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Schizophrenia linked to dysfunction in molecular brain pathway activated by marijuana
July 08, 2008Alterations in a molecular brain pathway activated by marijuana may contribute to the cognitive symptoms of schizophrenia, according to a report in the July issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
Expression of the cannabinoid 1 receptor (CB1R), the site of action of the main chemical ingredient of marijuana, is significantly reduced in the brains of individuals with schizophrenia. Activation of CB1R impairs signaling by gamma-aminobutyric acid (GABA), an important neurotransmitter essential for core cognitive processes such as working memory. The use of marijuana in individuals with schizophrenia appears to worsen this deficit in GABA synthesis.
Since reduced GABA is known to be present in schizophrenia, these findings suggest possible new drug targets that could help to improve function in people with the mental illness, University of Pittsburgh School of Medicine researchers report.
"Heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia, and the course of illness is worse for people with schizophrenia who use marijuana," said David A. Lewis, M.D., corresponding author of the study and UPMC Endowed Professor in Translational Neuroscience, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. "We wanted to understand the biological mechanisms that could explain these observations, and with this study, I believe that we can narrow down at least part of the 'why' to CB1R, the receptor for both tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and the brains own cannabinoid chemical messengers."
Dr. Lewis and his colleagues examined specimens of brain tissue collected after death from 23 people with schizophrenia and 23 normal comparison subjects matched for a number of factors, including age and sex. The researchers evaluated levels of CB1R messenger RNA and protein, and also measured levels of glutamic acid decarboxylase (GAD-67), an enzyme that makes GABA, and cholecystokinin (CCK), a neuropeptide released from GABA neurons that, among other actions, regulates the production of the brain's own cannabinoids.
"CB1R levels were significantly 15 percent lower in the subjects with schizophrenia," Dr. Lewis said. "We measured these biochemical messengers using three techniques, and each time got the same answer - less CB1R in people with schizophrenia." This reduction, he noted, appears to be the brain's way of compensating for lower levels of GABA, and the use of marijuana defeats this compensation.
"These findings may provide insight into the biological basis of why cannabis use worsens schizophrenia, and, as a result, identify a novel target for new drug development that could improve treatments available for schizophrenia," said Dr. Lewis.
University of Pittsburgh Schools of the Health Sciences
"Heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia, and the course of illness is worse for people with schizophrenia who use marijuana," said David A. Lewis, M.D., corresponding author of the study and UPMC Endowed Professor in Translational Neuroscience, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. "We wanted to understand the biological mechanisms that could explain these observations, and with this study, I believe that we can narrow down at least part of the 'why' to CB1R, the receptor for both tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and the brains own cannabinoid chemical messengers."
Dr. Lewis and his colleagues examined specimens of brain tissue collected after death from 23 people with schizophrenia and 23 normal comparison subjects matched for a number of factors, including age and sex. The researchers evaluated levels of CB1R messenger RNA and protein, and also measured levels of glutamic acid decarboxylase (GAD-67), an enzyme that makes GABA, and cholecystokinin (CCK), a neuropeptide released from GABA neurons that, among other actions, regulates the production of the brain's own cannabinoids.
"CB1R levels were significantly 15 percent lower in the subjects with schizophrenia," Dr. Lewis said. "We measured these biochemical messengers using three techniques, and each time got the same answer - less CB1R in people with schizophrenia." This reduction, he noted, appears to be the brain's way of compensating for lower levels of GABA, and the use of marijuana defeats this compensation.
"These findings may provide insight into the biological basis of why cannabis use worsens schizophrenia, and, as a result, identify a novel target for new drug development that could improve treatments available for schizophrenia," said Dr. Lewis.
University of Pittsburgh Schools of the Health Sciences
Schizophrenia Current Events and Schizophrenia News RSSMentally ill smoke at 4 times the rate of general population, says University of Melbourne study
Australians with mental illness smoke at four times the rate of the general population, says a new study from the University of Melbourne.
Newer antipsychotics no better than older drug in treating child and adolescent schizophrenia
Two newer atypical antipsychotic medications were no more effective than an older conventional antipsychotic in treating child and adolescent schizophrenia and may lead to more metabolic side effects, according to a new study funded by the National Institutes of Health's National Institute of Mental Health (NIMH).
First generation antipsychotic drugs as effective as newer ones in some children
Nearly every child who receives an antipsychotic medicine is first prescribed one of the second-generation, or "atypical" drugs, such as olanzapine and risperidone. However, there has never been evidence that these drugs are more effective than the older, first-generation medications.
Immaturity of the brain may cause schizophrenia
The underdevelopment of a specific region in the brain may lead to schizophrenia in individuals. According to research published today in BioMed Central's open access journal Molecular Brain, dentate gyrus, which is located in the hippocampus in the brain and thought to be responsible for working memory and mood regulation, remained immature in an animal model of schizophrenia.
Aberrations in region of chromosome 1q21.1 associated with broad range of disorders in children
Researchers have discovered a submicroscopic aberration in a particular region of human chromosome 1q21.1 that appears to be associated with a variety of developmental disorders in children.
Protein found that regulates gene critical to dopamine-releasing brain cells
Researchers have identified a protein they say appears to be a primary player in maintaining normal functioning of an important class of neurons - those brain cells that produce, excrete and then reabsorb dopamine neurotransmitters.
New way to help schizophrenia sufferers' social skills
Researchers from the University of Newcastle are investigating a new way to help schizophrenia patients develop their communication and social skills.
Hopkins researchers piece together gene 'network' linked to schizophrenia
Reporting this week in the Archives of General Psychiatry, researchers at the Johns Hopkins University School of Medicine have uncovered for the first time molecular circuitry associated with schizophrenia that links three previously known, yet unrelated proteins.
Risks and benefits of antipsychotics in children and adolescents
Many of the psychiatric disorders observed in adults have their onset in childhood or adolescence. In fact some studies show that at least 20% of children and adolescents will fulfil a diagnostic criterion for a mental disorder before reaching adulthood.
Children of older fathers more likely to have bipolar disorder
Older age among fathers may be associated with an increased risk for bipolar disorder in their offspring, according to a report in the September issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
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