Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of >or=2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction. Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

Jitteriness/anxiety syndrome remains poorly characterised. Despite this, clinicians' perception of this syndrome influences prescribing and it is cited to support postulated mechanisms of drug action. We recommend systematised evaluation of side-effects at earlier time points in antidepressant trials to further elucidate this clinically important syndrome.

IntroductionCerebral ischaemia is the defining pathophysiological abnormality in most forms of vascular dementia (VAD), but the pathogenesis of the dementia remains poorly understood. In Alzheimer's disease (AD), there is early loss of synaptic proteins, but these have been little studied in VAD.Materials and MethodsWe measured synaptophysin, postsynaptic density protein 95 (PSD-95), drebrin, synaptosomal-associated protein 25 (SNAP-25) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assays in superior temporal cortex from 11 patients with VAD and, initially, 11 non-dementia controls. We corrected for neuronal content by measurement of neuron-specific enolase. A further 11 controls were subsequently used in a validation study. Simulation of post-mortem delay found that PSD-95 was stable at 4°C but declined slightly at RT. SNAP-25 and drebrin showed good post-mortem stability. Previous studies had shown good post-mortem preservation of synaptophysin and VEGF.ResultsThe VAD cases had lower synaptophysin (but P > 0.05 in initial study), significantly lower SNAP-25 (P = 0.024) and significantly higher drebrin (P = 0.020). On comparison with the second control group, the reduction in synaptophysin was significant (P = 0.008), and the other results were confirmed.ConclusionThere is probably a reduction in presynaptic proteins in the temporal cortex in VAD, although not as marked as in AD. In VAD, there is also an increase in drebrin, which may be a response to reduced synaptic input.

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HighlightsE4 carriers self reported more memory problems, but no objective differences found.E2 carriers performed slightly better on episodic memory test.E2 carriers were faster in a test of executive function.

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Objectives. Drug-drug interactions (DDIs) present a serious, ever increasing clinical problem. Previous studies identified DDIs among psychiatric inpatients prescribed psychotropics, but none have focused on psychotropics prescribed to General Hospital inpatients. This study aimed to identify: putative drug-drug interactions; mechanisms; potential seriousness among patients prescribed psychotropes in both psychiatric and general hospital inpatients settings. We hypothesised that potential interactions per person would be greater in General Hospital inpatients on psychotropics, due to polypharmacy. Method. We surveyed psychotropic prescribing in hospital wards in a public sector mental health organisation and a 500-bed general hospital. Ward pharmacists collected drug prescription data. A computer based protocol evaluated DDIs. Results. A total of 7.4% of General Hospital inpatients and 100% of Psychiatric Unit inpatients surveyed were prescribed psychotropic medication. The General Hospital group had significantly more potential interactions per person (3.0) than Psychiatric inpatients (1.3) (P<0.05). There were significantly more potentially serious interactions in the general hospital group (P<0.025). Conclusions. DDIs affect those prescribed psychotropics in both General and Psychiatric Hospitals. The General Hospital patients had a higher number per person and more serious potential interactions, yet are often poorly served by psychiatric services, suggesting that liaison psychiatrists have a role in physician education and DDI assessment.

BackgroundPossession of the ε4 allele of the Apolipoprotein E (APOE) gene is associated with an increased risk of Alzheimer’s disease. Early adult life effects of ε4 are less well understood. Working memory has been relatively little studied (compared to episodic memory) in relation to APOE genotype despite its importance in cognitive functioning. Our hypothesis was that ε4 would lead to an impairment in working memory in young adults.MethodsWe studied working memory using a computerised n-back task in the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 18. Data was available for 1049–1927 participants and for the 2- and 3-back versions of the task. Using multiple and multi-level regression controlling for important confounders we examined the association between APOE genotype on accuracy and reaction times.ResultsThere was no evidence of a genotype effect on accuracy when the two difficulty levels were examined separately. There was some evidence to support a deleterious effect of the ε4 allele on n-back accuracy in the multi-level regression. There was weak evidence that the ε22 group were less accurate but the numbers were very low in this group. The ε34 group had faster reaction times than the reference ε33 group in all adjusted analyses but the ε44 group were only faster in the 3-back condition in multi-level analyses.ConclusionsThere was no evidence of benefit in ε4 carriers, but there was some evidence of a detrimental effect on working memory in this large study.