Definition of a Geriatric Depression Scale cutoff based upon quality of life: a population‐based study

Objectives

The cutoff scores for the Geriatric Depression Scale (GDS) commonly adopted in clinical and research settings are based upon other neuropsychological tests. However, any intervention for depression should aim at improving subjective quality of life (QoL). We searched for a GDS cutoff level that might identify a decrease in perceived QoL using a scale that also allows formal cost‐effectiveness calculations.

Methods

Quality of life was assessed by the Health Utilities Index, Mark 3 in all 344 residents of Tuscania (Italy) aged 75 years and above. Mood was assessed by both the 30‐item GDS and the derived 15‐item GDS. The association of GDS with low QoL was analyzed by multivariable logistic regression. Receiver operating characteristic curve analysis was adopted to estimate the overall predictive value and the best GDS cutoff for poor QoL.

Results

The 30‐item GDS score was associated with increased probability of a worse QoL (odds ratio (OR) = 1.07, 95% confidence (CI) = 1.02–1.12, p = 0.003); also, it was a fair predictor of worse QoL (area under the curve (AUC) = 0.72; 95% CI = 0.67–0.76). The best GDS score cutoff for identifying a poor QoL was above 9/30. Results were similar (OR = 1.07, 95% CI = 1.02–1.12, p = 0.003, and AUC = 0.72, 95% CI = 0.67–0.76) for the short GDS form for a cutoff above 5/15.

Conclusions

Among older subjects, depressive symptoms are associated with reduced QoL; GDS scores above 9/30 or 5/15 best predict poor perceived health‐related QoL. These cutoff scores could therefore identify subjects in whom treatment is more likely to improve QoL and to yield a favorable cost‐effectiveness ratio. Copyright © 2017 John Wiley & Sons, Ltd.     

Feasibility and effectiveness of cognitive remediation in the treatment of borderline personality disorder

Several studies have demonstrated that borderline personality disorder (BPD) is associated with neuropsychological deficits and there is evidence that the neurocognitive profile of patients with BPD may be related to the outcome of this disorder. The aim of this study was to investigate the feasibility and the effectiveness of a cognitive remediation intervention in patients with BPD. Thirty patients with a DSM-IV-TR diagnosis of BPD were assessed on clinical, neuropsychological and functional outcome measures at baseline and after 16 weeks of a computer-assisted cognitive remediation (CACR) intervention or treatment as usual (TAU). Patients who received CACR showed a greater improvement in working memory and psychosocial functioning measures than patients treated with TAU. Symptom severity was not significantly affected by CACR treatment. The findings of this pilot study suggest the feasibility and potential effectiveness on specific cognitive domains, but modest clinical usefulness of a computerised modality of cognitive remediation in the treatment of BPD.     

Altered dimerization of metabotropic glutamate receptor 3 in schizophrenia.

BACKGROUND: Metabotropic glutamate receptors (mGlus) may be involved in the pathophysiology of schizophrenia. Group II mGlus (mGlu2 and mGlu3) have attracted considerable interest since the development of potent specific agonists that exhibit atypical antipsychotic-like activity and reports of a genetic association between the mGlu3 gene and schizophrenia. METHODS: In this postmortem study, mGlu3 protein levels in Brodmann area 10 of prefrontal cortex from schizophrenic (n = 20) and control (n = 35) subjects were analyzed by western immunoblotting using a novel specific mGlu3 antibody and an antibody for the vesicular glutamate transporter 1 (VGluT1). RESULTS: We report a significant decrease in the dimeric/oligomeric forms of mGlu3 in schizophrenic patients compared with control subjects, whereas total mGlu3 and VGluT1 levels were not altered significantly. CONCLUSIONS: This is the first experimental evidence that mGlu3 receptor levels are altered in schizophrenia and supports the hypothesis that neurotransmission involving this particular excitatory amino acid receptor is impaired in schizophrenia.     

Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia.

BACKGROUND: There is an increasing recognition that the pathophysiology of mental disorders could be the result of deregulation of synaptic plasticity with alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant, located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been extensively studied through linkage and association approaches in several psychiatric disorders. METHODS: We performed a meta-analysis restricted to individual case-control studies in different categories of mental disorders and BDNF Val66Met polymorphism. We included data from 39 case-control studies encompassing psychiatric phenotypes: eating disorders, substance-related disorders, mood disorders, and schizophrenia, among others. RESULTS: The association of Val66Met was confined to three diagnoses: substance-related disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met genotypes increase the risk for eating disorders up to 33%, while these same genotypes confer a 21% protective effect in substance-related disorders. The homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with respect to the heterozygous state. CONCLUSIONS: The study confirms the association of Val66Met to substance-related disorders, eating disorders, and schizophrenia. It remains to be determined if other variants in tight linkage disequilibrium with Val66Met could configure an extended functional haplotype that would explain observed discrepancies in risk estimations across studies.     

Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs

PURPOSE: A biotechnologic breakthrough for the study of drug permeability across the blood-brain barrier (BBB) would be the use of a reproducible in vitro model that recapitulates the functional, structural, and pathologic properties of the BBB in situ. We developed a humanized dynamic in vitro BBB model (DIV-BBB) based on cocultures of human microvascular endothelial cells (HBMECs) from "normal" and drug-resistant epileptic brain tissue with human brain astrocytes (HAs) from epilepsy patients or controls. METHODS: HBMECs and HAs were cocultured for 28 days in polypropylene capillaries. HBMECs were exposed to physiologic levels of shear stress generated by intraluminal flow. Permeability to [3H]sucrose, [14C]phenytoin, and [14C]diazepam was measured in control and drug-resistant DIV-BBB with and without pretreatment with the MDR1 inhibitor XR9576. BBB integrity was monitored by transendothelial electrical resistance measurements (TEERs). Cell growth and viability were assessed by measurement of glucose consumption and lactate production. RESULTS: PSucrose and TEER values did not depend on the origin of the endothelium used (epileptic or normal). PPhenytoin was 10-fold less (1.54 x 10(-6) cm/s) in drug-resistant BBB models than in controls (1.74 x 10(-5) cm/s). MDR1 blockade with XR9576 was effective (3.5-fold increase) only in drug-resistant cultures. PDiazepam in control and drug-resistant DIV-BBB was not affected by XR9576 and did not depend on the epileptic or control origin of endothelia. The overall contribution of epileptic glia to pharmacoresistance was negligible. CONCLUSIONS: These results show that, for the substances used, the humanized DIV-BBB recapitulates the physiologic permeability properties of the BBB in vivo and is also capable of mimicking a drug-resistant BBB phenotype.     

Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis

The peri-ventricular area of the forebrain constitutes a preferential site of inflammation in multiple sclerosis, and the sub-ventricular zone (SvZ) is functionally altered in its animal model experimental autoimmune encephalomyelitis (EAE). The reasons for this preferential localization are still poorly understood. We show here that, in EAE mice, blood-derived macrophages, T and B cells and microglia (Mg) from the surrounding parenchyma preferentially accumulate within the SvZ, deranging its cytoarchitecture. We found that the chemokine Cxcl10 is constitutively expressed by a subset of cells within the SvZ, constituting a primary chemo-attractant signal for activated T cells. During EAE, T cells and macrophages infiltrating the SvZ in turn secrete pro-inflammatory cytokines such as TNFα and IFNγ capable to induce Mg cells accumulation and SvZ derangement. Accordingly, lentiviral-mediated over-expression of IFNγ or TNFα in the healthy SvZ mimics Mg/microglia recruitment occurring during EAE, while Cxcl10 over-expression in the SvZ is able to increase the frequency of peri-ventricular inflammatory lesions only in EAE mice. Finally, we show, by RT-PCR and in situ hybridization, that Cxcl10 is expressed also in the healthy human SvZ, suggesting a possible molecular parallelism between multiple sclerosis and EAE.     

Insomnia cycling with a 42-day infradian period: Evidence for two uncoupled circadian oscillators?

ObjectiveTo describe the unique case of a middle-aged woman with severe insomnia recurring with a regular infradian period without any other significant clinical condition. To infer the existence of a circadian dysfunction modeled according to the physical phenomenon of the “beats.”Patient/MethodsA two-year prospective observation by means of a sleep log was performed during the patient’s normal life. She underwent one month of motor activity recording and also polysomnography, circadian rhythm of body core temperature and psychiatric evaluation during periods with and without insomnia.ResultsVisual inspection of the 293-day plot of the sleep log disclosed a regular 42-day rhythm of insomnia recurrence confirmed by a Discrete Fourier Transform. During the periods of insomnia, lasting 5–7 days, only moderate mood symptoms (depressive overlapping hypomaniac symptoms) were present. Treatment with sodium valproate was effective in curtailing insomnia.ConclusionThe wax and wane infradian modulation of the sleep length suggested the presence of a basic mechanism similar to the physical phenomenon of the “beats,” i.e., a long period modulation of the amplitude of an oscillating system due to the interference of two uncoupled oscillators with a slightly different oscillation frequency. Hypothesizing a dysfunction of the circadian component of sleep, namely two uncoupled circadian cycles, a simple mathematical model estimated the difference of their periods of oscillation |34 ± 2 min| and reproduced the sleep-log data of the drug-free period of observation.     

Step‐by‐step: The effects of physical practice on the neural correlates of locomotion imagery revealed by fMRI

Previous studies have shown that mental imagery is a suitable tool to study the progression of the effect of practice on brain activation. Nevertheless, there is still poor knowledge of changes in brain activation patterns during the very early stages of physical practice. In this study, early and late practice stages of different kinds of locomotion (i.e., balanced and unbalanced) have been investigated using functional magnetic resonance imaging during mental imagery of locomotion and stance. During the task, cardiac activity was also recorded. The cerebral network comprising supplementary motor area, basal ganglia, bilateral thalamus, and right cerebellum showed a stronger activation during the imagery of locomotion with respect to imagery of stance. The heart beat showed a significant increase in frequency during the imagery of locomotion with respect to the imagery of stance. Moreover, early stages of practice determined an increased activation in basal ganglia and thalamus with respect to late stages. In this way, it is proposed the modulation of the brain network involved in the imagery of locomotion as a function of physical practice time. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

The GH–IGF system in amyotrophic lateral sclerosis: correlations between pituitary GH secretion capacity,insulin‐like growth factors and clinical features

Background and purpose: The growth hormone (GH) and insulin‐like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH–IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features. Methods: Serum levels of GH, IGF‐ I, IGF‐ II, insulin, IGF‐binding protein 1 (IGF‐BP1), and IGF‐binding protein 3 (IGF‐BP3) were measured in 25 patients with ALS and 25 age‐, gender‐, and BMI‐matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale – Revised (ALSFRS‐R) and upper motor neuron (UMN) score. Results:  GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF‐I levels were significantly higher in patients with ALS than in healthy controls (182.9 ± 90.8 vs. 139.4 ± 58.1 ng/ml; P = 0.015). IGF‐I levels were higher in patients with ALS with UMN score >10 than those with UMN score <10 (217.8 ± 100.8 vs. 155.5 ± 74.6 ng/ml, P = 0.05). IGF‐II levels were significantly lower in patients with ALS than in healthy controls (720.9 ± 215 vs. 1001.9 ± 475.4 ng/ml; P = 0.03). Conclusions: The results demonstrate an impairment of the GH–IGFs system in ALS. The degenerative process in ALS might lead to a compensatory increase in IGF‐I in an attempt to provide additional support to motor neurons or degenerating muscle fibers. The decrease in IGF‐II levels may also be of pathological significance.