Posts Tagged ‘neuropsychiatric disease’

With the pressure for a certain body type prevalent in the media, eating disorders are on the rise. But these diseases are not completely socially driven; researchers have uncovered important genetic and biological components as well and are now beginning to tease out the genes and pathways responsible for eating disorder predisposition and pathology.

As we enter the holiday season, shoppers will once again rush into crowded department stores searching for the perfect gift. They will be jostled and bumped, yet for the most part, remain cheerful because of the crisp air, lights, decorations, and the sound of Karen Carpenter’s contralto voice ringing out familiar carols.

While Carpenter is mainly remembered for her musical talents, unfortunately, she is also known for introducing the world to anorexia nervosa (AN), a severe life-threatening mental illness characterized by altered body image and stringent eating patterns that claimed her life just before her 33rd birthday in 1983.

Even though eating disorders (ED) carry one of the highest mortality rates of any mental illness, many researchers and clinicians still view them as socially reinforced behaviors and diagnose them based on criteria such as “inability to maintain body weight,” “undue influence of body weight or shape on self-evaluation,” and “denial of the seriousness of low body weight” (1). This way of thinking was prevalent when Michael Lutter, then an MD/PhD student at the University of Texas Southwestern Medical Center, began his psychiatry residency in an eating disorders unit. “I just remember the intense fear of eating that many patients exhibited and thought that it had to be biologically driven,” he said.

Lutter carried this impression with him when he established his own research laboratory at the University of Iowa. Although clear evidence supports the idea that EDs are biologically driven—they predominantly affect women and significantly alter energy homeostasis—a lack of well-defined animal models combined with the view that they are mainly behavioral abnormalities have hindered studies of the neurobiology of EDs. Still, Lutter is determined to find the biological roots of the disease and tease out the relationship between the psychiatric illness and metabolic disturbance using biochemistry, neuroscience, and human genetics approaches.

We’ve Only Just Begun

Like many diseases, EDs result from complex interactions between genes and environmental risk factors. They tend to run in families, but of course, for many family members, genetics and environment are similar enough that teasing apart the influences of nature and nurture is not easy. Researchers estimate that 50-80% of the predisposition for developing an ED is genetic, but preliminary genome-wide analyses and candidate gene studies failed to identify specific genes that contribute to the risk.

According to Lutter, finding ED study participants can be difficult. “People are either reluctant to participate, or they don’t see that they have a problem,” he reported. Set on finding the genetic underpinnings of EDs, his team began recruiting volunteers and found 2 families, 1 with 20 members, 10 of whom had an ED and another with 5 out of 8 members affected. Rather than doing large-scale linkage and association studies, the team decided to characterize rare single-gene mutations in these families, which led them to identify mutations in the first two genes, estrogen-related receptor α (ESRRA) and histone deacetylase 4 (HDAC4), that clearly associated with ED predisposition in 2013 (1).

“We have larger genetic studies on-going, including the collection of more families. We just happened to publish these two families first because we were able to collect enough individuals and because there is a biological connection between the two genes that we identified,” Lutter explained.

ESRRA appears to be a transcription factor upregulated by exercise and calorie restriction that plays a role in energy balance and metabolism. HDAC4, on the other hand, is a well-described histone deacteylase that has previously been implicated in locomotor activity, body weight homeostasis, and neuronal plasticity.

Using immunoprecipitation, the researchers found that ESRRA interacts with HDAC4, in both the wild type and mutant forms, and transcription assays showed that HDAC4 represses ESRRA activity. When Lutter’s team repeated the transcription assays using mutant forms of the proteins, they found that the ESRRA mutation seen in one family significantly reduced the induction of target gene transcription compared to wild type, and that the mutation in HDAC4 found in the other family increased transcriptional repression for ESRRA target genes.

“ESRRA is a well known regulator of mitochondrial function, and there is an emerging view that mitochondria in the synapse are critical for neurotransmission,” Lutter said. “We are working on identifying target pathways now.”

Bless the Beasts and the Children

Finding genes associated with EDs provides the groundwork for molecular studies, but EDs cannot be completely explained by the actions of altered transcription factors. Individuals suffering these disorders often experience intense anxiety, intrusive thoughts, hyperactivity, and poor coping strategies that lead to rigid and ritualized behaviors and severe crippling perfectionism. They are less aware of their emotions and often try to avoid emotion altogether. To study these complex behaviors, researchers need animal models.

Until recently, scientists relied on mice with access to a running wheel and restricted access to food. Under these conditions, the animals quickly increase their locomotor activity and reduce eating, frequently resulting in death. While some characteristics of EDs—excessive exercise and avoiding food—can be studied in these mice, the model doesn’t allow researchers to explore how the disease actually develops. However, Lutter’s team has now introduced a promising new model (3).

Based on their previous success with identifying the involvement of ESRRA and HDAC4 in EDs, the researchers wondered if mice lacking ESRRA might make suitable models for studies on ED development. To find out, they first performed immunohistochemistry to understand more about the potential cognitive role of ESRRA.

“ESRRA is not expressed very abundantly in areas of the brain typically implicated in the regulation of food intake, which surprised us,” Lutter said. “It is expressed in many cortical regions that have been implicated in the etiology of EDs by brain imaging like the prefrontal cortex, orbitofrontal cortex, and insula. We think that it probably affects the activity of neurons that modulate food intake instead of directly affecting a core feeding circuit.”

With these data, the team next tried providing only 60% of the normal daily calories to their mice for 10 days and looked again at ESRRA expression. Interestingly, ESRRA levels increased significantly when the mice were insufficiently fed, indicating that the protein might be involved in the response to energy balance.

Lutter now believes that upregulation of ESRRA helps organisms adapt to calorie restriction, an effect possibly not happening in those with ESRRA or HDAC4 mutations. “This makes sense for the clinical situation where most individuals will be doing fine until they are challenged by something like a diet or heavy exercise for a sporting event. Once they start losing weight, they don’t adapt their behaviors to increase calorie intake and rapidly spiral into a cycle of greater and greater weight loss.”

When Lutter’s team obtained mice lacking ESRRA, they found that these animals were 15% smaller than their wild type littermates and put forth less effort to obtain food both when fed restricted calorie diets and when they had free access to food. These phenotypes were more pronounced in female mice than male mice, likely due to the role of estrogen signaling. Loss of ESRRA increased grooming behavior, obsessive marble burying, and made mice slower to abandon an escape hole after its relocation, indicating behavioral rigidity. And the mice demonstrated impaired social functioning and reduced locomotion.

Some people with AN exercise extensively, but this isn’t seen in all cases. “I would say it is controversial whether or not hyperactivity is due to a genetic predisposition (trait), secondary to starvations (state), or simply a ritual that develops to counter the anxiety of weight related obsessions. Our data would suggest that it is not due to genetic predisposition,” Lutter explained. “But I would caution against over-interpretation of mouse behavior. The locomotor activity of mice is very different from people and it’s not clear that you can directly translate the results.”

For All We Know

Going forward, Lutter’s group plans to drill down into the behavioral phenotypes seen in their ESRRA null mice. They are currently deleting ESRRA from different neuronal cell types to pair individual neurons with the behaviors they mediate in the hope of working out the neural circuits involved in ED development and pathology.

In addition, the team has created a mouse line carrying one of the HDAC4 mutations previously identified in their genetic study. So far, this mouse “has interesting parallels to the ESRRA-null mouse line,” Lutter reported.

The team continues to recruit volunteers for larger-scale genetic studies. Eventually, they plan to perform RNA-seq to identify the targets of ESRRA and HDAC4 and look into their roles in mitochondrial biogenesis in neurons. Lutter suspects that this process is a key target of ESRRA and could shed light on the cognitive differences, such as altered body image, seen in EDs. In the end, a better understanding of the cells and pathways involved with EDs could create new treatment options, reduce suffering, and maybe even avoid the premature loss of talented individuals to the effects of these disorders.

References

1. Lutter M, Croghan AE, Cui H. Escaping the Golden Cage: Animal Models of Eating Disorders in the Post-Diagnostic and Statistical Manual Era. Biol Psychiatry. 2015 Feb 12.

2. Cui H, Moore J, Ashimi SS, Mason BL, Drawbridge JN, Han S, Hing B, Matthews A, McAdams CJ, Darbro BW, Pieper AA, Waller DA, Xing C, Lutter M. Eating disorder predisposition is associated with ESRRA and HDAC4 mutations. J Clin Invest. 2013 Nov;123(11):4706-13.

3. Cui H, Lu Y, Khan MZ, Anderson RM, McDaniel L, Wilson HE, Yin TC, Radley JJ, Pieper AA, Lutter M. Behavioral disturbances in estrogen-related receptor alpha-null mice. Cell Rep. 2015 Apr 21;11(3):344-50.

http://www.biotechniques.com/news/Exploring-the-Biology-of-Eating-Disorders/biotechniques-361522.html

by Jon Hamilton

A drug that’s already approved for treating leukemia appears to dramatically reduce symptoms in people who have Parkinson’s disease with dementia, or a related condition called Lewy body dementia.

A pilot study of 12 patients given small doses of nilotinib found that movement and mental function improved in all of the 11 people who completed the six-month trial, researchers reported Saturday at the Society for Neuroscience meeting in Chicago.

And for several patients the improvements were dramatic, says Fernando Pagan, an author of the study and director of the Movement Disorders Program at Georgetown University Medical Center. One woman regained the ability to feed herself, one man was able to stop using a walker, and three previously nonverbal patients began speaking again, Pagan says.

“After 25 years in Parkinson’s disease research, this is the most excited I’ve ever been,” Pagan says.

If the drug’s effectiveness is confirmed in larger, placebo-controlled studies, nilotinib could become the first treatment to interrupt a process that kills brain cells in Parkinson’s and other neurodegenerative diseases, including Alzheimer’s.

One of the patients in the pilot study was Alan Hoffman, 74, who lives with his wife, Nancy, in Northern Virginia.

Hoffman was diagnosed with Parkinson’s in 1997. At first, he had trouble moving his arms. Over time, walking became more difficult and his speech became slurred. And by 2007, the disease had begun to affect his thinking.

“I knew I’d dropped off in my ability to read,” Hoffman says. “People would keep giving me books and I’d have read the first chapter of about 10 of them. I had no ability to focus on it.”

“He had more and more difficulty making sense,” Nancy Hoffman says. He also became less active, less able to have conversations, and eventually stopped doing even household chores, she says.

But after a few weeks on nilotinib, Hoffman “improved in every way,” his wife says. “He began loading the dishwasher, loading the clothes in the dryer, things he had not done in a long time.”

Even more surprising, Hoffman’s scores on cognitive tests began to improve. At home, Nancy Hoffman says her husband was making sense again and regained his ability to focus. “He actually read the David McCullough book on the Wright Brothers and started reading the paper from beginning to end,” she says.

The idea of using nilotinib to treat people like Alan Hoffman came from Charbel Moussa, an assistant professor of neurology at Georgetown University and an author of the study.

Moussa knew that in people who have Parkinson’s disease with dementia or a related condition called Lewy body dementia, toxic proteins build up in certain brain cells, eventually killing them. Moussa thought nilotinib might be able to reverse this process.

His reasoning was that nilotinib activates a system in cells that works like a garbage disposal — it clears out unwanted proteins. Also, Moussa had shown that while cancer cells tend to die when exposed to nilotinib, brain cells actually become healthier.

So Moussa had his lab try the drug on brain cells in a Petri dish. “And we found that, surprisingly, with a very little amount of the drug we can clear all these proteins that are supposed to be neurotoxic,” he says.

Next, Moussa had his team give the drug to transgenic mice that were almost completely paralyzed from Parkinson’s disease. The treatment “rescued” the animals, he says, allowing them to move almost as well as healthy mice.

Moussa’s mice got the attention of Pagan from Georgetown’s Movement Disorders Program. “When Dr. Moussa showed them to me,” Pagan says, “it looked like, hey, this is type of drug that we’ve been looking for because it goes to the root of the problem.”

The pilot study was designed to determine whether nilotinib was safe for Parkinson’s patients and to determine how much drug from the capsules they were taking was reaching their brains. “But we also saw efficacy, which is really unheard of in a safety study,” Pagan says.

The study found that levels of toxic proteins in blood and spinal fluid decreased once patients began taking nilotinib. Also, tests showed that the symptoms of Parkinson’s including tremor and “freezing” decreased. And during the study patients were able to use lower doses of Parkinson’s drugs, suggesting that the brain cells that produce dopamine were working better.

But there are some caveats, Pagan says. For one thing, the study was small, not designed to measure effectiveness, and included no patients taking a placebo.

Also, nilotinib is very expensive. The cost of providing it to leukemia patients is thousands of dollars a month.

And finally, Parkinson’s and dementia patients would have to keep taking nilotinib indefinitely or their symptoms would continue to get worse.

Alan Hoffman was okay for about three weeks after the study ended and he stopped taking the drug. Since then, “There’s (been) a pretty big change,” his wife says. “He does have more problems with his speech, and he has more problems with cognition and more problems with mobility.”

The Hoffmans hope to get more nilotinib from the drug’s maker, Novartis, through a special program for people who improve during experiments like this one.

Meanwhile, the Georgetown team plans to try nilotinib in patients with another brain disease that involves toxic proteins: Alzheimer’s.

http://www.npr.org/sections/health-shots/2015/10/17/448323916/can-a-cancer-drug-reverse-parkinsons-disease-and-dementia

An automated speech analysis program correctly differentiated between at-risk young people who developed psychosis over a two-and-a-half year period and those who did not. In a proof-of-principle study, researchers at Columbia University Medical Center, New York State Psychiatric Institute, and the IBM T. J. Watson Research Center found that the computerized analysis provided a more accurate classification than clinical ratings. The study, “Automated Analysis of Free Speech Predicts Psychosis Onset in High-Risk Youths,” was recently published in NPJ-Schizophrenia.

About one percent of the population between the age of 14 and 27 is considered to be at clinical high risk (CHR) for psychosis. CHR individuals have symptoms such as unusual or tangential thinking, perceptual changes, and suspiciousness. About 20% will go on to experience a full-blown psychotic episode. Identifying who falls in that 20% category before psychosis occurs has been an elusive goal. Early identification could lead to intervention and support that could delay, mitigate or even prevent the onset of serious mental illness.
Speech provides a unique window into the mind, giving important clues about what people are thinking and feeling. Participants in the study took part in an open-ended, narrative interview in which they described their subjective experiences. These interviews were transcribed and then analyzed by computer for patterns of speech, including semantics (meaning) and syntax (structure).

The analysis established each patient’s semantic coherence (how well he or she stayed on topic), and syntactic structure, such as phrase length and use of determiner words that link the phrases. A clinical psychiatrist may intuitively recognize these signs of disorganized thoughts in a traditional interview, but a machine can augment what is heard by precisely measuring the variables. The participants were then followed for two and a half years.
The speech features that predicted psychosis onset included breaks in the flow of meaning from one sentence to the next, and speech that was characterized by shorter phrases with less elaboration. The speech classifier tool developed in this study to mechanically sort these specific, symptom-related features is striking for achieving 100% accuracy. The computer analysis correctly differentiated between the five individuals who later experienced a psychotic episode and the 29 who did not. These results suggest that this method may be able to identify thought disorder in its earliest, most subtle form, years before the onset of psychosis. Thought disorder is a key component of schizophrenia, but quantifying it has proved difficult.

For the field of schizophrenia research, and for psychiatry more broadly, this opens the possibility that new technology can aid in prognosis and diagnosis of severe mental disorders, and track treatment response. Automated speech analysis is inexpensive, portable, fast, and non-invasive. It has the potential to be a powerful tool that can complement clinical interviews and ratings.

Further research with a second, larger group of at-risk individuals is needed to see if this automated capacity to predict psychosis onset is both robust and reliable. Automated speech analysis used in conjunction with neuroimaging may also be useful in reaching a better understanding of early thought disorder, and the paths to develop treatments for it.

http://medicalxpress.com/news/2015-08-psychosis-automated-speech-analysis.html


Healthy people who are given commonly prescribed mood-altering drugs see significant changes in the degree to which they are willing to tolerate harm against themselves and others, according to a study published Thursday. The research has implications for understanding human morality and decision-making.

A team of scientists from the University College London (UCL) and Oxford University found that healthy people who were given the serotonin-boosting antidepressant citalopram were willing to pay twice as much to prevent harm to themselves or others, compared to those given a placebo. By contrast, those who were given a dose of the dopamine-enhancing Parkinson’s drug levodopa made more selfish decisions, overcoming an existing tendency to prefer harming themselves over others.

The researchers said their findings, published in the journal Current Biology, provided clues to the neurological and chemical roots of common clinical disorders like psychopathy, which causes people to disregard the emotions of others.

The researchers compared how much pain subjects were willing to anonymously inflict on themselves or other people in exchange for money. Out of 175 subjects, 89 were given citalopram or a placebo and 86 were given levodopa or a placebo.

They were anonymously paired up into decision-makers and receivers, and all subjects were given shocks at their pain threshold. The decision-makers were then allowed to choose a different amount of money in exchange for a different amount of shocks, either to themselves or the receivers.

On average, people who were given a placebo were willing to pay about 35p per shock to prevent harm to themselves and 44p per shock to prevent harm to others. Those who were given citalopram became more averse to harm, paying an average of 60p to avoid harm to themselves and 73p per shock to avoid harm to others. This meant that citalopram users, on average, delivered 30 fewer shocks to themselves and 35 fewer shocks to others.

However, those who were given levodopa became more selfish, showing no difference in the amount they were willing to pay to prevent shocks to themselves or others. On average, they were willing to pay about 35p per shock to prevent harm to themselves or others, meaning that they delivered on average about 10 more shocks to others during the trial than those who took a placebo. They also showed less hesitation about shocking others than those given the placebo.

Similar research conducted by the same team in November found that subjects were willing to spare the stranger pain twice as often as they spared themselves, indicating that they preferred harming themselves over others for profit, a behavior known as “hyper-altruism.”

“Our findings have implications for potential lines of treatment for antisocial behavior, as they help us to understand how serotonin and dopamine affect people’s willingness to harm others for personal gain,” Molly Crockett of UCL, the study’s lead author, said in a press release. “We have shown that commonly-prescribed psychiatric drugs influence moral decisions in healthy people, raising important ethical questions about the use of such drugs.

“It is important to stress, however, that these drugs may have different effects in psychiatric patients compared to healthy people. More research is needed to determine whether these drugs affect moral decisions in people who take them for medical reasons.”

http://www.ibtimes.com/antidepressants-affect-morality-decision-making-new-study-finds-1995363


An image depicting the measurement of nasal airflow while a child is presented with pleasant and unpleasant odors. Throughout the 10-minute study the children were seated comfortably in front of a computer monitor while viewing a cartoon. The nasal airflow measurement and the presentation of odorants were done using a modified pediatric nasal cannula and a custom built olfactometer.

Imagine the way you might smell a rose. You’d take a nice big sniff to breathe in the sweet but subtle floral scent. Upon walking into a public restroom, you’d likely do just the opposite–abruptly limiting the flow of air through your nose. Now, researchers reporting in the Cell Press journal Current Biology on July 2 have found that people with autism spectrum disorder (ASD) don’t make this natural adjustment like other people do. Autistic children go right on sniffing in the same way, no matter how pleasant or awful the scent.

The findings suggest that non-verbal tests related to smell might serve as useful early indicators of ASD, the researchers say.

“The difference in sniffing pattern between the typically developing children and children with autism was simply overwhelming,” says Noam Sobel of the Weizmann Institute of Science in Israel.

Earlier evidence had indicated that people with autism have impairments in “internal action models,” the brain templates we rely on to seamlessly coordinate our senses and actions. It wasn’t clear if this impairment would show up in a test of the sniff response, however.

To find out, Sobel, along with Liron Rozenkrantz and their colleagues, presented 18 children with ASD and 18 normally developing children (17 boys and 1 girl in each group) with pleasant and unpleasant odors and measured their sniff responses. The average age of children in the study was 7. While typical children adjusted their sniffing within 305 milliseconds of smelling an odor, the researchers report, children on the autism spectrum showed no such response.

That difference in sniff response between the two groups of kids was enough to correctly classify them as children with or without a diagnosis of ASD 81% of the time. Moreover, the researchers report that increasingly aberrant sniffing was associated with increasingly severe autism symptoms, based on social but not motor impairments.

The findings suggest that a sniff test could be quite useful in the clinic, although the researchers emphasize that their test is in no way ready for that yet.

“We can identify autism and its severity with meaningful accuracy within less than 10 minutes using a test that is completely non-verbal and entails no task to follow,” Sobel says. “This raises the hope that these findings could form the base for development of a diagnostic tool that can be applied very early on, such as in toddlers only a few months old. Such early diagnosis would allow for more effective intervention.”

The researchers now plan to test whether the sniff-response pattern they’ve observed is specific to autism or whether it might show up also in people with other neurodevelopmental conditions. They also want to find out how early in life such a test might be used. But the most immediate question for Sobel is “whether an olfactory impairment is at the heart of the social impairment in autism.”

Current Biology, Rozenkrantz et al.: “A Mechanistic Link between Olfaction and Autism Spectrum Disorder” http://dx.​doi.​org/​10.​1016/​j.​cub.​2015.​05.​048

Psychedelics were highly popular hallucinogenic substances used for recreational purposes back in the 1950s and 1960s. They were also widely used for medical research looking into their beneficial impact on several psychiatric disorders, including anxiety and depression. In 1967, however, they were classified as a Class A, Schedule I substance and considered to be among the most dangerous drugs with no recognized clinical importance. The use of psychedelics has since been prohibited.

Psychiatrist and honorary lecturer at the Institute of Psychiatry, Psychology and Neuroscience, at Psychiatrist and honorary lecturer at the Institute of Psychiatry, Psychology and Neuroscience, at King’s College London, James Rucker, MRCPsych, is proposing to reclassify and improve access to psychedelics in order to conduct more research on their therapeutic benefits. He believes in the potential of psychedelics so much that late last month he took to the pages of the prestigious journal the BMJ to make his case. He wrote that psychedelics should instead be considered Schedule II substances which would allow a “comprehensive, evidence based assessment of their therapeutic potential.”

“The Western world is facing an epidemic of mental health problems with few novel therapeutic prospects on the horizon,” Rucker told Psychiatry Advisor, justifying why studying psychedelics for treating psychiatric illnesses is so important.

Rucker recognizes that the illicit substance may be harmful to some people, especially when used in a recreational and uncontrolled context. He cited anecdotal reports of the substance’s disabling symptoms, such as long-term emotionally charged flashbacks. However, he also believes that psychedelic drugs can have positive outcomes in other respects.

“The problem at the moment,” he argued, “is that we don’t know who would benefit and who wouldn’t. The law does a good job of preventing us from finding out.”

From a biological perspective, psychedelics act as an agonist, a substance that combines with a receptor and initiates a physiological response to a subtype of serotonin known as 5HT2a. According to Rucker, this process influences the balance between inhibitory and excitatory neurotransmitters.

“The psychedelics may invoke a temporary state of neural plasticity within the brain, as a result of which the person may experience changes in sensory perception, thought processing and self-awareness,” Rucker speculated. He added that psychedelic drugs can act as a catalyst that stirs up the mind to elicit insights into unwanted cycles of feelings, thoughts and behaviors.

“These cycles can then be faced, expressed, explored, interpreted, accepted and finally integrated back into the person’s psyche with the therapist’s help,” he explained. Reclassifying psychedelics could mean that the mechanism by which these substances can help with anxiety, depression and psychiatric symptoms could be studied and understood better.

Several experts in the field of drug misuse have disagreed strongly with Rucker’s proposals in this area, and are quick to refute his findings and recommendations. Nora Volkow, MD, director of the National Institute on Drug Abuse (NIDA), emphasized the fact that psychedelics can distort a person’s perception of time, motion, colors, sounds and self. “These drugs can disrupt a person’s ability to think and communicate rationally, or even to recognize reality, sometimes resulting in bizarre or dangerous behavior,” she wrote on a NIDA webpage dealing with hallucinogens and dissociative drugs.

“Hallucinogenic drugs are associated with psychotic-like episodes that can occur long after a person has taken the drug,” she added. Volkow also says that, despite being classified as a Schedule I substance, the development of new hallucinogens for recreational purposes remains of particular concern.

Rucker has several suggestions to help mediate the therapeutic action of the drug during medical trials, and thereby sets out to rebut the concerns of experts such as Volkow. When a person is administered a hallucinogen, they experience a changed mental state. During that changed state, Rucker points out, it is possible to control what he describes as a “context,” and thereby make use of the drug more safe.

According to Rucker, the term “context” is divided into the “set” and the “setting” of the drug experience. “By ‘set,’ I mean the mindset of the individual and by ‘setting’ I mean the environment surrounding the individual,” he explained.

To prepare the mindset of the person, Rucker said that a high level of trust between patient and therapist is essential. “A good therapeutic relationship should be established beforehand, and the patient should be prepared for the nature of the psychedelic experience,” he suggested. The ‘setting’ of the drug experience should also be kept closely controlled — safe, comfortable and low in stress.

It is also necessary to screen participants who undergo the drug experience in order to minimize the risk of adverse effects. Rucker suggested screening patients with an established history of severe mental illness, as well as those at high risk of such problems developing. It is also important to screen the medical and drug history of participants.

“The action of psychedelics is changed by many antidepressant and antipsychotic drugs and some medications that are available over the counter, so a full medical assessment prior to their use is essential,” he said.

In order to avoid the danger of addiction, psychedelics should be given at most on a weekly basis. Indeed, for many patients, very few treatments should be required. “The patient may need only one or two sessions to experience lasting benefits, so the course should always be tailored to the individual,” Rucker advised.

If there are any adverse effects during the psychedelic experience, a pharmacological antagonist or antidote to the drug can be administered to immediately terminate the experience. “This underlines the importance of medical supervision being available at all times,” Rucker noted.

Psychedelics are heavily influenced by the environment surrounding the drug experience. Rucker is proposing they be administered under a controlled setting and with a trusted therapist’s supervision. Together with a reclassification of the drug, medical research could generate a better understanding and application of the benefits of psychedelics to mental health.

1.Rucker JJH. Psychedelic drugs should be legally reclassified so that researchers can investigate their therapeutic potential. BMJ. 2015; 350:h2902.

http://www.bmj.com/content/350/bmj.h2902/related

Depression and other behaviour changes may show up in people who will later develop Alzheimer’s disease even before they start having memory problems, according to a study published in the January 14, 2015, online issue of the journal Neurology.

“While earlier studies have shown that an estimated 90% of people with Alzheimer’s experience behavioural or psychological symptoms such as depression, anxiety, and agitation, this study suggests that these changes begin before people even have diagnosable dementia,” said Catherine M. Roe, PhD, Washington University School of Medicine, St. Louis, Missouri.

The study looked at 2,416 people aged 50 years and older who had no cognitive problems at their first visit to one of 34 Alzheimer’s disease centres across the country. The participants were followed for up to 7 years. Of the participants, 1,198 people stayed cognitively normal, with no memory or thinking problems, during the study. They were compared with 1,218 people who were followed for about the same length of time, but who developed dementia.

The people who developed dementia during the study also developed behaviour and mood symptoms such as apathy, appetite changes, irritability, and depression sooner than the people who did not develop dementia. For example, 30% of people who would develop dementia had depression after 4 years in the study, compared with 15% of those who did not develop dementia. Those who developed dementia were more than twice as likely to develop depression sooner than those without dementia and more than 12 times more likely to develop delusions than those without dementia.

Dr. Roe said the study adds to the conflicting evidence on depression and dementia.

“We still don’t know whether depression is a response to the psychological process of Alzheimer’s disease or a result of the same underlying changes in the brain,” she said. “More research is needed to identify the relationship between these two conditions.”

http://dgnews.docguide.com/depression-behaviour-changes-may-start-alzheimer-s-even-memory-changes?overlay=2&nl_ref=newsletter&pk_campaign=newsletter