This week the H1N1 influenza virus has dominated the news. However a new study in the American Journal of Psychiatry uses data from the STAR*D trial and shows significant differences between people who are and are not eligible for inclusion in Phase III trials an area which apparently is not yet regulated by the FDA. There are a number of Cochrane Database Reviews looking at various issues including the use of 24 hour care facilities in people with Schizophrenia, a comparison of Sertindole with other antipsychotics and also dosing of Chlorpromazine. There is some analysis from the CATIE-AD looking at a number of side-effects with second-generation antipsychotics in people with Alzheimer’s Disease, while the EUFEST trial looks at cognitive effects of antipsychotics in people with psychosis. There have been some recent genetic findings in autism, evidence for a benefit for Pregabalin in restless legs syndrome and an elucidation of the neurobiology of caffeine withdrawal. On a slightly different note, a large genetic study has recently been completed providing many interesting findings including the probable origins of modern humans somewhere on the borders of Namibia as well as some insights into genetic diversity in Africa and a possible period in which modern humans diverged and were separated into two groups perhaps for up to a period of 100,000 years. IBM’s artificial intelligence project – Blue Brain now has a virtual body and the research team are monitoring how it responds to a virtual environment.
Research in Psychosis
In the EUFEST study there was found to be an improvement in cognition in people treated for schizophreniform disorder or first-episode schizophrenia with either Haloperidol or a second-generation antipsychotic (Davidson et al, 2009). The authors of a recent paper defend the Wisconsin Card Sorting Test against critics who argue that it is not an effective measure of functioning of the frontal lobe and suggest theoretical and practical approaches to improving its validity. (Nyhus and Barcelo, 2009). The authors of a Cochrane review on 24-hour care for people with schizophrenia concluded after finding a single randomised trial with 22 participants and limited outcome measures that large scale service changes should be accompanied by efforts to obtain evidence of their effectiveness before the opportunity passes (Macpherson et al, 2009). The authors of a Cochrane review of Sulpiride verses placebo for people with schizophrenia concluded that there was limited evidence of superiority over placebo from randomised controlled trials (Omori and Wang, 2009).
The authors of a Cochrane review on dosing of Chlorpromazine in people with schizophrenia concluded that it has taken many decades for the average Chlorpromazine dose to decrease. They also found that the low-dose Chlorpromazine groups from randomised controlled trials experience less side-effects than those in the high dose group (as expected). The higher-dose group experienced higher drop-out rates due to side-effects. Interestingly, the author’s were able to identify only four studies of relevance with a total of 1012 participants (Liu and Haan, 2009). 70 relatives of people with schizophrenia and 63 controls were assessed on an emotion recognition test and the relatives were significantly more likely to assign negative attributes to neutral faces than the control group and also to attribute emotions to neutral faces. The authors interpret this as evidence of an impairment in social cognition (Eack et al, 2009). The authors of a meta-analysis looked at neurological soft signs in people with schizophrenia and their relation to cognitive performance and positive and negative symptoms. They found that up to 10 per cent of variance of neurological signs were shared with negative and positive symptoms and cognitive performance and concluded that these phenomenon were mostly distinct from each other (Chan et al, 2009).
A meta-analysis of alcohol use in schizophrenia provided evidence that roughly one-fifth of people with schizophrenia had a lifetime diagnosis of an alcohol use disorder (Koskinen et al, 2009). In a systematic review of the Sertindole compared with other atypical antipsychotics, the authors did not find any significant differences with the other antipsychotics other than risperidone. As they found only two studies of relevance they stated that their conclusions were therefore limited. (Komossa et al, 2009). In a small MRI study with 19 people with schizophrenia, 11 people with bipolar disorder and 20 controls, the left amygdala volume was associated with reduced immediate and delayed verbal recall in people with schizophrenia but increased corresponding responses in people with bipolar disorder (Killgore et al, 2009). In a study of 162 people with a diagnosis of schizophrenia or schizophrenia-related disorders and receiving risperidone, the use of the positive and negative syndrome scale for schizophrenia remission criteria provided evidence that remission fluctuated and that it was correlated with insight and social outcome. The authors however cautioned against the use of symptoms alone in defining remission (Eberhard et al, 2009).
Research in Dementia
In another study, 16 people with Alzheimer’s disease were compared with 22 people with Vascular Dementia. Researchers were interested in the vascular risk factors and although they found some trends there were no significant differences between the groups on the primary outcome measures. Perhaps the study was insufficiently powered to detect a difference (Morovic et al, 2009). In the CATIE-AD study, the researchers looked at 421 people with Alzheimer’s disease in an outpatient setting. They were interested in the effects of treatment with a second generation antipsychotic relative to a placebo group during a 36-week period. They found a significant association with weight gain in the Olanzapine and Quetiapine groups and also found that Olanzapine was associated with a significant decrease in HDL cholesterol compared to the placebo group (Zheng et al, 2009). In a small twin pair study (n = 17 pairs) with autopsy confirmed Lewy Body Dementia, 16 of the pairs were discordant for Lewy Body Dementia suggesting a role for environmental factors or else a need for a larger replication study (Wang et al, 2009).
In a cross-sectional study of 118 people with Parkinson’s disease, fatigue was significantly associated with scores of depression and anxiety, pain and Unified Parkinson’s Disease Rating Scale scores (Hagell and Brundin, 2009). In a study of 97 people over the age of 60 at death and not having dementia, 20% had neuropathological diagnoses of Alzheimer’s disease (Price at al, 2009). In a Cochrane review of the use of Rivastigmine in people with Alzheimer’s disease the authors examined nine trials with 4775 participants and used ADAS-Cog scores and 6-12 mg of Rivastigmine. With these doses there was a significant decrease in the rate of decline of cognition and activities of daily living. The authors included recent trials on the transdermal patch and found that there were fewer side effects with the smaller patch than with an equivalent capsule dose (Birks et al, 2009).
News in brief
The authors of a Japanese epidemiological study in the British journal of psychiatry report in association between increasing levels of lithium in the drinking water and reduced rates of suicide. A fascinating genetic study completed on 121 African populations and 60 non African populations in Africa identified the border of South Africa and Namibia as the most probable origin for modern humans as well as providing further evidence for the high levels of genetic diversity. This has been a large study with genetic samples obtained from the populations in sometimes remote places. The research found 14 ancestral population clusters. They also found evidence that two populations had been separated from each other as much as 100,000 years. In another study a gene mutation associated with bipolar disorder and schizophrenia was assessed in 115 healthy volunteers and using MRI the researchers found an association between the Amygdala’s connections to other regions and the dorsolateral prefrontal cortex connections also. Gangliosides have been shown to have a neuroprotective role in in Alpha-synuclein induced neuronal cell death. In this study, the researchers disrupted the action of lysosomes which degrade material in the cell and then used gangliosides to reduce the subsequent damage. They suggest this as the mechanism by which gangliosides exert their neuroprotective action. In another study, patients with epilepsy who were undergoing intra-operative electrode recordings of activity participated in a study which used a reward paradigm for assessment of decision-making. Activity in the hippocampus occurred transiently when the participants were assessing situations with high degrees of uncertainty. People undergoing caffeine withdrawal were found to have increased cerebral blood flow and increased theta activity with the latter was suggested as the neural correlate of tiredness.
In a placebo controlled trial with 58 participants with restless legs syndrome Pregabalin was associated with the resolution or improvements in the restless leg symptoms. In a study of short term memory researchers found that when people were presented with shapes or colours and asked to match this on a screen (e.g. match against a range of presented colours), retrieval was dichotomous rather continuous such that by 10 seconds participants either recalled the information accurately or not. The protein Oct3 transports dopamine into and out of cells and has been associated with both Parkinson’s disease and is also involved in the transport of MPTP (which is used in a model of Parkinson’s disease) in one study. This may open up a new therapeutic approach.
An electronic device developed by NASA which is able to detect odours at as low as one part in 1,000,000 has been used to discriminate between glioma and healthy cells. This would seem to suggest that glioma cells emanate particles and this might inform future research in this area. A new design approach for brain stimulating electrodes has been presented at a conference in Europe recently. A scientist and project manager at a company producing these devices, Wolfgang Eberle has suggested that future designs of deep brain stimulating electrodes need to incorporate smaller electrodes at the size of single neurons in order to produce a more selective response.
A study in the American journal of psychiatry included an analysis of data from the STAR*D trial and was used to evaluate the inclusion criteria for phase III studies. The researchers utilised data from 2855 citalopram treated patients and found that approximately 22 per cent of patients would be eligible for phase three trials. Those that met the inclusion criteria were more likely to experience remission from depression. (34.4% this is 24.7 per cent in the remainder of the group). As the inclusion criteria for studies is not regulated this may be a future area for regulation. Two studies examined the genetics of autism. In the first study, a genome wide association study was undertaken of people with autistic spectrum disorders, family members and controls. Gene variants were found in chromosome 5 with two candidates being Cadherin 9 and Cadherin 10 which code for neuronal cell adhesion molecules. In another study by the same group, there was further evidence to support an association with the neuronal cell adhesion molecule and a role for the ubiquitin degradation pathway was also found. An fMRI study of 13 children with high functioning autism and 13 controls provided evidence that children with autism were more likely to activate the supplementary motor area rather than the cerebellum during a finger tapping task. The reverse was the case in controls. The use of the supplement motor areas suggests a tendency towards conscious control of movement in the children with autism.
In a surface electrode recording study, children undergoing assessment prior to surgery for epilepsy, were tested on response to visual stimuli. A response was detected in the visual cortex as quickly as 100 ms after initial presentation of the stimulus. This demonstrates the speed with which the brain is able to respond to visually presented information. The creators of the IBM sponsored Blue Brain project have now incorporated the simulated brain into a virtual body and are looking at how it interacts with a virtual environment. A mutation in the Acta2 gene has been associated with a number of vascular disorders including premature thoracic aortic aneurysms and ischaemic stroke. While not directly related to psychiatry, news that a man delivered his baby son after studying YouTube footage shows the many ways in which this technology is influencing health related behaviours.
Birks J et al. Rivastigmine for Alzheimer’s Disease. Cochrance Database Syst Rev. 2009. Apr. CD001191.
Chan R et al. Neurological soft signs in schizophrenia: A meta-analysis. Schizophrenia bulletin. 2009 April E-pub.
Davidson M et al. Cognitive effects of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: A randomised, open-label clinical trail (EUFEST). Am J Psychiatry. 2009. Apr. Epub.
Eack S et al. Social cognition deficits among individuals at familial high risk for Schizophrenia. Schizophrenia Bull. 2009. Epub.
Eberhard J et al. Remission in schizophrenia: analysis in a naturalistic setting. Comp Psychiatry. 2009. 50(3). 200-8. Epub.
Hagell P and Brundin L. Towards an understanding of fatigue in Parkinson Disease. J Neurol Neurosurg Psychiatry. 2009. 80(5). 489-92. Epub.
Killgore W et al. Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder. Cogn Behav Neurol. 2009. 22(1). 28-37.
Komossa K et al. Sertindole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev. 2009. Apr. 2.
Koskinen J et al. Prevalence of alchol use disorers in schizophrenia – a systematic review and meta- analysis. Acta Psychiatr Scand. 2009. Apr. Epub.
Liu X and De Haan S. Chlorpromazine dose for people with schizophrenia. Cochrane Database Syst Rev. 2009. CD007778.
Macpherson R et al. Twenty-four hour care for schizophrenia. Cochrane Database Syst Rev. 2009. CD004409.
Morovic S et al. Vascular characteristics of patients with dementia. J Neurol Sci. 2009. Apr. Epub.
Nyhus E and Barcelo F. The Wisconsin Card Sorting Test and the cognitive assessment of prefrontal executive functions: A critical update. Brain Cogn. 2009. Epub.
Omori I and Wang J. Sulpiride versus placebo for schizophrenia. Cochrane Database System Rev. 2009. CD007811.
Price J et al. Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer Disease. Neurobiol Aging. 2009. Apr. Epub.
Wang C et al. Twin pairs discordant for neuropathologically confirmed Lewy Body Dementia. J Neurol Neurosurg Psychiatry. 2009. 80(5). 562-5.
Zheng L et al. Metabolic changes associated with second-generation antipsychotic use in Alzheimer’s Disease patients: The CATIE-AD study. Am J Psychiatry. 2009. Apr. Epub.
Steps To Treatment (STT)
STT = Steps To Treatment. An estimate of the number of steps between the results and translation into practice i.e. treatment. This is an opinion.
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