2013 was a year which saw a lot of important developments in Psychiatry. The arrival of DSM-5 was accompanied by a rich debate about the nature of diagnosis and a reflection on the revisions in the new manual. In the UK there was strong political support for improving services and quality of life for people with Dementia and their carers. For me one of the most remarkable findings was a study which found a 29 fold increase in urinary tract infections in people with Schizophrenia who had relapsed compared to a control group. Although this finding would benefit from replication it leads onto other interesting questions. There were other significant developments in genetics which we are going to see increasingly. Many mental illnesses now have a large number of gene associations although some of the effect sizes are small.
Mood Disorders
Researchers in this study looked at the outcome in mood disorders in the period before the widespread introduction of antidepressants, major tranquilisers and mood stabilisers. Subjects were follow up for between 1 and 30 years. The studies included 14,000 people and were published before 1970. The researchers had three main findings
1. Median rate of recovery was lower than in more recent studies
2. The time to recovery was longer than in more recent studies
3. The rate of recovery was higher than in more recent studies.
However there were methodological limitations. For instance antidepressants were introduced in the 1950′s and so this does not preclude the use of effective antidepressants in these older studies.
In one study (n=131) researchers looked at the relationship between depression and cognition in people with Alzheimer’s Disease. The researchers found that in their study there was no significant change in cognition in cases with remission of Depression at 24 weeks.
The relationship between Depressive symptoms in women over the age of 85 was examined in this study (n=302). Researchers used the 15 item Geriatric Depression Scale and found that with a score of <6 at baseline 46% had normal cognitive status 5 years later. With a score >6 at baseline 19% had normal cognitive status 5 years later.
There is a round-up of links at the BPS Research Digest which includes a TEDx collaboration with publishers Wiley to deliver a set of neuroscience talks with supplementary material. The Somatosphere blog features links to articles including one on lay accounts of Depression.
Professor Wray Herbert has a very good write-up of a study looking at memory in people with Depression. The researchers found that an ancient technique for storing memories – the method of loci – was effective in helping people with Depression improve their recall of positive memories.
Researchers at the Diabetes agency in Italy have undertaken a meta-analysis of longitudinal studies looking at the risk of Diabetes in people with Depression. The researchers looked at 1898 longitudinal studies and after excluding irrelevant studies were left with 23. These 23 studies included 424,557 subjects who were followed up on average for just over eight years. After adjusting for other risk factors the researchers found that people with Diabetes were 1.38 times more likely to develop incident Diabetes (new Diabetes) than people without Diabetes. The 95% confidence interval was 1.23 to 1.55 (P was less than 0.001). The adjusted risk of Diabetes in people with untreated depression was 1.56 although the confidence interval was wide and included values under one. The researchers suggest that this information can be used to help improve the health of people with Depression.
Simon and colleagues looked at how well people were able to recall their response to antidepressants. The researchers looked at 1878 people who had two more episodes of clinical depression. The subjects were asked to complete structured recall of response to previous medications. This was then compared against the medical records. In the medical records treatment response was evaluated using PHQ-9 scores. The researchers concluded that there was a low agreement (Kappa 0.10 with a 95% confidence interval of 0 to 0.25) between structured recall and PHQ-9 scores for response attributed to treatment. The researchers comment on the utility of interview assessments on the basis of their results.
There is an interesting study (via @claudiamegele) about the genetics of Depression. A study involving an international collaboration of 86 scientists looking at studies with a cumulative total of 34, 549 participants found no strong genetic links to Depression. There are various studies which show there can be a strong family history of Depression but these most recent findings suggest important lessons are yet to be learnt in understanding the relationship between genetics and unipolar Depression.
In a meta-analysis of Magnetic Resonance Imaging studies Sexton and colleagues identified a reduction in the volume of the Hippocampus in older adults with Depression compared to control groups. The researchers also identified similar volume reductions in the Thalamus, Putamen and Orbitofrontal Cortex.
At the American Academy of Neurology 65th Annual meeting in San Diego one research group will be presenting their research findings in a study involving 10,500 people aged 25-74. This was a 21-year prospective study. The researchers found a four-fold increase in mortality in people who had a Stroke with Depression compared to those with a Stroke without Depression after controlling for a number of confounding factors. These are the preliminary findings and it is more usual to look at these results after they have been published in a peer reviewed journal.
A study which is due to be presented at the American Academy of Neurology’s annual meeting looked at 250,000 people and investigated a possible relationship between the use of sweeteners and the prevalence of Depression. The researchers found that the prevalence of Dementia increased with an increasing use of sweeteners. However these results are preliminary and as above it is more usual to look at results after they are published in a peer reviewed journal. Indeed in the BBC article Gaynor Bussell of the British Dietetic association points out possible confounders while Beth Murphy from Mind points out the importance of people with Depression advises readers to follow the guidance of health professionals in the management of Depression.
A Canadian meta-analysis looked at the use of high frequency repetitive Transcranial Magnetic Stimulation in the treatment of Depression. This approach to treating Depression has been examined in the research setting. The authors of this study compared actual treatment with sham treatment. The meta-analysis included a cumulative total of 392 people with Major Depression. At the end of the study period for the trials the researchers found that the remission rate for treatment was higher than that for sham treatment. For those receiving the treatment there was a 53.8% remission rate compared to 38.64% in those receiving sham treatment. The odds ratio was 2.42 with a 95% confidence interval of 1.27-4.61 (p=0.007). Although the study does show benefit this does not mean that it would be used in routine clinical practice. This would depend on a number of factors including an evaluation of the technology in relevant policies.
There is a write-up of a study here on gene factors predicting response to antidepressants based on the genome wide analysis of 2799 people being treated for Major Depressive Disorder with antidepressants.
Psychiatrist Dr Alex Mitchell gives an excellent overview of clinical Depression for the general public in this video.
Researchers undertook a meta-analysis of 22 studies looking at the relationship between Mediterranean Diet adherence and risk for a number of diseases. They found a significant relationship between high adherence to the Mediterranean diet and reduced risk for Depression and Stroke as well as for cognitive impairment.
A write-up looking at British Journal of Psychiatry study, looks at arterial spin labelling to characterise depression.
Researchers looked at people with Bipolar Disorder and found a link with personality.
Depression increases the risk of mortality with cardiovascular disease. A new study suggests that sleep may link the two. Subjects were from the British Whitehall II study (n=5813), aged 50-74. Risk factors included less than 5 hours of sleep and disturbed sleep.
Research suggests exercise has complex relationship with mood in Bipolar Disorder via medwireNews.
In the PREDIMED study published in BMC Medicine, the researchers found that the Mediterranean diet was related to reduced Depression risk in Diabetes Type 2.
In this Finnish study a healthy diet which included vegetables and fruits was associated with less Depression. 2000 men were followed up for 13-20 years.
There is an interesting MedWire News write-up of research linking two genetic pathways to Bipolar Disorder. The genes code for proteins involved in synapse formation and an enzyme. The enzyme is thought to be influenced by mood stabilisers while the synapse forming protein is associated with increased excitation of neurons.
A look at the evidence for Depression screening in chronic illness in a cross-sectional PLOS One study (the review highlights recommendations on stratifying risk groups within populations with chronic illness as well as methodological limitations e.g. a need to focus on psychological therapies)
In a meta-analysis looking at Zinc levels in people with Depression, researchers included 17 studies (n=2447) and found statistically significant lower Zinc levels in subjects with Depression compared to controls (95% confidence interval of -2.51 to -1.19 µmol/L, p < .00001). Curiously the effect size for the difference was larger in inpatient versus community settings.
A look at research studies investigating complementary and alternative therapy in antenatal depression (the review comments on the lack of evidence and looks at some of the methodological difficulties that need to be addressed)
In a small fMRI study researchers looked at 15 people with late life depression and 13 controls . Previous research would suggest decreased executive performance in people with Depression. In this study the researchers found that on a test of executive performance there was increased activation in various parts of the Brain in people with late life Depression compared with controls. The study showed activation was increased in areas including the Superior Frontal cortex bilaterally, Insular cortex, Caudate and Putamen.
Mild Cognitive Impairment and Dementia
A recent audit of memory clinics by the Royal College of Psychiatrists shows a four-fold increase in the number of people attending memory clinics since 2011.
A look at cognitive tests that may be used in clinical trials with a mention of correlations with Amyloid load.
Results from the Whitehall II cohort study (a cohort of British civil servants) published in the British Journal of Psychiatry suggests that smoking in combination with drinking alcohol above the recommended limits was associated with a higher rate of cognitive decline. Compared to a group of people who did not smoke and drank moderately the high alcohol, smoking group experienced accelerated cognitive decline which was statistically significant. The decline amounted to an extra 2 years of cognitive decline for every 10 years of aging.
Interesting findings in a study showing correlations between blood pressure variability and cognition.
The researchers in this study find a possible relationship between bradycardia and Frontotemporal Dementia but recommend further research to confirm this relationship (Robles et al, 2013).
Researchers in this study identified differences in visual motion event related potentials between people with Alzheimer’s Disease and healthy controls (Fernandez et al, 2013).
There is a look at subjective cognitive impairment in this paper which is available at Neurologia (Garcia-Ptacek et al, 2013).
One research group suggests that a protein CD33 may be involved in the development of Late Onset Alzheimer’s Disease through an action on the brain’s support cells – the microglia http://bit.ly/14oIla3. The talk below covers CD33 amongst many other associations with Alzheimer’s Disease.
Several DNA regions have been identified in a Genome Wide Association study which may play a role in Alzheimer’s Disease (one of which is associated with Tau and Amyloid-Beta).
In this study there wasn’t found to be a difference in Hippocampal volume between people with Alzheimer’s Disease and behavioural variant Frontotemporal Dementia. The researchers suggest Hippocampal sclerosis in the latter group may account for this finding.
Researchers in this meta-analysis found a small but significant relationship between Amyloid Beta load and cognition.
The Alzheimer’s Society website features a cognitive assessment toolkit for professionals here. The toolkit was developed in conjunction with the Royal College of General Practitioners, the Department of Health, the Royal College of Psychiatrists, the College of Mental Health Pharmacy and the Dementia Action Alliance.
The Alzheimer’s Research Forum has just expanded and added to their risk factor database for Alzheimer’s Disease which includes a meta-analysis of study data on the 10 risk factors they include.
The Alzheimer’s Research Forum have a write-up on the 7th Human Amyloid Imaging Conference in Florida. The write-up includes a look at some of the work going on with Tau tracer compounds 18F-T807 and T808.
Hamilton and colleagues looked at the relationship between performance on a visuospatial task (Block design task) and subsequent development of visual hallucinations in people with Alzheimer’s disease and Lewy body dementia. The researchers found that severe visuospatial deficits (2.5 standard deviations below the mean) were associated with conversion to visual hallucinations of new onset in 61% of cases of people we’ve Lewy body dementia and 38% of those with Alzheimer’s disease. Mild visuospatial deficits were associated with a much lower percentage of people come developing new onset visual hallucinations. These findings therefore suggest that visuospatial performance may influence the likelihood of visual hallucinations in both Alzheimer’s disease and Lewy body dementia but more so in the latter condition.
A Cochrane Systematic Review concluded that although promising there was insufficient evidence to recommend Cerebrolysin for the treatment of Vascular Dementia at this point.
In a recent House of Commons debate several MP’s have told of their experience in looking after parents with dementia.
Alzheimer’s Disease is a degenerative condition which affects the brain and leads to problems with memory and other areas of cognition. While medication, exercise and a number of other approaches can slow down progression of the illness other approaches are being investigated. One of these approaches is Deep Brain Stimulation which has already produced positive results in the treatment of Parkinson’s Disease. In this write-up there is a look at the use of Deep Brain Stimulation in Alzheimer’s Disease. The researchers are stimulating selective areas in the brain including the Fornix and the Frontal Lobes. At the time of writing however it is too early to say whether this approach will be successful.
Researchers in this study (n=419, 70-90 years of age) looked at the relationship between Mild Cognitive Impairment (MCI) and the risk of falls. The researchers found that non-amnestic MCI was associated with an odds ratio of 1.98 for falls (95% Confidence Interval 1.11-3.53) compared to those without MCI.
Researchers in this study looked at risk factors associated with Mild Cognitive Impairment in their sample of 757 older adults aged 70-90 living in the community. The researchers found a variation in risk factors according to age and gender. In all group the APOE4 allele was a risk factor as were high Homocysteine levels and lower performance on identification of odours (although this can be confounded by smoking).
In this study, the researchers looked at risk factors for conversion from amnestic MCI to Dementia. There is a lot of research in this area. The researchers identified two aspects of memory function which were strong predictors of conversion to Dementia and to a lesser extent other factors such as age.
At the Alzheimer’s Research Forum there is coverage of a number of clinical trial results
There is a nice write-up of two studies at the Alzheimer’s Research Forum. The first study suggests that a better quality of sleep reduces the risk of developing Dementia of Alzheimer’s Type in people who have a gene that increases the risk of Dementia of Alzheimer’s Type. In our genome we have a lot of a genes. There can be many different versions of a gene in the population – these are known as alleles. One allele of the gene for the ApoE lipoprotein increases the risk of Dementia of Alzheimer’s Type 3-4 fold above that of people with other versions of the gene. The researchers in this study used sleep actigraphy to investigate sleep. The gold standards for investigating sleep has been an approach called overnight polysomnography which usually takes place in a sleep laboratory and includes techniques such as Electroencephalography. Actigraphy involves the use of sensors attached to the body (e.g. wrists) to detect movement and other measures. This is a relatively low cost approach and has been quickly gaining ground.
A write-up of an FDA approved Amyloid imaging agent.
Researchers find accumulation of alpha-synuclein in gastrointestinal system in Parkinson’s Disease.
Post-mortem brain biopsy study looks at sensitivity in the diagnosis of neurodegenerative disorders.
This study suggests DNA methylation may be a therapeutic target in FTLD. However further research needed.
This small study finds anterior Cingulate atrophy in bvFTD and posterior Cingulate atrophy in DAT.
This autopsy ADNI study show evidence of 100% specificity and 80% sensitivity for detecting DLB with Occipital FDG-PET.
Australian AIBL study finds 30.5% rate of conversion from MCI to DAT over 18 months in the study sample.
This CSF study investigates biomarkers to distinguish DAT from control and finds two metabolite candidates.
CSF-Presenilin 1 complexes were elevated in DAT in this post-mortem study.
A look at the evidence on omega-3 fatty acids and cognitive decline
An updated Cochrane review finds evidence for a benefit of exercise on cognition but not mood in Dementia. 16 trials were included with a total of 937 subjects.
Failure in reverse fox test was linked to Parietal hypoperfusion in DAT
Researchers develop new preparation of Methylene Blue using nanoparticles.
Researchers in this EEG study find difference in right temporal region frequencies in DAT compared with controls.
This Alzheimer’s Research Forum article looking at new international developments in sharing of clinical trial data.
Researchers have found a link between retinal thickness and Alzheimer’s Disease using optical coherence tomography.
There is an interesting Alzheimer’s Research Forum write-up of a study looking at amyloid plaques up to 1 year after TBI.
Researchers find Alzheimer’s Disease related Presenilin mutation increases the frequency of Dementia in Alzheimer’s Disease related Amyloid Precursor Protein cleavage.
The National Institute of Health has released the genome data from their Alzheimer’s Disease sequencing project. The project includes 410 people within 89 families.
In a meta-analysis of the effects of an antihistamine on cognition, researchers looked at 5 RCT’s and reported a finding for only one of several cognitive scores (NPI) in studies investigating Dementia in Alzheimer’s Disease.
New research suggests that the Alzheimer’s Disease associated Amyloid stimulates the alpha 7 nicotinic receptor causing Astrocytes to release Glutamate which is involved in a process leading to neuronal cell death.
A call for a national database of people with Dementia to help police has produced a mixed response with the Department of Health calling for evidence to support such a move.
The researchers found that if people in the study had the ApoE4 allele and they had a good quality of sleep, their risk of developing Dementia of Alzheimer’s Type was increased 2-fold instead of 3-4 fold (relative to those with other alleles). The researchers also looked at the brains of people who had died and found that better sleep quality was linked to a lower density of neurofibrillary tangles. Neurofibrillary tangles are another structure found in the brains of people with Dementia of Alzheimer’s Type and are thought to play a central role in Alzheimer’s Disease.
This type of result also gives us insight into another debate – genes versus environment. A longstanding debate is whether our fate is determined by the environment or by our genes. There are various ways our environment can impact on sleep e.g. noise, stressors and so these results might show one route through which the environment might modify genetic determinism.
In a widely reported study, researchers identified a compound which stopped the development of Prion disease in a model with similarities to Alzheimer’s Disease. However it will be interesting to see the results of clinical trials.
Duration, severity and age were risk factors for developing psychosis in Parkinson’s Disease in this study.
A group of researchers in Sweden followed up a cohort of people in three age groups: 85, 90 and over 90. The researchers found that people in these groups were less likely to develop Dementia if they scored more highly on cognitive testing (the Mini-Mental State Examination) or if they had more social contacts. Depression was associated with a higher incidence of Dementia over 5 years.
The Alzheimer’s Society has launched a new Dementia guide for people diagnosed with Dementia.
The rate of atrophy of the Hippocampus was examined in this study (n=277). The researchers compared the atrophy rate in mild cognitive impairment, Alzheimer’s Disease and controls. The researchers found a greater rate of atrophy in people with Alzheimer’s Disease. Although the size of the Hippocampus is more likely to be reduced in Alzheimer’s Disease compared to the other two groups knowing about differences in the rate of atrophy between groups is helpful.
Deputy Prime Minister Nick Clegg has become a Dementia Friend.
Researchers have identified ‘non-Amyloid’ forms of Dementia in Alzheimer’s Disease in up to one third of cases. While the presentation may be similar the underlying pathology is clearly different. Researchers have suggested a number of explanations. One possibility that has been raised is that the tracer compounds used for identifying plaques may be sensitive to subtle differences in Amyloid.
There is an interesting write up of research into the possible relationship between insulin and Alzheimer’s Disease.
A PLOS Medicine round-up looks at incontinence in Dementia.
Researchers suggest Heparan Sulfate Proteoglycans involved in Alzheimer’s Disease. Enzymes for receptors may be a target.
Researchers investigate Alzheimer’s Disease using EEG analysis and suggest characteristics based on their analysis.
Researchers are undertaking a study into the effects of tailored activity programs for people with Dementia.
The recently published Alzheimer’s Disease International ‘World Alzheimer’s Report‘ predicts that Dementia of Alzheimer’s Type will affect 277 million people globally by 2050.
Research suggests that PirB binds Beta Amyloid before it forms the Beta Amyloid plaque and this may contribute to the neurodegenerative process.
Researchers found a number of factors that help carers for people with strokes including reminiscing about past experiences, making sense of experiences an planning for the future.
A GBA gene mutation leads to early Parkinson’s Disease through lipid changes. The lipids also have an independent link with cognitive impairment in Parkinson’s Disease in people who do not have this gene mutation. http://bit.ly/1f4OQ6Z
The National Institutes of Health in America are allocating significant funding for Alzheimer’s Disease prevention studies.
In this study researchers found that detecting the smell of Peanut Butter through the left nostril was impaired in people with Alzheimer’s Disease. Smell can also be affected in Lewy Body Dementia but an important confounder is the history of smoking which can also lead to an impairment in smell.
There is an interesting write-up of a paper by Jucker and Walker in which they suggest Prion like proteins spread through brain in many neurodegenerative disease.
Researchers have developed three tracer compounds to help image the pathology in Alzheimer’s Disease. Thee are two write-ups of the studies (here and here) which discuss PBB3, THK’s and a third compound. With the PBB3 tau ligand the researchers suggest that it will bind many forms of tau aggregate that occur in different diseases including Frontotemporal Dementia.
Does tau travel between neurons?
PLOS One study – 95 older adults without Dementia – inflammation showed a negative correlation with Corpus Callosum integrity.
An Australian group have looked at the ability to think about the future in people with behavioural variant Frontotemporal Dementia (bvFTD). There were 30 subjects in the study, 10 with bvFTD, 10 with Alzheimer’s Disease and 10 controls. Amongst other results, the researchers found that atrophy in the medial temporal regions (specifically identifying the right Hippocampus) and Occipital Cortex was associated with impairments in thinking about the future. This is a small sized study and it would be interesting to see the results of further replication studies.
This interview looks at research into blocking mglu5 to restore memory.
In an interesting multifaceted study researchers looked at memory loss and aging. They identified a gene that was decreasingly expressed with age and found evidence that expression of the gene in the Dentate Gyrus was important for memory.
There is a write-up here of two studies on Dementia published in the Lancet. In one study (1) the researchers sampled 7635 people over the age of 65 screening for Dementia. Two decades later they screened 7796 people and compared the two groups using various statistical adjustments. The researchers concluded that there had been a lower prevalence in the latter group (6.5% v 8.3%) and that this was statistically significant. These results may not generalise to other areas and populations and there is also commentary in the above write-up. In the second study in Denmark, people who were in their 90′s were assessed on their cognition at two points in time a decade apart. The researchers found that there had been an improvement in the performance on a standardised cognitive test as well on activities of daily living over the study period.
There is a report here on the first Dementia dogs starting work with people with Dementia.
There is a brief write-up here of a study linking difficulties with emotive memories and the orbitofrontal cortex in Frontotemporal Dementia.
Researchers in one study found evidence that people with Alzheimer’s Disease may experience difficulties in recognising changes in affect in themselves* (Verhülsdonk S et al, 2013).
There is a look at Tetracyclines and Amyloidosis in this paper (Stoilova et al, 2013).
Researchers in Japan suggest that there may be subtypes of Alzheimer’s Disease determined by comorbidity on the basis of their neuroimaging findings (Fukazawa et al, 2013).
Researchers have characterised the Magnetic Resonance Imaging findings for a C9ORF72 variant of Amyotrophic Lateral Sclerosis. They distinguished these MRI findings from those in people with the C9O4F72 variant of Frontotemporal Dementia.
One or more reported episodes of Delirium occurred in 25% of people with Lewy Body Dementia in comparison with 7% of people with Alzheimer’s Disease in this retrospective study (n=180).
A Cochrane Database Systematic Review investigated Rivastigmine in the treatment of Vascular Dementia and Vascular Mild Cognitive Impairment. The researchers identified only three trials (n=800) with two trials showing no benefit but a third showing some benefit for cognition at 24 weeks versus placebo in Vascular Dementia (n=710). Nevertheless it will be interesting to see the findings in further meta-analyses as more studies become available for inclusion.
An intriguing Swedish study has looked at the effects of Acetylcholinesterase Inhibitors (ACHEI’s) on the risk of developing myocardial infarcts in people being treated for Alzheimer’s Disease (this included people with Alzheimer’s Mixed Dementia). This was a cohort study (n=7073) using data from the Swedish Dementia Register and national registers for other health outcomes. Amongst other findings the researchers found that people taking the highest dose of AChEI’s had a significantly lower risk of developing Myocardial Infarcts relative to the control group who had not used them. In this cases the hazard ratio was 0.35 (95% Confidence Interval 0.19-0.64).
Mild cognitive impairment was associated with a reduction in quality of life in this study (n=205). The QOL-AD (Alzheimer’s Disease) instrument was used to assess quality of life.
There is a detailed write-up at the Alzheimer’s Research Forum of a paper published in JAMA Neurology looking at the relationship between late onset Epilepsy or epileptiform activity and cognitive decline. The researchers examined people with mild cognitive impairment as well as Alzheimer’s Disease. They found that epileptiform activity was associated with cognitive decline.
Impaired glucose tolerance was associated with cognitive impairment in this study.
NHS Choices looks at the recent study suggesting slower decline in Dementia and an association with ACE inhibitors. There is other research which has also examined this relationship.
Researchers in this study found an association between Human Herpes Virus 6 infection and cognitive dysfunction.
Researchers have announced preliminary results suggesting alterations in a BCHE gene promoter linked to Lewy Body Dementia (LBD). They found a link with 20% of LBD cases but it is important to note that these are preliminary findings.
A Genome Wide Association study identified 11 new gene candidates for Alzheimer’s Disease.
A PLOS One study finds that Dementia tweets are mainly about research and health matters. The researchers encourage the Dementia research community to use this medium.
There is a write-up here of a study in which Anaemia was associated with a higher risk of incident Dementia in a cohort of 2552 older adults. The paper was published in the Journal Neurology.
One research group looked at classifying cognitive impairment in traumatic brain injury. There is a good write-up of the 3 clusters identified from the neuropsychological testing.
The authors of one paper on the aging brain conclude that although there is evidence of plasticity in older adulthood in response to cognitive stimulation there is still a need for research into how gains are generalised. The authors also cite evidence from studies such as the Experience Corps Project which show that the environment can play a significant role in achieving cognitive gains.
Apathy (measured using the apathy evaluation scale) in people with Dementia or Mild Cognitive Impairment was associated with reduced daytime activity (measured using a wrist-worn actigraph) in this study.
South Korea is reported to have a rapidly aging population and the anticipated increase in people with Dementia is examined in detail in this article.
Psychosis
Researchers looked at involuntary treatment in people with Schizophrenia in Denmark using a Psychiatry register. The researchers looked at the data for 18599 patients over a 7 year period. Of these patients 3078 underwent involuntary treatment. The researchers found that treatment with antipsychotics accounted for 99.5% of involuntary psychotropic drugs administered. Electroconvulsive therapy accounted for only 4.8% of all involuntary treatments. These findings may not be generalisable to other countries as there are many factors that can influence these results including the structure of health services.
There is a study from Hong Kong in the Australian and New Zealand Journal of Psychiatry looking at relapse rates in first-episode psychosis. The researchers looked at the cumulative relapse rate as well as risk factors for relapse. The researchers identified many risk factors for relapse which included non-concordance with medication (Hui et al, 2013).
There is an open-access article on structural MRI findings in Schizophrenia in the Journal of the Norwegian Medical Association available in both Norwegian and English. The researchers found evidence of reduced Hippocampal volume but increased volume in the Globus Pallidus in study subjects with Schizophrenia compared to controls.
In another experimental study (n=20) published in JAMA Psychiatry, researchers found that Sodium Nitroprusside was effective in the treatment of psychosis with the effect beginning within 4 hours and lasting up to 4 weeks after a single administration with these effects not observed in the placebo group. Further studies will be needed to see if this effect is seen in large samples and to assess the risk-benefit ratio of using this medication which like other medications has side-effects. It will be interesting to see the results of further research in this area.
Musical hallucinations were more likely in females and people with left-sided hearing impairment in this study looking at people undergoing audiometry testing. In their sample of 194 people, 3.6% experienced musical hallucinations. Age and severity of hearing impairment were not risk factors however.
Professor Julian Leff has been using virtual reality environments to help people with Schizophrenia who hear voices, manage their experiences. There is a write-up here.
Dr Emily Dean has an interesting piece on NMDA receptor antibody encephalitis as a cause of Schizophrenia with papers presented at the recent American Psychiatric Association annual meeting.
There is a recent case study of Olfactory Reference Syndrome misattributed to Trimethylaminuria in the Journal of Nervous and Mental Disease .
Via @SameiHuda there is an intriguing JAMA study looking at the effects of a vasodilator on symptoms in Schizophrenia and it will be interesting to see the results of follow-up studies in this area.
Smoking and Diabetes are risk factors that affect mortality during the 6.2 year follow-up period in this study. The study was looking at people with Schizophrenia and there is a good summary in the write-up above.
An American group have produced an overview of guidelines used for treatment approaches in Schizophrenia.
There is an interesting write-up at the Schizophrenia Research Forum on the psychosis prodrome from the 2013 International Prodromal Research Network Meeting in Florida.
The risk of urinary tract infections was found to be increased 29 fold in relapse of Schizophrenia compared to healthy controls in this study http://ow.ly/jL11G
A new rating scale for the negative symptoms of Schizophrenia – the CAINS is covered in this piece.
The Schizophrenia Bulletin features a large meta-analysis of the relationship between childhood adversity and the subsequent development of psychosis and the article is open-access. The authors concluded that people who had developed psychosis were 2.72 times as likely to have experienced childhood adversity as controls. The authors combined different types of studies (e.g crosssectional and longitudinal). The issue of integrating different types of adverse events is complex. However there are many outcomes including non-psychotic disorders or healthy adaptations. These findings provide evidence to better characterise one of the possible outcomes.
The New York Time has a piece by Professor Elyn Saks who discusses his diagnosis of Schizophrenia and how he has developed a successful academic career. Professor Saks offers many insights into how illness can impact on functioning and his own personal experience of overcoming these difficulties.
via @Keith_Laws there is an interesting study looking at language lateralisation in people with Schizophrenia. There is an evolutionary theory developed by Professor Tim Crow which states that language results from lateralisation in the brain and that this lateralisation process can be affected in Schizophrenia. The researchers in this study looked at previous investigations of lateralisation using dichotic listening tasks. These tasks involve the presentation of bilateral auditory stimuli. Subsequent testing can pick up subtle differences in the way the right or left auditory stimuli are processed if this difference is present. The researchers in this study found that subjects with Schizophrenia had a lower degree of language lateralisation compared to a control group. However the magnitude of this difference became much larger in the subgroup with auditory hallucinations.
McCarthy-Jones and colleagues have undertaken a fascinating study into auditory hallucinations in people with Schizophrenia and other diagnoses associated with hallucinations (n = 199). The researchers found that in 39% of people, auditory hallucinations were related to memories of conversations that people had experienced previously. 45% of the subjects reported the voices as manifesting the same content and the researchers have developed subtypes on the basis of a cluster analysis of their findings.
The effect of trauma/PTSD in people with Schizophrenia was investigated in this study (n=292). The researchers didn’t find evidence of cognitive impairment (using a neuropsychological test battery). However there was evidence of an increase in depression in the group with trauma/PTSD compared to those without.
The March 2013 edition of the American Journal of Psychiatry includes a meta-analysis of non-pharmacological interventions in Attention Deficit and Hyperactivity Disorder, a meta-analysis of Metabolic Syndrome comorbidity in Bipolar Disorder and a Swedish cohort study looking at comorbidity in Schizophrenia. There is an accompanying podcast.
The February 2013 edition of the Journal of Clinical Psychiatry features clinical trials of Desvenlafaxine in major Depression and Lurasidone in Schizophrenia, the use of high frequency Transcranial Magnetic Stimulation (see above) as well as a prevalence study on attenuated psychotic symptoms. There is an accompanying podcast.
There is an article into Journal of medical case reports where the researchers document a case of delusional parasitosis associated with hyperthyroidism. In Delusional Parasitosis a person believes that they have a parasitic infestation. This is a rare type of delusion. Few people with Hyperthyroidism would get this delusion and few people with this delusion would have Hyperthyroidism. That is what makes this case so interesting although the relationship with Hyperthyroidism had been previously documented. In this case study the researchers had followed the patient up over a prolonged period of time and identified the resolution and relapse of the delusion with the remission and relapse of Hyperthyroidism. The chronic course of this relationship strengthened the hypothesis that the Hyperthyroidism was linked. Nevertheless single case studies are usually interpreted with caution as there are many confounding factors which can also play a role.
The Schizophrenia Research Forum has an interesting piece looking at the negative symptoms in Schizophrenia. There is a detailed write-up which covers one study which looks at a subgroup of people with a specific genotype treated with Vitamin B12 supplements. The second study finds evidence of an association with interruption of the Right Arcuate Fasciculus, the Left Uncinate Fasciculus and the Right Inferior Longitudinal Fasciculus. Check out the write-up for further details.
Dr Oliver Sacks has published a paper in Brain describing a variation of musical hallucinations. In this form of musical hallucinations people see the musical score.
50 cases of Delusional Infestation are covered in the Asian Journal of Psychiatry.
Write up of genome wide association study finding new gene associations with Schizophrenia.
Study finds inflammatory markers raised in first-episode Schizophrenia (n=96).
This write-up at MedWire News looks at fMRI research suggesting complex differences between striatal-Prefrontal Cortex connections in people in this study with Schizophrenia compared with a control group.
via MedWire News the researchers in one study found that retinal venules were wider in people with Schizophrenia than in a control group (n=922) although the significance is unclear.
Researchers looked at auditory verbal hallucinations in older adults with Schizophrenia (n=198) and found that compared to younger adults with Schizophrenia in previous reports. The researchers findings included that in older adults with Schizophrenia auditory verbal hallucinations were more likely to be associated with depressive symptoms.
Mental Elf reviews the Cochrane Review of Fluphenazine treatment for Schizophrenia in this post.
Meta-cognitive training to address cognitive distortions was found to improve ratings of delusions in people with Schizophrenia in this study. The training had an additive effect to medication.
Research studies into telehealth in people with Schizophrenia were examined in this study. Both advantages and disadvantages to internet access were found with a benefit for empowerment and recommendations were made for future studies.
Researchers investigated various social neuroscience methodologies for use in trials for people with Schizophrenia. One approach in particular appeared to have advantages for use in research.
There have been a few new findings in 22q11.2 Deletion Syndrome which can leads to a number of conditions including Schizophrenia, Graves disease and Rheumatoid Arthritis and has a prevalence of 1 in 4,000 (although it may be more common). Both Velocardofacial syndrome or DiGeorge’s syndrome result from 22q11.2 deletion but the term ’22q11.2 Deletion Syndrome’ subsumes both of these syndrome names. There has been an established link with Autistic Spectrum Disorders but a recent study suggests this is not the case. Dr Angkustsiri and colleagues at UC Davis have found that although 22q11.2 Deletion Syndrome is associated with social impairment, this does not meet the criteria for Autistic Spectrum Disorders. In another study researchers found that 4 out 159 people with 22q11.2 Deletion Syndrome had Parkinson’s Disease with age of onset between 39 and 48 years of age. These initial findings will need further confirmation.
Garety and Freeman looked at Delusions in this November 2013 British Journal of Psychiatry paper. They found a link between worry, catastrophisation, attributional bias and jumping to conclusions and Delusions. They found no link between Delusions and theory of mind however.
There is an interesting MedWire News write-up of a study which found a link between self-reported mood stability and psychotic episodes. The researchers looked at the responses to a question about mood stability that was administered in a large survey. They found a link between a high self-rating of mood instability and likelihood of psychotic experiences.
Researchers in this small 12-week trial of an SSRI in depression looked at grey matter volume at the beginning of the trial and cognitive and mood changes by the end of the trial. Subjects were aged 55 and over (n=34). The researchers found that a larger improvement in mood was associated with greater grey matter volume in several areas including the Cingulate gyrus as well as the superior and middle Frontal gyri.
This Cochrane trial looked at methods for retaining recruits to randomised trials. The reviewers concluded that incentives either after return of a completed questionnaire or with the questionnaire with a further incentive were the most effective methods for retaining recruits.
There is an interesting MedWire News write-up of a meta-analysis in which researchers looked at cardiometabolic risk factors in people with Schizophrenia. There were 185, 606 people with Schizophrenia included in the meta-analysis and the control subjects across the studies totalled 3,900,000. The data showed that the people with Schizophrenia in this study were 4.43 times more likely to have abdominal obesity than the control subjects. Furthermore they found that the risk for Diabetes was doubled relative to the controls.
Delirium
Researchers in this study looked at people over the age of 65 with Dementia who developed Delirium while in hospital and found 25% mortality over 30 days. However there were 139 subjects in the study and it will be useful to see further replication studies.
In this study, researchers found evidence for the efficacy of the Observational Scale of Level of Arousal in detecting Delirium.
Researchers in this study found that severe white matter hyperintensities on MRI scans were a significant predictor of postoperative Delirium in Cardiac surgery (OR: 3.9; 95% CI: 1.2-12.5) and that this information could be clinically useful.
There is a small case series (n=5) looking at Ramelteon in Delirium. Ramelteon is a Melatonin receptor agonist. Further studies will be needed to see if this effect is seen in large samples and to assess the risk-benefit ratio of using this medication which like other medications has side-effects. It will be interesting to see the results of further research in this area.
In one study researchers looked at 581 people undergoing major non-cardiac surgery. They identified a number of risk factors for developing Delirium and stratified people into low and high risk groups. For the entire group the risk of postoperative delirum was 40% at 1-2 days post-op. The high risk group developed Delirium in 72% of cases if they had postoperative pain and used high dose Opioids. In comparison those in the low risk group who used low-dose Opioids and low level pain developed Delirium in 20% of cases. As Delirium is common, these findings are helpful in monitoring emerging Delirium.
A new tool for assessing Delirium has been published. The AWOL tool for Delirium allows risk stratification by utilising four risk factors: (A) age > 80, (W) results on a specific cognitive subtest (O) orientation and (L) nursing assessment of illness severity. There are a number of tools for assessing Delirium and this multidisciplinary assessment tool has the potential to support clinical decision making.
Mental and Behavioural Disorders Due to Psychoactive Substance Use
In a meta-analysis of pre-operative alcohol use and post-operative surgical complications, researchers found a statistically significant relationship between high alcohol use preoperatively and risk of post-operative mortality (relative risk 2.68 (95% CI 1.5-4.78)). Premorbid alcohol use was associated with an increased risk of postoperative general infections (relative risk 1.73 (95% CI 1.32-2.28) amongst other findings.
A look at a Cochrane review of evidence for psychosocial interventions in people with severe mental illness and substance misuse (in the review it is suggested that harm reduction can be a useful outcome and there is a need to address methodological difficulties in future studies).
In a longitudinal study by Bobo and colleagues the researchers looked at men aged 50 and over during a 10 year period to ide