Hello to all!  We are proud to announce the return of Living with Schizophrenia after a long hiatus.  If you haven't visited Schizophrenia.com in a while, you might want to check out our new discussion pages, search engine, and book reviews.   Below you will find news highlights from this spring and early summer, and we will continue to keep you updated of new developments on a regular basis.  We hope you find these articles informative and pertinent, and welcome your questions or comments.  You can email us at szwebmaster@yahoo.com.  Enjoy! 

2. Fourth Edition of Surviving Schizophrenia Published

3. Viral Genetic Material found in Cerebrospinal Fluid of Some Schizophrenics

4. Clinical Trials of Third-Generation Anti-Psychotic Look Promising

5. Ken Steele's Autobiography Released

6. Protein Model Points to Smoking, Alzheimers, and Schizophrenia Drugs

7. Dopamine-Dampening Gene Linked To Prefrontal Inefficiency, Schizophrenia

8. Oxygen Shortage at Birth Linked to Schizophrenia

Father's Age Linked to Risk of Schizophrenia

By ERICA GOODE

April 12, 2001

The risk of having a child with schizophrenia may increase with a father's advancing age, researchers reported yesterday.   The researchers, who examined the relationship between the fathers' ages and schizophrenia among 87,907 Israelis born from 1964 through 1976, found that the older the father, the more likely he was to have a child who suffered from schizophrenia, a devastating mental illness.   Men who were 45 through 49, for example, were twice as likely to have offspring with schizophrenia or a related disorder as were men under 25, the researchers found. The overall risk of having a child with the illness, however, remained small.

    "The finding is a very strong association of schizophrenia risk and father's age," said Dr. Delores Malaspina, an associate professor of clinical psychiatry at the Columbia University College of Physicians and Surgeons and the lead author of the report, which appears in this month's issue of the journal Archives of General Psychiatry.  

    Other scientists were more skeptical. They noted that confirmation through other studies was needed before such a link could be said to be established, and they cautioned that in the history of schizophrenia research, many apparent associations had eventually proved spurious or impossible to replicate.

    If the results of the study hold up to scrutiny, Dr. Malaspina said, "The next question is, `What might explain that finding?' " One possibility, the researchers argue in their report, is that some cases of schizophrenia are a result of genetic abnormalities in sperm cells that become more likely as a man ages.  Stem cells in the testicles divide throughout a man's life in a process that leads to the production of sperm. Each cell division carries the chance for copying errors in reproducing the DNA. By the age of 40, research suggests, about 660 such divisions have taken place. Genetic mutations can also occur from exposure to radiation or chemicals over a man's life.   In contrast, the divisions of cells that produce a woman's eggs occur only before birth.

        A number of physical illnesses and birth defects have been linked to genetic mutations during sperm production in older fathers, including Apert syndrome, a rare congenital deformity of the skull, fingers and toes, and achondroplasia, the most common form of dwarfism.  Some cases of schizophrenia, the researchers suggested, might be associated with similar mutations.

    The illness runs in families, and is known to have a strong genetic component, though efforts to identify the specific gene or genes that predispose a person to schizophrenia have so far been inconclusive. The disease affects 1 of every 100 Americans and is more common in men.  Full-blown symptoms often first appear in late adolescence or early adulthood.  In some cases, people who do not have a family history of schizophrenia also develop the illness. Dr. Malaspina said that the findings of her study "suggest that relevant mutations are there" in such sporadic cases "as well as in familial cases."   Dr. James F. Crow, a professor emeritus of genetics at the University of Wisconsin, said, "I think this is very strong evidence for a mutation component to schizophrenia, but it's quite an open question as to how much of a component."  

        But other scientists cautioned that other explanations beside spontaneous genetic mutation could also account for the study's results.  For example, said Dr. Ann Pulver, director of the epidemiology and genetics program in psychiatry at Johns Hopkins University, "It may be that the fathers of schizophrenics have unusual characteristics that delay reproduction." "I think this is an interesting contribution to the epidemiological literature, that paternal age may be a risk factor for a subgroup of schizophrenic patients," Dr. Pulver said. "And it may be that advanced paternal age is associated with a mutation. But that is a hypothesis and one would need to test it."

    In the study, Dr. Malaspina and her colleagues took advantage of the Jerusalem Perinatal Study, a research archive that includes information about all births in one area of Jerusalem. Records from the study were correlated with those of a national registry of psychiatric illness kept by the Israeli government.   The researchers found that in 1,337 people admitted to psychiatric hospitals before 1998, the fathers' ages were strongly associated with a diagnosis of schizophrenia or a related disorder. The risk of schizophrenia increased steadily with the father's increasing age. Advancing age of the fathers, the investigators reported, accounted for 26 percent of the cases of schizophrenia in the study; for fathers over 50, two out of every three cases of the illness could be attributed to the father's age.                                  

Surviving Schizophrenia, 4th edition E. Fuller Torrey, M.D. New York: HarperCollins, 2001, $15.

    The fourth edition of Surviving Schizophrenia: A Manual for Families, Consumers and Providers was published in May by HarperCollins. It is completely revised and updated. It includes information on all the new antipsychotics (except that the trade name of ziprasidone was changed from Zeldox to Geodon after the book went to press), as well as new information that has not been widely publicized, e.g., why pregnancies increase when women switch from first-generation (typical) to second-generation (atypical) antipsychotics, and why drinking coffee increases and smoking decreases the blood levels and thus the effectiveness of clozapine and olanzapine. The book also includes the latest research findings on the causes of schizophrenia and a comparison of schizophrenia with manic-depressive illness (bipolar disorder). Also included are summaries of 9 commercial films portraying individuals with schizophrenia, evaluations of the 9 best websites for information on schizophrenia, and summaries of 18 good videotapes and 50 useful books on this disease. Finally, Dr. Torrey summarizes his nominations for "the 15 worst books on schizophrenia." "It's getting harder to find worthy additions to this list," he told the Advocate. "This is a sign that the field is moving forward." Surviving Schizophrenia is available through your local bookstore and can also be ordered over the Internet at Amazon.com, BarnesandNoble.com, and Borders.com.

Check out the book review at http://www.schizophrenia.com/bookreviews/survschizreview.html

The Washington Post, April 10, 2001 

 Bits of genetic code resembling viral genes were found in the cerebrospinal fluid and brain tissue of schizophrenics in a study released yesterday that provides new evidence a virus may contribute to some cases of the devastating mental illness.

 A research team led by a Johns Hopkins School of Medicine scientist examined a group of 35 Germans who had been diagnosed with schizophrenia. The researchers found the molecular "footprint" of a retrovirus in the cerebrospinal fluid of 29 percent of subjects with newly diagnosed acute schizophrenia. It also was found in 7 percent of those with a chronic form of the disease. 

 In contrast, the retroviral genes were not present in the brains or cerebrospinal fluid of healthy people examined or people with other types of neurological illnesses.

 The researchers said the greater frequency of retroviral genes found in patients with newly diagnosed instead of chronic schizophrenia hinted that the activation of these genes may contribute to the onset and initial progression of the disease in some individuals. The study appears in the Proceedings of the National Academy of Sciences.

PRINCETON, N.J., and TOKYO, May 8, 2001

According to a new study presented today, aripiprazole, under development as a once-daily novel antipsychotic, is significantly better than placebo in controlling the positive and negative symptoms of schizophrenia.  The study also showed that risperidone is better than placebo in controlling positive and negative symptoms.  In addition, the side effect profile of aripiprazole in this study was very favorable.  Specifically, in this study:

 -- As with other Phase II and III clinical trials of aripiprazole, only a small percentage of patients experienced clinically significant weight gain.

     -- Mean change from baseline QTc was not statistically different in patients taking aripiprazole compared to placebo.

     -- Aripiprazole did not increase prolactin levels. In contrast, risperidone was associated with increased prolactin levels.

     -- As with other phase II and Phase III studies of aripiprazole, there were minimal reports of extrapyramidal symptoms (EPS).

     -- Aripiprazole was well tolerated in this study with few patients discontinuing treatment.  The most commonly-reported adverse events were headache, agitation, insomnia and nervousness. 

 "This study confirms the findings of two previous Phase III trials, which demonstrated that aripiprazole was superior to placebo in controlling the symptoms of schizophrenia and appeared to have a favorable tolerability profile," said Jeffrey Lieberman, MD, Vice Chairman of Psychiatry, Professor of Psychiatry and Pharmacology, at the University of North Carolina at Chapel Hill.  "Due to the major unmet need for this patient population, the results of ongoing aripiprazole clinical trials will be of great interest," he added. The "Aripiprazole and Risperidone versus Placebo in Schizophrenia and Schizoaffective Disorder," was a double-blind, multicenter, four-week study involving 404 hospitalized patients with a DSM-IV diagnosis of schizophrenia and schizoaffective disorder with acute relapse.  The patient population was approximately 70% male and 30% female, ranging in age from 18-65 with history of prior antipsychotic response.  Prior to starting double-blind administration of 20 mg of aripiprazole, 30 mg of aripiprazole, 6 mg of risperidone or placebo, patients were removed from previous medication for three to five days.  Aripiprazole doses were fixed from day one of treatment. Risperidone was administered 1 mg twice a day on day one, 2 mg twice a day on day two, and 3 mg twice a day thereafter.  

    "We are very excited about the latest phase III study results with aripiprazole," said Peter S. Ringrose, Ph.D., chief scientific officer and president of the Pharmaceutical Research Institute at Bristol-Myers Squibb Company (NYSE: BMY).  "These data, in addition to the positive results of our Phase III study comparing the efficacy of aripiprazole and haloperidol to placebo, suggest that aripiprazole holds a lot of promise for the millions of people worldwide who suffer from schizophrenia."

    "The Phase III clinical trial program is very encouraging and gives us great hope that aripiprazole may become an important treatment option," said Kazuhiro Tomita, director on board, research, Otsuka Pharmaceutical Co., Ltd. "We are very pleased with the outcome of this study and the possibility it demonstrates for providing patients with a therapeutic alternative."

 Ken Steele's autobiography, The Day the Voices Stopped, is now available. As you may know, Ken Steele lived with the devastating symptoms of schizophrenia for 32 years. Finally, Ken's voices stopped with the help of doctors, friends and a new medication to treat schizophrenia. His eventual treatment and recovery enabled him to become a leading figure in the mental health community. Tragically, two days after completing his book, Ken died of heart failure. Co-author, Claire Berman, a well-known public speaker and gifted author in her own right, has vowed to share Ken's story through her personal experience of working with and knowing him.   Ken was a big supporter of this site, and we are sorry he is not here to share in our pride of this accomplishment.

Thursday May 17 1:07 PM ET  LONDON (Reuters) - Dutch scientists said on Wednesday they had developed a three-dimensional model of a brain protein that may lead to new drugs to help people quit smoking or to treat Alzheimer's and schizophrenia. The protein, produced by glial cells in the central nervous system, helps to transmit messages between brain cells that control functions such as memory, attention and addiction. "It will give us a new goal and a new method for rational drug design," August Smith, a neurologist at Vrije University in Amsterdam, said in a telephone interview. In a study in the science journal Nature, Smith and his colleagues described how the protein acts as part of a receptor, a type of door or link, for a brain-signalling chemical called acetylcholine that is involved in memory. The three-dimensional structure of the protein, developed by Titia Sixma and structural biologists at the Dutch Cancer Institute, will allow researchers to look at it on a computer screen to see where acetylcholine binds to it. "By having the binding pocket we can try to make new drugs that target these receptors. By doing so we hope we can influence particular neuronal functions and not others," said Smith. Acetylcholine receptors are also involved in the release of other neurotransmitters including dopamine, which produces feelings of satisfaction and pleasure, and serotonin, the brain chemical associated with mood. Smokers get addicted to nicotine largely because it induces the release of dopamine. Smith said the research was still in its early phases but the discovery of the protein and its structural model would give researchers a new method to test drugs to treat addiction, memory loss and other symptoms related to brain disorders. "The next step is to try to develop drugs that are specific and that will activate specific types of receptors," said Smith.                                  

Also participating in the study were Terry Goldberg, Ph.D, Bhaskar Kolachan, Ph.D., Joseph Callicott, M.D., NIMH Clinical Brain Disorders Branch; and David Goldman, M.D., Chiara Mazzanti, Ph.D., Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism.

Monday June 4 1:29 PM ET  By Kristin Demos STOCKHOLM (Reuters Health) - Newborns who are deprived of oxygen at birth due to obstetric complications are at four times greater risk of schizophrenia later in life than other children, new research suggests. Many different obstetric complications during pregnancy and delivery are associated with a future risk of schizophrenia, said Dr. Christina Dalman, a psychiatrist who recently published her doctoral thesis at Gothenburg University.

     Schizophrenia, a mental disorder characterized by disturbances in thought and conduct, mood, sense of self, and relationship with the environment, affects about 1% of the world's population. A growing body of evidence links the disease with complications at birth. ``I've been looking at fetal factors like preeclampsia or if the fetuses are thin,'' Dalman told Reuters Health, ``and I've found that if the fetuses are thin or the mothers have preeclampsia, those babies have a doubled risk of schizophrenia later on in life. I've also looked at babies born before week 33 and they also have a doubled risk. And, then I've been looking at signs of asphyxia and those children have a four times higher risk of schizophrenia later in life.''

        Preeclampsia strikes about 5% of first-time mothers, and occurs less frequently among other pregnant women. Characterized by high blood pressure, swelling and protein in the urine, preeclampsia sometimes progresses to eclampsia, a life-threatening condition marked by convulsions. ``Dr. Dalman's work is among the most impressive of any research in this area and puts beyond doubt the evidence that a range of factors during pregnancy and birth can increase the later risk of schizophrenia,'' said Robin Murray, a professor of psychiatry at London's Institute of Psychiatry. ``These include poor nutrition and slow growth of the foetus, hypoxia (lack of oxygen) at birth, and neonatal jaundice.'' Every 10th child is exposed to some complication during childbirth that could lead to schizophrenia, explained Dalman, but most do not develop the illness. The origins of schizophrenia are largely unknown, but the greatest known risk factor is genetic, with a 10 times increased risk for children with one parent with the illness. 

        Dalman was able to take advantage of a large sampling of people with schizophrenia in Sweden because of the country's unique registering systems. The National Birth Register, for instance, contains information on all children born in Sweden, about 100,000 every year. The researcher was able to compare 524 schizophrenic persons in Stockholm with 1,043 people of the same sex who were born about the same time. After eliminating factors such as hereditary psychosis, Dalman found that the risk for schizophrenia was 4.4 times higher for children who suffer from hypoxia during childbirth.

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