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by Neuroskeptic in Neuroskeptic
A startling new paper from Tehran claims Antidepressant effects of magnetic resonance imaging-based stimulation on major depressive disorder.Yes, this study says that having an MRI scan has a powerful antidepressant effect.They took 51 depressed patients, and gave them all either an MRI scan or a placebo sham scan. The sham was a "scan" in a decommissioned scanner. The magnet was off but they played recorded scannerish sounds to make it believable. Patients were blinded to group.They found that people in the scanner group improved much more than those in the sham group over two weeks. Actually there were two different kinds of scans, T1 structural MRI and EPI functional MRI, but they were the same:Now, if this is true, it's huge. Obviously. For one thing, it would undermine the whole premise of functional MRI, which is that it's a method of recording brain activity. If it's also stimulating the brain in some way at the same time, then it would make it hard to interpret those activations. In particular it would cast all the studies using fMRI in depression into doubt.So is it true? I can't see any obvious flaws in the design. Assuming that the authors are right when they say that "patients could not distinguish the difference between the actual and sham MRI scan", i.e. assuming that the blind was truly blind, then the methodology was sound.But let's look at the statistics. The paper is full of very impressive p values less than 0.001 but those turn out to all be referring to the changes within each group, and those changes are fairly meaningless. What matters is the differences in the groups andChanges in BDI scores (between baseline and day 14) were significantly different among the three studied groups (F=5.48, p=0.007 overall) using ANOVA, and between the DWI group vs. Sham and T1 vs. Sham (p<0.05) using post hoc tests. Changes in HAMD24 scores (between baseline and day 14) were also compared among the 3 groups using ANOVA but the level of significance was slightly above the significance threshold (F=2.89, p=0.06).Which is rather less convincing. There was a close-to-significant group difference in the HAMD24, and a significant but only just effect on the BDI. Remember that there were only 17 people in each group.I'm inclined to think that this is one of the 5% of experiments which will produce a nominally significant result even assuming everything goes to plan and there are no confounds. My suspicion is that everyone in the trial got better (they were all on antidepressants, plus there's the placebo effect and the effect of time) - except a small number of people who didn't improve. And by chance they were all in the sham group.The reason I'm skeptical is that I just can't see a plausible mechanism. The authors suggest that MRI scans might stimulate the brain in a similar way to TMS and that this could have antidepressant effects.But there's a lot of problems with this: 1) the evidence is questionable whether TMS even works for depression 2) the magnetic stimulation of the brain generated during MRI is much weaker than in the case of TMS and 3) if MRI really stimulated the brain like TMS, then, like TMS, it would have a risk of triggering seizures in people with epilepsy. But it doesn't.Vaziri-Bozorg SM, et al (2011). Antidepressant effects of magnetic resonance imaging-based stimulation on major depressive disorder: a double-blind randomized clinical trial. Brain imaging and behavior PMID: 22069111... Read more »
Vaziri-Bozorg SM, Ghasemi-Esfe AR, Khalilzadeh O, Sotoudeh H, Rokni-Yazdi H, Ghanaati H, Firouznia K, Sharifi V, Tabatabayee M, Kooraki S.... (2011) Antidepressant effects of magnetic resonance imaging-based stimulation on major depressive disorder: a double-blind randomized clinical trial. Brain imaging and behavior. PMID: 22069111
by Neuroskeptic in Neuroskeptic
Videogames and neuroscience have a rocky relationship.On the one hand you have Susan Greenfield and her games-hurt-the-brain theory. But she's not representative of neuroscientists as a whole: games have also helped neuroscience, for example, in this study of the neural correlates of "flow" experiences. Now neuroscientists have another reason to be thankful for games, according to a new paper. It turns out that modern 3D graphics cards - which mostly exist in order to render videogame visuals - can be used to do fMRI data analysis.According to Sweden's Eklund et al, a graphics card can perform intensive fMRI analysis hundreds of times faster than a regular processor of the equivalent speed, because graphics processors make use of parallel computing optimized for 3D images and that's ultimately what all brain scans are.They developed a way to run non-parametric statistical analyses of brain imaging data. Proponents say that non-parametric stats have many advantages over conventional parametric ones - and they're certainly becoming increasingly popular. But they involve doing far more calculations. Thousands of times more, in some cases.It turns out though that armed with 2.5 GHz CPU and three NVidia GTX 480s, and making use of NVidia's graphics programming language, they were able to cut the time to analyse one person's brain from... down to just... the whole setup cost $4000, so it's not cheap, but they say it's "a fraction of the price for a PCcluster with equivalent computational performance" that didn't use graphics cards. Even on GTX480 did the job very well.Best of all, this gives neuroscientists an excuse to spend their grant money on awesome gaming rigs. Why do I want the latest GForce on my work computer? To do non-parametric data analysis, obviously. Sure, it would also allow me to run Modern Warfare 3 at the highest settings... but that's not why I want it.Eklund A, Andersson M, Knutsson H (2011). Fast random permutation tests enable objective evaluation of methods for single-subject FMRI analysis. International journal of biomedical imaging, 2011 PMID: 22046176... Read more »
Eklund A, Andersson M, & Knutsson H. (2011) Fast random permutation tests enable objective evaluation of methods for single-subject FMRI analysis. International journal of biomedical imaging, 627947. PMID: 22046176
by Neuroskeptic in Neuroskeptic
A new paper has caused a lot of excitement: it reports large increases in the number of neurons in children with autism. It comes to you from veteran autism researcher Eric Courchesne. Courchesne et al counted the number of cells in the prefrontal cortex of 7 boys with autism and 6 non-autistic control boys, aged 2-16 years old. The analysis was performed by a neuropathologist who was blind to the theory behind the study and to which brains were from which group. That's good.They found that the total brain weight of the brain was increased in autistic boys, by about 17% on average. But the number of neurons in the prefrontal cortex was increased by an even higher margin - about 60%. The difference was specific to neurons - glial cell counts were normal. Of the 7 autistic boys, 4 also had intellectual disability - an IQ less than 70. However, the 3 without showed broadly similar results.As well as having more prefrontal neurons, there were also some other issues in some but not all of the autism brains. Two had prefrontal cortical abnormalities - dysplasia in one case and abnormal cell orientation in another. And no fewer than 4 had flocculonodular lobe dysplasia in the cerebellum.None of the nonautistic brains had any abnormalities reported but they don't seem to have looked very closely in the controls because that was based on "coroner's report only", rather than a detailed neuropathological exam...It's a nice piece of work, but very small. These postmortem neuropathology studies always are because postmortem brain samples are in short supply, especially for disorders like autism.In fact, it's so small, that doing statistics on these data is not really meaningful. The authors do some stats and get some impressive p values but we should take those with a pinch of salt and just look at the individual data (see the scatterplots above).Now, prefrontal cortical neurons are generated while you're still in the womb. New ones can't be created after you're born - numbers can only decrease. So the increased neuron count in autism must have a very early origin, either genetic or caused by pre-natal environmental factors. Unless the timeline for cell genesis is totally different in autism.Still, it casts doubt on the idea that, in the brain, bigger is always "better". Assuming that we consider autism to be "bad" - which I'm not saying is necessarily right, but it's fair to say most people do assume that - then the common practice of equating volume increases with all kinds of good things seems rather silly.Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, & Pierce K (2011). Neuron number and size in prefrontal cortex of children with autism. JAMA : the journal of the American Medical Association, 306 (18), 2001-10 PMID: 22068992... Read more »
Courchesne E, Mouton PR, Calhoun ME, Semendeferi K, Ahrens-Barbeau C, Hallet MJ, Barnes CC, & Pierce K. (2011) Neuron number and size in prefrontal cortex of children with autism. JAMA : the journal of the American Medical Association, 306(18), 2001-10. PMID: 22068992
by Neuroskeptic in Neuroskeptic
Yet another up-and-coming antidepressant has flopped.A paper just out reveals that the snappily-named GSK372475 doesn't work and has lots of side effects. It's a report of two clinicals trials in which Glaxo's contender was pitched against placebo and against older antidepressants in the treatment of depression.GSK372475 failed to improve depression any better than placebo, even though the trials were large (393 and 504 patients respectively) and twice as long as most antidepressant trials (10 weeks whereas 4 or 6 is more usual)which ought to have given it plenty of room to shine.The comparison drugs, the widely used venlafaxine and paroxetine, did work. A bit.One of the trials even used the Bech "Melancholia Subscale" as an outcome measure, which Neuroskeptic readers may remember as I've praised it before. Venlafaxine worked on that, GSK's new pill didn't. If anything, the new drug was worse than placebo, in that patients improved slower.In terms of side effects it caused dry mouth, insomnia, and nausea serious enough to make many people quit the study early. But even worse, it raised heart rate by almost 10 beats per minute on average, which is really never a good sign.So, overall, it was an utter flop. In one sense this is not surprising. New "antidepressants" that don't work in trials have been all too common recently. Just last week we learned about the failure of "Serdaxin" in a Phase II trial. Actually Serdaxin isn't a new drug but an old antibiotic called clavulanic acid that a company was trying to rebrand as a mood lifter.However the failure of GSK372475 is a bit of a mystery. The drug is a potent triple reuptake inhibitor (TRI) which acts on the neurotransmitters serotonin, noradrenaline and dopamine. By contrast, venlafaxine is a double reuptake inhibitor which doesn't hit dopamine, and paroxetine only targets serotonin. I've written about other TRIs before.Now it seems surprising that venlafaxine worked, but a TRI didn't, in the same trial. That would imply that blocking the reuptake of dopamine makes you more depressed, enough to cancel out the other actions which are shared with venlafaxine. Which is not what I'd have predicted.There are other differences between the drugs though. Venlafaxine has a very short half-life - it's broken down in the body in a matter of hours. But GSK372475 has a halflife of 8-10 days. Could this be the problem?Learned S, Graff O, Roychowdhury S, Moate R, Krishnan KR, Archer G, Modell JG, Alexander R, Zamuner S, Evoniuk G, & Ratti E (2011). Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo- and active-controlled clinical trials. Journal of psychopharmacology (Oxford, England) PMID: 22048884... Read more »
Learned S, Graff O, Roychowdhury S, Moate R, Krishnan KR, Archer G, Modell JG, Alexander R, Zamuner S, Evoniuk G.... (2011) Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo- and active-controlled clinical trials. Journal of psychopharmacology (Oxford, England). PMID: 22048884
by Neuroskeptic in Neuroskeptic
According to a new paper, the brains of male-to-female transexuals are no more "female" than those of men.The authors write that "The present data do not support the notion that brains of male-to-female transexuals are feminized" and conclude "The present study does not support the dogma that male-to-female transexuals have atypical sex dimorphism in the brain".That last sentence has gained quite a bit of coverage, including a quote on the Wikipedia page for "transgender". But is it so simple?Structural MRI scans were used to compare the size of various brain structures between three groups of volunteers: heterosexual men, heterosexual women and the transexuals (or "MtF"s as I will call them for short) who were diagnosed with gender dysphoria and were "genetically and phenotypically males". There were 24 in each group, which makes it a decent sized study. None of the MtFs had started hormone treatment yet, so that wasn't a factor, and none of the women were on hormonal contraception.The scans showed that the non-transsexual male and female brains differed in various ways. Male brains were larger overall but women had increases in the relative volumes of various areas. Male brains were also more asymmetrical.The key finding was that on average, the MtF brains were not like the female ones. There were some significant differences from the male brains, but they weren't the same differences that distinguished the females from the males.This is a fairly crude approach. It looks at the groups on average. It's a finding, but there's more you could with this data. It would be better perhaps to look at the male and female groups, and then try to work out which group each individual MtF is most similar to. You could do that using a Support Vector Machine such as was previously used to detect autism.This would also have the advantage that it would integrate the results across different brain areas: maybe the important thing is not just the size of individual areas but the relative size of one area to another area.My real problem though is with the language used to discuss the data. The authors say that the study doesn't support "atypical sex dimorphism in the brain" yet this wasn't a study of "the brain". It was a study of one specific aspect of the brain, namely the volume of different regions. There could be all kinds of chemical and microstructural differences that don't show up on these scans.There are lots of people with severe epilepsy, for example, whose brains clearly differ in some major way from people without epilepsy, yet they look completely normal on MRI. Only using other methods, like EEG, reveals the difference. Because the difference is chemical, not structural. I have no idea how, or if, the brains of MtF transsexuals are "feminized" but this study doesn't rule it out. Now I'm sure the authors know all this. And in fact they themselves recently published a paper showing atypical neural responses to smelling "oderous steroids" in transsexual people. But while neuroscientists will know what they meant, I worry that studies like this could be miscontrued by other people (like Wikipedia readers) as a result of overenthusiastic language in papers.Link: Also blogged at BPS Research Digest. Savic I, & Arver S (2011). Sex dimorphism of the brain in male-to-female transsexuals. Cerebral cortex (New York, N.Y. : 1991), 21 (11), 2525-33 PMID: 21467211... Read more »
Savic I, & Arver S. (2011) Sex dimorphism of the brain in male-to-female transsexuals. Cerebral cortex (New York, N.Y. : 1991), 21(11), 2525-33. PMID: 21467211
by Neuroskeptic in Neuroskeptic
A neat little study has brought Inception one step closer to reality. The authors used fMRI to show that dreaming about doing something causes similar brain activation to actually doing it.The authors took four guys who were all experienced lucid dreamers - able to become aware that they're dreaming, in the middle of a dream. They got them to go to sleep in an fMRI scanner. Their mission was to enter a lucid dream and move their hands in it - first their left, then their right, and so on. They also moved their eyes to signal when they were about to move their hands.Unfortunately, only one of the intrepid dream-o-nauts succeeded, even though each was scanned more than once. Lucid dreaming isn't easy you know. Two didn't manage to enter a lucid dream. One thought he'd managed it, but the data suggested he might have actually been awake.But one guy made it and the headline result was that his sensorimotor cortex was activated in a similar way to when he made the same movements in real life, during the lucid dream - although less strongly. Depending on which hand he was moving in the dream, the corresponding side of the brain lit up:EEG confirmed that he was in REM sleep and electromyography confirmed that his muscles were not in fact being activated. (During REM sleep, an inhibitory mechanism in the brain prevents muscle movement. If the EMG shows activity this is a sign that you're actually partially awake).They also repeated the experiment with another way of measuring brain activation, NIRS. Out of five dudes, one made it. Interesting this showed the same pattern of results - weak sensorimotor cortex activation during movement - but it also showed stronger than normal supplementary motor area activation, which is responsible for planning movements. This is rather cool but in many ways not surprising. After all, if you think about it, dreaming presumably involves all of the neural structures that are involved in really perceiving or doing whatever it is you're dreaming about. Otherwise, why would we experience it so clearly as being a dream about that thing?It may be, however, that lucid dreaming is different, and that the motor cortex isn't activated in this way in normal dreams. I suppose it depends what the dream was about.That raises the interesting question of what someone with brain damage would dream about. On the theory that dream experiences come from the same structures as normal experiences, you shouldn't be able to dream about something that you couldn't do in real life... I wonder if there's any data on that?Dresler M, Koch SP, Wehrle R, Spoormaker VI, Holsboer F, Steiger A, Sämann PG, Obrig H, & Czisch M (2011). Dreamed Movement Elicits Activation in the Sensorimotor Cortex. Current biology : CB PMID: 22036177... Read more »
Dresler M, Koch SP, Wehrle R, Spoormaker VI, Holsboer F, Steiger A, Sämann PG, Obrig H, & Czisch M. (2011) Dreamed Movement Elicits Activation in the Sensorimotor Cortex. Current biology : CB. PMID: 22036177
by Neuroskeptic in Neuroskeptic
A new online resource has been launched which offers us the chance to find out what isn't happening in science.BioNOT is a free searchable database of negative findings in biology and medicine.Text mining approaches to the scientific literature have become increasingly popular as a way of helping researchers to make sense of a growing number of papers. But they've tended to focus on positive findings and skim over negative ones. In this sense they're following in the tradition of scientists themselves, unfortunately.It's also hard to search for negative findings on PubMed, because if you type in, say, vaccines NOT associated with autism in the hopes of finding papers showing that vaccines don't cause autism, it will think you are trying to search for "vaccines" and don't want to see any papers mentioning the words "associated with autism". So you end up with 160,000 hits about vaccines with no reference to autism at all. There are ways around this but it's surprisingly tricky.BioNOT uses text mining to mine null findings from a large database which includes everything you can find on PubMed and also a large number of full text articles (some behind paywalls).Authors Agarwal et al of Wisconsin say that this will help to map out the "incidentalome" (a brilliant word I'd never heard before) for a given disease or trait i.e. the regions of the genome that turned out not to be associated with it. It should work for anything, though, not just genes.However the BioNOT system isn't perfect. The authors note that it is rather over-enthusiastic in finding negative sentences.A quick try on the system bears this out. I searched for 5 HTTLPR, the claimed "happiness gene". This revealed many papers finding no link between the gene and various things. But it also threw up false positives (how ironic), such as: young rhesus monkeys were split into two groups... those having, or not, the short variant of the 5 -HTTLPR polymorphismThis is just telling us about the methods of a study. It's not a null finding, but it set the BioNOT alarm bells ringing, presumably because it contained the word "not".So BioNOT is only a first step, but it's an important one.Agarwal S, Yu H, & Kohane I (2011). BioNOT: A searchable database of biomedical negated sentences. BMC bioinformatics, 12 (1) PMID: 22032181... Read more »
Agarwal S, Yu H, & Kohane I. (2011) BioNOT: A searchable database of biomedical negated sentences. BMC bioinformatics, 12(1), 420. PMID: 22032181
by Neuroskeptic in Neuroskeptic
Whether you were happy with life as a teenager could be down to a certain gene, says a new study.In a large study of American adolescents, the AddHealth project, teens who carried the long form of the 5HTTLPR locus were more likely to say they were satisfied or very satisified with their lives (at age 18 to 26). People with two long variants were the most cheerful, with short/long carriers in the middle and short/short being the least so.The effect was significant controlling for ethnicity (p=0.013), however looking at the data shows that this effect was largely driven by the unhappy teens who reported being "Dissatisfied" or "Neither" on the 5 point scale of life satisfaction - but there were only a small number of these, because the great majority said they were "Satisfied" or "Very Satisfied". Still, there you go.Incidentally, Neuroskeptic readers may remember AddHealth because of its role in the "black women are ugly" race row from earlier this year.This study is the latest in a long, long line of attempts to correlate 5HTTLPR with happiness, depression, stress and so on. A few months ago I discussed the history of this busy little gene and covered a meta-analysis of no fewer than 54 papers which claimed that there was indeed a link, with the short allele increasing the risk of depression in response to stressful events. However many studies failed to find one, and worryingly the three largest studies were all negative which is a classic tell-tale sign of publication bias - maybe people were only bothering to publish smaller studies if they did find a link and hence were "exciting findings". This is quite possible because so many researchers collect DNA as part of psychology studies these days. When the 5HTTLPR story got big (about 5 years ago) I know a lot of people decided to jump on the bandwagon by looking at it in the context of their old data.Personally I have no idea whether 5HTTLPR is associated with anything. I used to think it probably did, but now I'm just confusion. There have been so many studies and so much inconsistency that it's very hard to know. What worries me is that I'm not sure whether we'll ever get a consensus. We've already had a gigantic study (over 80,000 people) showing no link and many meta-analyses coming to different conclusions.What will it take to settle the issue? An even bigger study? Would 200,000 people do it? A million? I don't know.De Neve JE (2011). Functional polymorphism (5-HTTLPR) in the serotonin transporter gene is associated with subjective well-being: evidence from a US nationally representative sample. Journal of human genetics, 56 (6), 456-9 PMID: 21562513... Read more »
De Neve JE. (2011) Functional polymorphism (5-HTTLPR) in the serotonin transporter gene is associated with subjective well-being: evidence from a US nationally representative sample. Journal of human genetics, 56(6), 456-9. PMID: 21562513
by Neuroskeptic in Neuroskeptic
Last year I covered the case of a young man born with a genetic disorder which caused him to suffer low levels of the monoamine neurotransmitters - serotonin, dopamine, and noradrenaline.These are the chemicals that are widely thought to be deficient in depression, and they're the target of antidepressant drugs (especially serotonin).If low monoamines cause depression, you'd expect someone with low monoamines to be depressed, at least on the simplest view. But the case from last year had no reported mood problems, although he did show appetite, sleep and concentration problems that were cured by serotonin replacement therapy.Now a new case report has just appeared that tells a different story. Gabriella Horvath and colleagues from British Columbia describe two sisters. Both had a normal birth and childhood, but at the ages of 11 and 15 respectively, began to suffer severe migraines and other symptoms. Sister 1:started having hemiplegic migraine at age 11 years, initially occurring every 3–8 weeks, lasting 4–48 hours, presenting with right or left-sided numbness and paralysis, no visual disturbances, but slurred speech, associated with vomiting, headache, and confusion, followed by weakness lasting up to 7 days, and then complete recovery. The frequency of her migraine increased slowly with age up to twice a month... Between 12 and 20 years she had developed progressive spastic paraparesis; sensory loss in stocking distribution... urinary and bowel incontinence; bladder instability... irritable bowel syndrome; sleep problems; depressed mood; and anxiety. She needed to use a wheelchair for most of the time by the age of 17.Sister 2 had a rather different course:The older sister originally presented at the age of 15 years with a history of hemiplegic migraine and seizures and myoclonic jerks. EEG showed generalized spike-and-wave activity, and polyspikes with photoconvulsive [light-induced seizures] response, in keeping with juvenile myoclonic epilepsy. Her seizures were brief and infrequent and not associated with the migraine episodes...She subsequently developed progressive weakness, frequent falls, depression, and mild bladder instability...Various blood and genetic tests failed to get to the bottom of it. MRI scans showed abnormalities in the spinal cord and parts of the brainstem in both cases, but why?Spinal tap studies in Sister 1 revealed very low levels of 5HIAA, which is a by-product of brain serotonin (5HT). This suggested low 5HT levels. So doctors started her on 5HTP to try to boost it.They report that 5HTP treatment caused "improvement" in all symptoms, including the migraines, slurred speech, depression, and movement, but not immediately. She gradually went from being in a wheelchair to being able to walk around the house on crutches, although she used a wheelchair outside. However, after 3 years of treatment, at age 20, she suddenly fell into a coma lasting 2 months. She is now recovering.Sister 2 also had low 5HIAA, and was given 5HTP. She also reported symptomatic improvement.Blood tests reported very low platelet serotonin levels. 5HTP treatment increased this but they were still below normal. Platelet 5HT reuptake rate was also low, suggesting a problem with the 5HT reuptake transporter protein 5HTT.But the 5HTT gene (famously known as "The Happiness Gene" although that's questionable) seemed entirely normal in these patients. The authors say however that the symptoms are, in some ways, reminiscent of mice who lack the 5HT reuptake protein (5HTT knockout mice), who also show low serotonin. Also, if it were genetic, that wouldn't explain why there were no problems at all during childhood.So this case is a mystery. The low serotonin has no known cause, and it might just be a side effect of a deeper underlying problem, but serotonin has long been linked to migraines so it might account for some of the symptoms. The fact that 5HTP helped supports this, though it wasn't a controlled trial so we can't know for sure.As for the depression and anxiety, improved by 5HTP, this could have been a result of low serotonin, but it could also have been a psychological reaction to the severe medical problems. It's impossible to know.Horvath GA, Selby K, Poskitt K, Hyland K, Waters PJ, Coulter-Mackie M, & Stockler-Ipsiroglu SG (2011). Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin. Cephalalgia : an international journal of headache PMID: 22013141... Read more »
Horvath GA, Selby K, Poskitt K, Hyland K, Waters PJ, Coulter-Mackie M, & Stockler-Ipsiroglu SG. (2011) Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin. Cephalalgia : an international journal of headache. PMID: 22013141
by Neuroskeptic in Neuroskeptic
Facebook friend tally is associated with differences in brain structurePeople with lots of Facebook friends have denser grey matter in three regions of the brain, a study suggestsWhen I heard about this, my heart sank. The Facebook area of the brain? It had all the hallmarks of a piece of media neuro-nonsense: a hook (Facebook!), a simplistic neo-phrenological story (bigger brains are better!)... so I was expecting to discover that the fuss was all about some tiny, statistically questionable study, which wasn't really about what the newspapers said it was, as is so often the case. So I was very surprised to find that it's actually an extremely good paper.Kanai et al from London took 125 young Facebookers (mostly students) and correlated their friend count with grey matter density across the brain. They found some correlations:The numbers seem solid. It was a large study. They used whole-brain correction for multiple comparisons (a=0.05 FWE corrected), controlling for age, gender and overall brain grey matter. Most importantly, they included a replication sample, something that very few neuroscience papers do. After having done the first 125 people, they got another 40, and looked in the areas where they'd previously found results. They found the same correlation in all three cases - in fact, it was even stronger.They even made sure to only display the scatterplots from the replication sample, thus avoiding the dreaded voodoo correlations problem that so often plagues such graphs. Note that the correlations are actually with the square root of the number of friends.As if this wasn't enough, they confirmed a previously reported correlation between amygdala size and social network size, in both of their samples. And to cap it all, they show that Facebook friends are correlated (albeit not hugely) with other measures of number of friends.So, as unlikely as it sounds, this Facebook finding is stronger than a good 90% of similar papers.What does it mean that the size of the amygdala, left MTG, right STS and right entorhinal cortex are correlated with your Friend count? Good question. The authors discuss the result in terms of the known functions of these areas, e.g. the entorhinal cortex is involved in learning to associate pairs of stimuli, such as matching names to faces, which might be related to keeping track of your friends... but frankly this is just a post-hoc story.You could tell an equally convincing tale about almost any part of the brain, if you found a correlation there. And as the authors point out, they didn't find correlations with other "social" areas you might expect like the mirror neuron system. But that doesn't change the fact that the results of the study seem rock solid. So what's going on? It could be that having lots of friends makes your brain bigger. Or it could be the reverse, that having a certain kind of brain wins you friends, or at least Facebook ones. Or it could be that there's some third factor underlying the correlation, although who knows what that is.Kanai, R., Bahrami, B., Roylance, R., & Rees, G. (2011). Online social network size is reflected in human brain structure Proceedings of the Royal Society B: Biological Sciences DOI: 10.1098/rspb.2011.1959... Read more »
Kanai, R., Bahrami, B., Roylance, R., & Rees, G. (2011) Online social network size is reflected in human brain structure. Proceedings of the Royal Society B: Biological Sciences. DOI: 10.1098/rspb.2011.1959
by Neuroskeptic in Neuroskeptic
Functional MRI is one of the most popular ways of measuring human brain activity. But what is "activity"?Fundamentally, neural activity is electical potentials and chemical signals. fMRI doesn't measure these directly. Rather, it measures changes in the oxygen content of blood in different parts of the brain.The more the brain cells are firing, the more oxygen they use up, although oxygenation actually increases as a kind of compensation for the activity and this increase is what gets measured. The oxygenation changes associated with neural firing is called the BOLD response.Using fMRI you can measure BOLD and end up with some pretty blobs of activation. But what does it mean for a region of the brain to be activated? Just as no man is an island, no brain region can do anything on its own. Every area gets inputs from other areas, and sends outputs as well.So if an area gets more active, that could mean one or more of three things:It's sending more outputsIt's getting more inputs It's doing more "internal" processing within that area - "talking to itself".Which of these contributes to BOLD? It's known that number 1 - output from the area in question - is not a major contributor to the fMRI signal, but what about 2 and 3? A 2010 paper that I just came across argues that 80% of the BOLD signal is caused by internal processing, and only 20% is due to input.They took some rats, and stimulated their whiskers. Using electrodes, they measured blood oxygenation changes in an area called the barrel cortex, which is known to deal with whisker-based sensations (they didn't actually use fMRI, but this would be seen as a BOLD signal if they had.)But they then added a drug called muscimol to the barrel cortex. Muscimol reduces neuronal firing, but it doesn't affect synaptic input. They show that muscimol strongly reduced the blood oxygenation response, by about 80%. This suggests that 80% of the signal was not caused directly by sensory input to the cortex, but was generated within the cortex.In many ways this is not surprising: it would be weird if the cortex were just picking up signals and doing nothing with them. However, it's good to be able to put a figure on just how much intra-cortical processing contributes to the fMRI signal. In rats, at any rate.Harris S, Jones M, Zheng Y, & Berwick J (2010). Does neural input or processing play a greater role in the magnitude of neuroimaging signals? Frontiers in neuroenergetics, 2 PMID: 20740075... Read more »
Harris S, Jones M, Zheng Y, & Berwick J. (2010) Does neural input or processing play a greater role in the magnitude of neuroimaging signals?. Frontiers in neuroenergetics. PMID: 20740075
by Neuroskeptic in Neuroskeptic
According to a neat little new paper, the placebo effect relies on the brain's own marijuana-like chemicals, endocannabinoids.Or rather, some kinds of placebo effects involve endocannabinoids. It turns out that "the placebo effect" is not one thing.The authors, led by Fabrizio Benedetti, have previously shown that placebo "opioids" - i.e. when you expect to get a painkiller such as morphine, but actually it's just water - relieve pain via the brain's own opioid system (endorphins). Blocking endorphins with certain drugs blocks the power of placebo morphine.But there are many painkillers that aren't opioids, leaving open the question of whether all placebo effects on pain are mediated by endorphins.The new study claims that endocannabinoids are involved in non-opioid placebo analgesia. They used rimonabant, a weight loss drug that was pulled from the market shortly after it appeared, because it caused depression. Rimonabant worked by blocking CB1 receptors, which are the main target of the psychoactive chemicals in cannabis - and also key players in the endogenous cannabinoid system.Here's the headline result:The graph on the left shows the relationship between the pain relieving power of morphine, and the pain relief caused by placebo "morphine" given on a subsequent day. As you can see, there was a strong correlation. People who had a strong response to real morphine, later responded well to the fake morphine. But rimonabant had no effect at all.Pain relief was measured using tolerance to the pain caused by a tightly fitting tourniquet.However, rimonabant did have a strong effect on the placebo response to a different drug, ketorolac, which is related to the better-known ibuprofen (Nurofen). As you can see in the graph on the right, people given rimonabant had a much lower response to the placebo "ketorolac".In other experiments, they showed that rimonabant alone had no effect on pain tolerance.This is a nice result. It shows that the placebo effect is not a single thing, but that it depends upon the nature of the drug that you believe you've got. It also reminds us that the placebo effect is not some magical power of mind-over-matter, but is in fact, well, matter-over-matter.Interestingly, ketorolac has no effect on endocannabinoids, or at least no direct effect. The mechanism of action, which is fairly well understood, has nothing to do with cannabinoids. Yet placebo "ketorolac" still seems to set endocannabinoids buzzing.Benedetti F, Amanzio M, Rosato R, & Blanchard C (2011). Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nature medicine, 17 (10), 1228-30 PMID: 21963514... Read more »
Benedetti F, Amanzio M, Rosato R, & Blanchard C. (2011) Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors. Nature medicine, 17(10), 1228-30. PMID: 21963514
by Neuroskeptic in Neuroskeptic
A new study offers support for the theory that mental illness is associated with "creative" achievement.The idea that madness is close to creative genius is a popular one. From the nutty professor to the tortured genius, there's no end of sterotypes, and pop culture seemingly offers plenty of examples, from Van Gogh and his ear to Charlie Sheen and his bi-winning.But is it true?A new study says yes. Kyaga et al looked at everyone in Sweden who had been treated as an inpatient for either schizophrenia, bipolar disorder, or depression, between 1973 and 2003. In total that meant about 300,000 people (two thirds of that was depression).They then matched this up with the Swedish national census which asks people their occupation. They looked to see whether the psychiatric cases were more likely to have been employed in a "creative" profession. They defined that as visual artists (photographers, designers, etc.) non-visual artists (musicians, actors, authors) and academics (university teachers).Finally, they pulled up the records on the patients' relatives, to see what their jobs were. This is one of those studies that could only happen in Scandinavia, because only those countries keep such comprehensive ( rather scarily so) info about their citizens.They found that being bipolar, or being a close relative of someone who's bipolar, was associated with having a creative job. For schizophrenia, the picture was more complex: being a schizophrenia inpatient was not linked to being a creative in itself, but being related to someone with schizophrenia was. The effects were fairly modest.For depression (not bipolar, just plain unipolar depression), there was no link at all, or even a slightly lower level.The correlation wasn't driven by differences in IQ (yes, they had data on that too, for males, thanks to military service records.) Creative types had higher IQs on average while psych inpatients had slightly lower IQs than others. So correcting for IQ made the associations even stronger.So it looks as though being bipolar, at any rate, is linked to creativity, and so is having bipolar and schizophrenia in the family - if you believe these findings. Should we?This study was huge and the data are, on the face of it, very comprehensive. However, it turns out that many people didn't state their occupation, especially the patients. Only 45% of people with schizophrenia gave a valid answer, compared to 75% of the bipolar and depressed. In the controls, it was about 80%.That's a serious issue. The authors did try to get around this by looking at the siblings of the patients with missing data. For schizophrenia, siblings of missing data schizophrenics were more creative than for the ones with full data, and for bipolar there was no difference. So the effects are not due to nonreporting of non-creative jobs.Another possible confound is family background and environment. Indeed, the fact that people with bipolar were no more likely to be in a creative job than their relatives who weren't bipolar (or, at least, never received inpatient treatment) rather supports this view. Maybe the relatives shared genes with the patients meaning that their creativity was associated with bipolar, but we can't know that.One reassuring piece of evidence against the idea that these results were driven by a general correlation between psychiatric hospitalization and "middle class professions" is that there was no association with the "non-creative" job of accountancy and auditing (sorry accountants and auditors).Overall, while this is an interesting study, and while I find the proposed link between mental illness and creativity plausible, we need more detailed research to ensure that the correlation isn't just a reflection of socioeconomic factors.Kyaga, S., Lichtenstein, P., Boman, M., Hultman, C., Langstrom, N. Landen, M. (2011). Creativity and mental disorder: family study of 300 000 people with severe mental disorder The British Journal of Psychiatry DOI: 10.1192/bjp.bp.110.085316... Read more »
Kyaga, S., Lichtenstein, P., Boman, M., Hultman, C., Langstrom, N., & Landen, M. (2011) Creativity and mental disorder: family study of 300 000 people with severe mental disorder. The British Journal of Psychiatry. DOI: 10.1192/bjp.bp.110.085316
by Neuroskeptic in Neuroskeptic
Earlier this year, a large group of autism experts signed a consensus statement condemning "Le Packing", a certain procedure used in children with autism.They said:This alleged therapy consists of wrapping the patient (wearing only underclothes or naked in the case of young children) several times a week during weeks or months in towels soaked in cold water (10°C to 15°C). The individual is wrapped with blankets to help the body warm up in a process lasting 45 minutes, during which time the child or adolescent is accompanied by two to four staff...The alleged goal of this technique is to “allow the child to rid him- or herself progressively of its pathological defense mechanisms against archaic anxieties,” by achieving “a greater perception and integration of the body, and a growing sense of containment..."We have reached the consensus that practitioners and families around the world should consider this approach unethical. Le Packing is almost unheard of outside France, where it was invented some years ago by M. A. Woodbury, an American psychiatrist. It's controversial even there.Now Pierre Delion, a French packer who's previously defended the approach, and even wrote the book on it, has penned an article which discusses the towel-based treatment: Towards a dialogue between psychoanalysis and neuroscience: Connections that are both possible and necessaryThe piece (part of a special issue on psychoanalysis and neuroscience) starts out with some general scholarly remarks about previous authors who have discussed Freud and the brain, but it moves on to autism, with some, well, puzzling remarks:During the first months of life, an infant will actively practice his or her archaic reflexes. Of these, the grasping, which will progressively disappear as voluntary prehension emerges around the age of 4–5 months, is of great interest. The facilitation and/or anaclitic relationships between this reflex and adhesive identification are even more interesting to study together because, for instance, in an autistic child, the first model will integrate under the form of pathological adhesive identification.In such an example, a strategy for thinking about these two phenomena and making them compatible is using a third term (e.g., Peircean logic, in which adhesive identification is an icon of grasping). If we refer to this important principle from this great American semiotician, the icon is part of the logical representation scheme from the most elementary, the icon, to the most evolved, the symbol, passing by the intermediate, the index... The relationships between neurological wiring and pre-wiring enable the effective installation of the theory of mind and the phenomenon of projective identification described by Melanie Klein and her students... Hmm.On Le Packing itself we get a curious paragraph which seems to be saying that the therapy itself works via a neurophysiological mechanism, but that Freudian theory can explain why the child and their caregivers are anxious. What the anxiety in question is about is not clear. About the packing? That seems the most natural reading:Another example taken from Pierre Delion’s practice as a therapist for children with autistic disorder is the ‘‘packing’’ technique (Goeb et al., 2008). This is the use of humid wrapping to prevent self-mutilation by using these two different levels [i.e. neuroscience and psychoanalysis] that are nonetheless joint during treatment. This technique uses a neurophysiological hypothesis to try to explain the therapeutic effects, but, at the same time, the psychopathological hypothesis that is given by psychoanalysis helps to format the anxieties that are experienced by the children and invariably shared by their caretakers. Clinical research regarding this topic is currently being undertaken in Pierre Delion’s child psychiatry department following a hospital program for clinical research (PHRC, NoEudra CT: 2007-A01376-47) entitled ‘‘Demonstration of the efficiency of packing treatments in children affected by autistic disorders with severe behavioral disorders’’.Delion P (2011). Towards a dialogue between psychoanalysis and neuroscience: Connections that are both possible and necessary. Journal of physiology, Paris PMID: 21963531... Read more »
Delion P. (2011) Towards a dialogue between psychoanalysis and neuroscience: Connections that are both possible and necessary. Journal of physiology, Paris. PMID: 21963531
by Neuroskeptic in Neuroskeptic
With the help of an MRI scanner and some child pornography, a new study claims to be able to tell whether someone is a paedophile: Assessment of Pedophilia Using Hemodynamic Brain Response to Sexual Stimuli.It was an fMRI study of 24 self-identified paedophiles (recruited through a clinic offering anonymous treatment) and 32 male controls. Everyone was shown a series of images of naked men, women, boys and girls. The neural response to child vs. adult images was the main outcome measure.Respect to the authors for getting that past the ethics committee.The blob-o-grams above show that the paedophile's brains reacted differently to the control brains, when shown images of naked children, which is not surprising because the brain is what makes you a paedophile (and everything else.)However, what's more interesting is that by comparing each individual's brain activity to the average activity of the paedophile group and the control group, it was possible to diagnose people as paedophiles or not with high accuracy (90 %).Plotting the "typical paedophile"-ness of the neural response to girls vs women and boys vs men, the paedophiles (triangles) form a clear cluster. There were also some differences between homosexual and heterosexuals in both groups.The statistics seem kosher: they used leave-one-out cross-validation to avoid the error of double dipping.What's not clear is whether this was measuring sexual attraction as such. All it's measuring is how much each person's activity correlated with the paedophile group average. Maybe it's picking up on the shame paedophiles feel over being reminded of what they've done. Maybe the controls were just averting their eyes when the child porn came on.However, you could say that if you're just interested in the practical business of catching paedophiles, that's academic. More concerning is the question of whether it would be possible to fool the technique. A recent study showed that it's easy to fool a brain scan designed to detect lying.But let's suppose it does work out. Would that be a good thing? What is "a paedophile", anyway? Is it someone's who's attracted to children, or someone who acts on that attraction?For example, there are people who are caught with child porn, and who admit they downloaded it, but who deny being attracted to children. The Who shredder Pete Townsend and comedian Chris Langham being two British examples. Both admit downloading illegal images, but say it was for 'research purposes'.Now it might be possible, using fMRI, to find out if they're telling the truth. Let's suppose it was doable.So what? Downloading child pornography is a crime - whatever your motivation. Being attracted to children is legal, in itself. So from a legal perspective it should make no difference at all in cases like this.Of course, we don't in fact go around seeing things from a purely legal perspective. We care whether someone is attracted to children or not. But should we care? Is that fair? You don't choose your sexual orientation. What you choose is whether to break the law by commiting the crime.There are surely people out there - no-one knows how many - who are attracted the children, and never act on it. Do we want to be able to "catch" them?Edit: The original version of this post linked to the wrong paper, an older paper by the same authors. This has been fixed now.Ponseti, J., Granert, O., Jansen, O., Wolff, S., Beier, K., Neutze, J., Deuschl, G., Mehdorn, H., Siebner, H., & Bosinski, H. (2011). Assessment of Pedophilia Using Hemodynamic Brain Response to Sexual Stimuli Archives of General Psychiatry DOI: 10.1001/archgenpsychiatry.2011.130... Read more »
Ponseti, J., Granert, O., Jansen, O., Wolff, S., Beier, K., Neutze, J., Deuschl, G., Mehdorn, H., Siebner, H., & Bosinski, H. (2011) Assessment of Pedophilia Using Hemodynamic Brain Response to Sexual Stimuli. Archives of General Psychiatry. DOI: 10.1001/archgenpsychiatry.2011.130
by Neuroskeptic in Neuroskeptic
The pharmaceutical industry is in trouble at the moment, with many companies pulling out of development in certain areas and psychiatry is high on the list.The tale of one troubled would-be antidepressant has just been published in the form of a clinical trial that was terminated early when the parent company went under. But another company came along to save the day, so the drug might live on.Amitifadine is a triple reuptake inhibitor (TRI). What's that? Prozac and other SSRI antidepressants work by blocking the reuptake of serotonin in the brain thus increasing levels of serotonin. Some other antidepressants block the reuptake of serotonin and noradrenaline, and these dual reuptake inhibitors may be slightly better than SSRIs (although maybe not).TRIs take this one step further: they add a third monoamine neurotransmitter, dopamine, to the list. If two monoamines are better than one, three ought to be even better... right?This was a clinical trial of amitifadine vs placebo in depressed adults. It was originally designed to have 200 depressed people, but it only got to 63 patients before the money ran out:The study was initiated in April 2008 and was halted by the sponsor, DOV Pharmaceuticals, early in December 2008 due to lack of funding.DOV were a small company best known in the financial world for the fact that their stock crashed spectacularly on the first day they went public on the markets. Investors who lost out subsequently sued the company and their main underwriters, a certain outfit you may have heard of called Lehman Brothers.After various (non-psychiatry) projects failed, DOV were bought out by a certain Euthymics Bioscience. DOV's old website, dovpharm.com, now offers Canadian Cialis. Don't wait! Order the cheapest medications now!What a sad fate. When Euthymics bought DOV, they also bought the rights to DOV 21,947 which they dubbed amitifadine. The takeover happened in June 2010, so I guess that after DOV pulled the plug on the trial in 2008, Euthymics came along and decided to try to finish the development of amitifadine. The lead author on the present paper is Chief Medical Officer at Euthymics.So what did they get for their money? Is amitifadine a goose that will lay some golden eggs, or the latest turkey?Take a look:People on amitifadine did slightly better than the ones on placebo over 6 weeks, on the MADRS depression scale (p=0.028). On the HAMD17 scale, which is more popular, there was no significant benefit (p=0.125), although it might have worked had the trial managed to recruit more people.The non-significant benefit over placebo on the HAMD was 3.1 points. How does that compare to other drugs? It's impossible to say for sure, but there are some reasons to think that it's nothing special.Patients in this study had very severe depression, with a baseline HAMD17 score of about 29.5. We know that the effect of antidepressants over placebo is correlated with severity. For what it's worth, with existing antidepressants, a baseline HAMD score of 29.5 would be expected to translate into a drug-placebo difference of about 4 HAMD points according to Fournier et al or about 5 in Kirsch et al. Plus, the odds were stacked in the drug's favour in this study. To get into the trial, patients needed to have shown a "significant clinical improvement" to at least one previous antidepressant. Anyone who'd failed to improve on two or more different drugs was excluded.In terms of side effects, there weren't many, and people on the drug actually reported no more adverse effects than those on placebo, in total. It lowered blood pressure and raised heart rate slightly. However, the small sample size is an issue here as well. The only way to know whether it's really better tolerated than other drugs would be to do a direct comparison.Overall, while amitifadine looks like it works to some extent, it's anyone's guess whether it will offer any advantages over existing, cheap drugs - a verdict that Neuroskeptic readers have heard before.Tran P, Skolnick P, Czobor P, Huang NY, Bradshaw M, McKinney A, & Fava M (2011). Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Journal of psychiatric research PMID: 21925682... Read more »
Tran P, Skolnick P, Czobor P, Huang NY, Bradshaw M, McKinney A, & Fava M. (2011) Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: A randomized, double-blind, placebo-controlled trial. Journal of psychiatric research. PMID: 21925682
by Neuroskeptic in Neuroskeptic
The present economic crisis has led to more suicides in Europe - but fewer deaths in road traffic accidents. So says a brief report in The Lancet. The authors show that suicide rates in people under the age of 65, which have been falling for several years in Europe, rose in 2008 and again in 2009, in line with unemployment figures. The overall effect was fairly small - 2009 was no worse than 2006. It still corresponds to a 5% annual increase in most countries. In Greece, Ireland, and Latvia the rise was about 15%.That's sad but not perhaps very surprising.What's interesting though is that road traffic fatalities fell sharply. In Lithuania, they dropped by nearly half, although they were very high to begin with, and in Spain and Ireland they fell by 25%.This presumably reflects the fact that people are just driving less, and perhaps slower. We've got less money to spend on fuel, and fewer jobs and things to need to drive to.The authors note that although fewer road deaths is generally a good thing, there's one downside - a shortage of donor organs for transplantation. Road accidents are a prime source of organs because they're one of the few times that young, healthy people die leaving most of the body intact.Stuckler D, Basu S, Suhrcke M, Coutts A, & McKee M (2011). Effects of the 2008 recession on health: a first look at European data. Lancet, 378 (9786), 124-5 PMID: 21742166... Read more »
Stuckler D, Basu S, Suhrcke M, Coutts A, & McKee M. (2011) Effects of the 2008 recession on health: a first look at European data. Lancet, 378(9786), 124-5. PMID: 21742166
by Neuroskeptic in Neuroskeptic
Here at Neuroskeptic we see a lot of dizzyingly bad (and sometimes even good) neuroscience, but did you know that brain scanners can literally send your head into a spin? A new paper explains why, with implications for all MRI researchers.MRI scanners rely on extremely powerful magnetic fields. This is why you can't take metal objects into the scanner room, as they'd be pulled into it. Yet the fields can also exert other kinds of effects on the body.I'd always been told that static, unchanging magnetic fields are biologically inert. But moving through the field too quickly can cause side effects. When an object moves through a magnetic field, induction happens - electrical currents are produced.In the case of the human body, these small currents can activate nerve cells. Depending on which cells they hit this can cause you to feel dizzy, see flashes of light, experience tingling sensations, and so on. Or so I thought.However, a new paper from Dale Roberts et al of Johns Hopkins shows that just being in a powerful magnetic field can cause dizziness and vertigo - with no movement required. They noticed that lying still in or near an MRI scanner causes nystagmus, abnormal horizontal eye movements, and that the amount of eye movement is directly correlated with the angle at which the head is positioned relative to the field.The nystagmus was caused by an automatic reflex in response to effects in the vestibular ("balance") system of the ear. Roberts et al realized that the static magnetic field causes electrical currents that activate vestibular cells, even when the head is perfectly still. It happens because there's a natural flow of electrically charged ions into these cells in a part of the ear called the semicircular canal. The magnetic field interacts with this ion current, in what's called a Lorentz force.The semicircular canals normally allow us to sense when our head is moving. Our eyes automatically compensate for head movement to keep us looking in the same direction. The MRI magnet fooled the ear into thinking the head was rotating, and the eyes produced nystagmus as a result.Two patients who had suffered damage to their semicircular canals were immune to the effect.This has important implications for functional MRI studies of brain function. Many people are interesting in measuring eye movements during MRI scans. This finding suggests that these movements may be unusual, compared to normal eye movements outside the scanner. Worst, the vestibular stimulation could alter brain activity:Vestibular stimulation induced by the magnetic field in healthy subjects simply lying in the bore could activate many brain areas related to vision, eye movements, and the perception of the position and motion of the body.Roberts, D., Marcelli, V., Gillen, J., Carey, J., Della Santina, C., & Zee, D. (2011). MRI Magnetic Field Stimulates Rotational Sensors of the Brain Current Biology DOI: 10.1016/j.cub.2011.08.029... Read more »
Roberts, D., Marcelli, V., Gillen, J., Carey, J., Della Santina, C., & Zee, D. (2011) MRI Magnetic Field Stimulates Rotational Sensors of the Brain. Current Biology. DOI: 10.1016/j.cub.2011.08.029
by Neuroskeptic in Neuroskeptic
A major international study threatens to overturn what we thought we knew about schizophrenia. People with schizophrenia are more likely to get better if they live in poor countries: that's been known for about 25 years. In the 1980s, a series of pioneering World Health Organization (WHO) studies looked at the prognosis for people diagnosed with schizophrenia around the world.All of the data showed that people in developed countries were less likely to recover than those from poorer areas.This paradoxical finding sparked no end of debate. What is it about these countries that makes them a better place to get schizophrenia? Patients in richer countries tend to have access to more and "better" psychiatric care, the latest drugs, and so on. Does this mean that those treatments are useless - worse, harmful? That's been the interpretation of some people.But is it true? Not always, says a new study, W-SOHO. It's out in the British Journal of Psychiatry.The authors compared schizophrenia outcomes in 37 countries. They recruited outpatients who were starting, or changing, antipsychotic medication. They found that in terms of "clinical" remission - i.e. improvement in the delusions, hallucinations, and other symptoms of schizophrenia - people in the developing world did indeed fare better than those from rich countries.Over a 3 year period, 80-85% of patients from East Asia, the Middle East, and Latin America who started off ill, showed clinical remission, compared to 60-65% in Europe. That's not new: it confirms what the old WHO data showed.But the new study also looked at "functional" remission - essentially, being able to participate in society:having good social functioning for a period of 6 months. Good social functioning included those participants who had: (a) a positive occupational/vocational status, i.e. paid or unpaid full- or part-time employment, being an active student in university or housewife; (b) independent living; and (c) active social interactions, i.e. having more than one social contact during the past 4 weeks or having a spouse or partner.For functional remission, Northern Europe (e.g. the UK, France, Germany) was the best place to get sick, with 35% achieving it. Not a very high figure, but better than elsewhere: it was just 18% in the Middle East and 25% in East Asia, despite these areas having the highest chances of clinical remission. Latin America did pretty well, however, at 29%.This is a very important finding if it's true. Is it solid? First off, were Northern European patients just less ill to start with? Not really. They had the highest rates of suicide attempts. They tended to be older, and to have been diagnosed at a later age, which was correlated with worse functional remission. Regression analyses confirmed that region was a predictor of remission controlling for all the other variables.However, Northern European patients did tend to have better function at baseline. They were more likely to be employed, living independently, and socially active when they entered the study. 63% were living independently which is much higher than anywhere else: it was 24% in Middle East and Latin America. 23% had a paid job compared to 17-19% in developing countries. That's not a flaw in the study as such but it does suggest that the differences, whatever they are, are already in place before people get treated.One concern I have is that the definition of "functional remission" may be North Europe-centric. "Living independently" is something we aspire to but in other places, with a strong tradition of the extended family household, the idea that it would be a bad thing for someone with schizophrenia to be living with their family might seem silly. If that means they'll be cared for and supported, what's wrong with it?And in terms of paid employment, Northern Europe just has a stronger economy than most other places (erm... well, it did back in 2000 when these data were collected), so maybe it's no surprise that people with schizophrenia were more likely to have paid jobs.In terms of the study itself, it was extremely large with over 17,000 patients enrolled. But here's the thing: this study was run by Lilly, the drug company who make olanzapine, an antipsychotic used in schizophrenia. Three of the authors on the paper are Lilly employees, and the lead author was a consultant for them. The study deliberately sampled lots of people taking olanzapine, presumably in order to find out whether they did better.None of this necessarily means that the data aren't valid, but I'm just not sure I trust Lilly over the WHO.Haro JM, Novick D, Bertsch J, Karagianis J, Dossenbach M, & Jones PB (2011). Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. The British journal of psychiatry : the journal of mental science, 199, 194-201 PMID: 21881098... Read more »
Haro JM, Novick D, Bertsch J, Karagianis J, Dossenbach M, & Jones PB. (2011) Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. The British journal of psychiatry : the journal of mental science, 194-201. PMID: 21881098
by Neuroskeptic in Neuroskeptic
Seen Contagion yet?It's pretty scary. A new epidemic disease comes out of nowhere and starts killing everyone. It infects the brain - victims suffer seizures, or fall into a coma, and die. It spreads like wildfire. Humanity's only hope lies in Lawrence Fishburne and Kate Winslet.Luckily, that's fiction. But only just.In the movie, the killer bug is called "MEV-1", but it might as well have been called the Nipah virus, because it was closely based on a real disease of the same name. So much so that this post about Nipah contains movie spoilers.The Nipah Virus came to the world's attention in late 1998. There was an outbreak of a severe fever accompanied in many cases by encephalitis (viral infection of the brain) in Malaysia and Singapore. 276 patients were recorded. 40% of them died.In the initial outbreak, there was probably no person-to-person transmission of the virus. Rather, only people who came into contact with Malaysian pigs - mainly farmers and butchers - caught the disease. Over a million pigs were culled in 1999 to try and contain the outbreak, and this seemed to be effective.But since then, there have been several other smaller Nipah outbreaks in Asia, one almost every year in fact. In some of these, person to person transmission has been detected, notably in Bangladesh and India. The fatality rate in these more recent outbreaks has also been higher (70-90%). Luckily, it doesn't seem to be very contagious - so far. Most years have seen only 10 or 12 cases. But who knows what the future holds?The virus is distantly related to measles, but is much more severe. Symptoms can begin anywhere from 4 days to 2 months after infection, but generally within 1 to 2 weeks. More recent outbreaks seem to have a shorter incubation period. The symptoms include fever, headache, vomiting, seizures, muscular jerks, and altered consciousness (confusion, coma).Even after the initial infection is over, a minority of patients (4-8%) later suffer a relapse encephalitis. The virus seems able to remain dormant in the body before re-emerging to infect the brain again. Survivors may suffer neurological problems such as epilepsy, movement disorders, fatigue, and others. This is especially common following relapse encephalitis.Where did it come from? It turns out that various strains of Nipah-like viruses are common in certain bats that inhabit various Asian countries, specifically fruit bats of the Pteropus genus, aka "flying foxes". The bats don't get sick, but infected bats are highly contagious, excreting the virus in their urine.The virus seems to have made the leap into humans not once but several times, from different kinds of bats. Each outbreak could represent a new crossover event. Often there was an intermediate animal host, such as the domestic pigs in Malaysia .Nipah is a classic zoonotic disease - it jumps from animals to humans. Zoonoses are scary for two reasons. They're new to humans, so humans haven't had a chance to develop immunity. And they may be especially deadly, because they haven't evolved not to be deadly to us.Viruses and bacteria don't actually want to kill you. They want you alive, so that you can keeping breathing, walking, having sex, and otherwise spreading them. So pathogens tend to evolve to be less lethal to their primary hosts. Unfortunately, that's only good news if you are the primary host, and in the case of zoonoses, we're not. Bats don't get sick, but we do.Lo, M., & Rota, P. (2008). The emergence of Nipah virus, a highly pathogenic paramyxovirus Journal of Clinical Virology, 43 (4), 396-400 DOI: 10.1016/j.jcv.2008.08.007... Read more »
Lo, M., & Rota, P. (2008) The emergence of Nipah virus, a highly pathogenic paramyxovirus. Journal of Clinical Virology, 43(4), 396-400. DOI: 10.1016/j.jcv.2008.08.007
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