Glutamate: Too much of a good thing in schizophrenia?

October 28, 2008

Is schizophrenia a disorder of glutamate hyperactivity or hypoactivity? While the predominant hypothesis for many years was that schizophrenia was a glutamate deficit disorder, there is growing evidence of glutamate hyperactivity as well. The study by Karlsson et al., appearing in the November 1st issue of Biological Psychiatry, reinforces this point with new data about the impact of deleting the gene for the glutamate transporter EAAT1. EAAT1, implicated in schizophrenia, plays a critical role in inactivating glutamate by removing it from the synaptic and extracellular spaces. The authors demonstrate that these "knockout" animals show increased responses to the NMDA glutamate receptor antagonist, MK-801. This drug causes the release of more glutamate into the synapse in the frontal cortex. This effect of MK-801 is reduced by a group II metabotropic glutamate receptor agonist, which reduces glutamate release. Dr. Andrew Holmes, corresponding author, further discusses their findings, "Our study adds a new twist to [glutamate] research by showing that genetically disrupting a major regulator of glutamate's ability to communicate between nerve cells produces certain 'schizophrenia-like' features in mice and, moreover, that these abnormalities can be corrected by a highly promising new class of glutamate-targeting antipsychotic treatments." In fact, this class of drugs has already shown some preliminary efficacy in its ability to treat individuals suffering from schizophrenia.

John H. Krystal, M.D., Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System, comments: "The NMDA receptor antagonist model and the EAAT1 knockout animal push us to take a fresh look at the obstacles to treating cognitive impairments associated with schizophrenia, in other words, optimizing their cortical network function. This new look can lead us to drugs that would have been completely surprising as recently as 10 years ago, such as the group II metabotropic glutamate receptor agonists."

Dr. Holmes does note that further research is warranted, stating, "What is now needed is more research to get a better handle on how disrupting this gene affects the brain's neural wiring and molecular signaling pathways to produce the symptoms of schizophrenia." This finding could ultimately help scientists develop new or improved treatments for this schizophrenia.

Elsevier

---

---

	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.
	Surviving Schizophrenia: A Memoir by Twynham Press What you are about to read is a true story. I am an apparently normal happily married middle class mother of four, living the humdrum existence of an ordinary housewife. And I have a diagnosis of schizophrenia, something that I have always felt a deep sense of shame and embarrassment about, and kept hidden for many years. I have agonised for many years over whether to make my story public – I have written this book, re-written it, changed the names, changed them back again, written it again under a pseudonym, tried to change it into a novel... Finally, last year on a writing holiday at the wonderful Arvon Centre in Totleigh Barton, Devon, matters became clear. This is my story, and I am ready to stand by it. It is a true story and any value that it has for others lies in...
	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 slow...
	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...
	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...
	Schizophrenia: Causes, Symptoms, Signs, Diagnosis and Treatments - Revised Edition - Illustrated by S. Smith by National Institute of Mental Health (Author), National Institutes of Health (Author), US Department of Health and Human Services (Author), S. Smith (Illustrator) This Schizophrenia Book is the revised version of the popular original version titled "Schizophrenia Causes, Symptoms, Signs, Diagnosis and Treatments", written by the: U.S. Department of Health and Human Services (Author), National Institute of Mental Health (Author), (Author), National Institutes of Health (Author) and S.Smith (Editor) and (Illustrator) This book has been professionally illustrated and edited with a fully hyper-linked table of contents for ease of navigation. A detailed booklet that describes Schizophrenia, symptoms, causes, and treatments, with information on getting help and coping. This booklet is also for family and friends that are looking for further understanding of schizophrenia. You will learn in this Booklet: What is schizophrenia? What are the symptoms of...
	Schizophrenia For Dummies 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.
	Schizophrenia Revealed: From Neurons to Social Interactions by Michael Foster Green (Author) For many years, schizophrenia was considered to be a deep and profound mystery. It was generally viewed as unknown and unknowable—beyond the reach of science.In the past ten years, major developments in scientific research have drastically changed the way schizophrenia is viewed. Neuroscience, in particular, has enabled researchers to frame different questions when investigating this illness and we are now coming to a deeper understanding of it. In this much-needed book, Michael Green, an expert in the neurocognition of schizophrenia, presents an integrated overview of schizophrenia covering a wide range of topics in lively, understandable prose. He outlines a neurodevelopmental model of schizophrenia, discusses neurocognitive indicators of genetic vulnerability, the...
	Schizophrenia by Daniel R. Weinberger (Editor), Paul Harrison (Editor) Schizophrenia is one of the most complex and disabling diseases to affect mankind.   Relatively little is known about its nature and its origins, and available treatments are inadequate for most patients. As a result, there are inevitable controversies about what causes it, how to diagnose it, and how best to treat it.   However, in the past decade, there has been an explosion of new research, with dramatic discoveries involving genetic etiology and epidemiological risk factors.  There has also been a catalog of new drugs coming to market, and controversy about the relative advantages and disadvantages of newer compared with older therapies.   In addition, developing technologies in genomics, molecular biology and neuroimaging provide streams of new information.This book represents a...
	Cognitive Therapy of Schizophrenia (Guides to Individualized Evidence-Based Treatment) by David G. Kingdon MD (Author), Douglas Turkington MD (Author) Drawing on the authors' decades of influential work in the field, this highly practical volume presents an evidence-based cognitive therapy approach for clients with schizophrenia. Guidelines are provided for collaborative assessment and case formulation that enable the clinician to build a strong therapeutic relationship, establish reasonable goals, and tailor treatment to each client's needs. Described in thorough, step-by-step detail are effective techniques for working with delusional beliefs, voices, visions, thought disorders, and negative symptoms; integrating cognitive therapy with other forms of treatment; reducing relapse risks; and enhancing client motivation. Special features include reproducible client handouts and assessment...