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The objective of this review is to investigate existing literature in order to delineate whether the use of anaesthesia and timing of seizure induction in a new and optimised way may improve the efficacy of electroconvulsive therapy (ECT).
PubMed/MEDLINE was searched for existing literature, last search on 24 June 2015. Relevant clinical studies on human subjects involving choice of anaesthetic, ventilation and bispectral index (BIS) monitoring in the ECT setting were considered. The references of relevant studies were likewise considered.
Propofol yields the shortest seizures, etomidate and ketamine the longest. Etomidate and ketamine+propofol 1 : 1 seems to yield the seizures with best quality. Seizure quality is improved when induction of ECT is delayed until the effect of the anaesthetic has waned – possibly monitored with BIS values. Manual hyperventilation with 100% O2 may increase the pO2/pCO2-ratio, which may be correlated with better seizure quality.
Etomidate or a 1 : 1 ketamine and propofol combination may be the best method to achieve general anaesthesia in the ECT setting. There is a need for large randomised prospective studies comparing the effect of methohexital, thiopental, propofol, ketamine, propofol+ketamine 1 : 1 and etomidate in the ECT treatment of major depressed patients. These studies should investigate safety and side effects, and most importantly have antidepressant efficacy and cognitive side effects as outcome measures instead of seizure quality.
Bipolar disorder (BD) patients have recently been shown to exhibit increased proinflammatory cytokine levels indicating the role of inflammation in this disease. As inflammatory responses often include complement level alterations and complement production is influenced by cytokines, we aimed to find out whether complement system is activated in BD in a time-dependent manner and complement factors are involved in BD pathogenesis.
Serum C4, factor B, sC5b-9 and neuron-specific enolase levels were measured by enzyme-linked immunosorbent assay, whereas peripheral blood mononuclear cell messenger RNA (mRNA) expression levels of C1q, C4, factor B and CD55 were measured by real-time polymerase chain reaction in chronic BD patients (n=22), first episode BD patients (n=24) and healthy controls (n=19).
Serum complement levels were significantly reduced in chronic BD patients as compared with first episode BD patients and healthy controls. Serum levels of complement factors showed significant inverse correlation with disease duration, severity of manic symptoms and serum neuron-specific enolase levels. In chronic BD patients, peripheral blood mononuclear cell mRNA expression levels of C1q, C4 and factor B were significantly elevated, whereas the mRNA expression level of the complement inhibitor CD55 was significantly reduced.
Our results suggest that complement factor levels are reduced in BD presumably due to overconsumption of the complement system and complement production is increased at mRNA level possibly as a compensation measure. Complement factors might potentially be used as indicators of disease severity, neuronal loss and cognitive dysfunction.
This study investigated immersive virtual reality (IVR), as a novel technique to test executive function of healthy younger and older adults. We predicted IVR tasks to have greater predictive power than traditional measures when assessing age-related cognitive functioning due to the real-world validity of the tasks.
Participants (n=40) completed the Stroop colour–word test and the trail-making test (TMT) as traditional and commonly used assessments of executive functioning. Participants then completed three IVR tasks; a seating arrangement task, an item location task (both set in a virtual chemistry lab), and a virtual parking simulator.
Younger adults completed significantly more parking simulator levels (p<0.001), placed significantly more objects (p<0.001), and located significantly more items than older adults (p<0.01), demonstrating higher levels of performance. Significant correlations were found between performance on traditional neuropsychological measures and IVR measures. For example, Stroop CW performance significantly correlated with the number of parking simulator levels completed (τ=0.43, p<0.01). This suggests that IVR measures assess the same underlying cognitive constructs as traditional tasks. In addition, IVR measures contributed a significant percentage of the explained variance in age.
IVR measures (i.e. number of parking simulator levels completed and number of objects placed in the seating arrangement task) were found to be stronger contributors than existing traditional neuropsychological tasks in predicting age-related cognitive decline. Future research should investigate the implementation of these real-world-based tasks in clinical groups given this promising initial work.
Patients with functional memory disorder (FMD) report significant memory failures in everyday life. Differentiating these patients from those with memory difficulties due to early stage neurodegenerative conditions is clinically challenging. The current study explored whether distinctive neuropsychological profiles could be established, suitable to differentiate patients with FMD from healthy individuals and those experiencing amnestic mild cognitive impairment (a-MCI).
Patients with a clinical diagnosis of FMD were compared with patients with a-MCI, and healthy matched controls on several tests assessing different cognitive functions. Patients with clinically established mood disorders were excluded. Patients with FMD and a-MCI were broadly comparable on the level of their subjective memory complaints as assessed by clinical interview.
The neuropsychological profile of the FMD patients, although they expressed subjective memory and attention concerns during their clinical interview was distinct from patients with a-MCI on tests of memory [semantic fluency, age of acquisition (AoA) analysis of semantic fluency, verbal and non-verbal memory]. FMD patients did not differ significantly from healthy controls, but their scores on the letter fluency and digit cancellation tasks were not significantly different from those of the a-MCI patients indicating a possible sub-threshold deficit on these tasks.
Whilst subjective complaints are common within the FMD population, no objective impairment could be detected, even on a sensitive battery of tasks designed to detect subtle deficits caused by an early neurodegenerative brain disease. This study indicates that FMD patients can be successfully differentiated from patients with neurodegenerative memory decline by characterising their neuropsychological profile.
Neurological soft signs (NSS) are a group of minor non-localisable neurological abnormalities found more often in patients with schizophrenia. The aim of the current study was to test for the effect of gender, age, parental age, age at onset and clinical symptomatology on NSS.
Material and methods
The study sample included 133 patients suffering from schizophrenia according to DSM-IV-TR (77 males and 56 females; aged 33.55±11.22 years old) and 122 normal controls (66 males and 56 females; aged 32.89±9.91 years old). The assessment included the Neurological Evaluation Scale (NES), and a number of scales assessing the clinical symptoms and adverse effects especially extrapyramidal. The statistical analysis included exploratory t-test, simple linear regression analysis, analysis of covariance and the calculation of correlation coefficients.
The results of the current study confirm that NSS are more frequent in patients with schizophrenia in comparison with normal controls (Wilks=0.622, p<0.0001), but do not support an effect of gender, age, age at onset, paternal or maternal age, education, medication status or clinical subtype of schizophrenia on NES scores.
Overall these results suggest that NSS constitute an independent (from the rest of symptoms), core (present in the vast majority of patients) and trait (unrelated to age and probably to the stage of schizophrenia) symptom of schizophrenia which could be of value in the clinical assessment and research of schizophrenia. Overall these results are not in full accord with the literature, but they could serve to fill in gaps and inconsistencies observed so far.
Combinations of genetic variants are the basis for polygenic disorders. We examined combinations of SNP genotypes taken from the 446 729 SNPs in The Wellcome Trust Case Control Study of bipolar patients.
Parallel computing by graphics processing units, cloud computing, and data mining tools were used to scan The Wellcome Trust data set for combinations.
Two clusters of combinations were significantly associated with bipolar disorder. One cluster contained 68 combinations, each of which included five SNP genotypes. Of the 1998 patients, 305 had combinations from this cluster in their genome, but none of the 1500 controls had any of these combinations in their genome. The other cluster contained six combinations, each of which included five SNP genotypes. Of the 1998 patients, 515 had combinations from the cluster in their genome, but none of the 1500 controls had any of these combinations in their genome.
Clusters of combinations of genetic variants can be considered general risk factors for polygenic disorders, whereas accumulation of combinations from the clusters in the genome of a patient can be considered a personal risk factor.
The identification of biomarkers for depression is of great clinical relevance as the diagnosis is currently subjective. Recent research points towards sortilin as a potential biomarker for depression, and the aim of the current study was to investigate the serum sortilin level in response to antidepressant treatment.
The study included 56 depressed individuals of which 41 responded to treatment. Depression scores and serum levels of sortilin were measured at baseline and after 12 weeks of antidepressant treatment. Statistical analyses were performed using Stata 13.
The depression score and response to treatment were not predicted by the sortilin level. Likewise, we observed no significant change in serum sortilin levels following 12 weeks of antidepressant treatment. Furthermore, no association between the serum sortilin level and depression score was observed.
The results do not point towards sortilin as a state-dependent biomarker.
Although alterations in the dendritic spine density in the brain regions may play a role in the stress-induced depression-like phenotype, the precise mechanisms are unknown. The aim was to investigate the role of spine density in the brain regions after chronic social defeat stress (CSDS).
We examined dendritic spine density in the medial prefrontal cortex (mPFC), CA1, CA3, dentate gyrus (DG) of hippocampus, nucleus accumbens (NAc), and ventral tegmental area (VTA) of susceptible and resilient mice after CSDS.
Spine density in the prelimbic area of mPFC, CA3, and DG in the susceptible group, but not resilient group, was significantly lower than control group. In contrast, spine density in the NAc and VTA in the susceptible group, but not resilient group, was significantly higher than control group.
The results suggest that regional differences in spine density may contribute to resilience versus susceptibility in mice subjected to CSDS.