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Aims: The diversity of treatment outcomes for major depressive disorder (MDD) remains uncertain in neuropathology. The current study aimed at exploring electrophysiological biomarkers associated with treatment response. Methods: The present study recruited 130 subjects including 100 MDD patients and 30 healthy controls. All subjects participated in a sad expression recognition task while their magnetoencephalography data were recorded. Patients who had a reduction of at least 50% in disorder severity at endpoint (>2 weeks) were considered as responders. Within‐frequency power and phase‐amplitude coupling were measured for the brain regions involved in the emotional visual information processing pathways. Results: The significant alpha–gamma decoupling from the right thalamus to the right amygdala in unconscious processing and from right orbital frontal cortices to the right amygdala in conscious processing was found in non‐responders relative to responders and healthy controls. These kinds of dysregulation could also predict the potential treatment response. Conclusion: The attenuated alpha–gamma coupling in dual pathways indicated increased sensitivity to the negative emotional information and reduced moderated effect of the amygdala, which might cause insensitivity to antidepressant treatment and could be regarded as potential neural mechanisms for treatment response prediction. [ABSTRACT FROM AUTHOR]

Background: Alterations in gray matter (GM) have been recognized as playing an important role in the neurobiological mechanism underlying major depressive disorder (MDD) and antidepressant responses. However, little is known about white matter (WM) connectivity in MDD, leaving an incomplete understanding of the pathophysiology of the disorder.Purpose: To examine the functional connectivity (FC) of WM, GM, and WM-GM in MDD patients and explore the relationship between FC and antidepressant response.Study Type: Longitudinal study.Subjects: In all, 129 MDD patients and 89 healthy controls (HC).Field Strength/sequence: Whole-brain blood oxygen level-dependent (BOLD) single-shot echo planar imaging was acquired at 3.0T.Assessment: At baseline, all participants received Hamilton depression rating scale (HAMD) assessment and an fMRI scan. After 2- and 8-week antidepressant treatment, patients completed the HAMD again. The HAMD reductive rate of 2- and 8-weeks were calculated.Statistical Tests: The comparisons of age, education, HAMD scores, and FC values (false discovery rate correction) between patients and controls were calculated with a two-sample t-test. The chi-square test was employed to compare the differences of gender between these two groups. Correlations between FC and HAMD, as well as the reductive rate of HAMD, were analyzed with Pearson or Spearman correlation. Receiver operator curve analysis was performed to predict the antidepressant response.Results: Compared to HC, MDD patients exhibited widespread decreases in FC of WM-GM. Furthermore, 28 GM regions and 11 WM bundles had lower connectivity in MDD patients. At baseline, four FC of WM-GM showed negative correlations with the HAMD scores. Six FC of WM-GM correlated with the 2-week reductive rate of HAMD. Moreover, FC in GM, WM, and WM-GM also exhibited significantly positive correlations with an 8-week reductive rate of HAMD.Data Conclusion: The FC of WM-GM was decreased in MDD and may play a role in its pathophysiology and antidepressant responses.Level Of Evidence: 2.Technical Efficacy Stage: 2. [ABSTRACT FROM AUTHOR]

Background: In order to reduce unsuccessful treatment trials for depression, neuroimaging and genetic information can be considered as biomarkers. Together with machine-learning methods, prediction models have proved to be valuable for baseline prediction.Purpose: To propose an ensemble learning modeling framework that integrates imaging and genetic information for individualized baseline prediction of early-stage treatment response of antidepressants in major depressive disorder (MDD).Study Type: Prospective.Subjects: In all, 98 inpatients with MDD.Field Strength/sequence: 3.0T MRI and gradient-echo echo-planar imaging sequence.Assessment: Participants were divided into responders and nonresponders based on reducing rates of HDRS-6 after early-stage treatment of 2 weeks. Fourteen brain regions of interest were selected according to previous studies. An ensemble learning modeling framework was used to integrate imaging data and genetic data.Statistical Tests: Support vector machine (SVM) with linear kernel was utilized to integrate multimode information and then to construct the prediction model. Leave-one-out cross-validation (LOOCV) was used to evaluate the performance. The position characteristics obtained through SVM-RFE (recursive feature elimination) algorithm and LOOCV was considered to compare each feature's relative importance for the prediction model.Results: Compared with the single-level prediction model, the ensemble learning prediction model showed improvement in prediction performance (accuracy from 0.61 to 0.86 with imaging data and genetic data). Integrated with 14 priori brain regions, the region of interest (ROI) map ensemble learning prediction model can achieve a performance that is analogous with the model with information from whole-brain regions (both with accuracy of 0.81). The integration of genetic features further improved the sensitivity of prediction (sensitivity from 0.78 to 0.87 under the ensemble learning framework).Data Conclusion: Our ensemble learning prediction model demonstrated significant advantages in interpretability and information integration. The findings may provide more assistance for clinical treatment selection in MDD at the individual level.Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;52:161-171. [ABSTRACT FROM AUTHOR]

Objective: This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.Methods: Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram + placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response.Results: We analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-α-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03).Conclusions: Remission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample. [ABSTRACT FROM AUTHOR]

Aims To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. Methods The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms ( SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form ( CTQ- SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. Results A functional polymorphism at 3′ UTR of the corticotropin-releasing hormone receptor 1 ( CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. Conclusions Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs. [ABSTRACT FROM AUTHOR]

Objective Whether responses to antidepressants differ in bipolar and unipolar depression remains unresolved. Method We analyzed patient characteristics and outcomes of antidepressant treatment of 1036 depressed patients with bipolar- I or bipolar- II disorder, or unipolar major depression, using bivariate and multivariate methods and survival analysis, testing the hypothesis that responses would be superior in unipolar depression. Results Antidepressants were given to 84.8% (878/1036) of depressed patients: 58.9% of 93 bipolar-I, 80.1% of 117 bipolar- II, and 91.3% of 668 unipolar disorder cases. The 158 not given antidepressants had more manias/year, spent more months in mania and depression, and were far more likely to receive mood stabilizers or antipsychotics long term. Improvement of HDRS21 depression ratings ranked: bipolar- II (69.6%) > bipolar-I (62.9%) > unipolar (57.9%; P < 0.0001), independent of initial illness severity. Responder rates (≥50% improved without switching) ranked: bipolar- II (77.0%) > bipolar-I (71.6%) > unipolar (61.7%; P < 0.0001). Remission rates (final HDRS < 7) ranked: 54.0%, 50.6%, and 40.8% respectively ( P = 0.02); 67.5% remitted within 12 weeks of treatment. Survival-computed median time to remission (15.0 weeks, overall) was shortest for bipolar- II patients (10.7 weeks). The 3-month risk of switching into mania-hypomania ranked: bipolar- II (15.8%) > bipolar-I (8.60%) > unipolar (0.56%). Multivariate modeling found bipolar diagnosis, shorter latency to remission, more recent trial year, and fewer weeks depressed before treatment to be associated with greater percent improvement of HDRS ratings. Conclusion Selective use of antidepressants with or without mood stabilizers in non-agitated, depressed bipolar disorder patients for short periods was effective with moderate risk of potentially dangerous, manic mood elevation. [ABSTRACT FROM AUTHOR]

Objective The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks' treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Methods Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Results Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks' treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Conclusions Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective Previous studies of mixed aged and older adult samples with major depressive disorder (MDD) reported reduced depression response in anxious patients, but a systematic review and analysis has not been performed. Our aim was to determine if anxiety predicts antidepressant response in previously identified placebo-controlled trials of second generation antidepressants for late-life depression. Method From a previous systematic review that identified ten randomized, placebo-controlled trials of community dwelling patients aged 60 or older with major depression, anxious patients were identified by a score ≥7 on the anxiety/somatization factor of the Hamilton Depression Rating Scale (HDRS). Response was defined as 50% or greater improvement on the HDRS or the Montgomery Asberg Depression Rating Scale. A meta-analysis was performed using a random effects model to calculate Odds Ratios (OR). Results Data were available from eight trials having ten drug-placebo contrasts that included 2322 anxious and 1387 non-anxious patients. The odds ratio for response to drug compared to placebo in anxious patients was 1.57 (95% CI 1.15, 2.14; z = 2.86, n = 10, p < 0.001), in non-anxious patients was 1.44 (95% CI 1.15, 1.80, z = 3.21, n = 10, p < 0.001), and did not differ between groups. Pooled response rates to drug and placebo respectively were 49.4% vs 37.4% in anxious patients and 44.2 vs 35.5% in non-anxious patients. Conclusions In randomized, placebo-controlled trials, anxiety in late-life depression was not associated with decreased response to second generation antidepressants. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective In an earlier report, response inhibition predict antidepressant non-response in late-life depression (Sneed et al., 2007). The purpose of this study was to ascertain whether this effect is specific to response inhibition or whether impairment in other cognitive domains also predicts non-response. Method Older depressed patients (n = 84) enrolled in an 8-week trial of citalopram were classified as impaired or non-impaired relative to the sample on mental status, psychomotor speed, reaction time, spatial judgment, and memory, and contrasted with regard to antidepressant response. Results Patients who were impaired relative to the sample on digit symbol performance did not respond as quickly to citalopram as those who were unimpaired. By the end of the 8-week trial, however, both groups reached the same level of response. Impairment in other domains had no impact on antidepressant response. Conclusions Non-response was not attributable to impairment on any of the neuropsychological tests suggesting that antidepressant non-response is specific to impaired response inhibition. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Gender differences in the treatment response to fluvoxamine (selective serotonin re-uptake inhibitor) and milnacipran (serotonin/norepinephrine re-uptake inhibitor) were investigated in Japanese major depressive patients. A total of 125 Japanese patients was included in the present study. Sixty-six patients received fluvoxamine treatment. The daily dose was 50 mg/day for the first week and increased to 100 mg after 1 week, up to 200 mg after another week. Fifty-nine patients were given milnacipran. The daily dose was 50 mg/day for the first week, and up to 100 mg/day thereafter. Patients were divided into three groups: younger women (<44 years of age), older women (≥44 years of age) and men. Depressive symptoms were evaluated using the Montgomery and Åsberg Depression Rating Scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of the study. In comparison with other groups, younger women treated with fluvoxamine demonstrated a significant difference in the time course of MADRS score change. However, these gender/age-related differences of antidepressant response were not observed in the patients treated with milnacipran. The results suggest that fluvoxamine is more effective in younger female patients than older female patients and male patients, while milnacipran is generally effective irrespective of gender or age. [ABSTRACT FROM AUTHOR]

Antidepressant-induced hippocampal neurogenesis (AHN) is hypothesized to contribute to increases in hippocampal volume among major depressive disorder patients after long-term treatment. Furthermore, rodent studies suggest AHN may be the cellular mechanism mediating the therapeutic benefits of antidepressants. Here, we perform the first investigation of genome-wide expression changes associated with AHN in human cells. We identify gene expression networks significantly activated during AHN, and we perform gene set analyses to probe the molecular relationship between AHN, hippocampal volume, and antidepressant response. The latter were achieved using genome-wide association summary data collected from 30,717 individuals as part of the ENIGMA Consortium (genetic predictors of hippocampal volume dataset), and data collected from 1,222 major depressed patients as part of the NEWMEDS Project (genetic predictors of response to antidepressants dataset). Our results showed that the selective serotonin reuptake inhibitor, escitalopram evoked AHN in human cells; dose-dependently increasing the differentiation of cells into neuroblasts, as well as increasing gliogenesis. Activated genome-wide expression networks relate to axon and microtubule formation, and ribosomal biogenesis. Gene set analysis revealed that gene expression changes associated with AHN were nominally enriched for genes predictive of hippocampal volume, but not for genes predictive of therapeutic response., (© 2017 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.)