Arquivo da tag: esquizofrenia

Estudo mostra que indústria e psiquiatria criaram doenças e remédios que não curam (Carta Campinas)

By Carta Campinas / sexta-feira, 01 jul 2016 10:38 AM

robert whitaker fotografia de videoUma série de reportagens e livros publicados ao longo de 25 anos pelo jornalista Robert Whitaker (foto), especialista em questões de ciência e medicina, abriu uma crise na prática médica da psiquiatria e na solução mágica de curar os transtornos mentais com medicação.

O jornalista, do The Boston Globe, o mesmo jornal das série de reportagens que gerou o filme Spotlight, levantou dados alarmantes sobre a indústria farmacêutica das doenças mentais e sua incapacidade de curar.  “Em 1955, havia 355.000 pessoas em hospitais com um diagnóstico psiquiátrico nos Estados Unidos; em 1987, 1,25 milhão de pessoas no país recebia aposentadoria por invalidez por causa de alguma doença mental; em 2007, eram 4 milhões. No ano passado, 5 milhões.

Para ele, associações médicas e a indústria estão criando pacientes e mercado para seus remédios. “Se olharmos do ponto de vista comercial, o êxito desse setor é extraordinário. Temos pílulas para a felicidade, para a ansiedade, para que seu filho vá melhor na escola. O transtorno por déficit de atenção e hiperatividade é uma fantasia. É algo que não existia antes dos anos noventa”, diz.

Mas essa não é uma crítica simplificada ou econômica, mas bem mais fundamentada durante mais de duas décadas.  “O que estamos fazendo de errado?”, questionam os estudos de Whitaker que também levantou informações de que pacientes de esquizofrenia evoluem melhor em países em que são menos medicados. Outro dado importante foi o estudo da Escola de Medicina de Harvard, que em 1994, mostrou que a evolução de pacientes com esquizofrenia, que foram medicados, pioraram em relação aos anos 70, quando a medicação não era dominante.

A batalha de Whitaker contra os comprimidos como solução tem ganhado apoio. Importantes escolas de medicina o convidam a explicar seus trabalhos e o debate está aberto nos Estados Unidos. “A psiquiatria está entrando em um novo período de crise no país, porque a história que nos contaram desde os anos 80 caiu por terra. A história falsa nos Estados Unidos e em parte do mundo desenvolvido é que a causa da esquizofrenia e da depressão seria biológica. Foi dito que esses distúrbios se deviam a desequilíbrios químicos no cérebro: na esquizofrenia, por excesso de dopamina; na depressão, por falta de serotonina. E nos disseram que havia medicamentos que resolviam o problema, assim como a insulina faz pelos diabéticos”, afirmou em entrevista ao jornal El Pais.

Para ele, os psiquiatras sempre tiveram um complexo de inferioridade. “O restante dos médicos costumava enxergá-los como se não fossem médicos autênticos. Nos anos 70, quando faziam seus diagnósticos baseando-se em ideias freudianas, eram muito criticados. E como poderiam reconstruir sua imagem diante do público? Vestiram suas roupas brancas, o que lhes dava autoridade. E começaram a se chamar a si mesmos de psicofarmacólogos quando passaram a prescrever medicamentos. A imagem deles melhorou. O poder deles aumentou. Nos anos 80, começaram a fazer propaganda desse modelo, e nos noventa, a profissão já não prestava atenção a seus próprios estudos científicos. Eles acreditavam em sua própria propaganda”, relata.

Para Whitaker, houve uma união do útil ao agradável.  Uma história que melhorou a imagem pública da psiquiatria e ajudou a vender medicamentos. No final dos anos oitenta, o comércio desses fármacos movimentava  US$ 800 milhões por ano. Vinte anos mais tarde, já eram US$ 40 bilhões. “Se estudarmos a literatura científica, observamos que já estamos utilizando esses remédios há 50 anos. Em geral, o que eles fazem é aumentar a cronicidade desses transtornos”, afirma de forma categórica.

Essa mensagem, segundo o próprio Whitaker, pode ser perigosa, mas ele não traz conselhos médicos nos estudos (Anatomy of an Epidemic ), não é para casos individuais. “Bom, se a medicação funciona, fantástico. Há pessoas para quem isso funciona. Além disso, o cérebro se adapta aos comprimidos, o que significa que retirá-los pode ter efeitos graves. O que falamos no livro é sobre o resultado de maneira geral. É para que a sociedade se pergunte: nós organizamos o atendimento psiquiátrico em torno de uma história cientificamente correta ou não?”, diz.

Whitaker foi muito criticado, apesar de seu livro contar com muitas evidências e ter recebido prêmios. Mas a obra desafiou os critérios da Associação Norte-Americana de Psiquiatria (APA) e os interesses da indústria farmacêutica. Mas desde 2010 novos estudos confirmaram suas pesquisas. Entre eles, os trabalhos dos psiquiatras Martin Harrow e Lex Wunderink e o fato de a prestigiada revista científica British Journal of Psychiatry já assumir que é preciso repensar o uso de medicamentos. “Os comprimidos podem servir para esconder o mal-estar, para esconder a angústia. Mas não são curativos, não produzem um estado de felicidade”, diz. Veja texto completo. Ou Aqui

Veja vídeo com Robert Whitaker, pena que ainda não está legendado em português.

 

Anúncios

What a Shaman Sees in A Mental Hospital (Waking Times)

By  August 22, 2014

Micro biomes of human throat may be linked to schizophrenia (Science Daily)

Studying microbiomes in throat may help identify causes and treatments of brain disorder

Date:
August 25, 2015
Source:
George Washington University
Summary:
In the most comprehensive study to date, researchers have identified a potential link between microbes (viruses, bacteria and fungi) in the throat and schizophrenia. This link may offer a way to identify causes and develop treatments of the disease and lead to new diagnostic tests.

In the most comprehensive study to date, researchers at the George Washington University have identified a potential link between microbes (viruses, bacteria and fungi) in the throat and schizophrenia. This link may offer a way to identify causes and develop treatments of the disease and lead to new diagnostic tests.

“The oropharynx of schizophrenics seems to harbor different proportions of oral bacteria than healthy individuals,” said Eduardo Castro-Nallar, a Ph.D. candidate at GW’s Computational Biology Institute (CBI) and lead author of the study. “Specifically, our analyses revealed an association between microbes such as lactic-acid bacteria and schizophrenics.”

Recent studies have shown that microbiomes — the communities of microbes living within our bodies — can affect the immune system and may be connected to mental health. Research linking immune disorders and schizophrenia has also been published, and this study furthers the possibility that shifts in oral communities are associated with schizophrenia.

Mr. Castro-Nallar’s research sought to identify microbes associated with schizophrenia, as well as components that may be associated with or contribute to changes in the immune state of the person. In this study, the group found a significant difference in the microbiomes of healthy and schizophrenic patients.

“Our results suggesting a link between microbiome diversity and schizophrenia require replication and expansion to a broader number of individuals for further validation,” said Keith Crandall, director of the CBI and contributing author of the study. “But the results are quite intriguing and suggest potential applications of biomarkers for diagnosis of schizophrenia and important metabolic pathways associated with the disease.”

The study helps to identify possible contributing factors to schizophrenia. With additional studies, researchers may be able to determine if microbiome changes are a contributing factor to schizophrenia, are a result of schizophrenia or do not have a connection to the disorder.


Journal Reference:

  1. Eduardo Castro-Nallar, Matthew L. Bendall, Marcos Pérez-Losada, Sarven Sabuncyan, Emily G. Severance, Faith B. Dickerson, Jennifer R. Schroeder, Robert H. Yolken, Keith A. Crandall. Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controlsPeer J, August 25th, 2015 [link]

Received wisdom about mental illness challenged by new report (Science Daily)

Date: March 11, 2015

Source: British Psychological Society

Summary: A new report challenges received wisdom about the nature of mental illness and has led to widespread media coverage and debate in the UK. Many people believe that schizophrenia is a frightening brain disease that makes people unpredictable and potentially violent, and can only be controlled by medication. However the UK has been at the forefront of research into the psychology of psychosis conducted over the last twenty years, and which reveals that this view is false.


21st March 2015 will see the US launch of the British Psychological Society’s Division of Clinical Psychology’s ground-breaking report ‘Understanding Psychosis and Schizophrenia’.

The report, which will be launched at 9am at the Cooper Union, Manhattan, NYC by invitation of the International Society for Psychological and Social approaches to Psychosis (ISPS), challenges received wisdom about the nature of mental illness and has led to widespread media coverage and debate in the UK.

Many people believe that schizophrenia is a frightening brain disease that makes people unpredictable and potentially violent, and can only be controlled by medication. However the UK has been at the forefront of research into the psychology of psychosis conducted over the last twenty years, and which reveals that this view is false.

Rather:

  • The problems we think of as ‘psychosis’ — hearing voices, believing things that others find strange, or appearing out of touch with reality — can be understood in the same way as other psychological problems such as anxiety or shyness.
  • They are often a reaction to trauma or adversity of some kind which impacts on the way we experience and interpret the world.
  • They rarely lead to violence.
  • No-one can tell for sure what has caused a particular person’s problems. The only way is to sit down with them and try and work it out.
  • Services should not insist that people see themselves as ill. Some prefer to think of their problems as, for example, an aspect of their personality which sometimes gets them into trouble but which they would not want to be without.
  • We need to invest much more in prevention by attending to inequality and child maltreatment.

Concentrating resources only on treating existing problems is like mopping the floor while the tap is still running.

The report is entitled ‘Understanding psychosis and schizophrenia: why people sometimes hear voices, believe things that others find strange, or appear out of touch with reality, and what can help’. It has been written by a group of eminent clinical psychologists drawn from eight UK universities and the UK National Health Service, together with people who have themselves experienced psychosis. It provides an accessible overview of the current state of knowledge, and its conclusions have profound implications both for the way we understand ‘mental illness’ and for the future of mental health services. ?

The report’s editor, Consultant Clinical Psychologist Anne Cooke from the Salomons Centre for Applied Psychology, Canterbury Christ Church University, said: “The finding that psychosis can be understood and treated in the same way as other psychological problems such as anxiety is one of the most important of recent years, and services need to change accordingly.

In the past we have often seen drugs as the most important form of treatment. Whilst they have a place, we now need to concentrate on helping each person to make sense of their experiences and find the support that works for them. My dream is that our report will contribute to a sea change in attitudes so that rather than facing prejudice, fear and discrimination, people who experience psychosis will find those around them accepting, open-minded and willing to help.”

Dr Geraldine Strathdee, NHS England’s National Clinical Director for Mental Health, said: “I am a passionate advocate of supporting people to develop an understanding of the events and difficulties that led them to mental health services.

That is the first step to getting back in control, and this important report will be a vital resource both for them and for those of us who design and deliver services. The British Psychological Society are a great force for change right at the grass roots of frontline services, in both acute care and long term conditions, and are at the forefront of innovations that integrate physical and psychological care in primary care, community and acute hospital settings.”

Rt Hon Norman Lamb, UK Minister of State for Care and Support, said: “I strongly welcome the publication of this report. The Government is committed to the provision of psychological therapies, and has recently announced that, for the first time, maximum waiting times will be introduced for NHS mental health services, including for Early Intervention in Psychosis.

We have also committed substantial resources to support the provision of psychological care for people with a range of mental health problems, including psychosis. I am delighted, therefore, to add my voice in recommending this report, which explains in everyday language the psychological science of why people sometimes hear voices, believe things other people find strange, or appear out of touch with reality. I am particularly pleased that it is the product of a partnership between expert psychologists in universities and NHS Trusts, and experts by experience — people who have themselves experienced psychosis. It helps us to understand such experiences better, to empathise with those who are distressed by them and to appreciate why the Government has made the psychological care of mental health problems a priority.”

Professor Jamie Hacker-Hughes, President Elect of the British Psychological Society, said: “This report will be remembered as a milestone in psychological health.”

Jacqui Dillon, Chair of the UK Hearing Voices Network, said “This report is an example of the amazing things that are possible when professionals and people with personal experience work together. Both the report’s content and the collaborative process by which it has been written are wonderful examples of the importance and power of moving beyond ‘them and us’ thinking in mental health.”

Beth Murphy, Head of Information at the UK Mental Health Charity Mind, said: “We welcome this report which highlights the range of ways in which we can understand experiences such as hearing voices. Anyone of us can experience problems with our mental health, whether we are diagnosed or not.

People describe and relate to their own experiences in very different ways and it’s important that services can accommodate the complex and varied range of experiences that people have. This can only be done by offering the widest possible range of treatments and therapies and by treating the person as whole, rather than as a set of symptoms.”

An evolutionary approach reveals new clues toward understanding the roots of schizophrenia (AAAS)

24-FEB-2015

MOLECULAR BIOLOGY AND EVOLUTION (OXFORD UNIVERSITY PRESS)

Is mental illness simply the evolutionary toll humans have to pay in return for our unique and superior cognitive abilities when compared to all other species? But if so, why have often debilitating illnesses like schizophrenia persisted throughout human evolutionary history when the affects can be quite negative on an individual’s chances of survival or reproductive success?

In a new study appearing in Molecular Biology and Evolution, Mount Sinai researcher Joel Dudley has led a new study that suggests that the very changes specific to human evolution may have come at a cost, contributing to the genetic architecture underlying schizophrenia traits in modern humans.

“We were intrigued by the fact that unlike many other mental traits, schizophrenia traits have not been observed in species other than humans, and schizophrenia has interesting and complex relationships with human intelligence,” said Dr. Joel Dudley, who led the study along with Dr. Panos Roussos. “The rapid increase in genomic data sequenced from large schizophrenia patient cohorts enabled us to investigate the molecular evolutionary history of schizophrenia in sophisticated new ways.”

The team examined a link between these regions, and human-specific evolution, in genomic segments called human accelerated regions, or HARs. HARs are short signposts in the genome that are conserved among non-human species but experienced faster mutation rates in humans. Thus, these regions, which are thought to control the level of gene expression, but not mutate the gene itself, may be an underexplored area of mental illness research.

The team’s research is the first study to sift through the human genome and identify a shared pattern between the location of HARs and recently identified schizophrenia gene loci. To perform their work, they utilized a recently completed, largest schizophrenia study of its kind, the Psychiatric Genomics Consortium (PGC), which included 36,989 schizophrenia cases and 113,075 controls. It is the largest genome-wide association study ever performed on any psychiatric disease.

They found that the schizophrenic loci were most strongly associated in genomic regions near the HARs that are conserved in non-human primates, and these HAR-associated schizophrenic loci are found to be under stronger evolutionary selective pressure when compared with other schizophrenic loci. Furthermore, these regions controlled genes that were expressed only in the prefrontal cortex of the brain, indicating that HARs may play an important role in regulating genes found to be linked to schizophrenia. They specifically found the greatest correlation between HAR-associated schizophrenic loci and genes controlling the expression of the neurotransmitter GABA, brain development, synaptic formations, adhesion and signaling molecules.

Their new evolutionary approach provides new insights into schizophrenia, and genomic targets to prioritize future studies and drug development targets. In addition, there are important new avenues to explore the roles of HARs in other mental diseases such as autism or bipolar disorder.

Casos de esquizofrenia poderiam ser evitados se fosse possível prevenir infecção por parasita, diz estudo (SBMT)

Proliferação do parasita, que também está relacionado a outros transtornos mentais, é mais comum em países tropicais

Cerca de 30% da população mundial está infectada com um dos parasitas que mais intriga a ciência, o Toxoplasma gondii. Apesar de inofensivo para a maioria das pessoas saudáveis, pesquisas científicas comprovaram que o protozoário é capaz de alterar o comportamento de seres humanos e animais, além de possível ligação com a esquizofrenia. Recentemente, um estudo produzido nos Estados Unidos foi além, sugerindo que cerca de um quinto dos casos de esquizofrenia entre os norte-americanos pode envolver o parasita. Nos países mais pobres, esse índice tende a ser ainda maior.

O estudo, publicado na revista Preventive Veterinary Medicine, foi conduzido pelo médico veterinário e professor Gary Smith, na Seção de Epidemiologia e Saúde Pública da Escola de Medicina Veterinária da Universidade da Pensilvânia. Smith elaborou um cálculo que mede o quão importante é o fator de risco à infecção, que aumenta com a idade.

“Há cada vez mais evidências por meio de estudos de que pessoas infectadas por Toxoplasma têm um risco aumentado para esquizofrenia”, explica o pesquisador. A partir desse pressuposto, o desafio foi descobrir qual a proporção de casos do transtorno mental poderia ser evitada se fosse possível para prevenir a infecção humana com o parasita.

Pelos cálculos feitos em um programa de computador, esse índice seria de 21,4% para países como os Estados Unidos e os da Europa Ocidental, em que a incidência de infecção pelo T. gondiinão varia com a idade. “O resultado, no entanto, seria diferente para muitos países da América do Sul, porque a não incidência de infecção é claramente maior nos grupos etários mais jovens, especialmente entre os mais pobres”, disse.

Só no Brasil – País que tem o maior índice mundial de infectados (66,7%), cerca de 126 milhões de pessoas são hospedeiras do parasita. A proliferação deste, aliás, é mais comum nos países de clima tropical, principalmente nas nações mais pobres, onde há grandes concentrações urbanas e sem saneamento básico.

O mal é transmitido tanto pela ingestão de carne crua e terra contaminada quanto por meio do contato direto com secreções e fezes de gato. Também pode ser repassada ao feto durante a gravidez através da placenta – sendo recomendado, inclusive, que mulheres grávidas evitem contatos com gatos durante o período de gestação. Apesar de ser uma infecção comum tanto em pessoas quanto em animais, o Toxoplasma afeta especialmente os gatos – únicos seres onde o parasita consegue se reproduzir.

Suicídio

Pesquisas feitas em diversos países têm demonstrado como o T. gondii pode estar relacionado a problemas neurológicos, como a depressão, principalmente em pessoas do sexo feminino. Segundo reportagem da revista Scientific American, um desses estudos, desenvolvido no Instituto de Pesquisas Médicas Stanley, em Maryland (EUA), concluiu que mulheres infectadas com quantidades altas de Toxoplasma apresentavam maior tendência a ter filhos esquizofrênicos.

Outro trabalho, produzido por cientistas dinamarqueses obteve um resultado ainda mais alarmante. Segundo a pesquisa, as mulheres que tinham infecções do parasita apresentaram tendência 54% maior de tentarem o suicídio. Em geral, as tentativas eram violentas, utilizando armas brancas e de fogo. Entre aquelas sem histórico de doenças mentais, o índice também foi alto: 56% tinham mais chances de cometerem atentado contra a própria vida.

A preocupação quanto os efeitos do protozoário no organismo são também evidentes em ratos. De acordo com pesquisas, o parasita pode alterar o comportamento desses animais, fazendo-os, por exemplo, perder o medo do cheiro de gatos – alguns chegam até mesmo a sentir atração sexual com o odor. Além disso, pesquisadores descobriram que ratos infectados conseguem recuperar o comportamento normal tanto com remédios antiparasitários quanto com antipsicóticos.

Já se descobriu que a infecção aumenta os níveis do neurotransmissor conhecido como dopamina, que é um dos fatores da esquizofrenia quando em altas doses. Isso porque oToxoplasma possui um gene que codifica uma enzima fundamental para a produção de dopamina, sendo este o método de influência sobre o cérebro de seres humanos e animais. Os cientistas, agora, tentam entender de forma clara como o parasita se comporta no cérebro.

(Newsletter da SBMT)

http://sbmt.org.br/portal/casos-de-esquizofrenia-poderiam-ser-evitados-se-fosse-possivel-prevenir-infeccao-por-parasita-diz-estudo/?locale=pt-BR

Ghost illusion created in the lab (Science Daily)

Date: November 6, 2014

Source: Ecole Polytechnique Fédérale de Lausanne

Summary: Patients suffering from neurological or psychiatric conditions have often reported ‘feeling a presence’ watching over them. Now, researchers have succeeded in recreating these ghostly illusions in the lab.

This image depicts a person experiencing the ghost illusion in the lab. Credit: Alain Herzog/EPFL

Ghosts exist only in the mind, and scientists know just where to find them, an EPFL study suggests. Patients suffering from neurological or psychiatric conditions have often reported feeling a strange “presence.” Now, EPFL researchers in Switzerland have succeeded in recreating this so-called ghost illusion in the laboratory.

On June 29, 1970, mountaineer Reinhold Messner had an unusual experience. Recounting his descent down the virgin summit of Nanga Parbat with his brother, freezing, exhausted, and oxygen-starved in the vast barren landscape, he recalls, “Suddenly there was a third climber with us… a little to my right, a few steps behind me, just outside my field of vision.”

It was invisible, but there. Stories like this have been reported countless times by mountaineers, explorers, and survivors, as well as by people who have been widowed, but also by patients suffering from neurological or psychiatric disorders. They commonly describe a presence that is felt but unseen, akin to a guardian angel or a demon. Inexplicable, illusory, and persistent.

Olaf Blanke’s research team at EPFL has now unveiled this ghost. The team was able to recreate the illusion of a similar presence in the laboratory and provide a simple explanation. They showed that the “feeling of a presence” actually results from an alteration of sensorimotor brain signals, which are involved in generating self-awareness by integrating information from our movements and our body’s position in space.

In their experiment, Blanke’s team interfered with the sensorimotor input of participants in such a way that their brains no longer identified such signals as belonging to their own body, but instead interpreted them as those of someone else. The work is published in Current Biology.

Generating a “Ghost”

The researchers first analyzed the brains of 12 patients with neurological disorders — mostly epilepsy — who have experienced this kind of “apparition.” MRI analysis of the patients’s brains revealed interference with three cortical regions: the insular cortex, parietal-frontal cortex, and the temporo-parietal cortex. These three areas are involved in self-awareness, movement, and the sense of position in space (proprioception). Together, they contribute to multisensory signal processing, which is important for the perception of one’s own body.

The scientists then carried out a “dissonance” experiment in which blindfolded participants performed movements with their hand in front of their body. Behind them, a robotic device reproduced their movements, touching them on the back in real time. The result was a kind of spatial discrepancy, but because of the synchronized movement of the robot, the participant’s brain was able to adapt and correct for it.

Next, the neuroscientists introduced a temporal delay between the participant’s movement and the robot’s touch. Under these asynchronous conditions, distorting temporal and spatial perception, the researchers were able to recreate the ghost illusion.

An “Unbearable” Experience

The participants were unaware of the experiment’s purpose. After about three minutes of the delayed touching, the researchers asked them what they felt. Instinctively, several subjects reported a strong “feeling of a presence,” even counting up to four “ghosts” where none existed. “For some, the feeling was even so strong that they asked to stop the experiment,” said Giulio Rognini, who led the study.

“Our experiment induced the sensation of a foreign presence in the laboratory for the first time. It shows that it can arise under normal conditions, simply through conflicting sensory-motor signals,” explained Blanke. “The robotic system mimics the sensations of some patients with mental disorders or of healthy individuals under extreme circumstances. This confirms that it is caused by an altered perception of their own bodies in the brain.”

A Deeper Understanding of Schizophrenia

In addition to explaining a phenomenon that is common to many cultures, the aim of this research is to better understand some of the symptoms of patients suffering from schizophrenia. Such patients often suffer from hallucinations or delusions associated with the presence of an alien entity whose voice they may hear or whose actions they may feel. Many scientists attribute these perceptions to a malfunction of brain circuits that integrate sensory information in relation to our body’s movements.

“Our brain possesses several representations of our body in space,” added Giulio Rognini. “Under normal conditions, it is able to assemble a unified self-perception of the self from these representations. But when the system malfunctions because of disease — or, in this case, a robot — this can sometimes create a second representation of one’s own body, which is no longer perceived as ‘me’ but as someone else, a ‘presence’.”

It is unlikely that these findings will stop anyone from believing in ghosts. However, for scientists, it’s still more evidence that they only exist in our minds.

Watch the video: http://youtu.be/GnusbO8QjbE


Journal Reference:

  1. Olaf Blanke, Polona Pozeg, Masayuki Hara, Lukas Heydrich, Andrea Serino, Akio Yamamoto, Toshiro Higuchi, Roy Salomon, Margitta Seeck, Theodor Landis, Shahar Arzy, Bruno Herbelin, Hannes Bleuler, Giulio Rognini. Neurological and Robot-Controlled Induction of an Apparition. Current Biology, 2014; DOI:10.1016/j.cub.2014.09.049

Parasite-schizophrenia connection: One-fifth of schizophrenia cases may involve the parasite T. gondii (Science Daily)

Date: October 29, 2014

Source: University of Pennsylvania

Summary: Many factors, both genetic and environmental, have been blamed for increasing the risk of a diagnosis of schizophrenia. Some, such as a family history of schizophrenia, are widely accepted. Others, such as infection with Toxoplasma gondii, a parasite transmitted by soil, undercooked meat and cat feces, are still viewed with skepticism. A new study used epidemiological modeling methods to determine the proportion of schizophrenia cases that may be attributable to T. gondii infection. The work suggests that about one-fifth of cases may involve the parasite.

The parasite T. gondii has been shown to alter behavior in rodents. Smith’s study supports a link to schizophrenia in humans. Credit: Image courtesy of University of Pennsylvania

Many factors, both genetic and environmental, have been blamed for increasing the risk of a diagnosis of schizophrenia. Some, such as a family history of schizophrenia, are widely accepted. Others, such as infection with Toxoplasma gondii, a parasite transmitted by soil, undercooked meat and cat feces, are still viewed with skepticism.

A new study by Gary Smith, professor of population biology and epidemiology at the University of Pennsylvania’s School of Veterinary Medicine, used epidemiological modeling methods to determine the proportion of schizophrenia cases that may be attributable to T. gondii infection. The work, published in the journal Preventive Veterinary Medicine, suggests that about one-fifth of cases may involve the parasite.

“Infection with Toxoplasma is very common, so, even if only a small percentage of people suffer adverse consequences, we could be talking about problems that affect thousands and thousands of people,” Smith said.

In the United States, just over a fifth of the population is infected with T. gondii. The vast majority aren’t aware of it. But there are some populations that need to be concerned. For example, if a woman becomes infected for the first time during pregnancy, her fetus can die or suffer serious developmental problems. People with HIV or other diseases that weaken the immune system are susceptible to a complication of T. gondii infection called toxoplasmic encephalitis, which can be deadly.

Though the medical community has long believed that most healthy people suffer no adverse effects from a T. gondii infection, recent studies have found evidence of worrisome impacts, including an association with schizophrenia because the parasite is found in in the brain as well as in muscles. Other work has shown that some antipsychotic drugs can stop the parasite from reproducing. In addition, field and laboratory studies in mice, rats and people have shown that infection with T. gondiitriggers changes in behavior and personality.

To further investigate this connection, Smith sought to calculate the population attributable fraction, or PAF, a metric epidemiologists use to determine how important a risk factor might be. In this case, Smith explained that the PAF is “the proportion of schizophrenia diagnoses that would not occur in a population if T. gondii infections were not present.”

The usual method of calculating the PAF was not well suited to examining the link between schizophrenia and T. gondii, because some of the variables are constantly in flux. For example, the proportion of people infected by T. gondii increases with age. Using a standard epidemiological modeling format, but taking into account all of the age-related changes in the relevant factors, Smith found the average PAF during an average lifetime to be 21.4 percent.

“In other words, we ask, if you could stop infections with this parasite, how many cases could you prevent?” Smith said. “Over a lifetime, we found that you could prevent one-fifth of all cases. That, to me, is significant.”

Smith noted that in some countries, the prevalence of T. gondii infection is much higher than in the U.S., and these countries also have a higher incidence of schizophrenia.

People with schizophrenia have greatly reduced life expectancies, and many are unable to work. Family members may also leave the workforce to care for relatives with the disease. For these reasons and others, schizophrenia acts as a large drain on the economy, responsible for $50 to $60 billion in health-care expenditures in the U.S. each year.

“By finding out how important a factor T. gondii infection is, this work might inform our attitude to researching the subject,” Smith said. “Instead of ridiculing the idea of a connection between T. gondii and schizophrenia because it seems so extraordinary, we can sit down and consider the evidence. Perhaps then we might be persuaded to look for more ways to reduce the number of people infected with Toxoplasma.”

The study was supported by the University of Pennsylvania School of Veterinary Medicine.


Journal Reference:

  1. Gary Smith. Estimating the population attributable fraction for schizophrenia when Toxoplasma gondii is assumed absent in human populations.Preventive Veterinary Medicine, 2014; DOI: 10.1016/j.prevetmed.2014.10.009

Discurso sobre o sonho pode ajudar no diagnóstico de doenças mentais (Fapesp)

Pesquisadores brasileiros desenvolvem técnica de análise matemática de relatos sobre sonhos, capaz de auxiliar na identificação de sintomas de esquizofrenia e bipolaridade (imagem: divulgação)

17/03/2014

Por Elton Alisson

Agência FAPESP – A pista dada por Sigmund Freud (1856-1939) no livro “A intepretação dos sonhos, de 1899, de que “os sonhos são a estrada real para o inconsciente”, chave para a Psicanálise, também pode ser útil na Psiquiatria, no diagnóstico clínico de transtornos mentais, como a esquizofrenia e a bipolaridade, entre outras.

A constatação é de um grupo de pesquisadores do Instituto do Cérebro da Universidade Federal do Rio Grande do Norte (UFRN), em colaboração com colegas do Departamento de Física da Universidade Federal de Pernambuco (UFPE) e do Centro de Pesquisa, Inovação e Difusão em Neuromatemática (Neuromat) – um dos CEPIDs da FAPESP.

Eles desenvolveram uma técnica de análise matemática de relatos de sonhos que poderá, no futuro, auxiliar no diagnóstico de psicoses.

A técnica foi descrita em um artigo publicado em janeiro na Scientific Reports, revista de acesso aberto do grupo Nature.

“A ideia é que a técnica, relativamente simples e barata, seja utilizada como ferramenta para auxiliar os psiquiatras no diagnóstico clínico de pacientes com transtornos mentais de forma mais precisa”, disse Mauro Copelli, professor da UFPE e um dos autores do estudo, à Agência FAPESP.

De acordo com Copelli – que realizou mestrado e doutorado parcialmente com Bolsa da FAPESP –, apesar dos esforços seculares para aumentar a precisão da classificação dos transtornos mentais, o atual método de diagnóstico de psicoses tem sido duramente criticado.

Isso porque ele ainda peca pela falta de objetividade e pelo fato de a maioria dos transtornos mentais não contar com biomarcadores (indicadores biométricos) capazes de auxiliar os psiquiatras a diagnosticá-los com maior exatidão.

Além disso, pacientes com esquizofrenia ou transtorno bipolar muitas vezes apresentam sintomas psicóticos comuns, como alucinações, delírios, hiperatividade e comportamento agressivo – o que pode comprometer a precisão do diagnóstico.

“O diagnóstico dos sintomas psicóticos é altamente subjetivo”, afirmou Copelli. “Por isso mesmo, a última versão do Manual Diagnóstico e Estatístico de Transtornos Mentais [publicado pela Associação Americana de Psiquiatria em 2013] foi muito atacada”, avaliou.

A fim de desenvolver um método quantitativo para avaliar sintomas psiquiátricos, os pesquisadores gravaram, com o consentimento dos envolvidos, os relatos dos sonhos de 60 pacientes voluntários, atendidos no ambulatório de psiquiatria de um hospital público em Natal (RN).

Alguns dos pacientes já tinham recebido o diagnóstico de esquizofrenia, outros de bipolaridade e os demais, que formaram o grupo de controle, não apresentavam sintomas de transtornos mentais.

Os relatos dos sonhos dos pacientes, feitos à psiquiatra Natália Bezerra Mota, doutoranda na URFN e primeira autora do estudo, foram transcritos.

As frases dos discursos dos pacientes foram transformadas por um software desenvolvido por pesquisadores do Instituto do Cérebro em grafos – estruturas matemáticas similares a diagramas nas quais cada palavra dita pelo paciente foi representada por um ponto ou nó, como o feito em uma linha de crochê.

Ao analisar os grafos dos relatos dos sonhos dos três grupos de pacientes os pesquisadores observaram que há diferenças muito claras entre eles.

O tamanho, em termos de quantidade de arestas ou links, e a conectividade (relação) entre os nós dos grafos dos pacientes diagnosticados com esquizofrenia, bipolaridade ou sem transtornos mentais apresentaram variações, afirmaram os pesquisadores.

“Os pacientes com esquizofrenia, por exemplo, fazem relatos que, quando representados por grafos, possuem menos ligações do que os demais grupos de pacientes”, disse Mota.

Diferenças de discursos

Segundo os pesquisadores, a diferenciação de pacientes a partir da análise dos grafos de relatos dos sonhos foi possível porque suas características de fala também são bastante diversificadas.

Os pacientes esquizofrênicos costumam falar de forma lacônica e com pouca digressão (desvio de assunto) – o que explica por que a conectividade e a quantidade de arestas dos grafos de seus relatos são menores em comparação às dos bipolares.

Por sua vez, pacientes com transtorno bipolar tendem a apresentar um sintoma oposto ao da digressão, chamado logorreia ou verborragia, falando atabalhoadamente frases sem sentido – chamado na Psiquiatria de “fuga de ideias”.

“Encontramos uma correlação importante dessas medidas feitas por meio das análises dos grafos com os sintomas negativos e cognitivos medidos por escalas psicométricas utilizadas na prática clínica da Psiquiatria”, afirmou Mota.

Ao transformar essas características marcantes de fala dos pacientes em grafos é possível dar origem a um classificador computacional capaz de auxiliar os psiquiatras no diagnóstico de transtornos mentais, indicou Copelli.

“Todas as ocorrências no discurso dos pacientes com transtornos mentais que no grafo têm um significado aparentemente geométrico podem ser quantificadas matematicamente e ajudar a classificar se um paciente é esquizofrênico ou bipolar, com uma taxa de sucesso comparável ou até mesmo melhor do que as escalas psiquiátricas subjetivas utilizadas para essa finalidade”, avaliou.

O objetivo dos pesquisadores é avaliar um maior número de pacientes e calibrar o algoritmo (sequência de comandos) do software desenvolvido para transformar os relatos dos sonhos em grafos que possam ser usados em larga escala na prática clínica de Psiquiatria.

Apesar de utilizada inicialmente para o diagnóstico de psicoses, a técnica poderá ser expandida para diversas outras finalidades, contou Mota.

“Ela poderá ser utilizada, por exemplo, para buscar mais informações sobre estrutura de linguagem aplicadas à análise de relatos de pessoas não apenas com sintomas psicóticos, mas também em diferentes situações de declínio cognitivo, como demência, ou em ascensão, como durante o aprendizado e o desenvolvimento da fala e escrita”, indicou a pesquisadora.

Papel dos sonhos

Os pesquisadores também desenvolveram e analisaram, durante o estudo, os grafos de relatos sobre atividades realizadas pelos pacientes voluntários na véspera do sonho.

Os grafos desses relatos do dia a dia, chamados de “relatos de vigília”, não foram tão indicativos do tipo de transtorno mental sofrido pelo paciente como outros, disse Copelli.

“Conseguimos distinguir esquizofrênicos dos demais grupos usando a análise dos grafos dos relatos de vigília, mas não conseguimos distinguir bem os bipolares do grupo de controle dessa forma”, contou.

Os pesquisadores ainda não sabem por que os grafos dos discursos sobre o sonho são mais informativos sobre psicose do que os grafos da vigília.

Algumas hipóteses esmiuçadas na pesquisa de doutorado de Mota estão relacionadas a mecanismos fisiológicos de formação de memória.

“Acreditamos que, por serem memórias mais transitórias, os sonhos podem ser mais demandantes cognitivamente e ter maior impacto afetivo do que as memórias relacionadas ao cotidiano, e isso pode tornar seus relatos mais complexos”, contou a pesquisadora.

“Outra hipótese é que o sonho está relacionado a um evento vivenciado exclusivamente por uma pessoa, sem ser compartilhado com outras, e por isso talvez seja mais complexo de ser explicado do que uma atividade relacionada ao cotidiano”, disse.

Para testar essas hipóteses, os pesquisadores pretendem ampliar a coleta de dados aplicando questionários em pacientes com registro de primeiro surto psicótico, com o objetivo de esclarecer se outros tipos de relatos, como de memórias antigas, podem se equiparar ao sonho em termos de informação psiquiátrica. Eles também querem verificar se podem usar o método para identificar sinais ou grupo de sintomas (pródromo) e acompanhar efeitos de medicações.

“Pretendemos investigar em laboratório, com eletroencefalografia de alta densidade e diversas técnicas de mensuração de distâncias semânticas e análise de estrutura de grafos, de que forma os estímulos recebidos imediatamente antes de dormir influenciam os relatos de sonhos produzidos ao despertar”, disse Sidarta Ribeiro, pesquisador do Instituto do Cérebro da UFRN.

“Estamos particularmente interessados nos efeitos distintos de imagens com valor afetivo”, afirmou Ribeiro, que também é pesquisador associado do Neuromat.

O artigo Graph analysis of dream reports is especially informative about psychosis (doi: 10.1038/srep03691), de Mota e outros, pode ser lido na revista Scientific Reports emwww.nature.com/srep/2014/140115/srep03691/full/srep03691.html.

New research helps explain how social understanding is performed by the brain (Science Daily)

Date:

February 24, 2014

Source: Aarhus University

Summary: An important question has been answered about how social understanding is performed in the brain. The findings may help us to attain a better understanding of why people with autism and schizophrenia have difficulties with social interaction. Using magnetic stimulation to temporarily disrupt normal processing of the areas of the human brain involved in the production of actions of human participants, it is demonstrated that these areas are also involved in the understanding of actions. The study is the first to demonstrate a clear causal effect, whereas earlier studies primarily have looked at correlations, which are difficult to interpret.

A new study from Aarhus University, Denmark, helps us understand why people with autism and schizophrenia have difficulties with social interaction. Credit: © styleuneed / Fotolia

In a study to be published in Psychological Science, researchers from Aarhus University and the University of Copenhagen demonstrate that brain cells in what is called the mirror system help people make sense of the actions they see other people perform in everyday life.

Using magnetic stimulation to temporarily disrupt normal processing of the areas of the human brain involved in the production of actions of human participants, it is demonstrated that these areas are also involved in the understanding of actions. The study is the first to demonstrate a clear causal effect, whereas earlier studies primarily have looked at correlations, which are difficult to interpret.

One of the researchers, John Michael, explains the process: “There has been a great deal of hype about the mirror system, and now we have performed an experiment that finally provides clear and straightforward evidence that the mirror system serves to help people make sense of others’ actions,” says John Michael.

Understanding autism and schizophrenia

The study shows that there are areas of the brain that are involved in the production of actions. And the researchers found evidence that these areas contribute to understanding others’ actions. This means that the same areas are involved in producing actions and understanding others’ actions. This helps us in everyday life, but it also holds great potential when trying to understand why people with autism and schizophrenia have difficulties with social interaction.

“Attaining knowledge of the processes underlying social understanding in people in general is an important part of the process of attaining knowledge of the underlying causes of the difficulties that some people diagnosed with autism and schizophrenia experience in sustaining social understanding. But it is important to emphasize that this is just one piece of the puzzle.”

“The findings may be interesting to therapists and psychiatrists who work with patients with schizophrenia or autism, or even to educational researchers,” adds John Michael.

Facts about the empirical basis

The participants (20 adults) came to the lab three times. They were given brain scans on the first visit. On the second and third, they received stimulation to their motor system and then performed a typical psychological task in which they watched brief videos of actors pantomiming actions (about 250 videos each time). After each video they had to choose a picture of an object that matched the pantomimed video. For example, a hammer was the correct answer for the video of an actor pretending to hammer.

This task was intended to gauge their understanding of the observed actions. The researchers found that the stimulation interfered with their performance of this task.

Innovative method

The researchers used an innovative technique for magnetically stimulating highly specific brain areas in order to temporarily disrupt normal processing in those areas. The reason for using this technique (called continuous theta-burst stimulation) in general is that it makes it possible to determine which brain areas perform which functions. For example, if you stimulate (and thus temporarily impair) area A, and the participants subsequently have difficulty with some specific task (task T), then you can infer that area A usually performs task T. The effect goes away after 20 minutes, so this is a harmless and widely applicable way to identify which tasks are performed by which areas.

With continuous theta-burst stimulation, you can actually determine that the activation of A contributes as a cause to people performing T. This method thus promises to be of great use to neuroscientists in the coming years.

Journal Reference:

  1. J. Michael, K. Sandberg, J. Skewes, T. Wolf, J. Blicher, M. Overgaard, C. D. Frith.Continuous Theta-Burst Stimulation Demonstrates a Causal Role of Premotor Homunculus in Action UnderstandingPsychological Science, 2014; DOI: 10.1177/0956797613520608

Cientistas identificam gene que relaciona estrutura cerebral à inteligência (O Globo)

JC e-mail 4892, de 11 de fevereiro de 2014

Descoberta pode ter implicações importantes para a compreensão de transtornos psiquiátricos como esquizofrenia e autismo

Cientistas do King’s College London identificaram, pela primeira vez, um gene que relaciona a espessura da massa cinzenta do cérebro à inteligência. O estudo foi publicado nesta terça-feira na revista “Molecular Psychiatry” e pode ajudar a entender os mecanismos biológicos por trás de determinados danos intelectuais.

Até agora já se sabia que a massa cinzenta tinha um papel importante para a memória, atenção, pensamento, linguagem e consciência. Estudos anteriores também já mostravam que a espessura do córtex cerebral tinha a ver com a habilidade intelectual, mas nenhum gene tinha sido identificado.

Um time internacional de cientistas, liderado pelo King´s College, analisou amostras de DNA e exames de ressonância magnética por imagem de 1.583 adolescentes saudáveis de 14 anos, que também se submeteram a uma série de testes para determinar inteligência verbal e não verbal.

– Queríamos descobrir como diferenças estruturais no cérebro tinham a ver com diferenças na habilidade intelectual. Identificamos uma variação genética relacionada à plasticidade sináptica, de como os neurônios se comunicam – explica Sylvane Desrivières, principal autora do estudo, pelo Instituto de Psiquiatria do King’s College London. – Isto pode nos ajudar a entender o que acontece em nível neuronal com certas formas de comprometimento intelectual, onde a habilidade de comunicação dos neurônios é, de alguma forma, comprometida.

Ela acrescenta que é importante apontar que a inteligência é influenciada por muitos fatores genéticos e ambientais. O gene que identificamos só explica uma pequena proporção das diferenças nas habilidades intelectuais e não é, de forma alguma, “o gene da inteligência”.

Os pesquisadores observaram 54 mil possíveis variações envolvidas no desenvolvimento cerebral. Em média, adolescentes com uma variante genética particular tinham um córtex mais fino no hemisfério cerebral esquerdo, particularmente nos lobos frontal e temporal, e executavam bem testes de capacidade intelectual. A variação genética afeta a expressão do gene NPTN, que codifica uma proteína que atua nas sinapses neuronais e, portanto, afeta a forma como as células do cérebro se comunicam.

Para confirmar as suas conclusões, os pesquisadores estudaram o gene NPTN em células de camundongo e do cérebro humano. Os pesquisadores verificaram que o gene NPTN tinha uma atividade diferente nos hemisférios esquerdo e direito do cérebro, o que pode fazer com que o hemisfério esquerdo seja mais sensível aos efeitos das mutações NPTN. Os resultados sugerem que algumas diferenças na capacidade intelectual podem resultar da diminuição da função do gene NPTN em determinadas regiões do hemisfério esquerdo do cérebro.

A variação genética identificada neste estudo representa apenas uma estimativa de 0,5% da variação total em inteligência. No entanto, as descobertas podem ter implicações importantes para a compreensão dos mecanismos biológicos subjacentes de vários transtornos psiquiátricos, como esquizofrenia e autismo, nas quais a capacidade cognitiva é uma característica fundamental da doença.

http://oglobo.globo.com/ciencia/cientistas-identificam-gene-que-relaciona-estrutura-cerebral-inteligencia-11563313#ixzz2t1amCUSy

Schizophrenia Symptoms Eliminated in Animal Model (Science Daily)

May 22, 2013 — Overexpression of a gene associated with schizophrenia causes classic symptoms of the disorder that are reversed when gene expression returns to normal, scientists report. 

Overexpression of a gene associated with schizophrenia causes classic symptoms of the disorder that are reversed when gene expression returns to normal, scientists report. Pictured are (left to right) Drs. Lin Mei, Dongmin Yin and Yongjun Chen, Medical College of Georgia at Georgia Regents University. (Credit: Phil Jones, Georgia Regents University Photographer)

They genetically engineered mice so they could turn up levels of neuregulin-1 to mimic high levels found in some patients then return levels to normal, said Dr. Lin Mei, Director of the Institute of Molecular Medicine and Genetics at the Medical College of Georgia at Georgia Regents University.

They found that when elevated, mice were hyperactive, couldn’t remember what they had just learned and couldn’t ignore distracting background or white noise. When they returned neuregulin-1 levels to normal in adult mice, the schizophrenia-like symptoms went away, said Mei, corresponding author of the study in the journal Neuron.

While schizophrenia is generally considered a developmental disease that surfaces in early adulthood, Mei and his colleagues found that even when they kept neuregulin-1 levels normal until adulthood, mice still exhibited schizophrenia-like symptoms once higher levels were expressed. Without intervention, they developed symptoms at about the same age humans do.

“This shows that high levels of neuregulin-1 are a cause of schizophrenia, at least in mice, because when you turn them down, the behavior deficit disappears,” Mei said. “Our data certainly suggests that we can treat this cause by bringing down excessive levels of neuregulin-1 or blocking its pathologic effects.”

Schizophrenia is a spectrum disorder with multiple causes — most of which are unknown — that tends to run in families, and high neuregulin-1 levels have been found in only a minority of patients. To reduce neuregulin-1 levels in those individuals likely would require development of small molecules that could, for example, block the gene’s signaling pathways, Mei said. Current therapies treat symptoms and generally focus on reducing the activity of two neurotransmitters since the bottom line is excessive communication between neurons.

The good news is it’s relatively easy to measure neuregulin-1 since blood levels appear to correlate well with brain levels. To genetically alter the mice, they put a copy of the neuregulin-1 gene into mouse DNA then, to make sure they could control the levels, they put in front of the DNA a binding protein for doxycycline, a stable analogue for the antibiotic tetracycline, which is infamous for staining the teeth of fetuses and babies.

The mice are born expressing high levels of neuregulin-1 and giving the antibiotic restores normal levels. “If you don’t feed the mice tetracycline, the neuregulin-1 levels are always high,” said Mei, noting that endogenous levels of the gene are not affected. High-levels of neuregulin-1 appear to activate the kinase LIMK1, impairing release of the neurotransmitter glutamate and normal behavior. The LIMK1 connection identifies another target for intervention, Mei said.

Neuregulin-1 is essential for heart development as well as formation of myelin, the insulation around nerves. It’s among about 100 schizophrenia-associated genes identified through genome-wide association studies and has remained a consistent susceptibility gene using numerous other methods for examining the genetics of the disease. It’s also implicated in cancer.

Mei and his colleagues were the first to show neuregulin-1’s positive impact in the developed brain, reporting in Neuron in 2007 that it and its receptor ErbB4 help maintain a healthy balance of excitement and inhibition by releasing GABA, a major inhibitory neurotransmitter, at the sight of inhibitory synapses, the communication paths between neurons. Years before, they showed the genes were also at excitatory synapses, where they also could quash activation. In 2009, the MCG researchers provided additional evidence of the role of neuregulin-1 in schizophrenia by selectively deleting the gene for its receptor, ErbB4 and creating another symptomatic mouse.

Schizophrenia affects about 1 percent of the population, causing hallucinations, depression and impaired thinking and social behavior. Babies born to mothers who develop a severe infection, such as influenza or pneumonia, during pregnancy have a significantly increased risk of schizophrenia.

Journal Reference:

  1. Dong-Min Yin, Yong-Jun Chen, Yi-Sheng Lu, Jonathan C. Bean, Anupama Sathyamurthy, Chengyong Shen, Xihui Liu, Thiri W. Lin, Clifford A. Smith, Wen-Cheng Xiong, Lin Mei.Reversal of Behavioral Deficits and Synaptic Dysfunction in Mice Overexpressing Neuregulin 1.Neuron, 2013; 78 (4): 644 DOI:10.1016/j.neuron.2013.03.028

Gene Today, Gone Tomorrow: Genes for Autism and Schizophrenia Only Active in Developing Brains (Science Daily)

Feb. 11, 2013 — Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a study in mice led by researchers at the University of Oxford.

This new study adds to the evidence that autism and schizophrenia are neurodevelopmental disorders, a term describing conditions that originate during early brain development.

The researchers studied gene expression in the brains of mice throughout their development, from 15-day old embryos to adults, and their results are published recently inProceedings of the National Academy of Sciences.

The study is a collaboration between researchers from the University of Oxford, King’s College London and Imperial College London, and was funded by the Medical Research Council and the Wellcome Trust.

The research focused on cells in the ‘subplate’, a region of the brain where the first neurons (nerve cells) develop. Subplate neurons are essential to brain development, and provide the earliest connections within the brain.

‘The subplate provides the scaffolding required for a brain to grow, so is important to consider when studying brain development,’ says Professor Zoltán Molnár, senior author of the paper from the University of Oxford, ‘Looking at the pyramids in Egypt today doesn’t tell us how they were actually built. Studying adult brains is like looking at the pyramids today, but by studying the developing brains we are able to see the transient scaffolding that has been used to construct it.’

The study shows that certain genes linked to autism and schizophrenia are only active in the subplate during specific stages of development. ‘The majority of the autism susceptibility genes are only expressed in the subplate of the developing mouse brain,’ explains Dr Anna Hoerder-Suabedissen, who led the study at the University of Oxford, ‘Many can only be found at certain stages of development, making them difficult to identify at later stages using previous techniques.’

The group were able to map gene activity in full detail thanks to powerful new methods which allowed them to dissect and profile gene expression from small numbers of cells. This also enabled them to identify the different populations of subplate neurons more accurately.

Subplate neurons were first discovered in the 1970s by Professors Ivica Kostović and Pasko Rakic of Yale University.

‘I am excited to see tangible genetic links supporting, even indirectly, the idea of a possible role of the transient embryonic subplate zone in the origin of disorders such as autism and schizophrenia,’ says Professor Rakic, ‘If this is possible to show in mice, where the subplate is relatively small, it is likely to be even more pronounced in humans, where it is much more evolved.

‘The study from Professor Molnár’s group at Oxford may be the first step toward finding more such links in the future and opens the possibility of directly examining the roles of genetic variation and exposure to various environmental factors in animal models.’

Professor David Edwards, Director of the Centre for the Developing Brain at King’s College London, and co-author of the paper, said: ‘Using advanced techniques we have been able to define the biochemical pathways that are important during a particular phase of brain developme

nt. It has been suspected for a long time that if the development of the cortex is disrupted by genetic abnormalities or environmental stress (such as prematurity) this would have long-lasting adverse effects on brain development and could lead to problems like ADHD or autism. This study defines genes that are important in mice at this critical period and this does indeed seem to include genes known to predispose to autism and schizophrenia. It focuses attention even more firmly on early brain development as a cause of these distressing neuropsychological problems.’

Professor Hugh Perry, chair of the Medical Research Council’s Neuroscience and Mental Health Board, said: ‘By being able to pinpoint common genetic factors for neurological conditions such as autism and schizophrenia, scientists are able to understand an important part of the story as to why things go awry as our brains develop. The Medical Research Council’s commitment to a broad portfolio of neuroscience and mental health research places us in a unique position to respond to the challenge of mental ill health and its relationship with physical health and wellbeing.’

Schizophrenia Linked to Social Inequality (Science Daily)

Dec. 14, 2012 — Higher rates of schizophrenia in urban areas can be attributed to increased deprivation, increased population density and an increase in inequality within a neighbourhood, new research reveals. The research, led by the University of Cambridge in collaboration with Queen Mary University of London, was published today in the journal Schizophrenia Bulletin.

Dr James Kirkbride, lead author of the study from the University of Cambridge, said: “Although we already know that schizophrenia tends to be elevated in more urban communities, it was unclear why. Our research suggests that more densely populated, more deprived and less equal communities experience higher rates of schizophrenia and other similar disorders. This is important because other research has shown that many health and social outcomes also tend to be optimal when societies are more equal.”

The scientists used data from a large population-based incidence study (the East London first-episode psychosis study directed by Professor Jeremy Coid at the East London NHS Foundation Trust and Queen Mary, University of London) conducted in three neighbouring inner city, ethnically diverse boroughs in East London: City & Hackney, Newham, and Tower Hamlets.

427 people aged 18-64 years old were included in the study, all of whom experienced a first episode of psychotic disorder in East London between 1996 and 2000. The researchers assessed their social environment through measures of the neighbourhood in which they lived at the time they first presented to mental health services because of a psychotic disorder. Using the 2001 census, they estimated the population aged 18-64 years old in each neighbourhood, and then compared the incidence rate between neighbourhoods.

The incidence of schizophrenia (and other similar disorders where hallucinations and delusions are the dominant feature) still showed variation between neighbourhoods after taking into account age, sex, ethnicity and social class. Three environmental factors predicted risk of schizophrenia — increased deprivation (which includes employment, income, education and crime) increased population density, and an increase in inequality (the gap between the rich and poor).

Results from the study suggested that a percentage point increase in either neighbourhood inequality or deprivation was associated with an increase in the incidence of schizophrenia and other similar disorders of around 4%.

Dr Kirkbride added: “Our research adds to a wider and growing body of evidence that inequality seems to be important in affecting many health outcomes, now possibly including serious mental illness. Our data seems to suggest that both absolute and relative levels of deprivation predict the incidence of schizophrenia.

“East London has changed substantially over recent years, not least because of the Olympic regeneration. It would be interesting to repeat this work in the region to see if the same patterns were found.”

The study also found that risk of schizophrenia in some migrant groups might depend on the ethnic composition of their neighbourhood. For black African people, the study found that rates tended to be lower in neighbourhoods where there were a greater proportion of other people of the same background. By contrast, rates of schizophrenia were lower for the black Caribbean group when they lived in more ethnically-integrated neighbourhoods. These findings support the possibility that the socio-cultural composition of our environment could positively or negatively influence risk of schizophrenia and other similar disorders.

Dr John Williams, Head of Neuroscience and Mental Health at the Wellcome Trust said: “This research reminds us that we must understand the complex societal factors as well as the neural mechanisms that underpin the onset of mental illness, if we are to develop appropriate interventions.”

Journal Reference:

  1. J. B. Kirkbride, P. B. Jones, S. Ullrich, J. W. Coid. Social Deprivation, Inequality, and the Neighborhood-Level Incidence of Psychotic Syndromes in East London.Schizophrenia Bulletin, 2012; DOI: 10.1093/schbul/sbs151

Link between creativity and mental illness confirmed (Karolinska Institutet)

[PRESS RELEASE 16 October 2012] People in creative professions are treated more often for mental illness than the general population, there being a particularly salient connection between writing and schizophrenia. This according to researchers at Karolinska Institutet, whose large-scale Swedish registry study is the most comprehensive ever in its field.

Last year, the team showed that artists and scientists were more common amongst families where bipolar disorder and schizophrenia is present, compared to the population at large. They subsequently expanded their study to many more psychiatric diagnoses – such as schizoaffective disorder, depression, anxiety syndrome, alcohol abuse, drug abuse, autism, ADHD, anorexia nervosa and suicide – and to include people in outpatient care rather than exclusively hospital patients.

The present study tracked almost 1.2 million patients and their relatives, identified down to second-cousin level. Since all were matched with healthy controls, the study incorporated much of the Swedish population from the most recent decades. All data was anonymized and cannot be linked to any individuals.

The results confirmed those of their previous study: certain mental illness – bipolar disorder – is more prevalent in the entire group of people with artistic or scientific professions, such as dancers, researchers, photographers and authors. Authors specifically also were more common among most of the other psychiatric diseases (including schizophrenia, depression, anxiety syndrome and substance abuse) and were almost 50 per cent more likely to commit suicide than the general population.

The researchers also observed that creative professions were more common in the relatives of patients with schizophrenia, bipolar disorder, anorexia nervosa and, to some extent, autism. According to Simon Kyaga, consultant in psychiatry and doctoral student at the Department of Medical Epidemiology and Biostatistics, the results give cause to reconsider approaches to mental illness.

“If one takes the view that certain phenomena associated with the patients illness are beneficial, it opens the way for a new approach to treatment,” he says. “In that case, the doctor and patient must come to an agreement on what is to be treated, and at what cost. In psychiatry and medicine generally there has been a tradition to see the disease in black-and-white terms and to endeavour to treat the patient by removing everything regarded as morbid.”

The study was financed with grants from the Swedish Research Council, the Swedish Psychiatry Foundation, the Bror Gadelius Foundation, the Stockholm Centre for Psychiatric Research and the Swedish Council for Working Life and Social Research.

Publication

Simon Kyaga, Mikael Landén, Marcus Boman, Christina M. Hultman och Paul Lichtenstein. Mental illness, suicide and creativity: 40-Year prospective total population study. Journal of Psychiatric Research, corrected proof online 9 October 2012

As linguagens da psicose (Revista Fapesp)

Abordagem matemática evidencia as diferenças entre os discursos de quem tem mania ou esquizofrenia

CARLOS FIORAVANTI | Edição 194 – Abril de 2012

Como o estudo foi feito: os entrevistados relatavam um sonho e a entrevistadora convertia as palavras mais importantes em pontos e as frases em setas para examinar a estrutura da linguagem

Para os psiquiatras e para a maioria das pessoas, é relativamente fácil diferenciar uma pessoa com psicose de quem não apresentou nenhum distúrbio mental já diagnosticado: as do primeiro grupo relatam delírios e alucinações e por vezes se apresentam como messias que vão salvar o mundo. Porém, diferenciar os dois tipos de psicose – mania e esquizofrenia – já não é tão simples e exige um bocado de experiência pessoal, conhecimento e intuição dos especialistas. Uma abordagem matemática desenvolvida no Instituto do Cérebro da Universidade Federal do Rio Grande do Norte (UFRN) talvez facilite essa diferenciação, fundamental para estabelecer os tratamentos mais adequados para cada enfermidade, ao avaliar de modo quantitativo as diferenças nas estruturas de linguagem verbal adotadas por quem tem mania ou esquizofrenia.

A estratégia de análise – com base na teoria dos grafos, que representou as palavras como pontos e a sequência entre elas nas frases por setas – indicou que as pessoas com mania são muito mais prolixas e repetitivas do que as com esquizofrenia, geralmente lacônicas e centradas em um único assunto, sem deixar o pensamento viajar. “A recorrência é uma marca do discurso do paciente com mania, que conta três ou quatro vezes a mesma coisa, enquanto aquele com esquizofrenia fala objetivamente o que tem para falar, sem se desviar, e tem um discurso pobre em sentidos”, diz a psiquiatra Natália Mota, pesquisadora do instituto. “Em cada grupo”, diz Sidarta Ribeiro, diretor do instituto, “o número de palavras, a estrutura da linguagem e outros indicadores são completamente distintos”.

Eles acreditam que conseguiram dar os primeiros passos rumo a uma forma objetiva de diferenciar as duas formas de psicose, do mesmo modo que um hemograma é usado para atestar uma doença infecciosa, desde que os próximos testes, com uma amostra maior de participantes, reforcem a consistência dessa abordagem e os médicos consintam em trabalhar com um assistente desse tipo. Os testes comparativos descritos em um artigo recém-publicado na revista PLoS One indicaram que essa nova abordagem proporciona taxas de acerto da ordem de 93% no diagnóstico, enquanto as escalas psicométricas hoje em uso, com base em questionários de avaliação de sintomas, chegam a apenas 67%. “São métodos complementares”, diz Natália. “As escalas psicométricas e a experiência dos médicos continuam indispensáveis.”

“O resultado é bastante simples, mesmo para quem não entende matemática”, diz o físico Mauro Copelli, da Universidade Federal de Pernambuco (UFPE), que participou desse trabalho. O discurso das pessoas com mania se mostra como um emaranhado de pontos e linhas, enquanto o das com esquizofrenia se apresenta como uma reta, com poucos pontos. A teoria dos grafos, que levou a esses diagramas, tem sido usada há séculos para examinar as trajetórias pelas quais um viajante poderia visitar todas as cidades de uma região, por exemplo. Mais recentemente, tem servido para otimizar o tráfego aéreo, considerando os aeroportos como um conjunto de pontos ou nós conectados entre si por meio dos aviões.

“Na primeira vez que rodei o programa de grafos, as diferenças de linguagem saltaram aos olhos”, conta Natália. Em 2007, ao terminar o curso de medicina e começar a residência médica em psiquiatria no hospital da UFRN, Natália notava que muitos diagnósticos diferenciais de mania e de esquizofrenia dependiam da experiência pessoal e de julgamentos subjetivos dos médicos – os que trabalhavam mais com pacientes com esquizofrenia tendiam a encontrar mais casos de esquizofrenia e menos de mania – e muitas vezes não havia consenso. Já se sabia que as pessoas com mania falam mais e se desviam do tópico central muito mais facilmente que as com esquizofrenia, mas isso lhe pareceu genérico demais. 
Em um congresso científico em 2008 em Fortaleza ela conversou com Copelli, que já colaborava com Ribeiro e a incentivou a trabalhar com grafos. No início ela resistiu, por causa da pouca familiaridade com matemática, mas logo depois a nova teoria lhe pareceu simples e prática.

Para levar o trabalho adiante, ela gravou e, com a ajuda de Nathália Lemos e Ana Cardina Pieretti, transcreveu as entrevistas com 24 pessoas 
(oito com mania, oito com esquizofrenia e oito sem qualquer distúrbio mental diagnosticado), a quem pedia para relatar um sonho; qualquer comentário fora desse tema era considerado um voo da imaginação, bastante comum entre as pessoas com mania.

“Já na transcrição, os relatos dos pacientes com mania eram claramente maiores que os com esquizofrenia”, diz. Em seguida, ela eliminou elementos menos importantes como artigos e preposições, dividiu a frase em sujeito, verbo e objetos, representados por pontos ou nós, enquanto a sequência entre elas na frase era representada por setas, unindo dois nós, e assinalou as que não se referiam ao tema central do relato, ou seja, o sonho recente que ela pedira para os entrevistados contarem, e marcavam um desvio do pensamento, comum entre as pessoas com mania.

Um programa específico para grafos baixado de graça na internet indicava as características relevantes para análise – ou atributos – e representava as principais diferenças de discurso entre os participantes, como quantidades de nós, extensão e densidade das conexões entre os pontos, recorrência, prolixidade (ou logorreia) e desvio do tópico central. “É supersimples”, assegura Natália. Nas validações e análises dos resultados, ela contou também com a colaboração de Osame Kinouchi, da Universidade de São Paulo (USP) em Ribeirão Preto, e Guillermo Cecchi, do Centro de Biologia Computacional da IBM, Estados Unidos.

Resultado: as pessoas com mania obtiveram uma pontuação maior que as com esquizofrenia em quase todos os itens avaliados. “A logorreia típica de pacientes com mania não resulta só do excesso de palavras, mas de um discurso que volta sempre ao mesmo tópico, em comparação com o grupo com esquizofrenia”, ela observou. Curiosamente, os participantes do grupo-controle, sem distúrbio mental diagnosticado, apresentaram estruturas discursivas de dois tipos, ora redundantes como os participantes com mania, ora enxutas como os com esquizofrenia, refletindo as diferenças entre suas personalidades ou a motivação para, naquele momento, falar mais ou menos. “A patologia define o discurso, não é nenhuma novidade”, diz ela. “Os psiquiatras são treinados para reconhecer essas diferenças, mas dificilmente poderão dizer que a recorrência de um paciente com mania está 28% menor, por mais experientes que sejam.”

“O ambiente interdisciplinar do instituto foi essencial para realizar esse estudo, porque eu estava todo dia trocando ideias com gente de outras áreas. Nivaldo Vasconcelos, um engenheiro de computação, me ajudou muito”, diz ela. O Instituto do Cérebro, em funcionamento desde 2007, conta atualmente com 13 professores, 22 estudantes de graduação e 42 de pós, 8 pós-doutorandos e 30 técnicos. “Vencidas as dificuldades iniciais, conseguimos formar um grupo de pesquisadores jovens e talentosos”, comemora Ribeiro. “A casa em que estamos agora tem um jardim amplo, e muitas noites ficamos lá até as duas, três da manhã, falando sobre ciência e tomando chimarrão.”

Artigo científico
MOTA, N.B. et al
Speech graphs provide 
a quantitative measure of thought disorder 
in psychosis. PLoS ONE (no prelo).

Putting the Body Back Into the Mind of Schizophrenia (Science Daily)

ScienceDaily (Oct. 31, 2011) — A study using a procedure called the rubber hand illusion has found striking new evidence that people experiencing schizophrenia have a weakened sense of body ownership and has produced the first case of a spontaneous, out-of-body experience in the laboratory.

These findings suggest that movement therapy, which trains people to be focused and centered on their own bodies, including some forms of yoga and dance, could be helpful for many of the2.2 million people in the United States who suffer from this mental disorder.

The study, which appears in the Oct. 31 issue of the scientific journal Public Library of Science One, measured the strength of body ownership of 24 schizophrenia patients and 21 matched control subjects by testing their susceptibility to the “rubber hand illusion” or RHI. This tactile illusion, which was discovered in 1998, is induced by simultaneously stroking a visible rubber hand and the subject’s hidden hand.

“After a while, patients with schizophrenia begin to ‘feel’ the rubber hand and disown their own hand. They also experience their real hand as closer to the rubber hand.” said Sohee Park, the Gertrude Conaway Vanderbilt Chair of Psychology and Psychiatry, who conducted the study with doctoral candidate Katharine Thakkar and research analysts Heathman Nichols and Lindsey McIntosh.

“Healthy people get this illusion too, but weakly,” Park said. “Some don’t get it at all, and there is a wide range of individual differences in how people experience this illusion that is related to a personality trait called schizotypy, associated with psychosis-proneness.”

Body ownership is one of two aspects of a person’s sense of self awareness. (The other aspect is self-agency, the sense that a person is initiating his or her own actions.) According to the researchers, the finding that schizophrenia patients are more susceptible to the rubber hand illusion suggests that they have a more flexible body representation and weakened sense of self compared to healthy people.

“What’s so interesting about Professor Park’s study is that they have found that the sense of bodily ownership does not diminish among patients with schizophrenia, but it can be extended to other objects more easily,” observed David Gray, Mellon assistant professor of philosophy at Vanderbilt, who is an expert on the philosophy of the mind. He did not participate in the study but is familiar with it. “Much of the literature concerning agency and ownership in schizophrenia focuses on the sense of lost agency over one’s own movements: But, in these cases, the sense of ownership is neither diminished nor extended.”

Before they began the procedure, the researchers gave participants a questionnaire to rate their degree of schizotypy: the extent to which they experience perceptual effects related to the illusion. The researchers found that the individuals who rated higher on the scale were more susceptible to the illusion.

The researchers gauged the relative strength of the RHI by asking participants to estimate the position of the index finger of their hidden hand on rulers placed on top of the box that conceals it before and after stimulation. The stronger the effect, the more the subjects’ estimate of the position of their hidden hand shifted in the direction of the rubber hand. Even the estimates of those who did not experience the effect subjectively shifted slightly.

The rubber hand illusion also has a physiological signature. Scientists don’t know why, but the temperature of the hidden hand drops by a few tenths of a degree when a person experiences the illusion. “It’s almost as if the hand is disowned and rejected, no longer part of the self,” Park commented.

The researchers were surprised when one of the patients undergoing the procedure experienced a full out-of-body experience. He reported that he was floating above his own body for about 15 minutes. According to Park, it is extremely rare to observe spontaneous out-of-body experiences in the laboratory. When they invited the patient back for a second session, he once again had an out-of-body experience during the rubber hand procedure, proving that the experience is repeatable.

“Anomalous experiences of the self were considered to be core features of schizophrenia decades ago but in recent years much of the emphasis has been on cognitive functions such as working memory,” said Park.

According to the psychologist, out-of-body experiences and body ownership are associated with a particular area in the brain called the temporoparietal junction. Lesions in this area and stimulation by strong magnetic fields can elicit out-of-body experiences. The new study suggests that disorders in this part of the brain may also contribute to the symptoms of schizophrenia.

The relationship between schizophrenia and body ownership may help explain the results of a German study published in 2008 that found a 12-week exercise program reduced the symptoms and improved the behavior of a small group of patients with chronic schizophrenia when compared to a control group that did not exercise. The study also found that the exercise increased size of the patients’ hippocampus slightly — a smaller-than-normal hippocampus is a well established symptom of schizophrenia.

“Exercise is inexpensive and obviously has a broad range of beneficial effects, so if it can also reduce the severity of schizophrenia, it is all to the good,” said Park. These findings suggest that focused physical exercise which involves precise body control, such as yoga and dancing, could be a beneficial form of treatment for this disorder.

The study was partly funded by a grant from the National Institutes of Health and the Gertrude Conaway Vanderbilt Endowed Chair.