A new study by researchers at the Karolinska Institutet,Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings appear in the journal EMBO Reports .The MYC gene encodes the protein with the same name, and has an important role in many cellular processes such as proliferation, metabolism, cell death and the potential of differentiation from immature stem cell s to different types of specialized cells . Importantly it is also one of the most frequently activated genes in human cancer.Read More... Read more »
Zinin N, Adameyko I, Wilhelm M, Fritz N, Uhlén P, Ernfors P, & Henriksson MA. (2014) MYC proteins promote neuronal differentiation by controlling the mode of progenitor cell division. EMBO reports. PMID: 24599748
Today I'm highlighting the paper by Krystle Graham and colleagues  which talked about a possible association between the presence of urinary tract infections (UTIs) in various types of psychosis. With my interest in all things biology-behaviour, remembering such posts as impulsivity and uric acid (see here), once again we have an example of how the two areas just might fit together.The bullfighter (deceased) @Manet @Wikipedia So, take several groups of adult participants who were admitted "for an acute episode of DSM-IV nonaffective psychosis..., affective psychosis... or alcohol detoxification" and compare with an asymptomatic control group. Analyse for the presence of laboratory-confirmed UTI and voilà, after controlling for potentially confounding variables "UTI was almost 11 times more likely in subjects with nonaffective psychosis than controls". That and the fact that in cases of affective psychosis (major depressive disorder with psychotic features) the odds ratio for a UTI was up at nearly 9x more likely.Coincidence I hear you cry. Well it certainly could be. But the data is strengthened by the fact that this is not the first time that this association has cropped us as per another paper by the same authors  covered by Dr Emily Deans over at Evolutionary Psychiatry. The fact that UTIs show more than a passing connection to behavioural and psychiatric features as per the evidence looking at delerium  for example should also be mentioned.As to the reason for the association, well to quote from the NHS Choices entry on the causes of UTI: "Most urinary tract infections (UTIs) are caused by bacteria that live in the digestive system". The process of how said bacteria get from bowel to erm, nether regions is slightly more complex and could be related to hygiene practices (remember: wipe from front to back after going to the toilet) or other behaviours. One can't exclude the possibility that where psychosis occurs, such factors might come into play.That being said, I'm also quite interested in whether there may be other reasons for the association made by Graham et al. Readers might remember back to a post I wrote recently on bacterial infections and behaviour (see here) part of which mentioned the paper by Blomström and colleagues  on bacterial infections requiring hospital admission and risk of later nonaffective psychosis. Given the focus on childhood in that paper, which I assume to some degree negates the possibility of sexual activity or kidney stones or a urinary catheter as being a primary cause of a bacterial infection like a UTI, one wonders if there may be something more biologically fundamental to account for the association.Indeed, a quick trawl through the collected research literature in this area reveals some potentially relevant findings in relation, for example, to the development of psychosis after a kidney transplant  (open-access) and how this particular patient developed anti-NMDAR encephalitis (see here). I'm wondering whether immune suppression may be a contributing factor to the UTI - psychosis correlation, as per data on the infections favoured following something like organ transplant  and the degree to which UTIs are involved. That being said, a role for the immune system in psychosis is a mighty complicated subject as per other posts on this blog (see here and see here) and short of suggesting that immune function might be involved in the link with elevated rates of UTIs in cases, there's few comprehensive answers to account for the association at the current time.Still it is an interesting area of work, also raising the question: does the treatment of UTIs have any effect on presented psychosis symptoms? Bearing in mind, the evidence so far seems a little bit contrary... [Finish post with head scratch and confused look].Music to close. Pavement and Cut Your Hair...----------- Graham KL. et al. Urinary tract infections in acute psychosis. J Clin Psychiatry. 2014. Jan 21. [Epub ahead of print] Miller BJ. et al. A prevalence study of urinary tract infections in acute relapse of schizophrenia. J Clin Psychiatry. 2013 Mar;74(3):271-7. Lin RY. et al. Clinical associations of delirium in hospitalized adult patients and the role of on admission presentation. Int J Geriatr Psychiatry. 2010 Oct;25(10):1022-9. Blomström A. et al. Hospital Admission With Infection During Childhood and Risk for Psychotic Illness--A Population-based Cohort Study. Schizophr Bull. 2013 Dec 23. Zhao CZ. et al. Clinical reasoning: agitation and psychosis in a patient after renal transplantation. Neurology. 2012 Jul 31;79(5):e41-4. Galindo Sacristán P. et al. Predictive factors of infection in the first year after kidney transplantation. Transplant Proc. 2013 Dec;45(10):3620-3.---------- Graham KL, Carson CM, Ezeoke A, Buckley PF, & Miller BJ (2014). Urinary tract infections in acute psychosis. The Journal of clinical psychiatry PMID: 24499998... Read more »
Prehistoric giant virus buried in the Siberian ice recovered from a scientific expedition. No, it is not the plot of “The Thing”, but the utter truth: a thirty- thousand- year old virus, whose dimensions are 50 times bigger than the ones of average virus from today, was found by Abergel and Claverie’s team in the Russian permafrost.... Read more »
Legendre M, Bartoli J, Shmakova L, Jeudy S, Labadie K, Adrait A, Lescot M, Poirot O, Bertaux L, Bruley C.... (2014) Thirty-thousand-year-old distant relative of giant icosahedral DNA viruses with a pandoravirus morphology. Proceedings of the National Academy of Sciences of the United States of America. PMID: 24591590
Philippe N, Legendre M, Doutre G, Couté Y, Poirot O, Lescot M, Arslan D, Seltzer V, Bertaux L, Bruley C.... (2013) Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes. Science (New York, N.Y.), 341(6143), 281-6. PMID: 23869018
Therapeutic alliance is often highlighted in studies looking at treatment effectiveness, both in and beyond the realm of eating disorder therapy. Evidently, there are a number of factors that can impact how well we get along with our therapists, ranging from disagreements with the course of treatment or type of therapy to a simple, unnamable dislike for the person. But what about their appearance? What kind of impact could a therapist’s body size have on the therapy relationship?
Rance, Clarke & Moller (2014) sought out to investigate this issue, looking specifically at how clients evaluate therapists’ body size and speculate on their relationship with food, with an eye to determine what impact this might have on the therapeutic process.
I was immediately drawn to this study when I was browsing the latest literature; I wondered why this hadn’t been studied before. In some ways it seems obvious; we’re bound to compare ourselves with others, social beings that we are. So when looking at the therapeutic alliance, it would be illogical to assume that physical appearance could be left …
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Rance, N,M., Clarke, V., & Moller, N.P. (2014) "If I See Somebody … I'll Immediately Scope Them Out": Anorexia Nervosa Clients' Perceptions of Their Therapists' Body. Eating Disorders, 22(2), 111-20. PMID: 24555509
That an early pregnancy is protective against breast cancer is something I've known for ten years now. I remember one of my professors, back when I started studying genetics, saying: "Having a baby at 16 may ruin your life but it sure protects you from breast cancer." Today we know a lot more about the cellular and genetic mechanisms that a first pregnancy triggers in the body. And yet how these mechanisms turn out to be protective against breast cancer is still a mystery. "The ovarian hormones, estrogen and progesterone, play a pivotal role in normal and neoplastic development of the mammary gland. These hormones have a paradoxical role as long duration of estrogen and progesterone are associated with increased breast cancer risk, while short duration of pregnancy level doses are associated with a reduced breast cancer risk ."Pregnancy levels of these two hormones induce permanent changes in gene expression that result in the life-long protective effect against breast cancer. This has been achieved in mouse models, too, by mimicking pregnancy through hormonal administration, followed by carcenogenesis challenges (the poor little mice are exposed to stuff that normally raises breast cancer risk). What I found surprising, and that I didn't know ten years ago, is that there is a slight increase in breast cancer risk after pregnancy, and this risk increases with age, as shown in the graph below (from ):The graph above, published in , is a qualitative summary from various epidemiological studies. The "base-level" risk for breast cancer is by definition the risk of a nulliparous woman (a woman who's never been pregnant). I originally thought that a full term pregnancy had a protective effect on breast cancer, no matter at what age, and that the protection diminished with age. However, there is a temporary increase in risk following the pregnancy, and this temporary increase grows with age. During pregnancy, both estrogen and progesterone levels rise drastically and temporarily increase the risk of breast cancer. The earlier in life the pregnancy, the lower this increase in risk, and, in the long term, the risk gets reversed drastically. However, for first pregnancies at an older age the temporary increase in risk is much higher and it takes much longer to reverse to the protective effect. As a consequence, having a first child after 35 years of age puts a woman at a higher risk compared to a woman who has never been pregnant. Furthermore, the protective effect is negligible in the presence of the BRCA1 and/or BRCA2 mutations, or with breast cancers that are estrogen/progesterone negative (the cancer cells do not have estrogen/progesterone receptors). Finding the epidemiological mechanisms that establish the life-long protection inferred by an early pregnancy could pave the way to better prevention and treatments. Meier-Abt and Bentires-Alj's review  is available for free from Cell and I highly recommend it as it has a nice overview of breast cancer risk as well as the current knowledge on the mechanisms that link early pregnancy to protection:"Most probably, the individual mechanisms are not mutually exclusive and the full protective effect results from a combination of several processes ."Besides estrogen and progesterone, the growth hormone (GH) and prolactin (PRL) also control the development of the mammary gland. And while estrogen and progesterone levels do not change after a woman has had her first child, PRL levels do. Mouse models have found that decreased PRL and GH levels favor cancer regression in animals with mammary tumors, whereas other studies have associated increased levels of PRL and GH with a higher incidence of breast cancer. Another theory is that mammary cells become less responsive to estrogen and progesterone after pregnancy, and this could be another factor lowering the risk of cancer. It is consistent with the fact that longer exposure to these hormones, on the other hand, increases the risk. In , the authors also list some interesting pathway signaling changes observed after early pregnancy that could be associated with breast cancer protection. One pathway in particular, called wingless related protein (Wnt) signaling, is downregulated after early pregnancy. The pathway is involved in binding ligands from the outside surface of the cell and passing the signal to the inside."In women, pregnancy leads to a reduction in the number of hormone-responsive cells and preferential downregulation of protumorigenic genes and pathways in a subset of progenitor cells isolated from normal human breast tissue. The studies point towards the use of Wnt inhibitors to mimic the protective effect against breast cancer of early pregnancy, a finding consistent with the known potent antiproliferation and anticancer activity of Wnt inhibition ."The authors conclude with some outstanding questions that still need to be answered before we can use the information to develop a successful preventive strategy. In particular:"Does pregnancy at a late age (late pregnancy) fail to induce similar cellular and molecular changes as pregnancy at an early age? And if so, does this explain the absence of parity-induced protection against breast cancer after late pregnancy?" Medina D (2005). Mammary developmental fate and breast cancer risk. Endocrine-related cancer, 12 (3), 483-95 PMID: 16172188 Meier-Abt F, & Bentires-Alj M (2014). How pregnancy at early age protects against breast cancer. Trends in molecular medicine, 20 (3), 143-153 PMID: 24355762... Read more »
Medina D. (2005) Mammary developmental fate and breast cancer risk. Endocrine-related cancer, 12(3), 483-95. PMID: 16172188
Meier-Abt F, & Bentires-Alj M. (2014) How pregnancy at early age protects against breast cancer. Trends in molecular medicine, 20(3), 143-153. PMID: 24355762
The Effect of Cadence Manipulation on Plantar Pressures... Read more »
Wellenkotter, J., Kernozek, T., Meardon, S., & Suchomel, T. (2014) The Effects of Running Cadence Manipulation on Plantar Loading in Healthy Runners. International Journal of Sports Medicine. DOI: 10.1055/s-0033-1363236
To identify the mutations that generated the most relapse-prone leukemia, the scientists competed single cancer cells against each other within a zebrafish.Credit: Jessica Blackburn/Massachusetts General HospitalHarvard stem cell scientists have identified a mutation in human cases of acute lymphoblastic leukemia that likely drives relapse. The research, published in Cancer Cell, could translate into improved patient care strategies for this particular blood cancer, which typically affects children but is more deadly in adults.In recent years, a trend toward single-cell analysis has shown that individual cells within a tumor are capable of amassing mutations to make them more aggressive and treatment resistant. So while 99% of a tumor may be destroyed by the initial treatment, a particularly aggressive cell can survive and then cause a cancer patient with the "all clear" to relapse six months later.Harvard Stem Cell Institute Principal Faculty member David Langenau, PhD, and his lab members in the Department of Pathology at Massachusetts General Hospital used zebrafish to search for these rare, relapse-driving leukemia cells and then designed therapies that could kill these cells.Read More... Read more »
Jessica S. Blackburn, Sali Liu, Jayme L. Wilder, Kimberly P. Dobrinski, Riadh Lobbardi, Finola E. Moore, Sarah A. Martinez, Eleanor Y. Chen, Charles Lee, David M. Langenau. (2014) Clonal Evolution Enhances Leukemia-Propagating Cell Frequency in T Cell Acute Lymphoblastic Leukemia through Akt/mTORC1 Pathway Activation. Cancer Cell. info:/10.1016/j.ccr.2014.01.032
The paper by Michael Benrós and colleagues  talking about an "increased risk of subsequent autoimmune diseases in individuals with schizophrenia" caught my eye recently. Based on a trawl of the records of several thousands of people with "schizophrenia-like psychosis" or "individuals with autoimmune disease" derived from Danish nationwide registers (see here for some background), the authors were able to conclude that "Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia". By the way, this is not the first time that authors linked to this paper have published on this topic  based on similar analyses. Further coverage of this paper can also be found here.And don't forget your lute.. @ Wikipedia As far as I'm aware, I've not yet covered the issue of autoimmune conditions being correlated with a diagnosis of schizophrenia on this blog. Regular readers might already know about my interest in all things autoimmunity when it comes to autism. Be it the markers of autoimmunity (see here and see here) or the seemingly wide range of conditions correlating with the appearance of autism (see here), I certainly believe that there is more to see here from a research point of view. With the schizophrenia data in mind it appears that I should perhaps be casting the research net a little wider; perhaps even talking about some closer links?As Benrós et al note there is already some research form in the area linking schizophrenia and autoimmune conditions. Outside of the autoantibody side of things  and that very interesting link to anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis  I note some of the data available in this area to be quite nicely summarised by Davison  (open-access) specifically with the Chen paper  (open-access) in mind. Taking a few conditions noted by Chen and colleagues, I was interested to see that risk of psoriasis was elevated in cases of schizophrenia as per my interest in this skin condition with autism in mind (see here). Given my focus on / obsession with all things gluten too, the fact that a diagnosis of schizophrenia also elevated the risk of coeliac (celiac) disease similarly piqued my interest and brought back floods of memories about the late Curt Dohan and his life's work in this area (see here). In light of the not-quite-coeliac-disease-but-something-else paper on autism and gluten-related serology it also asks the question of how deep the rabbit hole might actually go?The same questions remain about this work as they do when it comes to examining any link between autism and autoimmune conditions - whether first person or familial: What are the common denominators in terms of genes and biochemistry? Are there shared susceptibility factors evident in schizophrenia and selected autoimmune diseases including infection? But also I'm getting pretty interested in some new areas of potential overlap such as any effects from those very old HERVs (human endogenous retroviruses) and whether through expression of HERV proteins, for whatever reason(s), they are participating in a series of events heading towards autoimmunity? Well, it's not as if HERVs haven't been mentioned with schizophrenia  or autoimmune diseases in mind  but I'll wait and see how this pans out.Fantastic Mr Fox y'say.... Will you join me? (whistle/click)---------- Benrós ME. et al. A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. Am J Psychiatry 2014;171:218-226. Eaton WW. et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry. 2006 Mar;163(3):521-8. Ezeoke A. et al. A systematic, quantitative review of blood autoantibodies in schizophrenia. Schizophr Res. 2013 Oct;150(1):245-51.  Pollak TA. et al. Prevalence of anti-N-methyl-d-aspartate (NMDA) antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis. Psychol Med. 2013 Dec 13:1-13. Davison K. Autoimmunity in psychiatry. Br J Psychiatry. 2012 May;200(5):353-5. Chen SJ. et al. Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study. Br J Psychiatry. 2012 May;200(5):374-80. Frank O. et al. Human endogenous retrovirus expression profiles in samples from brains of patients with schizophrenia and bipolar disorders. J Virol. 2005 Sep;79(17):10890-901. Brodziak A. et al. The role of human endogenous retroviruses in the pathogenesis of autoimmune diseases. Med Sci Monit. 2012 Jun;18(6):RA80-8.----------Benrós ME, Pedersen MG, Rasmussen H, Eaton WW, Nordentoft M, & Mortensen PB (2013). A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. The American journal of psychiatry PMID: 24129899... Read more »
Benrós ME, Pedersen MG, Rasmussen H, Eaton WW, Nordentoft M, & Mortensen PB. (2013) A Nationwide Study on the Risk of Autoimmune Diseases in Individuals With a Personal or a Family History of Schizophrenia and Related Psychosis. The American journal of psychiatry. PMID: 24129899
Engineering artificial teeth without current complications.... Read more »
Bullock, M. (2013) Principles and practice of single implant and restoration. BDJ, 215(2), 100-100. DOI: 10.1038/sj.bdj.2013.733
Patients in the Intensive Care Unit (ICU) often develop cognitive deficits. The symptoms are very similar to Alzheimer’s and other forms of dementia. New research focuses on this link. ... Read more »
Pandharipande PP1, Girard TD, Jackson JC, Morandi A, Thompson JL, Pun BT, Brummel NE, Hughes CG, Vasilevskis EE, Shintani AK, Moons KG, Geevarghese SK, Canonico A, Hopkins RO, Bernard GR, Dittus RS, Ely EW; BRAIN-ICU Study Investigators. (2014) Long-Term Cognitive Impairment after Critical Illness. New England Journal of Medicine, 370(2), 184-186. DOI: 10.1056/NEJMc1313886
Bohannon, R., Maljanian, R., & Ferullo, J. (2013) Mortality and readmission of the elderly one year after hospitalization for pneumonia. Aging Clinical and Experimental Research, 16(1), 22-25. DOI: 10.1007/BF03324527
I have an awkward relationship with mathematical oncology, mostly because oncology has an awkward relationship with math. Although I was vaguely familiar that evolutionary game theory (EGT) could be used in cancer research, mostly through Axelrod et al. (2006), I never planned to work on cancer. I wasn’t eager to enter the field because I […]... Read more »
National Eating Disorder Awareness Week came and went (in the US, anyway). Posters were shared, liked, and tweeted. Pretty (but often misguided) infographics made the rounds on the internet. Local ED groups visited schools and college campuses to educate students about eating disorders. To, you know, increase awareness.
The thing is, awareness is not always a good thing. For one, as Carrie over at ED Bites mentioned, there’s a whole lot of misinformation masquerading as fact. And two, awareness campaigns, even when the information in them is correct, may have unintended consequences, like, for example, increasing stigma or self-stigma.
Moreover, not all approaches to increasing awareness or decreasing stigma are equally effective, and the effectiveness of a particular approach may differ depending on the population studied.
So, what about the effectiveness of EDAW? In 2012, Kathleen Tillman and colleagues published a study looking at the impact of a “campus-wide, week-long series of psycho-educational and awareness program designed for National Eating Disorders Awareness Week.”
In particular, they assessed individuals’ willingness to seek help, their levels …
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It all starts with a mosquito bite. When a hungry mosquito pierces someone’s skin to gorge herself, she also pumps …Continue reading →... Read more »
Miotto O, Almagro-Garcia J, Manske M, Macinnis B, Campino S, Rockett KA, Amaratunga C, Lim P, Suon S, Sreng S.... (2013) Multiple populations of artemisinin-resistant Plasmodium falciparum in Cambodia. Nature genetics, 45(6), 648-55. PMID: 23624527
We love gadgets in EMS.
Dr. Bryan Bledsoe tells us that if we paint it orange and put a star of life on it, we can sell any product for a lot more money.
How much would you pay to not improve outcomes?
$50,000.00?... Read more »
Rubertsson S, Lindgren E, Smekal D, Östlund O, Silfverstolpe J, Lichtveld RA, Boomars R, Ahlstedt B, Skoog G, Kastberg R.... (2014) Mechanical chest compressions and simultaneous defibrillation vs conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: the LINC randomized trial. JAMA : the journal of the American Medical Association, 311(1), 53-61. PMID: 24240611
Tracy Young-Pearse (left) and Christina Muratore (right)Researchers from Harvard have successfully converted skins cells from patients with early onset Alzheimer’s into the types of neurons that are affected by the disease, making it possible for the first time to study this leading form of dementia in living human cells. The research may also help in developing therapies more quickly and accurately than before.The study, led by Tracy Young-Pearse and published in the journal Human Molecular Genetics, confirmed what had long been observed in mouse models: that the mutations associated with early onset Alzheimer’s are directly related to protein cleavage errors that cause a rise in amyloid-beta (Aβ) protein 42, which all people produce but which somehow clumps together to form plaques in Alzheimer’s patients.Read More... Read more »
Muratore CR, Rice HC, Srikanth P, Callahan DG, Shin T, Benjamin LN, Walsh DM, Selkoe DJ, & Young-Pearse TL. (2014) The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons. Human molecular genetics. PMID: 24524897
The dissociative anesthetic and ravey club drug ketamine has been hailed as a possible “miracle” cure for depression. In contrast to the delayed action of standard antidepressants such as SSRIs, the uplifting effects of Special K are noticeable within an hour. “Experimental Medication Kicks Depression in Hours Instead of Weeks,” says the National Institute of Mental Health. NIMH has been bullish on ketamine for years now. Prominent researchers Duman and Aghajanian called it the “the most important discovery in half a century” in a recent Science review.But in 2010, I pondered whether this use of ketamine was entirely positive:Drawbacks include the possibility of ketamine-induced psychosis (Javitt, 2010), limited duration of effectiveness (aan het Rot et al., 2010), potential long-term deleterious effects such as white matter abnormalities (Liao et al., 2010), and an inability to truly blind the ketamine condition due to obvious dissociative effects in many participants.Ketamine can also cause memory impairments, and abuse of the drug can result in severe bladder damage. There's even a model of schizophrenia based on antagonism of glutamate NMDA receptors, ketamine's main mechanism of action.Now, in the latest issue of the American Journal of Psychiatry, Dr. Alan F. Schatzberg of Stanford University School of Medicine has a commentary entitled, A Word to the Wise About Ketamine. He first acknowledges the excitement about acute ketamine for refractory depression, then raises several cautionary notes and warns:“This unbridled enthusiasm needs to be tempered by a more rational and guarded perspective.”He notes that the drug is administered off-label in free-standing private psychiatry clinics without regulation by the FDA. Some leading proponents have advocated for strictly inpatient use, but that cat is already out of the bag. Another potential issue is abuse liability. The antidepressant effects of ketamine are short-lived (less than a week), which means that repeated infusions are required. The published literature suggests a relatively safe profile over two weeks in a hospital setting, but patients at commercial clinics are unlikely to be monitored as closely.The commentary also suggests that “We Need To Know More About the Mechanism of Action of the Mood-Elevating Effects” – but that is true of all drugs with antidepressant properties. The Slippery Ketamine SlopeIn response to the question, “Should Clinicians Prescribe Ketamine for Patients With Refractory Depression?” Dr. Schatzberg answers:Without more data on what ketamine can do clinically, except to produce brief euphoriant effects after acute administration, and knowing it can be a drug of abuse, it is difficult to argue that patients should receive an acute trial of ketamine for refractory depression. ... The recent ketamine studies are exciting, and they open up important avenues for investigation that should be supported; however, until we know more, clinicians should be wary about embarking on a slippery ketamine slope.However, in the midst of all this naysaying, it's important to note that Dr. Schatzberg has extensive ties to the pharaceutical and biotech industries. He receives consulting fees from 19 different companies and has equity in 16 different companies, including one for which he is a co-founder. Ketamine of course is not under patent and is cheap to purchase. Perhaps not coincidentally, he does not receive fees from AstraZeneca, which (until recently) was developing a “low-trapping” NMDA antagonist that does not cause the hallucinogenic effects of ketamine (AZD6765, aka lanicemine).In the past, I have suggested that short-term use for immediate relief of life-threatening symptoms (i.e. suicidal ideation) or end-of-life depression seem to be the best indications. Neuroskeptic has argued for the use of an active placebo condition (i.e, a non-dissociative comparison drug) in clinical trials, which has happened only rarely (Murrough et al., 2013), and for better assessment of dissociative behavioral effects.At this point, the long-term ramifications of ketamine use for treatment-resistent depression remain to be seen...In a future post I'll investigate the potential side effects in more detail. DeclarationI have no financial conflicts to declare. But if some company wants to employ a critic for some bizarre reason, I'll take this under advisement. Further ReadingKetamine for Depression: Yay or Neigh?Chronic Ketamine for Depression: An Unethical Case Study?While I Was Away... (more on ketamine for depression)Update on Ketamine in Palliative Care SettingsReferenceSchatzberg AF (2014). A word to the wise about ketamine. The American journal of psychiatry, 171 (3), 262-4 PMID: 24585328
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At the time of writing this post, the media is awash with two stories with an autism research slant to them. So we have the paper by Brian D’Onofrio and colleagues  talking about older, sorry, advancing paternal age and the risk of various conditions for offspring, including autism, and the paper by Sébastien Jacquemont and colleagues  on a female protective model for autism. Y'know these are serious pieces of research when the good old BBC (Auntie) puts its 10p worth into the media pot as per its headlines: "Child health problems 'linked to father's age'" and "Girls' growing brains 'more resilient', study suggests" respectively.El coloso @ Wikipedia Personally, I have little more to add to the myriad of comments made about these studies, aside from saying 'yes', both represent very detailed and potentially important areas of work. For people with autism and their families or caregivers however, I am inclined to suggest that such news from these studies is not going to be particularly useful in the day-to-day context.Hence then why I've decided to focus instead on the paper by Adler and colleagues  in this post, and their rather less publicised work on "drug-refractory aggression, self-injurious behavior, and severe tantrums" in the context of autism.To talk about aggression and autism has the ability to invoke emotion. On the one hand is the realisation that aggression can be part and parcel of the presentation of some autism, and both for the person themselves and their families, can have a profound effect on quality of life. As one example, I'll take you back to a post I did a while back on self-aggression, otherwise known as self-injurious behaviour (SIB), and autism and the extreme consequences it can sometimes have (see here).On the other hand, there is the risk that talking about aggression with autism in mind may unfairly stereotype such behaviours to autism, all autism. In much the same way that the label schizophrenia carries with it some often over-emphasised links (see here) so one has to be mindful of the possible effects of talking about such behaviours and in particular, the over-generalisation that can accompany discussions. Just for the record, I'll bring the paper by Farmer and colleagues  to your attention and their conclusion: "children with autism spectrum disorder were reported to have less aggression and were more likely to be rated as reactive rather than proactive". Indeed, reactive or spontaneous aggression is also a theme when it comes to autism and the CJS too (see here).That all being said, the Adler paper is an interesting one in terms of their assertion that from a total of 250 cases, 135 participants were diagnosed with an autism spectrum condition, and "53 of these individuals met drug-refractory symptom criteria" when it came to definitions of aggression and its relations. I should also add that drug refractory means resistant to change following the use of pharmacotherapy. Not wishing to dwell too much on the methodology employed by Adler et al - based on medical records and medication history charts - the authors set about looking for what characteristics may be correlated with drug-refractory aggression among their cohort. In the end, they determined a few important factors to be related: (a) a diagnosis of autism, (b) being over the age of 12 years, and (c) the presence of intellectual disability (or learning disability).I hope you don't feel cheated by my highlighting what are three very general factors when it comes to aggression. Personally I feel that these represent important factors not least because the issue of intellectual disability in particular, does show more than a passing connection to challenging behaviours including those with an aggression element to them (see here). Indeed within that Moss paper  there are also a few other important points which may well be important; not least the association between things like depression and anxiety when it comes to the presentation of aggression and self-injury. One might even assume that this could be evidence for the presence of anxiety symptoms / disorders as being present where SIB is a feature of autism? Just sayin'.The fact also that Adler and colleagues were looking at medication resistant aggressive behaviours in the first place is important. As they note: "We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole". In other words, such behaviours were not managed by something like risperidone or aripiprazole (which itself is having a bit of a hard time at the moment). This point in particular brings me back to some interesting work looking at the use of antipsychotics in other conditions and how one might extrapolate from other experiences to autism. In other words, before reaching for the antipsychotics, make reasonable efforts to see if there may be other reasons / causes for challenging behaviours like aggression. Certainly take some time to look at guidance like that produced by NICE (see here) and remember the weight gain issue  too.Finally, I'm not saying that pharmacotherapy may not have a place when it comes to some aggression and some autism as per other research literature on this topic . Indeed, it is timely to mention something like naltrexone as one medicinal option  given the reported recent passing of Dr Jaquelyn McCandless (RIP). Indeed, naltrexone looks like it may very well be coming out of the research wilderness if the paper by Roy and colleagues  is anything to go by [watch this space for more news from our research team on this stuff...]Not to make light of today's subject matter, I close with some music by a man who some of my brood have just discovered via the wonders of YouTube... and they are absolutely enthralled by his dancing.---------- D’Onofrio BM. et al. Paternal Age at Childbearing and Offspring Psychiatric and Academic Morbidity. JAMA Psychiatry. 2014. February 26. Jacquemont S. et al. A Higher Mutational Burden in Females Supports a “Female Protective Model” in Neurodevelopmental Disorders. The American Journal of Human Genetics. 2014. Feburary 27. Adler BA. et al. Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study. Autism. 2014 Feb 26.... Read more »
Adler BA, Wink LK, Early M, Shaffer R, Minshawi N, McDougle CJ, & Erickson CA. (2014) Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study. Autism : the international journal of research and practice. PMID: 24571823
The risk of anterior cruciate ligament (ACL) revision is relatively low after an autograft reconstruction. Revision rates may be slightly lower for patellar autografts compared with hamstring autografts.... Read more »
Rahr-Wagner, L., Thillemann, T., Pedersen, A., & Lind, M. (2013) Comparison of Hamstring Tendon and Patellar Tendon Grafts in Anterior Cruciate Ligament Reconstruction in a Nationwide Population-Based Cohort Study: Results From the Danish Registry of Knee Ligament Reconstruction. The American Journal of Sports Medicine, 42(2), 278-284. DOI: 10.1177/0363546513509220
Persson, A., Fjeldsgaard, K., Gjertsen, J., Kjellsen, A., Engebretsen, L., Hole, R., & Fevang, J. (2013) Increased Risk of Revision With Hamstring Tendon Grafts Compared With Patellar Tendon Grafts After Anterior Cruciate Ligament Reconstruction: A Study of 12,643 Patients From the Norwegian Cruciate Ligament Registry, 2004-2012. The American Journal of Sports Medicine, 42(2), 285-291. DOI: 10.1177/0363546513511419
Vascular compliance is a characteristic of the blood vessel wall to expand or contract with changes in pressure, and is reduced with aging or diseases like arteriosclerosis. Our goal was to investigate how hand-volume changes differ with age and to provide a simple non-invasive method to assess vascular compliance. We hypothesized that gravity-related, hand-wrist volume changes are greater in younger than in older healthy volunteers. Thirty-five healthy volunteers were classified into two age groups: young (18-35 years, n=16) and old (50-65 years, n=19).... Read more »
EA Kraus, JM Kim, AR Hargens. (2014) Gravitational Changes in Hand -Wrist Volume are Smaller in Older Adults as Compared to Younger Adults. Journal of Cardiology and Vascular Medicine, 2(1), 1-6. info:/2: 102
An embryonic stem cell differentiating into a neuronal cell under the microscope.Credit: Anne Rupprecht/Vetmeduni ViennaCells have a metabolism that can be altered according to its function and requirements. If cellular metabolism is disturbed, it can lead to disease of the entire organism. Now, researchers at the University of Veterinary Medicine in Vienna say that they have discovered that the uncoupling proteins UCP2 and UPC4 are involved in different types of cellular metabolism.The proteins provide information about the condition of cells. As a result, cell alterations can now be detected much earlier than it was previously possible.UCPs or uncoupling proteins are present in mitochondria, the powerhouses of each cell in our body. The functions of most of the five known UCPs remain mysterious (UCP2-UCP5), whereby only the distinct function for UCP1 has thus far been discovered. UCP1 is responsible for heat production when muscle activity is deficient such as is the case with babies and animals in hibernation.Read More... Read more »
Rupprecht A, Sittner D, Smorodchenko A, Hilse KE, Goyn J, Moldzio R, Seiler AE, Bräuer AU, & Pohl EE. (2014) Uncoupling Protein 2 and 4 Expression Pattern during Stem Cell Differentiation Provides New Insight into Their Putative Function. PloS one, 9(2). PMID: 24523901
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