The association between serum tumor necrosis factor-alpha (sTNF-α) levels and antidepressant treatment responses remains controversial.

This study aimed to examine the impact of sTNF-α levels on 12-week antidepressant treatment outcomes, and to explore the moderating effects of functional status on this relationship in patients with depressive disorders.

We measured baseline sTNF-α and evaluated functional status with the Social and Occupational Functioning Assessment Scale (SOFAS) in 1086 patients undergoing stepwise antidepressant treatment. Remission, defined as a score of ≤7 on the Hamilton Rating Scale for Depression, was assessed at 12 weeks. Logistic regression analyses were performed to adjust for relevant covariates.

Higher sTNF-α levels were significantly associated with non-remission at 12 weeks. This association was particularly evident among patients with higher SOFAS scores, whereas no significant association was observed in patients with lower SOFAS scores. The interaction between sTNF-α levels and SOFAS scores remained significant even after adjusting for relevant covariates.

Baseline sTNF-α levels may serve as a useful predictor of 12-week antidepressant treatment outcomes. Incorporating functional status into the predictive model enhances the accuracy of treatment response predictions.

In patients with remitted psychosis, the dosage of antipsychotics can be lowered without increased risk of relapse. Whether dose tapering can lead to improved cognition is unclear. We compared changes in cognitive performance between patients undergoing dose tapering and those receiving a fixed maintenance dose.

A 2-year prospective trial of patients with stable schizophrenia-related psychotic disorders was conducted: one group received guided dose reduction (GDR) and one group received maintenance treatment. Cognitive function was assessed using the Wechsler Adult Intelligence Scale-Third Edition, Mandarin Chinese version, at baseline, 1, and 2 years. The relations between the ratio of reduced dose and the extent of cognitive improvement were examined by Spearman’s correlation coefficient. We also examined cognitive performance between aripiprazole (ARI) users and non-ARI users.

GDR patients exhibited significantly greater improvements in total intellectual quotient (IQ), particularly working memory, and information and arithmetic subtest scores, with no significant difference in relapse rates between groups. Statistically significant dose–response correlations were found between the degree of dose reduction and improvements in total IQ (n = 72, r = 0.242, p = 0.041), Working Memory Index (n = 72, r = 0.284, p = 0.016), and Arithmetic subtest (n = 72, r = 0.295, p = 0.012). There were no differences in cognitive changes between ARI users and non-users.

Lowering antipsychotic dosage may ameliorate patient performance in several cognitive domains. This finding is worthy of consideration while evaluating the risk-to-benefit ratio of tapering antipsychotics in patients with remitted psychosis.

Network analysis is a promising approach for elucidating the dynamics of the transition from psychopathology to well-being. Recently, symptom connectivity strength has been proposed as a measure of plasticity – the capacity to change disease severity. Yet, empirical findings remain inconsistent. We propose that this inconsistency can be resolved by recognizing that the interpretation of connectivity strength varies along the recovery process from depression, whether at baseline or during clinical change.

We analyzed 2,710 depressed patients from the STAR*D dataset, grouped by the magnitude of change in depressive score. Symptom network connectivity was estimated from QIDS-C items at three time points: (i) baseline, (ii) change – defined as when clinical change in depression score occurs, (iii) post-change - corresponding to when the maximum clinical change is achieved.

At baseline, connectivity strength predicts the maximum clinical change, inversely correlating with its magnitude (ρ = −0.95, p = 0.001). At the change time point, connectivity strength parallels clinical change (ρ = 0.92, p = 0.002). A direct and significant association between connectivity strength and depression severity emerges only at the change (ρ = 0.98, p = 0.0003) and post-change (ρ = 0.95, p = 0.001) time points.

The interpretation of connectivity strength for predicting depression trajectories varies by timepoint: at baseline, it measures plasticity -- the capacity for change -- whereas during clinical change, it indicates the magnitude of change in symptom severity. This framework supports the reliability of this prognostic marker for designing personalized therapeutic interventions in psychiatry.

Improving Access to Psychological Therapies (IAPT), an NHS England service providing talking therapies, is meeting its target recovery rate of 50%. However, engagement in treatment, as well as recovery rates, may be lower for some groups.

To assess variation in treatment completion and recovery rates by demographic and socioeconomic group and to describe rates of further referrals for patients to IAPT and secondary mental health services.

Using 121 548 administrative records for 2019–2020 and 2022–2023 for the Norfolk and Waveney area, we estimated associations of age, gender, ethnicity and deprivation with the likelihood of treatment completion and recovery using logistic regression modelling. We also described rates of further referrals.

Younger people and those living in deprived areas were less likely to recover or complete treatment, with those aged 16–17 years (n = 735) having the lowest adjusted odds for recovery (adjusted odds ratio = 0.5, 95% CI: 0.5–0.6) compared with those aged 36–70 years, and those aged 18–24 years (n = 23 563) having the lowest rate of completion (adjusted odds ratio = 0.5, 95% CI: 0.5–0.6). Further referrals before April 2022 were recorded for 45.4% of 6513 patients who had completed treatment and 68.8% of 9469 who had not completed treatment, and for 39.4% of 2007 recovered patients in 2019–2020 and 53.1% of 1586 who had not recovered. Non-completers had relatively more further referrals to secondary mental health services compared with completers (43.6% v. 22.8%; P < 0.01).

Younger people and those living in deprived areas have lower recovery and completion rates. Those who have completed treatment and not recovered have higher rates of further referrals.

Esketamine nasal spray (ESK) is approved in combination with an oral antidepressant (OAD) for the treatment of adults with treatment-resistant depression (TRD); however, direct comparisons with atypical antipsychotics for TRD are limited. This secondary analysis of the ESCAPE-TRD study compared rates of remission and response, and improvements in depressive symptoms over time, between ESK and quetiapine extended-release (XR) in patients with TRD treated in accordance with US prescribing information (USPI).

ESCAPE-TRD (NCT04338321) was a randomized, open-label, rater-blinded phase 3b trial investigating ESK versus quetiapine XR for acute and maintenance treatment of patients with TRD. This secondary analysis included patients aged 18–64 years who were treated/dosed according to USPI. The primary endpoint was remission, defined as Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≤ 10. Treatment-emergent adverse events (TEAEs) leading to discontinuation were summarized descriptively.

Among 636 patients in this secondary analysis (ESK, n = 316; quetiapine XR, n = 320), significantly more ESK-treated patients achieved remission starting at week 8 (28.3% versus 18.6%; P = 0.005) through week 32 (55.7% versus 36.3%; P < 0.001), compared with quetiapine XR–treated patients. There were clinically and statistically significant improvements in MADRS scores with ESK versus quetiapine XR at each visit from day 8 onwards. Fewer patients discontinued treatment because of TEAEs with ESK (4.5%) versus quetiapine XR (10.1%).

Consistent with the primary analysis, this secondary analysis demonstrated that ESK improves short- and long-term outcomes compared with quetiapine XR in patients with TRD treated according to USPI.

Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies.

Probands and relatives with current DSM-IV BED (n = 156) from a family study of BED (‘baseline’) were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints.

Of participants with follow-up data (n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables.

Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.

Individuals in a depressive episode and healthy controls exhibit robust differences on affect dynamics captured with ecological momentary assessment (EMA). However, few studies have explored affect dynamics in individuals in remission from depression, and results have been mixed.

A community sample of 18-year-olds (N = 345) completed diagnostic interviews and EMA probing emotions and low interest/motivation 5× daily for 2 weeks. Affect home base, variability, and inertia were compared across currently depressed, remitted, and never-depressed groups.

Both depression groups had a higher negative affect (NA) and low interest/motivation home base, lower positive affect (PA) home base, greater variability of NA, PA, and low interest/motivation, and greater NA and low interest/motivation inertia than never-depressed participants. Additionally, the currently depressed group had a higher sad home base specifically, greater variability across most negative emotions and low interest/motivation, and greater low interest/motivation inertia than the remitted group. The currently depressed and remitted groups did not differ in anxious, upset, or PA home base, anxious or PA variability, and inertia of all negative emotions and PA.

Findings suggest that a number of abnormalities in emotion and reward functioning persist after a depressive episode resolves, however, the tendency to experience higher levels of sadness, greater range of a variety of negative emotions, and more variable and persistent low interest/motivation are exacerbated during depressive episodes. Conversely, greater intensity and persistence of some negative emotions (anxiety, upset) and blunted positive emotions appear to equally characterize depression in both the symptomatic and remitted state.

Remitted psychotic depression (MDDPsy) has heterogeneity of outcome. The study's aims were to identify subgroups of persons with remitted MDDPsy with distinct trajectories of depression severity during continuation treatment and to detect predictors of membership to the worsening trajectory.

One hundred and twenty-six persons aged 18–85 years participated in a 36-week randomized placebo-controlled trial (RCT) that examined the clinical effects of continuing olanzapine once an episode of MDDPsy had remitted with sertraline plus olanzapine. Latent class mixed modeling was used to identify subgroups of participants with distinct trajectories of depression severity during the RCT. Machine learning was used to predict membership to the trajectories based on participant pre-trajectory characteristics.

Seventy-one (56.3%) participants belonged to a subgroup with a stable trajectory of depression scores and 55 (43.7%) belonged to a subgroup with a worsening trajectory. A random forest model with high prediction accuracy (AUC of 0.812) found that the strongest predictors of membership to the worsening subgroup were residual depression symptoms at onset of remission, followed by anxiety score at RCT baseline and age of onset of the first lifetime depressive episode. In a logistic regression model that examined depression score at onset of remission as the only predictor variable, the AUC (0.778) was close to that of the machine learning model.

Residual depression at onset of remission has high accuracy in predicting membership to worsening outcome of remitted MDDPsy. Research is needed to determine how best to optimize the outcome of psychotic MDDPsy with residual symptoms.

Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit.

Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively.

Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression.

Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Mothers with perinatal depression can show different symptom trajectories and may spontaneously remit from depression, however, the latter is poorly understood. This is the first study which sought to investigate predictors of spontaneous remission and longer-term recovery among untreated women with perinatal depression.

We analysed data from two randomised controlled trials in women with perinatal depression in India and Pakistan. Analyses were restricted to women in the control groups who did not receive active treatment. Generalised estimating equations and logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for within-person correlation.

In multivariable analyses, remission was associated with a husband who is not working (adjusted OR, aOR = 2.04, 95% CI 1.02–4.11), lower Patient Health Questionnaire-9 score at baseline (aOR = 0.43, 95% CI 0.20–0.90 for score of ≥20 vs. 10–14) and better social support at baseline (aOR = 2.37, 95% CI 1.32–4.27 for high vs. low social support).

Women with low baseline severity may remit from perinatal depression with adequate social support from family and friends. These factors are important contributors to the management of perinatal depression and the prevention of clinical worsening, and should be considered when designing low-threshold psychological interventions.

Nonsuicidal self-injury (NSSI) is prevalent in adolescent clinical samples. There is evidence that NSSI can be treated effectively but data on individual treatment outcomes is limited. The goal of this study was to examine response, remission, exacerbation, and relapse rates over one and two years, respectively, among a clinical sample of adolescents with NSSI. Furthermore, we aimed to identify clinically relevant predictors of NSSI trajectories.

The sample consists of n = 203 adolescents (12–17 y., 94% female) from a specialized outpatient clinic for risk-taking and self-harming behavior with NSSI on at least five days in the six months before first assessment. Assessments were completed at baseline and one (FU1) and two (FU2) years later using structured clinical interviews and self-report questionnaires.

At FU1, 75% reported a reduction in NSSI frequency by at least 50% (treatment response); among those, one third (25% of the entire sample) achieved a remission (0 NSSI); an exacerbation (⩾50% more NSSI) was observed in 11% of patients. Of those in remission, 41% relapsed one year later. Predictors of non-response or non-remission were inpatient treatment and depressive symptoms. Adolescents with lower NSSI frequency at baseline had a higher risk of exacerbation. Due to limited sample size at FU2 no prediction model for relapse was established.

While most adolescents presenting with NSSI achieved significant improvement, more attention should be paid to the rather low rates of full remission. Prediction and early detection of individuals who deteriorate during or relapse after treatment is critical.

Vortioxetine has demonstrated dose-dependent efficacy in patients with major depressive disorder (MDD), with the greatest effect observed with vortioxetine 20 mg/day. This analysis further explored the clinical relevance of the more rapid and greater improvement in depressive symptoms observed with vortioxetine 20 mg/day vs 10 mg/day.

Analysis of pooled data from six short-term (8-week), randomized, placebo-controlled, fixed-dose studies of vortioxetine 20 mg/day in patients with MDD (N = 2620). Symptomatic response (≥50% decrease in Montgomery–Åsberg Depression Rating Scale [MADRS] total score), sustained symptomatic response, and remission (MADRS total score ≤10) were assessed by vortioxetine dosage (20 or 10 mg/day).

After 8 weeks, 51.4% of patients receiving vortioxetine 20 mg/day had achieved symptomatic response vs 46.0% of those receiving vortioxetine 10 mg/day (P < .05). Significantly more patients achieved symptomatic response vs placebo from week 2 onwards for vortioxetine 20 mg/day and from week 6 onwards for vortioxetine 10 mg/day (both P ≤ .05). Sustained response was achieved from week 4 for 26.0% of patients receiving vortioxetine 20 mg/day vs 19.1% of those receiving vortioxetine 10 mg/day (P < .01), increasing to 36.0% and 29.8%, respectively, over the 8-week treatment period (P < .05). At week 8, 32.0% of patients receiving vortioxetine 20 mg/day were in remission vs 28.2% of those receiving vortioxetine 10 mg/day (P = .09). Rates of adverse events and treatment withdrawal were not increased during the week following vortioxetine dose up-titration to 20 mg/day.

Vortioxetine 20 mg/day provides more rapid and more sustained symptomatic response than vortioxetine 10 mg/day in patients with MDD, without compromising tolerability.

Approximately one-third of patients with psychotic disorders does not respond to standard antipsychotic treatments. Consensus criteria for treatment resistance (TR) may aid the identification of non-response and subsequent tailoring of treatments. Since consensus criteria require stability of clinical status, they are challenging to apply in first-episode psychosis (FEP). This study aims to investigate (a) if an adaptation of consensus criteria can be used to identify FEP patients with early signs of TR (no early clinical recovery—no-ECR) after 1 year in treatment and (b) to what extent differences in antipsychotic treatments differentiate between outcome groups.

Participants with FEP DSM-IV schizophrenia spectrum disorders were recruited during their first treatment. A total of 207 participated in the 1-year follow-up. Remission and recovery definitions were based on adaptations of the “Remission in Schizophrenia Working Group” criteria and TR on adaptations of the “Treatment Response and Resistance in Psychosis” (TRRIP) working group criteria.

97 participants (47%) could be classified as no-ECR, 61 (30%) as ECR, and 49 (23%) as with partial ECR (P-ECR). Statistically significant baseline predictors of no-ECR matched previously identified predictors of long-term TR. Only 35 no-ECR participants had two adequate treatment trials and met the full TRRIP criteria. 21 no-ECR participants were using the same medication over the follow-up year despite the lack of significant effects.

The difference in the percentage of FEP participants classified as no-ECR versus TR indicates that we may underestimate the prevalence of early TR when using consensus criteria.

Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.

A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.

A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.

GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

In difficult-to-treat depression (DTD) the outcome metrics historically used to evaluate treatment effectiveness may be suboptimal. Metrics based on remission status and on single end-point (SEP) assessment may be problematic given infrequent symptom remission, temporal instability, and poor durability of benefit in DTD.

Self-report and clinician assessment of depression symptom severity were regularly obtained over a 2-year period in a chronic and highly treatment-resistant registry sample (N = 406) receiving treatment as usual, with or without vagus nerve stimulation. Twenty alternative metrics for characterizing symptomatic improvement were evaluated, contrasting SEP metrics with integrative (INT) metrics that aggregated information over time. Metrics were compared in effect size and discriminating power when contrasting groups that did (N = 153) and did not (N = 253) achieve a threshold level of improvement in end-point quality-of-life (QoL) scores, and in their association with continuous QoL scores.

Metrics based on remission status had smaller effect size and poorer discrimination of the binary QoL outcome and weaker associations with the continuous end-point QoL scores than metrics based on partial response or response. The metrics with the strongest performance characteristics were the SEP measure of percentage change in symptom severity and the INT metric quantifying the proportion of the observation period in partial response or better. Both metrics contributed independent variance when predicting end-point QoL scores.

Revision is needed in the metrics used to quantify symptomatic change in DTD with consideration of INT time-based measures as primary or secondary outcomes. Metrics based on remission status may not be useful.

Analysis of the first-episode psychosis remission, including post-psychotic affective and primary negative symptoms as well as personality changes, is necessary to personalize therapy and rehabilitation.

We aimed to identify different trajectories of psychosis remission in young adults.

First-episode psychosis patients (n=56, mean age 19.8±2.5 years, all males) underwent psychopathological assessment at the stage of remission.

Three trajectories of remission were identified. The thymopathic trajectory (33.93%, 19 patients) was characterized by the gradual increase of subclinical affective symptoms and resulted with a high-quality remission. In 63.61% cases in this group persistent depressed mood was present after a psychotic episode. Some patients (36.84%) became prone to depressive reactions. The pathocharacterological trajectory (39.28%, 22 patients) was characterised by personality changes with increase of existing traits or the development of traits previously not present. Types with an increase of schizoid (14.29%), histrionic (19.64%), and anxiety-hypochondriacal (5.36%) traits were identified. Patients in this group had high- as well as low-quality remission. The destructive trajectory (26.79%, 15 patients) was characterised by residual positive or single negative symptoms. Patients in this subgroup had low-quality remission with poor functioning and signs of treatment resistance.

Analysis of trajectories of the first-episode psychosis remission allowed us to choose the most effective strategy for personalized supportive treatment.

No significant relationships.

Research in recent decades focuses on understanding the role of the immune system in First-Episode Psychosis (FEP) at a young age. Our studies indicate that different stages of schizophrenia differ in the spectrum of inflammation markers. These indicators reflect the activity of the pathological process, using them as markers of the clinical state of patients at different stages of the disease.

To assess the relationship of immune markers with the clinical features of remission in patients after FEP.

Fifty patients aged 15-25 years with post-psychotic depression (PD) after FEP (F20, F25) and 30 healthy men were included in the study. The follow-up period was two years. PD typological variants with positive affectivity (PA) (n=30) and negative affectivity (NA) (n=20) were distinguished. Leukocyte elastase (LE), a1-proteinase inhibitor (a1-PI) activity, and S-100B autoantibodies in plasma samples were measured.

The increase of LE and a1-PI activity in plasma of both types of PD patients compared to controls was detected (p<0.01). There was the highest LE activity and S-100B autoantibodies in PD with NA (p<0.05). The different dynamics of immune markers in both groups were correlated to the clinical features of remission. PD with PA was associated with a decrease in inflammatory markers (p<0.05) and a favorable prognosis. PD patients with NA had a further increase in LE activity and S-100B autoantibodies (p<0.01), and an unfavorable prognosis.

The results confirm using the immune indicators as markers to assess the quality of remission after FEP in young adult age and the risk of recurrent psychotic attacks.

No significant relationships.