Early life Adversity,functional connectivity and cognitive performance in Schizophrenia: The mediating role of IL-6

ObjectiveExposure to childhood trauma (CT) is associated with cognitive impairment in schizophrenia, and deficits in social cognition in particular. Here, we sought to test whether IL-6 mediated the association between CT and social cognition both directly, and sequentially via altered default mode network (DMN) connectivity.MethodsThree-hundred-and-eleven participants (104 patients and 207 healthy participants) were included, with MRI data acquired in a subset of n = 147. CT was measured using the childhood trauma questionnaire (CTQ). IL-6 was measured in both plasma and in toll like receptor (TLR) stimulated whole blood. The CANTAB emotion recognition task (ERT) was administered to assess social cognition, and cortical connectivity was assessed based on resting DMN connectivity.ResultsHigher IL-6 levels, measured both in plasma and in toll-like receptor (TLR-2) stimulated blood, were significantly correlated with higher CTQ scores and lower cognitive and social cognitive function. Plasma IL-6 was further observed to partly mediate the association between higher CT scores and lower emotion recognition performance (CTQ total: β_indirect −0.0234, 95% CI: −0.0573 to −0.0074; CTQ physical neglect: β_indirect = −0.0316, 95% CI: −0.0741 to −0.0049). Finally, sequential mediation was observed between plasma IL-6 levels and DMN connectivity in mediating the effects of higher CTQ on lower social cognitive function (β_indirect = −0.0618, 95% CI: −0.1523 to −0.285).ConclusionThis work suggests that previous associations between CT and social cognition may be partly mediated via an increased inflammatory response. IL-6′s association with changes in DMN activity further suggest at least one cortical network via which CT related effects on cognition may be transmitted.     

The TEACCH program for children and adults with autism: A meta-analysis of intervention studies

The intervention program for autism known as Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH) is considered an emerging practice for autism. In the present study we used state-of-the-art meta-analytical procedures to examine the pooled clinical effects of TEACCH in a variety of outcomes. A total of 13 studies were selected for meta-analysis totaling 172 individuals with autism exposed to TEACCH. Standardized measures of perceptual, motor, adaptive, verbal and cognitive skills were identified as treatment outcomes. We used inverse-variance weighted random effects meta-analysis supplemented with quality assessment, sensitivity analysis, meta-regression, and heterogeneity and publication bias tests. The results suggested that TEACCH effects on perceptual, motor, verbal and cognitive skills were of small magnitude in the meta-analyzed studies. Effects over adaptive behavioral repertoires including communication, activities of daily living, and motor functioning were within the negligible to small range. There were moderate to large gains in social behavior and maladaptive behavior. The effects of the TEACCH program were not moderated by aspects of the intervention such as duration (total weeks), intensity (hours per week), and setting (home-based vs. center-based). While the present meta-analysis provided limited support for the TEACCH program as a comprehensive intervention, our results should be considered exploratory owing to the limited pool of studies available.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

The Quick Mild Cognitive Impairment screen correlated with the Standardized Alzheimer's Disease Assessment Scale–cognitive section in clinical trials

ObjectivesThe Alzheimer's Disease Assessment Scale–cognitive section and its standardized version (SADAS-cog) are the current standard for assessing cognitive outcomes in clinical trials of dementia. This study compares a shorter cognitive instrument, the Quick Mild Cognitive Impairment (Qmci) screen, with the SADAS-cog as outcome measures in clinical trials.Study Design and SettingThe SADAS-cog, Qmci, Clinical Dementia Rating (CDR) scale, and the Lawton–Brady activities of daily living (ADL) scale were assessed at multiple time points, over 1 year in a multicenter randomized clinical trial of 406 patients with mild to moderate Alzheimer's dementia. Correlations were estimated using regression at each time point, all time points, and mean values across time. Responsiveness was assessed using the standardized response mean (SRM).ResultsRegression for pooled time points showed strong and significant correlation between the SADAS-cog and Qmci (r = −0.75, P < 0.001). Correlations remained strong for mean values across time and at each time point. The SADAS-cog and Qmci also correlated with CDR and ADL scores. There was no difference in SRMs between the SADAS-cog and Qmci [t(357) = −0.32, P = 0.75].ConclusionThe Qmci correlated strongly with the SADAS-cog and both were equally responsive to deterioration. We suggest that clinicians and investigators can substitute the shorter Qmci for the SADAS-cog.     

Screening and Quantification of Depression in Mild-to-Moderate Dementia Through the GDS Short Forms

Abstract

We evaluated the validity of the 1-, 4- and 15-item versions of the GDS in 51 patients affected by mild to moderate dementia, using the long form as standard. The following sensitivity and specificity values were obtained: 66% and 91% for GDS-1, 93% and 87% for GDS-4, 79% and 100% for GDS-15. GDS-15 also showed good agreement with GDS-30 in defining the severity of depression. These findings support the use of GDS-4 for the screening of depression and of GDS-15 for its severity assessment.     

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized,double-blinded sham-controlled periods

BackgroundThere is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome.ObjectivesIn this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation.MethodsWe included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety.ResultsActive stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae.ConclusionOur results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.     

Cronbach's α reliability,concurrent validity,and factorial structure of the Death Depression Scale in an Iranian hospital staff sample

ObjectiveDeath depression is an important component in the process of death and dying. Death depression is the second element of death. Depression is one of the important features in death distress. The aim of this study was to explore the performance of the Farsi version of the Death Depression Scale with an Iranian convenience sample of nurses (n = 106).MethodsNurses were selected using a convenience sampling method, and completed the Death Depression Scale (DDS), Death Concern Scale (DCS), Collett-Lester Fear of Death Scale (CLFDS), Reasons for Death Fear Scale (RDFS), Templer's Death Anxiety Scale (DAS), and Death Obsession Scale (DOS).ResultsThe results of exploratory factor analysis on DDS identified 4 factors (56.16% of variance). Factor 1 labeled “Death sadness”, Factor 2 labeled “Death finality/end and Death dread/fear”, Factor 3 labeled “Death despair and Death depression”, and Factor 4 labeled “Death loneliness”. Cronbach's α coefficient was 0.84, Spearman-Brown coefficient 0.85, and Guttman Split-Half coefficient 0.81 The DDS correlated 0.40 with the DCS, 0.39 with the CLFDS, 0.50 with the DAS, 0.35 with the RDFS, and 0.44 with the DOS, indicating good construct and criterion-related validity. Concurrent validity for the DDS with the other scales were significant.ConclusionsThe DDS has good validity and reliability, and it can use in clinical and research settings.