Almost a decade after it was suggested that the measles, mumps and rubella (MRR) vaccine caused autism, a recent study has pushed another nail into the coffin of this supposed connection between autism and the MMR jab.
Published in the February 5 issue of Archives of Disease in Childhood, researchers from the UK and Australia tested the blood of 240 children aged 10–12 years who were born between July 1990 and December 1991 in the South Thames area of England, all of whom had received the MMR vaccine. Of the 240 children, 98 had been diagnosed with autism, 52 were not autistic but had special educational needs and 90 had no developmental problems.
In order to test whether the MMR vaccine had caused an abnormal immune result that could have triggered autism, the researchers tested the blood samples for circulating measles viruses and antibody levels. An increase in antibody levels would have indicated a link between the vaccine and an abnormal immune response. However, there were no differences found between the blood samples of all three groups of children.
David Brown, of the Health Protection Agency (London, UK) and coauthor of the study commented, “The study found no evidence linking MMR to autistic spectrum disorder and the paper adds to the overwhelming body of evidence from around the world supporting the use of MMR.”
Fears regarding the connection between the MMR vaccine and autism were first raised in 1998, when Andrew Wakefield and colleagues published a report in the Lancet claiming that the MMR jab caused autism.
The researchers hope that this new evidence, combined with previous results demonstrating no connection between the MMR vaccine and autism, will encourage parents to consider having their children vaccinated against MMR. “We’ve really gone for every possible control group and we found no difference,” Gillian Baird, a Professor and Children’s Neurologist at Guy’s Hospital (London, UK) and lead author of the study commented “I hope that this will give parents confidence that they can have their children vaccinated with MMR.”
Sources: Wakefield AJ, Murch SH, Anthony A et al. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. Lancet 351(9103), 637–641 (1998); Baird G, Pickles A, Simonoff E et al. Measles vaccination and antibody response in autism spectrum disorders. Arch. Dis. Child. PMID: 18252754 (2008) (Epub ahead of print).
Bipolar test kits available over the web
Two tests for bipolar disorder are now available over the internet. The kits, which come complete with instructions and references, are for sale to patients and doctors. The test uses a saliva sample to analyze the DNA of the patient, the results of which are sent confidentially to the patient’s doctor.
However, diagnosis of a neuropsychiatric illness should not be made solely on the basis of the results of this test. Although the tests provide objective data, doctors must take into account other evaluations before any conclusions about a patient’s condition can be made. What the tests will provide is a more accurate, rapid diagnosis and a guide as to what the most appropriate treatment for that patient is. Currently, the average time between first bipolar symptoms and average diagnosis is 7 years; time better spent treating the patient. The hope is that these tests can reduce this delay.
Two mutations in the G protein receptor kinase 3 (GRK3) gene have been associated with bipolar disorder and it is these mutations that are detected by the Psynome™ test. GRK3 regulates sensitivity to brain neurotransmitters such as dopamine. A single nucleotide polymorphism mutation in the promoter region of GRK3 causes bipolar disorder in up to 10% of bipolar cases.
A second test, Psynome2™ tests for serotonin transporter response. This is designed to ascertain if the patient is likely to respond to serotonin-based drugs.
The tests are made by Psynomics Inc., a company based in San Diego (CA, USA) that offer genetic screening products and services for patients with neuropsychiatric illnesses.
Source: Psynomics.com
Deep brain stimulation to be tested for the treatment of depression
Permission has recently been granted by the FDA for St Jude Medical Inc. (MN, USA) to begin enrollment for a controlled, multi-site, blinded clinical study into the use of DBS for the treatment of MDD.
“Major depressive disorder is severely disabling,” commented researcher Andres Lozano. “Currently, there are no widely-accepted treatment options for patients with this condition once multiple medications, psychotherapy and electroconvulsive therapy have failed.”
The study will follow-on from research published in Neuron in 2005, in which it was demonstrated that Brodmann’s area 25 is overactive during periods of profound sadness or depression.
“This area of the brain lights up when people are sad, and it’s active all the time in people with severe depression,” Lozano explained.
The BRAODEN™ study will enroll patients with MDD for whom all other current treatments have been ineffective. A stimulator will be implanted near to the collar bone which will be connected by leads to the region of the brain to be stimulated. The study will be testing the safety and effectiveness of the treatment.
“The idea is that this area of the brain is abnormal in patients with depression,” Lozano commented. “What we’re essentially doing is applying a dimmer switch.”
In a recent pilot study: four of six depressed patients experienced significant improvements in depression after DBS.
“We are hopeful that this trial will lead to the successful development of a sustainable therapy for those patients who have exhausted other treatment options.” Chris Chavez, president of St. Jude Medical’s Neuromodulation Division commented.
Sources: Mayberg HS, Lozano AM, Voon V et al. Deep brain stimulation for treatment-resistant depression. Neuron 45, 651–660 (2005); St Jude Medical Inc. News Release. St. Jude Medical announces clinical study of deep brain stimulation for depression. http://phx.corporate-ir.net/phoenix.zhtml?c=73836&p=IROL-SingleRelease_print&t=NewsRelease&id=1105490&highlight=
Opposite roles of STAT3 in glioblastoma
It has previously been shown that STAT3 acts as an oncogene in several tumors. Therefore, inhibiting the gene should, in theory, be an effective treatment for these tumors.
However, in a recent study published in the February 15 issue of Genes and Development, researchers at Harvard Medical School (MA, USA) found that, depending on the tumor’s genetic make-up, STAT3 could act as an oncogene or a tumor suppressor gene.
Using genetically modified mice, the researchers studied how EGFRvII and PTEN, mutations of which have been linked to glioblastoma, affect STAT3 function in astrocytes. They found that STAT3 functioned as an oncogene when EGFRvII was mutated, but was a tumor suppressor when PTEN was mutated.
Explaining the results with regards to EGFR, Azad Bonni, commented “EGFR, in its normal state, is a transmembrane receptor, usually performing its functions at the cell surface. However, when it’s mutated, we find it in the cell’s nucleus interacting with STAT3 – and turning it into an oncogene. STAT3 itself is not mutated or damaged. It’s the process of regulating STAT3 that gets damaged.”
This new finding is not only important for glioblastoma therapy, but also for the understanding of other cancers in which STAT3 is involved, such as breast and prostate cancer.
“The belief that STAT3 can only be an oncogene has been a pretty entrenched dogma in the field,” commented Bonni, “so we performed many, many experiments to make sure this was correct. It took some very persistent investigators in my lab to get the job done. As a result, we’re convinced of our data.”
The results also highlight the need to carry out further research into the field of personalized medicine, as Bonni explained, “This discovery lays the foundation for a more tailored therapeutic intervention, and that’s really important. You can’t just go blindly treating people by inhibiting STAT3.”
Source: de la Iglesia N, Konopka G, Puram SV et al. Identification of a PTEN-regulatedSTAT3 brain tumor suppressor pathway. Genes Dev. 22(4), 449–462 (2008).
Genetic variant may protect against depression
A recent study, published in the February 4 issue of Archives of General Psychiatry has not only added weight to the corticotrophin-releasing hormone (CRH) hypothesis of depression, but has also identified a gene variant linked to the likelihood of suffering depression in adulthood following childhood abuse.
“There are all kinds of reasons to think the CRH receptor could be important for the biology of depression,” commented NIMH Director Thomas Insel. “Early activation of the receptors could change the way they work and how sensitive they are. They have these imprinting effects where you often see very long-term consequences.”
Two groups of participants, from different ethnic and socioeconomic backgrounds, were interviewed and had their DNA tested. Participants were asked to complete questionnaires about childhood trauma and were ranked as having suffered from mild, moderate or severe abuse, depending on their answers. The researchers also looked for any of 15 variations in the CRHR1 gene.
In the first group of 422 adults, 97.4% of whom were African–American, who had a monthly income of less than US$1000, it was found that those who had suffered moderate-to-severe levels of abuse had approximately double the levels of depressive symptoms than those with low or mild abuse scores.
“We know that childhood abuse and early life stress are among the strongest contributors to adult depression, and this study again brings to light the importance of preventing them,” explained Kerry Ressler, lead author of the study. “But when these tragic events do occur, studies like this one ultimately can help us learn how we might be able to better intervene against the pathology that often follows.”
In addition, approximately 30% of the 422 participants had a variation in CRHR1 that appeared to be protective if the patient had suffered from moderate or severe abuse. Approximately half the levels of depressive symptoms were experienced by those with two copies of the most protective halotype of the gene compared with those who did not have any copies. However, this was only found in those who had suffered from moderate-to-severe abuse, and not in people who had low or mild abuse scores.
“You see these kids who go through the worst experiences and they seem to come out stronger, whereas other kids come out bruised,” commented Insel. “The way they’re responding to loss or traumatic events is partly encoded in their genomes.”
Similar results were also found in a group of 199 middle class people (87.7% Caucasian), demonstrating that this association was found across ethnic and socioeconomic groups.
“Our results suggest that genetic differences in signals mediated by CRH may amplify or soften the developmental effects that childhood abuse can have – effects that can raise the risk of depression in adults.” commented Ressler.
The importance of combining knowledge about both genetic and environmental risk factors in order to fully understand the underlying causes was also highlighted in this study, as Insel explained, “For 100 years we’ve argued about depression: is it nature or is it nurture? When you look at something as complicated as depression, if you just look at genes or just look at environment, the effects aren’t there. But if you look at them together, you start to see these interesting interactions. Studies like this are getting us beyond nature versus nurture to understand how nature interacts with nurture. It’s a very different discussion now.”
Source: Bradley RG, Binder EB, Epstein MP et al. Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch. Gen. Psychiatry 65(2), 190–200 (2008).