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.

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.

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.

Brazil and Turkey, a comparative analysis of both countries' economic development and institutional design from the Great Depression to the early 21st century

Apos uma década de rápido crescimento econômico na primeira década do século 21, Brasil e Turquia foram considerados duas das economias emergentes mais dinâmicas e promissoras. No entanto, vários sinais de dificuldades econômicas e tensões políticas reapareceram recentemente e simultaneamente nos dois países. Acreditamos que esses sinais e a sua simultaneidade podem ser entendidos melhor com um olhar retrospectivo sobre a história econômica dos dois países, que revela ser surpreendentemente paralela. Numa primeira parte, empreendemos uma comparação abrangente da história econômica brasileira e turca para mostrar as numerosas similaridades entre os desafios de política econômica que os dois países enfrentaram, assim como entre as respostas que eles lhes deram desde a virada da Grande Depressão até a primeira década do século 21. Essas escolhas de política econômica comuns dão forma a uma trajetória de desenvolvimento notavelmente análoga, caracterizada primeiro pela adoção do modelo de industrialização por substituição das importações (ISI) no contexto da recessão mundial dos anos 1930; depois pela intensificação e crise final desse modelo nos anos 1980; e finalmente por duas décadas de estabilização e transição para um modelo econômico mais liberal. Numa segunda parte, o desenvolvimento das instituições econômicas e políticas, assim como da economia política subjacente nos dois países, são analisados comparativamente a fim de prover alguns elementos de explicação do paralelo observado na primeira parte. Sustentamos que o marco institucional estabelecido nos dois países durante esse período também têm varias características fundamentais em comum e contribui a explicar as escolhas de política econômica e as performances econômicas comparáveis, detalhadas na primeira parte. Este estudo aborda elementos do contexto histórico úteis para compreender a situação econômica e política atual nos dois países. Potencialmente também constitui uma tentativa de considerar as economias emergentes numa perspectiva histórica e comparativa mais ampla para entender melhor as suas fraquezas institucionais e adotar um olhar mais equilibrado sobre seu potencial econômico.

Economic recovery from the Argentine great depression : institutions, expectations, and the change of macroeconomic regime

This work explores how Argentina overcame the Great Depression and asks whether active macroeconomic interventions made any contribution to the recovery. In particular, we study Argentine macroeconomic policy as it deviated from gold-standard orthodoxy after the final suspension of convertibility in 1929. As elsewhere, fiscal policy in Argentina was conservative, and had little power to smooth output. Monetary policy became heterodox after 1929. The first and most important stage of institutional change took place with the switch from a metallic monetary regime to a fiduciary regime in 1931; the Caja de Conversión (Conversion Office, a currency board) began rediscounting as a means to sterilize gold outflows and avoid deflationary pressures, thus breaking from orthodox "mIes of the game." However, the actual injections of liquidity were small' and were not enough to fully offset the incipient monetary contractions: the "Keynes" effect was weak or negative. Rather, recovery derived from changes in beliefs and expectations surrounding the shift in the monetary and exchange-rate regime,and the delinking of gold flows and the money base. Agents perceivod a new regime, as shown by the path of consumption, investment, and estimated ex ante real interest rates: the "Mundell" effect was dominant. Notably, this change of regime predated a later, and supposedly more significant, stage of institutional reform, namely the creation of the central bank in 1935. Still, the extent of intervention was weak, and insufficient to fully offset externaI shocks to prices and money. Argentine macropolicy was heterodox in terms of the change of regime, but still conservative in terms of the tentative scope of the measures taken .

Are affects important for the definition of depression?

Many of the nosological features, subtypes, biochemical, neurophysiological mechanisms, and therapeutic proposals are controversial in depression. Methods: We review theories and discuss affects and mood as criteria For depression or mania diagnosis. Results: Our work was to show that mood and affections are poorly conceived. Conclusions: Mood and affection do not serve as a basis for the diagnosis of depression or mania.

Relations between Depression, Alcohol and Gender in the Metropolitan Region of São Paulo, Brazil

Como parte do projeto GENACIS, este artigo visou estimar a prevalência de depressão em amostra urbana de São Paulo, Brasil, assim como a associação entre depressão e padrão de uso de álcool segundo gênero. Para tanto, foi realizado inquérito epidemiológico com amostra probabilística e por conglomerados, com um total de 2083 adultos. Utilizou-se o CIDI SF para identificação de depressão. A análise estatística utilizou o teste de Rao Scott e regressão logística multivariada. A taxa de resposta foi de 74,9%. Predominaram mulheres (58,8%), menores de 40 anos de idade (52%). A prevalência de depressão foi de 28,3% para as mulheres e 12,7% para os homens. Entre os homens, 61,1% são de bebedores no último ano e a depressão esteve associada ao padrão de consumo de álcool, à maior frequência de binge drinking e à presença de problemas decorrentes do álcool. Entre as mulheres, 69,5% são abstinentes e a depressão se associou à convivência com cônjuge com problemas devidos ao álcool. Os resultados ressaltam que a associação entre depressão e consumo de álcool é distinta entre os gêneros.

Sleep bruxism increases the risk for painful temporomandibular disorder, depression and non-specific physical symptoms

To explore the relationship between sleep bruxism (SB), painful temporomandibular disorders (TMD) and psychologic status in a cross-sectional study. The sample consisted of 272 individuals. The Research Diagnostic Criteria for TMD (RDC/TMD) was used to diagnose TMD; SB was diagnosed by clinical criteria proposed by The American Academy of Sleep Medicine. The sample was divided into four groups: (1) patients without painful TMD and without SB, (2) patients without painful TMD and with SB, (3) patients with painful TMD and without SB and (4) patients with painful TMD and with SB. Data were analysed by Odds Ratio test with a 95% confidence interval. Patients with SB had an increased risk for the occurrence of myofascial pain (OR = 5.93, 95% CI: 3.1911.02) and arthralgia (2.34, 1.583.46). Group 3 had an increased risk for moderate/severe depression and non-specific physical symptoms (10.1, 3.6727.79; 14.7, 5.3939.92, respectively), and this risk increased in the presence of SB (25.0, 9.6564.77; 35.8, 13.9491.90, respectively). SB seems to be a risk factor for painful TMD, and this in turn is a risk factor for the occurrence of higher depression and non-specific physical symptoms levels, but a causeeffect relationship could not be established.

Depression in patients with Parkinson's disease: Impact on functioning

Depression is a frequently observed neuropsychiatric phenomenon in Parkinson's disease (PD) and it has been lately considered as a manifestation of such disease. The aim of the study was to investigate the relationship between depression and clinical aspects of PD and to assess the impact of the co-occurrence of such condition on the burden imposed by PD. Fifty Outpatients diagnosed with idiopathic PD according to the London Brain Bank criteria were examined. PD was evaluated using Hoehn & Yahr staging (H&Y), United Parkinson's Disease Rating Scale (UPDRS) and Schwab & England (S&E) functional capacity evaluation. A semi-structured clinical interview was used. The diagnosis of PD was made by neurologist experts on movement disorders, and the diagnosis of depression was trade by a psychiatrist, according to the ICD-10 diagnostic criteria. Depressive symptoms were additionally measured using the Montgomery-Asberg Depression Scale. The analysis of quantitative data was performed using descriptive statistics, Univariate linear regression, T-Student Test and ANOVA. Seventeen (34%) patients were diagnosed as clinically depressed and, when compared to the non-depressed ones, presented the following results: H&Y: 3.2 vs. 2.8; UPDRS total: 75.7 vs. 65.3; S&E: 53.5% vs. 65.8% and PD duration: 114.4 months vs. 125.8 months. Depressed patients showed more advanced staging (H&Y), a more severe global clinical condition (UPDRS) and also a greater decrease in their functional capacity (S&E). These data reinforce the hypothesis that depression is associated to poorer functioning in patients with PD. (C) 2008 Elsevier B.V All rights reserved.

Seasonal metabolic depression, substrate utilisation and changes in scaling patterns during the first year cycle of tegu lizards (Tupinambis merianae)

The tegus increase in body mass after hatching until early autumn, when the energy intake becomes gradually reduced. Resting rates of oxygen consumption in winter drop to 20% of the values in the active season (Vo(2)=0.0636 ml g(-1) h(-1)) and are nearly temperature insensitive over the range of 17-25degreesC (Q(10)=1.55). During dormancy, plasma glucose levels are 60% lower than those in active animals, while total protein, total lipids and beta-hydroxybutyrate are elevated by 24%, 43% and 113%, respectively. In addition, a significant depletion of liver carbohydrate (50%) and of fat deposited in the visceral fat bodies (24%) and in the tail (25%) and a slight loss of skeletal muscle protein (14%) were measured halfway through the inactive period. Otherwise, glycogen content is increased 4-fold in the brain and 2.3-fold in the heart of dormant lizards, declining by the onset of arousal. During early arousal, the young tegus are still anorexic, although Vo(2) is significantly greater than winter rates. The fat deposits analysed are further reduced (62% and 45%, respectively) and there is a large decrease in tail muscle protein (50%) together with a significant increase in glycogen (2-3-fold) and an increase in plasma glucose (40%), which suggests a role for gluconeogenesis as a supplementary energy source in arousing animals. No change is detectable in citrate synthase activity, but beta-hydroxyacyl CoA dehydrogenase activities are strongly affected by season, reaching a Mold and 5-fold increase in the liver tissue of winter and arousing animals, respectively, and becoming reduced by half in skeletal muscle and heart of winter animals compared with late fall or spring active individuals. From hatching to late autumn, the increase of the fat body mass relatively to body mass is disproportionate (b=1.44), and the mass exponent changes significantly to close to 1.0 during the fasting period. The concomitant shift in the Vo(2) mass exponent in early autumn (b=0.75) to values significantly greater than 1.0 in late autumn and during winter dormancy indicates an allometric effect on the degree of metabolic depression related to the size of the fat stores and suggests greater energy conservation in the smaller young.