Central Institute of Psychiatry

Exposure to traffic related air pollution is associated with an increased likelihood of having multiple long-term physical and mental health conditions according to a new study of more than 364,000 people in England. Exposure to traffic related air pollution is associated with an increased likelihood of having multiple long-term physical and mental health conditions according to a new study of more than 364,000 people in England. Led by researchers from Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, this is the largest study worldwide to examine whether air pollution exposure is linked with the occurrence of multiple long-term health conditions. Multimorbidity is defined as having two or more physical or mental health conditions and affects 27 per cent of adults in UK primary care. It increases the use of healthcare services and the costs of primary and secondary care, but its association with air pollution has not been studied in the UK until now. Published in Frontiers in Public Health the study showed that high levels of traffic-related air pollution -- fine particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) -- were associated with an increased risk of having at least two long term health conditions. The strongest associations were observed for co-occurring neurological, respiratory, cardiovascular and common mental health conditions such as depression and anxiety. This research was funded by National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and NIHR Applied Research Collaboration (ARC) South London. Dr Amy Ronaldson, Research Associate at Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London and first author on the study said: "People with more than one long-term health condition have a lower quality of life and greater dependence on the healthcare system. Our NIHR funded research has indicated that those people that live in areas of higher traffic-related air pollution are at greater risk of having multiple health conditions. The study does not prove that air pollution causes multimorbidity, but it does warrant further research in this area. It could be that simple measures to reduce traffic levels could potentially improve lives and lessen the pressure on our healthcare systems." Researchers analysed data from UK Biobank -- a large-scale biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants. aged between 40 and 69 years. Participants were assessed for 36 physical and five mental health chronic conditions. Multimorbidity was defined as having two or more of these conditions. Physical and mental health data from UK Biobank in 2010 were linked with the estimated concentration of air pollution at the residential address of the participants. The study found that those participants exposed to higher concentrations (above 10µg/m3) of fine particulate matter had a 21 per cent increased risk of two or more co-occurring conditions compared to those exposed to concentrations below 10µg/m3. For participants exposed to above 30µg/m3 of NO2 the research showed a 20 per cent increased risk of having two or more co-occurring conditions compared to those participants that were exposed to concentrations of NO2 below 20µg/m3. Amongst those with multiple conditions, increased exposure to both PM2.5 and NO2 was linked to a greater severity of the co-occurring conditions. Dr Ioannis Bakolis, Reader at IoPPN, King's College London and senior author on the study said: "How air pollution affects multiple organs and systems at the same time is not yet fully understood, but there is some evidence that mechanisms such as inflammation, oxidative stress and immune activation could be triggered by air particulates, which can cause damage to the brain, heart, blood, lungs and gut. "Our study suggests that it could be through shared mechanisms that air pollution negatively impacts several body systems and increases the likelihood of people developing multiple long term health conditions. More research is needed to understand just how air pollution affects the different bodily systems, but it may be that tackling air pollution could help prevent and alleviate the debilitating impact of multiple long-term health conditions." Researchers identified several patterns in the associations: the strongest links were primarily between conditions relating to the respiratory system (asthma, chronic obstructive pulmonary disease) as well as the cardiovascular system (atrial fibrillation, coronary heart disease, heart failure) but also to neurological and common mental conditions (stroke, substance abuse, depression, anxiety). The study, 'Associations between air pollution and multimorbidity in the UK Biobank: A cross-sectional study' was published in Frontiers in Public Health. This study has been funded by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London and the NIHR Applied Research Collaboration South London.

New research has identified a new hallmark of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS), revealing a likely molecular trigger of the disease. New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has identified a new hallmark of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS), revealing a likely molecular trigger of the disease. The study, published in Nature Communications, found that loss of the RNA processing protein, SFPQ, in motor neurons results in their 'dying back'. This involves destruction of the axon (the part of the neuron responsible for connecting to and communicating with the rest of the body) and later, cell body death. Using zebrafish, the investigators explored what happens inside SFPQ-depleted motor neurons before they degenerate. They found that draft messenger-RNAs (mRNAs) that are normally regulated by SFPQ are only partially edited and become truncated. To their surprise, these defective mRNAs are not degraded but instead stably localise to axons, where they accumulate and interfere with normal function. This is the first study to show the cascade of molecular events in axons triggered by loss of the protein. As loss of SFPQ is strongly associated with ALS, the authors took their findings from the zebrafish and analysed data from ALS patients. They found that the unusual defective mRNAs are enriched in patient neurons, pointing to these axonal mRNAs to be a cause for degeneration in the disease. Corinne Houart, Professor of Developmental Neurobiology at King's IoPPN and the study's lead author said, "Finding the same mRNA abnormalities in zebrafish SFPQ mutant and in human ALS neurons is opening a new path in understanding the neurodegenerative process. Our findings as well as those of international colleagues show that controlling mRNA diversity in axons is essential of neuronal health. Uncovering the local changes in mRNA regulation in neurons affected by aging or neurological disorders will provide great progress in tackling these issues." It's estimated that around 5000 people in the UK live with ALS at any one time. The average survival time following diagnosis is between two to five years, and as yet there is no available cure. The findings open a possible new avenue of therapy in ALS patients, aimed at restoring SFPQ function in neurons. In doing so, one may be able to prevent their degeneration. Dr. Richard Taylor, the study's first author said, "We were surprised to find that these abnormal mRNAs, forming upon loss of SFPQ function, are not degraded in the nucleus. Instead, contrary to dogma they seem to escape and specifically localise to axons. Their effects either at the RNA level, or protein level if translated, are likely detrimental to axon integrity and may initiate the "dying back" sequence of degeneration observed in ALS neurons." The researchers will now turn their focus to determining the mechanisms by which these defective mRNAs are toxic in ALS patient axons, and will investigate the effect of introducing normal SFPQ into patient iPSC-derived degenerating neurons.

New research has found no evidence that cannabidiol (CBD) reduces the negative effects of cannabis. New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King's College London has found no evidence that cannabidiol (CBD) reduces the negative effects of cannabis. The research, published in Neuropsychopharmacology, challenges the commonly held belief that using cannabis that contains higher levels of CBD protects the user from psychotic experiences and memory problems, and suggests that this should be considered by policy makers currently exploring the topic of medicinal and recreational use. 46 healthy volunteers completed a randomised and double-blind trial. Over the course of four experiments, each participant inhaled cannabis vapour containing 10mg of THC and a differing level of CBD (0mg, 10mg, 20mg, or 30mg). They then completed a series of tasks, questionnaires and interviews designed to measure the effect on their cognitive abilities, severity of psychotic symptoms, and how pleasurable the drug was. The same research team had previously found that pre-emptively taking a high dose of CBD in a capsule a few hours before using cannabis may reduce the adverse effects of THC In this study, they explored the effect of altering the CBD:THC ratio in cannabis.However, they found increasing the dose of CBD did not significantly change the effects of THC on cognitive performance, psychotic symptoms or how pleasurable the drug experience was. Dr Amir Englund, a research fellow at King's IoPPN and the study's lead author said, "None of the CBD levels studied protected our volunteers from the acute negative effects of cannabis, such as anxiety, psychotic symptoms, and worse cognitive performance. It also did not change the quality of the intoxication in any way. The only effect of CBD we saw was that as the concentration of CBD increased, the more the participants coughed. We asked volunteers to listen to a favourite song on each visit and taste a piece of chocolate. Although cannabis increased the pleasurability of music and chocolate compared to when volunteers were sober, CBD had no impact." "THC and CBD are both produced from the same compound in the cannabis plant, so a variety which produces higher of amounts of CBD will naturally be lower in THC. It may still be safer for users to choose cannabis with higher CBD:THC ratios, but that's because the same amount of cannabis will contain less THC than a lower CBD:THC variety. Overall, our advice to people wanting to avoid the negative effects of THC is to use less of it." Professor Philip McGuire, the study's senior author and former Head of the Department of Psychosis Studies at King's IoPPN said, "These findings make an important contribution to the ongoing debate around the risks of cannabis use. While CBD on its own is known to have a number of positive effects in humans, our data suggest that, at the doses that are typically present in cannabis, it does not protect against the negative effects of THC. This challenges the commonly held view by many cannabis users that cannabis with a higher CBD content provides a buffer against the adverse effects of cannabis." This study was funded by a research grant from the Medical Research Council.