Hamilton Depression Rating Scores Research Articles

Patient Characteristics Associated with Opioid Abstinence after Participation in a Trial of Buprenorphine versus Injectable Naltrexone

Background and Objectives: Better understanding of predictors of opioid abstinence among patients with opioid use disorder (OUD) may help to inform interventions and personalize treatment plans. This analysis examined patient characteristics associated with opioid abstinence in the X:BOT (Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment) trial. Methods: This post-hoc analysis examined factors associated with past-month opioid abstinence at the 36-week follow-up visit among participants in the X:BOT study. 428 participants (75% of original sample) attended the visit at 36 weeks. Logistic regression models were used to estimate the probability of opioid abstinence across various baseline sociodemographics, clinical characteristics, and treatment variables. Results: Of the 428 participants, 143 (33%) reported abstinence from non-prescribed opioids at the 36-week follow-up. Participants were more likely to be opioid abstinent if randomized to XR-NTX (compared to BUP-NX), were on XR-NTX at week 36 (compared to those off OUD pharmacotherapy), successfully inducted onto either study medication, had longer time on study medication, reported a greater number of abstinent weeks, or had longer time to relapse during the 24-week treatment trial. Participants were less likely to be abstinent if Hispanic, had a severe baseline Hamilton Depression Rating (HAM-D) score, or had baseline sedative use. Conclusions: A substantial proportion of participants was available at follow-up (75%), was on OUD pharmacotherapy (53%), and reported past-month opioid abstinence (33%) at 36 weeks. A minority of patients off medication for OUD reported abstinence and additional research is needed exploring patient characteristics that may be associated with successful treatment outcomes.

Large-scale structural network change correlates with clinical response to rTMS in depression.

Response to repetitive transcranial magnetic stimulation (rTMS) among individuals with major depressive disorder (MDD) varies widely. The neural mechanisms underlying rTMS are thought to involve changes in large-scale networks. Whether structural network integrity and plasticity are associated with response to rTMS therapy is unclear. Structural MRIs were acquired from a series of 70 adult healthy controls and 268 persons with MDD who participated in two arms of a large randomized, non-inferiority trial, THREE-D, comparing intermittent theta-burst stimulation to high-frequency rTMS of the left dorsolateral prefrontal cortex (DLPFC). Patients were grouped according to percentage improvement on the 17-item Hamilton Depression Rating Score at treatment completion. For the entire sample and then for each treatment arm, multivariate analyses were used to characterize structural covariance networks (SCN) from cortical gray matter thickness, volume, and surface area maps from T1-weighted MRI. The association between SCNs and clinical improvement was assessed. For both study arms, cortical thickness and volume SCNs distinguished healthy controls from MDD (p = 0.005); however, post-hoc analyses did not reveal a significant association between pre-treatment SCN expression and clinical improvement. We also isolated an anticorrelated SCN between the left DLPFC rTMS target site and the subgenual anterior cingulate cortex across cortical measures (p = 0.0004). Post-treatment change in cortical thickness SCN architecture was associated with clinical improvement in treatment responders (p = 0.001), but not in non-responders. Structural network changes may underpin clinical response to rTMS, and SCNs are useful for understanding the pathophysiology of depression and neural mechanisms of plasticity and response to circuit-based treatments.

Prevalence of Anxiety and Depression in Pregnant Women at Tertiary Care Hospital

Background: Pregnancy is a period of strength and optimism for a woman, even though it is a period of vulnerability. As many as one in ten new mothers have clinical depression or anxiety before or throughout the first year after the delivery of a baby, regardless of financial status. Objective: To evaluate prevalence of anxiety and depression in pregnant women at tertiary care hospital Methodology: This cross sectional study was carried out at the department of Obstetrics and Gynaecology, Women and Children Hospital, Charsadda for a period of six months from July 2021 to December 2021. A total of 250 pregnant women were included in our study based on WHO, sample size calculator. To assess Anxiety and depression, Hamilton anxiety rating scale and Hamilton depression rating scale were employed. IBM SPSS version 24 was used for all the data analysis. Results: Based on Hamilton depression rating score, amongst 250 participants, 47 (18.8%) participants were normal, 75 (30%) participants were observed with mild depression, moderate depression was observed in 70 (28%) participants, severe depression was observed in 33 (13.2%) participants and very severe depression was observed in 25 (10%) participants while Based on Hamilton anxiety rating score, the number of participants in normal, mild, moderate and severe anxiety range were 88 (35.2%), 45 (18%), 171 (31.2%) and 39 (15.2%) respectively. Conclusion: Our study concludes that depression and anxiety is highly prevalent in our population. Majority of the women from rural areas were uneducated. Keywords: Prevalence; Anxiety; Depression; Pregnancy

Omega-3 as an Adjunctive Therapy of Sertraline and Venlafaxine Substantially Improves Symptoms of Major Depressive Disorder: A Double-blind, Placebo-controlled Study

Background: Due to the possible effect of omega-3 fatty acids on reducing depressive symptoms, in this study, we investigated these effects in combination with other antidepressants. Methods: The study was a double-blind clinical trial on 100 patients with major depressive disorder who were divided into four groups of 25 each and treated with 50 mg daily sertraline plus placebo, 50 mg daily sertraline plus two grams Omega 3 daily, 75 mg daily venlafaxine plus placebo, and 75 mg daily venlafaxine plus 2 g Omega 3 daily for 6 weeks. Results: The mean Hamilton depression rating score of sertraline and venlafaxine plus omega-3 after treatment were 4.42 and 4.23 respectively versus sertraline and venlafaxine plus placebo 14.4 and 14.2 respectively (P value=0.0001). Conclusion: Omega-3 enhanced the clinical function of sertraline and venlafaxine to reduce the severity of depression. Adding omega-3 to either sertraline or venlafaxine does not have a comparative advantage over each other in terms of the improvement of severity of depressive symptoms.

A Prospective Observational Study on the Effects of Antidepressant Treatment on Hypothalamic-Pituitary-Adrenal Axis Regulation in Treatment-Resistant Depression

Introduction: Dysregulation of Hypothalamic-Pituitary-Adrenal (HPA) axis can reduce the effects of antidepressants. Salivary cortisol level and Hamilton Depression Rating (HAM-D) score can be used to assess the level of improvement in the HPA axis and depressive disorders. Aim: To evaluate the changes in salivary cortisol level and HAM-D score in patients of Treatment Resistant Depression (TRD) and to investigate the association between them. Materials and Methods: The present prospective cohort study was conducted in the Department of Pharmacology and Psychiatry at Pt. JNM Medical College and Dr. BRAM Hospital Raipur (CG) over a period of one year, from June 2014 to June 2015. The participants were 52 diagnosed cases of TRD according to Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria, who were taking antidepressant medications for at least four weeks. The salivary cortisol values and HAM-D scoring were done at baseline and follow-up at 8 weeks and 16 weeks and compared by student’s t-test and one-way ANOVA. Results: A significant difference (p<0.001) was noted in the mean salivary cortisol levels (1.15±0.31 and 0.72±0.24) mean HAM-D (29.67±1.43 and 16.26±7.08) scores at baseline and subsequent follow-up respectively. Conclusion: The therapeutic benefit of antidepressants could be due to alteration of HPA axis functioning.

Comparison of clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram, and impact on prognostic quality of life in treating patients with epilepsy and depressive disorder.

This study aimed to investigate the clinical efficacy of oxcarbazepine and lamotrigine combined with escitalopram in treating patients with epilepsy and depressive disorder, and their influence on the prognostic quality of life. A total of 108 patients with epilepsy and depression were selected as research participants. Among them, 53 patients were treated by oxcarbazepine combined with escitalopram (group A) and 55 patients were treated by lamotrigine combined with escitalopram (group B). Following six-month treatment, efficacy, epilepsy frequency and duration, Hamilton Depression Rating (HAMD) and Montgomery-Asberg Depression Rating (MADRS) scores, adverse reactions, improvement of electroencephalogram (EEG) epileptic discharge, quality of life, 1-year drug retention rate and withdrawal reasons of the two groups were compared. There was no remarkable difference in the total efficacy rate between both groups. The number and duration of epileptic seizures, improvement of EEG epileptic discharge and quality of life in the two groups significantly improved after treatment, with no marked difference. HAMD and MADRS scores of patients from group B were significantly lower after treatment compared with those of patients from group A. The incidence rate of adverse reactions in group B was dramatically lower compared with group A, and the 1-year drug retention rate of group B was dramatically higher compared with that in group A. Both oxcarbazepine and lamotrigine combined with escitalopram exhibited good efficacy in patients with epilepsy and depressive disorder, and they may effectively improve the prognostic quality of life of patients. Lamotrigine combined with escitalopram presented with a better antidepressant effect and safety, with higher patient tolerance.

Attenuated Visual Function in Patients with Major Depressive Disorder.

Background: We sought to investigate visual function, primarily, and structural changes in retinal ganglion cells, secondarily, in patients with major depressive disorder. Methods: A total of 50 normal participants and 49 patients with major depressive disorder were included in this cross-sectional study. The participants underwent 24–2 standard automated perimetry and spectral-domain optical coherence tomography. Results: The pattern standard deviation (PSD) in the visual field test was higher in the major depressive disorder patients than in the normal control subjects (p = 0.017). The patients with major depressive disorder showed reduced minimum ganglion cell–inner plexiform layer (GCIPL) thickness relative to the normal control participants (p = 0.015). The average score on the Hamilton Depression Rating scale showed a significant correlation with the PSD, minimum GCIPL thickness, and inferior GCIPL thickness (r = 0.265, p = 0.009; r = −0.239, p = 0.017; and r = −0.204, p = 0.043, respectively). The multivariate analysis of factors associated with PSD showed old age and a high Hamilton Depression Rating score to be relevant (p = 0.002 and 0.028, respectively). Conclusions: Visual function was decreased and the GCIPL thickness was reduced in major depressive disorder patients. The retinal neurodegenerative process in depression might be considered in patients with depression.

Abnormal large-scale resting-state functional networks in drug-free major depressive disorder.

Major depressive disorder (MDD) is associated with aberrant function and interaction encompassing large parts of cortical, subcortical and limbic regions that always organized into integrative networks implicated in specific tasks. And cumulative evidence suggests that MDD can be understood as a disorder of dysregulated network. Our study used resting-state fMRI and independent component analysis (ICA) to investigate intrinsic functional connectivity (FC) within and between resting-state networks (RSNs) in 27 drug-free MDD patients and 54 healthy control subjects (HCs). Granger causality analysis (GCA) was further used to identify the direct functional interaction between RSNs. We identified sixteen independent components (ICs) as meaningful RSNs. Compared with HCs, the MDD had significantly decreased intra-FC within lateral visual network (VN), parietal network (PN) and posterior default mode network (pDMN), decreased inter-FC between fronto-parietal network (FPN) and subcortical network, between pDMN and anterior DMN, and increased inter-FC between salience network and FPN, and enhanced effective connectivity from VN to PN and to cerebellum network. The functional synchronization of pDMN was negatively correlated with Hamilton Depression Rating Scores. The relatively small number of MDD, the use of medication and the application challenges of GCA on fMRI data may limit the interpretability. These findings indicated that MDD is indeed a disorder of dysregulated network, especially in the functional networks implicated in self-referential activities and emotional visual processing.

Altered serum interleukin-7 and interleukin-10 are associated with drug-free major depressive disorder.

Background:Abnormal expression of inflammatory cytokines in major depressive disorder (MDD) suggests the activation of an inflammatory process. The pattern of alterations in cytokine levels is still ambiguous. The present study aimed to evaluate interleukin-7 (IL-7) and interleukin-10 (IL-10) for their involvement in the pathophysiology of MDD and determine their relationships with depression risk.Methods:The study included 166 medication-free subjects: 84 MDD patients and 82 sex- and age-matched healthy controls (HCs). A qualified psychiatrist diagnosed patients and evaluated controls based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Hamilton depression rating scale (Ham-D) was used to measure the severity of depression in MDD patients. Serum IL-7 and IL-10 levels were measured using enzyme-linked immunosorbent assay (ELISA) kits.Results:Compared with HCs, the serum levels of IL-7 were significantly decreased, whereas that of IL-10 increased in MDD patients. Moreover, the severity of depression is correlated with the altered levels of IL-7 and IL-10 in MDD patients. We found a negative correlation between IL-7 and Hamilton depression rating (Ham-D) scores (r = –0.580, p < 0.05), whereas there was a positive correlation between IL-10 and Ham-D scores (r = 0.555, p < 0.05).Conclusions:The altered levels of serum IL-7 and IL-10 in MDD patients may represent a homeostatic mechanism that enhances the inflammatory process during depression. The alterations of these cytokine levels in MDD and their association with the severity of depression support them as promising, but there may still be controversial factors for understanding the pathophysiology of depression.

Once daily versus twice daily theta-burst stimulation in the treatment of major depression disorder

Introduction Intermittent theta-burst stimulation (iTBS) is a well-tolerated, time efficient yet not inferior [1] alternative to conventional repetitive transcranial magnetic stimulation (rTMS) protocols in the treatment of major depression disorder (MDD). While the consensus recommendation is 15–30 treatment sessions over a course of 3–6 weeks [2] , the ideal stimulation parameters (e.g., number and frequency of stimulation sessions) have yet to be determined. Methods In this double-blind randomized trial, 26 inpatients diagnosed with MDD were treated with neuronavigated iTBS over the left dorsolateral prefrontal cortex on 15 weekdays over the course of three weeks. On each treatment day, patients received either two active iTBS sessions (‘twice-daily’ group, n = 17) or one active and one sham iTBS session (‘once-daily’ group, n = 9). Results While patients in both groups showed a significant reduction of Hamilton Depression rating scores (HDRS-17), preliminary analyses show a significantly larger decrease in depressive symptoms among patients in the ‘twice-daily’ group (mean = 53%) compared to the ‘once-daily’ group (mean = 37%; F(1,24) = 5.17, P = .032). No increase in side effects was observed in the ‘twice-daily’ compared to the ‘once-daily’ group. Conclusion These findings suggest that two daily iTBS sessions increase the therapeutic effect of iTBS while being just as well tolerated as one daily session. Future studies should consider whether a twice-daily treatment regimen might be a feasible alternative to a conventional six-week treatment course.

Once daily versus twice daily theta-burst stimulation in the treatment of major depression disorder

Introduction Intermittent theta-burst stimulation (iTBS) is a well-tolerated, time efficient yet not inferior [1] alternative to conventional repetitive transcranial magnetic stimulation (rTMS) protocols in the treatment of major depression disorder (MDD). While the consensus recommendation is 15–30 treatment sessions over a course of 3–6 weeks [2] , the ideal stimulation parameters (e.g., number and frequency of stimulation sessions) have yet to be determined. Methods In this double-blind randomized trial, 26 inpatients diagnosed with MDD were treated with neuronavigated iTBS over the left dorsolateral prefrontal cortex on 15 weekdays over the course of three weeks. On each treatment day, patients received either two active iTBS sessions (‘twice-daily’ group, n = 17) or one active and one sham iTBS session (‘once-daily’ group, n = 9). Results While patients in both groups showed a significant reduction of Hamilton Depression rating scores (HDRS-17), preliminary analyses show a significantly larger decrease in depressive symptoms among patients in the ‘twice-daily’ group (mean = 53%) compared to the ‘once-daily’ group (mean = 37%; F(1,24) = 5.17, P = .032). No increase in side effects was observed in the ‘twice-daily’ compared to the ‘once-daily’ group. Conclusion These findings suggest that two daily iTBS sessions increase the therapeutic effect of iTBS while being just as well tolerated as one daily session. Future studies should consider whether a twice-daily treatment regimen might be a feasible alternative to a conventional six-week treatment course.

Spectral Dynamics of Resting State fMRI Within the Ventral Tegmental Area and Dorsal Raphe Nuclei in Medication-Free Major Depressive Disorder in Young Adults.

Background: Dorsal raphe nucleus (DRN) and ventral tegmental area (VTA) are major brainstem monamine nuclei consisting of serotonin and dopamine neurons respectively. Animal studies show that firing patterns in both nuclei are altered when animals exhibit depression like behaviors. Functional MRI studies in humans have shown reduced VTA activation and DRN connectivity in depression. This study for the first time aims at investigating the functional integrity of local neuronal firing concurrently in both the VTA and DRN in vivo in humans using spectral analysis of resting state low frequency fluctuation fMRI.Method: A total of 97 medication-free subjects—67 medication-free young patients (ages 18–30) with major depressive disorder and 30 closely matched healthy controls were included in the study to detect aberrant dynamics in DRN and VTA. For the investigation of altered localized dynamics we conducted power spectral analysis and above this spectral cross correlation between the two groups. Complementary to this, spectral dependence of permutation entropy, an information theoretical measure, was compared between groups.Results: Patients displayed significant spectral slowing in VTA vs. controls (p = 0.035, corrected). In DRN, spectral slowing was less pronounced, but the amount of slowing significantly correlated with 17-item Hamilton Depression Rating scores of depression severity (p = 0.038). Signal complexity as assessed via permutation entropy showed spectral alterations inline with the results on spectral slowing.Conclusion: Our results indicate that altered functional dynamics of VTA and DRN in depression can be detected from regional fMRI signal. On this basis, impact of antidepressant treatment and treatment response can be assessed using these markers in future studies.

A pilot study on the effects of hormonal contraceptives on beta‐arrestin1 levels in peripheral blood mononuclear leukocytes

OBJECTIVEWomen are twice as likely as likely as men to develop depression during reproductive years. Use of hormonal contraceptives, during reproductive years, may be causal with development of depression in a subgroup of women because observational studies indicate an association between use of progestin (Depo‐Provera) and development of depressive symptoms. Previously we have reported reduced levels of beta arrestin 1(β‐AR‐1) during premenstrual depressive disorder, may be a potential biomarker of depression. In this study we compared the β‐AR‐1 protein levels and the Hamilton Depression Rating Scores (HDRS) as well, in women on non‐hormonal contraceptives (control), combine‐only contraceptives (COC), and progestin‐only contraceptives (POC).METHODSStudy participants (n=29) were non‐pregnant women between 18–42 years of age, not taking any antidepressants/therapy and at the luteal phase of menstruation. The participants were evaluated with Neuropsychiatric Interview (DSMIV‐TR). The severity of depression were determined by the HDRS. The protein levels of beta‐arrestin1 in the in peripheral blood mononuclear leukocytes (PBMC) were determined by ELISA.RESULTSThe magnitude of the different parameters for Axis 1 mental disorders were significantly higher and beta arrestin1 protein levels in PBMC were significantly lower in women currently using progestin‐only contraceptives as compared to the control.CONCLUSIONThese findings indicate the possibility of reduced levels of β‐AR‐1 and associated symptoms of depression in a subgroup of women may results from the use of POC.Support or Funding InformationClinical Research Education and Career Development in Minority R25RR17577 (NCRR/NIMHD) and U54 MD007593 (NIMHD) and U54 RR026140 (NCRR) at NIH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Non response at week 4 as clinically useful indicator for antidepressant combination in major depressive disorder. A sequential RCT

We aimed to compare the efficacy and tolerability of mirtazapine versus SSRIs and to assess whether “non-response at week 4” may be a clinical indicator for combining mirtazapine and SSRIs for subsequent treatment. One-hundred fifty-four outpatients with MDD were randomized to receive mirtazapine or SSRIs in step I (4 weeks). Non-responders in step I were randomly assigned to either mirtazapine or SSRIs monotherapy or their combination in step IIa while responders in step I continued the same monotherapy in step IIb for 4 weeks. In step I, mirtazapine showed significantly faster improvement as shown by higher remission rate at week 2 with NNT = 8 compared to SSRIs. Somnolence rate was higher in mirtazapine and nausea rate was higher in SSRIs. In step IIa, combination therapy showed a more favorable time course than SSRIs monotherapy. For subjects taking SSRIs in step I, combination therapy showed significant better improvement in the Hamilton Depression Rating (HAM-D) score both at week 6 (p = 0.006) and 8 (p = 0.013) than SSRIs monotherapy. About 80% of responders at week 4 could reach remission at week 8 and 64% of non-responders could not reach remission at week 8 for patients who continued monotherapy. When mirtazapine was added on for SSRIs non-responders at week 4, the remission rate increased by 5% and HAM-D score improved by 4 points. While for mirtazapine non-responders, SSRIs add-on was not equally effective.Mirtazapine may provide a faster improvement and “non-response at week 4” may be indicator to mirtazapine add-on for patients receiving SSRIs.

Serotonin transporter gene (SLC6A4) polymorphisms are associated with response to fluoxetine in south Indian major depressive disorder patients

Up to 30-40% of the major depressive disorder patients do not respond sufficiently to antidepressant treatment. Genetic variations in the serotonin transporter gene have been implicated in modulating treatment response to selective serotonin reuptake inhibitors, and this association is influenced by ethnicity. We investigated the influence of serotonin transporter gene variants 5-HTTLPR and rs25531 in Indian population on fluoxetine response. One hundred and two major depressive disorder patients were started on fluoxetine treatment and after 6weeks, classified as responders (n=56) and non-responders (n=46) using Hamilton depression rating scale and genotyped. Fisher's exact test was used to compare genotype frequencies between responders and non-responders. One-way analysis of variance and student t test were used to compare the percentage reduction (week 0-6) in Hamilton depression rating scores between genotype and haplotype groups. We observed a significant association between LL genotype of 5-HTTLPR and fluoxetine treatment response (p=0.0066, OR (95%)=4.0 (1.45-11.03)) but not with the functional groups of 5-HTTLPR -rs25531. However, there was a significant difference in percentage reduction in HAM-D scores (week 0-6) between 5-HTTLPR genotypes (LL vs. LS+SS, p=0.0036; LL vs. LS, p=0.0109) as well as the functionally grouped haplotypes of 5-HTTLPR -rs25531 (LALA carriers vs. non-carriers of LALA, p=0.0118; LALA vs. LAS+ LALG, p=0.0419). The LL genotype and LALA haplotype of SLC6A4 are associated with favorable treatment response to fluoxetine in south Indian major depression patients.

Excessive daytime sleepiness among patients with metabolic syndrome

BackgroundMetabolic syndrome is a medical disorder that predisposes to cardiovascular diseases. Excessive daytime sleepiness (EDS) is a common finding in patients with metabolic syndrome. AimTo assess the presence of EDS among subjects with metabolic syndrome and to find its correlations with apnea hypopnea index (AHI), Hamilton depression rating score (HDRS), body mass index (BMI), age and fasting plasma glucose (FPG). Method76 patients with metabolic syndrome were evaluated for EDS by Epworth sleepiness score (ESS) and for sleep apnea by polysomnography. Results22 subjects (28.9%) had EDS, 37 subjects (48.7%) had sleep apnea and 28 subjects (36.8%) had depression. ESS showed no significant association with AHI while it showed significant associations with each of HDRS, BMI, age and FPG. ConclusionsOther explanations of EDS in subjects with metabolic syndrome can be related to obesity, depression, or diabetes rather than to sleep apnea. Subjects with metabolic syndrome should be screened for EDS regardless of sleep apnea.

Association analysis for corticotropin releasing hormone polymorphisms with the risk of major depressive disorder and the response to antidepressants

Hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis is one of the most consistent neuroendocrine abnormalities observed in patients with major depressive disorder (MDD). The peptide corticotropin-releasing hormone (CRH) is a key mediator for HPA axis function during stress. This study evaluated the associations of CRH polymorphisms with susceptibility to MDD and response to antidepressant treatment, and the gene–environment interaction with stressful life events (SLEs). After screening 31 polymorphisms in the gene encoding CRH, we evaluated the association of polymorphisms with MDD susceptibility in 149 patients with MDD and 193 control subjects; in patients, we also evaluated the response to treatment with antidepressants. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) than were remitters (P=0.019–0.038), when only patients without SLE were included; however, the association was not significant after correction for multiple comparisons. Additionally, after 4 and 8 weeks of treatment in patients who experienced no SLEs, significantly higher 21-item Hamilton Depression Rating scores were found in MDD subjects who were CRH ht1 homozygotes compared to patients carrying one or no ht1 alleles (P=0.007 and 0.027 at 4 and 8 weeks, respectively). Although these preliminary observations require further confirmation in future studies, these results on the interaction between CRH haplotypes and SLEs, suggest that CRH ht1 which is moderated by SLEs, may be associated with antidepressant treatment outcomes in patients with MDD.

Grey matter volume abnormalities in patients with bipolar I depressive disorder and unipolar depressive disorder: a voxel-based morphometry study.

Bipolar disorder and unipolar depressive disorder (UD) may be different in brain structure. In the present study, we performed voxel-based morphometry (VBM) to quantify the grey matter volumes in 23 patients with bipolar I depressive disorder (BP1) and 23 patients with UD, and 23 age-, gender-, and education-matched healthy controls (HCs) using magnetic resonance imaging. We found that compared with the HC and UD groups, the BP1 group showed reduced grey matter volumes in the right inferior frontal gyrus and middle cingulate gyrus, while the UD group showed reduced volume in the right inferior frontal gyrus compared to HCs. In addition, correlation analyses revealed that the grey matter volumes of these regions were negatively correlated with the Hamilton depression rating scores. Taken together, the results of our study suggest that decreased grey matter volume of the right inferior frontal gyrus is a common abnormality in BP1 and UD, and decreased grey matter volume in the right middle cingulate gyrus may be specific to BP1.

The association of proopiomelanocortin polymorphisms with the risk of major depressive disorder and the response to antidepressants via interactions with stressful life events.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is among the most consistent neuroendocrine abnormalities in major depressive disorder (MDD). The peptide adrenocorticotropin hormone (ACTH) mediates HPA axis function during stress and is encoded by the proopiomelanocortin (POMC) gene polycistronically. After screening 39 POMC polymorphisms, we evaluated the association of polymorphisms with susceptibility to MDD in 145 MDD patients and 193 normal subjects; in patients, we also evaluated the response to treatment with antidepressants. Additionally, we investigated the role of gene-environment interaction between POMC haplotypes and stressful life events (SLE) in the treatment response. Although genotypes and haplotypes were not significantly associated with the risk of MDD, non-remitters were more likely to carry haplotype 1 (ht1) and to have no ht2 than were remitters (corrected P=0.010-0.035). Although observations were limited in patients without SLE, a significant haplotype-SLE interaction was observed (P=0.020). Additionally, at 1, 2, and 8weeks of treatment, the 21-item Hamilton Depression Rating scores of MDD subjects with POMC ht2 were significantly (P=0.003-0.044) lower than those of patients with ht1 in subjects those did not experience SLE. MDD subjects possessing POMC ht2 achieved remission significantly (P=0.013; survival analysis) faster than patients with ht1. This study suggests that POMC haplotypes, via an interaction with SLE, are associated with antidepressant treatment outcomes in MDD patients. Regarding SLE, haplotypes of the POMC gene could be useful markers for predicting the response to antidepressant treatment in MDD patients.

High baseline BDNF serum levels and early psychopathological improvement are predictive of treatment outcome in major depression

Major depressive disorder has been associated with low serum levels of brain-derived neurotrophic factor (sBDNF), which is functionally involved in neuroplasticity. Although sBDNF levels tend to normalize following psychopathological improvement with antidepressant treatment, it is unclear how closely sBDNF changes are associated with treatment outcome. To examine whether baseline sBDNF or early changes in sBDNF are predictive of response to therapy. Twenty-five patients with major depressive disorder underwent standardized treatment with duloxetine. Severity of depression, measured by the Hamilton Depression Rating Scale, and sBDNF were assessed at baseline, and after 1, 2, and 6weeks of treatment. Therapy outcome after 6weeks was defined as response (≥50% reduction in baseline Hamilton Depression Rating score) and remission (Hamilton Depression Rating score <8). The predictive values for treatment outcome of baseline sBDNF, and early (i.e., ≤2weeks) changes in sBDNF and Hamilton Depression Rating score were also assessed. At baseline, sBDNF correlated with Hamilton Depression Rating scores. Treatment response was associated with a higher baseline sBDNF concentration, and a greater Hamilton Depression Rating score reduction after 1 and 2weeks. A greater early rise in sBDNF correlated with a decreased early Hamilton Depression Rating score reduction. Even though higher baseline sBDNF levels are associated with more severe depression, they may reflect an increased capacity to respond to treatment. In contrast, changes in sBDNF over the full course of treatment are not associated with psychopathological improvement.