First Episode Of Major Depression Research Articles

Exploring the Interplay between Family History of Depression, Negative Life Events, and Social Support in First-Episode Major Depression: Insights from a Pilot Case-Control Study

Exploring the Interplay between Family History of Depression, Negative Life Events, and Social Support in First-Episode Major Depression: Insights from a Pilot Case-Control Study

Associations of dysfunctional attitudes, ruminations and metacognitive beliefs about rumination with pharmacological treatment response in patients with first episode of major depression

Introduction The aim of this study is to investigate whether treatment with selective serotonin reuptake inhibitors (SSRI) has an effect on the ruminative response, ruminative beliefs and dysfunctional attitudes (DA), and to evaluate the effects of pre-treatment dysfunctional attitudes and rumination levels on treatment response in individuals diagnosed with the first episode of major depression (MD). Methods 110 patients with MD participated in this study. Participants were evaluated with the Hamilton Depression Rating Scale (HDRS), the Clinical Global Impression Scale (CGI), the Short Version of Ruminative Response Scale (RRS), the Positive Beliefs about Rumination Scale (PBRS), the Negative Beliefs about Rumination Scale (NBRS), and the Dysfunctional Attitude Scale form A (DAS-A) before receiving SSRI treatment and 2 months after the onset of treatment. Results After two months of SSRI treatment, patients were divided into two groups, remission and non-remission groups. The decrease in RRS subscales and total scores, NBRS uncontrollability and danger of ruminations score, PBRS total score and DAS-A autonomous attitude scores were significantly higher in the remission group. RRS and DAS-A scores were found to be predictors of remission. Conclusions DA and ruminations may be associated with poor response to SSRI treatment in depression. KEY POINTS After treatment with selective serotonin reuptake inhibitors, ruminations, dysfunctional attitudes, and positive and negative metacognitions on ruminations significantly decreased in patients with a first episode of major depression. The decrease in ruminations, autonomous attitudes, the metacognitions on the uncontrollability and danger of ruminations, and positive metacognitions on ruminations was higher in remission group compared to the non-remission group. Ruminations and dysfunctional attitudes significantly predicted remission in first episode of major depression.

Canonical insulin signaling is not significantly impaired in early stages of depression.

Patients with major depression (MD) are at high-risk for insulin resistance (IR), type-2 diabetes, metabolic syndrome, cardiovascular morbidity and mortality. However, our recent study published in this journal [Eur Arch Psychiatry Clin Neurosci. 2019 Jun;269(4):373-377], found no evidence of IR in acutely-ill drug-naive first-episode MD (FEMD) using the homeostatic model assessment of insulin resistance (HOMA-IR). We concluded, that MD may be related to impaired glucose/insulin homeostasis in the long-term but not in early disease stages. Now, we performed a complementary analysis of the canonical insulin signalling pathway containing the set of control and FEMD samples from the study mentioned above. The first node (pS312-IRS-1, pY-IRS-1) and downstream pathway which affects glucose and lipid homeostasis (phosphorylated proteins: pS473-AKT, pS9-GSK3β, pS2448-mTOR, pT389-p70S6K; total proteins AKT, GSK3β, mTOR, p70S6K) were analyzed by electrochemiluminescence (ECL) in neuronalextracellular vesicles (nEVs) enriched for L1 neural cell adhesion molecule (L1CAM) expression. No significant diagnosis-related differences were observed for the pS312-IRS-1 / pYIRS-1 ratio (P = 0.093), but the mean ratio was reduced by ~ 70% in FEMD versus controls. Moreover, omnibus analysis of downstream phosphorylated / total signaling protein ratios and respective post-hoc analyses revealed no significant changes in FEMD patients versus controls (P = 0.734). HAMD-21 scores were not correlated with pS312-IRS-1 / pY-IRS-1 or downstream phosphorylated/total signaling protein ratios. In summary, we did not find evidence for altered neuronal insulin signaling in early disease stages of MD. This is in contrast to schizophrenia, where we and otherresearchers have seen evidence of IR in first-episode patients.

Hippocampal Volume and Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Depression and Healthy Controls.

The aim of the present study was to investigate associations between hippocampal subfield volumes and plasma levels of brain-derived neurotrophic factor (BDNF) in patients experiencing a first episode of major depression (MD) (n = 30) as compared to healthy controls (HC) (n = 49). Covariate-adjusted linear regression was performed to compare the MD and healthy groups, adjusting for age, sex, and total estimated intracranial volume. We demonstrated that there were no differences in total hippocampal volume between the MD and HC groups. However, the volumes of the hippocampus-amygdala-transition-area (HATA) on the left side of the brain as well as the parasubiculum, presubiculum, and fimbria on the right side were statistically significantly smaller in the MD group than in the HC group. Furthermore, the volume of the hippocampal fissure on the right side was statistically significantly smaller in the HC group than in the MD group. In the MD group, we found a positive linear correlation between hippocampal volume and plasma BDNF concentrations in the CA4 area on the left side (p = 0.043). In contrast, in the HC group, we found a negative linear correlation between parasubiculum volume on the right side and plasma BDNF concentrations (p = 0.04). These results suggest that some hippocampal subfields may already be atrophic at the start of MD. In addition, our findings suggest that the sensitivity of the right parasubiculum region to BDNF may differ between MD and HC groups. These findings guide future research directions and, if confirmed, may ultimately inform medical guidelines.

Absence of an association between serum interleukin-6 and brain-derived neurotrophic factor in drug-naïve first-episode major depression

Absence of an association between serum interleukin-6 and brain-derived neurotrophic factor in drug-naïve first-episode major depression

Volume of Amygdala Subregions and Clinical Manifestations in Patients With First-Episode, Drug-Naïve Major Depression.

We examined amygdala subregion volumes in patients with a first episode of major depression (MD) and in healthy subjects. Covariate-adjusted linear regression was performed to compare the MD and healthy groups, and adjustments for age, gender, and total estimated intracranial volume showed no differences in amygdala subregion volumes between the healthy and MD groups. Within the MD group, we examined the association between amygdala subregion volume and the 17-item Hamilton Rating Scale for Depression (HAMD) score and the HAMD subscale score, and found no association in the left amygdala. In the right amygdala, however, there was an inverse linear association between the HAMD total and the HAMD core and lateral nucleus and anterior-amygdaloid-regions. Furthermore, an inverse linear association was seen between the HAMD psychic and the lateral nucleus, anterior-amygdaloid-regions, transition, and whole amygdala. The findings of this study suggest that the severity of MD and some symptoms of MD are associated with right amygdala volume. There have been few reports on the relationship between MD and amygdala subregional volume, and further research is needed to accumulate more data for further validation.

Potential biomarkers of major depression diagnosis and chronicity.

BackgroundMolecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity.MethodsWe tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease’s chronicity using regression models, and ROC curve.ResultsFor diagnosis model, two groups were analyzed: patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity.ConclusionThese results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice.

Religious Coping, Hopelessness, and Suicide Ideation in Subjects with First-Episode Major Depression: An Exploratory Study in the Real World Clinical Practice.

Background. This study aimed to evaluate the potential relationships between religious coping, hopelessness, and suicide ideation in adult outpatients with the first episode of major depressive disorder (MDD). Methods. Ninety-four adult outpatients with MDD were assessed through the Hamilton Depression Rating Scale (HAM-D), the Beck Hopelessness Scale (BHS), and the Scale of Suicide Ideation (SSI). Religious coping was assessed with the Italian version of the Brief RCOPE scale, consisting of seven positive coping items (PosCop) and seven negative coping items (NegCop). Results. The results showed that the Brief RCOPE PosCop scale exhibited a strong inverse correlation with HAM-D, BHS, and SSI, whereas HAM-D and BHS were positively correlated with SSI. Brief RCOPE NegCop scores were positively correlated only with SSI. Regression analysis with SSI as the dependent variable showed that higher Brief RCOPE PosCop scores were associated with lower suicide ideation, whereas higher HAM-D and BHS scores were associated with higher suicide ideation. Conclusion. Positive religious coping may be a protective factor against the development of suicide ideation, perhaps counteracting the severity of depressive symptoms and hopelessness. The evaluation of religious coping should be performed in all subjects with MDD in everyday clinical practice. However, this study was preliminary, and limitations must be considered.

Life stress and major depression: The mysteries of recurrences.

Approximately half of the people who suffer a major depressive episode for the first time experience recurrences, while the other half do not. Among the initially depressed, however, who will have recurrences remains a mystery, and cannot be forecasted with any statistical or clinical confidence. It is well documented, though, that highly stressful life events commonly precede first episodes of major depression, and that these experiences become progressively less common prior to recurrences. Determining the basis for this consistent empirical observation holds promise for discovering among the initially depressed who will become recurrent, helping to solve the current-day conundrum of recurrences. The present article has 2 overarching objectives. First, we evaluate stress sensitization, the prevailing theory for explaining the decreasing association of major life events with successive recurrences. Conceptual gaps, discrepancies, and misunderstandings are found for understanding the decreasing association, as well as for understanding recurrences. Research practices and logical errors also are exposed that compromise the integrity of the existing empirical record. Second, alternative theoretical accounts are proposed to explain the decreasing association of major life stress with recurrences. Two "dual pathway models" provide viable alternative explanations, fill in existing theoretical gaps, and supply additional advantages for understanding life stress, depression, and recurrences. Recommendations are made for evaluating the 3 respective models. In closing, limitations and remaining questions are discussed for discovering who, early in the lifetime course of major depression, is likely to have a lifetime of repeated recurrences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Trajectory analysis of single-drug therapy for first-episode major depression disorder

Objective To analyze the treatment trajectory and revelant factors of serotonin reuptake inhibitors (SSRIs) in patients with first-episode major depression after single-drug treatment.And to provide ideas for early optimal treatment. Methods This study was a real-world study in which 82 untreated outpatients with first-episode depression were enrolled for SSRIs monotherapy.The Eysenck Personality Test (EPQ), the Liebowitz Social Anxiety Scale (LSAS), Yale -Brown Forced Scale (Y-BOCS), Social Function Deficit Scale (SDSS) were used to assess all patients at baseline.Then the patients were treated with SSRIs monotherapy.Patients who did not achieve a HAMD-17 20% reduction rate in the second week switched to receive another SSRIs monotherapy application.Follow-up to the 12th week to analyze treatment trajectory and identify factors associated with treatment trajectory. Results The psychotism personality trait (B=-0.287, 95%CI=-0.701~-0.071, P=0.009) and age (B=0.099, 95%CI=0.014~0.244, P=0.017) were related to treatment trajectories.The psychotism personality trait did not directly influence the treatment trajectory but influenced the treatment indirectly through agitation and the effect value was 0.016, which accounted for 10.76% of the total effect.Social anxiety and avoidance, depression, anxiety, obsessive-compulsive symptoms and social dysfunction at baseline were not associated with antidepressant efficacy. Conclusion Psychoticism can predict the efficacy of antidepressants treatment as a mediator at the second week of treatment. Key words: Major depressive disorder; Psychotism; Trajectory analysis; Early improvement; Eisenck personality test

Facing recovery: Emotional bias in working memory, rumination, relapse, and recurrence of major depression; an experimental paradigm conducted five years after first episode of major depression

Identifying vulnerability factors for relapse of depression is essential in planning preventive interventions. Emotional face processing in major depression (MDD) shows promise as a potential cognitive marker for depression. The current study investigates how working memory (WM) load in face processing relates to rumination and new episodes of MDD in a novel explorative paradigm. It was expected that history of MDD is associated with reduction of the ability to process sad stimuli in high WM load conditions and reduction of the ability to process happy stimuli in low WM conditions. It was further predicted that these relations are associated with rumination and risk for relapse. The experiment was included as a cross sectional part in a follow-up study of a population that previously experienced first episode (FE) depression. The FE (N = 23) and a healthy control group (N = 22) completed a WM face processing task. In the task, three happy or sad faces were presented, processed in either a high or low WM taxing manner, followed by a target stimulus consisting of one of the previous pictures. Response time and accuracy were dependent variables. Rumination and number of relapses or recurrences were measured. The FE group recalled the placement of significantly fewer happy faces in the low WM load condition, and significantly fewer sad faces in the high WM load condition compared to controls. Significantly different scores between groups predicted trait rumination. Poor accuracy in the sad high WM load condition correlated with high degree of rumination. Relapse or recurrence was predicted by rumination. The present study supports an emotional WM deficit in remitted MDD. This suggests that deficits in manipulation of sad faces could represent a trait bias related to rumination and depression.

SSRI maintenance therapy reduces rate of recurrence for elderly patients with first episode of major depression

SSRI maintenance therapy reduces rate of recurrence for elderly patients with first episode of major depression

Adverse Childhood Experiences and Risk for First-Episode Major Depression During the Menopause Transition.

Stress exposures may have a differential impact on risk and resilience for depression depending on their timing across development. We sought to determine whether adverse childhood experiences (ACEs) and their onset with respect to puberty contribute to the increased risk observed in first-episode major depressive disorder (MDD) during the menopause transition. Participants were from the Penn Ovarian Aging Study cohort, which is composed of women from Philadelphia County, Pennsylvania, who underwent behavioral, cognitive, and endocrine evaluations approximately yearly from 1996 to 2012 and completed the Adverse Childhood Experiences Questionnaire at study end point (n = 243). ACEs that first occurred 2 or more years before menarche were considered prepubertal. Incident menopause MDD was defined as first observed onset of the disorder in the perimenopause to postmenopause transition using the Structured Clinical Interview for DSM-III-R and the Primary Care Evaluation of Mental Disorders. Incident menopause MDD occurred in 48% of the 100 women who reported lifetime MDD. Women reporting ≥ 2 total ACEs were at significantly greater risk for lifetime MDD (adjusted odds ratio [aOR] = 2.05, P = .034) and incident menopause MDD (aOR = 2.58, P = .03) compared to those reporting 0 ACEs; women with ≥ 2 postpubertal ACEs were 2.3 times more likely to experience incidence menopause MDD (P = .024) after controlling for race, smoking, body mass index, and employment. Experiencing only 1 ACE in the prepubertal window, regardless of additional ACEs in postpuberty, was associated with reduced risk for lifetime and incident menopause MDD. Timing and number of adverse experiences with respect to puberty differentially impacted risk and resilience for MDD across the female life span and during the menopause transition in this community cohort.

Pseudo-continuous arterial spin labeling imaging of cerebral blood perfusion asymmetry in drug-naïve patients with first-episode major depression.

Many previous studies have reported that regional cerebral blood flow (rCBF) aberrations may be one of the pathological characteristics of depression and rCBF has demonstrated a certain degree of asymmetry. However, studies investigating the cerebral blood perfusion asymmetry changes of drug-naïve patients experiencing their first episode of major depression using pseudo-continuous arterial spin labeling (pCASL) are rare. Ten drug-naïve patients experiencing their first major depression episode and 15 healthy volunteers were enrolled in the current study. A novel pCASL method was applied to whole brain MRI scans of all of the samples. The Statistics Parameter Mapping and Relative Expression Software Tool software packages were used for the pre-processing and statistical analysis of the two sets of images, and the differences in the cerebral blood perfusion at the whole brain level were compared between the two groups. Compared with the healthy control group, the cerebral perfusion of the depression patients showed an asymmetric pattern. Decreased cerebral blood perfusion regions were primarily located in the left hemisphere, specifically in the left temporal lobe, frontal lobe and cingulate cortex [P<0.05 and cluster size ≥30 with false discovery rate (FDR) correction]. Simultaneously, increased perfusion regions were predominantly located in the right hemisphere, specifically in the right cerebellum, thalamus, frontal lobe and anterior cingulate cortex (P<0.05 and cluster size ≥30, with FDR correction). Thus, pCASL may characterize the alterations in cerebral blood perfusion of patients with depression.

P.2.f.022 - First-episode major depression and treatment with escitalopram: an fMRI study

P.2.f.022 - First-episode major depression and treatment with escitalopram: an fMRI study

Elevated Brain-Derived Neurotrophic Factor Correlates Negatively with Severity and Duration of Major Depressive Episodes

Major depressive disorder is a neuropsychiatric condition associated with neurochemical changes that alter levels of neurotrophins. We aimed to measure serum levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in patients experiencing their first episode of major depression and to examine those levels in relation to the severity and duration of the depressive episode. We recruited 85 participants: 44 drug-free patients with major depression (35 women, 9 men) and 41 healthy controls (32 women, 9 men). We used the Hamilton Rating Scale for Depression to assess the severity of the patients' depression. We assessed the controls' mental health according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed, criteria. To assess all participants' stress levels, we used the Holmes and Rahe stress scale. We measured all participants' serum BDNF and NGF levels via enzyme-linked immunosorbent assay. The mean stress score was significantly higher in the patients than the controls (P=0.03). The patients had higher serum BDNF than the controls (P=0.001), but similar NGF levels. BDNF levels correlated negatively with symptom severity (r=-0.33, P=0.03) and duration (r=-0.2, P=0.06). NGF levels did not correlate with stress or with severity or duration of depressive episode. These findings suggest that an elevated serum BDNF level may contribute to the pathophysiology of major depressive disorder. The findings also indicate a possible role for BDNF in altering the clinical course of the condition.

Predictors of first-episode unipolar major depression in individuals with and without sub-threshold depressive symptoms: A prospective, population-based study

BackgroundThe aim of this study is to assess predictors of first-episode major depression in a community-based sample of adults with and without sub-threshold depression. MethodData were from Waves 1 and 2 of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC). Participants meeting criteria for a sub-threshold depressive episode (sMDE; n=3901) reported lifetime depressed mood/loss of interest lasting at least two weeks and at least two of the seven other DSM-IV symptoms of MDD. Predictors of MDE 3 years later were compared in those with and without (n=31022) sMDE. ResultsBeing female, history of alcohol or substance use, and child abuse increased the odds of developing MDD to a greater degree in individuals without sMDE relative to those with sMDE. Among those with sMDE and additional risk factors (low education, substance use), younger age was associated with marginally increased risk of MDD. ConclusionSeveral demographic risk factors may help identify individuals at risk for developing MDD in individuals who have not experienced an sMDE who may be candidates for early intervention. Future work should assess whether preventative interventions targeting substance/alcohol use and child abuse could reduce the risk of depression.

A Randomized, Double-blind, Placebo-controlled Trial of Celecoxib Augmentation of Sertraline in Treatment of Drug-naive Depressed Women: A Pilot Study.

This study was designed to examine the antidepressant effect of celecoxib (200 mg/day) augmentation of sertraline in the treatment of female patients with first episode of major depression over 8 weeks of therapy. Thirty female outpatients diagnosed with first episode of major depression, were recruited for this study. Participants were randomly assigned into two equal groups receiving either sertraline plus celecoxib 100 mg twice daily or sertraline plus placebo twice daily. Patients were assessed by Hamilton Depression and Anxiety Rating Scale at baseline, week 4 and week 8 of treatment. Both treatment groups showed notable improvement in their symptoms from baseline; however, celecoxib group showed greater decrease in Hamilton Depression Scores compared to the placebo group after four weeks of treatment. Response rates were also found to be significantly higher in the celecoxib group compared to the placebo group over 4 weeks. Nevertheless, the mentioned differences between two groups were not significant at the end of week 8. Also, remission rate was remarkably higher in celecoxib group in comparison with placebo at the end point. The results suggested that celecoxib may hasten the onset of therapeutic action of sertraline and increase response and remission rate in depressive disorders.

Risk Factors of Recurrence in Major Depressive Disorders

Introduction About 60 % of the subjects with a first episode of major depression will present a second episode lifetime. Thus, it is important to determine the risk factors of recurrence. Aims To identify the risk factors of depressive recurrence. Methods It is a retrospective study conducted in university hospital of Mahdia including 150 patients hospitalized in psychiatric ward for major depressive disorder according to DSM-IV-TR. Data were collected using a questionnaire of 89 items. Statistical analysis was done using the Kaplan-Meier method. The Cox test was used to check for recurrence risk factors. Results The sample was divided into: • Group 1: diagnosed with major depressive disorder, single episode (MDD, n = 63) • Group 2: diagnosed with recurrent major depressive disorder (MDDr, n = 87) Family history of mood disorders were found in 25,4% and 59,7% of patients in respectively group 1 and 2. The age of onset was less than 25 years in 34.48% of Group 2 against 22.2% in group 1. Residual symptoms were similar in both groups. The mean time to recurrence was 109 months. Multivariate analysis retained 5 risk factors: early age of onset disorders (p = 0.02), family history of mood disorder (p = 0.04), the severity of depressive index episode (p = 0.03), the persistence of residual symptoms (p = 0.02) and early interruption of the treatment (p = 0.04). Conclusion The identification of risk factors for recurrence before a first depressive episode is very important to prevent recurrence and chronicity.

Neurophysiological handover from MMN to P3a in first-episode and recurrent major depression

BackgroundMismatch negativity (MMN) and P3a components are sequential and co-occur. MMN represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Major depressive disorder (MDD) is characterized by impaired pre-attentive information processing. To assess whether impaired pre-attentive information processing can lead to an impairment of subsequent orienting process as the neurophysiological transmission spreads from MMN to P3a in MDD. MethodsMMN/P3a was obtained during a two-tone auditory paradigm with 8% duration deviants in 45 first-episode major depression subjects (F-MD), 40 recurrent major depression subjects (R-MD), and 46 healthy controls (HC). ResultsCompared with HC, F-MD and R-MD had lower MMN amplitudes and no differences were found between F-MD and R-MD. Notably, R-MD had lower P3a amplitudes and longer P3a latencies compared to HC, while F-MD had no differences. Interestingly, no correlations were found between the severity of depression and the deficits of MMN amplitude. The deficits of P3a amplitude, however, were negatively correlated with the severity of depression in F-MD and R-MD. Furthermore, the P3a amplitude deficits were positively correlated with the number of episodes in R-MD. LimitationsPatients were on antidepressant medication. ConclusionsThe recurrence of depressive episodes can lead to impaired pre-attentive information processing, causing an impairment of subsequent orienting process as the neurophysiological transmission from MMN to P3a. It further suggests that the impaired processing indexed by MMN amplitude may be a stable trait biomarker for the appearance of depression, while P3a amplitude can be used a potential biomarker for recurrence.