Search

It remains unclear why many patients with depression do not respond to antidepressant treatment. In three cohorts of individuals with depression and treated with serotonin-norepinephrine reuptake inhibitor (N = 424) we show that responders, but not non-responders, display an increase of GPR56 mRNA in the blood. In a small group of subjects we also show that GPR56 is downregulated in the PFC of individuals with depression that died by suicide. In mice, we show that chronic stress-induced Gpr56 downregulation in the blood and prefrontal cortex (PFC), which is accompanied by depression-like behavior, and can be reversed by antidepressant treatment. Gpr56 knockdown in mouse PFC is associated with depressive-like behaviors, executive dysfunction and poor response to antidepressant treatment. GPR56 peptide agonists have antidepressant-like effects and upregulated AKT/GSK3/EIF4 pathways. Our findings uncover a potential role of GPR56 in antidepressant response.

MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of desvenlafaxine (50-100 mg die), 20 patients were scanned with 3T magnetic resonance imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition. Blood samples were collected at both time points. During resting state, lower baseline miR-1202 levels were predictive of increased connectivity from T0 to T8 between the posterior cingulate and the prefrontal, parietal, and occipital cortices. Changes in miR-1202 levels following desvenlafaxine treatment were negatively correlated with changes in activity in right precuneus within the default-mode network, and in connectivity between the posterior cingulate and the temporal and prefrontal cortices, and the precuneus. During the Go/NoGo task, baseline miR-1202 levels and changes in these levels were correlated with activity changes in different regions, including bilateral prefrontal, insular, cingulate, and temporal cortices, and left putamen and claustrum. Finally, secondary analyses in a subset of patients showed a trend for a significant correlation between miR-1202 levels and glutamate levels measured by spectroscopy. Changes in peripheral miR-1202 levels were therefore associated with changes in brain activity and connectivity in a network of brain regions associated with depression and antidepressant response. These effects may be mediated by the glutamatergic system.

Background: Major depressive disorder is a debilitating illness, which is most commonly treated with antidepressant drugs. As the majority of patients do not respond on their first trial, there is great interest in identifying biological factors that indicate the most appropriate treatment for each patient. Studies suggest that microRNA represent excellent biomarkers to predict antidepressant response., Methods: We investigated the expression of miR-1202, miR-135a, and miR-16 in peripheral blood from 2 cohorts of depressed patients who received 8 weeks of antidepressant therapy. Expression was quantified at baseline and after treatment, and its relationship to treatment response and depressive symptoms was assessed., Results: In both cohorts, responders displayed lower baseline miR-1202 levels compared with nonresponders, which increased following treatment., Conclusions: Ultimately, our results support the involvement of microRNA in antidepressant response and suggest that quantification of their levels in peripheral samples represents a valid approach to informing treatment decisions., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

Objective: The Inuit population in Canada's North has suffered from high rates of death by suicide. We report on the first large-scale, controlled, epidemiologically representative study of deaths by suicide in an Indigenous population, which investigates risk factors for suicide among all Inuit across Nunavut who died by suicide during a 4-year period., Methods: We identified all suicides by Inuit (n = 120) that occurred between January 1, 2003, and December 31, 2006, in Nunavut. For each subject, we selected a community-matched control subject. We used proxy-based procedures and conducted structured interviews with informants to obtain life histories, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I and II diagnoses, and measures of impulsive and (or) aggressive traits., Results: Compared with control subjects, subjects who died by suicide were more likely to have experienced childhood abuse (OR 2.38; 95% CI 1.39 to 4.08), have family histories of major depressive disorder (P = 0.002) and suicide completion (P = 0.02), and have been affected by major depressive disorder (OR 13.00; 95% CI 6.20 to 27.25), alcohol dependence (OR 2.90; 95% CI 1.59 to 5.24), or cannabis dependence (OR 3.96; 95% CI 2.29 to 6.8) in the last 6 months. In addition, subjects who died by suicide were more likely to have been affected with cluster B personality disorders (OR 10.18; 95% CI 3.34 to 30.80) and had higher scores of impulsive and aggressive traits (P < 0.001)., Conclusions: At the individual level, clinical risk factors for suicide among Inuit are similar to those observed in studies with the general population, and indicate a need for improved access to mental health services. The high rate of mental health problems among control subjects suggests the need for population-level mental health promotion.

Objectives: Deep transcranial magnetic stimulation (DTMS) has been shown to be efficacious and relatively safe for major depressive disorder (MDD). However, its clinical utility as an augmenting strategy for treatment-resistant depression (TRD) remains unexplored., Methods: In an open label trial, 17 outpatients with severe TRD received 4 weeks of daily high frequency DTMS over the left dorsolateral prefrontal cortex. Depressive and anxious symptoms, suicidality and quality of life (QOL) were measured at baseline (i.e., in the week prior to the start of the DTMS treatment) and at week 5 (i.e., in the week following the end of the DTMS treatment). Primary outcome measures were rates of response and remission at week 5 using an intention-to-treat approach., Results: Response and remission rates at week 5 were 70.6 and 41.2%, respectively. Also, depression, anxiety, and suicidality ratings were significantly improved by week 5 (with Hedges' g estimates ranging from 0.6 to 1.72), as well as four of the five QOL domain scores (i.e., global, psychological, environmental and social). Finally, two patients dropped out of the study at week 1 because of significant scalp discomfort during stimulation., Conclusions: Our study suggests that DTMS, when used as an augmenting strategy for antidepressants in severe TRD, is efficacious, safe and relatively well tolerated. However, controlled studies with larger samples are needed to confirm and expand our preliminary findings.

Background: Prognostication is poor in repetitive transcranial magnetic stimulation (rTMS) treatment for major depressive disorder (MDD). Personality traits, particularly extraversion and neuroticism, have attracted increasing attention for both trait- and state-dependent characteristics in predicting response to pharmacotherapy, psychotherapy, and more recently to therapeutic neuromodulation for MDD. The advent of deep rTMS (DTMS) allows stimulation of deeper cortical regions, and we aimed to prospectively characterize personality dimensions and antidepressant response to DTMS in treatment-resistant MDD., Methods: A convenience sample of 15 patients with treatment-resistant MDD received four weeks of daily sessions of DTMS (20 Hz, 3000 pulses/session) of the left dorsolateral prefrontal cortex (DLFPC). At baseline and at the conclusion of treatment, patients completed the Big Five Inventory, a five-factor assessment of major personality dimensions. Clinical response was measured using the 21-item Hamilton Depression Rating Scale., Results: Four weeks of DTMS treatment were not associated with changes in personality measures. Clinical remission was associated with higher baseline levels of agreeableness (score ≥ 29:100% sensitive and 72.7% specific) and conscientiousness (score ≥ 30:75% sensitive and 81.8% specific). Levels of agreeableness and extraversion were linearly associated with antidepressant response. Neuroticism was not associated with the antidepressant effects of DTMS in this cohort., Conclusions: Five-factor personality assessment may have prognostic value in DTMS for resistant MDD. Agreeableness, extraversion, and conscientiousness are associated with decreases in depressive symptoms during treatment with DTMS., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The impact of major depression on quality of life (QOL) and aging experiences in older adults has been reported. Studies have demonstrated that the clinical diagnosis of major depression is the strongest predictor for QOL. We postulate that some findings are biased because of the use of inadequate instruments. Although subsyndromal depression is more prevalent than major depression, there are no reports on its impact on QOL or attitudes toward aging. In the present study we aim at assessing the association of major and subsyndromal depression on QOL and attitudes toward aging in a large international sample., Design and Methods: Our cross-sectional study assessed 4,316 respondents in 20 countries from five continents. The study used the World Health Organization Quality of Life (WHOQOL) Assessment for Older Adults, known as the WHOQOL-OLD; the brief version of the WHOQOL instrument, known as the WHOQOL-BREF; and the Attitudes to Ageing Questionnaire. Statistical analyses involved hierarchical multiple regression, as well as comparison of means., Results: Even relatively minor levels of depression are associated with a significant decrease in all QOL domains and with a pattern of negative attitudes toward aging (overall WHOQOL-OLD R(2) change =.421). QOL and attitudes toward aging scores are lower as depression intensity is increased, even in subsyndromal levels (overall WHOQOL-OLD mean scores of 95.7 vs 86.4, p <.001). This phenomenon happens not only for clinically depressed individuals but also for subsyndromic individuals., Implications: Present findings suggest that classifying a respondent as nondepressed is not sufficient and is still not informative about his or her QOL and attitudes toward aging status.