the study's lead author. "To amplify some of these subtle effects, we and others are looking how the genes affect brain function, rather than just behavior."
The team - which included investigators from the University of New Mexico, University of Iowa and University of Minnesota through the MIND Clinical Imaging Consortium - used functional MRI to scan an area of the prefrontal cortex known to be critical to working memory in 79 schizophrenia patients and 75 healthy controls as they completed a memory task. Levels of cortical activity were then analyzed for any association with common variants in two genes: MTHFR, which regulates folate metabolism and has been associated with schizophrenia risk, and COMT, which is involved with dopamine processing during working memory.
Although the schizophrenia-associated variant of MTHFR was found in both patients and controls, when the working memory task become more difficult, weaker cortical function associated with that variant was seen only in the schizophrenia patients, not in controls. While variations in COMT did not influence cortical activation patterns on their own, the combined effects of both genes did make a difference. The reduction in cortical function seen in patients with the schizophrenia-associated MTHFR variant was even more pronounced in patients who also had a COMT variant previously associated with less efficient working-memory-related brain activity.
"Based on the known effects of these alleles on brain biochemistry, it is likely that our results reflect cumulative impacts of the gene variants on dopamine signaling, particularly in the prefrontal cortex. These findings may help us to identify patients more likely to benefit from new treatments targeting the dopamine and folate systems," Roffman says. "We are hopeful that this approach will catalyze the development of individualized treatment regimens, since it will allow us to examine the effects of treatment-related genes on brain function using a much smaller groups of study participants."
Massachusetts General Hospital
The team - which included investigators from the University of New Mexico, University of Iowa and University of Minnesota through the MIND Clinical Imaging Consortium - used functional MRI to scan an area of the prefrontal cortex known to be critical to working memory in 79 schizophrenia patients and 75 healthy controls as they completed a memory task. Levels of cortical activity were then analyzed for any association with common variants in two genes: MTHFR, which regulates folate metabolism and has been associated with schizophrenia risk, and COMT, which is involved with dopamine processing during working memory.
Although the schizophrenia-associated variant of MTHFR was found in both patients and controls, when the working memory task become more difficult, weaker cortical function associated with that variant was seen only in the schizophrenia patients, not in controls. While variations in COMT did not influence cortical activation patterns on their own, the combined effects of both genes did make a difference. The reduction in cortical function seen in patients with the schizophrenia-associated MTHFR variant was even more pronounced in patients who also had a COMT variant previously associated with less efficient working-memory-related brain activity.
"Based on the known effects of these alleles on brain biochemistry, it is likely that our results reflect cumulative impacts of the gene variants on dopamine signaling, particularly in the prefrontal cortex. These findings may help us to identify patients more likely to benefit from new treatments targeting the dopamine and folate systems," Roffman says. "We are hopeful that this approach will catalyze the development of individualized treatment regimens, since it will allow us to examine the effects of treatment-related genes on brain function using a much smaller groups of study participants."
Massachusetts General Hospital
Schizophrenia Current Events and Schizophrenia News RSSSchizophrenia gene's role may be broader, more potent, than thought
UCSF scientists studying nerve cells in fruit flies have uncovered a new function for a gene whose human equivalent may play a critical role in schizophrenia.
Full recovery now possible for an 'untreatable' mental illness
Patients coping with the chaos and misery of Borderline Personality Disorder now have reason for strong confidence in making major life changes through a new treatment, Schema Therapy.
Immune system activated in schizophrenia
Researchers at the Swedish medical university Karolinska Institutet have discovered that patients with recent-onset schizophrenia have higher levels of inflammatory substances in their brains. Their findings offer hope of being able to treat schizophrenia with drugs that affect the immune system.
Why can't chimps speak?
If humans are genetically related to chimps, why did our brains develop the innate ability for language and speech while theirs did not?
Developmental delay could stem from nicotinic receptor deletion
The loss of a gene through deletion of genetic material on chromosome 15 is associated with significant abnormalities in learning and behavior, said a consortium of researchers led by Baylor College of Medicine (www.bcm.edu) in a report that appears online today in the journal Nature Genetics.
Fighting Sleep, Penn Researchers Reverse the Cognitive Impairment Caused By Sleep Deprivation
A research collaboration led by biologists and neuroscientists at the University of Pennsylvania has found a molecular pathway in the brain that is the cause of cognitive impairment due to sleep deprivation.
Testicular tumors may explain why some diseases are more common in children of older fathers
A rare form of testicular tumour has provided scientists with new insights into how genetic changes (mutations) arise in our children.
CSHL-led team discovers rare mutation dramatically increasing schizophrenia risk
An international team of researchers led by geneticist Jonathan Sebat, Ph.D., of Cold Spring Harbor Laboratory (CSHL), has identified a mutation on human chromosome 16 that substantially increases risk for schizophrenia.
Faulty 'wiring' in the brain triggers onset of schizophrenia
A new study by researchers at the Institute of Psychiatry (IoP), King's College London has discovered abnormalities in the white matter of the brain that seem to be critical for the timing of schizophrenia.
General anesthetics lead to learning disabilities in animal models
Studies by researchers at Wake Forest University School of Medicine have shown that blocking the NMDA receptor in immature rats leads to profound, rapid brain injury and disruption of auditory function as the animals mature.
More Schizophrenia Current Events and Schizophrenia News Articles
 |
Surviving Schizophrenia: A Manual for Families, Patients, and Providers by E. Fuller Torrey (Author) Since its first publication in 1983, Surviving Schizophrenia has become the standard reference book on the disease and has helped thousands of patients, their families and mental health professionals. In clear language, this much–praised and important book describes the nature, causes, symptoms, treatment and course of schizophrenia and also explores living with it from both the patient and the family's point of view. This new, completely updated fifth edition includes the latest research findings on what causes the disease as well as information about the newest drugs for treatment and answers to the questions most often asked by families, consumers and providers. |
 |
Schizophrenia Revealed: From Neurons to Social Interactions by Michael Foster Green (Author) A modern view of schizophrenia based on neuroscience that goes far beyond the symptoms of the illness. "Green has lifted the bar in this realm of explanatory neuroscience-based psychiatry. If you wish to read an enjoyable and instructive primer on what we know about schizophrenia at the beginning of the 21st century, you could do no better than to choose Schizophrenia Revealed." —New England Journal of Medicine |
 |
The Quiet Room: A Journey Out of the Torment of Madness by Lori Schiller (Author), Amanda Bennett (Author) Schiller's gripping, heart-rending and ultimately triumphant story of her journey into madness and back to reality is told through the voices of Lori and her family, friends and doctor, and captures a rare, astoundingly vivid view into the inner life of a schizophrenic. "A stunning story of courage, persistence, and hope."--Publishers Weekly. |
 |
ABC News 20/20 Schizophrenia It's all in their minds: visions, voices, taunting, never ending, driving them crazy or worse. It's hard to imagine, but now, an amazing device lets you feel their pain. The technology lets you go inside the mind of a schizophrenic. See what they see. Hear what they hear. Using the technique of virtual reality, Janssen Pharmaceuticals has developed a device to stimulate the visual and auditory hallucinations of a schizophrenic patient. Dr. Timothy Johnson explores the world of people struggling with the voices within. This "20/20" show contains the following additional stories: Victim's Comp Windsheilds |
 |
The Complete Family Guide to Schizophrenia: Helping Your Loved One Get the Most Out of Life by Kim T. Mueser PhD (Author), Susan Gingerich MSW (Author) Will the person you love ever get better? Chances are you've grappled with the question. With care and support from their families, people with schizophrenia can and do make vast improvements. Noted therapists Kim Mueser and Susan Gingerich deepen your understanding of the illness and cover a wide range of effective treatments. Based on decades of research and experience, they offer pragmatic suggestions for dealing with depression, psychosis, and other symptoms. They show you how to prioritize needs, resolve everyday problems, and encourage your loved one to set life goals. Plus, individual sections highlight special issues for parents, children, siblings, and partners. Whether you’re facing schizophrenia for the first time or you’ve dealt with its impact for years, you’ll discover... |
 |
Me, Myself, and Them: A Firsthand Account of One Young Person's Experience with Schizophrenia (Adolescent Mental Health Initiative) by Kurt Snyder (Author), Raquel E. Gur M.D. (Author), Linda Wasmer Andrews (Author) During his second semester at college, Kurt Snyder became convinced that he was about to discover a fabulously important mathematical principle, spending hours lost in daydreams about numbers and symbols. In time, his thoughts took a darker turn, and he became preoccupied with the idea that cars were following him, or that strangers wanted to harm him. Kurt's mind had been hijacked by schizophrenia, a severe mental disorder that typically strikes during the late teen or young adult years. In Me, Myself, and Them, Kurt, now an adult, looks back from the vantage point of recovery and eloquently describes the debilitating changes in thoughts and perceptions that took hold of his life during his teens and twenties. As a memoir, this book is remarkable for its unvarnished look at the... |
 |
Recovered, Not Cured: A Journey Through Schizophrenia by Richard McLean (Author) This very personal exploration of schizophrenia explores each stage, from the early signs and reactions from friends and family to seeking help and the challenges of recovery. McLean bravely shares his paranoid delusions and offers both a verbal and a visual experience by including digital artwork he created to help objectify and control his impulses and fears. As McLean relates his experiences step by step, issues of sexuality, identity, and drug abuse are discussed, along with the overarching issues relating to mental health and the medical profession. Messages from online posters who either have suffered from mental illness or have cared for the mentally ill are included throughout, adding more perspectives to the author's personal experiences. This powerful combination of words and... |
 |
Getting Your Life Back Together When You Have Schizophrenia by Roberta Temes (Author) |
 |
Understanding Mental Illness and Schizophrenia (Home Use) Part of the award winning public television series Healthy Body/Healthy Mind. Mental Illnesses are complex diseases of the brain affecting thoughts, moods, and coping ability. There are many diseases you can see, feel and understand, but there are others that aren't as easy to comprehend. Education and compassion are key. Untreated mental illness costs Americans more than 100 billion dollars each year. Fear of Mental Illness and the lack of understanding prevent millions of people from seeking much needed treatment. Meet some of these people in this program. This product is manufactured on demand using DVD-R recordable media. Amazon.com's standard return policy will apply. |
 |
Schizophrenia For Dummies (For Dummies (Health & Fitness)) by Jerome Levine (Author), Irene S. Levine (Author) Practical tools for leading a happy, productive life Schizophrenia is a chronic, severe, and disabling mental disorder that afflicts one percent of the population, an estimated 2.5 million people in America alone. The firsthand advice in this reassuring guide will empower the families and caregivers of schizophrenia patients to take charge, offering expert advice on identifying the warning signs, choosing the right health professional, understanding currently available drugs and those on the horizon (as well as their side effects), and evaluating traditional and alternative therapies. |
| © 2009 BrightSurf.com |