Delusions in Schizophrenia Linked to Abnormal Midbrain Activation to Neutral Stimuli

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Patients with schizophrenia exhibit impaired activation of the midbrain when shown neutral stimuli during aversive conditioning, according to a small functional magnetic resonance imaging (fMRI) study.

The abnormal activation of this region, which is responsible for associative learning, appeared to be linked to the severity of the patients’ delusional symptoms, report the researchers.

“We found that the patients with schizophrenia, and especially the ones who had the most delusional symptoms, showed responses in the parts of the brain that normally tell you what’s important when they shouldn’t have done, such as in a neutral phase. And that was in line with our expectations,” study coauthor Jeremy Hall, PhD, MRCPsych, senior research fellow in psychiatry in the Division of Psychiatry at the University of Edinburgh and the Royal Edinburgh Hospital in Scotland, told Medscape Medical News.

Reported by Deborah Brauser
Medscape Today
http://www.medscape.com/viewarticle/734630
Reference: Arch Gen Psychiatry. 2010;67:1246-1254.

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Scans could predict onset of schizophrenia

Brain scans could be used to predict the onset of schizophrenia in young people with a family history of the disease, a new study suggests.

An Edinburgh University study has shown people who later develop schizophrenia suffer from an accelerated brain shrinking before they become unwell.

Schizophrenia is a condition involving delusions and hallucinations.

It is associated with a reduction in brain tissue but the timing of these changes has, until now, been unclear.

Schizophrenia affects one in every 100 people.

The study examined people at high risk of schizophrenia who had two close relatives with the disorder and were between 16 and 25 at the beginning of the research.

This is the first time such changes in the brain size have been found in people at high risk of schizophrenia before they develop any symptoms.

Unlike previous studies, the changes cannot be due to medication as all of the people in the study were un-medicated when they took part.

In healthy people, the brain begins to shrink from early adulthood onwards.

Medical treatment

It is known that accelerated brain shrinkage occurs in people with bipolar disorder, or manic-depression, and schizophrenia, but until now it was not known whether these changes occurred before people became unwell.

Researchers said scans could be used to identify shrinkage of the brain in people at high risk of schizophrenia and may help doctors to diagnose the condition and start treatment at an earlier stage or even before illness first appears.

The study, published in the journal Biological Psychiatry, shows the loss of brain tissue is concentrated in areas of the brain that control personality, decision making and social behaviour.

Dr. Andrew McIntosh, at Edinburgh University’s division of psychiatry, said: “This study represents the culmination of more than 10 years of work and is a significant step to understanding the origins of schizophrenia years before the onset of disability and medical treatment.”

The team analysed brain scans of 146 people with a family history of schizophrenia but who had not yet experienced any symptoms and compared them with scans of 36 people with no such risk.

The scans were taken every 18 months over a 10 year period.

BBC News
http://www.bbc.co.uk/news/uk-scotland-edinburgh-east-fife-12059444

Reference: Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis. McIntosh AM, Owens DC, Moorhead WJ, Whalley HC, Stanfield AC, Hall J, Johnstone EC, Lawrie SM. Biol Psychiatry. 2010 Dec 16. [Epub ahead of print] PMID: 21168123 [PubMed – as supplied by publisher]

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Genetic Factors for Neuropsychiatric Disorders Influence Brain Structure

Genetic variants associated with increased risk for neuropsychiatric disorders are associated with altered brain structure in apparently healthy individuals who carry these variants, according to a new study by Dutch researchers. Their finding raises the potential for using brain structure as an “intermediate phenotype” in identifying risk genes associated with neuropsychiatric disorders.

Barbara Franke, PhD, associate professor of molecular psychiatry, Department of Human Genetics and Department of Psychiatry, Institute for Genetic & Metabolic Diseases, Radboud University Nijmegen Medical Center, the Netherlands, presented the study findings here at American Society of Human Genetics 60th Annual Meeting.

Altered regional brain structure is often seen in patients who have neuropsychiatric disorders, although the relation between brain structure and pathology is poorly understood. “There are basically 2 scenarios: the alterations that we see mediate the increased risk for mental disorders; and the alterations are epiphenomena and, although they co-occur with disease susceptibility, they do not contribute to them,” said Dr. Franke via email to Medscape Medical News after her presentation.

“The fact that we find brain structure alterations for so many psychiatric risk genes suggests that [the first option] is more likely, and [the alterations] are part of disease etiology,” Dr. Franke observed…..

Jacquelyn K. Beals, PhD
Medscape Medical News
http://www.medscape.com/viewarticle/732207

American Society of Human Genetics (ASHG) 60th Annual Meeting: Abstract 77. Presented November 3, 2010.

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Scientists Discover How Estrogen Works and Flip Its Switch to Reap Benefits Without Risks

Estrogen is an elixir for the brain, sharpening mental performance in humans and animals and showing promise as a treatment for disorders of the brain such as Alzheimer’s disease and schizophrenia. But long-term estrogen therapy, once prescribed routinely for menopausal women, now is quite controversial because of research showing it increases the risk of cancer, heart disease and stroke.

Northwestern Medicine researchers have discovered how to reap the benefits of estrogen without the risk. Using a special compound, they flipped a switch that mimics the effect of estrogen on cortical brain cells. The scientists also found how estrogen physically works in brain cells to boost mental performance, which had not been known.

When scientists flipped the switch, technically known as activating an estrogen receptor, they witnessed a dramatic increase in the number of connections between brains cells, or neurons. Those connections, called dendritic spines, are tiny bridges that enable the brain cells to talk to each other…..

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.
http://www.sciencedaily.com/releases/2010/11/101117161246.htm

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Differences in Brain Development Between Males and Females May Hold Clues to Mental Health Disorders

Many mental health disorders, such as autism and schizophrenia, produce changes in social behavior or interactions. The frequency and/or severity of these disorders is substantially greater in boys than girls, but the biological basis for this difference between the two sexes is unknown.

Researchers at the University of Maryland School of Medicine have discovered differences in the development of the amygdala region of the brain — which is critical to the expression of emotional and social behaviors — in animal models that may help to explain why some mental health disorders are more prevalent among boys. They also found a surprising variable — a difference between males and females in the level of endocannabinoid, a natural substance in the brain that affected their behavior, specifically how they played…..

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Maryland Medical Center, via EurekAlert!, a service of AAAS.
http://www.sciencedaily.com/releases/2010/11/101117121809.htm

Journal Reference: Desiree L. Krebs-Kraft, Matthew N. Hill, Cecilia J. Hillard, and Margaret M. Mccarthy. Sex difference in cell proliferation in developing rat amygdala mediated by endocannabinoids has implications for social behavior. PNAS, November 8, 2010 DOI: 10.1073/pnas.100500310

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Does Sex Matter? It May When Evaluating Mental Status

Schizophrenia is a mental disorder that differs between the sexes in terms of age at onset, symptomatology, response to medication, and structural brain abnormalities. Now, a new study from the Université de Montréal shows that there is gender difference between men and women’s mental ability — with women performing better than men…..

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Montreal.
http://www.sciencedaily.com/releases/2010/11/101118123840.htm

Journal Reference: José A. Jiménez, Adham Mancini-Marïe, Nadia Lakis, Melissa Rinaldi, Adrianna Mendrek. Disturbed sexual dimorphism of brain activation during mental rotation in schizophrenia. Schizophrenia Research, 2010; 122 (1-3): 53 DOI: 10.1016/j.schres.2010.03.011

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Selective Strategy Could Lead to New Approaches Against Schizophrenia

A new class of compounds identified by researchers at Emory University School of Medicine could be developed into drugs for the treatment of schizophrenia. The compounds enhance signaling by molecules in the brain called NMDA receptors, which scientists believe are functioning at low levels in people with schizophrenia.

Led by Stephen Traynelis, PhD, professor of pharmacology, a team of Emory researchers sifted through thousands of chemicals and found one, called CIQ, which could selectively enhance the function of certain NMDA receptors without affecting others.

The results were published Oct. 5, 2010 by the journal Nature Communications.

The first author of the paper is Praseeda Mullasseril, PhD. The research was a collaboration with Dennis Liotta, PhD, professor of chemistry, and his colleagues.

Doctors now treat schizophrenia with a variety of antipsychotic drugs, but these can have several long-term side effects. The rationale for treating schizophrenia via NMDA receptors comes from the observation that when healthy people take the drugs ketamine or phencyclidine (PCP or angel dust), they temporarily experience the symptoms of schizophrenia, such as hallucinations, disorganized thoughts and flattened emotions.

“There is room for improvement in therapeutic treatment of schizophrenia,” Traynelis says. “Exploration of alternative targets, such as the NMDA receptor, could potentially lead to expanded treatment options and improved outcomes for patients with schizophrenia.”

Ketamine and phencyclidine both interfere with NMDA receptors. This has led scientists to the idea that pushing in the opposite direction chemically — enhancing rather than blocking NMDA receptors — may help relieve schizophrenia’s symptoms……

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Emory University, via EurekAlert!, a service of AAAS.
http://www.sciencedaily.com/releases/2010/10/101012114226.htm

Journal Reference: Praseeda Mullasseril, Kasper B. Hansen, Katie M. Vance, Kevin K. Ogden, Hongjie Yuan, Natalie L. Kurtkaya, Rose Santangelo, Anna G. Orr, Phuong Le, Kimberly M. Vellano, Dennis C. Liotta, Stephen F. Traynelis. A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors. Nature Communications, 2010; 1 (7): 1 DOI: 10.1038/ncomms1085

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Brain Chemical Finding Could Open Door to New Schizophrenia Drugs

New research has linked psychosis with an abnormal relationship between two signalling chemicals in the brain. The findings, published in tomorrow’s edition of the journal Biological Psychiatry, suggest a new approach to preventing psychotic symptoms, which could lead to better drugs for schizophrenia.

Schizophrenia is one of the most common severe mental health conditions. Sufferers experience symptoms of psychosis — an inability to distinguish between reality and imagination — such as hallucinations and delusions. The condition tends to begin in the late teens or twenties, and usually persists for the rest of the sufferer’s life.

Brain chemicals called neurotransmitters carry signals from one nerve cell to another. Research has linked schizophrenia with abnormally high levels of a neurotransmitter called dopamine in a region of the brain called the striatum. Drugs currently used to treat schizophrenia block the effects of dopamine in the brain. These drugs are not effective for all patients, and can have serious side effects.

The new pilot research, funded by the Medical Research Council (MRC), provides evidence that high levels of dopamine in people with psychotic symptoms occur as a consequence of changes in another brain chemical, glutamate. Glutamate-releasing cells in a brain region called the hippocampus connect to the striatum and influence the activity of dopamine-releasing cells. Drugs that interfere with glutamate signals in the brain might therefore be able to prevent psychotic symptoms in people with schizophrenia…..

Reported by ScienceDaily
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Imperial College London, via EurekAlert!, a service of AAAS.
http://www.sciencedaily.com/releases/2010/09/100930101543.htm

Journal Reference: Stone. Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis. Biological Psychiatry, 2010; 68 (7): 599 DOI: 10.1016/j.biopsych.2010.05.034

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New Genetic Risk Factor for Both Autism and Schizophrenia

Researchers have uncovered a prominent genetic risk factor for autism spectrum disorders and schizophrenia. The study, published by Cell Press on Nov. 4 in the American Journal of Human Genetics, reports a small genomic deletion in patients with these neurological conditions. The region includes a gene in which mutations cause a kidney disease (renal cysts and diabetes syndrome, RCAD).

ASDs include a range of neurodevelopmental conditions that are being diagnosed at an increasing rate. The Center for Disease Control and Prevention estimates that ASD currently affects 1 in 110 people. The prevalence of schizophrenia, with a diagnostic rate of 1 in 100 to 1 in 20, is similar. ASD and schizophrenia affect males more often than females, and both are thought to have a strong and overlapping genetic component.

“The genetic overlap between ASD and schizophrenia, both of which have a high heritability, has been the focus of several recent studies; however, no single specific genetic cause accounts for more than 1%-2% of cases,” says Dr. Daniel Moreno-De-Luca, the lead author of the study.

Dr. Moreno-De-Luca and colleagues analyzed genomic DNA from more than 23,000 patients with ASD, developmental delay, or schizophrenia. They were looking for DNA duplications or deletions referred to as copy-number variants (CNV). Remarkably, they found the same deletion on chromosome 17 in 24 separate patients. This CNV was absent in 52,448 controls, making the finding statistically significant…..

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Cell Press, via EurekAlert!, a service of AAAS.

Journal Reference:
1. Daniel Moreno-De-Luca , Jennifer G. Mulle , Erin B. Kaminsky , Stephan J. Sanders , Scott M. Myers , Margaret P. Adam , Amy T. Pakula , Nancy J. Eisenhauer , Kim Uhas , LuAnn Weik , Lisa Guy , Melanie E. Care , Chantal F. Morel , Charlotte Boni , Bonnie Anne Salbert , Ashadeep Chandrareddy , Laurie A. Demmer , Eva W.C. Chow , Urvashi Surti , Swaroop Aradhya , Diane L. Pickering , Denae M. Golden , Warren G. Sanger , Emily Aston , Arthur R. Brothman , Troy J. Gliem , Erik C. Thorland , Todd Ackley , Ram Iyer , Shuwen Huang , John C. Barber , John A. Crolla , Stephen T. Warren , Christa L. Martin and David H. Ledbetter. Deletion 17q12 Is a Recurrent Copy Number Variant that Confers High Risk of Autism and Schizophrenia. American Journal of Human Genetics, 2010; DOI: 10.1016/j.ajhg.2010.10.004

Reported by ScienceDaily (Nov. 5, 2010)
http://www.sciencedaily.com/releases/2010/11/101104154221.htm

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NIH LAUNCHES GENOTYPE-TISSUE EXPRESSION PROJECT—PROJECT TO CHART INFLUENCE OF DNA CHANGES ON GENE FUNCTION IN HUMAN TISSUES AND ORGANS

The National Institutes of Health announced awards to support an initiative to understand how genetic variation may control gene activity and its relationship to disease. Launched as a pilot phase, the Genotype-Tissue Expression (GTEx) project will create a resource researchers can use to study inherited susceptibility to illness and will establish a tissue bank for future biological studies.

http://www.nimh.nih.gov/science-news/2010/nih-launches-genotype-tissue-expression-project.shtml

Submitted by Anna

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