Posts tagged schizophrenia

7 August 2012

New NeuRA research shows that the brains of people with schizophrenia may attempt to repair damage caused by the disease, in another example of the adult brain’s capacity to change and grow.

Prof Cyndi Shannon Weickert, Dr Dipesh Joshi and colleagues from Neuroscience Research Australia studied the brains of people with schizophrenia and focussed on one of the hardest-hit regions, the orbitofrontal cortex, which is the part of the brain involved in regulating emotional and social behaviour.

Most neurons – brain cells that transmit information – are found in tissue near the surface of the brain. However, in the brains of people with schizophrenia, the team found a high density of neurons in deeper areas.

“For over a decade we’ve known about the high density of neurons in deeper brain tissue in people with schizophrenia. Researchers thought these neurons were simply forgotten by the brain, and somehow didn’t die off like they do during development in healthy people,” says Prof Shannon Weickert.

“What we now have is evidence that suggests these neurons are derived from the part of the brain that produces new neurons, and that they may be in the process of moving. We can’t be sure where they are moving to, but given their location it is likely they are on their way to the surface of the brain, the area most affected by schizophrenia,” Prof Shannon Weickert concluded.

ScienceDaily (July 17, 2012) — Johns Hopkins researchers say they have discovered a cause-and-effect relationship between two well-established biological risk factors for schizophrenia previously believed to be independent of one another.

The findings could eventually lead researchers to develop better drugs to treat the cognitive dysfunction associated with schizophrenia and possibly other mental illnesses.

Researchers have long studied the role played in the brain’s neurons by the Disrupted-in-Schizophrenia 1 (DISC1) gene, a mutation with one of the strongest links to an increased risk of developing the debilitating psychiatric illness.

In a study published in the journal Molecular Psychiatry, the laboratory of Mikhail V. Pletnikov, M.D., Ph.D., in collaboration with the laboratory of Solomon H. Snyder, M.D., D.Sc., instead looked at the role the DISC1 gene plays in glia cells known as astrocytes, a kind of support cell in the brain that helps neurons communicate with one another.

"Abnormalities in glia cells could be as important as abnormalities in neuronal cells themselves," says Pletnikov, an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine, and the study’s leader. "Most gene work has been done with neurons. But we also need to understand a lot more about the role that genetic mutations in glia cells play because neuron-glia interaction appears crucial in ensuring the brain operates normally."

Besides the paranoia and hallucinations that characterize the disease, schizophrenics have cognitive deficits, leaving them unable to think clearly or organize their thoughts and behavior.

Previous studies found that one of the roles of astrocytes is to secrete the neurotransmitter D-serine, which helps promote the transmission of glutamate in the brain, believed to be a key to cognitive function. Schizophrenics have decreased glutamate transmission. It appears, Pletnikov says, that people with DISC1 mutations associated with the psychiatric illness are faster to metabolize D-serine, which leads to a decrease in the apparently crucial transmitter.

In clinical trials, other researchers are trying to boost D-serine levels in people with schizophrenia to see if they can boost cognitive function.

In the new study, the Johns Hopkins researchers found that DISC1 is directly involved in regulating the production of D-serine by the enzyme known as serine racemase.

The researchers found that DISC1 normally binds to serine racemase and stabilizes it. The mutant DISC1 in patients with schizophrenia cannot bind with serine racemase, and instead destabilizes and destroys it. The result is a deficiency of D-serine.

The Hopkins researchers bred mice with the mutant DISC1 protein expressed only in astrocytes and, as predicted, the animals had decreased levels of D-serine. These mice also showed abnormal behavior “consistent with schizophrenia,” Pletnikov says. For example, the rodents showed sensitivity to psycho-stimulants that target glutamate transmission. By treating the mice with D-serine, the scientists were able to ameliorate the schizophrenic-like symptoms. Mice without the DISC1 mutation in astrocytes had normal D-serine levels.

Pletnikov says that in the future, researchers hope that they can target the unstable junction between the abnormal DISC1 and serine racemase. If drugs, for example, can be found to increase glutamate transmission in humans, doctors may be able to improve cognitive function in schizophrenics. He says a DISC1 mutation may also be an important risk factor in other psychiatric disorders.

"Abnormal glutamate transmission is believed to be present in patients with bipolar disorder, major depression and possibly anxiety disorders, so our findings could apply to other psychiatric diseases," he says.

Source: Science Daily

FRIDAY, July 13 (HealthDay News) — Movies often stereotype people with schizophrenia as being violent and unpredictable, says a researcher who claims Hollywood dispenses misinformation about symptoms, causes and treatment of this mental illness.

Hollywood portrayals are often inaccurate, misleading, study shows.

For the study, published in the July issue of Psychiatric Services, Patricia Owen of the psychology department at St. Mary’s University in San Antonio, Texas, reviewed 41 English-language films released between 1990 and 2010 that featured at least one main character with schizophrenia.

Owen found that 83 percent of those characters were portrayed as dangerous or violent to others or themselves. Almost one-third engaged in homicidal behavior, and one-quarter committed suicide, the researcher said.

According to the U.S. National Institute of Mental Health, the risk of violence is small among people with schizophrenia. But suicide risk is higher than average. About 10 percent, mostly young men, do kill themselves, the agency notes.

Delusions, auditory and visual hallucinations, and disorganized speech or thought were displayed by most of the characters, the study author pointed out in a news release from the American Psychiatric Association.

But much more common symptoms of schizophrenia — such as flat affect, lack of speech and lack of motivation — were seen much less frequently.

Although schizophrenia incidence is nearly equal among women and men, almost 80 percent of the characters with schizophrenia were male, the study found.

The review noted, however, the movies did get some characterizations of schizophrenia right. Specifically, about half of the characters had low socioeconomic status, which is consistent with data on the illness. Moreover, about half of the movies depicted or alluded to the use of medication to treat the mental illness. Psychotherapy and group therapy were not portrayed often.

Owen suggested that more research is needed to understand how films influence public perceptions about schizophrenia, and to determine how to increase empathy and understanding.

Films featuring a character with schizophrenia include A Beautiful Mind and Donnie Darko.

Source: DoctorsLounge

ScienceDaily (July 11, 2012) — In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.

"A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes," said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. "Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences."

Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.

"Schizophrenia is among the most severe and disabling conditions across all categories of medicine," said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.

The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.

Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.

"But even the best clinicians struggle with diagnostic complexities based on sometimes fuzzy clinical phenomenology," said Light. The clinical challenge is compounded by the fact that "many schizophrenia patients have cognitive and functional impairments," said Light. They may not be able to reasonably explain how or what they think.

Light and colleagues investigated whether a select battery of neurophysiological and neurocognitive biomarkers could provide clinicians with reliable, accurate, long-term indicators of brain dysfunction, even when overt symptoms of the disorder were not apparent. These markers ranged from tests of attention and memory to physiological assessments of basic perceptual processes using scalp sensors to measure brain responses to simple sounds.

The researchers measured the biomarkers in 550 schizophrenia patients, and then re-tested 200 of the patients one year later. They found that most of the markers were significantly abnormal in schizophrenia patients, were relatively stable between the assessments and were not affected by modest fluctuations in clinical status of the patient.

Light said further research is required, including whether the endophenotypes can differentiate other psychiatric disorders, be used to anticipate patient response to different kinds of drugs or non-pharmacological interventions or even be used to predict which subjects are at high risk of developing a psychotic illness.

"We believe this paper is an important step towards validating laboratory-based biomarkers for use in future genomic and clinical treatment studies of schizophrenia," Light said.

Source: Science Daily

May 11th, 2012

Babies born to women with sensitivity to gluten appear to be at increased risk for certain psychiatric disorders later in life, according to research by scientists at Karolinska Institutet in Sweden and Johns Hopkins Children’s Center in Baltimore.

The team’s findings, published in The American Journal of Psychiatry, add to a growing body of evidence that many “adult” diseases may take root before and shortly after birth.

“Lifestyle and genes are not the only factors that shape disease risk, and factors and exposures before, during and after birth can help pre-program much of our adult health,” said investigator Robert Yolken, M.D., a neuro-virologist at Johns Hopkins Children’s Center. “Our study is an illustrative example suggesting that a dietary sensitivity before birth could be a catalyst in the development of schizophrenia or a similar condition 25 years later.”

Maternal infections and other inflammatory disorders during pregnancy have long been linked to greater risk for schizophrenia in the offspring but, the Swedish and U.S. investigators say, this is the first study that points to maternal food sensitivity as a possible culprit in the development of such disorders. The findings establish a strong link but do not mean that gluten sensitivity will invariably cause schizophrenia, the investigators caution. The research, however, does suggest an intriguing new mechanism that may drive up risk and illuminate possible prevention strategies.

“Our research not only underscores the importance of maternal nutrition during pregnancy and its lifelong effects on the offspring, but also suggests one potential cheap and easy way to reduce risk if we were to find further proof that gluten sensitivity exacerbates or drives up schizophrenia risk,” said study lead investigator Håkan Karlsson, M.D., Ph.D., a neuroscientist at Karolinska Institutet and former neuro-virology fellow at Johns Hopkins.

The team’s findings are based on an examination of 764 birth records and neonatal blood samples of Swedes born between 1975 and 1985. Some 211 of them subsequently developed non-affective psychoses, such as schizophrenia and delusional disorders.

Using stored neonatal blood samples, the investigators measured levels of IgG antibodies to milk and wheat. IgG antibodies are markers of immune system reaction triggered by the presence of certain proteins. Because a mother’s antibodies cross the placenta during pregnancy to confer immunity to the baby, a newborn’s elevated IgG levels are proof of protein sensitivity in the mother.

Children born to mothers with abnormally high levels of antibodies to the wheat protein gluten had nearly twice the risk of developing schizophrenia later in life, compared with children who had normal levels of gluten antibodies. The link persisted even after researchers accounted for other factors known to increase schizophrenia risk, including maternal age, gestational age, mode of delivery and the mother’s immigration status. The risk for psychiatric disorders was not increased among those with elevated levels of antibodies to milk protein.

The researchers say the suspicion that food sensitivity in the mother can affect her child’s risk for psychiatric disorders stems from an observation made in the wake of the World War II by U.S. Army researcher F. Curtis Dohan, M.D. Dohan noted that food scarcity in post-war Europe and wheat-poor diets led to notably fewer hospital admissions for schizophrenia.  The link was merely observational, but it has piqued the curiosity of scientists ever since.

Researchers in the past also have observed that people diagnosed with schizophrenia have disproportionately high rates celiac disease, a rare autoimmune disorder characterized by gluten sensitivity. Although it is a hallmark of the condition, gluten sensitivity alone is not enough to diagnose celiac disease. Other studies have found that some people with schizophrenia have gluten sensitivity without other signs of celiac disease, the researchers note.

Yolken and Karlsson say the team already is conducting follow-up studies to clarify how gluten or sensitivity to it increases schizophrenia risk and whether it does so only in those genetically predisposed.

Source: Neuroscience News

ScienceDaily (May 8, 2012) — New research from the Royal College of Surgeons in Ireland (RCSI) published in Nature’s Neuropsychopharmacology has shown physical changes to exist in specific brain areas implicated in schizophrenia following the use of cannabis during adolescence. The research has shown how cannabis use during adolescence can interact with a gene, called the COMT gene, to cause physical changes in the brain.

The COMT gene provides instructions for making enzymes which breakdown a specific chemical messenger called dopamine. Dopamine is a neurotransmitter that helps conduct signals from one nerve cell to another, particularly in the brains reward and pleasure centres. Adolescent cannabis use and its interaction with particular forms of the COMT gene have been shown to cause physical changes in the brain as well as increasing the risk of developing schizophrenia.

Dr Áine Behan, Department of Physiology, RCSI and lead author on the study said ‘This is the first study to show that the combined effects of the COMT gene with adolescent cannabis use cause physical changes in the brain regions associated with schizophrenia. It demonstrates how genetic, developmental and environmental factors interact to modulate brain function in schizophrenia and supports previous behavioural research which has shown the COMT gene to influence the effects of adolescent cannabis use on schizophrenia-related behaviours.

The three areas of the brain assessed in this study were found to show changes in cell size, density and protein levels.

'Increased knowledge on the effects of cannabis on the brain is critical to understanding youth mental health both in terms of psychological and psychiatric well-being,' Dr Behan continued.

Source: Science Daily