A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients

Genetic Factors Influence the Clustering of Depression among Individuals with Lower Socioeconomic Status

Objective: To investigate the extent to which shared genetic factors can explain the clustering of depression among individuals with lower socioeconomic status, and to examine if neuroticism or intelligence are involved in these pathways. Methods: In total 2,383 participants (1,028 men and 1,355 women) of the Erasmus Rucphen Family Study were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale (HADSD). Socioeconomic status was assessed as the highest level of education obtained. The role of shared genetic factors was quantified by estimating genetic correlations (rG) between symptoms of depression and education level, with and without adjustment for premorbid intelligence and neuroticism scores. Results: Higher level of education was associated with lower depression scores (partial correlation coefficient 20.09 for CESD and 20.17 for HADS-D). Significant genetic correlations were found between education and bo

Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS

It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume

Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression

<p>Abstract</p> <p>Background</p> <p>Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.</p> <p>Methods</p> <p>The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.</p> <p>Trial registration</p> <p>Local Ethics Committee: H-KF 307413</p> <p>Danish Medicines Agency: 2612-3162.</p> <p>EudraCT: 2006-001750-28.</p> <p>Danish Data Agency: 2006-41-6737.</p> <p>ClinicalTrials.gov: NCT 00386841</p

Electroforming of 3D microstructures on highly structured surfaces

Electrodeposition of photoresist on highly structured surfaces is combined with electroplating to fabricate three new types of advanced 3D metal microstructures. In one application, electroplated nickel cantilever arrays are formed on the sloped sidewalls of KOH etched silicon. The cantilevers are released by sacrificial etching of copper. In another application it is shown how KOH etched silicon V-grooves can be patterned by electrodeposited photoresist to generate versatile 3D electroforming moulds. To demonstrate the potential of this technology, an innovative all-nickel cantilever structure with V-shaped cross section and integrated reflection mirror for optical readout has been fabricated. Cantilevers with V-cross section can be designed to have significantly larger out of plane bending stiffness or higher resonant frequency compared to rectangular cantilevers with similar dimensions. A third application uses electrodeposited photoresist to fabricate copper solenoids on an oxidised silicon support

A digital therapeutic for management of psychosocial aspects of psoriasis: A pre‐post proof of concept study

Background: Despite the psychosocial challenges of living with psoriasis many patients may not be able to access appropriate services to manage these challenges. Mobile health interventions may be helpful as a means to support patients in managing the impact of their condition. Objective: To conduct a preliminary examination of the feasibility and acceptability of a bespoke psoriasis‐specific digital therapeutic solution (hereafter termed Allay), and to provide initial data on psychological changes pre‐post. Methods: Phase one proof of concept pre‐post study. Eligible patients were provided with Allay on their smartphone and assessed at baseline and at 12 weeks on a range of indices of well‐being. Participants experiences on usability were collected by telephone interview at 4 weeks, 8 and 12 weeks. Results: Out of 66 participants recruited, 59 persisted in using Allay after the familiarisation phase, and 34 participants completed the 12 weeks programme. Participants showed a statistically significant improvement between induction and the end of the 12 weeks programme on Quality of life, Resilience, Perceptions of ‘Overall impact’ of psoriasis, and ‘Emotional impact’. There was a significant change over the course of using Allay for symptoms of depression but not anxiety. While there was an interaction effect of changes in severity of psoriasis symptoms over the course of the study for dermatology‐specific measures, there was no interaction between such changes in psoriasis symptoms and changes in depression, resilience or beliefs in emotional impact. Conclusions: Study results suggest that the use of Allay as an adjunct to medical management of psoriasis may help patients improve resilience, mood, beliefs about their condition and enhance their quality of life. Given that this is a phase one proof of concept study, and our rates of attrition further research is necessary to examine comparative effectiveness and stability of these findings