Electroconvulsive Therapy for Affective Disorders in Persons with Mental Retardation

Despite the efficacy of electroconvulsive therapy for the treatment of affective disorders there are no systematic studies of its effectiveness or safety in the mentally retarded population. A literature search revealed 16 case reports that suggests that it is both as effective and safe with mentally retarded persons as in the general population. Four additional clinical vignettes, with extensive follow-up observation from four to eleven years, are presented in an effort to enrich the literature on this subject. They include patients with rapid cycling bipolar disorder, bipolar disorder, manic phase, major depression with psychotic features and schizoaffective disorder. Issues of diagnostic difficulty and pharmacologic prophylaxis are addressed.     

Abnormal prediction error is associated with negative and depressive symptoms in schizophrenia

Prediction error in learning is where learning occurs to the degree to which an outcome consequent to a stimulus is surprising. It has been suggested that abnormal use of prediction error in schizophrenia may underlie the formation of inappropriate associations giving rise to psychotic symptoms. Kamin blocking is a phenomenon that demonstrates prediction error. Kamin blocking is shown where prior learning about a stimulus A paired with an outcome retards learning about a stimulus B when presented subsequently as part of a stimulus compound AB paired with the same outcome. Prior studies have indicated reduced Kamin blocking in schizophrenia specifically in non-paranoid patients. It is however unclear how reduced Kamin blocking is associated with specific symptoms in schizophrenia. The present study examined Kamin blocking performance in a high functioning community-based sample of 34 people with schizophrenia and 48 controls closely matched for pre-morbid IQ. In these patients we measured Kamin blocking and symptoms using positive and negative symptom scales (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) and Scale for the Assessment of Positive Symptoms (SAPS). Results confirmed that people with schizophrenia had significantly reduced Kamin blocking. Kamin blocking performance was associated with negative and depressive symptoms. These associations with symptoms were crucially not found with baseline associative learning or unblocking measures, confirming specificity to the Kamin blocking effect. These data demonstrate first that abnormal prediction error as assessed in the Kamin blocking task is associated with negative and depressive symptoms rather than positive symptoms in high functioning schizophrenia patients. Second this strongly suggests that reduced Kamin blocking may be useful as an animal model of specific relevance to negative and depressive symptoms in schizophrenia.     

Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT).ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression.MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests.ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response.ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.     

Dual-modality imaging of function and physiology

Dual-modality imaging is a technique in which computed tomography (CT) or magnetic resonance imaging is combined with positron emission tomography or single-photon emission CT to acquire structural and functional images with an integated system. The data are acquired in a single procedure; the patient remains on the scanner table while undergoing both x-ray and radionuclide studies to facilitate correlation between the structural and functional images. The resulting data can aid in localization, enabling more specific diagnosis than can be obtained with a conventional imaging study. In addition, the anatomic information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems are also being developed for biologic research involving small animals. Small-animal dual-modality systems offer advantages for measurements that currently are performed invasively with autoradiography and tissue sampling. By acquiring data noninvasively, dual-modality imaging permits serial studies in a single animal, enables measurements to be performed with fewer animals, and improves the statistical quality of the data.     

The relationship of concurrent benzodiazepine administration to seizure duration in ECT

The relationship of concurrent benzodiazepine administration to seizure duration in ECT was examined. Administration of a standard oral dose of 10 mg diazepam to a series of patients suffering from major depressive disorder produced a significant reduction in men seizure length during ECT compared to length of ECT-induced seizure in those patients when they were benzodiazepine free. This finding is discussed.     

Utility of FDG-PET in differential diagnosis of benign and malignant fractures in acute to subacute phase

OBJECTIVE: To evaluate the usefulness of positron emission tomography with [fluorine-18] 2-deoxy-2-fluoro-D-glucose (FDG-PET) for early differential diagnosis of benign and malignant fractures. MATERIALS AND METHODS: Among 1,164 patients who had received FDG-PET between January 1999 and December 2000, 20 patients were found to have an acute fracture on review of clinical charts and/or radiologic images taken within one month before or after FDG-PET examination. The fractures were finally diagnosed by clinical follow up of at least five months duration. Standardized uptake values (SUV) for the benign and malignant bone lesions were calculated and compared. RESULTS: Ten of the 20 patients were finally diagnosed to have a benign fracture, nine patients to have a malignant fracture, and one patient to have both a benign and a malignant fracture at different locations. A statistically significant difference in the SUV was found between the benign group (SUV: 1.36 +/- 0.49) and the malignant group (SUV: 4.46 +/- 2.12) (p = 0.0006, the nonparametric Mann-Whitney U test). CONCLUSIONS: FDG-PET can be a useful method for early differentiation between acute benign and metastatic fractures. Our retrospective study indicates that an acute benign fracture itself does not show significant FDG uptake.     

电化学治疗昆明小鼠肉瘤及其机理分析

研究了电化学治疗昆明小鼠肉瘤的疗效,并分析其机理。在体外将S-180细胞用不同参数的电场处理,研究适合电化学治疗的电场条件。通过复制肉瘤模型,将肉瘤小鼠随机分成4组:对照组、电疗组、化疗组、电化疗组。研究了不同处理组的肿瘤抑瘤率、治愈率以及小鼠的自由基代谢水平。结果电化疗组的抑瘤率、治愈率都显著高于化疗组和电疗组(P<0.05),电化疗组小鼠受到氧自由基的攻击显著降低,免疫力提高。分析机理发现,电化学治疗肿瘤的机理可能至少涉及细胞膜通透性提高、细胞的耐药性降低、机体的免疫力提高三个方面。     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.