When matters of the mind meet ailments of the body: exploring the power of big data

AFP6E1 Silhouette of a woman sitting by a window in a dim room and holding her head
AFP6E1 Silhouette of a woman sitting by a window in a dim room and holding her head

According to the charity Mind 1 in 4 people in the UK are expected to experience some type of mental health problem each year. Importantly, those suffering from severe mental illness (SMI) also tend towards poorer physical health and higher mortally rates than those without a SMI. This link was investigated in a large longitudinal study published last September in the British Medical Journal from the University of Manchester’s Institute of Population Health and Lancaster University’s Division of Health Research, and offers new insight into the well-established link between poor physical and mental health.

Researchers used data from the Clinical Practice Research Datalink (CPRD) – a powerful not-for-profit research service which has been collecting anonymised medical data since 1987 – to explore SMI across the UK and probe how this is linked to social factors and a range of physical conditions. The researchers collected data annually between 2000 and 2012 from patients suffering from SMI* alongside control subjects with no SMI diagnosis. Control subjects were matched for age, sex and general practice (GP) – 5 controls for each SMI sufferer. The power of this research lies in both the number of individuals studied (more than 300,000 SMI sufferers and more than 1,700,000 matched controls) and the timescale over which the data was collected (12 years) – this being the first study of its kind to analyse mental health data in this way.

From these data the researchers found that the total number of individuals diagnosed with a SMI increased over the period between 2000 and 2010, with this increase being most striking in areas of higher social deprivation (social deprivation being estimated by GP postcode). These findings also highlighted an improvement in SMI diagnosis, indicating that people are now routinely receiving an SMI diagnosis earlier in life.

With regard to the association between mental and physical health the study found that all 16 physical conditions studied** were more common in patients with a SMI than in control patients. It was also observed that, over the study period, SMI sufferers showed a higher yearly increase in diagnosis rates for a range of conditions (including: diabetes, hypothyroidism, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD) and stroke) compared to matched controls. This increase appeared to coincide with increased prescription of atypical antipsychotic medication in the SMI group. Indeed, this and previous studies suggest that a range of complex factors may interact in SMI patients to produce this effect. Specifically, a combination of antipsychotic medication, unhealthy lifestyles, social withdrawal and challenges associated with seeking and following medical advice may all lead to poor physical health in SMI sufferers. However, further research is still needed to fully understand which factors play a role in the link between mental illness and poor physical health.

The findings concerning associations between SMI, physical health and social deprivation are more complicated. This study suggests that SMI sufferers living in deprived regions are more likely to be diagnosed with diabetes mellitus, asthma, coronary  heart  disease, COPD, learning disability, osteoarthritis or epilepsy, whereas those living in more affluent conditions are more often diagnosed with CKD,  psoriasis,  cancer,  stroke  or dementia.

Although the researchers involved in this study stress that there are limitations to these findings, some important points have been raised, particularly in relation to mental health care and policy. Specifically, findings suggest that patients suffering from a SMI are indeed more likely to suffer from one or more associated physical condition. This points to the possible benefit of increased training for mental health professionals, especially in recognising indicators of poor physical health and identifying the complex needs of the patients in their care. Also, these results suggest that social and regional factors might influence treatment and diagnosis of certain physical conditions in patients with SMI. These findings warrant further study as this knowledge may be beneficial in shaping and targeting mental health care at the regional level.

With the cost of care for individuals with both mental and physical health problems exceeding the cost of treating either condition alone, it is important that mental health funding be prioritised and that studies such as this be encouraged.

*defined as: schizophrenia, affective disorder or other types of psychoses.

**Hypertension, diabetes (type I and II), asthma, hypothyroidism, osteoarthritis, chronic kidney disease (CKD), learning disability,  coronary  heart  disease,  epilepsy,  chronic obstructive pulmonary disease (COPD), cancer, stroke, heart failure, rheumatoid arthritis, dementia and psoriasis.

Post by: Sarah Fox

Save

The Case of the Jumping Carbons

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish our winning article written by Tilly Hancock from Oswestry School:

Screen Shot 2016-06-19 at 19.09.50

Imagine you are inside a nuclear reactor, a UK design. Not only are you inside it, but you are part of it; a carbon atom inside the graphite core which houses the control rods and fuel rods (the ‘moderator’). Around you the environment is glowing with heat and radiation, all given off in the splitting (fission) of uranium-235 nuclei. The temperature of 450°C is no problem, and you remain tightly bound in a lattice arrangement with your fellow carbons.

However, when the uranium nuclei split, they spit out more neutrons which pelt towards you at high speeds. One slams into you, and you slow it down, as is your job, so it travels at a suitable speed to cause more fission events. In this process you absorb the neutron’s energy, and get knocked out of your slot in the lattice. You whiz towards your fellow carbon atoms, knocking more out of their spaces like a billiard ball, wreaking havoc in the strict order of the graphite crystal. Eventually you transfer all of your extra energy to your neighbours and come to rest, filling a vacancy left by another displaced carbon or squeezing in between the orderly lattice layers (as an ‘interstitial’). Here you wait, ready to absorb the excess energy of the next neutron. The upheaval is routine to you, as during your life in the reactor you may switch places up to 30 times.

This is just one atom, but what are the consequences of millions jumping around like this?

Screen Shot 2016-06-07 at 16.46.44
A finite element model of a graphite sample and how the model behaves when irradiated or heated. Image credit: Dr Graham Hall. Manchester University

Well, the effects are unpredictable. The radiation barrage that the graphite endures can cause it to change its material properties; its thermal expansion, strength and even its dimensions, in strange ways. Even to the human eye, these changes would be noticeable. The moderator can change shape by up to 2%, depending on the grade of graphite; a surface that started smooth may finish rough. The dimensions may warp so that the control rods used to restrain the nuclear reaction may no longer fit into their channels. It is clearly important to completely understand how the graphite will change when designing new reactors or maintaining the existing ones. The problem is that we don’t.

For years, the only way to investigate the effects of the jumping carbon atoms has been using ‘materials test reactors’, which can take over 3 years and £10 million to complete a single experiment.

Is there an easier way to predict what the carbons’ dance can lead to?

Like in so many fields, computers are now proving their worth. Manchester University’s Dr Graham Hall designs models which do part of the test reactors’ job. He imagines how those millions of carbon atoms move around and uses similar previous models to predict some of the complex property changes. What’s more, to model a lump of graphite in a reactor-like environment, just one week would be expended, as opposed to those three years required by the test reactors. Although these models are unlikely to be used to design new reactors, they are tackling the problem of the variability between different grades of graphite.

Screen Shot 2016-06-06 at 13.44.03
The irradiation-induced dimensional changes of graphite at two irradiation temperatures predicted from finite element models compared with the experimental data. Image and data courtesy Dr Graham Hall, Manchester University.

Comparing computer predictions to experimental data has helped researchers advance their understanding of what those carbon atoms really get up to inside the reactors and more importantly, how this affects the moderator as a whole. Hopefully, one day soon only minimal usage of materials test reactors will be needed, to calibrate models like this one, sparing millions of pounds and many, many years, but for now the jumping carbon atoms will continue to keep researchers on their toes.

Post by: Tilly Hancock – courtesy of Sarah Fox (Volunteer with the British Science Association)

For more amazing scientific articles please visit our friends at Things We Don’t KnowThings We Don’t Know is a not-for-profit organisation that seeks to explain the cutting edge questions scientists are trying to solve, in everyday language.

Save

Shedding Light on the Nucleus

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish one of our runner up articles written by Hayley Martin from Oswestry School

“The nucleus can be thought of like an engine of a car – driving the actions of the cell”. This is an analogy made by Professor Dean Jackson at Manchester University. With a passion for the genome and forty years of research behind him Professor Jackson has become an expert in understanding mammalian nuclei and chromosomes and how the organisation of their structures defines the cell’s behaviour. In order for these cells to function correctly the genetic code stored in the DNA of each gene has to be interpreted by a process called gene expression, where information from the gene is used in the synthesis of the gene product. These gene products often include proteins such as enzymes, hormones and antibodies, all vital to our survival. Gene expression is immensely complicated due to the number of processes involved. Professor Jackson has been studying these processes and has helped to shed light on exactly why this expression is so complicated.

Figure 1 – The nucleus of a human cell – showing the distribution of DNA (blue), the transcription factories (green) and proteins (red) involved in further modification of RNA.
Figure 1 – The nucleus of a human cell – showing the distribution of DNA (blue), the transcription factories (green) and proteins (red) involved in further modification of RNA.

Transcription is the first process that contributes to gene expression – it is the process whereby information from DNA is copied and made into a new strand of RNA which goes on to synthesize proteins. Professor Jackson has been able to tag newly formed RNA with a fluorescent antibody that can be detected using a laser scanning confocal microscope. This equipment scans a beam of a specific wavelength of light through the specimen, causing the antibodies to fluoresce. The resulting image is displayed in Figure 1. Images such as this have allowed him to locate the areas in the nucleus where this RNA is formed – he refers to these areas as “transcription factories”. He has also found that these factories are made up of many other genes and proteins which assemble into specific complexes. Such knowledge is key to defining the required level of synthesis of each gene product. It also provides the potential for co-regulation of genes in that the way that one gene in this complex is expressed will affect the expression of another gene. Recent work has concluded that genes can have as many as 20 other genetic elements, known as enhancers, that contribute to the gene’s overall expression, which is why it is so complex.

Gene therapy is an exciting modern concept: It offers the prospect of improving lives without the need for drugs with potential side effects and offers possibilities for treating diseases that previously had limited therapeutic options. So far it has been considered as an approach to replacing mutated genes with normal functioning copies, inactivating or removing damaged genes and introducing a new gene that might help the body fight off a disease. With the use of new techniques such as ‘CRISPR’ gene insertion is relatively easy. However Professor Jackson’s research has highlighted how gene therapy isn’t as simple as just inserting a gene – it has to be controlled in the right way by these complex processes in order for the cell to have control of its actions. The difficulty in controlling these actions means that gene therapy is currently a risky process and is not a common treatment. Trials are underway to develop effective gene therapy methods of treating inherited disorders including haemophilia, cystic fibrosis and viral infections such as HIV. We can hope, with advances in the understanding of nuclear structure and processes of gene expression, that safe and effective gene therapy treatments will become a reality.

Post by: Hayley Martin – courtesy of Sarah Fox (Volunteer with the British Science Association)

Can the Onset of Psychosis Be Predicted by the Presence of Neuro-inflammation?

Screen Shot 2016-06-05 at 21.12.02This year the Manchester branch of the British Science Association launched it’s first ever science journalism competition. They presented AS and A-level students across Greater Manchester with the daunting task of interviewing an academic researcher then using this material to create an article accessible to someone with no scientific background. This was by no means a simple task, especially since many of the researchers were working on basic research – the type of work which may not be sensational but which represents the real ‘nuts and bolts’ of scientific research and without which no major breakthroughs would ever be made. Despite the challenges implicit in this task all our entrants stepped up and we were astounded by the quality of work submitted.

Today we’re proud to publish one of our runner up articles written by Maaham Saleem from Withington Girls’ School:

Imagine a life where the dawn of each new day is accompanied by severe hallucinations, delusions and an inability to respond to stimuli in a way that is deemed ‘normal’. Where the problems that you face heavily impair your ability to carry out social interactions, and leave you in a debilitated state. This life is reality for patient with psychosis, a mental health problem that causes people to perceive and interpret events differently from the average human mind. Psychosis can occur in a number of different conditions such as schizophrenia and bipolar disorder.

5147733588_e263f2b3f5_z
During recent times, a great deal of interest has arisen within the scientific community regarding the link between this condition and inflammation in the brain. In the late 20th century, post-mortem studies in patients with schizophrenia showed the presence of inflammation. However, these results were not always consistent, possibly due to differences in the regions of the brains which were examined. However, more recent studies, using brain scans in living patients, did find a more consistent increase in microglial activation in patients with psychosis, which is an indicator of neuro-inflammation. Microglia are resident, innate immune cells in the brain which have long been connected with the pathology of neurodegenerative diseases. The activation of these cells indicates inflammation, and it was suggested that individuals that display such inflammation may have a pre-disposition to developing psychotic disorders later in life.

At the Wolfson Molecular Imaging Centre of the University of Manchester, researchers are investigating whether this link between neuro-inflammation and psychosis does indeed exist. In order to ensure that the conclusions are valid, a large amount of evidence must be generated to support it and so a study is conducted in collaboration with other centres around the country. In this study, three groups of volunteers are tested; patients who have had psychosis for many years, patients for whom the onset of psychosis is recent, and healthy volunteers to act as controls. Each of these groups consists of twenty patients, therefore a total sample size of sixty patients is used in order to increase the statistical power of the results and increase the likelihood that they are representative of the majority of patients with psychosis.

3576501997_c519a2bfa4_z
All volunteers undergo a brain-scan called Positron Emission Tomography, or PET scan. PET scans involve the injection of a radioactive tracer into the body which emits positrons as it decays inside the tissues. This radiation can be detected by cameras. By using a specific radioactive tracer called [11C]PK11195, microglial activation can be measured in order to determine the amount of inflammation in the brain. Many of the results from studies to investigate this link between neuro-inflammation and psychosis seem to suggest that neuro-inflammation does indeed exist. Although of course more studies must be carried out in order to confirm this hypothesis, it does present an exciting new prospect of a possible treatment and establishment of preventative measures to assist patients with psychosis.

Post by: Maaham Saleem – courtesy of Sarah Fox (Volunteer with the British Science Association)