HDRS Scores Research Articles

Systematic review and meta-analysis comparing iTBS vs. TMS vs. sham in randomized controlled trials.

Background: The objective was to evaluate the outcomes (response and safety/adverse events) of intermittent theta burst stimulation (iTBS) to repetitive transcranial magnetic stimulation (rTMS) and to sham (iTBS v. sham) when used in patients with major depressive disorder (MDD) in randomized controlled trials (RCTs). Methods: The use of preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA) was utilized. The Cochrane methodology for evaluating RCTs was employed using risk of bias assessments, data synthesis, and statistical methods, including forest plots (risk ratio; M-H random effects; 95% CI). Eligibility criteria for study inclusion/exclusion were formulated a priori. Eligibility criteria included: primary diagnosis of MDD, reporting of outcome(s) [response of ≥50% reduction in HDRS score; yes/no], ≥1 week duration of therapy, manuscript only publication, and safety. Results: A systematic review of the literature identified 270 records of which 8 manuscripts were used for qualitative and 7 for meta-analyses. Risk of bias demonstrated an overall low risk of bias (Fig 1; green, blank, red – low, unclear, high risk); forest plots of response rates of iTBS v sham (Fig 1; iTBS ≥50% response reduction v. sham; RR=1.91; 95% CI: 1.19-3.06; I2=0%; P=0.007); iTBS v. rTMS (no statistical difference on outcome of response; P=0.57); and adverse events iTBS v. sham (no statistical difference v. sham).Fig 1 Conclusions: The response rates to iTBS v. sham were significantly improved; iTBS v. rTMS were statistically similar and adverse events no worse than sham. iTBS should be considered as an alternative to rTMS in those MDD patients where it is indicated.

The bi-factor structure of the 17-item Hamilton Depression Rating Scale in persistent major depression; dimensional measurement of outcome

The 17-item Hamilton Depression Rating Scale (HDRS17) is used world-wide as an observer-rated measure of depression in randomised controlled trials (RCTs) despite continued uncertainty regarding its factor structure. This study investigated the dimensionality of HDRS17 for patients undergoing treatment in UK mental health settings with moderate to severe persistent major depressive disorder (PMDD). Exploratory Structural Equational Modelling (ESEM) was performed to examine the HDRS17 factor structure for adult PMDD patients with HDRS17 score ≥16. Participants (n = 187) were drawn from a multicentre RCT conducted in UK community mental health settings evaluating the outcomes of a depression service comprising CBT and psychopharmacology within a collaborative care model, against treatment as usual (TAU). The construct stability across a 12-month follow-up was examined through a measurement equivalence/invariance (ME/I) procedure via ESEM. ESEM showed HDRS17 had a bi-factor structure for PMDD patients (baseline mean (sd) HDRS17 22.6 (5.2); 87% PMDD >1 year) with an overall depression factor and two group factors: vegetative-worry and retardation-agitation, further complicated by negative item loading. This bi-factor structure was stable over 12 months follow up. Analysis of the HDRS6 showed it had a unidimensional structure, with positive item loading also stable over 12 months. In this cohort of moderate-severe PMDD the HDRS17 had a bi-factor structure stable across 12 months with negative item loading on domain specific factors, indicating that it may be more appropriate to multidimensional assessment of settled clinical states, with shorter unidimensional subscales such as the HDRS6 used as measures of change.

Effectiveness of Emotional Memory Reactivation vs Control Memory Reactivation Before Electroconvulsive Therapy in Adult Patients With Depressive Disorder

Although electroconvulsive therapy (ECT) is often effective, approximately half of patients with depression undergoing ECT do not benefit sufficiently, and relapse rates are high. ECT sessions have been shown to weaken reactivated memories. The effect of emotional memory retrieval on cognitive schemas remains unknown. To assess whether emotional memory retrieval just before patients receive ECT sessions weakens underlying cognitive schemas, improves ECT effectiveness, increases ECT response, and reduces relapse rates. In this multicenter randomized clinical trial conducted from 2014 to 2018 in the departments of psychiatry in 3 hospitals in the Netherlands, 72 participants were randomized 1:1 to 2 parallel groups to receive either emotional memory reactivation (EMR-ECT) or control memory reactivation (CMR-ECT) interventions before ECT sessions. The Hamilton Depression Rating Scale (HDRS [total score range: 0-52, with 0-7 indicating no depression and ≥24 indicating severe depression]) was used to measure symptoms of depression during and after ECT, with a 6-month follow-up period. Participants were between ages 18 and 70 years with a primary diagnosis of unipolar major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) and in whom ECT was indicated. Data analysis was performed from July to November 2019. EMR-ECT or CMR-ECT interventions prior to ECT sessions. Depression scores and relapse rates within 6 months were assessed with the HDRS and analyzed using logistic and linear multiple regression analyses. A total of 66 patients (mean [SD] age, 49.3 [12.3] years; 39 [59.1%] women) were randomized to the EMR-ECT group (n = 32) or the CMR-ECT group (n = 34). Regardless of the memory intervention, 42.4% (28 of 66) of patients responded (≥50% decrease of symptom severity on the HDRS). Of patients who responded, 39.3% (11 of 28) relapsed within 6 months. Remission rates (CMR-ECT group, 29.4% [10 of 34] vs EMR-ECT group, 25.0% [8 of 32]; P = .58), mean (SD) HDRS scores after the ECT course (CMR-ECT group, 14.6 [8.6] vs EMR-ECT group, 14.9 [8.8]; P = .88), total mean (SD) number of required ECT sessions for response (CMR-ECT group, 14.9 [7.9] vs EMR-ECT group, 15.6 [7.3]; P = .39), and relapse rates (CMR-ECT group, 46.7% [7 of 15] vs EMR-ECT group, 30.8% [4 of 13]; P = .33) were not significantly altered by the intervention. Study findings suggest that the EMR-ECT intervention just before patient receipt of ECT for depression did not improve effectiveness, increase speed of response, or reduce relapse rates after the ECT course compared with patients receiving CMR-ECT. Trialregister.nl Identifier: NL4289.

Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder

IntroductionAnimal models of depression have reported elevated levels of T helper 17 (Th17) and T helper 1 (Th1) cells along with a decrease in T regulatory (Treg) cell percentage. However, there is ambiguity in the results of clinical studies investigating Th17 cells in Major Depressive Disorder (MDD). No studies have investigated the role of Interferon gamma positive Th17 cells (IFNγ+ Th17) in MDD yet. MethodsThe study population included 53 patients of first episode, drug naïve MDD patients, and 53 non-psychiatric healthy volunteers as healthy controls. Th17, Th1, IFNγ+ Th17 and Treg cell percentages were assessed by flow cytometry. ResultsThe mean (±SD) percentage of Th17 cells in cases (1.87 ± 1.03) was significantly higher than the mean in controls (1.1 ± 0.94) (p < 0.001). There was no significant difference in the Treg percentages between the cases (2.1 ± 2.0) and controls (2.23 ± 0.95). The Th17:Treg ratio was significantly higher in cases (5.41 ± 10.84) compared to the controls (0.69 ± 0.89) (p < 0.05). Further analysis of data has also revealed that IFNγ+ Th17 subsets secreted more IL-17 in cases (515.7 ± 423.4) compared to controls (509.6 ± 337.4). Intracellular IL-17 levels in this subset also showed a weak though insignificant positive correlation with HDRS scores in the cases. ConclusionElevated circulating Th17 cell percentage and Th17:Treg ratio in MDD cases thus add to the evidence suggesting Th17 mediated pro-inflammatory state in MDD. The study also provides preliminary findings of the more pathogenic IFNγ+ Th17 cell subset in MDD.

Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)

IntroductionThe BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in...

Collaborative care for primary care treatment of late-life depression in Singapore: Randomized controlled trial.

The effectiveness and portability of the collaborative care model in the primary care treatment of depression has not been demonstrated in many randomized controlled trials in healthcare settings across the world. We determined the effectiveness of collaborative care management of elderly depression in the primary care setting in Singapore. Eligible participants with depressive symptoms were randomized to 6-month duration usual care (UC, N = 112) or collaborative care (CC, N = 102). Outcome measures were HDRS-17, GDS, BDI and SF-12 MCS QOL measured at 3, 6, and 12-month, care satisfaction at 6-month, and also measured on 120 participants who refused referral (non-receipt of care, NC). Primary outcome was HDRS-17 measure of depression severity, response and remission at 6-month. HDRS scores in CC group compared to UC group were reduced more at 6-month (1.5 points difference in change from baseline), and also at 3 and 12-month, with similar observations of differences for GDS and BDI. There was significantly greater improvement for both CC and UC groups compared to NC group. The CC group was about 1.5 times more likely to show HDRS treatment response and remission, and more than two times likely to show GDS treatment response and remission than the UC and NC groups, as well as better quality of life improvement (P < .001) and better care satisfaction (P < .001). Collaborative care is effective for primary care treatment of older persons with depression and is portable in diverse health care settings.

A randomized controlled trial of a standard 4-week protocol of repetitive transcranial magnetic stimulation in severe treatment resistant depression

BackgroundTreatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research QuestionDoes high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? MethodWe performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. ResultsAn interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p < 0.01). There were no differences however between the treatment arms (F(1.30) = 1.5;p = 0.23). We did find a negative correlation between the change in HDRS score and DM-TRD in the active rTMS group, but this correlation was not significantly different from the sham group. Conclusion“Standard” 4-week rTMS treatment is not effective in chronic, severe treatment-resistant depressed patients. While a replication of our data in this patient group may be ethically difficult, further research with less treatment resistant patients might help in positioning rTMS within the current stepped care approach to depression.

Effectiveness of electroconvulsive therapy in patients with "less treatment-resistant" depression by the Maudsley Staging Model.

IntroductionElectroconvulsive therapy (ECT) is an effective treatment for patients with mood disorders and is most often used for treatment‐resistant cases. This study aimed to examine the effectiveness of ECT in a real‐world treatment sample in a Chinese psychiatric hospital which included both treatment‐resistant and nontreatment‐resistant patients.MethodsAn observational study of symptom outcomes from admission to the time of discharge was conducted with 37 inpatients diagnosed with unipolar or bipolar depression treated with ECT. Symptom severity was assessed with the 17‐item Hamilton Rating Scales for Depression (HRSD‐17) and treatment‐resistance with the Maudsley Staging Model (MSM). Stratifying at the MSM median admission characteristics and symptom change was compared between patients who were treatment‐resistant (n = 18) and who were not (n = 19). The outcome difference between groups was compared using analyses of covariance adjusted for baseline characteristics including symptom severity, followed by linear regression to identify factors associated symptom improvement in the entire sample.ResultsThe sample (n = 37) showed moderate treatment‐resistance (MSM = 7.30 ± 1.13) at admission and both groups received 8.3 ± 2 ECT sessions. The treatment‐resistant group had a smaller proportion of bipolar patients and more severe symptoms, but showed no significant difference from the nontreatment‐resistant group in HDRS‐17 scores at the time of discharge (adjusted means = 6.23 ± 1.00 vs. 5.94 ± 0.97, Partial η 2 = 0.001, p = .845). Baseline symptom severity was the strongest correlate of reduction in HDRS‐17 scores (β = 0.891, p < .001).ConclusionsSymptom change with ECT in depression did not differ by level of treatment‐resistance but was greatest among those with more severe baseline symptoms. Correlates of ECT effectiveness should be further evaluated in stratified randomized trials.

Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population.

Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder. A total of 148 depressive patients receiving escitalopram 10-20mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA. Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, LALA haplotypes, and 2 LA functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous LA carriers compared with other groups. Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LALA haplotypes being the predictors of better treatment response.

Unmet Need for Social and Emotional Support and Lack of Recalled Screening Is Associated with Depression in the Long-Term Course After Stroke.

PurposeDetails on adequate care and prevalence of depression in long-term stroke aftercare are limited. We aimed to determine long-term depression rates after stroke and to test for an association between depression and inadequate screening, socio-economic complications and lack of sub-optimal care.Patients and MethodsIn this cross-sectional study, 57 patients were re-invited into the clinic 2–3 years after stroke. Patients were interviewed about recalled screening concerning depression and unmet needs. Depression, the patient’s social situation, and confounders were assessed by standardized scores.ResultsIn our study, 20% (n = 11) of patients were classified as depressed by the HDRS-17 score result. However, only 36% of all patients recalled to have been previously screened for depression and only 43% of those patients also recalled out-patient screening. Patients classified as depressed reported significantly lower recalled screening rates (9% vs 43%; p = 0.036) and higher rates of self-reported unmet need with emotional problems (72% vs 18%; p < 0.001). Depression in our study was further associated with a worse socio-economic situation, fewer social contacts, unmet needs with regard to emotional problems and higher rates of recommendations to apply for additional social support.ConclusionOur data suggest that systematic out-patient screening for depression is lacking in stroke aftercare. Furthermore, the high rate of unmet emotional needs, the poor socio-economic situation and the higher rates of recommendations for social counselling and application for benefits suggest an undersupply of care in the out-patient setting that is more prominent in patients with depression and warrants further studies to investigate the underlying causes.

Hemodiyaliz Hastalarında Progresif Gevşeme Egzersizinin Konfor Düzeyine Etkisi

Amaç: Hemodiyaliz tedavisi alan hastalara uygulanan progresif gevşeme egzersizinin konfor düzeyine etkisini değerlendirmektir. Gereç ve Yöntem: Bu araştırma, ön test-son test kontrol gruplu yarı deneysel olarak, 15 Nisan- 30 Mayıs 2019 tarihleri arasında bir diyaliz merkezinde, kontrol grubu 20 ve girişim grubu 20 hasta ile yapılmıştır. Araştırma verileri, “Hasta Tanıtım Formu” ve “Hemodiyaliz Konfor Ölçeği (HDKÖ)” kullanılarak toplanmıştır. Frekans dağılımı, ortalama, standart sapma ile veriler sunulmuş istatistiksel analizlerde, bağımsız gruplarda t testi kullanılmıştır. Çalışmada anlamlılık düzeyi p<0.05 olarak kabul edilmiştir. Bulgular: Çalışmaya katılan girişim grubu hastaların %50’si kadın, %60‘ı 40-59 yaş aralığında; kontrol grubundaki hastaların %50’si kadın, %40‘ı 40-59 yaş aralığındadır. Girişim grubundaki hastaların HDKÖ ortalama puanlarının ön testte 25,4±4,84, son testte 27,6±3,96 olduğu saptanmıştır. Kontrol grubundaki hastaların HDKÖ ortalama puanlarının ön testte 25,4±2,58; son testte 24,25±2,67 olduğu saptanmıştır. Sonuç: Progresif gevşeme egzersizlerinin hemodiyaliz tedavisi alan hastaların konfor düzeyini arttırdığı saptanmıştır.

Melancholic versus Nonmelancholic Major Depression Compared

BackgroundThe concept of melancholia has been associated with psychiatric nosology for centuries. Nevertheless, its definition, relationship to the contemporary concept of Major Depressive Disorder, and clinical implications remain uncertain. MethodsIn a total sample of 3211 closely evaluated patient-subjects diagnosed with DSM-5 Major Depressive or Bipolar Disorder and meeting DSM-5 criteria for major depression with melancholic features or not at a European mood disorder center, we matched 1833 for depression severity (baseline HDRS21 score ≥18) and compared rates and ratings of characteristics of interest between the subgroups, using bivariate and multivariate methods. ResultsObserved prevalence of melancholic features was 35.2% in the 1833 subjects matched for severity, and 21.0% among all 3211 subjects. Diagnosis was highly dependent on depression-severity measured three ways. Very few clinical characteristics differed between melancholic and nonmelancholic subjects matched for illness-severity; more suicidal ideation with melancholic features was a notable exception. ConclusionsStudy findings leave the distinction of melancholic features from depression-severity unclear and the potential clinical value of diagnosing melancholic features uncertain.

Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial.

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD). The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week, double-blind, randomized, placebo-controlled study. Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), following a 4-week observation period (week 8). The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8. Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17, the proportion of participants having improvement in the clinical global impression-improvement, the change in HDRS-17 score (range, 0–52, with higher scores indicating more depression) over the study, and variations of brain imaging and neurocognition from baseline to week 4. Safety will be assessed by vital signs at weeks 4 and 8, and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.Trial registration:Chinese Clinical Trial Registry, ChiCTR1800016479; http://www.chictr.org.cn/showproj.aspx?proj=22048.

Impact of Pharmacogenomics on Clinical Outcomes for Patients Taking Medications With Gene-Drug Interactions in a Randomized Controlled Trial

The objective of the Genomics Used to Improve DEpression Decisions (GUIDED) trial was to evaluate the utility of pharmacogenomic testing to improve outcomes among patients with major depressive disorder (MDD) who had not responded to at least 1 prior medication trial. The objective of the present analysis was to assess outcomes for the subset of patients expected to benefit from combinatorial pharmacogenomic testing because they were taking medications with predicted gene-drug interactions. Participants (enrolled from April 14, 2014, to February 10, 2017) had an inadequate response to at least 1 psychotropic medication in the current episode of MDD. Patients were randomized to treatment as usual (TAU) or the guided-care arm, in which clinicians had access to a combinatorial pharmacogenomic test report to inform medication selection. Patients and raters were blinded to study arm through week 8. The following outcomes were assessed using the 17-item Hamilton Depre​ssion Rating Scale (HDRS-17): symptom improvement (percent change in HDRS-17 score), response (≥ 50% decrease in HDRS-17 score), and remission (HDRS-17 score ≤ 7). In the GUIDED trial, the primary endpoint of symptom improvement did not reach significance in the intent-to-treat cohort (P = .069). Here, a post hoc analysis of patients who were taking medications subject to gene-drug interactions at baseline as predicted by combinatorial pharmacogenomic testing (N = 912) is presented. Among participants taking medications subject to gene-drug interactions at baseline, outcomes at week 8 were significantly improved for those in the guided-care arm compared to TAU (symptom improvement: 27.1% versus 22.1%, P = .029; response: 27.0% versus 19.0%, P = .008; remission: 18.2% versus 10.7%, P = .003). When patients who switched medications were assessed, all outcomes were significantly improved in the guided-care arm compared to TAU (P = .011 for symptom improvement, P = .011 for response, P = .008 for remission). By identifying and focusing on the patients with predicted gene-drug interactions, use of a combinatorial pharmacogenomic test significantly improved outcomes among patients with MDD who had at least 1 prior medication failure. ClinicalTrials.gov identifier: NCT02109939​.

Sex differences in the prevalence and clinical features of comorbid depressive symptoms in patients with never-treated, first-episode schizophrenia

BackgroundMany aspects of schizophrenia are thought to be sex-specific, and patients with schizophrenia experience depressive symptoms at all disease phases. We investigated sex differences in patients with co-occurring schizophrenia and depressive symptoms, and investigated sex-specific relationships between depressive symptoms and clinical correlates. MethodsIn this cross-sectional study, we recruited Han Chinese inpatients (aged 16–45 years) in the Huilongguan mental hospital (Beijing, China) who had an acute, untreated first episode of schizophrenia that met the American Psychiatric Association's DSM-IV criteria for schizophrenia. Symptoms at the time of recruitment had to be moderate or severe according to the Clinical Global Impression Scale (≥4 points) and could not have lasted for more than 60 months. The Positive and Negative Syndrome Scale (PANSS) was used to assess clinical psychopathological symptoms and the 17-item Hamilton Depression Rating Scale (HDRS-17) for comorbid depressive symptoms. Pearson's χ2 test was used to calculate the incidence of co-occurring depressive symptoms in male and female patients. Odds ratios (ORs) were calculated using logistic regression comparing patients with and without depressive symptoms. The study was approved by the Insitutional Review Board of Huilongguan hospital and participants gave written informed consent before recruitment. FindingsBetween June 1, 2013, and Dec 20, 2015, 267 inpatients were recruited from consecutive admissions to the hospital. 27 were excluded because of documented medical abnormalities (n=7), substance dependence other than tobacco (n=5), other comorbid psychiatric disorders (n=6), or refusal or inability to provide consent (n=9). 240 patients (111 men and 129 women) were evaluable. Significantly more men (69 [62%]) than women (62 [48%]; χ2=4·28, p=0·039) had depressive symptoms (defined as total HDRS-17 score ≥8 points), which were also more severe (t=2·75, p=0·0058). Age, age at schizophrenia onset, and smoking were associated with significant sex differences for female patients, as were total, general psychopathology, negative PANSS symptoms, and cognitive factor subscale PANSS scores (all p<0·05). We found sex differences in the correlation between HDRS score and clinical phenotype, showing that in men, the PANSS general psychopathology subscore (β=0·75, t=7·72, p<0·0001) and the PANSS total score (β=0·44, t=4·81, p<0·0001) significantly predicted the HDRS-17 total score, whereas in women, the HDRS-17 total score was significantly predicted by the PANSS general psychopathology subscore (β=0·74, t=8·45, p<0·0001), the PANSS total score (β=0·47, t=5·71, p<0·0001), and the PANSS cognitive factor score (β=0·24, t=2·60, p=0·011). InterpretationOur results indicate that there are sex differences in the prevalence and severity of comorbid depressive symptoms, as well as their association with clinical correlates, in patients with never-treated, first-episode schizophrenia. Men had more severe depression, whereas disease in women was affected more by external factors. However, a cross-sectional deisgn could not establish definitive causative associations between sex and depressive or psychotic symptoms. FundingNational Natural Science Foundation of China (grant 81371477) and CAS Pioneer Hundred Talents Program.

Сomparative efficiency of rTMS in combined treatment of pharmaco-resistant depression

Objective The aim of the study was comparative assessment of efficiency of combined TMS included treatment of pharmaco-resistant depression upon reduction of clinical symptoms and neurocognitive deficits. Methods 50 female patients aged 18 to 56 years (mean age 36.3 ± 13.1) with pharmaco-resistant depression (F31.3, F33.0, F33.1 by ICD-10) were enrolled in the study. 23 patients (control group) were treated with SSRI antidepressants, while 27 patients (TMS group) received the same pharmacotherapy together with the course of TMS. Both groups did not differ statistically in demographics parameters and depression severity (mean HDRS-17 scores were 21.0 and 23.2, respectively). High frequency rTMS (25 Hz, intensity of 60–80% of motor threshold, 40 series by 2 s with 14 s intervals–that may be called “beta-bursts” mode, total 1600 pulses, 15 daily sessions) was applied to the projection of the left dorsolateral prefrontal cortex. Relatively low TMS intensity was chosen to prevent facial muscles jerks and to make the procedure more comfortable for patients. Results After 3 weeks of treatment both previously resistant groups demonstrated highly significant (P Conclusions Even low intensity high frequency rTMS of the left dorsolateral prefrontal cortex appeared to be useful method for overcoming the pharmaco-resistance and for improvement of decision-making functions in depressive patients.

MicroRNA-140-5p: A novel circulating biomarker for early warning of late-onset post-stroke depression

We aimed to explore the circulating microRNAs biomarkers in the acute stage following cerebral ischemia to earlier warn late-onset post-stroke depression (PSD). A total of 251 consecutive patients with acute ischemic stroke were recruited. They were divided into three groups depending on whether PSD had occurred at 2 weeks or 3 months since stroke: early-onset PSD, late-onset PSD, and non-depressed group. Microarray assay was conducted to identify the different expression profiles of plasma miRNAs. Comprehensive bioinformatics analysis for their integrating putative target genes was performed. The key miRNA was validated in a larger cohort and its function was further studied in ischemic mice brain. We screened three differentially expressed miRNAs in the late-onset PSD individuals, miR-140-5p and miR-221-3p were significantly upregulated while miR-1246 was downregulated. The bioinformatics analysis demonstrated that their predicted target genes were mainly enriched in axon development and Ras signaling pathway. Logistic regression analysis revealed that miR-140-5p was an independent risk factor for late-onset PSD (P = 0.017, OR = 2.313, 95%CI 1.158 to 4.617). The miR-140-5p expression on admission was significantly positively correlated with HDRS scores assessed at 3 months after stroke (P = 0.0007). The predictive value of miR-140-5p for late-onset PSD is 83.3% sensitivity and 72.6% specificity (AUC = 0.8127, P < 0.0001). AAV-mediated overexpression of miR-140-5p decreased the protein level of IL1rap, IL1rapl1, VEGF, and MEGF10 in the ischemic mouse hippocampus and inhibited neurogenesis and capillary density. MiR-140-5p might be involved in the pathogenesis of late-onset PSD and used as a novel early warning biomarker.

Social Support and Depression Related to Older Adults’ Hypertension Control in Rural China

This study aimed to investigate association between social support and hypertension (HTN) control in rural China older adults, and to what extent depression mediates this relationship. The authors hypothesized that depression severity mediated the relationship between social support and HTN control. Data for the analyses were obtained from baseline data from a randomized controlled clinical trial of a collaborative depression care management intervention conducted in rural villages of China, with older adults with comorbid depression and HTN. Data included baseline assessments of 2,351 subjects aged 60 years and older, whose blood pressure and depression severity were measured using a calibrated manual sphygmomanometer and the 17-item Hamilton Depression Rating Scale (HDRS-17), respectively. Social support was measured using the 20-item Medical Outcomes Study-Social Support Survey. Uncontrolled HTN was associated with older age (t[df = 2349] = 3.16; p < 0.01), higher HDRS-17 score (t[df = 1488] = 5.89; p < 0.001), and lower social support (t[df = 2349] = 5.37; p < 0.001). A significant indirect effect of social support via depression severity in relation to HTN control (a × b = -0.04[0.01]), bootstrap p = 0.0015, and 95% confidence interval (-0.07, -0.02), accounting for 11% of the effect of social support on HTN control. These findings imply that social support impacts HTN control directly and indirectly through depression. Intervention approaches such as primary care-based collaborative care models should address social support to achieve greater outcomes for depression and HTN management.

Effect of a 10-day transcutaneous trigeminal nerve stimulation (TNS) protocol for depression amelioration: A randomized, double blind, and sham-controlled phase II clinical trial

BackgroundMajor depressive disorder (MDD) is one of the leading causes of disability in the world. However, treatment options are still limited, and marked by high refractoriness rates, new approaches are needed to optimize clinical improvement. Trigeminal nerve stimulation (TNS) is an innovative neuromodulation strategy consisting on the application of an electric current over the trigeminal nerve that propagates stimuli towards brain areas involved in mood control. ObjectiveWe examined the effects of TNS in MDD after a 10-day experimental protocol. MethodsThis was a randomized, double blind, and sham-controlled phase II study with 24 patients with severe MDD. Patients underwent a 10-day intervention protocol and were assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17) at following three observation points: baseline (T1), after 10 days (T2), and after one month of the last stimulation session (T3). Main clinical outcome analysis of variance (ANOVA) was performed. ResultsPatients in the active group presented a mean reduction of 36.15% in depressive symptoms after the stimulation protocol. There was a significant interaction between group and time regarding HDRS-17 scores (F = 3.18; df = 2; p = 0.0456). Post hoc analyses exhibited a statistically significant difference between active and sham group symptoms at T2 (p = 0.040) and T3 (p = 0.026), which highlights the sustained amelioration of depressive symptoms. ConclusionThe present study found amelioration of depressive symptoms for patients undergoing a 10-day stimulation protocol of TNS, and this was sustained after one month of follow-up.

Baseline serum C-reactive protein levels may predict antidepressant treatment responses in patients with major depressive disorder

BackgroundInflammation has been shown previously to predict antidepressant treatment response. This retrospective study was conducted to test if the baseline serum C-reactive protein (CRP) levels could predict antidepressant treatment responses in a Chinese sample. Methods75 adult inpatients (26 male, 49 female) with major depressive disorder (MDD) diagnosed according to DSM-5 were included in this study. Sociodemographic and clinical features, baseline CRP levels, 17-item Hamilton Depression Rating Scale (HDRS-17) and Hamilton Anxiety Rating Scale (HARS) scores assessed at baseline and weeks 1, 2, 3 and 4 were then collected. Afterwards patients were divided into two groups: the low CRP group (baseline CRP < 1 mg/L, n = 47) and the high CRP group (baseline CRP ≥ 1 mg/L, n = 28). Depression severity and treatment response were compared between the two groups. ResultsRepeated-measures ANOVA showed a significant group * assessments interaction in HDRS-17 scores (F = 4.754; p = 0.005). Post-hoc test showed that the two groups differed in HDRS-17 scores at week 4 (F = 6.698; p = 0.012), with the low CRP group having lower HDRS-17 scores than the high CRP group. Moreover, the low CRP group exhibited higher percent reduction in HDRS-17 scores at week 3 (F = 5.016; p = 0.028) and week 4 (F = 9.865; p = 0.003) as compared to the high CRP group. Cox proportional hazard model showed that the remission rate was higher in the low CRP group (p = 0.010). LimitationsPatients received uncontrolled antidepressant therapy and the sample size was limited. ConclusionsBaseline serum CRP levels may predict antidepressant treatment responses in patients with MDD and patients with higher levels of CRP were less likely to get remission.