Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort

Background Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. Methods CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. Discussion From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research.

Neural signals of “Intensity” but not “Wanting” or “Liking” of rewards may be trait markers for depression

We have shown previously that particpants “at risk” of depression have decreased neural processing of reward suggesting this might be a neural biomarker for depression. However, how the neural signal related to subjective experiences of reward (wanting, liking, intensity) might differ as trait markers for depression, is as yet unknown. Using SPM8 parametric modulation analysis the neural signal related to the subjective report of wanting, liking and intensity was compared between 25 young people with a biological parent with depression (FH) and 25 age/gender matched controls. In a second study the neural signal related to the subjective report of wanting, liking and intensity was compared between 13 unmedicated recovered depressed (RD) patients and 14 healthy age/gender matched controls. The analysis revealed differences in the neural signal for wanting, liking and intensity ratings in the ventral striatum, dmPFC and caudate respectively in the RD group compared to controls . Despite no differences in the FH groups neural signal for wanting and liking there was a difference in the neural signal for intensity ratings in the dACC and anterior insula compared to controls. These results suggest that the neural substrates tracking the intensity but not the wanting or liking for rewards and punishers might be a trait marker for depression.

Assessment of inbreeding depression in a Guzerat dairy herd: Effects of individual increase in inbreeding coefficients on production and reproduction

Influences of inbreeding on daily milk yield (DMY), age at first calving (AFC), and calving intervals (CI) were determined on a highly inbred zebu dairy subpopulation of the Guzerat breed. Variance components were estimated using animal models in single-trait analyses. Two approaches were employed to estimate inbreeding depression: using individual increase in inbreeding coefficients or using inbreeding coefficients as possible covariates included in the statistical models. The pedigree file included 9,915 animals, of which 9,055 were inbred, with an average inbreeding coefficient of 15.2%. The maximum inbreeding coefficient observed was 49.45%, and the average inbreeding for the females still in the herd during the analysis was 26.42%. Heritability estimates were 0.27 for DMY and 0.38 for AFC. The genetic variance ratio estimated with the random regression model for CI ranged around 0.10. Increased inbreeding caused poorer performance in DMY, AFC, and CI. However, some of the cows with the highest milk yield were among the highly inbred animals in this subpopulation. Individual increase in inbreeding used as a covariate in the statistical models accounted for inbreeding depression while avoiding overestimation that may result when fitting inbreeding coefficients.

Rod bipolar cells in the retina of the capuchin monkey (Cebus apella): Characterization and distribution

Rod bipolar cells in Cebus apella monkey retina were identified by an antibody against the alpha isoform of protein kinase C (PKC alpha). which has been shown to selectively identify rod bipolars in two other primates and various mammals. Vertical sections were used to confirm the identity of these cells by their characteristic morphology of dendrites and axons. Their topographic distribution was assessed in horizontal sections; counts taken along the dorsal, ventral, nasal, and temporal quadrants. The density of rod bipolar cells increased from 500 to 2900 cells/mm(2) at 1 mm from the fovea to reach a peak of 10,000-12,000 cellss/mm(2) at 4 mm, approximately 5 deg of eccentricity, and then gradually decreased toward retinal periphery to values of 5000 cells/mm(2) or less. Rod to rod bipolar density ratio remained between 10 and 20 across most of the retinal extension. The number of rod bipolar cells per retina was 6,360,000 +/- 387,433 (mean +/- S.D., n = 6). The anti-PKC alpha antibody has shown to be a good marker of rod bipolar cells of Cebus, and the cell distribution is similar to that described for other primates. In spite of the difference in the central retina, the density variation of rod bipolar cells in the Cebus and Macaca as well as the convergence from rod to rod bipolar cells are Generally similar, suggesting that both retinae stabilize similar sensitivity (as measured by rod density) and convergence.

Symptomatic expression of depression among Jewish adolescents: effects of gender and age

Background Depression symptomatology was assessed with the Beck Depression Inventory (BDI) in a sample of Jewish adolescents, in order to compare the frequency and severity of depression with non-Jewish adolescents as well as examine gender difference of the expression of depressive symptomatology. Method Subjects comprised 475 students from Jewish private schools, aged 13-17 years, who were compared with an age-matched non-Jewish sample (n = 899). Kendall`s definition was adopted to classify these adolescents according to level of depressive symptoms. The frequency of depression was calculated for ethnicity, gender and age strata. Discriminant analysis and principal component analysis were performed to assess the importance of depression-specific and non-specific items, along with the factor structure of the BDI, respectively. Results The overall mean score on the BDI in the Jewish and the non-Jewish sample was 9.0 (SD = 6.4) and 8.6 (SD = 7.2), respectively. Jewish girls and boys had comparable mean BDI scores, contrasting with non-Jewish sample, where girls complained more of depressive symptoms than boys (p < 0.001). The frequency of depression, adopting a BDI cutoff of 20, was 5.1% for the Jewish sample and 6.3% for the non-Jewish sample. The frequency of depression for Jewish girls and boys was 5.5% (SE = 1.4) and 4.6% (SE = 1.5), respectively. On the other hand, the frequency of depression for non-Jewish girls and boys was 8.4% (SE = 1.2) and 4.0% (SE = 1.0), respectively. The female/male ratio of frequency of BDI-depression was 1.2 in the Jewish sample, but non-Jewish girls were twice (2.1) as likely to report depression as boys. Discriminant analysis showed that the BDI highly discriminates depressive symptomatology among Jewish adolescents, and measured specific aspects of depression. Factor analysis revealed two meaningful factors for the total sample and each gender (cognitive-affective dimension and somatic dimension), evidencing a difference between Jewish boys and Jewish girls in the symptomatic expression of depression akin to non-Jewish counterparts. Conclusions Ethnic-cultural factor might play a role in the frequency, severity and symptomatic expression of depressive symptoms in Jewish adolescents. The lack of gender effect on depression, which might persist from adolescence to adulthood among Jewish people, should be investigated in prospective studies.

Abnormal Corpus Callosum Integrity in Bipolar Disorder: A Diffusion Tensor Imaging Study

Objective: Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in bipolar disorder (BID). In this study, we used complementary diffusion tensor imaging methods to study the structural integrity of the CC and localization of potential abnormalities in BD. Methods: Subjects included 33 participants with BID and 40 healthy comparison participants. Fractional anisotropy (FA) measures were compared between groups with region of interest (ROD methods to investigate the anterior, middle, and posterior CC and voxel-based methods to further localize abnormalities. Results: In ROI-based analyses, FA was significantly decreased in the anterior and middle CC in the BID group (p <.05). Voxel-based analyses similarly localized group differences to the genu, rostral body, and anterior midbody of CC (p <.05, corrected). Conclusion: The findings demonstrate abnormalities in the structural integrity of the anterior CC in BID that might contribute to altered interhemispheric connectivity in this disorder.

Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging

Background Convergent evidence implicates white matter abnormalities in bipolar disorder. The cingulum is an important candidate structure for study in bipolar disorder as it provides substantial white matter connections within the corticolimbic neural system that subserves emotional regulation involved in the disorder. Aims To test the hypothesis that bipolar disorder is associated with abnormal white matter integrity in the cingulum. Method Fractional anisotropy in the anterior and posterior cingulum was compared between 42 participants with bipolar disorder and 42 healthy participants using diffusion tensor imaging. Results Fractional anisotropy was significantly decreased in the anterior cingulum in the bipolar disorder group compared with the healthy group (P=0.003); however, fractional anisotropy in the posterior cingulum did not differ significantly between groups. Conclusions Our findings demonstrate abnormalities in the structural integrity of the anterior cingulum in bipolar disorder. They extend evidence that supports involvement of the neural system comprising the anterior cingulate cortex and its corticolimbic gray matter connection sites in bipolar disorder to implicate abnormalities in the white matter connections within the system provided by the cingulum.

Depression Hos Tonåringar : Möjligheter för tidig upptäckt och behandling av tonåringar med depressioner

Denna litteraturstudie syftar till att undersöka hur tonåringar med depressioner tidigt kan upptäckas och få hjälp och vilken roll sjuksköterskan har i detta samt vad tonåringar själva tycker är viktigt i mötet med vården. Till resultatdelen har 17 vetenskapliga artiklar valts ut efter litteratursökning ifrån databaserna Cinahl, Elin och Pubmed. Depressioner hos tonåringar är ett allvarligt problem som innebär ett stort lidande och som i värsta fall kan leda till självmord. Förekomsten av depressioner hos tonåringar ökar och detta ställer allt högre krav på både skolhälsovård och primärvård. Resultatet visade att tonåringar i allmänhet hellre söker sig till skolhälsovården och ungdomsmottagningar än till primärvården och specialister. Genom att finnas nära tonåringarna har skolsköterskan och ungdomsmottagningar unika möjligheter att kunna upptäcka och hjälpa tonåringar som har depressioner eller nedstämdhet. För att öka möjligheterna till tidig upptäckt och behandling av tonåringar med depressioner är det viktigt att satsa resurser på skolhälsovård och ungdomsmottagningar. Det bör också spridas mer kunskap om systematisk screening som har visat sig vara ett värdefullt verktyg för att upptäcka depressioner.

Synthesis of a PEG-bipolar-dimyristoylphosphatidylethanoline

The problem of drug delivery has been of continuous research interest to the biomedical scientific community. The basic problem of drug delivery is to facilitate the transport of medication via the bloodstream to the target organs. This process can be significantly hampered by the hydrophobic nature of most medications. Pharmaceutical compounds and in particular chemotherapeutics (which are a specific area of research at the Cornell Medical Center and the Sloan-Kettering Institute) tend to be extremely hydrophobic. Blood is a hydrophilic environment, so the hydrophobic drugs simply cannot dissolve in the bloodstream. As a result they cannot be transported successfully to the target tissues. For example, Sloan-Kettering possesses compounds that kill cancer cells 100ln vitro, yet those same compounds are virtually inactive in vivo because of their insolubility in the blood. It was our purpose, therefore, to develop an appropriate and successful drug delivery system.

A Pollen Chase Experiment; Examining Varying Levels of Embryonic Inbreeding Depression

A pollen chase experiment was performed upon three Costa Rican populations of Witheringia solanacea to examine the breakdown of genetically enforced self incompatibility (SI) and the extent of embryonic inbreeding depression. Self-pollen was applied in the bud, with outcross pollen applied one day later, and outcross pollinations at both intervals as a control. A variety of responses were found among the populations. BOHS readily accepted self pollen and suffered from very low inbreeding depression. Monteverde and Las Cruces both have lower fruit set with self-pollination precedence indicating that bud pollinations can overcome the self-incompatibility response and that embryonic death due to inbreeding depression causes fruit failure. The treatment:control fruit set is higher for the Las Cruces plants indicating stronger SI response Self-precedence seeds from the Las Cruces plants are likely to be outcrossed. Self-precedence seeds from Monteverde are likely selfed.