Teasing out the insulin effect.
On the face of it, the study seems to come out of left field: A group of researchers claimed that marijuana smokers showed 16 per cent lower fasting insulin levels than non-smokers. The study, called “The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults,” is in press for The American Journal of Medicine. The authors are a diverse group of medical researchers from Harvard, Beth Israel Deaconess Medical Center, and the University of Nebraska College of Medicine. The study concluded: “We found that marijuana use was associated with lower levels of fasting insulin and HOMA-IR [a measure of insulin resistance], and smaller waist circumference.”
Of course, it was that last tidbit about waist circumference that was picked up by the media. “Why Pot Smokers Are Skinnier,” headlined the Atlantic. However, the important implications are not so much for weight control, or the discovery of some built-in offsetting mechanism for the marijuana munchies, but rather for insulin control and the treatment of diabetes.
But in a clinical study, remarkable observations require remarkable documentation. What does the research actually say?
There are problems with the study worth noting. While researchers took blood samples after a 9-hour fast to determine insulin and glucose levels, they relied on self-reporting for marijuana use data. And self-reporting for alcohol and drug use has its limitations as an investigative tool. Namely, lack of honesty. But let’s get beyond that for a moment: From a database of 4, 657 men and women who participated in the National Health and Nutrition Examination Survey, the researchers determined that 579 were current marijuana users, while 1, 975 were pot smokers in the past.
The marijuana-smoking cohort tended to be young males who also smoked cigarettes. After running everything through a series of complicated multivariable-adjusted models, marijuana came out associated with lower insulin levels, and “lower waist circumference” than those who reported never using marijuana. And the results didn’t change much after adjusting for BMI numbers and excluding participants who actually had diabetes. Furthermore, the association was strongest in current smokers, “suggesting that the impact of marijuana use on insulin and insulin resistance exists during periods of recent use.” (It should also be noted that other health habits can effect glucose and insulin activity, including cigarettes, alcohol, and lack of physical activity.)
The investigators don’t offer a solution to the increased appetite/decreased waistline conundrum they claim to have identified. “We did not find any significant associations between marijuana use, and triglyceride levels, systolic blood pressure, or diastolic blood pressure,” they concluded.
We know marijuana has a complicated relationship with appetite mechanisms, as evidence by its use with chemotherapy patients who need to eat. The theory is that the metabolic effects are mediated by a complex mix of cannabinoid type 1 and type 2 receptor interactions, since type 1 receptor antagonists like rimonabant improve insulin resistance in humans, and type 1 knockout mice also show resistance to diet-induced obesity.
Does marijuana smoking protect against diabetes? Wisely, the researchers don’t go that far, on the basis of this one uncontrolled study. The researchers’ conclusions neatly hedge the bets, suggesting that with recent trends in the direction of marijuana legalization, “physicians will increasingly encounter patients who use marijuana and should therefore be aware of the effects it can have on common disease processes, such as diabetes mellitus.”
As it happens, the findings aren’t entirely new. Anecdotal reports abound. Back in 2010, on the Diabetes Daily support board, there was a long discussion of marijuana’s effect on blood glucose levels in diabetics. And there are several mouse models showing the same effects. In a prepared statement, lead investigator Murray A. Mittleman of Beth Israel Deaconess Medical Center in Boston conceded that previous epidemiological studies have found “lower prevalence rates of obesity and diabetes mellitus in marijuana users compared to people who have never used marijuana, suggesting a relationship between cannabinoids and peripheral metabolic processes.” However, he believes that “ours is the first study to investigate the relationship between marijuana use and fasting insulin, glucose, and insulin resistance.”
Perhaps so. A 2011 study in the American Journal of Epidemiology concluded that “the prevalence of obesity is lower in cannabis users than in nonusers.” And the British Medical Journal featured a finding in 2012 by Los Angeles researchers that marijuana use was “independently associated with a lower prevalence of diabetes mellitus.” But the online patient guide for marijuana offered by Mayo Clinic says without equivocation that “cannabis may lower blood sugar. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar.” In fact, Mayo Clinic advises that patients may want to monitor their blood glucose levels if they smoke medical marijuana.
Regarding the current study, the editor-in-chief of the American Journal of Medicine said in a statement that there is a need for “a great deal more basic and clinical research into the short- and long-term effects of marijuana in a variety of clinical settings such as cancer, diabetes, and frailty of the elderly.” Editor Joseph S. Alpert also called on the National Institutes of Health (NIH) and the Drug Enforcement Administration (DEA) to collaborate in “developing policies to implement solid scientific investigations that would lead to information assisting physicians in the proper use and prescription of THC in its synthetic or herbal form.”
Penner E.A., Buettner H. & Mittleman M.A. (2013). The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults, The American Journal of Medicine, DOI: 10.1016/j.amjmed.2013.03.002
Photo Credit: http://www.herbalmission.org/
... Read more »
Penner Elizabeth A., Buettner Hannah, & Mittleman Murray A. (2013) The Impact of Marijuana Use on Glucose, Insulin, and Insulin Resistance among US Adults. The American Journal of Medicine. DOI: 10.1016/j.amjmed.2013.03.002
A few of us have started a Decision Theory journal club where we plan on reading papers from a variety of fields that examine how decisions are made. We have people from neuroscience, economics, and cognitive science participating (so far), including people participating through Google+ hangouts!, which will hopefully make lead to some productive discussions. […]... Read more »
Brunton, B., Botvinick, M., & Brody, C. (2013) Rats and Humans Can Optimally Accumulate Evidence for Decision-Making. Science, 340(6128), 95-98. DOI: 10.1126/science.1233912
Znamenskiy, P., & Zador, A. (2013) Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination. Nature, 497(7450), 482-485. DOI: 10.1038/nature12077
Canine cognition is a hot topic these days, using experiments and brain imaging as research tools. The trouble with brain imaging work is that it is invasive, to the extent that animals may have to be sedated or anaesthetized for the study. All that changed with the amazing work of Gregory Berns et al and the first-ever fMRI study on awake, unrestrained dogs last year. Now Miiamaaria Kujala et al in Finland have shown that it is also possible to do a non-invasive EEG with dogs.An EEG measures brain activity by placing electrodes across the scalp. These pick up oscillations in electrical activity, which can be measured for changes. One common use of EEG is in assessing epilepsy in dogs (and people). We aren’t talking about veterinary EEGs here, however, but those designed to learn something about how a healthy brain works.If animals have to be anaesthetized for an EEG to occur, it’s a problem because a drowsy brain does not function in the same way as an alert brain. Awake animals are typically restrained. For example, Hanlu Ma et al (2013) anaesthetized cats and surgically implanted metal tubes through which electrodes could be inserted. After the cats were given a couple of weeks to recover from surgery, the electrodes were used to test the cats’ responses to meows and to human voices making vowel sounds. The cat’s body was wrapped in a cotton bag and its head was immobilized while the sounds were played. The cats were trained for this (though the paper doesn't say how) and monitored for signs of distress. The results showed which parts of the brain were activated, and found no significant difference in response to meows and vowels. In this study, the cats were awake. But it is still invasive, since they had to be operated on and were restrained for several hours at a time. Could there be another way?Since dogs are easily trainable using operant conditioning, Kujala et al in Finland thought it might be possible to train dogs for EEG. Using positive reinforcement, they trained eight beagles to take part in their study. The beagles were purpose-bred for laboratory work and live in a group kennel environment. First of all they took part in training. For the study, their heads had to be shaved, cleaned and prepped so that electrodes could be applied. They wore seven electrodes on the head, one in each ear, and a ground electrode on the back. Then they had to lie still and look at a TV screen while measurements were taken. At the same time, they also wore eye-tracking equipment. A beagle in the study. Source: PLoS OneThe experiment itself took place in twenty-minute sessions over four days for each dog, so that they did not get too tired. Of course, it took much longer to train the dogs to get used to the laboratory and the equipment in the first place, with twice-weekly training sessions over one and a half years.The dogs were shown photographs of human and dog faces, mostly the right way up but with some upside-down. They were shown a batch of photos, then had a short break in which they were rewarded with some food, then led to settle down and watch another batch. The authors point out that the experimental set-up is very similar to that used in human studies. The results showed a change in a type of electrical activity called the beta range (15-30Hz); oscillations in this band were suppressed when the dog was looking at a face, compared to the rest period. This probably reflects the activity of a part of the brain called the occipital cortex. In addition, the researchers found a suppression of activity at the 2-6Hz range. This coincided with the beginning of looking at an image, and was noticed most in the sensors at the front of the head. The authors say this may relate to eye movements as the dog looks at an image that has just appeared on the TV.There were individual differences between the dogs which is not surprising, as this is also the case for humans. The authors conclude that “the study opens the possibility to implement cognitive neuroscience studies with dogs and to examine the evolutionary background and divergence of brain function associated with cognition.”This is similar to the study by Gregory Berns et al that was published last year. They trained two dogs – Callie the rescue feist and McKenzie the agility-loving border collie – to take part in an fMRI. They began training the dogs using a mock-up of the equipment before moving on to the real version. After two months, they were able to take part in the fMRI study. Each dog had to keep absolutely still; if they moved by as little as 3mm, it would make the data useless. Source: PLoS OneThe picture shows Callie during a training session (A) and McKenzie during the study itself (B). The study found that the reward centre of the brain lit up when the dog saw a hand signal that meant a treat would soon be forthcoming. These EEG and fMRI studies are a tremendous achievement on the part of both the humans and dogs that took part. So how were the dogs trained? They did not use electric shocks or ‘corrections’ or punishment. Instead they relied on positive reinforcement. (You will have noticed ongoing positive reinforcement in the EEG study, with pauses in which the dog was given a treat before returning to the experiment).These two studies were designed to find out about the canine brain, but they also show the effectiveness of training using positive reinforcement.Some people (even some dog trainers) try to argue that positive reinforcement is not the right way to train a dog. And yet, it has been used to train dogs to take part in an EEG study and in fMRI without the need for sedation or restraint. Isn’t that amazing?! ReferencesBerns, G., Brooks, A., & Spivak, M. (2012). Functional MRI in Awake Unrestrained Dogs ... Read more »
Kujala, M., Törnqvist, H., Somppi, S., Hänninen, L., Krause, C., Vainio, O., & Kujala, J. (2013) Reactivity of Dogs' Brain Oscillations to Visual Stimuli Measured with Non-Invasive Electroencephalography. PLoS ONE, 8(5). DOI: 10.1371/journal.pone.0061818
Ma, H., Qin, L., Dong, C., Zhong, R., & Sato, Y. (2013) Comparison of Neural Responses to Cat Meows and Human Vowels in the Anterior and Posterior Auditory Field of Awake Cats. PLoS ONE, 8(1). DOI: 10.1371/journal.pone.0052942
Mr. Lonely 1Does Smoking Pot Offer Relief to the Lonely? A new paper by the original Tylenol and social pain researchers claims that it does (Deckman et al., 2013). Let's take a closer look.Comfortably Numb: Marijuana Use Reduces Social Pain, Research FindsMarijuana use buffers people from experiencing social pain, according to research published online on May 14 in Social Psychological and Personality Science."Prior work has shown that the analgesic acetaminophen, which acts indirectly through CB1 receptors, reduces the pain of social exclusion," Timothy Deckman of the University of Kentucky and his colleagues wrote in the study. "The current research provides the first evidence that marijuana also dampens the negative emotional consequences of social exclusion on negative emotional outcomes."You could be forgiven if you thought, as I initially did, that the University of Kentucky IRB must hold a liberal view on the administration of controlled substances to undergrads participating in psychology experiments. But that's not what happened here... the data are entirely correlational, based on self-report, and largely problematic (in my view).Marijuana Lowers Self-Worth and Worsens Mental Health in Those Who Are Not LonelyThat's my interpretation of the article, which is SO clunky compared to the fun and breezy query, Can Marijuana Reduce Social Pain? 2The paper begins with the premise that "Social and physical pain share common overlap at linguistic, behavioral, and neural levels" (Deckman et al., 2013). So let's give a pain reliever to reduce the sting of rejection! A critique of the original work asked why the authors chose Tylenol, as opposed to an NSAID like aspirin, ibuprofen, or naproxen. In the current study they tried to develop a mechanistic account of why acetaminophen might reduce social pain:Prior research has shown that acetaminophen—an analgesic medication that acts indirectly through cannabinoid 1 receptors—reduces the social pain associated with exclusion. Yet, no work has examined if other drugs that act on similar receptors, such as marijuana, also reduce social pain.The problem is that acetaminophen's mechanism of action is surprisingly unclear (Toussaint et al., 2010). One prominent hypothesis claims that Tylenol might exert its analgesic effects through descending serotonergic pathways at the level of the spinal cord. In fact, the paper that Deckman et al. cited in favor of cannabinoid 1 (CB1) receptors describes a very complex pathway that includes indirect involvement of CB1, with actual pain suppression occurring in the spinal cord. 3An even more basic question: if acetaminophen acts through CB1 receptors, then why isn't it a potential drug of abuse, or known by experienced pharmanauts for its psychoactive properties? The drug experience vault Erowid says:Acetaminophen is a non-salicylate analgesic and antipyretic (pain killer and fever reducer). It is a common over-the-counter pain medication found in hundreds of products around the world. At higher doses it is known to cause liver-damage and has a low therapeutic index (ratio of effective dose to toxic dose), making it dangerous when included in recreationally used pharmaceuticals [e.g., Tylenol with codeine]. It is not known to be psychoactive.On the other hand, we all know that cannabis is psychoactive. The design of the cannabis study included cross-sectional national survey data, a two year longitudinal survey of 400 high school students, and a Mechanical Turk-implemented version of cyberball, an online game to simulate social exclusion. In all cases, participants reported their marijuana use, and this was related to the variables of interest.I'll focus on the national survey data in this post, which comprised Study 1 (Marijuana Use Buffers Lonely People From Lower Self-Worth and Self-Rated Mental Health) and Study 2 (Marijuana Use Predicts Fewer Major Depressive Episodes Among the Lonely).Study 1 used data from the National Comorbidity Survey: Baseline (NCS-1), 1990-1992 (ICPSR 6693), which you can download for yourself. The survey recruited 8,098 individuals from the ages of 15 to 54 living in the U.S., and included over 4,000 variables. Only four variables were chosen for the present study: self-reported loneliness (1= often, 4 = never), marijuana use (0 = none, 1 = daily, 8 = once or twice a year), self-worth (1 = high, 4 = low), and overall mental health (1 = excellent, 5 = poor).Loneliness was used as a proxy for social pain. Contrary to what the headlines suggested, the impact of pot smoking on social pain was not directly examined. Instead, the study assessed the effects of loneliness (high, low), marijuana use (high, low) and their interaction on self-worth and mental health.Loneliness and pot smoking interacted to predict feelings of self-worth [B = 0.03, t(5609) = 2.20, p = .03]. Given the huge number of participants, this level of statistical significance is not very impressive.Fig. 1 (modified from Deckman et al., 2013). Study 1: Marijuana use moderates the relationship between loneliness and self-reported feelings of self-worth. [NOTE: items were reverse-scored for display purposes.]For lonely people, the amount of pot smoked didn't make too much of a difference in their self-worth (see red arrow above). For socially connected people, greater marijuana use resulted in lower self-worth, although it's not clear this was significant (pairwise statistical tests were not reported).I also question how the High Marijuana Use and Low Marijuana Use groups were determined, because over 5,000 participants did not smoke pot at all in the last 12 months. Does the heavy use group combine those who smoke 6 joints a year with those who smoke daily?... Read more »
Newly discovered papers have shed light on a fascinating episode in the history of neuroscience: Weighing brain activity with the balance The story of the early Italian neuroscientist Dr Angelo Mosso and his ‘human circulation balance’ is an old one – I remember reading about it as a student, in the introductory bit of a [...]... Read more »
Sandrone S, Bacigaluppi M, Galloni MR, Cappa SF, Moro A, Catani M, Filippi M, Monti MM, Perani D, & Martino G. (2013) Weighing brain activity with the balance: Angelo Mosso's original manuscripts come to light. Brain : a journal of neurology. PMID: 23687118
Men might have found themselves an excuse not to listen to women. New research suggests that men have twice more difficulty reading emotions in women than in men. This may not sound surprising, but evidence that men have trouble understanding women is, at best, scarce.Being able to guess someone else’s thoughts, feelings and intentions is an instinctive social skill that develops in early childhood. We might take it for granted, but people who struggle or are unable to read other people, like people with autism spectrum disorders, have serious problems in communicating and interacting socially. This important ‘mindreading’ trait, so far thought to be unique to our species, recruits a complex brain network. Different, but partially overlapping, brain regions are activated when we perceive mental states like beliefs, intentions or desires (mentalizing) and when we ‘feel’ the emotions of another person (empathy). In a new PLoSONE study, Boris Schiffer’s research group at the University of Duisburg-Essen, Germany, investigates whether there are differences in neural activation when men recognise emotions in women when compared to men. The researchers asked 22 healthy adult men to do a modified version of the ‘Reading the Mind in the Eyes’ (RME) test while their brain activity was measured using functional magnetic resonance imaging (fMRI). The RME test has been used in countless studies to measure mentalizing and empathy (you can take the test here). In this study, each participant had to guess what either a man or a woman in a photo was thinking or feeling from looking only at his or her eyes. For each of the 36 pairs of eyes, there was a choice of two mental states, for instance ‘terrified’ or ‘upset’. The participants performed better in the test when the eyes belonged to men, suggesting that men have greater difficulty in recognising mental states in women than in their own gender. But the question is… why? The fMRI readings shed some light into this.Schiffer and colleagues predicted that recognising mental states in male or female eyes would activate brain areas involved in mentalizing and empathy, and this is what they found. But there was more. Some areas were more active when the participants were guessing emotions in men, and others when they were recognising emotions in women. It isn't clear what these results mean though. As these differently activated brain regions have in one way or another previously been involved in memory, the authors speculate that they are recruited to retrieve either autobiographical emotional memories (when the participants look at male eyes) or memories of past encounters with women (when they look at female eyes). But this doesn’t explain why men have more difficulty in perceiving women’s emotions. There was, however, another clue in the fMRI readings. Just looking at male eyes, without having to do any particular task, activated the amygdala, which is a brain region associated with processing of emotions and empathy. The authors suggest that when men respond to their own gender, emotion and empathy brain networks are recruited (because men can more easily relate to other men), and this might enhance their ability to perceive mental states. A few studies support this idea. For instance, one study showed that men are better than women at recognising angry faces in men. Schiffer and colleagues further speculate that in evolutionary terms, ‘it makes more sense’, they claim, that we should be better at mentalizing about people that are most similar to us. This would have been particularly important for men in the ‘ancient times’, the authors add, as men were hunting and fighting for territory and it was advantageous for them to predict the intentions of their male rivals. But while this is an attractive hypothesis, it remains rather speculative.And what about women? The main lingering question from this research is perhaps whether women are also better at reading mental states in individuals of their own gender. According to the authors, the prediction is that they should. So men should not be too quick to blame their gender for not understanding the opposite sex- this may backfire. Reference:... Read more »
Schiffer Boris, Pawliczek Christina, Müller Bernhard W., Gizewski Elke R., Walter Henrik, & Krueger Frank. (2013) Why Don't Men Understand Women? Altered Neural Networks for Reading the Language of Male and Female Eyes. PLoS ONE, 8(4). DOI: 10.1371/journal.pone.0060278.g003
tumblr: bellapaige88On average, 9.5/1000 population has epilepsy in Low and Middle Income Countries (LAMIC). A research which has resulted in the global campaign against epilepsy has shown, the gap between treatment need and the treatment provision worldwide is approximately 70% . This large ‘treatment gap’, i.e., lack of appropriate treatment for a large number of patients with epilepsy, due to a number of causes including inability to identify cases, inability to deliver adequate treatment, people’s attitudes and perception, availability of anti-epileptic drugs and finally, health policies of individual countries and the priority given to epilepsy. The first step towards narrowing the treatment gap is improving diagnosis. Clinical investigations that help in the diagnosis of epilepsy include electroencephalography (EEG), neuro-imaging techniques such as computed axial tomograpy (CT) and magentic resonance imaging (MRI). Simple blood tests, including haematological, liver and kidney function profiles can reveal treatable causes of epilepsy, such as parasitic infections. Neuropsychological evaluation identifies areas of function and dysfunction. Long term video monitoring can greatly improve the diagnosis of epilepsy. Therapeutic drug monitoring can ensure that patients are receiving optimal doses of medication and can help greatly in avoiding toxicity. However, the availability of investigative procedures varies greatly, from 82.4% for EEG, 70.5% for CT, 45% for therapeutic drug monitoring to only 20.6 % for MRI, 21.7% for long-term video monitoring and in LAMICs. Special investigations of brain function such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) are not available in most LAMIC centres.Epilepsy services in low and middle income countries are almost non-existent and service organization is a challenge. Epilepsy services should be community based and it is important to integrate these services into the primary health care structure to ensure sustainability. The Indian model is one such example, where epilepsy care has been incorporated into programmes for poverty alleviation . Public-private partnerships and non-governmental organizations (NGO) are also important components of the Indian model. The ultimate goal of all workers in the epilepsy field is to improve the quality of the life of people with epilepsy and their families. The prime manner in which this is aimed for is by the provision of good medical care.Wang WZ, Wu JZ, Wang DS, Dai XY, Yang B, Wang TP, Yuan CL, Scott RA, Prilipko LL, de Boer HM, & Sander JW (2003). The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study. Neurology, 60 (9), 1544-5 PMID: 12743252Mbuba CK, Ngugi AK, Newton CR, & Carter JA (2008). The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies. Epilepsia, 49 (9), 1491-503 PMID: 18557778 Pal, D., Das, T., & Sengupta, S. (2000). ... Read more »
Mbuba CK, Ngugi AK, Newton CR, & Carter JA. (2008) The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes, and intervention strategies. Epilepsia, 49(9), 1491-503. PMID: 18557778
Pal, D., Das, T., & Sengupta, S. (2000) Case-control and qualitative study of attrition in a community epilepsy programme in rural India. Seizure, 9(2), 119-123. DOI: 10.1053/seiz.1999.0357
Mani KS, Rangan G, Srinivas HV, Srindharan VS, & Subbakrishna DK. (2001) Epilepsy control with phenobarbital or phenytoin in rural south India: the Yelandur study. Lancet, 357(9265), 1316-20. PMID: 11343735
Wang WZ, Wu JZ, Wang DS, Dai XY, Yang B, Wang TP, Yuan CL, Scott RA, Prilipko LL, de Boer HM.... (2003) The prevalence and treatment gap in epilepsy in China: an ILAE/IBE/WHO study. Neurology, 60(9), 1544-5. PMID: 12743252
The U.S. Centers for Disease Control has published a comprehensive summary of the epidemiology of childhood brain disorders in the most recent Morbidity and Mortality Weekly Report.This report produced some sensationalized headlines that up to 20% of children suffer from a mental disorder. However, I was more interested in looking at the prevalence estimates for some of the individual disorders from the report.The report collates data collected from a variety of surveys and data sets including the NHANES, NHIS and the National Survey of Children's Health (NSCH). These surveys typically use parental report to estimate prevalence ratesFor the purposes of this post, I will focus on two childhood brain disorders: attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).The key findings from the report in ADHD include:7.6% of parents reported their child between 3-17 years had received a diagnosis of ADHD in the NHIS8.9% of parents reported their child received a diagnosis of ADHD in the NSCH study9.6% to 12.3% of boys had received a diagnosis of ADHD3.8% to 5.4% of girls had received a diagnosis of ADHDA diagnosis of ADHD was more with older age, in children with health insurance and higher income groupsA diagnosis of ADHD was not related to parental education level The key findings from the report for autism and autism spectrum disorder include:.8% to 1.1% of parents reported their child between 3-17 years had received a diagnosis of autism1.8% of parents reported their child had received a diagnosis of ASDSurveys consisted noted a male predominance with boys having an estimated 3.5 to 4.5 times higher rate of autism and ASD diagnosisAgain having health insurance increased the rate of autism or ASD diagnosis by around two foldAutism and ASD prevalence rates were somewhat higher in the Northeast region of the U.S. and in white, non-Hispanic childrenIn contrast to ADHD, ASD rates were similar across parental income categoriesThe report notes in the discussion section: "Substantial but not insurmountable challenges to surveillance of mental disorders in children exists." They note current methods focus on parental reports and are biased by variability in access to health and mental health providers. The also note the imperfect diagnostic approach to childhood mental disorders and the need for more consistent diagnostic approaches.This report is a good comprehensive summary of what we know about these childhood brain disorders in the United States. Readers with more interest in this topic can access the free full text report in the citation below. In the next two posts, I will summarize key findings in the conduct disorder and affective disorder categories.Photo of clown fish from the Oklahoma Aquarium is from the author's files.Perou R, Bitsko RH, Blumberg SJ, Pastor P, Ghandour RM, Gfroerer JC, Hedden SL, Crosby AE, Visser SN, Schieve LA, Parks SE, Hall JE, Brody D, Simile CM, Thompson WW, Baio J, Avenevoli S, Kogan MD, Huang LN, & Division of Human Development and Disability, National Center on Birth Defects and Developmental Disabilities, CDC, Atlanta, Georgia (2013). Mental health surveillance among children - United States, 2005-2011. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 62 (2), 1-35 PMID: 23677130... Read more »
Perou R, Bitsko RH, Blumberg SJ, Pastor P, Ghandour RM, Gfroerer JC, Hedden SL, Crosby AE, Visser SN, Schieve LA.... (2013) Mental health surveillance among children - United States, 2005-2011. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002), 62(2), 1-35. PMID: 23677130
“Our ancient countess was refused her desires will To bathe in pure fresh blood She’d peasant virgins killed Elizabeth, in the chasm where was my soul Forever young, Elizabeth Bathorii in the castle of your death You’re still alive, Elizabeth” -“Elizabeth”, Ghost As folklore has it, Elizabeth Bathorii, Countess of Hungary, often bathed in […]... Read more »
Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, Stan TM, Fainberg N, Ding Z, Eggel A.... (2011) The ageing systemic milieu negatively regulates neurogenesis and cognitive function. Nature, 477(7362), 90-4. PMID: 21886162
Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR, Yalamanchi P, Sinha M, Dall'osso C, Khong D, Shadrach JL.... (2013) Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell, 153(4), 828-39. PMID: 23663781
Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, & Cai D. (2013) Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature, 497(7448), 211-6. PMID: 23636330
A new paper in the journal European Neurology reports on a remarkable case of perceptual distortion that’ll please any connoisseur of neurogothic: A 48-year-old woman woke up one morning without knowing where she was. She recognized her husband and finally realized that she was at home, but reported that she felt that all surroundings appeared [...]... Read more »
Delgado MG, & Bogousslavsky J. (2013) 'Distorteidolias' - Fantastic Perceptive Distortion. A New, Pure Dorsomedial Thalamic Syndrome. European neurology, 70(1), 6-9. PMID: 23652461
Synapses, the connections between neurons can strengthen and weaken depending on the specific activity at that synapse. This is called synaptic plasticity, and we've talked about it a lot on this blog (here, here, here and here).the strengthening and weakening of synaptic connections corresponds to the spine growing or shrinking (Matsuzaki 2007)However, there is another kind of plasticity that can occur at synapses. This is called homeostatic plasticity. And instead of the synapse strengthening or weakening depending on the specific activity at that synapse, the synapses strengthen and weaken in homeostatic plasticity depending on the activity of the whole cell. To drastically simplify, each cell 'wants' to fire about a certain amount, if it suddenly starts to fire a lot less, it will take steps to strengthen its connections or make itself more 'excitable' so it can get back to its preferred amount of firing. Similarly if the cell starts to fire a lot more than normal, it will take steps to make itself less excitable and to weaken its connections until it reaches the right amount of firing. Thorny Excrescences from Lee et al., (2013)A recent paper from the Pak lab explains how in some specific neurons in the hippocampus (CA3 pyramidal cells), the activity of the whole cell is strongly controlled by a some very peculiar synapses. These synapses are close to the cell body, and are on these HUGE weirdly shaped spines (see above) called "Thorny Excrescences". For comparison 'normal' spines look more like this:Spines from Lee et al. (2013)The Thorny Excrescences (TEs) are massive spines that contain many separate synapses on them, but connect to the dendrite through 1 neck. 'Normal' spines, on the other hand, usually have 1 synapse at the spine head, and connect to the dendrite through 1 neck.The size of the TEs, and their proximity to the soma makes them an extremely powerful way to control the signals that the soma receives. Lee et al (2013) shows that when you drastically reduce activity by blocking action potentials (using TTX), you get massive growth of these TEs, but the normal spines further away from the soma stay the same.They test 3 things to determine whether the TEs have undergone homeostatic plasticity. They look at the morphology (they are bigger), the activity (the electrical signals from them are bigger) and the molecular signatures (the molecules indicative of new synapses are more plentiful). The paper is a really nice complete story showing that these TEs have a lot of control over the general activity of the cell.It also solves an important problem with homeostatic plasticity. That is, how can the general activity of the cell be modulated without the specific differences between synapses being erased, and consequently the memories or pieces of information they encode? If homeostatic plasticity occurs at spines dedicated to it, then the other spines can still encode specific signals while the activity of the cell as a whole changes. © TheCellularScaleLee KJ, Queenan BN, Rozeboom AM, Bellmore R, Lim ST, Vicini S, & Pak DT (2013). Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons. Neuron, 77 (1), 99-114 PMID: 23312519 ... Read more »
Lee KJ, Queenan BN, Rozeboom AM, Bellmore R, Lim ST, Vicini S, & Pak DT. (2013) Mossy fiber-CA3 synapses mediate homeostatic plasticity in mature hippocampal neurons. Neuron, 77(1), 99-114. PMID: 23312519
Researchers have found that the people, who develop skin cancer, may have less chances of developing Alzheimer’s disease in the older ages.
Alzheimer’s disease is a degenerative disorder that affects the brain and causes dementia, especially late in life.
In this new study, researchers worked on 1,102 volunteers with an average age of 79. They were studied for about 3.7 years. In the beginning of the study, 109 people reported that they had skin cancer in the past. During the study, 32 people developed skin cancer and 126 people developed dementia, including 100 with Alzheimer's dementia.
Researchers found that the people, who had skin cancer, had nearly 80% less chances of developing Alzheimer’s disease than the people who did not have skin cancer. Out of 141 patients of skin cancer, only two developed the Alzheimer’s disease.
The mechanism behind the less chances of Alzheimer’s disease in the patients of skin cancer is not clear. However, "One possible explanation could be physical activity," he said. "Physical activity is known to protect against dementia, and outdoor activity could increase exposure to UV radiation, which increases the risk of skin cancer," Study author Richard B. Lipton, MD, of Albert Einstein College of Medicine in Bronx, NY, and a Fellow of the American Academy of Neurology, said in a statement.
According to Lipton, other possible factors such as genetic factors could also be involved in this. "The hope is that these results help us learn more about how Alzheimer's develops so we can create better preventive methods and treatments,” he said.
White, R., Lipton, R., Hall, C., & Steinerman, J. (2013). Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk Neurology, 80 (21), 1966-1972 DOI: 10.1212/WNL.0b013e3182941990... Read more »
White, R., Lipton, R., Hall, C., & Steinerman, J. (2013) Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology, 80(21), 1966-1972. DOI: 10.1212/WNL.0b013e3182941990
A few entries ago I uploaded a fragment from a study that discusses an intriguing experiment with three chimpanzees (Pan troglodytes) which were trained to tap regularly on a piano keyboard...... Read more »
Hattori, Y., Tomonaga, M., & Matsuzawa, T. (2013) Spontaneous synchronized tapping to an auditory rhythm in a chimpanzee. Scientific Reports. DOI: 10.1038/srep01566
Hasegawa, A., Okanoya, K., Hasegawa, T., & Seki, Y. (2011) Rhythmic synchronization tapping to an audio–visual metronome in budgerigars. Scientific Reports. DOI: 10.1038/srep00120
Honing, H., Merchant, H., Háden, G., Prado, L., & Bartolo, R. (2012) Rhesus Monkeys (Macaca mulatta) Detect Rhythmic Groups in Music, but Not the Beat. PLoS ONE, 7(12). DOI: 10.1371/journal.pone.0051369
The breakthrough technique that allowed scientists to obtain one-of-a-kind, colorful images of the myriad connections in the brain and nervous system is about to get a significant upgrade.... Read more »
Peter Reuell. (2013) ‘Brainbow,’ version 2.0. Harvard Gazette. info:/
A recent study found that people high in agreeableness, ego-resiliency, and low in neuroticism have a stronger response to placebo pain relief. The placebo effect may be related to a person's capacity for self-control. ... Read more »
Peciña M, Azhar H, Love TM, Lu T, Fredrickson BL, Stohler CS, & Zubieta JK. (2013) Personality trait predictors of placebo analgesia and neurobiological correlates. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 38(4), 639-46. PMID: 23187726
Little note: Since this post, I’ve been mulling over why Ritalin/Adderall don’t affect cognitive performance of healthy volunteers. Several reasons come to mind. I wasn’t reading the “right” literature (ie studies with positive results – any suggestions?). Stimulants may only influence brain activation patterns, but not performance. In this case, we can only detect differences […]... Read more »
Jacobs E, & D'Esposito M. (2011) Estrogen shapes dopamine-dependent cognitive processes: implications for women's health. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(14), 5286-93. PMID: 21471363
The month of May is a violent thingIn the city their hearts start to singWell, some people sing, it sounds like they're screamingI used to doubt it, but now I believe itMonth Of May ------The Arcade FireToday is Mental Health Month Blog Day, sponsored by the American Psychological Association (APA). It's designed to:...educate the public about mental health, decrease stigma about mental illness, and discuss strategies for making lasting lifestyle and behavior changes that promote overall health and wellness.If the public has been following the recent hullabaloo about how to diagnose mental illnesses, they might be confused about the current and future direction of the field. How did we get here?As most of you know, the American Psychiatric Association (the other APA) is about to release its updated Diagnostic and Statistical Manual of Mental Disorders, the much maligned DSM-5. Weeks before the big launch, however, the National Institute of Mental Health (NIMH) stole the show by announcing that it will be re-orienting its research away from DSM categories:...While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. Instead, the Research Domain Criteria (RDoC) framework would become the preferred method for organizing biologically-based research on mental illnesses, with the ultimate goal of constructing a new classification scheme.This caused quite a commotion, leading many to comment on NIMH's shocking repudiation of DSM-5. However, to long-time observers of RDoC's development, this was not a surprise. And the initial lack of clarity on the distinction between the RDoC Dimensional Approach for Research vs. DSM-5 for Diagnosis didn't help matters, nor did the uncertainty about whether NIMH would fund DSM-based research at all.1NIMH issued a press release on May 13 to clarify its position:DSM-5 and RDoC: Shared InterestsThomas R. Insel, M.D., director, NIMHJeffrey A. Lieberman, M.D., president-elect, APANIMH and APA have a shared interest in ensuring that patients and health providers have the best available tools and information today to identify and treat mental health issues, while we continue to invest in improving and advancing mental disorder diagnostics for the future.Today, the APA's Diagnostic and Statistical Manual of Mental Disorders (DSM), along with the International Classification of Diseases (ICD) represents the best information currently available for clinical diagnosis of mental disorders Patients, families, and insurers can be confident that effective treatments are available and that the DSM is the key resource for delivering the best available care. The NIMH has not changed its position on DSM-5. As NIMH’s Research Domain Criteria (RDoC) project website states, “The diagnostic categories represented in the DSM-IV and the International Classification of Diseases-10 (ICD-10, containing virtually identical disorder codes) remain the contemporary consensus standard for how mental disorders are diagnosed and treated.”Yet, what may be realistically feasible today for practitioners is no longer sufficient for researchers. Looking forward, laying the groundwork for a future diagnostic system that more directly reflects modern brain science will require openness to rethinking traditional categories. It is increasingly evident that mental illness will be best understood as disorders of brain structure and function that implicate specific domains of cognition, emotion, and behavior. This is the focus of the NIMH’s Research Domain Criteria (RDoC) project. RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness.So what is RDoC, and how might it be applied to new research projects? From the DSM perspective of categorical disorders (e.g, schizophrenia, major depression, and obsessive compulsive disorder), RDoC embraces diagnostic messiness. Patients previously excluded from a study due to comorbidities, or because they don't meet full criteria? Misfits from the "Not Otherwise Specified" (NOS) category? Now they're in. Specifically, the instructions for RFA-MH-14-050 state:Priority will be given to applications that have a well-justified plan to include patients from multiple diagnostic groups (including Not Otherwise Specified and forme fruste diagnoses) as appropriate for explicating the dimensions and constructs of interest in the study design. Studies that include patients from a single diagnostic group may also be considered if there is a particularly strong justification for examining constructs of interest within one diagnostic category. A defensible approach might be to study all patients presenting themselves at a specialty clinic, e.g., mood disorders clinic, anxiety clinic, or psychotic disorders clinic, regardless of whether they meet criteria for a particular DSM diagnosis.One potential pitfall of this approach is the money required to enroll huge numbers of patients. If commonalities in cognitive function or brain circuitry or especially genetic risk factors are to emerge from studying all patients with mood disorder-like symptoms, then sample sizes must be very large to overcome potential noise in the system(s).The applicant would propose to study one or more of the five different domains, or constructs, that have been fleshed out at NIMH Workshops:Negative Valence SystemsPositive Valence SystemsCognitive SystemsSystems for Social ProcessesArousal/Regulatory SystemsThe possible units of analysis run the gamut from genes to circuits to behavior, and the studies should use specific tasks (paradigms) and self-report measures, as shown in the Negative Valence Systems matrix below.Draft Research Domain Criteria Matrix Animal ... Read more »
Vaidyanathan, U., Nelson, L., & Patrick, C. (2011) Clarifying domains of internalizing psychopathology using neurophysiology. Psychological Medicine, 42(03), 447-459. DOI: 10.1017/S0033291711001528
Dichter, G., Damiano, C., & Allen, J. (2012) Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings. Journal of Neurodevelopmental Disorders, 4(1), 19. DOI: 10.1186/1866-1955-4-19
The public will never tire of the nature versus nurture debate but here’s a hint: the answer in biology is always both. But if you’ve ever known any twins, you know they can have quite different personalities which, you would think, are attributable to differences in nurture of one sort or another. To understand this better, some scientists […]... Read more »
Freund, J., Brandmaier, A., Lewejohann, L., Kirste, I., Kritzler, M., Kruger, A., Sachser, N., Lindenberger, U., & Kempermann, G. (2013) Emergence of Individuality in Genetically Identical Mice. Science, 340(6133), 756-759. DOI: 10.1126/science.1235294
by Liz in Science of Eating Disorders
I have been fascinated and perplexed by reports of the seemingly invigorating and anxiety reducing effects of bingeing and purging (purging by self-induced vomiting). Personally, I cringe at the idea of self-induced vomiting and have always wanted to avoid vomiting at all costs, including during food poisoning. The insight from recent blog entries and the subsequent comments has made an impact on me. I see that the motivation to engage in bingeing/purging (b/p-ing) behavior can be intense and can provide an effective way increase positive affect and reduce stress. The ameliorating effects of b/p-ing remind me of drug addiction, with b/p-ing behavior as the “drug.” This made me wonder, what happens in the brain to impart such “addiction-like” reinforcement?
I know there are reports of opiate and endorphin release following purging, but to me, this seemed like an effect meant to counter the intense aversion (and discomfort?) of the act of purging itself. Correct me if I’m wrong, but it seems like the feeling of being “empty” should be reinforcing as well. As someone who used to restrict quite a bit, I certainly found that feeling …
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... Read more »
Avena, N., Rada, P., Moise, N., & Hoebel, B. (2006) Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response. Neuroscience, 139(3), 813-820. DOI: 10.1016/j.neuroscience.2005.12.037
How do organisms evolve into individuals that are distinguished from others by their own personal brain structure and behaviour? Scientists in Dresden, Berlin, Münster, and Saarbrücken have now taken a decisive step towards clarifying this question. Using mice as an animal model, they were able to show that individual experiences influence the development of new neurons, leading to measurable changes in the brain. The results of this study are published in Science on May 10th. The DFG-Center for Regenerative Therapies Dresden – Cluster of Excellence at the TU Dresden (CRTD), the Dresden site of the German Center for Neurodegenerative Diseases (DZNE), and the Max Planck Institute for Human Development in Berlin played a pivotal role in the study.... Read more »
Britta Grigull. (2013) Experience leads to the growth of new brain cells. Max Planck Institute for Human Development. info:/
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