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  • August 11, 2014
  • 11:42 AM
  • 225 views

Clinical Drug Trials for Pathological Gambling

by William Yates, M.D. in Brain Posts

Several drug classes hold promise for reduction in pathological gambling behavior.However, there are very few published randomized and controlled clinical drug trials in gambling subjects.Searching clinical trials and gambling on PubMed yields only one small open-label proof of concept trial for the drug tolcapone within the last year.This study found evidence that this COMT inhibitor drug reduced gambling symptoms and was accompanied by fronto-parietal activation on fMRI imaging.However, on searching the clinicaltrials.gov website there are a few trials in progress or recently completed for gambling.Here are a few interesting studies from clinicaltrials.gov with public information about the trials that is listed on the site.Investigation of Naltrexone for Pathological GamblingThis Yale University study is currently listed as ongoing but not recruiting participants. This is a placebo controlled study using 50 mg of naltrexone, an opiate antagonist as active drug.  The primary outcome measure is the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (YBOCS-PG). The study has an estimated date of completion of February 2015.Memantine Treatment Study of Pathological GamblingThis open label study of the Alzheimer's drug memantine has some results published at clinicaltrials.gov but I could not find any on PubMed. Subjects in this study were treated with memantine 10 to 30 mg daily as tolerated. Mean YBOCS-PG scores decreased from 22 at baseline to 9 at 10 weeks. Open label studies are vulnerable to placebo effects.Clinical Study to Determine if Ecopipam Can Reduce Urges to GambleThis open label study investigated the effects of ecopipam a selective dopamine 1 receptor antagonist. Subjects were instructed to take a 50 mg tablet when they experienced an urge to gamble. The dose could be increased to 100 mg if the lower dose was ineffective. The study is listed as being completed in December of 2012 but I could find no published results on PubMed. The drug is reported to have reduced the YBOC-PG score from 28 to 14. An undefined safety issue is noted in the clinicaltrials.gov listing.Commentary:The relative paucity of published drug trial studies with only a few in progress suggests we are not really close to an effective drug treatment for gambling.In a future post, I will summarize some of the psychological treatment research on this topic.Photo of poker hand is from the author's files.Follow the author on Twitter WRY999.Grant JE, Odlaug BL, Chamberlain SR, Hampshire A, Schreiber LR, & Kim SW (2013). A proof of concept study of tolcapone for pathological gambling: relationships with COMT genotype and brain activation. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 23 (11), 1587-96 PMID: 23953269... Read more »

Grant JE, Odlaug BL, Chamberlain SR, Hampshire A, Schreiber LR, & Kim SW. (2013) A proof of concept study of tolcapone for pathological gambling: relationships with COMT genotype and brain activation. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 23(11), 1587-96. PMID: 23953269  

  • August 11, 2014
  • 09:38 AM
  • 197 views

Lithium For Aging Brain

by Vivek Misra in The UberBrain

Recent studies investigating Lithium, a drug commonly used for the treatment of mood disorders in humans, found its robust neurotrophic and neuroprotective effects which can help us exploring new novel, exciting, and promising targets. The molecular mechanism underlying lithium’s mood stabilizing effect is not yet unraveled. Suggested hypotheses include inositol-depletion via inhibition of inositol- monophosphatase and neuroprotection, via inhibition of GSK-3. Chronic lithium treatment increases dentate-gyrus neurogenesis in adult rodents [1], reduces mice immobility in the forced-swim test (FST) model of depression [2] and attenuates amphetamine-induced hyperlocomotion model of mania [3]. Bessa et al [4] showed that antidepressants retain antidepressant-like effect in the FST even when neurogenesis is blocked. It has been hypothesized that blockade of neurogenesis will not affect lithium’s behavioral impact. Specifically, we studied whether lithium-induced decreased immobility in the FST and attenuated amphetamine-induced hyperactivity remain under neurogenesis-arrest conditions. The results suggest that lithium’s effect on neurogenesis is not involved in its antidepressant-like mechanism. Given ample evidence suggesting that lithium promotes neurogenesis via GSK-3β inhibition [5] it is plausible that lithium’s antidepressant-like effect is not mediated via GSK-3β inhibition. Studies reported that, there is an increased neurogenesis in homozygote knockout mice of the inositol transporter. Since these mice exhibit lithium-like reduced brain inositol and behavioral phenotype [6] which suggest that inositol depletion rather than GSK-3 inhibition mediate lithium’s mood stabilizing effects. How this will benefit People with Dementia? One of the hallmarks of Alzheimer’s disease is the build-up of plaques of amyloid-beta, along with the neurofibrillary tangles, cause neurons to die, which leads […]
The post Lithium For Aging Brain appeared first on The UberBrain.
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Chen G, Rajkowska G, Du F, Seraji-Bozorgzad N, & Manji HK. (2000) Enhancement of hippocampal neurogenesis by lithium. Journal of neurochemistry, 75(4), 1729-34. PMID: 10987856  

O'Brien WT, Harper AD, Jové F, Woodgett JR, Maretto S, Piccolo S, & Klein PS. (2004) Glycogen synthase kinase-3beta haploinsufficiency mimics the behavioral and molecular effects of lithium. The Journal of neuroscience : the official journal of the Society for Neuroscience, 24(30), 6791-8. PMID: 15282284  

Berggren U, Tallstedt L, Ahlenius S, & Engel J. (1978) The effect of lithium on amphetamine-induced locomotor stimulation. Psychopharmacology, 59(1), 41-5. PMID: 100811  

Agam G, Bersudsky Y, Berry GT, Moechars D, Lavi-Avnon Y, & Belmaker RH. (2009) Knockout mice in understanding the mechanism of action of lithium. Biochemical Society transactions, 37(Pt 5), 1121-5. PMID: 19754464  

Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, Yang TH, Kim HM, Drake D, Liu XS.... (2014) REST and stress resistance in ageing and Alzheimer's disease. Nature, 507(7493), 448-54. PMID: 24670762  

  • August 11, 2014
  • 03:43 AM
  • 164 views

Risk of neurodevelopmental disorder in cases of hypospadias

by Paul Whiteley in Questioning Answers

"This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD [autism spectrum disorders] in their brothers, suggesting a common familial (genetic and/or environmental) liability".Rainy days and Mondays... @ Wikipedia That was the conclusion reached in the study by Agnieszka Butwicka and colleagues [1] looking at various neurodevelopmental outcomes associated with a diagnosis of hypospadias, a congenital condition characterised by an "aberrant opening of the urethra on the underside of the penis". The authors noted that: "Patients with hypospadias were more likely to be diagnosed with intellectual disability... ADHD... and behavioral/emotional disorders" compared with asymptomatic controls. Further: "Brothers of patients with hypospadias had an increased risk of ASD" when compared with siblings of asymptomatic controls. Ergo, the possibility of a 'link' between a physical condition and neurodevelopment potentially with a familial link.Whilst being the first study to look at the possible behavioural correlates associated with hypospadias, I might draw your attention to some mention of this condition and the presentation of autism or autistic-like behaviour as per papers like the one from Willatt and colleagues [2] or in the case of ADHD (attention-deficit hyperactivity disorder), the paper by Battaglia and colleagues [3]. In both cases, the focus of these papers were rare genetic conditions hinting as some shared role for genomic factors.That being said, the jury is still to some degree out about the possible cause(s) of hypospadias. The paper by Sharma and colleagues [4] talked about elevated blood cadmium and/or lead levels as being "associated with the increased risk of hypospadias". Knowing what we know about something like lead for example, and it's potential to affect developmental processes in quite small amounts (see here) might tie in well with such findings. Maternal exposure to specific chemicals (yes, that word again) has also been suggested to be potentially linked to hypospadias [5]. Certain pesticides reside in that 'chemical' category association too [6]. What this collected work points to is something suggesting that genes and environment variably interacting might also be a route to hypospadias, and onwards the correlation with neurodevelopmental conditions.Although the Butwicka paper talked about a sibling link between hypospadias and autism, my mind drifted back to the quite recent study by Rzhetsky and colleagues [4] (open-access) looking at congenital malformations of the reproductive study as surrogate markers for environmental exposures being linked to cases of autism (see here for that entry). At the time, I seem to remember there was some chatter about the usefulness of such data as surrogate markers for environmental exposure. What I think we might be able to draw from the Butwicka data is that hypospadias at least, might actual be quite a useful area for the continued study with neurodevelopmental conditions in mind.And to complement that painting, here are The Carpenters... (which might be particularly apt after the weather we've had here in Blighty recently).----------[1] Butwicka A. et al. Hypospadias and increased risk for neurodevelopmental disorders. Journal of Child Psychology and Psychiatry. 2014. July 22.  doi: 10.1111/jcpp.12290[2] Willatt L. et al. 3q29 microdeletion syndrome: clinical and molecular characterization of a new syndrome. Am J Hum Genet. 2005 Jul;77(1):154-60.[3] Battaglia A. et al. The FG syndrome: report of a large Italian series. Am J Med Genet A. 2006 Oct 1;140(19):2075-9.[4] Sharma T. et al. Heavy metal levels in adolescent and maternal blood: association with risk of hypospadias. ISRN Pediatr. 2014 Mar 4;2014:714234.[5] Thorup J. et al. Genetic and environmental origins of hypospadias. Curr Opin Endocrinol Diabetes Obes. 2014 Jun;21(3):227-32.[6] Michalakis M. et al. Hypospadias in offspring is associated with chronic exposure of parents to organophosphate and organochlorine pesticides. Toxicol Lett. 2013 Oct 25. pii: S0378-4274(13)01358-1.[7] Rzhetsky A. et al. Environmental and State-Level Regulatory Factors Affect the Incidence of Autism and Intellectual Disability. PLoS Comput Biol. 2014;  10(3): e1003518.----------Butwicka A, Lichtenstein P, Landén M, Nordenvall AS, Nordenström A, Nordenskjöld A, & Frisén L (2014). Hypospadias and increased risk for neurodevelopmental disorders. Journal of child psychology and psychiatry, and allied disciplines PMID: 25048198... Read more »

Butwicka A, Lichtenstein P, Landén M, Nordenvall AS, Nordenström A, Nordenskjöld A, & Frisén L. (2014) Hypospadias and increased risk for neurodevelopmental disorders. Journal of child psychology and psychiatry, and allied disciplines. PMID: 25048198  

  • August 11, 2014
  • 12:05 AM
  • 209 views

Emergency Room Visits for Sports Injuries

by Nicole Cattano in Sports Medicine Research (SMR): In the Lab & In the Field

Take Home Message: Sports-related injuries among teenagers accounts for over 430,000 emergency room visits in the United States in 2008 and represent a significant financial burden to the healthcare system.

Sports-related injuries in teenagers result in a significant number of emergency room visits, which can result in relatively large direct costs. However, little is known about national estimates of how many emergency room visits actually occur as well as the direct costs affiliated with this. The authors of this retrospective research study analyzed the 2008 Nationwide Emergency Department Sample data set for patient variables (e.g., age, sex, type of injury) among patients aged 13 to 19 years who visited an emergency room for a sports-related injury.... Read more »

Nalliah RP, Anderson IM, Lee MK, Rampa S, Allareddy V, & Allareddy V. (2014) Epidemiology of Hospital-Based Emergency Department Visits Due to Sports Injuries. Pediatric Emergency Care, 30(8), 511-515. PMID: 25062295  

  • August 10, 2014
  • 12:03 PM
  • 198 views

Pregnancy and Antibacterial Soap a Potentially Dangerous Combination

by Gabriel in Lunatic Laboratories

My wife likes to sanitize everything with bleach. I don’t really approve, but I bite my tongue because it makes her feel better. Germs are everywhere and honestly there is […]... Read more »

Pycke BF, Geer LA, Dalloul M, Abulafia O, Jenck AM, & Halden RU. (2014) Human biomonitoring of prenatal exposure to triclosan and triclocarban in a multiethnic urban population from Brooklyn, New York. Environmental Science , 8831-8838. info:/10.1021/es501100w

  • August 9, 2014
  • 01:45 PM
  • 474 views

Marijuana and the Developing Brain

by Gabriel in Lunatic Laboratories

You can’t get away from it, the big marijuana debate here in the US. Is it good? Is it bad? What are other countries doing? There are also a lot of claims made about marijuana, most of which aren’t true, namely the big medical claims. Then there is the other side of that fence, what about some of the health issues that are claimed, where does science sit on that?[…]... Read more »

Giedd JN, Blumenthal J, Jeffries NO, Rajapakse JC, Vaituzis AC, Liu H, Berry YC, Tobin M, Nelson J, & Castellanos FX. (1999) Development of the human corpus callosum during childhood and adolescence: a longitudinal MRI study. Progress in neuro-psychopharmacology , 23(4), 571-88. PMID: 10390717  

Giedd, J. N. (2004) Structural magnetic resonance imaging of the adolescent brain. Adolescent Brain Development: Vulnerabilities and Opportunities. info:/

Choo EK, Benz M, Zaller N, Warren O, Rising KL, & McConnell KJ. (2014) The impact of state medical marijuana legislation on adolescent marijuana use. The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 55(2), 160-6. PMID: 24742758  

Joffe A, American Academy of Pediatrics Committee on Substance Abuse, & American Academy of Pediatrics Committee on Adolescence. (2004) Legalization of marijuana: potential impact on youth. Pediatrics, 113(6), 1825-6. PMID: 15173518  

  • August 9, 2014
  • 12:46 PM
  • 234 views

Terminal Lucidity: Myth, Mystery or Miracle?

by Neuroskeptic in Neuroskeptic_Discover

Can sick people gain mental clarity just before they die? University of Virginia researchers Michael Nahm and Bruce Greyson explore this issue in a gripping (if macabre) paper published in the journal Omega: The death of Anna Katharina Ehmer: a case study in terminal lucidity.The authors discuss the case of Anna Katharina Ehmer, a German […]The post Terminal Lucidity: Myth, Mystery or Miracle? appeared first on Neuroskeptic.... Read more »

  • August 8, 2014
  • 06:00 PM
  • 166 views

Psychiatry and inflammation (again)

by Paul Whiteley in Questioning Answers

I'd like to bring two papers to your attention in today's very quick post."The Death Star plans are not in the main computer"First up is the article by Kahn & Sommer [1] (open-access) titled: 'The neurobiology and treatment of first-episode schizophrenia'. It's about as good a read as we have so far on the topic of "brain changes in the first phase of schizophrenia" and the various management options for first-episode schizophrenia. Outside of the very important fact that "It is highly unlikely that the pathogenesis of all patients with schizophrenia will be uniform", the authors make mention of the growing interest that "the signs and symptoms of schizophrenia is an increased proinflammatory status of the brain".Continuing on the topic of inflammation and psychiatry, which has been mentioned previously on this blog, the article by Friedrich [2] (open-access) is also worth a read which also covers anti-inflammatory treatment in schizophrenia. This paper has also been talked about with reference to inflammatory mechanisms potentially related to cases of autism (see here for some commentary).Cumulatively, these papers do a good job of bringing immune involvement in psychiatry to the forefront. The recent publication [3] suggestive of common genetic variants linked to schizophrenia and in particular "loci found in areas of the genome associated with the immune system" ties in well with the increased interest in issues like inflammation in relation to schizophrenia. The next question is 'where next?'.Music from a local band to finish: Frankie and the Heartstrings with Hunger. They also run quite a nice shop/store too (see here).----------[1] Kahn RS. Sommer IE. The neurobiology and treatment of first-episode schizophrenia. Mol Psychiatry. 2014. July 22.[2] Friedrich MJ. Research on Psychiatric Disorders Targets Inflammation. JAMA 2014. July 23.[3] Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014; 511: 421-427.----------Kahn RS, & Sommer IE (2014). The neurobiology and treatment of first-episode schizophrenia. Molecular psychiatry PMID: 25048005Friedrich MJ (2014). Research on Psychiatric Disorders Targets Inflammation. JAMA : the journal of the American Medical Association PMID: 25054339... Read more »

  • August 8, 2014
  • 03:36 PM
  • 237 views

The Self Assembling Brain

by Gabriel in Lunatic Laboratories

Let’s face it, if the brain were a lego set I would still be staring at the box wondering what I got myself into. So I guess we can just […]... Read more »

Lorenzo I. Finci et. al. (2014) The Crystal Structure of Netrin-1 in Complex with DCC Reveals the Bifunctionality of Netrin-1 As a Guidance Cue. Neuron. info:/http://dx.doi.org/10.1016/j.neuron.2014.07.010

  • August 8, 2014
  • 12:13 PM
  • 145 views

Melanoma, UV radiation, and TP53

by Aurelie in Coffee break Science

It’s summer, and time to get some tan. Many people flock to beaches and parks and expose as much skin as possible, bathing in sunlight – and ultraviolet (UV) radiation. Over the past decades, public health campaigns have rather successfully … Continue reading →... Read more »

Viros A, Sanchez-Laorden B, Pedersen M, Furney SJ, Rae J, Hogan K, Ejiama S, Girotti MR, Cook M, Dhomen N.... (2014) Ultraviolet radiation accelerates BRAF-driven melanomagenesis by targeting TP53. Nature, 511(7510), 478-82. PMID: 24919155  

  • August 8, 2014
  • 09:13 AM
  • 111 views

Translational Findings: How fruit fly research has already contributed to human health

by Bethany Christmann in Fly on the Wall

How have fruit flies already contributed to human health? I review four landmark fly papers that won their authors Nobel Prizes in Physiology or Medicine. ... Read more »

  • August 8, 2014
  • 08:01 AM
  • 194 views

Researchers Uncover Stem Cell Behaviour of Human Bowel

by beredim in Stem Cells Freak

For the first time, researchers say they have uncovered new information on how stem cells in the human bowel behave, revealing vital clues about the earliest stages in bowel cancer development and how we may begin to prevent it.The research, led by Queen May University of London (QMUL) and published yesterday the journal Cell Reports, discovered how many stem cells exist within the human bowel and how they behave and evolve over time.Read More... Read more »

Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon. (2014) Ann-Marie Baker, Biancastella Cereser, Samuel Melton, Alexander G. Fletcher, Manuel Rodriguez-Justo, Paul J. Tadrous, Adam Humphries, George Elia, Stuart A.C. McDonald, Nicholas A. Wright, Benjamin D. Simons, Marnix Jansen, Trevor A. Graham. Cell Reports. info:/10.1016/j.celrep.2014.07.019

  • August 7, 2014
  • 02:11 PM
  • 280 views

Nerve Regeneration: Another Piece of the Stem Cell Puzzle

by Gabriel in Lunatic Laboratories

Almost everyone regenerates nerves, but you! Sure, yesterday we talked about how other animals in the kingdom regenerate damaged nerves and how we got left in the dust. But we […]... Read more »

  • August 7, 2014
  • 01:06 PM
  • 188 views

Researchers Grow Human Gastrointestinal Cells Using Epithelial Stem Cells

by beredim in Stem Cells Freak

Kelli L. VanDussen, PhD, and Matthew A. CiorbaA method of growing human cells from tissue removed from a patient's gastrointestinal (GI) tract may one day help scientists develop tailor-made therapies for inflammatory bowel disease and other GI-related conditions.Reporting online recently in the journal Gut, researchers from the Washington University School of Medicine in St. Louis said they have made cell lines from individual patients in as little as two weeks.They have created more than 65 such cell lines using tissue from 47 patients who had routine endoscopic screening procedures, such as colonoscopies. A cell line is a population of cells in culture with the same genetic makeup.The researchers said the cell lines can help them understand the underlying problems in the GI tracts of individual patients and be used to test new treatments.Read More... Read more »

  • August 7, 2014
  • 12:53 PM
  • 207 views

Harvard Researchers Identify New Potential Treatment for Amyotrophic Lateral Sclerosis

by beredim in Stem Cells Freak

This image depicts graduate student Sophie De Boer, (left), and Prof. Kevin Eggan (right) discussing their latest work.Credit: B. D. Colen/Harvard UniversityAbout eight years ago, researchers at the Harvard Stem Cell Institute (HSCI) begun a series of studies that led to a report published today which may be a major step forward in thequest to developing real treatments for amyotrophic lateral sclerosis (ALS).The findings by Harvard professor of Stem Cell and Regenerative Biology (HSCRB) Kevin Eggan and his team have also produced functionally identical results in human motor neurons in a laboratory dish and in a mouse model of the disease, demonstrating that the modeling of human disease with customized stem cells in the laboratory could someday relatively soon eliminate some of the need for animal testing.The new study, appearing in Science Translational Medicine, suggests that compounds already in clinical trials for other purposes may be promising candidate therapeutics for ALS.Read More... Read more »

de Boer, A., Koszka, K., Kiskinis, E., Suzuki, N., Davis-Dusenbery, B., & Eggan, K. (2014) Genetic validation of a therapeutic target in a mouse model of ALS. Science Translational Medicine, 6(248), 248-248. DOI: 10.1126/scitranslmed.3009351  

  • August 7, 2014
  • 08:00 AM
  • 228 views

Thinking Makes My Head Hot

by Mark E. Lasbury in The 'Scope

The new movie, Lucy, contends that we only use 10% of our brain. Interesting, and true if you interpret the statement in one particular way. The interesting thought experiment is a contemplation of what would happen to us if we did only use 10% of our brain and then learned to use 100%. We would probably starve and die of fever. Research studies show that increased mental activity can lead to increased brain temperature, so should we should be picking kids for the gifted/talented program by temperature?... Read more »

Mrozek, S., Vardon, F., & Geeraerts, T. (2012) Brain Temperature: Physiology and Pathophysiology after Brain Injury. Anesthesiology Research and Practice, 1-13. DOI: 10.1155/2012/989487  

  • August 7, 2014
  • 03:42 AM
  • 165 views

Vitamin D and schizophrenia meta-analysed

by Paul Whiteley in Questioning Answers

It's been a few weeks since I last talked about vitamin D on this blog and some finding or other talking about a deficiency of the stuff. Indeed, the last occasion was the publication of the Eva Kočovská study (see here) talking about issues with vitamin D being present across quite a few people on the autism spectrum, continuing a research trend (see here).So as to remedy this vitamin D blogging deficiency, today I'm talking about the systematic review and meta-analysis by Ghazaleh Valipour and colleagues [1] who concluded: "the overall prevalence of vitamin D deficiency in schizophrenic patients was 65.3% (95% CI 46.4%–84.2%)". They called it a 'strong' association between issues with vitamin D and schizophrenia and add that there is a requirement for quite a bit more research in this area. Some of the accompanying media to this research can be seen here.A quick look at some of the studies included in the Valipour paper and the wider peer-reviewed evidence on the topic of vitamin D and schizophrenia suggests that there is quite a bit of research history in this area. The paper by McGrath and colleagues [2] (open-access here) quite neatly summarises some of the possible hows and whys of the 'vitamin D hypothesis of schizophrenia' covering variables like "season of birth, place of birth, and migrant status". Some of the same authors have looked at issues such as neonatal vitamin D status and subsequent risk of schizophrenia [3], reporting some intriguing results based on both low and high concentrations "associated with increased risk of schizophrenia". Quite a lot of the research literature has also focused on the psychosis aspect to schizophrenia and how that might fit with the vitamin D aspect. Crews and colleagues [4] for example, reported "higher rates of vitamin D deficiency in people with FEP [first episode psychosis] compared to matched controls". This follows other research hinting at similar findings [5].The issue of vitamin D supplementation as potentially modifying either risk of schizophrenia or the course of the condition is a slightly more under-researched aspect. Again, McGrath and colleagues [6] have reported results based on retrospective analysis of vitamin D supplementation during infancy impacting on adult risk of schizophrenia, indicating that "either irregular or regular vitamin D supplements was associated with a reduced risk of schizophrenia". Without any medical or clinical advice given or intended they suggested that "the use of at least 2000 IU of vitamin D was associated with a reduced risk of schizophrenia (RR=0.23, 95% CI 0.06-0.95) compared to those on lower doses". When it comes to vitamin D as an intervention for current presentation of schizophrenia, the research literature is a little less generous in terms of output.Reproduced from Gröber et al (2013)The question of how and why vitamin D might impact on the risk or presentation of schizophrenia is as yet unanswered. The excellent review on all-things vitamin D by Uwe Gröber and colleagues [7] (open-access) offers quite a few possible suggestions why vitamin D might impact on the condition. I've taken the liberty of reproducing a diagram from their paper, so take your pick.The brain is one of the target organs for vitamin D as for example, discussed by Groves and colleagues [8]. My continuing interest in all-things epigenetic is also served by the paper from Fetahu and colleagues [9] (open-access) talking about vitamin D and epigenome. Immune system effects associated with vitamin D [10] (open-access) also represents a growth area which might be pertinent to cases of schizophrenia particularly when it comes to inflammation or inflammatory responses and something like gastrointestinal inflammation [11] in light of other findings in schizophrenia. The immune system effects of vitamin D might also be regarded more highly in light of the recent news that among the increasing number of genes potentially related to schizophrenia are some "providing support for the speculated link between the immune system and schizophrenia" [12]. I'm sure there are other potentially important variables too.Anyone who follows the peer-reviewed literature on vitamin D will not doubt have noted a bit of an explosion in interest on the sunshine vitamin/hormone. You name the condition, and someone, somewhere, will probably have investigated the link with vitamin D. Hypertension, check [13]. Cancer mortality, check [14]. Depression, check (see here). ADHD, check (see here). And the list goes on and on, bearing in mind the old adage: correlation is not the same as causation. Given the pervasiveness of vitamin D deficiency and it's potential links to so many different conditions or health issues, it is tempting to think that any correlation is merely coincidental or spurious. Surely this vitamin/hormone could not be acting so widely?Personally, I'm keeping an open mind about the many and varied links reporting in the scientific literature about vitamin D. The Valipour paper at the very least, suggests that quite a bit more research effort might need to be directed towards vitamin D and schizophrenia; if not universally relevant to the condition, perhaps just to a subgroup or two...Music. The Lovecats by The Cure.----------[1] Valipour G. et al. Serum Vitamin D Levels in Relation to Schizophrenia: A Systematic Review and Meta-Analysis of Observational Studies. JCEM. 2014. July 22.[2] McGrath JJ. et al. Developmental vitamin D deficiency and risk of schizophrenia: a 10-year update. Schizophr Bull. 2010 Nov;36(6):1073-8.[3] McGrath JJ. et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010 Sep;67(9):889-94.[4] Crews M. et al. Vitamin D deficiency in first episode psychosis: a case-control study. Schizophr Res. 2013 Nov;150(2-3):533-7.[5] Belvederi Murri M. et al. Vitamin D and psychosis: mini meta-analysis. Schizophr Res. 2013 Oct;150(1):235-9.[6] McGrath J. et al. Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study. Schizophr Res. 2004 Apr 1;67(2-3):237-45.[7] Gröber U. ... Read more »

  • August 6, 2014
  • 03:46 PM
  • 124 views

Molecular Competition Drives Adult Stem Cells to Specialize

by beredim in Stem Cells Freak

All adult organisms ranging from fruit flies to humans harbor adult stem cells, some of which renew themselves through cell division while others differentiate into the specialized cells needed to replace worn-out or damaged organs and tissues.Understanding the molecular mechanisms that control the balance between self-renewal and differentiation in adult stem cells is an important foundation for developing therapies to regenerate diseased, injured or aged tissue.Now, in the latest issue of the journal Nature, researchers at the Stowers Institute for Medical Research report that competition between two proteins, Bam and COP9, balances the self-renewal and differentiation functions of ovarian germline stem cells (GSCs) in fruit flies (Drosophila melanogaster).Read More... Read more »

  • August 6, 2014
  • 01:29 PM
  • 348 views

Nerve Regeneration: Everyone does it, but you

by Gabriel in Lunatic Laboratories

Dogs do it, frogs do it, and even whales do it! No this isn’t everyone poops. I’m talking about regrowing nerves after an injury and sadly, we don’t do it… yet. […]... Read more »

  • August 6, 2014
  • 12:01 PM
  • 200 views

Brain Striatum and Loss-Chasing in Gambling

by William Yates, M.D. in Brain Posts

Pathological gambling (PG) is a pattern of gambling characterized by loss of control and large gambling debts.The near-miss phenomenon in gambling is the gaming scenario where gamblers sense they were very close to winning.This near-miss phenomenon can be programmed into slot machines. For example, a gambler might be presented frequently with four cherries when five cherries would result in a huge payout.The response to the near-miss in PG is often a sense that a big win is just around the corner prompting continued gambling losses.Ruth J. van Holst from the University of Cambridge recently present an interesting study of brain connectivity and the near-miss phenomenon.In this study, a series of twenty regular gamblers rated on gambling severity were compared to fifteen non-regular gamblers using brain connectivity imaging with fMRI.Subjects were scanned while being presented three slot machine scenarios including win, near-miss loss, and loss. Subjects received a monetary reward (0.5 pounds or about .85 U.S. dollars).The brain region known as the striatum (caudate nucleus and putamen) are known to be key regions in reward processing. With this knowledge, the research team examined connectivity patterns in the case and control group starting with the striatum as a "seed" region.The key findings from the study included the following:Gambling severity ratings positively correlated with enhanced connectivity between the ventral striatum and brain insula bilaterallyGambling wins versus near-miss and non-near miss losses were correlated with enhanced connectivity between striatum, left orbitofrontal cortex and posterior insulaGambling wins versus near-miss and non-near miss losses were correlated with reduced connectivity between striatum and the left anterior cingulate cortexThe authors note their research support a key cognitive distortion in gamblers. A near-miss and a non near-miss scenario produce the same payout, zero. Statistically, they are identical outcomes.However, gamblers appear to have a heightened false positive reward signal along with "illusion of control" when a near-miss gambling episode is experienced.The authors note:"Based on the present findings, we would hypothesize that excessive insula recruitment during illusion of control may be a risk factor for the cognitive distortions and loss-chasing that are characteristic of problem gambling."This current study is promising and will need replication. However, it suggests there may be a way to use fMRI functional connectivity to assess abnormal brain circuitry in those with a pathological gambling problem.Additionally, these gambling circuit abnormalities may be targeted in designing and assessing response to cognitive interventions in those with pathological gambling.Readers with more interest in this research can find the free full-text manuscript by clicking on the PMID link below.Figure is an iPad screen shot from app 3D Brain from the author's files.Follow the author on Twitter at WRY999 van Holst RJ, Chase HW, & Clark L (2014). Striatal connectivity changes following gambling wins and near-misses: Associations with gambling severity. NeuroImage. Clinical, 5, 232-9 PMID: 25068112... Read more »

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