schizophrenia

Posted on ADHD, Mental health, Multiple Sclerosis

Multiple sclerosis drug may help with poor working memory

A USC study of prescription data shows that people with Medicaid or Medicare Part D may be missing out on powerful new obesity and diabetes drugs

Fampridine is currently used to improve walking ability in individuals with multiple sclerosis. A new study indicates that it may also assist people with reduced working memory, which is often observed in mental health conditions like schizophrenia or depression.

Working memory is essential for everyday tasks, such as remembering a code long enough to type it in and engaging in conversations by reacting appropriately to what others say. It allows us to retain information for a brief period actively, typically a few seconds. However, certain conditions, including schizophrenia, depression, and ADHD, can impair working memory. Individuals affected by these conditions may struggle to follow conversations and to organize their thoughts effectively.

Fampridine is a drug that could help in such cases, as researchers led by Professor Andreas Papassotiropoulos and Professor Dominique de Quervain at the University of Basel have shown.

Practical only if working memory is poor

In their study, the researchers tested the effectiveness of fampridine on working memory in 43 healthy adults. Fampridine showed a more pronounced effect in participants whose baseline working memory was low. After taking the active substance for three days, they scored better in the relevant tests than those who took the placebo. In contrast, the drug showed no effect in people with good baseline working memory.

The researchers also observed that fampridine increased brain excitability in all participants, thus enabling faster processing of stimuli. The study was randomized and double-blind.

The established drug, a new application

“Fampridine doesn’t improve everyone’s working memory. But it could be a treatment option for those with reduced working memory,” explains Andreas Papassotiropoulos. Dominique de Quervain adds: “That’s why, together with researchers from the University Psychiatric Clinics Basel (UPK), we’re planning studies to test the efficacy of fampridine in schizophrenia and depression.”

The drug is currently used to improve walking ability in multiple sclerosis (MS). Particularly in capsule form, which releases the active ingredient slowly in the body, fampridine has shown effects on cognitive performance in MS patients. For some, it alleviates the mental fatigue that can accompany MS.

The researchers did not select the drug at random. This study followed comprehensive analyses of genome data to find starting points for repurposing established drugs. Fampridine acts on specific ion channels in nerve cells that, according to the researchers’ analyses, also play a role in mental disorders such as schizophrenia.

Posted on Autism, Epilepsy, Mental health, Patient Talk

Brain molecule makes neurons less selective, deepening understanding of human cognition

Excitatory neurons from the brains of mice

Excitatory neurons from mice’s brains are depicted in green, and PV inhibitory neurons are pictured in magenta. Cells in the deep hippocampus, which helps navigate space, are represented toward the left side of the image. Toward the right side, cells are defined in the visual cortex. Findings from Johns Hopkins Medicine may help scientists better understand the causes of autism, schizophrenia and epilepsy.

Neuroscientists from Johns Hopkins Medicine say they have determined how a brain cell surface molecule shapes certain neurons’ behaviour.

The research, which was published on October 2 in Nature, reveals how a molecule called the calcium-permeable (CP)-AMPA receptor suppresses a specific neuron’s ability to pay attention to specific external cues, such as your friend’s earrings. The study was conducted on genetically engineered mice. Understanding why some neurons are less “selective” about their response to certain cues may also help researchers study conditions such as schizophrenia, epilepsy, and autism, which are marked by the faulty processing of external cues and misfirings of neurons in the mammalian brain.

“We have found that the calcium-permeable subtype of AMPA receptors plays an additional role in suppressing the selectivity of a specific neuron,” says Dr. Ingie Hong, the first author and a neuroscience instructor at Johns Hopkins University School of Medicine. “Until now, the function of these particular receptors in the broader mammalian brain during everyday activities has been a mystery.”

AMPA receptors are critical to the fast transfer of information and memory formation in the brain, such as hearing and remembering a person’s name. The subtype of AMPA receptors in this study, CP-AMPA receptors, act as a “gate” that lowers the selectivity of parvalbumin (PV) neurons, which are inhibitory and thereby cast unselective inhibition to nearby neurons, the researchers say.

“Selective neurons will respond to something really specific, for example, your grandfather’s mustache, whereas less selective neurons will respond to different faces or people as well,” Hong says. “We’ve been looking for the mechanisms and molecules that control this specificity, or selectivity, and how it goes awry in conditions such as autism and epilepsy, where excitatory neurons can become overstimulated.”   

The researchers also found that mutations of GluA2, a protein subunit within the CP-AMPA receptor, are associated with intellectual disabilities.

“Human mutations in the GluA2 subunit of the AMPA receptors, which regulates the calcium permeability of the receptor, can lead to intellectual disability and autism,” says senior author Huganir. “This suggests tight control of AMPA receptor calcium permeability is essential for human cognition.”

Specifically, the investigators focused on CP-AMPA receptors in two distinct areas of the brain, the visual cortex, where neurons process visual information, and the hippocampus, where neurons respond to “where you are, where you are headed, or where you have been,” Hong says.

To conduct their research, the scientists developed novel adeno-associated virus vectors to replace calcium permeable AMPA receptors with impermeable counterparts and express them in the mouse brain. They say they hope these vectors can help treat disorders that arise from AMPA receptor mutations in the future.

To map out PV neuron selectivity, the scientists used advanced imaging techniques to observe neuron structure and activity deep within genetically engineered mice brains while showing them video stimuli.

“In most cases, we found that these PV neurons, which are typically less selective, became more selective to visual stimuli as well as spatial location when we swapped out CP-AMPA receptors for impermeable molecules, making inhibitory neurons act more like excitatory neurons,” Hong says.

The researchers say the high amount of CP-AMPA receptors in PV neurons is well-conserved across many species of mammals, including humans.

“Making neuron inhibition less selective makes our neural circuits more efficient than species that don’t have this molecular feature,” Hong says. “It probably also means that our neural networks are more stable.”

Hong says the new research may also have implications for machine learning used in artificial intelligence.

“In machine learning, there are many computerized ‘artificial’ neurons that are trained to be very selective or less selective,” he says. “We’re trying to find how specific and less specific units can work together to give us smarter machines and smarter AI.”

Credit David Cheon and Ingie Hong

Posted on Diet, Mental health

Keto diet improves severe mental illness says new research

A small clinical trial led by Stanford Medicine found that the metabolic effects of a ketogenic diet may help stabilize the brain.
A small clinical trial led by Stanford Medicine found that a ketogenic diet’s metabolic effects may help stabilize the brain.

For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword. While these drugs help regulate brain chemistry, they often cause metabolic side effects such as insulin resistance and obesity, which are distressing enough that many patients stop taking the medications.

Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results,suggest that a dietary intervention can be a powerful aid in treating mental illness.

“It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care,” said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper.

The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan.

Making the connection

Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet.

That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures.

“The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain,” Sethi said. “We thought it would be worth exploring this treatment in psychiatric conditions.”

A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective.

Meat and vegetables

In the four-month pilot trial, Sethi’s team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality — such as weight gain, insulin resistance, hypertriglyceridemia, dyslipidemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories.

“The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats,” said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach. 

The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels. (Ketones are acids produced when the body breaks down fat — instead of glucose — for energy.) By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent.

Feeling better

The participants underwent a variety of psychiatric and metabolic assessments throughout the trial.

Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome.

On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance.

“We’re seeing huge changes,” Sethi said. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”

The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction.

“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said. “They feel healthier and more hopeful.”

The researchers were impressed that most of the participants stuck with the diet. “We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship,” Sethi said.

Alternative fuel for the brain

There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said.

The researchers hypothesize that just as a ketogenic diet improves the rest of the body’s metabolism, it also improves the brain’s metabolism.

“Anything that improves metabolic health in general is probably going to improve brain health anyway,” Sethi said. “But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction.”

Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies.  

As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population.

She is founder and director of the metabolic psychiatry clinic at Stanford Medicine

“Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them,” she said. “They are seeking more help. They are looking to just feel better.”

Leave a comment Posted on Mental health

Is schizophrenia risk ‘around 80% genetic’?




Schizophrenia

Schizophrenia

“Genetics account for almost 80 per cent of a person’s risk of developing schizophrenia, according to new research,” the Mail Online reports. That is the main finding of a study looking at how often schizophrenia affected both twins of a pair, looking at identical and non-identical twins.

Schizophrenia is a serious mental health condition that can cause delusions and hallucinations. There is no single “cause” of schizophrenia. It is thought to result from a complex combination of both genetic and environmental factors.




The researchers looked at twins born in Denmark and found that if one identical twin had schizophrenia, the other twin (with the same genes) was also affected in about a third of cases. For non-identical twins, who only share on average half of their genes, this was true only in about 7% of cases. Based on these figures, the researchers calculated that 79% of the risk of developing schizophrenia was down to their genes.

While the findings suggest genes do play an important role in schizophrenia, this is only an estimate and the true picture is likely to be more complicated. Environmental factors clearly still have an influence on whether the person actually develops schizophrenia.

If you do have a history of schizophrenia in your family, this doesn’t mean you will automatically get the condition yourself. But it may be a good idea to avoid things that have been linked to the condition, such as drug use (particularly cannabis, cocaine, LSD or amphetamines).

 

Where did the story come from?

The study was carried out by researchers from the Center for Neuropsychiatric Schizophrenia Research at Copenhagen University Hospital in Denmark. Funding was provided by the Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, and Lundbeck Foundation Initiative for Integrative Psychiatric Research.

The study was published in the peer-reviewed journal Biological Psychiatry, and is available to read for free online.

The Mail’s report that: “The findings suggest the genes we inherit play a far bigger role than previously believed and mean the seeds are sown before birth” isn’t strictly correct. The estimates from the current study are similar to those from some previous studies.

 

What kind of research was this?

This was a twin cohort study using data from the Danish Twin Register combined with the psychiatric registry, aiming to better quantify the extent to which schizophrenia risk may be explained by the genes we inherit. Previous studies have suggested that genes play an important role, but researchers wanted to use some updated statistical methods and newer data to come up with a more up-to-date estimate.

Both genetics and environmental factors are thought to play a role in the risk of schizophrenia. Twin studies are a standard way to estimate the extent to which genetics plays a role. Both identical and non-identical twins may be assumed to have the same environmental exposure. However, identical twins have 100% of their genes in common, while non-identical twins share only 50% on average.

Therefore if identical twins are more alike than non-identical twins, marked differences in health outcomes are likely to be down to genetics. Researchers used statistical methods to estimate what role genes play in the development of a particular characteristic (called “heritability”).

Previous studies show that schizophrenia affects both members of identical twins in 41% to 61% of cases, but only 0 to 28% in non-identical twins. A previous pooling of twin studies has suggested that the “heritability” of schizophrenia is 81%.

It is worth bearing in mind that this type of twin cohort study makes various assumptions to simplify the picture.




It assumes that genes and the environment do not interact. This assumption may result in over-estimating the impact of genes. For example, it could be the case that people with a specific genetic profile are more likely to use drugs. Drug use (an environmental risk factor), rather than the genes directly, could then increase the risk of schizophrenia.

Also, the results obtained are very dependent on the environment the twins are living in. So results would likely differ if the same study were carried out in different societies at different time points throughout history.

Finally, this type of study does not identify specific genes that may be involved in the risk of schizophrenia.

 

What did the research involve?

The Danish Twin Register, started in 1954, includes all twins born in Denmark. The Danish Psychiatric Central Research Register includes data on all psychiatric hospital admissions since 1969, and all outpatient visits since 1995. Diagnoses in the register are based on the long-established International Classification of Diseases (ICD), which is a way of classifying diseases according to standard criteria.

The researchers used data on 31,524 twin pairs born up to the year 2000, linked with the psychiatric registry data, and knew whether they were identical or not.

They identified the twins who had been diagnosed with schizophrenia or schizophrenia spectrum disorders (this means not fulfilling diagnostic criteria for schizophrenia, but having a disorder with similar characteristics).

They then looked at how many of these diagnoses affected both twins in a pair. They used statistical methods to estimate how much of a role genes played in the development of schizophrenia. One of the new features of the methods used was that they took into account how long each twin had been followed up.

The researchers’ results only apply to schizophrenia diagnosed up to the age of 40.

 

What were the basic results?

448 of the included twin pairs (about 1% of the sample) were affected by schizophrenia, and 788 were affected by schizophrenia spectrum disorders. Average age of diagnosis of these conditions was about 28 or 29 years.

The researchers found that if one identical twin was affected by schizophrenia or schizophrenia spectrum disorders, the chance of the second being affected was about a third. For non-identical twins, the chance was far lower – only 7% for schizophrenia and 9% for schizophrenia spectrum disorders.

The researchers estimated that in the population studied, about 78% of the “liability” for schizophrenia and 73% for schizophrenia spectrum disorders could come down to genetic factors. This means that a high proportion of the co-twins may be carrying genes that make them “vulnerable” to the condition, even if they haven’t developed it in this study.

 

How did the researchers interpret the results?

The researchers conclude: “The estimated 79% heritability of schizophrenia is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader [range of] schizophrenia spectrum disorders. The low [co-diagnosis] rate of 33% in [identical] twins demonstrates that illness vulnerability is not solely indicated by genetic factors.”

 

Conclusion

This study explores how much of the risk of developing schizophrenia or related disorders may be explained by genetics.

It shows that schizophrenia and related disorders are quite rare – affecting about 1% of the general population.

Their observed co-diagnosis rate in both twins – about a third for identical and less than 10% for non-identical twins – was lower than has been observed in other studies. This seems to suggest that while a high proportion of an individual’s susceptibility may come down to hereditary factors, environmental factors must still be play a substantial role.

This type of study makes a number of assumptions to simplify the picture, and these may not accurately portray reality. For example, it assumes that identical and non-identical twins would share similar environmental exposures.

However, this may not be the case. It also assumes that genes and the environment do not interact, but in reality, people with different genetic makeups may react to the same exposure in different ways.

Other reasons for the low co-diagnosis rate could be, as the researchers acknowledge, down to study methods. For example, some may have had different severity or presentation of illness influencing diagnosis. The study also does not have lifelong data for all of the twins. Though most people with schizophrenia are diagnosed before 40 years of age, longer follow-up times would be ideal.

One final point: estimates that come out of this type of study are dependent on the environment the twins are living in. So results would likely differ if the same study were carried out in very different societies, or at different time points throughout history. Though this study benefits from using a large population-wide registry, study members were all Danish residents. The findings may not apply to different populations, with different ethnic and cultural makeups.

The study will add to the large body of literature exploring the role of hereditary and environmental risk factors for schizophrenia. However, it certainly doesn’t mean we fully understand the causes of the condition, including the impact of environment on this condition.

Leave a comment Posted on Pain Management

Acupuncture – Does it work? Read some of the evidence here




Acupuncture

Acupuncture

Have you ever used Acupuncture?

Did it work?  Tell us your view in the comments section below?

Acupuncture is a treatment derived from ancient Chinese medicine in which fine needles are inserted at certain sites in the body for therapeutic or preventative purposes.

It is often seen as a form of complementary or alternative medicine (CAM), although it is used in many NHS general practices, as well as the majority of pain clinics and hospices in the UK.

Theory

Western medical acupuncture is the use of acupuncture after a proper medical diagnosis. It is based on scientific evidence that shows the treatment can stimulate nerves under the skin and in muscle tissue.




This results in the body producing pain-relieving substances, such as endorphins. It is likely these substances are responsible for any beneficial effects seen with this form of acupuncture.

Traditional acupuncture is based on the belief that an energy, or “life force”, flows through the body in channels called meridians. This life force is known as Qi (pronounced “chee”).

Practitioners who adhere to traditional beliefs about acupuncture believe that when Qi does not flow freely through the body, this can cause illness. They also believe acupuncture can restore the flow of Qi, and so restore health.

Read more about what happens during acupuncture.

What is it used for?

Acupuncture practitioners – sometimes called acupuncturists – use acupuncture to treat a wide range of health conditions.

It is often used to treat pain conditions such as headache, lower back pain and osteoarthritis, but is also sometimes used in an attempt to help people with conditions ranging from infertility to anxiety and asthma.




Acupuncture is occasionally available on the NHS, although access is limited. Most acupuncture patients pay for private treatment.

Read more about the common uses of acupuncture.

Does it work?

Currently, the National Institute for Health and Care Excellence (NICE) only recommends considering acupuncture as a treatment option for chronic lower back pain, chronic tension-type headaches and migraines. NICE makes these recommendations on the basis of scientific evidence.

There is also some evidence that acupuncture works for a small number of other problems, including neck pain and post-chemotherapy nausea and vomiting.

Acupuncture is sometimes used for a variety of other conditions as well, but the evidence is not conclusive for many of these uses.

Read more about the evidence for and against acupuncture.

Having acupuncture

When it is carried out by a qualified practitioner, acupuncture is generally very safe. Some people experience side effects such as feeling drowsy or dizzy, but these are usually mild and short-lived.

If you choose to have acupuncture, make sure your acupuncture practitioner is either a regulated healthcare professional or a member of a recognised national acupuncture organisation.

Read more about acupuncture safety and regulation.

[Original article on NHS Choices website]

Evidence for and against acupuncuture

There is some scientific evidence acupuncture has a beneficial effect for a number of health conditions.

However, there is less clear scientific evidence about the benefits of acupuncture in the majority of conditions it is often used for.

The National Institute for Health and Care Excellence (NICE) only recommends considering acupuncture as a treatment option for chronic lower back pain, chronic tension-type headaches and migraine.

Assessing the evidence

One of the best ways researchers can assess the evidence behind a particular treatment is by carrying out a systematic review. This is a “study of studies” that combines findings from separate but similar studies to come up with an overall conclusion.

Systematic reviews are an important part of health research because they can identify findings that might otherwise be missed in individual studies. They can also help distinguish the effects of treatment from the effects of chance.

It is important to remember that when we use a treatment and feel better, this can be because of a phenomenon called the placebo effect and not because of the treatment itself. Systematic reviews can help reduce the potential influence of the placebo effect.

While systematic reviews cannot always determine conclusively whether a treatment does or does not work, they can be useful in assessing how a particular treatment (such as acupuncture) compares to another (such as “sham” acupuncture or medication).

However, even this can be challenging – both acupuncture and placebo treatments can stimulate the release of natural painkilling substances called endorphins, which can make it difficult to distinguish between them.

What evidence is there for acupuncture?

One of the largest and most respected organisations that carries out and publishes systematic reviews into the effectiveness of medical treatments is The Cochrane Collaboration.

A number of systematic reviews into the effectiveness of acupuncture have been published by The Cochrane Collaboration, and the basic results are summarised below.

Some positive evidence

Systematic reviews carried out by The Cochrane Collaboration have found there is some evidence acupuncture may have a beneficial effect on the following conditions:

However, because of disagreements over the way acupuncture trials should be carried out and over what their results mean, the existence of some positive evidence does not mean acupuncture definitely works for these conditions.

In many cases, the evidence appears contradictory. For example, some high-quality studies may suggest acupuncture is no better than “sham” acupuncture, whereas some lower-quality studies may suggest acupuncture is better than an established medical treatment.

The issue is sometimes also further complicated by the fact some “sham interventions” include active needling and are therefore not true placebos.

In addition, it can be difficult to make sure the patients involved in acupuncture studies are unaware of the specific treatment they are receiving (known as “blinding”).

This is because it is obvious whether you are receiving a conventional medical treatment such as medication or if you are receiving acupuncture, for example. This is a problem as it means the preconceptions of the person being treated may influence the result.

Some systematic reviews, however, have demonstrated the effects of acupuncture over sham treatment in studies where patients are unaware whether they are having real acupuncture or sham treatment.

For example, one large meta-analysis (a type of systematic review) not carried out by The Cochrane Collaboration included data from more than 17,000 patients. It compared acupuncture to sham acupuncture or no acupuncture without patients being aware of whether they had received real or sham treatment.

This review found acupuncture to be superior to both sham and no treatment for headaches, osteoarthritis, back pain and neck pain.

Little or no evidence

In many conditions where acupuncture is used, there is not enough good quality evidence to draw any clear conclusions over its relative effectiveness compared with other treatments.

For example, systematic reviews published by The Cochrane Collaboration have suggested more research is needed to assess whether acupuncture is effective for: asthma, glaucoma, schizophrenia, depression, shoulder, pain, elbow, pain, rheumatoid arthritis, Bell’s palsy, restless legs syndrome, insomnia vascular ,dementia, stroke, stroke rehabilitation and swallowing problems caused by stroke

More research is needed to establish whether acupuncture is better or worse than best standard treatments for these conditions.

More information and research

If you want to find out more about studies into acupuncture, you can search for high-quality research using the NHS Evidence and Cochrane Library websites.