Remission Of Major Depressive Disorder Research Articles

Cognitive impairment of medicated patients with remitted depression and low anticholinergic activity

BackgroundA recent meta-analysis has found that patients who have achieved remission of major depressive disorder (MDD) show cognitive dysfunction. Moreover, anticholinergic activity levels are associated with cognitive dysfunction, although the extent of these effects is unclear. Therefore, we measured serum anticholinergic activity (SAA) in blood samples of patients with remitted MDD and examined its relationship with cognitive function. MethodsWe recruited 49 patients with remitted MDD following treatment and 165 healthy subjects. Subjects completed the Stroop test and the logical memory (LM) and visual reproduction (VR) subtests from the Wechsler Memory Scale-Revised. We compared cognitive function scores among those with SAA below the limit of quantification (SAA [−]), those with SAA above the limit of quantification (SAA [+]), and healthy controls. ResultsThe SAA (+) group scored significantly lower (p < 0.001) than the healthy control group on all tests, and the VR score of the SAA (−) group was significantly lower than that of the healthy control group (p = 0.024). LM scores in the SAA (+) group were significantly lower than that of the SAA (−) group (p = 0.033). Multiple regression analysis revealed a significant effect of SAA on the LM score (p = 0.015). LimitationsOur study was a cross-sectional analysis of a small number of patients. ConclusionsOur results support previous findings that the anticholinergic effect of antidepressants adversely affects cognitive function. Additionally, the cognitive impairment observed may persist because of MDD.

Correlating plasma protein profiles with symptomatology and treatment response in acute phase and early remission of major depressive disorder.

This study aimed to explore the relationship between plasma proteome and the clinical features of Major Depressive Disorder (MDD) during treatment of acute episode. In this longitudinal observational study, 26 patients hospitalized for moderate to severe MDD were analyzed. The study utilized Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) alongside clinical metrics, including symptomatology derived from the Montgomery-Åsberg Depression Rating Scale (MADRS). Plasma protein analysis was conducted at the onset of acute depression and 6 weeks into treatment. Analytical methods comprised of Linear Models for Microarray Data (LIMMA), Weighted Correlation Network Analysis (WGCNA), Generalized Linear Models, Random Forests, and The Database for Annotation, Visualization and Integrated Discovery (DAVID). Five distinct plasma protein modules were identified, correlating with specific biological processes, and uniquely associated with symptom presentation, the disorder's trajectory, and treatment response. A module rich in proteins related to adaptive immunity was correlated with the manifestation of somatic syndrome, treatment response, and inversely associated with achieving remission. A module associated with cell adhesion was linked to affective symptoms and avolition, and played a role in the initial episodes and treatment response. Another module, characterized by proteins involved in blood coagulation and lipid transport, exhibited negative correlations with a variety of MDD symptoms and was predominantly associated with the manifestation of psychotic symptoms. This research points to a complex interplay between the plasma proteome and MDD's clinical presentation, suggesting that somatic, affective, and psychotic symptoms may represent distinct endophenotypic manifestations of MDD. These insights hold potential for advancing targeted therapeutic strategies and diagnostic tools. The study's limited sample size and its naturalistic design, encompassing diverse treatment modalities, present methodological constraints. Furthermore, the analysis focused on peripheral blood proteins, with potential implications for interpretability.

Adjunctive use of mindfulness-based mobile application in depression: randomized controlled study.

Mindfulness-based interventions (MBI) are effective in relapse prevention in Major Depressive Disorder (MDD). Internet-based interventions have been demonstrated to be effective in the treatment of MDD. Consequently, the integration of MBI through mobile applications emerges as a promising supplementary intervention for MDD, contributing to the augmentation of mental health services, particularly within ambulatory care contexts. The current randomized controlled study is designed to evaluate the efficacy of adjunctive MBI delivered via a mobile app in mitigating symptom severity and stress levels. This assessment involves a comparison with standard treatment practices in an ambulatory setting among individuals diagnosed with MDD. A total of 83 patients diagnosed with MDD (depressive episode, recurrent depression or depressive phase of bipolar disorder) were randomly allocated to the intervention (41 patients) or control condition (42 patients). The intervention consisted of the daily use of the mindfulness mobile application "Headspace" for thirty days. The control condition was treatment as usual (TAU) only. The symptom severity has been assessed by the Beck Depression Inventory (BDI-II) as well as the Hamilton Depression Rating Scale (HDRS-17). Blood pressure and resting heart rate have been assessed as secondary outcome. Upon hospital discharge, the mean scores on the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS) signaled partial remission of MDD in both treatment arms. In both groups, a subsequent decrease in both self-reported and expert-rated scores was evident after a 30-day period. However, the decrease in depression severity as measured by HDRS was significantly higher in the MBI group compared to the control group after 30days. For secondary outcomes, systolic blood pressure was lower in the intervention group compared to control group. The total drop-out rate was 29%. Short term mindfulness intervention via mobile application (30days) can be beneficial as adjunctive therapy to treatment as usual in patients with MDD.

Hemiplegic Migraines Exacerbated using an Injectable GLP-1 Agonist for Weight Loss.

The widespread adoption of Glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of obesity and diabetes has raised concerns about their potential adverse effects, including the induction of depression and suicide ideation. We report on a male patient in his early 50s with a complex medical history, including adult Attention-Deficit/Hyperactive Disorder, narcolepsy with cataplexy, and major depressive disorder in remission, who experienced exacerbated hemiplegic migraines after initiating treatment with an injectable GLP-1 agonist (Saxenda) for weight loss. Despite a previous history of experiencing hemiplegic migraines once or twice a year, the patient reported daily occurrences of migraines, many of which were hemiplegic, during the 60 days of GLP-1 agonist treatment. The migraines abated only upon discontinuation of the medication. This case underscores the need to carefully consider patient history and potential genetic predispositions when prescribing GLP-1 agonists, highlighting the complex interactions between these medications, existing comorbidities, and the dopaminergic and calcitonin gene-related peptide pathways. Our findings suggest that GLP-1 agonists, while beneficial for some, may pose significant risks for patients with specific genetic backgrounds or neurological conditions, calling for personalized approaches to treatment and increased awareness of potential adverse effects.

A Case Series Study of Weekly or Fortnightly Transcranial Magnetic Stimulation (TMS) in Major Depressive Disorder.

Major depressive disorder (MDD) is frequently chronic and relapsing. The use of maintenance or continuation transcranial magnetic stimulation (TMS) has received clinical and some research support. To conduct a case series study to report the outcomes of once-weekly (OW) or once-fortnightly (OF) continuation TMS in a real-life setting. We offered OW or OF TMS sessions to patients with MDD in remission or partial remission/relapse. Ten patients received OW TMS and four received OF TMS, for 8 to 46 weeks. No patients in either group who were in remission or partial remission at baseline experienced a relapse. Improvements in HAMD6 and CGI-S scores were statistically significant or of borderline significance for the total sample and the OW group. This naturalistic, open-label observational study indicates that OW TMS is effective as maintenance therapy in MDD, while also offering some support for OF TMS maintenance in preventing relapse.

Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PurposeTo assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. MethodsTen adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. ResultsNine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges’ g = 0.84–2.13). There were small-to-moderate increases in MCA velocity (g = 0.32–0.57) and conductance (g = 0.20–0.76) across time, with minimal changes in pulsatility (all g < 0.21). ConclusionsPreliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET’s efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Fear of depression recurrence among individuals with remitted depression: a qualitative interview study.

Major Depressive Disorder (MDD) is a prevalent psychiatric condition and the largest contributor to disability worldwide. MDD is highly recurrent, yet little is known about the mechanisms that occur following a Major Depressive Episode (MDE) and underlie recurrence. We explored the concept of fear of depression recurrence (FoDR) and its impact on daily functioning among individuals in remission from MDD. 30 participants (83% female; 37% White; Mage = 27.7, SD = 8.96) underwent semi-structured qualitative interviews. The interviews explored participants' experiences of FoDR including the frequency, severity, content, triggers, and impact of fears and associated coping strategies. We used content analysis to analyze the transcriptions. Most participants (73%) reported having FoDR, with varying frequency, severity, and duration of fears. The triggers and content of participants' fears often mirrored the symptoms (e.g., low mood, anhedonia) and consequences (e.g., job loss, social withdrawal) endured during past MDEs. Some participants reported a minimal impact of FoDR on daily functioning, whereas others reported a positive (e.g., personal growth) or negative (e.g., increased anxiety) influence. Our sample size did not allow for explorations of differences in FoDR across unique MDD subtypes or sociocultural factors. The concept of FoDR may present a window into understanding the unique cognitive and behavioural changes that occur following MDD remission and underlie depression recurrence. Future research should aim to identify underlying individual differences and characteristics of the disorder that may influence the presence and impact of FoDR. Finally, a FoDR measure should be developed so that associations between FoDR and recurrence risk, depressive symptoms, and other indices of functioning can be determined.

Predicting risk of dementia among the elderly with major depressive disorder in remission: A prospective study.

Cognitive impairment and change are a focus of research into late-life depression. The aims of this 5-year prospective study were (1) to observe cognitive status change; (2) to investigate the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5years among a clinical cohort with remitted major depressive disorder (MDD). The study cohort included 130 elderly persons with late-life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow-up visit at the 5-year point. In total, 98 cases and 55 normal controls completed the 5-year follow-up assessment. Of the study cohort with late-life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5years. Patients with late-life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information-processing speed (p=0.009) and memory (p=0.041) could predict subsequent progression to dementia within 5years among patients with MDD. This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5years. Further, we found that in depressed patients, deficits in information-processing speed and memory domains were highly suggestive of progression to dementia within 5years.

Effect of Vortioxetine in Comparison to Fluoxetine on Metabolic Parameters in Patients With Depressive Disorder: A Randomized Controlled Trial.

Background Major depressive disorder (MDD) is a debilitating mood disorder that increases the risk of metabolic syndrome (MS), emphasizing the need for mental and physical health treatments. Although many studies have linked atypical antipsychotics to metabolic disturbances, there is limited evidence linking selective serotonin reuptake inhibitor use to MS. This study aimed to assess the risk of MS among patients with MDD who were administered vortioxetine and fluoxetine. Methodology This was a prospective, open-label, randomized controlled trial conducted in the psychiatry department. Using computer-generated random numbers, the physician assigned fluoxetine 20 mg or vortioxetine 10 mg and recorded MS parameters at baseline and each visit (4, 8, 12, 16, 20, and 24 weeks). This study was registered with CTRI (CTRI/2021/07/034892). Results A total of 122 participants were allocated randomly to the following two groups: group A (n = 60) and group B (n = 62). An independent-sample t-test showed a significant improvement in fasting plasma glucose (FPG) at week eight (p = 0.005), triglycerides (TGs) at week 16 (p = 0.005), high-density lipoprotein (HDL) at week 20 (p = 0.005), and waist circumference at week 24 (p = 0.005) in group A compared to group B.However, systolicblood pressure (SBP) and diastolic blood pressure (DBP) were not significantly associated with either group (p = 0.126 and p = 0.793, respectively). Overall depression remission (Hamilton Depression Rating Scale (HAM-D)) and medication adherence rating scale scores were similar between groups (p = 0.337 and 0.325, respectively). Furthermore, most adverse drug reactions were possibly associated with the study drugs. Conclusions In comparison to group B, group A showed significant improvements in FPG, HDL, and waist circumference more effectively; however, both groups led to higher TG levels, with non-significant numerical improvements observed in SBP and DBP in both groups. In addition, both treatment groups reduced the HAM-D score and had a similar MDD remission rate.

Assessing remission in major depressive disorder using a functional-structural data fusion pipeline: A CAN-BIND-1 study

Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity (awFC)). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the ‘full picture’ of connectivity changes for REMs and NREMs while making for an easy intuitive approach.

Analysis of implementation processes in a hybrid effectiveness-implementation trial of interpersonal psychotherapy (IPT) for major depressive disorder in prisons: Training, supervision, and recommendations.

There are 10 million admissions to U.S. prisons and jails each year. More than half of those admitted have mental health problems. The goal of this article is to inform: (1) implementation of evidence-based mental health treatments in prisons and jails, an important effort that needs more evidence to guide it; (2) psychotherapy and interpersonal psychotherapy (IPT) training efforts, especially in low-resource settings. A randomized hybrid effectiveness-implementation trial of group IPT for major depressive disorder (MDD) in state prisons found that IPT increased rates of MDD remission and lowered posttraumatic stress disorder symptoms relative to prison treatment as usual. The trial used prison counselors, only some of whom had prior psychotherapy training/experience, to deliver IPT. IPT treatment adherence was high (96%), but trial training and supervision were too costly to be scalable outside the trial. The current article reports results from a planned qualitative analysis of 460 structured implementation and supervision documents in that trial to describe training and supervision processes and lessons learned, inform training recommendations, and facilitate future work to optimize training and supervision for under-resourced settings. Themes identified in implementation and supervision process notes reflected: work on psychotherapy basics (reflective listening, focusing on emotions, open-ended questions, specific experiences), IPT case conceptualization (forming a conceptualization, what is and is not therapeutic work, structure and limit setting, structure vs. flexibility), IPT techniques (enhancing social support, role plays, communication analysis), psychotherapy processes (alliance repair, managing group processes), and managing difficult situations (avoidance, specific clients, challenging work settings). Counselors were receptive to feedback; some relied on study supervisors for support in managing stressful prison working conditions. Findings can be used to make future training and supervision more efficient. Based on our results, we recommend that initial and refresher training focus on IPT case conceptualization, steps for addressing each IPT problem area, and reflective listening. We also recommend supervision through at least counselors' first two rounds of groups. More low-cost, scalable training methods are needed to get mental health treatment to individuals who need it most, who are often served in challenging, low-resource settings such as prisons. This is a mental health access and equity issue. The trial was registered at clinicaltrials.gov (NCT01685294).

C-Reactive Protein As A Response Indicator In Drug-Naïve Patients With Major Depressive Disorder: A Hospital-Based Study

Abstract Objective: C-reactive protein (CRP) is an indicator of the inflammatory process in the body, and is associated with the pathogenesis of depression through its purported effect on neurotransmitter function in the brain. Current research aims to study the relationship between the levels of CRP and the rate of remission of major depressive disorder with first-line antidepressant therapy. Methods: This hospital-based prospective study included thirty patients by purposive sampling technique. Patients with first-episode MDD with no history of antidepressant exposure and other medical comorbidity were recruited for pharmacotherapy with escitalopram, a first-line antidepressant. Patients taking antidepressants, anti-inflammatory medicines, having co-morbid conditions or other psychiatric conditions were excluded. The baseline CRP levels were measured and depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HRSD) at weeks 0, 6 and 12. The patients with low (≤5 mg/l) and high (&gt;5 mg/l) CRP levels were compared for remission rates at week 12 using Kaplan–Meier survival analysis. Results: Amongst the 30 cases, 11(36.7%) were males and 19(63.3%) were female patients. The mean age was 35.95±7.85 years. Both groups were matched concerning age, gender, BMI and baseline HRSD score (p&gt;0.05). As per Kaplan–Meier survival analysis, a significantly higher proportion of patients had remission of MDD at the 12th week having CRP levels ≤5 mg/l than the patients with CRP levels &gt;5 mg/dl (p=0.002). Conclusion: This research concluded that after an adequate trial with a standard antidepressant, higher levels of CRP could lead to poorer remission rates in MDD subjects and could represent a sub-group of patients with treatment resistance.

Treatments for partial remission of major depressive disorder: a systematic review and meta-analysis

QuestionPartial remission of major depressive disorder (MDD) is a debilitating and distressing clinical state related to chronicity, morbidity and relapse. Although one-third of patients remit partially, evidence for treatment efficacy...

Estradiol effects on an emotional interference task in adolescents with current and remitted depression

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

A blended module (STAIRS) to promote functional and personal recovery in patients with a major depressive disorder in remission: study protocol of a concurrent mixed methods randomized controlled trial

BackgroundDespite the availability of a wide variety of evidence-based treatments for major depressive disorder (MDD), many patients still experience impairments in their lives after remission. Programs are needed that effectively support patients in coping with these impairments. The program Storytelling and Training to Advance Individual Recovery Skills (STAIRS) was developed to address this need and combines the use of peer contact, expert-by-experience guidance, family support and professional blended care. The aim of the planned study is (1) to assess the efficacy of the STAIRS program in patients with remitted MDD, (2) to investigate patients’ subjective experiences with STAIRS, and (3) to evaluate the program’s cost-effectiveness.MethodsA concurrent mixed-methods randomized controlled trial design will be used. Patients aged between 18 and 65 years with remitted MDD (N = 140) will be randomized to either a group receiving care as usual (CAU) + the STAIRS-program or a control group receiving CAU + some basic psychoeducation. Quantitative efficacy data on functional and personal recovery and associated aspects will be collected using self-report questionnaires at the start of the intervention, immediately following the intervention, and at the six-month follow-up. Insights into patients’ experiences on perceived effects and the way in which different program elements contribute to this effect, as well as the usability and acceptability of the program, will be gained by conducting qualitative interviews with patients from the experimental group, who are selected using maximum variation sampling. Finally, data on healthcare resource use, productivity loss and quality of life will be collected and analysed to assess the cost-effectiveness and cost-utility of the STAIRS-program.DiscussionWell-designed recovery-oriented programs for patients suffering from MDD are scarce. If efficacy and cost-effectiveness are demonstrated with this study and patients experience the STAIRS program as usable and acceptable, this program can be a valuable addition to CAU. The qualitative interviews may give insights into what works for whom, which can be used to promote implementation.Trial registrationThis trial was registered at ClinicalTrials.gov on 1 July 2021, registration number NCT05440812.

Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality

BackgroundEsketamine (ESK) nasal spray, taken with oral antidepressant therapy, is approved for the treatment of depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior. In pooled analyses of two pivotal phase 3 studies, ASPIRE I and II, remission rates were consistently higher among patients with MDD with active suicidality who were treated with ESK + standard of care (SOC) versus placebo (PBO) + SOC at all time points in the double-blind and most time points in the follow-up phases. The current analysis of the ASPIRE data sets assessed the effect of ESK + SOC versus PBO + SOC on additional remission-related endpoints: time to achieving remission and consistent remission, proportion of patients in remission and consistent remission, and days in remission.MethodsPost hoc analysis of pooled data from ASPIRE I and II (N = 451). Remission and consistent remission were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≤ 12 at any given visit or two consecutive visits, respectively. Combined endpoints utilizing Clinical Global Impression-Severity of Suicidality-revised version [CGI-SS-r] ≤ 1 (i.e., not suicidal/questionably suicidal) along with the remission and consistent remission definitions (i.e., MADRS total score ≤ 12) were also examined.ResultsThe median times to remission and consistent remission of MDD were significantly shorter in ESK + SOC versus PBO + SOC (15 versus 23 [p = 0.005] and 23 versus 50 days [p = 0.007], respectively) and a greater proportion of patients in ESK + SOC achieved remission and consistent remission by Day 25 (65.2% versus 55.5% and 54.2% versus 39.8%, respectively). Similar results were obtained using the combined endpoint for both remission definitions. The median percent of days in remission during the double-blind treatment phase was significantly greater in ESK + SOC (27.1% or 5 days) versus PBO + SOC (8.3% or 2 days; p = 0.006), and the significant difference was maintained during follow-up.ConclusionTreatment with ESK + SOC versus PBO + SOC resulted in significantly shorter time to remission, greater proportion of patients in remission, and greater percent of days in remission using increasingly rigorous definitions of remission. These findings underscore the clinical benefits of ESK for adults with MDD with suicidality.Trial registrationClinicalTrials.gov registry NCT03039192 (registered February 1, 2017) and NCT03097133 (registered March 31, 2017).

Multimodal Data Integration Advances Longitudinal Prediction of the Naturalistic Course of Depression and Reveals a Multimodal Signature of Remission During 2-Year Follow-up

BackgroundThe ability to predict the disease course of individuals with major depressive disorder (MDD) is essential for optimal treatment planning. Here, we used a data-driven machine learning approach to assess the predictive value of different sets of biological data (whole-blood proteomics, lipid metabolomics, transcriptomics, genetics), both separately and added to clinical baseline variables, for the longitudinal prediction of 2-year remission status in MDD at the individual-subject level. MethodsPrediction models were trained and cross-validated in a sample of 643 patients with current MDD (2-year remission n = 325) and subsequently tested for performance in 161 individuals with MDD (2-year remission n = 82). ResultsProteomics data showed the best unimodal data predictions (area under the receiver operating characteristic curve = 0.68). Adding proteomic to clinical data at baseline significantly improved 2-year MDD remission predictions (area under the receiver operating characteristic curve = 0.63 vs. 0.78, p = .013), while the addition of other omics data to clinical data did not yield significantly improved model performance. Feature importance and enrichment analysis revealed that proteomic analytes were involved in inflammatory response and lipid metabolism, with fibrinogen levels showing the highest variable importance, followed by symptom severity. Machine learning models outperformed psychiatrists’ ability to predict 2-year remission status (balanced accuracy = 71% vs. 55%). ConclusionsThis study showed the added predictive value of combining proteomic data, but not other omics data, with clinical data for the prediction of 2-year remission status in MDD. Our results reveal a novel multimodal signature of 2-year MDD remission status that shows clinical potential for individual MDD disease course predictions from baseline measurements.

Impulsivity in Depression: Its Relation to Suicidality.

Impulsivity is an important risk for suicidality, which is common in patients with major depressive disorder (MDD). The goal of this study was to examine multiple facets of impulsivity in depressed patients compared with healthy controls and to assess their relationship to suicidality. Outpatients diagnosed with MDD using the Structured Clinical Interview for DSM-IV were recruited. Two groups were constituted as "MDD in remission" (n=32) and "MDD" (n=71). The "healthy control" group (n=30) consisted of individuals who had never been diagnosed with any psychiatric disorder. Impulsivity was assessed with the Barratt Impulsivity Scale (BIS), a self-rating measure, and with the following behavioral tasks: Go/No-go Task, Iowa Gambling Task, and Balloon Analogue Risk Task. The scores of the 3 groups (n=133) were compared to evaluate the effect of MDD. The scores were also analyzed and compared in the patients in the 2 MDD groups (n=103) with respect to their current and lifetime suicidality. There was no difference in the 3 groups in task scores, but nonplanning BIS was correlated with the severity of depressive symptoms. Patients with suicidal ideation (SI) had higher BIS total and attention impulsivity scores and more commission errors on the Go/No-go Task, reflecting failure in response inhibition, compared with the patients without SI. Failure to show differences in impulsivity-related tasks suggests that there might be no relationship between the state of depression and impulsivity. However, these findings confirm that there is an association between SI and response inhibition and the attention facet of impulsivity in depression.

Intranasal Esketamine administration in catatonia: a case report.

IntroductionCatatonia is a complex psychomotor syndrome that often goes unrecognized and, consequently, untreated. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. Benzodiazepines and electroconvulsive therapy (ECT) are the most widely studied treatment methods. However, no uniform treatment method has yet been brought forward and no previous attempts to treat catatonia on a patient suffering concomitant major depressive disorder (MDD) with NMDA receptor antagonists have been documented so far.ObjectivesTo describe the unknown and novel management of catatonia and MDD with intranasal esketamine, a NMDA receptor antagonist.MethodsA 55-year-old woman with a diagnosis of long-standing recurrent major depressive disorder who was admitted to the psychiatric inpatient unit of UniversityHospital Marqués de Valdecilla (Santander, Spain) suffering a complex catatonic, mutative state framed on a severe MDD. Different ineffective therapeutic interventions were deployed during the course of her illness. After failing to improve under conventional pharmacological treatment and ECT, and given the complexity of peripheral venous access on this patient (which disabled the option for iv ketamine use), we decided to initiate compassionate treatment with intranasal esketamine.ResultsIntranasal esketamine was effective in the resolution of patient’s complex catatonic state. Clinical response from catatonia was observed after 6 intranasal esketamine administrations (2-week follow-up), reaching full catatonia and MDD remission after 12 sessions in absence of significant adverse eventsConclusionsEsketamine showed promising effectiveness for the treatment of catatonia in the context of MDD, although further research on this topic is needed.Disclosure of InterestNone Declared

Somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and its neuroimaging mechanisms

BackgroundSubclinical anxiety, depressive and somatic symptoms appear closely related. However, it remains unclear whether somatic symptoms mediate the association between subclinical anxiety and depressive symptoms and what the underlying neuroimaging mechanisms are for the mediating effect.MethodsData of healthy participants (n = 466) and participants in remission of major depressive disorder (n = 53) were obtained from the Human Connectome Project. The Achenbach Adult Self-Report was adopted to assess anxiety, depressive and somatic symptoms. All participants completed four runs of resting-state functional magnetic resonance imaging. Mediation analyses were utilized to explore the interactions among these symptoms and their neuroimaging mechanisms.ResultsSomatic symptoms partially mediated the association between subclinical anxiety and depressive symptoms in healthy participants (anxiety→somatic→depression: effect: 0.2785, Boot 95% CI: 0.0958–0.3729; depression→somatic→anxiety: effect: 0.0753, Boot 95% CI: 0.0232–0.1314) and participants in remission of MDD (anxiety→somatic→depression: effect: 0.2948, Boot 95% CI: 0.0357–0.7382; depression→somatic→anxiety: effect: 0.0984, Boot 95% CI: 0.0007–0.2438). Resting-state functional connectivity (FC) between the right medial superior frontal gyrus and the left thalamus and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in healthy participants (effect: 0.0020, Boot 95% CI: 0.0003–0.0043). The mean strength of common FCs of subclinical depressive and somatic symptoms, somatic symptoms, and the mean strength of common FCs of subclinical anxiety and somatic symptoms as chain mediators partially mediated the effect of subclinical depressive symptoms on subclinical anxiety symptoms in remission of MDD (effect: 0.0437, Boot 95% CI: 0.0024–0.1190). These common FCs mainly involved the insula, precentral gyri, postcentral gyri and cingulate gyri. Furthermore, FC between the triangular part of the left inferior frontal gyrus and the left postcentral gyrus was positively associated with subclinical anxiety, depressive and somatic symptoms in remission of MDD (FDR-corrected p < 0.01).ConclusionsSomatic symptoms partially mediate the interaction between subclinical anxiety and depressive symptoms. FCs involving the right medial superior frontal gyrus, left thalamus, triangular part of left inferior frontal gyrus, bilateral insula, precentral gyri, postcentral gyri and cingulate gyri maybe underlie the mediating effect of somatic symptoms.