Diagnosis and Treatment Interventions

Medication Information and Innovation

In Community, Society, and Media

Biology and Current Research:

New Test May Detect Parkinson's Disease and Schizophrenia Early, and Aid Search for Drugs
 

Source: WALL STREET JOURNAL

The Wall Street Journal reported this morning that Pfizer has developed a relatively simple computer-based speach analysis test that, in initial tests, appears able to diagnose Parkinsons disease and schizophrenia.

The Journal reports that:

"Now scientists at drug giant Pfizer think they have stumbled on a simple test that is both sensitive enough to detect subtle biological changes due to Parkinson's [and schizophrenia] and specific enough to avoid false alarms: analyzing how people speak. If further studies confirm their conclusion, the test could offer a more accurate way to diagnose Parkinson's before large numbers of brain cells are irreversibly lost, and speed the development of new drugs for the disease.

The Pfizer researchers ... believed it might be possible to detect the illness by analyzing speech patterns. In Parkinson's, the characteristic decline in muscle control stems from the loss of dopamine-producing nerve cells in the substantia nigra, a compact region in the middle of the brain. Building on insights from other scientists, Pfizer researchers reasoned that hesitation and hitches later seen in the movement of large muscles might be apparent earlier in shaking or trembling of the tiny muscles involved in speech, including the vocal cords."

Pfizer doesn't plan to market the speech test itself but may explore licensing the technology to other companies. Its goal is to find drugs that would change the course of Schizophrenia and Parkinson's and related diseases by protecting nerve cells.

Pfizer neuroscientist Peter Snyder acknowledges that his method must be validated in further tests before it can be used routinely. But in the meantime, his team has successfully applied the speech test to patients with depression and schizophrenia (in addition to Parkinson's Disease), all of which are diseases that can involve abnormal levels of dopamine in the brain.

 

Special IQ Test for Schizophrenia

The Times of London reported today that:

"A SIMPLE IQ test developed by Scottish scientists will be able to predict whether people are likely to suffer schizophrenia up to three years in advance. Researchers at Edinburgh University believe their test — which measures IQ, memory, motor skills and verbal learning — can be used to take action against the illness, which typically strikes people aged between 17 and 30, from being triggered.

Although schizophrenia cannot be cured, early treatment has been shown to improve recovery rates.

The study, published in the British Journal of Psychiatry, is part of the Edinburgh High-Risk Study led by Professor Eve Johnstone at the university’s department of psychiatry. Over a 10-year period the team examined 163 people, aged 16-24, with a family history of schizophrenia and did brain scans on them.

The results were compared with a group who had no family history of the illness. While 45% of the high-risk group showed symptoms of schizophrenia, only 12% went on to became sick. The differences were identified between two and three years before they fell ill.

“We can now very accurately identify those who do not have to worry, despite having a family history of schizophrenia,” said Johnstone. "

For more information see:

http://www.timesonline.co.uk/article/0,,2090-1432347,00.html

http://www.patienthealthinternational.com/news/4469.aspx

http://www.pst.ed.ac.uk/neuro.shtml

 

 

SZ Prediction Possible, Study Says

A new study from Edinburgh University says that people in high-risk categories for schizophrenia who go on to develop the disease show subtle early warning signs that distinguish them from others in their group.

The study, which began in 1994, tracked 163 young adults identified as "at-risk" for schizophrenia (based on the fact that each subject had two relatives diagnosed with schizophrenia). According to the data, those in this group who actually developed schizophrenia had more pre-diagnosis anxiety, social withdrawal, and "schizotypal" thoughts than those who remained well. Such eary symptoms were subtle in nature, tending not to be debilitating to daily life. However, researchers say that even these small indicators can be identified using behavioural tests.

Another important finding of the study is that many more people are genetically at-risk for schizophrenia than the actual number who will eventually develop the illness. Out of the 163 at-risk subjects (identified based on their genetic susceptibility), only 20 eventually developed schizophrenia.

Based on the early symptoms of those who actually develop schizophrenia, the scientists believe that the basis of schizophrenia may lie in problems with the temporal lobe.

Given that such problems may develop slowly over several years before they become debilitating, this strongly supports the benefits of early screening, identification, and treatment of those who are at genetic and/or environmental risk for developing schizophrenia.

Says Paul Correy of the U.K. mental illness charity Rethink: "It will be some time before studies of this kind lead to improvements in treatment, but we can already see the importance of stepping up government investment in early intervention services that aim to make contact with people in the first stages of illness. Today, there is an average waiting time between the first signs of illness and treatment of 18 months. This study reinforces our belief that this is totally unacceptable."

Marjorie Wallace of the mental health organization SANE agrees, pointing out that many families notice odd behavioural and/or developmental signs in their children well before full-blown symptoms appear. These observations can prove extremely valuable to physicians, especially if the child has a family history of psychiatric disorders.

"The more we understand about what causes an illness like schizophrenia and the earlier we are able to identify those at risk the better we will be able to treat it before long term damage is done," she says.

The full study appears in the British Journal of Psychiatry, (2005) 186: 18-25.

Read the full article online: "Schizophrenia Prediction Possible." BBC News (http://news.bbc.co.uk), Jan 5 2005.

Read about early diagnosis and prevention techniques currently in use or in development. (http://www.schizophrenia.com/diag.html#early)
 

New Schizophrenia Web Tool for Treatment

NASHVILLE, Tenn., Dec. 29 (Source: AScribe Newswire) -- A new Web-based tool will be available January 1, 2005 to help clinicians determine the best medication for patients with schizophrenia. An international team led by Vanderbilt University Medical Center's Herbert Meltzer, M.D., recently completed the new algorithms, or step-by-step protocols, which will provide clinicians a resource as they make treatment decisions.

The value of the algorithms was recently acknowledged by the World Health Organization (WHO), which has committed to establishing a Web link to the algorithms from its Web site. This will allow clinicians and patients worldwide to access the algorithms.

The International Psychopharmacology Algorithm Project (IPAP), a team of psychiatrists, psychopharmacologists and algorithm designers, was founded by Knoxville, Tenn. psychiatrist Kenneth Jobson, M.D., to develop new Web-based tools to improve the treatment of psychiatric disorders. In 2000, Meltzer joined in their efforts and organized a group to develop the algorithms for schizophrenia treatment.

"The idea was that we would come up with evidence-based medicine for schizophrenia, providing clinicians with a resource as they make decisions in standard situations, as well as in crises like suicidality, violence, and severe drug side effects," said Meltzer, the Bixler/Johnson/Mays Professor of Psychiatry and director of the Division of Psychopharmacology at Vanderbilt.

"The algorithms are unique in many ways," Meltzer said. "First, they require clinicians to evaluate patients for these crises before deciding on the course of drug therapy. Also, the algorithms are designed to help clinicians who are not psychiatrists evaluate a patient's medication regimen."

"The kind of people now prescribing drugs include nurse practitioners, as well as family doctors," Meltzer said. In addition, patients are often seen infrequently on an outpatient basis under managed care. Such changes have led to serious problems, which includes patients not using medications correctly and/or using multiple drugs without good evidence that multiple drugs should be used." Among patients with schizophrenia, around 20 percent are taking two or more antipsychotics," Meltzer said.

"Algorithms have come into favor to give strong guidance to people who aren't fully knowledgeable about the literature or have very limited time with patients."

This double- and triple-treatment, known as polypharmacy, leads to higher drug costs, both to traditional insurance plans and governmental health care plans like TennCare, Tennessee's Medicaid program. The IPAP algorithms are designed to limit this phenomenon of polypharmacy, which Meltzer expects will lead to a tremendous savings in drug costs.

"Following the algorithms could save a minimum of 40 percent on the antipsychotics for schizophrenia," estimated Meltzer. Regarding the TennCare budget crisis, Meltzer added, "I think (use of the algorithms) could provide a way of reducing the cost of psychotropic drugs to the state."

Meltzer's current research also suggests that limiting polypharmacy improves patient outcomes. In a study set to be published in the spring, Meltzer and colleagues found that adding a placebo to the standard antipsychotic medication, Clozaril, was better than adding a second antipsychotic in terms of improving psychosis and cognitive function. These findings strongly advocate limiting the use of multiple drugs.

"I think patients will get much better care," Meltzer said.

"We are excited to be involved in the implementation of these algorithms," said Karen Rhea, M.D., vice president for Medical Services at Centerstone, the largest behavioral health care provider in Tennessee. With approximately 2,000 schizophrenic patients seen by providers in the Centerstone system, the availability of such a tool will be a highly valuable asset to mental health care in the state.

"We are particularly pleased with their being available online. It's going to make it much simpler for us to implement," Rhea said." As our system is completely paperless, this is a modality we use anyway, and will allow our providers to quickly access the portions of the algorithms that are of interest."

Another strength of the IPAP algorithms is their incorporation of evidence-based medicine." Protocols and algorithms are one source of collecting information from the literature," Jobson said." And information from the literature is one of the data streams used to make clinical decisions.

"So this will provide, we hope, salient information for health care providers in this country and abroad, to have the opinion of a large group of international experts on best treatment practices."

The Web-based format will allow health care providers to not only see the recommendations, but also see the level of supporting evidence and the references that back those recommendations up.

However, cautioned Jobson, "It is not prescriptive in the sense of being a recommendation for any single patient."

Being Web-based, the IPAP algorithms can also be easily adapted to reflect the results of the most recent research advances -- a problem inherent in print-based algorithms. Its Web-based format also allows the algorithms to be adapted for use by clinicians in any country.

"We devised a number of variations on the algorithms for different countries where the same medications are not available," Meltzer said.

"Dr. Meltzer was able to recruit an extraordinary faculty through his international work, his international contacts," said Jobson. "It's the most international a faculty that's ever addressed schizophrenia, certainly in a Web-based way."

To access the algorithm, visit http://www.ipap.org

 

 

 

 

 

 

 

 

Pets Can Help People with SZ

A research team in the U.K. is studying how bringing a pet to therapy sessions can help the long-term recovery of people with schizophrenia.

A group of 10 schizophrenia patients who had animal-assisted therapy (dogs involved in therapy sessions) showed improved motivation, improved "hedonic tone" (an improved ability to enjoy things), and improved ability to use leisure time as compared to a group of 10 patients who did not have animals included in their therapy.

Ahedonia (inability to enjoy or take an interest in things) and lack of motivation are two of the most troubling symptoms of schizophrenia that are not well managed by medications. Alternate therapy programs such as animal-assisted therapy may be key to managing these symptoms during the course of chronic schizophrenia.

Although experts caution that more research needs to be done in this area before we know whether this sort of therapy can help the thousands of people with mental illness, the research team on this particular study hopes that animal-assisted therapy "may contribute to the psychosocial rehabilitation and quality of life of chronic schizophrenia patients."

Read the full article online at BBC News (http://news.bbc.co.uk): Pet therapy 'helps schizophrenia', Jan 15 2005

Read more about other treatments for schizophrenia symptoms and side effects that can be used in addition to medications. (http://www.schizophrenia.com/treatments.htm)

 

 

 

 

 

 

 

 

Gene Test to Determine Med Doses

The FDA has just approved the first-ever laboratory test system that will allow physicians to observe certain portions of a patient's genetic information. The results of this test can be used to help select medications and dosages that may be more compatible with that person's unique biology.

The DNA microarray test analyzes the genetic information from the "cytochrome P450" gene family. These genes code for enzymes that act in the liver to metabolize drugs and other foreign compounds in the body. Specifically, this test looks at variations in a gene that codes the enzyme P4502D6, which the rate of metabolism of some common antidepressants, antipsychotics, beta-blockers, and chemotherapy drugs.

Although this microarray analysis is not intended to be the only factor in determining drug choice and dosage, it will be a valuable tool alongside clinical and medical history evaluations.

The AmpliChip Cytochrome P450 Genotyping Test is made by Roche Molecular Systems, and will operate with the Affymetric Genechip Microarray Instrumentation System (Affymetrix).

To read the full FDA news release, see: "FDA Clears First of Kind Genetic Lab Test" (Dec 23, 2004). Available at http://www.fda.gov

Read about another genetic test for medication compatibility on the horizon: "Future Clozapine Compatibility Genetic Test." Schizophrenia Newsblog Entry, Dec 20 2004.

 

 

 

 

 

 

 

 

Olanzapine, Clozapine, and Diabetes Risk

Two Atypical Anti-psychotic Drugs May Be Associated With An Increased Risk Of Diabetes For Patients With Schizophrenia

CHICAGO -- Patients treated with the atypical anti-psychotic agents clozapine and olanzapine may be at an increased risk for insulin resistance, which is a major risk factor for diabetes mellitus, according to a study in the January issue of the Archives of General Psychiatry, one of the JAMA/Archives journals.

"Compared with the general population, life expectancy in patients with schizophrenia is shorter by as much as 20 percent, attributable to higher rates of suicide, accidental deaths, and natural causes such as cardiovascular disease, infectious disease, and endocrine disorders," according to background information in the article. "Recently, the newer 'atypical' antipsychotic agents have been linked to several forms of morbidity, including obesity; hyperlipidemia; type 2 diabetes mellitus; and diabetic ketoacidosis [a severe complication of diabetes]."

David C. Henderson, M.D., from Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues, evaluated 36 non-obese outpatients with schizophrenia or schizoaffective disorder who were treated with clozapine, olanzapine, or another medication, risperidone. Participants were given a diet to follow to maintain body weight and were told to fast for 12 hours prior to undergoing a frequently sampled intravenous glucose tolerance test.

"Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects," the researchers found.

In conclusion, the authors write: "Psychiatrists and primary care professionals should be aware that patients treated with clozapine and olanzapine may be at increased risk for insulin resistance, even if not obese. Insulin resistance is associated with hyperlipidemia, hypertension, and cardiovascular disease and over time may increase the risk for diabetes mellitus in vulnerable individuals. Patients treated with these agents should be routinely screened, counseled to reduce risk, and provided early interventions."

(Arch Gen Psychiatry. 2005;62:19–28. Available post-embargo at archgenpsychiatry.com)

Editor's Note: This study was supported by a grant from the National Institutes of Health General Clinical Research Center, Bethesda, Md.; a Young Investigator Award from the National Alliance for Research of Schizophrenia and Depression, Great Neck, N.Y. (Dr. Henderson); and an Investigator-Initiated Independent Research Grant from Janssen Pharmaceutica, Beerse, Belgium.

Souce: JAMA (Journal of the American Medical Association) Press Release

 

 

 

 

 

Sexual Side Effects of Antipsychotic Medication

Several recent literature surveys, according to a review article in Mental Health Nursing, report that patients on antipsychotic medications often consider sexual side effects to be one of the most troubling aspects of taking their medication. However, this particular topic is often glossed over by medical professionals. Discomfort from the patient, their significant other, and the physicians can prevent the problem from being discussed and dealt with.

The sexual side effects (such as decreased libido, menstrual irregularity, and infertility) are often caused by a condition known as hyperprolactinaemia. Prolactin is a natural hormone in the human body that plays a role in several reproductive and sexual function. It is normally inhibited by the neurotransmitter dopamine. Thus, the dopamine-antagonist properties of many antipsychotic medications may cause prolactin production to exceed normal levels, resulting in some of the physiological and behavioural side effects noted above.

The newer, atypical antipsychotics have more specific dopamine-blocking action, and are therefore less likely to cause chronic hyperprolactinaemia or other associated side effects.

The article suggests that sexual side effects can often be relieved by reducing the dosage of current medication, or by switching to another medication that has less of an effect on prolactin levels. Talk to your psychiatrist and/or physician if you experience any troubling side effects. There is often a solution that eliminates the trouble without compromising health benefits.

For the full article, see "Sexual Dysfunction - the Forgotten Taboo." Online at RedNova News (http://www.rednova.com), Jan 13 2005.

 

 

 

 

 

 

 

Making Mental Health a Priority in the EU

At the World Health Organization Conference on Mental Health in Helsinki (opened Jan 18, 2005), the European Commissioner for Health and Consumer Protection called mental illness an "unseen killer" in Europe. Statistics showing the high number of suicides in the EU (around 58,000 annually, as compared with about 50,700 from motor vehicle accidents and 5,350 from murder or homicide), led Comissioner Markos Kyprianou to say that "mental illness is just as deadly as physical illnesses like cancer," and call upon the EU to place a weightier priority on a comprehensive Mental Health program for Europe.

As part of the EU Public Health Programme 2003-2008, some projects will address the causes of mental illness, as well as effective interventions. Results from these projects and statements from the Helsinki and other conferences will be used to design an official EU Strategy on Mental Health. Consultations on the Strategy will hopefully begin around mid-2005.

For the full story, see: " 'Mental Illness is Europe's unseen killer' says Markos Kyprianou' " (Jan 18, 2005). Available at http://www.eurofounding.com.

 

 

 

 

 

 

 

New Book: "Legacy of Madness" portrays growing up w/ mentally ill parent

Lisa Lieberman, author of "Leaving You: The Cultural Meaning of Suicide" has written an excellent and insightful memoir about the costs and responsibilities of growing up with a mentally ill parent. She includes some of her own anecdotes and experiences, as well as those of others she has interviewed. Read the entire article online by clicking on the link below:

"The Legacy of Madness: The Hidden Cost and Continuing Legacy of Growing Up with a Mentally Ill Parent." Hartford Advocate News (http://www.hartfordadvocate.com), Dec 30 2004.

 

 

 

 

 

 

 

 

 

New Movie: See Grace Fly

A new Canadian movie that is a fictional story of a woman that has schizophrenia, was released last month. We haven't seen the movie - but it sounds (perhaps) a little too dark for viewing by people with schizophrenia. It does sound like a good film for people inexperienced in schizophrenia, and who want to see a realistic movie related to the topic.

The basic overview of the movie is:

Grace McKinley is a brilliant 38 year-old woman with schizophrenia. When her mother dies, Grace's actions become increasingly erratic. She takes two weeks to report the death, and in that time is sent a shattering message that only she can decipher.

Grace's younger brother Dominic is a repressed yet courageous missionary working in war-ravaged Sierra Leone. Called home to arrange his mother's funeral, he is at the same time forced to deal with Grace's uncertain future and their forgotten past. The problem is, wanted by the police for questioning, and with her life threatened, Grace has disappeared onto the streets of Vancouver, fuelled by an indomitable will to spread her secret to the masses.

Reviews of the movie have stated:

""See Grace Fly", an award winning Canadian Independent Film, is finally ending its long battle for the big screen. Shot over 20 days in various locations around Vancouver, British Columbia in 2003, the film was made for a minuscule $65,000 and "the kind of favours you only ask once," as one of its stars Paul McGillion put it. Obviously the audience at the Vancouver Film Festival last September didn't notice, because both original showings received a standing ovation.

From Dark Horizons http://www.darkhorizons.com/news04/041203h.php

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"Portrayals of mental illness on-screen tend to fall into one of two extremes: incredibly convincing (think Rain Man or What's Eating Gilbert Grape) or painfully embarrassing (think Radio or The Other Sister). When directors attempt to deal with schizophrenia they take on an even greater challenge, as it's arguably the most misunderstood mental illness. Ron Howard went the biographic route in 2001 with A Beautiful Mind, focusing on the romantic, dramatic and academic life of John Forbes Nash Jr. Now, Canadian director Pete McCormack tackles a grittier, darker side of the disease with his debut film See Grace Fly.

Set in and around a perpetually overcast Vancouver (even interior shots seem especially shady), the film follows a schizophrenic woman (Gina Chiarelli), recently off her medication, who abandons her home when her mother dies and then roams the streets proclaiming the second coming."

There are a number of negatives aspects to the film cited in the review... "there's a host of yawn-inducing cinematic techniques, such as the old open-the-closet-door-to-reveal-a-painful-childhood-flashback scene. And when Dominic won't quit harping about how tormented he is from his experiences baptizing children in Sierra Leone, it just makes the ears ache."

"But focus on Grace, and the slip-ups begin to fade into the background. This may be a typically Canadian film, what with its bleak landscape and strained dialogue -- but it's more than just a rough-around-the-edges treatment of schizophrenia. See Grace Fly is an unsettling yet endearing portrait of a woman who doesn't know whether to challenge her family or herself.

Rating two 1/2"

Source: The National Post (Canada)

For more information see:

See Grace Fly - Movie Web Site - http://www.seegracefly.com/index2.html

 

 

 

 

 

 

 

 

 

 

Media Pop Portrayals of 'Madness'

The Washington Times recently published a critical article about pop media's overly-dramatic, unrealistic portrayal of people with mental illness. The article highlights recent films such as "The Aviator" (about Howard Hughes who suffered from OCD), "The Hours" (Virginia Woolf and major depression), and "Me, Myself, and Irene" (protagonist with schizophrenia), as well as TV shows such as ER (Sally Fields appears with rapid-cycling bipolar disorder).

Although Hollywood portrayals have progressed since movies such as "One Flew Over the Cuckoo's Nest", which shows frightening and practically torturous methods of "treating" sick patients, mental illness advocates and experts complain that the brief and dramatized portrayals in films and TV shows today send grossly incorrect messages: that mental illness is primarily caused by childhood trauma or upbringing, overbearing parents, or rigid societal labels, that characters need not or cannot take responsibility for their own recovery, or that extremely rare or difficult cases of recovery (such as John Nash's decision to "ignore" his schizophrenia without the help of medication) are more common than they really are.

Advocates encourage all of us to counter such unrealism with our own experiences of reality, sharing and spreading a true but hopeful message about the complexities and complications of living with a mental illness.

Read the full article: "The Film Industry's Mental Problem." Washington Times, Dec 31 2004. http://www.washingtontimes.com

 

 

Links Between Bipolar and SZ

Despite the fact that schizophrenia and bipolar disorder have different diagnostic credentials in the bible of American psychiatric medicine (the DSM-IV), the two disorders show a significant overlap of symptoms, as well as some similar treatment strategies. Now, scientists are discovering some of the key biological similarities that may link these diseases even more strongly.

For example, Dr. Amy Arnsten at Yale University Medical School has found what she calls a "molecular trigger" for both bipolar disorder and schizophrenia. This trigger appears to be stress, which can over-activate a brain protein called protein kinase C (PKC) in the prefrontal cortex. Dr. Arnsten points out that increased PKC activity (noted in the brains of people with schizophrenia and bipolar disorder) can lead to some of the common symptoms of the two disorders, such as distractibility, impulsivity, poor judgment, and hallucinations. Moreover, medications for schizophrenian and bipolar disorder often decrease PKC activity.

More evidence is coming in from the field of genetics. Dr. James Potash of Johns Hopkins University Medical School says that "schizophrenia and bipolar disorder [appear to] share at least a few genetic roots." He gives the example of research that traces genes suspected as important to both disorders to the same region of chromosome 13.

In other fields, researchers like Dr. E. Fuller Torrey are examining the role that infections play in the development of both diseases. Torrey notes that antibody response to some infectious agents are elevated in people with schizophrenia, and also people with bipolar disorder.

The ramifications of such findings are many. One consequence may be a restructuring of diagnostic categories; for example, some medical experts are discussing whether people who experience psychosis along with the symptoms of bipolar disorder should be diagnosed under schizophrenia spectrum disorders rather than with mood disorders. Similarities in underlying biological pathology may also lead to new treatments that will be effective for both disorders. Finally, further understanding of these links provides even more evidence that psychiatric illnesses are diseases of the brain, just like diabetes is a disease of the pancreas and hepatitis is a disease of the liver.

Read more about research that shows schizophrenia and bipolar disorder are diseases of the brain:

1. Schizophrenia is a disease of the brain (http://www.schizophrenia.com/disease.htm)
2. Bipolar Disorder is a disease of the brain (http://www.moodswing.org/disease.htm)

Read about the link between stress and schizophrenia risk

For the original news story, see: "Stress May Link Bipolar Disorder and Schizophrenia" (Jan 16 2005). Available online at http://www.sun-sentinel.com

Another Gene Linked to Schizophrenia

A news report out of India states that another gene(that when changed, or damaged) has been linked to Schizophrenia.

Director of IGIB, Prof Samir K Brahmachari, who is at present attending the 92nd Indian Science Congress in the city said, ‘‘A consortium of scientists currenlty working on identifying and mapping of genes associated with diseases (Single Nucleotide Polymorphism or SNP) prevalent in India has succeded in identifying ‘cynaptogyrin’, a gene responsible for schizophrenia.’’

‘‘Scientists during their study found that change in the structure of the gene was responsible for causing the brain disorder,’’ said professor Parth Majumdar, head of genetics centre at ISI (Indian Statistical Institute), Kolkata.

For the full story, go to:
http://cities.expressindia.com/fullstory.php?newsid=113088

 

Cannabis and Schizophrenia

New Perspectives in the Studies on Endocannabinoid and Cannabis: Cannabinoid Receptors and Schizophrenia

Hiroshi Ujike and Yukitaka Morita

J Pharmacol Sci 96, 376 – 381 (2004)

This article reviews the evidence of cannabis (marijuana) with respect to psychosis and schizophrenia. The authors pose adding another element to the model of schizophrenia that includes cannabinoid receptors. These receptors (referred to as CB-1 receptors) are increased in the brains of many people with schizophrenia. Recently, there was an attempt at using a medication designed to target these receptors that did not show a benefit over a placebo (Click here for my review). However, there is evidence that cannabis can cause similar cognitive (thinking) deficits in someone acutely intoxicated from THC (the active ingredient in marijuana).

Additionally, many people experience some degree of psychosis/hallucination while under the influence of THC. Some have described a more persistent “cannabinoid psychosis” in ultra-high level users. In people with schizophrenia, positive symptoms are typically worsened by the use of cannabis, even if the person is regularly taking antipsychotic medications. Some studies have also argued that the use of cannabis in a high risk population may precipitate the development of schizophrenia. In other words, people with a genetic predisposition may receive the trigger to develop schizophrenia from using marijuana heavily, though this is not fully proven yet.

Cannabinoid receptors are found in both the brain and the body’s periphery. When they are in the brain they are referred to as CB-1 and in the rest of the body they are called CB2. Why has the human body got receptors for use with THC? It is because there are endogenous (produced by our own body) molecules that have evolved to fit in these receptors .The most studied is called anandamide and it is a fatty-acid derivative. When rodents have been given synthesized anandamide, they behaved just as if they were given marijuana. In one study of the fluid around the brain and spinal cord (CSF) of people with schizophrenia, it was found that there was a 2-fold increase in the amount of anandamide compared to healthy controls. This level did not change even with the administration of antipsychotic medications. In people with schizophrenia, there is an increase in the CB-1 receptors located in the caudate and putamen (areas of the brain associated with the dysfunctions found in schizophrenia.) It is thought that this increase in receptors may have to do with negative symptoms and with some of the cognitive (thinking) disturbances found in schizophrenia.

There are many genetic variations of the CB-1 receptor. It is possible that having a particular genotype (genetic variation) of the receptor may put someone at greater risk of cannabinoid psychosis. Some have described this type of condition as “amotivational syndrome” because of the profound negative symptom quality to it. One particular genotype has been most clearly linked to people with disorganized type of schizophrenia; a type more characterized by inability to maintain activities of daily living than with positive/psychotic symptoms. This variation has also been seen in people with the amotivational syndrome due to marijuana but not with psychosis due to amphetamine (speed, etc.) or other drug use. However, this genetic variation is merely an association and not yet determined to actually be a testable risk factor for schizophrenia. The role of cannabinoids will be the subject of much further research over the upcoming years.

Click here for the ariticle on PubMed (or go to http://www.pubmed.com and do a search on the primary author or the study title, both listed at the top of this article).

For more information on Marijuana/cannabis and schizophrenia risk, see: http://www.schizophrenia.com/hypo.html#street

 

 

 

 

 

 

 

 

 

 

 

SZ Risk from Short-Term Birth Intervals

Association between short birth intervals and schizophrenia in the offspring.

Smits L, Pedersen C, Mortensen P, van Os J.
Schizophr Res. 2004 Sep 1;70(1):49-56.

Background: Conceiving immediately after delivering a baby has been found to increase risk for premature births, maturity problems and birth defects in the child. Some have hypothesized that this increased risk may be due to incomplete restoring of nutrients such as folic acid, vitamins B6 and B12 in the mother at the time of conception. These nutrients usually take up to 1 year to return to recommended levels. Since there may be a link between prenatal deficiencies of these nutrients and schizophrenia, this study looked at the relationship between the length of the preceding birth interval and the risk of schizophrenia in the offspring.

Method: This was a Danish study that collected information from a huge number of individuals - over 1.4 million Danish-born individuals and their families - and linked it to data from the Danish Psychiatric Central Register which contained data on all admissions to Danish psychiatric inpatient facilities over a certain time period. Using this database, they calculated birth order, size of family and birth interval to nearest older and younger sibling and did various other analyses.

Results: From their group, they found that a total of 5095 persons were diagnosed with schizophrenia. They found that schizophrenia risk changed depending on the birth interval. Those born after long birth intervals (27 months and longer) had the lowest chance of having schizophrenia, while those with moderately short birth intervals (15 to 20 months) showed highest rates. Contrary to what you would expect, they found that there was less risk in those born after very short birth intervals (<15 months) or after intermediate birth intervals (21 to 26 months). All these associations were independent of history of mental illness in a parent or sibling, season of birth, parental age, birth order, level of urbanization at birth, or calendar year.

Interpretation and Limitations: This study suggests that there is a link between birth spacing and the risk of schizophrenia in the child. Individuals born after birth intervals of up to 26 months, and predominantly those born within 15 to 20 months after their preceding sibling, had higher risks of developing schizophrenia than those born after birth intervals of 45 months or more. However, they had an interesting finding where the shortest interval did not result in the greatest risk, as you’d expect if the hypothesis is true about incomplete restoration of maternal nutrients of B-vitamins such as folic acid and vitamin B6. The authors try to explain this contradiction by suggesting that the shortest birth intervals may have occurred in non-lactating women who tend to have more favorable folic acid levels than lactating women. But this is just a hypothesis and needs to be researched further. Also, while this study focused on those with at least one older sibling, they also looked at data from first-born individuals and found that the highest rates associated with short birth interval was about the same as being an only child.

There are several limitations to this study. Since the authors did not have information on duration of pregnancy, they used birth intervals as estimation for inter-pregnancy interval – which might result in overrepresentations of things like premature births in the shortest birth intervals. Since prematurity may also be a risk factor for schizophrenia, this may have biased the results. Also, this study did not look at the effects of some other hypothesized environmental risk factors of schizophrenia possibly associated with birth interval such as maternal stress during pregnancy, later infections or others such as smoking, socio-economic status, planned pregnancy etc. Additionally, since this was a Danish study, their sample may not be representative of other countries with different levels of nutritional problems in the population.

Support: This study was supported by the Stanley Medical Research Institute, the Maastricht Care and Prevention Research Institute (CAPHRI) and the European Graduate School for Neuroscience (EURON) and the National Centre for Register-based Research is funded by the Danish National Research Foundation.

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