Brain displays an intrinsic mechanism for fighting infection

Dec. 10, 2012 — White blood cells have long reigned as the heroes of the immune system. When an infection strikes, the cells, produced in bone marrow, race through the blood to fight off the pathogen. But new research is emerging that individual organs can also play a role in immune system defense, essentially being their own hero. In a study examining a rare and deadly brain infection, scientists at The Rockefeller University have found that the brain cells of healthy people likely produce their own immune system molecules, demonstrating an "intrinsic immunity" that is crucial for stopping an infection.

Shen-Ying Zhang, a clinical scholar in the St. Giles Laboratory of Human Genetics of Infectious Diseases, has been studying children with Herpes simplex encephalitis, a life-threatening brain infection from the herpes virus, HSV-1, that can cause significant brain damage. The scientists already knew from previous work that children with this encephalitis have a genetic defect that impairs the function of an immune system receptor -- toll-like receptor 3 (TLR3) -- in the brain. For this study they wanted to see how the defect in TLR3 was hampering the brain's ability to fight the herpes infection.

When TLR3 detects a pathogen it triggers an immune response causing the release of proteins called interferons to sound the alarm and "interfere" with the pathogen's replication. It's most commonly associated with white blood cells, found throughout the body, but here the researchers were examining the receptor's presence on neurons and other brain cells.

"One interesting thing about these patients is that they didn't have any of the other, more common herpes symptoms. They didn't have an infection on their skin or their mouths, just in their brains. We therefore hypothesized that the TLR3 response must be specifically responsible for keeping the herpes virus from infecting the brain and not necessary in other parts of the body," says Zhang.

The lab, headed by Jean-Laurent Casanova, collaborated with scientists at Harvard Medical School and Memorial Sloan-Kettering Cancer Institute to create induced pluripotent stem cells. Made from the patients' own tissue, the stem cells were developed into central nervous system cells that carried the patients' genetic defects. Zhang exposed the cells to HSV-1 and to synthetic double-stranded RNA, which mimics a byproduct of the virus that spurs the toll-like receptors into action. By measuring levels of interferon, Zhang showed that the patients' TLR3 response was indeed faulty; their cells weren't making these important immune system proteins, leaving them unable to fight off the infection.

Zhang also exposed the patients' blood cells to the virus and found that the TLR3 defect was not an issue there as it was in the brain -- interferons were released by other means.

Because the toll-like receptors on neurons proved to be vital in preventing the encephalitis infection, the researchers concluded that brain cells use it as an in-house mechanism to fight infection, rather than relying on white blood cells. When its function was impaired, patients couldn't get better.

"This is evidence of an intrinsic immunity, a newly-discovered function of the immune system," says Zhang. "It's likely that other organs also have their own specific tools for fighting infection."

The researchers are putting together a pilot study to test an interferon-based treatment in patients with the encephalitis, believing it will help speed recovery and increase the survival rate when used alongside antiviral drugs. They'll also explore whether the brain displays an intrinsic immunity to other types of viral infection.

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The above story is reprinted from materials provided by Rockefeller University.

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Journal Reference:

Fabien G. Lafaille, Itai M. Pessach, Shen-Ying Zhang, Michael J. Ciancanelli, Melina Herman, Avinash Abhyankar, Shui-Wang Ying, Sotirios Keros, Peter A. Goldstein, Gustavo Mostoslavsky, Jose Ordovas-Montanes, Emmanuelle Jouanguy, Sabine Plancoulaine, Edmund Tu, Yechiel Elkabetz, Saleh Al-Muhsen, Marc Tardieu, Thorsten M. Schlaeger, George Q. Daley, Laurent Abel, Jean-Laurent Casanova, Lorenz Studer, Luigi D. Notarangelo. Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells. Nature, 2012; DOI: 10.1038/nature11583

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Sleeping Beauty hooks up with herpes to fight brain disease

ScienceDaily (Jan. 9, 2010) — Neuroscientists have forged an unlikely molecular union as part of their fight against diseases of the brain and nervous system.

The team has brought together the herpes virus and a molecule known as Sleeping Beauty to improve a technology known as gene therapy, which aims to manipulate genes to correct for molecular flaws that cause disease.

The work, detailed in a paper published online in Gene Therapy, has allowed scientists at the University of Rochester Medical Center to reach a long-sought goal: Shuttling into brain cells a relatively large gene that can remain on for an extended period of time.

"We've broken what is in effect a size barrier -- a limit to how much genetic material we can put into the nucleus of a cell and keep functioning for a long period of time," said neuroscientist William Bowers, Ph.D., a scientist in the Center for Neural Development and Disease and the leader of the team. "That opens up more diseases to possible treatment with gene therapy."

The first author of the paper is Biochemistry graduate student Suresh de Silva, who defends his doctoral thesis later this month.

The molecular rendezvous of Sleeping Beauty and herpes in human brain cells could spell good news in the search for treatments for horrific brain diseases known as pediatric leukodystrophies, or a group of diseases known as lysosomal storage disorders. In many of these diseases, even though just a single gene or protein is defective, the effects are devastating -- the diseases slowly rob children of their brain cells and are often fatal after years of severe symptoms.

The findings bolster the tools that researchers have when approaching certain diseases, said Bowers, including Usher syndrome, which results in deafness and vision loss; Niemann-Pick disease Type C, a fatal childhood lysosomal storage disorder; and von Willebrand disease, an inherited disease that causes extensive, chronic bleeding.

"The field of gene therapy is just beginning to yield some successes for patients. Improvements like this are crucial for increasing the number of patients who might benefit from such an approach," said Bowers, who is an associate professor of Neurology, Microbiology and Immunology, and of Pharmacology and Physiology.

The research is part of a decades-long endeavor by scientists trying to get the right genes into the right cells at the right time to improve human health.

In the new work, scientists dramatically increased the size of the "genetic payload" they can deliver to brain cells compared to some conventional techniques, nearly tripling the amount of genetic material by some measures. They hope to deliver even bigger genes in the future.

The team did this by bringing together in a new way two molecular players, herpes and Sleeping Beauty, which are commonly used in molecular technology.

For years Bowers' team has been using the herpes virus -- HSV-1, the type that causes cold sores -- to shuttle genes into cells. Viruses like herpes are adept at infecting human cells, and scientists like Bowers use such viruses to carry into cells genes that would help people who are sick. Bowers and colleagues modify the viruses extensively, removing the portions that could make a person sick and using the portions that the virus uses to gain access to human cells.

Many scientists use other viruses, such as lentiviruses or a cold-related virus known as adeno-associated virus (AAV), to do a similar job. Each virus has its strengths and weaknesses when it comes to gene therapy. Herpes, for instance, readily infects cells, and it can carry a huge amount of genetic material, typically 15 to 30 times the amount of DNA that other viruses can carry into a cell.

But herpes as a genetic tool has a couple of big weaknesses. While the virus can deliver DNA into the nucleus of a cell, the genetic payload it carries does not become part of the package of genes that cells pass from one to another. Simply put, herpes cannot integrate the new DNA into the host genome. Instead, the DNA is adrift in the nucleus, where it's silenced within a few weeks. The short time span spells trouble when scientists are trying to treat a disease that requires the genes to be active for months or years.

That's where Sleeping Beauty comes in.

In molecular biology, Sleeping Beauty is a mobile genetic element that jumps into and out of longer segments of DNA. It's normally silent, but years ago a team of scientists was able to activate or "awaken" the snippet -- hence, Sleeping Beauty. Since Sleeping Beauty actually integrates segments of DNA into mammalian genomes, it sidesteps the main difficulties that herpes encounters inside a cell: Genes integrated within the cell's chromosomes by Sleeping Beauty operate for much longer periods of time. The drawback: The molecule can insert only small snippets of DNA.

So the Rochester team brought herpes and Sleeping Beauty together in an attempt to get the best of both worlds: Delivery of the bigger genetic package made possible by herpes, and the integration of the DNA into the host genome made possible by Sleeping Beauty.

And that's exactly what happened. In the tag-team approach funded by the National Institute of Neurological Disorders and Stroke, herpes gets the genetic package into the right neighborhood, the cell's nucleus, and then Sleeping Beauty delivers the package precisely where it needs to go to be most effective -- into the cellular genome.

In the current experiments, the herpes virus carried into cell nuclei the gene for green fluorescent protein, which allows scientists to track where the gene is active. The team also outfitted the herpes package with special molecular signals that Sleeping Beauty would recognize. Separately, the team introduced Sleeping Beauty into the cells. When the two met, Sleeping Beauty transferred the gene for GFP from the herpes package to the genome of the human cells, where the gene was stably expressed.

The team has previously shown that the Sleeping Beauty/herpes combination works efficiently in brain cells known as neural progenitor cells, which go on to form brain cells known as neurons. Modifying these cells -- perhaps by adding a gene that creates a protein crucial for health -- is one technique scientists are experimenting with to try to treat several brain diseases that are currently untreatable.

The gene segment used in the experiment described in Gene Therapy was about 12 kilobases long, which is larger than the limit of either AAV (4.5 kb) or lentiviruses (9 kb). Those few kilobases matter, a lot. The ability to transfer bigger genes gives scientists room to try to address more diseases with a gene therapy approach. The added space also makes it possible to include more regulatory elements -- instructions that help determine how and when genes are turned on or off. This allows scientists to package additional safety directives, in the form of more DNA, along with the gene designed to treat the disease.

In addition to de Silva and Bowers, authors include technical associates Michael Mastrangelo, Louis T. Lotta Jr., and Clark Burris, as well as Howard J. Federoff, M.D., Ph.D., a former Rochester faculty member who is now executive vice president for health sciences at Georgetown University.

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The above story is reprinted from materials provided by University of Rochester Medical Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Immunogene therapy combined with standard treatment is safe for patients with brain tumors, study suggests

ScienceDaily (Sep. 6, 2011) — A clinical trial has shown that a form of gene therapy is safe for treating a deadly form of brain cancer, even when combined with radiation therapy.

The phase 1b trial was conducted at the Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC -- James) and at Methodist at Hospital in Houston, TX.

The novel treatment uses an adenovirus vector called AdV-tk. The vector is taken up by cancer cells where it activates a drug that kills the cells. The vector is applied in the operating room after removing brain tumors such as glioblastoma multiforme, the most common and dangerous form of brain cancer.

The findings, published online in the Journal of Clinical Oncology, suggest that the therapy might also stimulate an immune response against the tumor.

"This is the first time that a gene therapy approach was combined with radiation in patients with newly diagnosed glioblastoma," says first author Dr. E. Antonio Chiocca, professor and chair of neurological surgery and co-director of the Dardinger Center for Neuro-oncology and Neurosciences at Ohio State.

"There had been a concern that combining these two treatments could be too toxic for patients, but this was not the case. We do not know yet if this will improve survival, but these findings are encouraging," he says.

Glioblastomas occur in about 18,500 Americans annually and kill nearly 13,000 of them yearly. Glioblastoma multiforme is the most common and lethal form of the malignancy, with an average survival of 15 months after diagnosis.

The tumors often recur because cancer cells typically migrate into adjacent brain tissue where they can give rise to a recurrent tumor. This study examines an immunogene therapy approach that is designed to kill these undetected cancer cells and prevent recurrence.

This clinical trial involved 10 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma. The procedure works as follows:

After removing the tumor, the neurosurgeon injects the tumor bed with 1 milliliter (1/30th oz) of a solution containing the AdV-tk vector. The vector carries a gene from herpes simplex virus for an enzyme called thymidine kinase (the '-tk' in AdV-tk). Cancer cells infected with the vector begin making the enzyme.Patients then take the anti-herpes virus drug valacyclovir for two weeks.Inside the cancer cells, the herpes thymidine kinase enzyme converts valacyclovir into DNA building blocks that the rapidly growing cancer cells cannot use to make DNA, and this kills them.Radiation therapy begins halfway through the course of valacyclovir. The radiation damages the DNA in the cancer cells, which then try to repair it, using the toxic valacyclovir building blocks.

In addition to improved overall survival, studies revealed a significant rise in the number of T lymphocytes in the tumors. This suggests that the gene therapy stimulated an immune response against the tumor, producing an "immunogene therapy" effect.

Cancer immunogene therapy refers to genetically manipulating cancer cells to stimulate an immune response against a tumor. (Note: This differs from "immunotherapy," which attempts to stimulate the immune system directly against tumor cells.)

"If the results of another recently completed phase 2 efficacy trial are also encouraging, the next step will be to compare this therapy head-to-head with the current standard of care," Chiocca says.

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The above story is reprinted from materials provided by Ohio State University Medical Center, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

E. A. Chiocca, L. K. Aguilar, S. D. Bell, B. Kaur, J. Hardcastle, R. Cavaliere, J. McGregor, S. Lo, A. Ray-Chaudhuri, A. Chakravarti, J. Grecula, H. Newton, K. S. Harris, R. G. Grossman, T. W. Trask, D. S. Baskin, C. Monterroso, A. G. Manzanera, E. Aguilar-Cordova, P. Z. New. Phase IB Study of Gene-Mediated Cytotoxic Immunotherapy Adjuvant to Up-Front Surgery and Intensive Timing Radiation for Malignant Glioma. Journal of Clinical Oncology, 2011; DOI: 10.1200/JCO.2011.35.5222

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Cold sore virus may contribute to cognitive and brain abnormalities in schizophrenia

ScienceDaily (May 29, 2010) — Exposure to the common virus that causes cold sores may be partially responsible for shrinking regions of the brain and the loss of concentration skills, memory, coordinated movement and dexterity widely seen in patients with schizophrenia, according to research led by Johns Hopkins scientists.

"We're finding that some portion of cognitive impairment usually blamed solely on the disease of schizophrenia might actually be a combination of schizophrenia and prior exposure to herpes simplex virus 1 infection, which reproduces in the brain," says study leader David J. Schretlen, Ph.D., an associate professor in the Department of Psychiatry at Johns Hopkins University School of Medicine.

The research, described in the May Schizophrenia Research, could lead to new ways to treat or prevent the cognitive impairment that typically accompanies this mental illness, including with antiviral drugs, the scientists say.

Doctors have long known that cognitive impairment, including problems with psychomotor speed, concentration, learning, and memory, are prevalent features of schizophrenia, which affects an estimated one percent of the U.S. population. Cognitive deficits often surface months to years before symptoms that are traditionally used to diagnose this disease, such as delusions or hallucinations.

Some previous studies have shown that schizophrenic patients with antibodies to herpes simplex virus 1 (HSV-1), the virus that causes cold sores, often have more severe cognitive deficits than patients without these antibodies. Other studies have shown that patients with HSV-1 antibodies have decreased brain volumes compared to patients without the antibodies. However, it has been unclear whether the cognitive deficits are directly related to the decreased brain volume.

To investigate, Schretlen and his colleagues recruited 40 schizophrenic patients from outpatient clinics at the Johns Hopkins and Sheppard Enoch Pratt hospitals in Baltimore, Md. Blood tests showed that 25 of the patients had antibodies for HSV-1 and 15 didn't. The researchers gave all of the patients tests to measure speed of coordination, organizational skills and verbal memory. The patients then underwent MRI brain scans to measure the volume of particular regions of their brains.

As in previous studies, results showed that patients with antibodies to HSV-1 performed significantly worse on the cognitive tests than patients without the antibodies. But expanding on those earlier studies, analysis of the brain scans showed that the same patients who performed poorly on the tests also had reduced brain volume in the anterior cingulate, which controls processing speed and the ability to switch tasks. There was also shrinkage in the cerebellum, which controls motor function.

These results suggest that HSV-1 might be directly causing the cognitive deficits by attacking these brain regions, Schretlen says.

Though the researchers aren't sure why schizophrenia might make brains more vulnerable to a viral assault, Schretlen says the results already suggest new ways of treating the disorder. Data from other studies has shown that antiviral medications can reduce psychiatric symptoms in some patients with schizophrenia. "If we can identify schizophrenic patients with HSV-1 antibodies early on, it might be possible to reduce the risk or the extent of cognitive deficits," he adds.

Other Johns Hopkins researchers who participated in this study include Tracy D. Vannorsdall, Ph.D., Jessica M. Winicki, B.A., Takatoshi Hikida, M.D., Akira Sawa, M.D., Ph.D., Robert H. Yolken, M.D., and Nicola G. Cascella, M.D.

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The above story is reprinted from materials provided by Johns Hopkins Medical Institutions, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

David J. Schretlen, Tracy D. Vannorsdall, Jessica M. Winicki, Yaser Mushtaq, Takatoshi Hikida, Akira Sawa, Robert H. Yolken, Faith B. Dickerson, Nicola G. Cascella. Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia. Schizophrenia Research, 2010; 118 (1-3): 224 DOI: 10.1016/j.schres.2010.01.008

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Sleeping Beauty hooks up with herpes to fight brain disease

ScienceDaily (Jan. 8, 2010) — Neuroscientists have forged an unlikely molecular union as part of their fight against diseases of the brain and nervous system.

The team has brought together the herpes virus and a molecule known as Sleeping Beauty to improve a technology known as gene therapy, which aims to manipulate genes to correct for molecular flaws that cause disease.

The work, detailed in a paper published online in Gene Therapy, has allowed scientists at the University of Rochester Medical Center to reach a long-sought goal: Shuttling into brain cells a relatively large gene that can remain on for an extended period of time.

"We've broken what is in effect a size barrier -- a limit to how much genetic material we can put into the nucleus of a cell and keep functioning for a long period of time," said neuroscientist William Bowers, Ph.D., a scientist in the Center for Neural Development and Disease and the leader of the team. "That opens up more diseases to possible treatment with gene therapy."

The first author of the paper is Biochemistry graduate student Suresh de Silva, who defends his doctoral thesis later this month.

The molecular rendezvous of Sleeping Beauty and herpes in human brain cells could spell good news in the search for treatments for horrific brain diseases known as pediatric leukodystrophies, or a group of diseases known as lysosomal storage disorders. In many of these diseases, even though just a single gene or protein is defective, the effects are devastating -- the diseases slowly rob children of their brain cells and are often fatal after years of severe symptoms.

The findings bolster the tools that researchers have when approaching certain diseases, said Bowers, including Usher syndrome, which results in deafness and vision loss; Niemann-Pick disease Type C, a fatal childhood lysosomal storage disorder; and von Willebrand disease, an inherited disease that causes extensive, chronic bleeding.

"The field of gene therapy is just beginning to yield some successes for patients. Improvements like this are crucial for increasing the number of patients who might benefit from such an approach," said Bowers, who is an associate professor of Neurology, Microbiology and Immunology, and of Pharmacology and Physiology.

The research is part of a decades-long endeavor by scientists trying to get the right genes into the right cells at the right time to improve human health.

In the new work, scientists dramatically increased the size of the "genetic payload" they can deliver to brain cells compared to some conventional techniques, nearly tripling the amount of genetic material by some measures. They hope to deliver even bigger genes in the future.

The team did this by bringing together in a new way two molecular players, herpes and Sleeping Beauty, which are commonly used in molecular technology.

For years Bowers' team has been using the herpes virus -- HSV-1, the type that causes cold sores -- to shuttle genes into cells. Viruses like herpes are adept at infecting human cells, and scientists like Bowers use such viruses to carry into cells genes that would help people who are sick. Bowers and colleagues modify the viruses extensively, removing the portions that could make a person sick and using the portions that the virus uses to gain access to human cells.

Many scientists use other viruses, such as lentiviruses or a cold-related virus known as adeno-associated virus (AAV), to do a similar job. Each virus has its strengths and weaknesses when it comes to gene therapy. Herpes, for instance, readily infects cells, and it can carry a huge amount of genetic material, typically 15 to 30 times the amount of DNA that other viruses can carry into a cell.

But herpes as a genetic tool has a couple of big weaknesses. While the virus can deliver DNA into the nucleus of a cell, the genetic payload it carries does not become part of the package of genes that cells pass from one to another. Simply put, herpes cannot integrate the new DNA into the host genome. Instead, the DNA is adrift in the nucleus, where it's silenced within a few weeks. The short time span spells trouble when scientists are trying to treat a disease that requires the genes to be active for months or years.

That's where Sleeping Beauty comes in.

In molecular biology, Sleeping Beauty is a mobile genetic element that jumps into and out of longer segments of DNA. It's normally silent, but years ago a team of scientists was able to activate or "awaken" the snippet -- hence, Sleeping Beauty. Since Sleeping Beauty actually integrates segments of DNA into mammalian genomes, it sidesteps the main difficulties that herpes encounters inside a cell: Genes integrated within the cell's chromosomes by Sleeping Beauty operate for much longer periods of time. The drawback: The molecule can insert only small snippets of DNA.

So the Rochester team brought herpes and Sleeping Beauty together in an attempt to get the best of both worlds: Delivery of the bigger genetic package made possible by herpes, and the integration of the DNA into the host genome made possible by Sleeping Beauty.

And that's exactly what happened. In the tag-team approach funded by the National Institute of Neurological Disorders and Stroke, herpes gets the genetic package into the right neighborhood, the cell's nucleus, and then Sleeping Beauty delivers the package precisely where it needs to go to be most effective -- into the cellular genome.

In the current experiments, the herpes virus carried into cell nuclei the gene for green fluorescent protein, which allows scientists to track where the gene is active. The team also outfitted the herpes package with special molecular signals that Sleeping Beauty would recognize. Separately, the team introduced Sleeping Beauty into the cells. When the two met, Sleeping Beauty transferred the gene for GFP from the herpes package to the genome of the human cells, where the gene was stably expressed.

The team has previously shown that the Sleeping Beauty/herpes combination works efficiently in brain cells known as neural progenitor cells, which go on to form brain cells known as neurons. Modifying these cells -- perhaps by adding a gene that creates a protein crucial for health -- is one technique scientists are experimenting with to try to treat several brain diseases that are currently untreatable.

The gene segment used in the experiment described in Gene Therapy was about 12 kilobases long, which is larger than the limit of either AAV (4.5 kb) or lentiviruses (9 kb). Those few kilobases matter, a lot. The ability to transfer bigger genes gives scientists room to try to address more diseases with a gene therapy approach. The added space also makes it possible to include more regulatory elements -- instructions that help determine how and when genes are turned on or off. This allows scientists to package additional safety directives, in the form of more DNA, along with the gene designed to treat the disease.

In addition to de Silva and Bowers, authors include technical associates Michael Mastrangelo, Louis T. Lotta Jr., and Clark Burris, as well as Howard J. Federoff, M.D., Ph.D., a former Rochester faculty member who is now executive vice president for health sciences at Georgetown University.

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Story Source:

The above story is reprinted from materials provided by University of Rochester Medical Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Cold sore virus may contribute to cognitive and brain abnormalities in schizophrenia

ScienceDaily (May 28, 2010) — Exposure to the common virus that causes cold sores may be partially responsible for shrinking regions of the brain and the loss of concentration skills, memory, coordinated movement and dexterity widely seen in patients with schizophrenia, according to research led by Johns Hopkins scientists.

"We're finding that some portion of cognitive impairment usually blamed solely on the disease of schizophrenia might actually be a combination of schizophrenia and prior exposure to herpes simplex virus 1 infection, which reproduces in the brain," says study leader David J. Schretlen, Ph.D., an associate professor in the Department of Psychiatry at Johns Hopkins University School of Medicine.

The research, described in the May Schizophrenia Research, could lead to new ways to treat or prevent the cognitive impairment that typically accompanies this mental illness, including with antiviral drugs, the scientists say.

Doctors have long known that cognitive impairment, including problems with psychomotor speed, concentration, learning, and memory, are prevalent features of schizophrenia, which affects an estimated one percent of the U.S. population. Cognitive deficits often surface months to years before symptoms that are traditionally used to diagnose this disease, such as delusions or hallucinations.

Some previous studies have shown that schizophrenic patients with antibodies to herpes simplex virus 1 (HSV-1), the virus that causes cold sores, often have more severe cognitive deficits than patients without these antibodies. Other studies have shown that patients with HSV-1 antibodies have decreased brain volumes compared to patients without the antibodies. However, it has been unclear whether the cognitive deficits are directly related to the decreased brain volume.

To investigate, Schretlen and his colleagues recruited 40 schizophrenic patients from outpatient clinics at the Johns Hopkins and Sheppard Enoch Pratt hospitals in Baltimore, Md. Blood tests showed that 25 of the patients had antibodies for HSV-1 and 15 didn't. The researchers gave all of the patients tests to measure speed of coordination, organizational skills and verbal memory. The patients then underwent MRI brain scans to measure the volume of particular regions of their brains.

As in previous studies, results showed that patients with antibodies to HSV-1 performed significantly worse on the cognitive tests than patients without the antibodies. But expanding on those earlier studies, analysis of the brain scans showed that the same patients who performed poorly on the tests also had reduced brain volume in the anterior cingulate, which controls processing speed and the ability to switch tasks. There was also shrinkage in the cerebellum, which controls motor function.

These results suggest that HSV-1 might be directly causing the cognitive deficits by attacking these brain regions, Schretlen says.

Though the researchers aren't sure why schizophrenia might make brains more vulnerable to a viral assault, Schretlen says the results already suggest new ways of treating the disorder. Data from other studies has shown that antiviral medications can reduce psychiatric symptoms in some patients with schizophrenia. "If we can identify schizophrenic patients with HSV-1 antibodies early on, it might be possible to reduce the risk or the extent of cognitive deficits," he adds.

Other Johns Hopkins researchers who participated in this study include Tracy D. Vannorsdall, Ph.D., Jessica M. Winicki, B.A., Takatoshi Hikida, M.D., Akira Sawa, M.D., Ph.D., Robert H. Yolken, M.D., and Nicola G. Cascella, M.D.

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Story Source:

The above story is reprinted from materials provided by Johns Hopkins Medical Institutions, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

David J. Schretlen, Tracy D. Vannorsdall, Jessica M. Winicki, Yaser Mushtaq, Takatoshi Hikida, Akira Sawa, Robert H. Yolken, Faith B. Dickerson, Nicola G. Cascella. Neuroanatomic and cognitive abnormalities related to herpes simplex virus type 1 in schizophrenia. Schizophrenia Research, 2010; 118 (1-3): 224 DOI: 10.1016/j.schres.2010.01.008

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here