Schizophrenia Research Blog: October 2004 Archives

October 18, 2004

Change disease name to decrease stigma?

Can a less pejorative Chinese translation for schizophrenia reduce stigma? A study of adolescents' attitudes toward people with schizophrenia

Psychiatry and Clinical Neurosciences
Volume 58 Issue 5 Page 507 - October 2004

The name schizophrenia (from the Greek meaning "split mind") has been in use for decades to describe schizophrenia. While it isn't the original term used for the disorder (Emil Kraepelin first described schizophrenia in modern medical literature and called it dementia praecox) it has come to be the most commonly used term and one that carries with it much information but also the stigma that is often associated with major mental illness. In China, the word schizophrenia was translated to essentially mean "mind-split disease." The authors of this study wanted to determine what the effect would be of re-translating the word for schizophrenia to mean "dys-regulation of thought and perception" which would convey a more clinical/biological connotation than "mind-split disease." The authors gave a survey to 314 10th/11th graders in an average (academically) school in Hong Kong. They gave the students a story that was about someone who met criteria for diagnosis of schizophrenia and used either the common label for the disease, the new term or no word at all for the symptoms that the patient had in the story. Students were then asked to give their impression on various topics including social distance, stereotypes of schizophrenia, and attributions regarding mental illness. Students were also asked if they knew anyone with mental illness, if they were themselves religious and if they had ever received a diagnosis of any kind of mental illness.

The authors found that the use of the more "politically correct" term had little to no impact on how the students rated the various patients in their vignettes. The students tended to show less stigma than the authors anticipated in general, regardless of the label given to the patient in the story. Interestingly, religious students tended to give less attribution to the patients for their disease than did agnostic students.

There have been studies over the years that have shown that patients generally prefer less pejorative ways of describing their conditions. There are many features of mental illness care that are generally stigmatized: speaking with a psychiatrist, taking medication, difficulty with social functioning/hygiene/work. In Hong Kong a recent campaign has tried to teach people of the new terms in an effort to help decrease stigma and barriers to treatment. The effects of this campaign are difficult to evaluate and perhaps it may have been partially responsible for the overall decreased stigma seen regardless of description given that the students were told of the symptoms that the patient was suffering from. It should also be noted that this study only looked at a small, specific population (high school students) and so the general results are difficult if not impossible to generalize to the overall community of Hong Kong, much less to people in the United State or Europe. However it does present a dilemma with respect to how to most effectively decrease stigma. Would changing the name of schizophrenia to something clinical or biological in English (such as dopamine dysregulation or neurobiological disease) actually help? There probably is no way to know for sure, but efforts to help decrease stigma are still definitely needed worldwide as shame and misunderstanding of mental illness still creates a difficulty for many of those affected by schizophrenia whether consumer or family member.

Click here to find article on PubMed

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October 17, 2004

Pleasurable Voices?

Pleasurable auditory hallucinations.

Sanjuan J, Gonzalez JC, Aguilar EJ, Leal C, Os J.
Acta Psychiatr Scand. 2004 Oct;110(4):273-8.

Auditory hallucinations (AH) or voices are one of the most frequent symptoms of schizophrenia. Some studies have suggested that hallucinatory voices can also be heard by members of the non-psychiatric general population. The authors suggest that these AH’s may range from a spectrum of those who are at ease with their AH and who are not identified as a patient, to individuals with a severe psychotic disorder who are tormented by intrusive voices. The emotional value of these voices may determine the extent of the distress that they cause. Some researchers have made the point that not many people have investigated voices that are perceived as being pleasurable. As a result, this study aimed to assess the frequency of voices as a pleasurable experience in a patient group and also cross-validate the pleasurable aspect of the experience using established scales.

This study was conducted in Spain. The authors used a standard rating scale (PSYRATS) to ask patients with AHs (89 schizophrenia and 17 other psychoses) who were taking anti-psychotic medications, about their experiences with voices. They added extra items to the questionnaire to inquire if the experience was pleasurable.

They found that 26% of the patients reported the voices as pleasurable at least occasionally, and for 10 individuals the experience of pleasurable voices was the norm and not the exception. Those who said they had pleasurable voices felt like the negative component of the voices was much lower and resulted in better scores on the rating scale. Those who had pleasurable hallucinations had less distress, less negative content, quieter voices and more control over their voices. The authors suggest that these results have implications for therapy. They suggest that since coping training and taking medications can be affected by the presence of pleasurable hallucinations, clinicians need to modify their technique depending on the patient’s response to his/her voices. Some individuals might need more psychoeducation, family therapy, cognitive-behavioral interventions that focus on adjustment to daily life, perhaps with conservation of pleasurable hallucinatory experiences.

This study is limited in several ways. First, the relative proportion of those with pleasurable voices was small and hence statistically, the study may have lacked power. Second, the questions that were attached to the standard questionnaire were not standardized (i.e. gone through statistical tests) and as such may have presented a response bias. Also, clinical information was collected based on patient's recollection without corroboration on all occasions. Nevertheless, this study highlights the need for family, doctors and therapists to discuss the possibility of pleasurable AH with all patients before starting any form of treatment.

This study was supported by Spanish grants from Generalitat Valenciana (GV01-93), Red de Genotipación y Psiquiatría Genética (ISCIII 2003- G03/184), FISS P.I. 02/0018, and Eli Lilly Company Spain.

Click here to find this article on PubMed

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Does season of birth affect schizophrenia?

Summer birth and deficit schizophrenia: a pooled analysis from 6 countries.

Messias E, Kirkpatrick B, Bromet E, Ross D, Buchanan RW, Carpenter WT Jr, Tek C, Kendler KS, Walsh D, Dollfus S.
Arch Gen Psychiatry. 2004 Oct;61(10):985-9.

Schizophrenia is an illness due to interactions between genes and environmental factors. Although it has been debated by researchers, one of the environmental risk factors suggested is season of birth. Winter birth was first reported to be a risk factor for schizophrenia in 1929 and many other studies have replicated this finding. Researchers have suggested that family history and the prevalence of certain viruses (eg Borna Disease Virus seropositivity), seasonal variations in infectious agents (eg viruses), sunlight exposure and vitamin D, and the availability of nutrients are all explanations that could explain this seasonality of birth effect noticed in schizophrenia.

Some researchers have gone on to further suggest that the clinical features associated with winter births differ from those of “deficit schizophrenia”. Deficit schizophrenia is defined with respect to the lack of positive symptoms, where a person has mainly negative symptoms (eg. lack of emotion, lack of pleasure etc) and a relatively severe form of the illness. But other researchers have suggested that there are more summer births in patients with deficit schizophrenia. Since it is unclear whether summer or winter births affect this type of “deficit” schizophrenia, this study looked at pooled data from the previously published studies as well as unpublished data in order to clarify the role of season of birth in schizophrenia.

The researchers looked at studies of season of birth in which it was possible to make a deficit/nondeficit categorization based on clinical scales/questionnaires. They selected published studies with samples of convenience and all known population-based studies with the deficit/nondeficit categorization. The studies came from 6 countries including the United States, Ireland, England, Scotland, Spain and France. They ended up extracting 3 published studies of samples of convenience, 2 population-based prevalence studies, and 5 population-based studies that approximated incident samples.

They found that there was a significant difference between deficit and nondeficit people in season of birth and that this difference was largely due to an increase in deficit schizophrenia births in June and July. From this, they concluded that deficit schizophrenia has a season of birth pattern that differs from that of nondeficit schizophrenia. And the authors suggest that deficit schizophrenia may be a separate disease within the syndrome of schizophrenia.

It is important to note the limitations of this study. First, data was only collected from northern hemisphere countries. An unpublished multi-center prevalence study by a group from Australia has failed to show an association between deficit schizophrenia and summer birth. It is also difficult to decide from this study whether the association between deficit schizophrenia and summer births is due to an increase in summer births in the deficit group compared with the general population or a decrease in summer births in the nondeficit group. Third, although this season of birth effect is one type of hypothesis proposed, it is by no means written in stone. There are many researchers who argue against this idea. More research is needed to clarify this relationship.

This study was supported in part by grants MH44801 (Dr Bromet), MH41953 (Dr Kendler), MH40279 (Dr Carpenter), and MH60487 (Dr Messias) from the National Institutes of Health, Rockville, Md.

Click here to find this article on PubMed

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How does the brain change in schizophrenia?

Neuroplasticity and schizophrenia.

Frost DO, Tamminga CA, Medoff DR, Caviness V, Innocenti G, Carpenter WT.
Biol Psychiatry. 2004 Oct 15;56(8):540-3.

This article was based on a workshop sponsored by the International Congress on Schizophrenia Research that looked at how changes in the brain’s structure and function (neuroplasticity) affect schizophrenia. The workshop brought together researchers specializing in schizophrenia as well as other doctors who try to understand how the brain works. By using neuroplasticity as a way to understand the illness, they wanted to find special ways to increase our knowledge and understanding of schizophrenia, its treatment and its prevention. This has already been done in other medical conditions For example, those who are deaf or blind from a young age show that lesions/cuts in one part of the brain can cause functional changes in other parts of the brain. This is evidence of neuroplasticity and how it can help us understand behavior changes.

Changes in the brain occur during normal brain development, help with learning and memory and occur in other diseases such as epilepsy. Since it is often difficult to look at brain cells directly, researchers have tried to look at the neuroplasticity in schizophrenia in indirect ways. They’ve looked at 1) observable behavioral changes (phenotypes) as they emerge, 2) early risk factors for schizophrenia and 3) the what happens over time due to the disease and its response to medication.

Based on this type of research, the workshop outlined different stages in the development of schizophrenia with respect to brain changes. These were:

1) Prodromal stage: This can be either months to years (slow onset) or can be as fast as weeks to months. With a slow onset, this could reflect increasing changes in the brain over time or a response to altered brain activity. In this stage, some changes in behavior are noticed, although not all patients with such symptoms will have schizophrenia. There is much more work needed at this stage to figure out the risk factors for later psychotic symptoms.

2) Psychosis onset stage: This is when symptoms of psychosis begin (eg hearing voices). There are two hypotheses for how neuroplasticity could contribute to schizophrenia. The Developmental hypothesis says that there are abnormal changes that occur early in life (perhaps even during conception of the baby) which reach critical levels and then result in the disease later on. The Two Hit hypothesis says that an early developmental defect could increase an individual’s chances of becoming psychotic in response to a second trigger that occurs at the end of the teenage years. This then affects how the illness changes over time. Since the connections in the brain are complex, it may be difficult to bring the brain back to a "normal" state once psychosis develops. But, with medications, it may be possible to bring the brain back to a near-normal pattern, even while the underlying brain system remains abnormal.

3) Symptom stabilization phase: After taking regular medication, about 25-35% of patients can go back to a “quiet period” where psychotic symptoms decrease. This could be because of brain plasticity that occurs with medications, where the brain adapts to the drugs and results in a state of reduced risk for relapse. But the early fluctuations in psychosis may have already affected social, cognitive and emotional functioning. More research is needed to figure out things that can help stabilize the brain.

4) Late-life heterogeneity phase: Long-term studies of schizophrenia show a reduction in psychosis and improved function with aging, although some patients can go into a rapidly progressing dementia after age 65. These aging-related changes could be due to hormones and more research is needed to understand these changes in older people.

In terms of future research, the workshop participants hoped to introduce new ways of looking at schizophrenia and call for more research to figure out which features of the brain are normal or abnormal at various ages, different stages of the disease and different behaviors due to the illness. More research is needed with children who are at high risk for the illness as well as the effects of chronic medicine on the brain over time. The idea of schizophrenia as a syndrome with a spectrum of those who have active psychosis and those who do not is also pushed forward by this article.

Click here to find this article on PubMed

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October 12, 2004

Sex hormones in psychotic men

Sex hormones in psychotic men
Thomas J. Hubera, Christian Tettenborna, Eckhard Leifkeb and Hinderk M. Emrich
Psychoneuroendocrinology, Volume 30, Issue 1 , January 2005, Pages 111-114

The authors of this study wanted to look at hormone levels in male patients with psychosis because there has been a theory that estrogen (the female sex hormone) has some kind of protective effect on women. Women with psychosis often have lower levels of estrogen (or similar compounds) in their blood compared to healthy controls. Estrogen may have an impact on the dopamine system (the neurotransmitter in the brain most closely linked to psychosis.) The significance of this observation is not known, but nevertheless the observation has at least been made.

It has also been seen that excess androgens (male sex hormones, like testosterone) can lead to psychosis. Perhaps this is best seen when people take steroids which are similar structurally to male sex hormones and can have profound side effects on their thinking. While certain hormones are often referred to as "male" or "female" sex hormones, it should be noted that while they may be in higher concentrations in particular sexes, both sexes produce an amount of these hormones and they serve various different and similar functions in both sexes.

The authors of this study took blood samples from 34 consecutive male inpatient admissions who met criteria for inclusion (no major medical illnesses, no substance abuse, could not be currently manic, etc.) hormones studied were testosterone, free testosterone, estradiol, oestrone, luteinizing hormone (LH) and follicle stimulating hormone (FSH). They were compared with 34 age and size (BMI) matched controls who were similar in as many ways as possible with the inpatients but they did not have a psychotic disorder.

The study showed that men with psychosis had a statistically significant lower level of estradiol and estrone (which are relatives of estrogen that circulate in the blood) compared to the controls. Both groups had similar levels of testosterone and male sex hormones. Some antipsychotic drugs can influence the production of sex hormones and the authors tried to exlude those effects by excluding patients on the drugs that cause the most significant effect. However, it is possible that some of the effect nonetheless may be due to the influence of the hormone prolactin. Prolactin increases when dopamine is blocked (which is the general mechanism of antipsychotic medications.) Increased prolactin (which is a hormone that regulates breast tissue growth and milk production in women) can have an influence also on the menstrual cycle and on female sex hormone production and likewise may have an impact on the estrogen levels in men. Prolactin levels were not measured in this study and the hormone's effect therefore is not certain in the results. Also, the levels of hormones in the blood may not necessarily correlate exactly with the levels that are around the brain and that could have an impact. Also, this is a small study and so the ability of this study to predict for all people with psychosis is limited.

Ultimately this is an interesting study that at this point does not influence the treatment of schizophrenia. As hormone replacement therapy is currently controversial, and has been shown to have many side effects, this study should not be used as the basis for taking estrogen or estrogn-like products (soy, black cohosh, etc.) to help with psychosis.

Click here to find this article on PubMed

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October 11, 2004

TMS and schizophrenia

Transcranial Magnetic Stimulation in the investigation and treatment of schizophrenia: a review

H. Magnus Haraldsson, Fabio Ferrarelli, Ned H. Kalin and Giulio Tononi.

Schizophrenia Research
Volume 71, Issue 1, 1 November 2004, Pages 1-16

Transcranial magnetic stimulation is a technology that is increasingly being harnessed for use in psychiatry both therapeutically and as a tool for research. It works based on creating a targeted magnetic field that can interact with brain cells and cause them to be excited and fire more frequently. There are 2 main types of TMS and both have different uses. The most common side effect of TMS is headache.

There are 2 kinds of TMS. One offers a single pulse, while another technique utilizes more rapid, repeating pulses. In each, a coil is placed on the patients head and the magnetic field is applied. There are different shaped coils (circular or figure of eight) intended to reach either a more diffuse or more focused area of the brain. The circular coils tend to give a more diffuse area of stimulation. A number of variables influence how accurately a specific brain area can be stimulated with TMS. These variables include the intensity of stimulation, the shape and orientation of the stimulating coil and the excitability, type and orientation of the neurons in the area of stimulation. One can use one or two coils to acheive different electrical effects in the brain and to target different areas.

Is TMS effective in treating mental illness? Well, the research is just beginning...There is some evidence that it might help with depression when applied to either the Left or Right prefrontal cortex of the brain. Research has been limited until recently be difficulty in creating a "sham" condition. It is important to have a "sham" that seems like the patient is getting TMS, and appears/feels exactly the same, but does not have magnetic current that has any effect. This is needed to help eliminate placebo effect and more certainly attribute any benefits seen to the TMS than to the patient's psychological hope that the treatment is better. There is now a new sham technique so hopefully research into TMS will increase. It is still not known exactly what settings or locations to place the coils are best in schizophrenia.

Results with TMS have at best been mixed so far. Most studies have not shown a significant benefit, but not much is known about the most optimal way to utilize the technology. There is some hope that perhaps if the part of the brain that processes auditory hallucinations receives a signal from TMS it might decrease the hallucinations. This however, will be a long way off from being clinically useful.

Overall, TMS is a new technology that may eventually have clinical benefit and currently is helpful in researching isolated parts of the brain. It may prove more beneficial as an adjunct to other technologies or may ultimately be useful on its own in treating schizophrenia.

This work was supported by a grant from the families of Donald and Patricia Cheney and Jack and Patricia Lane

Click here to find the article on PubMed

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Ziprasidone vs. Olanzapine (short term)

Randomized, Controlled, Double-Blind Multicenter Comparison of the Efficacy and Tolerability of Ziprasidone and Olanzapine in Acutely Ill Inpatients With Schizophrenia or Schizoaffective Disorder

George M. Simpson, M.D., Ira D. Glick, M.D., Peter J. Weiden, M.D., Steven J. Romano, M.D., and Cynthia O. Siu, Ph.D.

Am J Psychiatry 161:1837-1847, October 2004

This is a study that compares both the effectiveness and side effects of two second generation antipsychotics: Olanzapine (Zyprexa, by Eli Lilly) and Ziprasidone (Geodon, by Pfizer). The authors state that there have not been very many direct comparisons between the newer drugs but that each drug seems to have various side effects labeled on them.

The study was set up very well to help eliminate confounding variables (things that can alter a study other than what one is looking for.) It is a double-blind (neither the patient or the people working on the study know what drug the patient is on), randomized (anyone is equally likely to get one drug or the other), and it takes place throughout the US to help eliminate regional differences. The authors used a number of common rating scales to asses for changes in symptoms both positive symptoms and negative symptoms. They also looked at weight gain (body mass index), insulin levels (to see of increased risk of diabetes) and cholesterol levels. However, the authors only looked at 6 weeks worth of data so long-term implications of these data are hard to decipher and can only at best be inferred.

The results showed that both groups were the same with respect to the number of patients who dropped out of the study because the drug did not work. However, ultimately, a statistically significant number of patients dropped out from the ziprasidone group vs the olanzapine group, however the reasons are not made clear (lost to followup or withdrawn consent perhaps.) This may or may not be clinically meaningful. Having patients withdraw early from a study potentially can distort results and lead to statistical confusion and less accurate results depending on how the lost patients are tabulated.

The main results of the study showed that both drugs had approximately equal efficacy on treating the core symptoms of schizophrenia. Where thedifferences were seen was primarily in side effects. This is where the withdrawal of patients makes things difficult as well as the short duration of the study. The side effects looked at were weight gain, cholesterol changes and diabetes parameters. Many of these things take time to develop and while a change in six weeks is suggestive of future problem it does not necessarily speak to the long term significance. However, this study showed that olanzapine had a more serious side effect profile than ziprasidone which is something that many people have noted over recent years. They also showed that cardiac conduction defects often attributed to ziprasidone were not clinically seen here.

Overall, does this mean that olanzapine is a bad medication compared to ziprasidone? Well, this is one case where it is definitely helpful to see who sponsored this study: Pfizer, who makes ziprasidone (geodon) in the US. Ziprasidone has had a lower market share since coming onto the market several years ago. While there may be many reasons for this, perhaps this study was done to help bolster ziprasidone's position in the marketplace. Regardless of intention, data is data (statistical manipulation aside) and this is important information.

However, it cannot be denied that olanzapine does have severe metabolic side effects that should be considered when one starts on an antipsychotic. If someone you know is already on one of these or another, this study is not enough to warrant a change, especially if the medication is working. HOwever, it does point out again the importance of maintaining a close eye on the overall health of someone with schizophrenia and not settling for merely the reduction of symptoms to be enough when one is taking care of such a patient.

This study was supported by Pfizer Inc. (maker of Geodon which is the tradename for ziprasidone).

Click here for a link to this study on PubMed

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October 04, 2004

Cognitive Behavioral Therapy and Schizophrnia

Trower P, Birchwood M, Meaden A, Byrne S, Nelson A, Ross K.
Cognitive therapy for command hallucinations: randomised controlled trial.
Br J Psychiatry. 2004 Apr;184:312-20.

Startup M, Jackson MC, Bendix S.
North Wales randomized controlled trial of cognitive behaviour therapy for acute schizophrenia spectrum disorders: outcomes at 6 and 12 months.
Psychol Med. 2004 Apr;34(3):413-22.

I want to focus on these two papers for this posting which both talk about the use of Cognitive Behavioral Therapy and its role in treating schizophrenia.

Cognitive behavioral therapy (CBT) is a form of psychotherapy in which the patient is given challenges to certain beliefs they have. Using changes in behavior and changes in the way people process certain ideas, a patient can try and understand the world differently. CBT is very often used to treat depression; patients often perceive the world negatively and put a negative spin on most thoughts. CBT is used to help change those perceptions to a view more based on reality. In this way, people with depression are more able to focus on their problems and solve them rather than letting them build up to insurmountable obstacles.

In schizophrenia, CBT can be useful for many symptoms. Other studies have shown benefits in stable outpatients in decreasing rehospitalizations, increased social skills and decreased distress from symptoms such as voices and other hallucinations/delusions. It also has shown benefit in treating negative symptoms (flat affect, decreased pleasure, decreased emotion, etc.) However, conventional wisdom used to hold that in an acute setting such as the hospital, patients were too sick to utilize psychotherapy because they were too symptomatic to concentrate on the ideas of the therapy. These articles begin to break down that assumption.

In the first article, the authors describe the use of CBT to treat command auditory hallucinations (CAH). CAH can cause significant damage to people with schizophrenia because they are often destructive messages that the person feels compelled to follow or else they may face serious risks. THe voices often speak very sternly and invoke the power of god or the devil to compel the person to act in ways they might not otherwise. CBT can be useful in trying to utilize what the authors describe as "social rank" theory. This theory ultimately tries to teach the consumer that they "outrank" the voices and therefore will help to diminish the importance of the message from the voices. It does not decrease the loudness, frequency or change the messages necessarily, but can help make the voices less of a threat. The subjects of this study had all complied with their voices in some sort of destructive manner prior to entering the study and were considered to be very high risk of doing so again. They were either given this special therapy or randomized to not get the therapy in addition to receiving their regular treatment and medications. The authors of this study found that their therapy did as they expected. The voices "topography", meaning how they sounded, what they said, and how often they were present did not change but the patients who recieved the psychotherapy had fewer episodes or compliance or other acts that were seen to appease the voices. Though this therapy can be labor intensive and expensive, the benefits were notable and ultimately could be seen as cost effective in addition to symptomatically effective.

The second study was done with inpatients admitted for psychotic exacerbation in Wales. Patients were randomized to either receive regular treatment or regular treatment plus CBT. THey could have up to 25 weekly sessions and were followed over the course of one year. The authors found that at one year, the patients who had the CBT, starting with their hospitalization and while acutely psychotic, showed benefits over those who did not receive the additional therapy. They noted that the benefits extended to both positive (delusions, hallucinations, paranoia) symptoms and negative symptoms as well as overall social functioning.

Both of these studies looked at the use of CBT, a very commonly practiced form of psychotherapy, on people with schizophrenia in more acute and high risk settings. The use of CBT in conjunction with medications seems to have benefits. It should be noted that not everyone with schizophrenia may benefit from CBT. However, people who are able to attend to the group and have the cognitive capacity to follow the thinking in CBT can show great progress and may ultimately require fewer hospitalizations and have better quality of life. CBT is not a replacement for medication but should if used should be used in conjunction with medications.

Click here for the link to article #1 on PubMed

Click here for the link to article #2 on PubMed

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October 02, 2004

Twins and Brain size

A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia.
Biol Psychiatry. 2004 Sep 15;56(6):454-61
Van Haren NE, Picchioni MM, McDonald C, Marshall N, Davis N, Ribchester T, Hulshoff Pol HE, Sharma T, Sham P, Kahn RS, Murray R.

Technologies such as magnetic resonance imaging (MRI) allow researchers to take pictures of the brain. Such imaging studies have found that there are brain abnormalities in those suffering from schizophrenia. These include changes in volume of the brain, larger ventricles and decreases in sizes of certain structures (eg hippocampus and amygdala). Where do such brain changes come from? The environment or genes (characteristics you are born with that you get from your parents).

Studies done with twins who have schizophrenia suggest that both genes and environment play a role in such brain abnormalities. This current study looked at the effect of genetic vulnerability to develop schizophrenia and the role of genetic and environmental factors in any brain abnormalities found. Unlike previous MRI studies, this study was able to include a good sized sample of 82 participants that included monozygotic (identical twins, same egg) twin pairs where both had schizophrenia (concordant) as well as twins where only one had schizophrenia (discordant). They also included control twin pairs without schizophrenia and discordant same-gender siblings and pairs of unrelated control subjects.

They found that MRI brain scans showed that similarities in brain volume increased as pair members were more closely related genetically (monozygotic twins > siblings > unrelated control subjects). Twins with schizophrenia, whether from concordant or discordant pairs, had smaller whole brain volumes than control twins. Also, the person with schizophrenia in the discordant pair had more abnormalities in certain parts of the brain (eg hippocampus, third and lateral ventricles).

From this, the researchers concluded that brain size is affected by genetics and a smaller brain may be because of a genetic vulnerability to develop schizophrenia. However, the environment also seems to be involved, since there were twins who had identical genes yet the one with schizophrenia showed abnormal brain structures.

A limitation of this study is that the control twins were allowed to have other psychiatric conditions which can also affect the brain. Also, the researchers did not get information on the role of environmental events such as birth complications which could explain the difference in the brain volumes. They were also unable to get information on medications which could also have played a role. In the future, including healthy dizygotic (different eggs) twin pairs would also provide more information about the role of genes and environment in schizophrenia.

This research was sponsored by a travel grant (Neeltje van Haren) of the Netherlands Organization of Scientific Research (NWO: R56–465), Wellcome Trust, and Stanley Medical Research Institute.

Click here to find this article on PubMed

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October 01, 2004

Why do schizophrenic patients smoke?

NOTE: for additional information on schizophrenia and Smoking or Nicotine

Why do schizophrenic patients smoke?

Persons with serious mental illness, especially schizophrenia, smoke at much higher rates (45% to 88%) than those without mental illness (23%). Patients with schizophrenia also have a harder time in quitting smoking. Researchers have found this when they looked at abstinence rates in smoking cessation trials using nicotine replacement patches (36% to 42% abstinence in schizophrenia) and bupropion (11% to 50% abstinence in schizophrenia). In comparision, non-psychiatric smokers have higher abstinence rates at the end of such trials (50% to 75%). Below are two studies that were published this month, that discuss why this may be.

The German article (Cattapan-Ludewig et al) reviews studies that discuss why individuals with schizophrenia smoke chronically. Certain thinking patterns are affected in schizophrenia including sustained attention, focused attention, working memory, short-term memory, recognition memory and even processes that are preattentive (eg reflexes). Some studies have suggested that there may be improvements in these areas after treatment with nicotine. So, it maybe that nicotine is used as a "self-medication" strategy by those with schizophrenia to improve these difficulties with attention, cognition, and information processing as well as the side effects of antipsychotic medications (eg extrapyramidal effects).

The second recent study (Dolan et al) specifically looked at what happens if a smoking cessation intervention is used. They investigated whether the presence of these cognitive problems prior to smoking cessation treatment was associated with smoking cessation treatment failure in schizophrenia as compared to non-psychiatric control smokers. They looked at performance on neuropsychological tests of thinking, planning, visual-spatial skills and attention.

After going through the smoking cessation program, those with schizophrenia who initially had more difficulity with visual-spatial skills, thinking and planning prior to the starting the program, were significantly less likely to quit smoking. This was not true for controls.

Interestingly, they also found that differences between quitters and non-quitters were not likely to be related to the medications or depressive symptoms. Previous work has shown that treatment with atypical antipsychotic medications can reduce smoking behaviors in schizophrenics, so in this study the relationship between impaired baseline neuropsychological test performance and smoking cessation outcome was not likely related to improvements produced by the medications.

They conclude from these results that in schizophrenia, neuropsychological problems are associated with smoking cessation treatment failure. There are parts of the brain that are affected in schizophrenia (eg prefrontal cortex or PFC) that control certain chemicals (eg dopamine). Based on the results here, it maybe that patients "self medicate" to remediate the chemical imbalance in the brain (dopamine hypofunction in the PFC) which may help with certain difficulties with thinking tasks involving this PFC area and might explain why there is smoking persistence in schizophrenia. With the higher risk of nicotine addiction in schizophrenia, comes a greater risk for the development of smoking-related medical problems and mortality. So, it becomes important to develop improved methods for smoking cessation in schizophrenia.

In terms of clinical interventions, the authors suggest that programs aimed at remediating PFC-related neuropsychological deficits may assist patients in efforts to quit smoking, especially for those with more severe difficulites. The authors report that there are mixed findings about the impact of medications on these cognitive problems. Some have found that risperidone can improve spatial working memory deficits, others have found that clozaril helps with psychomotor speed, attention, verbal fluency & executive thinking, while olanzapine may also help with thinking and planning. The authors also discuss other non-medication based interventions such as Neurocognitive Enhancement Therapy and Cognitive Remediation Therapy which involve intensive practice of skills found to be deficient in schizophrenia.

There are several limitations of their study including small sample size, the use of two separate clinical trials with different pharmacological smoking cessation interventions (bupropion in schizophrenia patients and selegiline in controls), lack of long term evaluation, multiple statistical comparisons, no measure of pre-trial IQ, and smoking deprivation.


Why do Schizophrenic patients smoke?
Cattapan-Ludewig K, Ludewig S, Jaquenoud Sirot E, Etzensberger M, Hasler F.Nervenarzt. 2004 Sep 23.

Neuropsychological deficits are associated with smoking cessation treatment failure in patients with schizophrenia.Schizophr Res. 2004 Oct 1;70(2-3):263-75.
Dolan SL, Sacco KA, Termine A, Seyal AA, Dudas MM, Vessicchio JC, Wexler BE, George TP.

Click here to find the first article on PubMed

Click here to find the second article on PubMed

NOTE: for additional information on schizophrenia and Smoking or Nicotine

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