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  • April 23, 2014
  • 04:25 AM
  • 1 view

Phenylalanine and schizophrenia: new directions for intervention?

by Paul Whiteley in Questioning Answers

As regular readers might already have noticed, amino acids are a bit of a obsession of mine on this blog. Out of all of them - and there are quite a few - I'm particularly interested in the aromatic amino acids and the their various connections to health and wellbeing. I've talked at length about some of the proposed connections made between amino acids such as tryptophan, tyrosine and phenylalanine to all manner of conditions but specifically with the autism spectrum in mind (see here).The conversion. Matthews (2007) J Nutr. 137: 15495-15555.Phenylalanine (or Phe) has been a particular favourite on this blog, not least because of its connection to that most classical 'diet can affect mental health' condition known as Phenylketonuria (PKU). As per other research chatter however, the connection between phenylalanine and PKU might just be the tip of the iceberg (see here). Indeed, today that iceberg just got a little bigger as I discuss the paper by Olaoluwa Okusaga and colleagues* (open-access) and their observations of elevated blood levels of phenylalanine in cases of schizophrenia. Such findings might indeed have some important management consequences as you'll see shortly when it comes to the use of something called BH4.The Okusaga paper is open-access but a few of the important details:Well, one can't say that this was an under-powered study from a participant number point of view, as blood samples from 950 adult participants with a confirmed diagnosis of schizophrenia via the SCID were compared with 1000 asymptomatic controls for levels of phenylalanine and tyrosine.Analysis of samples was via HPLC with fluorescence detection, which whilst OK as a separative-detection method is not exactly the gold-standard that is mass spectrometry (MS) or nuclear magnetic resonance (NMR). From the measures of phenylalanine and tyrosine, an estimate of the activity of phenylalanine hydroxylase (PAH) was also calculated and expressed as a phenylalanine: tyrosine ratio**. PAH represents an important step in the conversion of phenylalanine to tyrosine, which then proceeds down a metabolic pathway to eventually end up as dopamine. It's worth pointing out that dopamine has some important research history when it comes to the presentation of schizophrenia or at least, that's the suggestion (see here).Results: well bearing in mind some issues with the matching of the two sample groups in terms of age and BMI (a higher BMI in the schizophrenia group bearing in mind that these were not medication-naive participants), the schizophrenia group "had significantly higher Phe (geometric mean difference 1.26 µmol/L; CI 1.18 to 1.36, p<0.0001) and Phe:Tyr ratio (geometric mean difference 1.41; CI 1.33 to 1.48, p<0.0001) compared to healthy controls and this finding persisted after controlling for gender, age, education, and BMI differences between the 2 groups". As a group however, there was no significant differences for the schizophrenia and control groups when it came to measures of tyrosine although "lower levels of Tyr are more common among schizophrenia patients".The authors conclude that alongside further, more controlled study with regards to sample collection (including looking at measures of inflammation), there may also be some merit in looking at the potential effects of "Phe-lowering interventions in schizophrenia".As I mentioned before, Phe-lowering interventions very much includes the use of BH4, but could also mean the rather more invasive use of a low phenylalanine diet (and then tyrosine supplements?) more commonly indicated for cases of PKU. I should point out that this does not mean I am in any way endorsing such a dietary change or pharmacological action at this time as a function of my caveat on this blog about not giving medical or clinical advice. That being said, the research gauntlet has been thrown down by the results of the Okusaga study so I'll be keeping my eyes open for future work in this area. There is other evidence suggestive of issues with the availability of BH4 in cases of schizophrenia as per the results from Richardson and colleagues*** which also extended to related schizoaffective disorder too****. Given that BH4 provides an important support service to a variety of enzymes relevant to the metabolism of aromatic amino acids (think tryptophan hydroxylase, TPH, for example), lower levels are probably not all that desirable. This might be particularly important to ensuring phenylalanine does not build up to too higher levels and the effects that can have*****.Aside from the phenylalanine-lowering interventions call made from the Okusaga study, a few other questions are floating round my mind. So, at what point do phenylalanine levels become elevated in some cases of schizophrenia? I'd assume that as per the quite comprehensive use of the Guthrie test these days, we aren't talking about participants reaching the cut-off points for PKU in early infancy, so when does this issue present itself in cases of schizophrenia and why? I'm also interested in the cognitive effects of [chronic] elevated phenylalanine levels and how this might also map onto similar elevations noted in cases of schizophrenia too. Noting the increasing interest in cognition and schizophrenia (see this paper****** for example) and the growing  importance of cognitive impairment to cases, could the elevated phenylalanine results merely reflect this one facet of schizophrenia?So you can see that there is a lot more to do in this area. Given also that schizophrenia, like autism, is probably better represented on a spectrum model, the question is also whether hyperphenylalaninemia in relation to cases of schizophrenia might represent one particular part of that schizophrenia spectrum? At least one other study suggests possibly******* (open-access) with quite a novel alternative method for detecting phenylalanine used. A lot more to do in this area methinks.Music to close. Driftwood by Travis.----------* Okusaga O. et al. Elevated Levels of Plasma Phenylalanine in Schizophrenia: A Guanosine Triphosphate Cyclohydrolase-1 Metabolic Pathway Abnormality? PLoS ONE 2014. 9(1): e85945.** Matthews DE. An Overview of Pheny... Read more »

Olaoluwa Okusaga, Olesja Muravitskaja, Dietmar Fuchs, Ayesha Ashraf, Sarah Hinman, Ina Giegling, Annette M. Hartmann, Bettina Konte, Marion Friedl, Jason Schiffman.... (2014) Elevated Levels of Plasma Phenylalanine in Schizophrenia: A Guanosine Triphosphate Cyclohydrolase-1 Metabolic Pathway Abnormality?. PLoS ONE. DOI: 10.1371/journal.pone.0085945  

  • April 22, 2014
  • 10:40 PM

Autism, SSRIs, and Epidemiology 101

by in Neuroscientifically Challenged

I can understand the eagerness with which science writers jump on stories that deal with new findings about autism spectrum disorders (ASDs). After all, the mystery surrounding the rapid increase in ASD rates over the past 20 years (see right) has made any ASD-related study that may offer some clues inherently interesting. Because people are anxiously awaiting some explanation of this medical enigma, it seems like science writers almost have an obligation to discuss new findings concerning the causes of ASD.The problem with many epidemiological studies involving ASD, however, is that we are still grasping at straws. There seem to be some environmental influences in ASD, but the nature of those influences is, at this point, very unclear. This lack of clarity means that the study of nearly any environmental risk factor starts out having potential legitimacy. And I don't mean that as a criticism of these studies -- it's just where we're at in our understanding of the rise in ASD rates. After we account for mundane factors like increases in diagnosis due simply to greater awareness of the disorder, there's a lot left to figure out.So, with all this in mind, it's understandable (at least in theory) to me why a study published last week in the journal Pediatrics became international news. The study looked at a sample of children that included healthy individuals along with those who had been diagnosed with ASD or another disorder involving delayed development. They asked the mothers of these children about their use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. 1 in 10 Americans is currently taking an antidepressant, and SSRIs are the most-frequently prescribed type of antidepressant. Thus, SSRIs are administered daily by a significant portion of the population.Before I tell you what the results of the study were, let me tell you why we should be somewhat cautious in interpreting them. This study is what is known as a case-control study. In a case-control study, investigators identify a group of individuals with a disorder (the cases) and a group of individuals without the disorder (the controls). Then, the researchers employ some method (e.g. interviews, examination of medical records) to find out if the cases and controls were exposed to some potential risk factor in the past. They compare rates of exposure between the two groups and, if more cases than controls had exposure to the risk factor, it allows the researchers to make an argument for this factor as something that may increase the risk of developing the disease/disorder.If you take any introductory epidemiology (i.e. the study of disease) course, however, you will learn that a case-control study is fraught with limitations. For, even if you find that a particular exposure is frequently associated with a particular disease, you still have no way of knowing if the exposure is causing the disease or if some other factor is really the culprit. For example, in a study done at the University of Pennsylvania in the late 1990s, researchers found that children who slept with nightlights on had a greater risk of nearsightedness when they got older. This case-control study garnered a lot of public attention as parents began to worry that they might be ruining their kids' eyesight by allowing them to use a nightlight. Subsequent studies, however, found that children inherit alleles for nearsightedness from their parents. Nearsighted parents were coincidentally more likely to use nightlights in their children's rooms (probably because it made it easier for the nearsighted parents to see).A variable that isn't part of the researcher's hypothesis, but still influences a study's results is known as a confounding variable. In the case of the nearsightedness study, the confounding variable was genetics. Case-control studies are done after the fact, and thus experimenters have little control over other influences that may have affected the development of disease. Thus, there are often many confounding influences on relationships detected in case-control studies.So, a case-control study can't be used to confirm a cause-and-effect connection between an exposure and a disorder or disease. What it can do is provide leads that scientists can then follow up on using a more rigorous experimental design (like a cohort study or randomized trial). Indeed, the scientific literature is replete with case-control studies that ended up being false leads. Sometimes, however, case-control results have been replicated with better designs, leading to important discoveries. This is exactly what happened with early reports examining smoking and lung cancer.Back to the recent study conducted by Harrington et al. The authors found that SSRI use during the first trimester was more common in mothers whose children went on to develop ASD than in mothers who had children who developed normally. The result was only barely statistically significant. This fact combined with the variability seen in the confidence interval suggests it is not an overly-convincing finding - but it was a finding nonetheless. In addition to an increased risk of ASD, the authors also point out that SSRI exposure during the second and third trimesters was higher among mothers of boys with other developmental delays. Again, however, the effect was just barely statistically significant and even less convincing than the result concerning ASD.So, the study ended up with some significant results that aren't all that impressive. Regardless, because this was a case-control design, there is little we can conclude from the study. To realize why, think about what other factors women who take SSRIs might have in common. Perhaps one of those influences, and not the SSRI use itself, is what led to an increased risk of ASD. For example, it seems plausible that the factors that make a mother more susceptible to a psychiatric disorder might also play a role in making her child more susceptible to a neurodevelopmental disorder. In fact, a cohort study published last year with a much larger sample size found that, when the influence of the condition women were taking SSRIs for was controlled for, there was no significant association between SSRI use during pregnancy and ASD.The fact that this case-control study doesn't solve the mystery of ASD isn't a knock on the study itself. If anything, it's a knock on science journalism. I can't go so far as to say these types of studies shouldn't be reported on. But, they should be reported on responsibly, and by writers who fully understand and acknowledge their shortcomings. For, it is somewhat misleading to the general public (who likely isn't aware of the limitations of a case-control study) when headlines like this appear: "Study: Moms on antidepressants risk having autistic baby boys."The safety of SSRI use during pregnancy is still very unclear. But both SSRIs and untreated depression during pregnancy have been linked to negative health outcomes for a child. Thus, using SSRIs during pregnancy is something a woman should discuss at length with her doctor to determine if treatment of the underlying condition poses more of a risk than leaving the condition untreated. In making that decision, however, the barely significant findings from a case-control study should not really be taken into consideration.Study: Moms on antidepressants risk having autistic baby boysRead more at Read more »

  • April 22, 2014
  • 09:15 PM

Removal of crop residue for biofuels increases CO2 emissions

by Jonathan Trinastic in Goodnight Earth

A computational study has shown that removal of residue from crop fields increases CO2 emissions... Read more »

Liska, A., Yang, H., Milner, M., Goddard, S., Blanco-Canqui, H., Pelton, M., Fang, X., Zhu, H., & Suyker, A. (2014) Biofuels from crop residue can reduce soil carbon and increase CO2 emissions. Nature Climate Change. DOI: 10.1038/nclimate2187  

  • April 22, 2014
  • 06:04 PM

SARS-CoV v. MERS-CoV: differences and similarities, what do we know?

by thelonevirologist in Virology Tidbits

Coronaviruses are important animal and human pathogens and are the causative agent of 30-40% community acquired upper respiratory tract infections, most of them mild diseases. Besides relatively benign infections, the infection of infants and children has been implicated in some cases to acute asthmatic attacks and the onset of croup (whizzing cough). With the identification of SARS-CoV in 2003 became associated with more severe pulmonary disease particularly in immunocompromised individuals. To understand the pathogenesis, it is vital to compare various aspects of the disease, including but not limited to the receptor distribution, viral entry and affected organs as well the interference with antiviral signaling.... Read more »

Barlan A, Zhao J, Sarkar MK, Li K, McCray PB Jr, Perlman S, & Gallagher T. (2014) Receptor variation and susceptibility to middle East respiratory syndrome coronavirus infection. Journal of virology, 88(9), 4953-61. PMID: 24554656  

Raj, V., Mou, H., Smits, S., Dekkers, D., Müller, M., Dijkman, R., Muth, D., Demmers, J., Zaki, A., Fouchier, R.... (2013) Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature, 495(7440), 251-254. DOI: 10.1038/nature12005  

Chu KH, Tsang WK, Tang CS, Lam MF, Lai FM, To KF, Fung KS, Tang HL, Yan WW, Chan HW.... (2005) Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney international, 67(2), 698-705. PMID: 15673319  

Roper, R., & Rehm, K. (2009) SARS vaccines: where are we?. Expert Review of Vaccines, 8(7), 887-898. DOI: 10.1586/erv.09.43  

Payne DC, Iblan I, Alqasrawi S, Al Nsour M, Rha B, Tohme RA, Abedi GR, Farag NH, Haddadin A, Al Sanhouri T.... (2014) Stillbirth During Infection With Middle East Respiratory Syndrome Coronavirus. The Journal of infectious diseases. PMID: 24474813  

Drosten, C. (2013) Is MERS another SARS?. The Lancet Infectious Diseases, 13(9), 727-728. DOI: 10.1016/S1473-3099(13)70159-2  

  • April 22, 2014
  • 02:56 PM

Polar Opposites? The Social Construction of Bulimia and Anorexia Nervosa

by Andrea in Science of Eating Disorders

Some might argue that bulimia nervosa is more “hidden” than anorexia nervosa — it is not always obvious that someone is suffering from bulimia (though, I would argue, it is not always obvious that someone is suffering from any eating disorder). Even when it is “discovered,” BN is often placed in opposition with AN — as if the two were polar opposites.
Indeed, attempts to define a phenotype (a set of observable traits or characteristics) for AN and BN tend to oppose the two and to suggest that the people who develop AN are inherently different from those who develop BN. While I believe there is some scientific evidence for personality differences between the two, the degree of diagnostic crossover and symptom variability in eating disorders makes me feel like this split is at the very least overly simplistic.
What is interesting is how BN has come to occupy a very different place in our collective social imagination than AN. We know that preconceived notions about what it means to be an individual with an eating disorder in general can …

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Hide or Seek? Social Support and Eating Disorders
The “Double Life” of Bulimia Nervosa: Patients’ Perspectives
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... Read more »

  • April 22, 2014
  • 01:42 PM

Most Efficient Thermoelectric Material Created

by dailyfusion in The Daily Fusion

Northwestern University scientists have discovered a material—tin selenide—that is, according to a press release, “the best in the world at converting waste heat to useful electricity.”... Read more »

Zhao, L., Lo, S., Zhang, Y., Sun, H., Tan, G., Uher, C., Wolverton, C., Dravid, V., & Kanatzidis, M. (2014) Ultralow thermal conductivity and high thermoelectric figure of merit in SnSe crystals. Nature, 508(7496), 373-377. DOI: 10.1038/nature13184  

  • April 22, 2014
  • 10:22 AM

Frogs Survive Subzero Temperatures by Living as Ice Cubes

by Elizabeth Preston in Inkfish

No matter how rough a winter you think you had, it was nothing compared to what a wood frog survives every year. Some of these little amphibians are still waiting for spring, when they’ll thaw out and turn from frog-shaped blocks of ice back into animals. Recently, scientists took a close look at wood frogs […]The post Frogs Survive Subzero Temperatures by Living as Ice Cubes appeared first on Inkfish.... Read more »

Larson DJ, Middle L, Vu H, Zhang W, Serianni AS, Duman J, & Barnes BM. (2014) Wood frog adaptations to overwintering in Alaska: New limits to freezing tolerance. The Journal of experimental biology. PMID: 24737762  

  • April 22, 2014
  • 10:21 AM

Religious Belief Linked to Brain Cortex Thickness

by William Yates, M.D. in Brain Posts

In a previous post, I reviewed a longitudinal study of religious belief and major depression.This study by Lisa Miller and colleagues found a reduced risk of depression in subjects who rated religious belief or spirituality as an important factor in their lives.Reduction in depression risk with religiosity/spirituality was largest (90% smaller risk) in those with a family history of depression.This correlation may not be causal and may be explained by some common third factor between religion and depression.A recent study explored further a potential mechanism for a protective effect of religious belief/spirituality on depression risk.Miller further studied the cohort using brain magnetic resonance imaging (MRI) to estimate cortical structure volumes. Brain structure measures were compared in three groups of subjects:High stable: subjects reporting religion or spirituality as being of high importance on two separate ratings five years apartLow stable: subjects reporting religion or spirituality as being of low importance on two separate ratings five years apartUnstable: subjects with inconsistent ratings of the importance of religion or spiritualityThe key findings from this brain imaging study were:Subjects in the high stable group showed statistically thicker brain cortex measures in the left and right parietal lobes, left cuneus and precuneus regions and in the mesial frontal lobe of the right hemisphereHigh risk subjects (family history of depression) showed stronger effects of high religiosity/spirituality on cortical thickness and this was noted to be evident in the mesial frontal lobe regionsSubject ratings of depression severity at the time of imaging correlated inversely with temporal lobe brain cortex thickness The authors note the parietal cortex and cuneaus brain regions are involved in spatial processing, sensory processing, sense of self and reflective self-awareness.They summarize their study and implications with the following:"The importance of religion or spirituality therefore likely reinforces persons who are at greater familial and neuoranatomical risk for developing depression against actually becoming ill by providing reserve in the regions within the (depression) endophenotype.."This is an important study that is likely to lead to further structural and functional brain imaging research in risk and resilience to major depression. Readers with more interest in this study can access the free full-text manuscript by clicking on the PMID link in the citation below.Image of brain parietal lobe and cuneus regions is a screen shot from the iPad 3D Brain. 3D Brain is produced by the Cold Spring Harbor Laboratory DNA Learning Center with funding from the Dana Foundation and the William and Flora Hewlett Foundation.Follow the author on Twitter at WRY999Miller L, Bansal R, Wickramaratne P, Hao X, Tenke CE, Weissman MM, & Peterson BS (2014). Neuroanatomical correlates of religiosity and spirituality: a study in adults at high and low familial risk for depression. JAMA psychiatry, 71 (2), 128-35 PMID: 24369341... Read more »

  • April 22, 2014
  • 04:22 AM

Are Neuroimaging researchers headed the Sheldon Cooper way?

by Harsha Radhakrishnan in United Academics

The ultimate goal of all these projects is to be able to reconstruct the human brain – have a definitive computer model or a database of every neuron and its cell type and the connections between each individual cell. Is this feasible?... Read more »

Oh SW, Harris JA, Ng L, Winslow B, Cain N, Mihalas S, Wang Q, Lau C, Kuan L, Henry AM.... (2014) A mesoscale connectome of the mouse brain. Nature, 508(7495), 207-14. PMID: 24695228  

  • April 21, 2014
  • 04:27 PM

Daylight Savings is a Public Health Concern. Who is responsible? The circadian system or sleep homeostat?

by Allison in Dormivigilia

A study published in 2013 did a US examination of the risk for heart attack from falling back or springing forward (Daylight Savings). The results mirror those of a landmark study on the subject. But neither study seems to think that disruption of circadian rhythms is responsible, but rather that one hour of precious sleep lost or gained...... Read more »

Jiddou MR, Pica M, Boura J, Qu L, & Franklin BA. (2013) Incidence of myocardial infarction with shifts to and from daylight savings time. The American journal of cardiology, 111(5), 631-5. PMID: 23228926  

  • April 21, 2014
  • 04:03 PM

Pyrolysis Biofuel Production Process Simplified

by dailyfusion in The Daily Fusion

Innovations at the U.S. Department of Agriculture (USDA) are bringing researchers one step closer to developing “green” biofuel production systems farmers can use to meet on-farm energy needs, or to produce renewable fuels for commercial markets.... Read more »

  • April 21, 2014
  • 03:00 PM


by Alex Giffen in Antisense Science

The health benefits of chocolate explained this Easter... Read more »

Katz, D., Doughty, K., & Ali, A. (2011) Cocoa and Chocolate in Human Health and Disease. Antioxidants , 15(10), 2779-2811. DOI: 10.1089/ars.2010.3697  

Franco R, Oñatibia-Astibia A, & Martínez-Pinilla E. (2013) Health benefits of methylxanthines in cacao and chocolate. Nutrients, 5(10), 4159-73. PMID: 24145871  

Selmi C, Cocchi CA, Lanfredini M, Keen CL, & Gershwin ME. (2008) Chocolate at heart: the anti-inflammatory impact of cocoa flavanols. Molecular nutrition , 52(11), 1340-8. PMID: 18991246  

Ellam S, & Williamson G. (2013) Cocoa and human health. Annual review of nutrition, 105-28. PMID: 23642199  

  • April 21, 2014
  • 12:47 PM

X-Rays Help Understand High-Temperature Superconductivity

by dailyfusion in The Daily Fusion

A new study pins down a major factor behind the appearance of laser-induced high-temperature superconductivity in a promising copper-oxide material.... Read more »

  • April 21, 2014
  • 09:00 AM

Rethinking anger on the road to peace

by Katharine Blackwell in Contemplating Cognition

Cognitive reappraisal, a technique for reinterpreting negative emotions in a more balanced or detached way, may have come across as a weak link in the mental modification toolkit last week: it did not succeed in making people more compassionate, and in fact seemed to make it easier for people to push away any guilt about taking a more selfish path. But while cognitive appraisal might not make people more altruistic, that reevaluation of emotion can make people less angry, and therefore more forgiving.... Read more »

  • April 21, 2014
  • 07:18 AM

What makes music groovy?

by Henkjan Honing in Music Matters

Last week PLOS ONE published an interesting study on rhythm, groove and syncopation that uses an often criticized methodology: questionnaire and web-based research...... Read more »

Witek, M., Clarke, E., Wallentin, M., Kringelbach, M., & Vuust, P. (2014) Syncopation, Body-Movement and Pleasure in Groove Music. PLoS ONE, 9(4). DOI: 10.1371/journal.pone.0094446  

Honing, H., & Reips, U.-D. (2008) Web-based versus lab-based studies: a response to Kendall (2008). Empirical Musicology Review, 3(2), 73-77. info:/

  • April 21, 2014
  • 05:15 AM

Lathosterolosis, cholesterol and autism?

by Paul Whiteley in Questioning Answers

Although intrigued by the findings reported by Pier Luigi Calvo and colleagues [1] describing a "unique case" potentially linking liver functions and cognitive functions with a hat-tip to the presentation of autistic behaviours, I'll readily admit that I am way out of my comfort and competence zones when discussing this paper so please be ready with that pinch of salt.How do you like your eggs in the morning? @ Wikipedia As per what the paper and accompanying press release (see here) indicate, this was a case report of a young girl diagnosed with lathosterolosis [2] - a rare inborn error of metabolism characterised by the accumulation of 5α-Cholest-7-en-3β-ol (lathosterol), an intermediate compound tied into the metabolism of cholesterol - and her changing clinical presentation following a liver transplant. The authors note that this was the "only surviving patient with lathosterolosis" such is the seriousness of the condition.In case you want the real heavy biochemistry, have a look at the paper by Brunetti-Pierri and colleagues [3] discussing all-things lathosterolosis and in particular, the crucial part played by the enzyme 3-beta-hydroxysteroid-delta-5-desaturase (sterol-C5-desaturase or SC5D) in the condition.The suggestion from the Calvo study that "timely liver transplantation might arrest the progression of neurological damage caused by diseases related to problems with cholesterol production" whilst sounding pretty invasive is nonetheless, of potential importance to a wider area of research. The details of outcome describing "a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture" at 5-year follow-up are nothing short of remarkable.As far as I can make out, quite a bit of the discussion where autism or autistic behaviours is mentioned revolves around the correlation between issues with social interaction, exploration of her environment and cholesterol biosynthesis, and what happened when cholesterol levels were normalised as a consequence of the liver transplant. Certainly this is not the first time that cholesterol and autism have been mentioned in the same breath together. In a post going back some years now, I talked about the various research in this area, and specifically a condition called Smith-Lemi Opitz syndrome (SLOS) which represents the prototypical 'issues with cholesterol formation can affect physiology and behaviour' condition. The paper by Sikora and colleagues [4] titled: 'The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome' kinda hinted at the link between SLOS and the presentation of autism/autistic behaviours, compounded by other data [5] (open-access here) correlating low cholesterol levels and autism in some cases. Remember: autisms not autism.Just in case anyone gets the wrong idea about my interpretation of this research, I'm not for one minute suggesting that a liver transplant is indicated for cases of autism outside of when medically required. As the study author notes: "We were dealing with a unique case—literally, as the child is the only known surviving patient with the condition—so it is difficult drawing inferences of broader significance". That however the liver provides an indispensable array of functions (see here too) might however mean that any whole body research approach applied to autism (not just looking at the grey/pinkish matter floating in the skull) might include some basic analysis of it's function too. As noted from other research in this area such as that included in the paper by Horvath & Perman [4] discussing sulphation (sulfation) capacity of the liver and cases of autism, there is potentially more to do in this area. Other work by Wakefield and colleagues [6] (open-access here) suggesting that: "hepatic encephalopathy represents a prototypic afferent gut–brain interaction that may provide insight into other encephalopathic states that have been linked to extra-cranial pathology", might also provide some food for thought in this area too.Finally, continuing the possibility of a cholesterol connection to some autisms, I'll refer you back to some very interesting data talked about on the SFARI blog last year (2013) on the possibility of statins and cholesterol supplements as areas of future investigation (with no medical or clinical advice given or intended). A hat-tip also goes to Peter over at the Epiphany blog and his series of articles on statins and autism too with some accompanying information about side-effects too [7].Music to close. And after recently watching the documentary on the reformation of the Stone Roses, a pretty famous song... Waterfall and memories of growing up listening to the Stone Roses the first time around come flooding back. ----------[1] Calvo PL. et al. Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis. Am J Transplant. 2014. March 12.[2] Krakowiak PA. et al. Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet. 2003 Jul 1;12(13):1631-41.[3] Brunetti-Pierri N. et al. Lathosterolosis, a Novel Multiple-Malformation/Mental Retardation Syndrome Due to Deficiency of 3β-Hydroxysteroid-Δ5-Desaturase. Am J Hum Genet. Oct 2002; 71(4): 952–958.[4] Sikora DM. et al. The near universal presence of autism spectrum disorders in children with Smith-Lemli-Opitz syndrome. Am J Med Genet A. 2006 Jul 15;140(14):1511-8.[5] Horvath K. & Perman JA. Autism and gastrointestinal symptoms. Curr Gastroenterol Rep. 2002 Jun;4(3):251-8.[6] Wakefield AJ. et al. Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands. Aliment Pharmacol Ther. 2002 Apr;16(4):663-74.[7] Finegold JA. et al. What proportion of symptomatic side effects in patients taking statins are genuinely caused by the drug? Systematic review of randomized placebo-controlled trials to aid individual patient choice. Euro J Preventive Cardiology. 2014;  March 12.----------... Read more »

Calvo, P., Brunati, A., Spada, M., Romagnoli, R., Corso, G., Parenti, G., Rossi, M., Baldi, M., Carbonaro, G., David, E.... (2014) Liver Transplantation in Defects of Cholesterol Biosynthesis: The Case of Lathosterolosis. American Journal of Transplantation. DOI: 10.1111/ajt.12645  

  • April 20, 2014
  • 11:45 PM

Cross-validation in finance, psychology, and political science

by Artem Kaznatcheev in Evolutionary Games Group

A large chunk of machine learning (although not all of it) is concerned with predictive modeling, usually in the form of designing an algorithm that takes in some data set and returns an algorithm (or sometimes, a description of an algorithm) for making predictions based on future data. In terminology more friendly to the philosophy […]... Read more »

  • April 20, 2014
  • 03:34 PM

420: How Marijuana Messes With the Brain

by Alexis Delanoir in How to Paint Your Panda

Cannabis use has previously been associated with cognitive impairment, and Smith et al. (2013) showed that heavy marijuana use was associated with poor working memory and brain abnormalities. Now, Gilman et al. (2014) propose that even casual use of marijuana is associated with such negative effects. Is this an issue of correlation/causation, of funding bias, or are the world's weed smokers really in neurological danger? In this post, in celebration of 4/20, I provide context for the recent study associating casual marijuana use with brain abnormalities and pose these questions.... Read more »

Meier, M., Caspi, A., Ambler, A., Harrington, H., Houts, R., Keefe, R., McDonald, K., Ward, A., Poulton, R., & Moffitt, T. (2012) Persistent cannabis users show neuropsychological decline from childhood to midlife. Proceedings of the National Academy of Sciences, 109(40). DOI: 10.1073/pnas.1206820109  

  • April 20, 2014
  • 09:31 AM

Was Lamarck right after all? A look at epigenetic inheritance

by EE Giorgi in CHIMERAS

Myths © EEGFrom the Wikipedia definition of epigenetics: "In biology, and specifically genetics, epigenetics is the study of heritable changes in gene activity that are not caused by changes in the DNA sequence."Wait a minute... how can we inherit anything that's not encoded in the DNA? All the information we inherit from our parents is coded in the DNA ... Right?That's correct. However, there's something very important that goes hand in hand with the information contained in the genes: how and when to use those genes. Not all genes are expressed in all cells at all times: different cells express different genes, depending on the tissue and function they need to fulfill. Epigenetics studies the changes inside the nucleus that determine which genes are expressed and which are, instead, silenced. It turns out, these changes happen throughout our life. And even though they are not "written" in our DNA, in some instances these acquired changed can indeed be passed on to future generations. This should be surprising. A mouse that loses its tail can still have offsprings with tails because the loss of the tail has not altered the DNA inside the mouse's cells. Yet, studies have altered in a similar way the eye color in fruit flies and the coat color in mice and shown that the changes were preserved in the next generation. In humans, there have been studies indicating that changes established not only through the mother's diet, but even through the father's diet could possibly affect the health of the embryo and be carried down to future generations."Animal models have also revealed that these diet-induced epigenetic changes are not limited to one generation, but can ripple down to descendants. Females with an increased disposition to metabolic problems during pregnancy can transfer this to their offspring [3]."Why is this relevant? Because some of these changes can increase the risk of diseases like cancer.For years we've been looking at associations between genetic variants and disease risks. Yet for most of the observed heritable diseases and cancers no responsible genes or alleles have been found. Could this be because the majority of heritable diseases are caused not by genetic mutations, but by epigenetic ones?As Heard and Martienssen state in a recent review Cell [1]:"Since the human genome was sequenced, the term epigenetics is increasingly being associated with the hope that we are more than just the sum of our genes [1]."Epigenetics makes you rethink genetics. Back in school we studied that Darwin was right and Lamarck was wrong: Lamarck's view of evolution was that phenotypes developed out of necessity to survive to the environment. For example, according to Lamarck, giraffes developed a long neck because they kept reaching for higher branches when feeding, and then this acquired trait was passed on to the next generations. Darwin, on the other hand, pointed out that the longer neck was just a random trait that appeared at some point during the evolution of giraffes. Giraffes with longer necks experienced an advantage over the ones with shorter necks because they could reach for better food. The long-neck giraffes had an advantage and had more and stronger offsprings than short-neck giraffes, and were therefore selected for. This view has led to two common misconceptions:Misconception #1: All genes we have today have been selected for. This is absolutely not true. Many of the mutations we see in the human genome today are due to random drift, basically the "reshuffling" of genes that happens from one generation to the next.Misconception #2: The environment cannot change our genome and therefore environmental exposures on one generation bear no effect on the following generation. Though this is what Darwin taught us, today we know that Lamarck was not completely wrong after all: while the environment cannot change our genes, it can indeed alter the way the genes work, and these changes can indeed be passed on to future generation. This has been the most surprising lesson epigenetics has taught us in the past few decades. Jean-Baptiste Lamarck was wrong because acquired traits cannot be inherited -- they need to be encoded in the genome in order to be passed on to the next generation. If you cut the tail of a mouse, the offsprings will still have tails. The theory that giraffes elongated their necks by stretching it farther to higher branches and that by doing so, their offsprings would naturally acquire a longer neck is wrong. However, it's interesting to note that Lamarck was a botanist and plants do employ epigenetics to pass acquired traits on to the next generation, a phenomenon called "epigenetic inheritance." The key point is this: the environment cannot change our genome, but it can indeed change the way our genes work (the "epigenome"). Epigenetics studies how these changes can be inherited across generations without being encoded in the genome. The paradox is the following: we, as individuals, constantly adapt to the environment around us. The best example is certainly the immune system, which, throughout our lifetime, learns to recognize pathogens and kill them. So, what pathogens we are exposed to can induce epigenetic changes. Stress and diet can also affect our metabolism through, again, epigenetic changes. These environment-induced changes affect different cells in our body. Yet, when an offspring is conceived, the very first cells during embryonic development have to be completely reset as they are the cells that will make all different organs in the new organism. It's like completely erasing your hard drive so you can start over. Mother nature does that through a mechanism called "epigenetic reprogramming:" all the lifelong acquired information from the parents is erased in the germline (cells that originate oocytes and spermcytes) and erased again during the first phases of embryonic development. Epigenetic changes not only take place during embryonic development, but also throughout the lifetime of an organism. The same mechanisms—notably DNA methylation and histone modification—have a role in the acquisition and maintenance of epigenetic changes induced by dietary or other environmental factors. [...] For a long time, scientists assumed that these environmentally induced changes lasted, at most, for the lifetime of the individual organism, but did not influence its offspring because gametogenesis would ‘wipe the slate clean' and the offspring would inherit a completely unadulterated set of genes. However, the specific mechanisms that cause the epigenetic modification of gene expression are now known to be involved in non-Mendelian—i.e. non-genetic—inheritance [3].Though the mechanism of "epigenetic inheritance" is not yet fully understood, scientists hypothesize that it could happen during this reprogramming when some markers are not completely erased. Another theory is that the intestinal flora could be transmitting information across generations. And finally, the information could be carried on to the next generation through modifications in the RNA.[1] Heard E, & Martienssen RA (2014). Transgenerational Epigenetic Inheritance: Myths and Mechanisms. Cell, 157 (1), 95-109 PMID: 24679529[2] Lim JP, & Brunet A (2013). Bridging the transgenerational gap with epigenetic memory. Trends in genetics : TIG, 29 (3), 176-86 PMID: ... Read more »

  • April 20, 2014
  • 06:03 AM

The Mystery of “Quantum Resonance Spectroscopy”

by Neuroskeptic in Neuroskeptic_Discover

Can quantum physics help to diagnose schizophrenia and depression? A paper just published in the Journal of Nervous and Mental Disease claims that a technique called ‘quantum resonance spectroscopy’ (QRS) can accurately diagnose various mental health problems. But is it quantum wizardry or magic quackery? According to the authors of the new paper, Zhang et […]The post The Mystery of “Quantum Resonance Spectroscopy” appeared first on Neuroskeptic.... Read more »

Zhang Y, Liu F, Shi J, Yue X, Zhang H, Du X, Sun L, & Yuan J. (2014) Exploratory quantum resonance spectrometer as a discriminator for psychiatric affective disorders. The Journal of nervous and mental disease, 202(4), 287-91. PMID: 24647211  

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