Routine mental health care in Europe generates a large amount of data that to date has not much been used for guiding treatment decisions: On the one hand, data primarily generated for billing purposes (care-related data, routine health insurance data), such as ICD-10 diagnosis codes, information on hospital stays and interventions or outpatient medication prescriptions. On the other hand, specific clinical data. Examples include data from Access to Psychological Therapies (IAPT) services or the Mental Health Services Data Set (MHSDS) in Great Britain, the National Health Data System (SNDS) in France or the extension module Mental Health of the German Medical Informatics Initiative’s core data set, which is currently under development.

Which variables should be included in these datasets for a reliable treatment response prediction in routine unipolar Major Depression (MD) treatment?

Umbrella review of individual participant data (IPD) meta-analyses on predictors and moderators in the treatment of MD, compliant with the PRISMA-IPD statement. Mapping of results to routine mental health datasets.

From the 1548 articles identified by the systematic literature search, 25 eligible studies were included. The review identified predictors and moderators in the areas of depression history and course, comorbidities, sociodemographic factors, psychosocial factors, and aversive life events. The method used did not identify any biological or imaging markers as predictors or moderators. Most of the identified variables could be approximated using routine data sets, but in many cases only using complex indicators.

Available routine data sets seem to be interesting for treatment response prediction in routine care, but in many cases complex indicators would have to be constructed. The clinical benefits would have to be tested in studies. Using available routine data would offer the opportunity to apply the results of therapy response prediction research in routine practice.

None Declared

Treatment-resistant depression (TRD), a persistent condition impacting up to 30% of patients with major depressive disorder, carries substantial personal and economic burden. There remains an unmet need for therapies that provide both rapid and durable improvements in TRD. Preliminary clinical trials indicate that GH001, a synthetic, inhalable formulation of mebufotenin, has the potential for rapid improvement of depressive symptoms in this population.

This trial investigated the efficacy and safety of GH001 in patients with TRD in a Phase 2b randomized double-blind trial with a 6-month follow-up.

In the double-blind part, patients received an individualized dosing regimen (IDR) of up to three escalating doses of GH001 (6, 12, and 18 mg) or placebo IDR on a single day. During the 6-month open-label extension (OLE), patients received up to five GH001 IDR re-treatments.

Eighty-one patients were enrolled (GH001: n = 40; placebo: n = 41; all entered the OLE). GH001 led to a significantly greater reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Day 8 (primary endpoint) vs placebo (least squares mean difference: -15.5; P<0.0001), with significant effects observed from 2 hours post-dose and onwards. Day 8 remission rates (MADRS ≤10) were 57.5% with GH001 vs 0% with placebo. At 6 months, 73.0% (46/63) of OLE completers were in remission. Patients received a mean of four GH001 treatments; 63.5% (n=40) received 1-4 doses. Most adverse events (AEs) were mild or moderate; one serious treatment-emergent AE in the OLE (Migraine) was unrelated to treatment.

GH001 treatment was well tolerated and produced rapid and significant improvements in depressive symptoms in patients with TRD.

E. Vieta Grant / Research support from: AB-Biotics, Abbott, AbbVie, Adamed, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Clariane, Compass, Dainippon Sumitomo Pharma, Esteve, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Intra-Cellular therapies, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Mitsubishi Tanabe Pharma, Otsuka, Rovi, Sanofi-Aventis, Sunovion, and Takeda, Consultant of: Abbott, AbbVie, Adamed, Alcediag, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Casen-Recordati, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Esteve, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Intra-Cellular therapies, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Mitsubishi Tanabe Pharma, Newraxpharm, Newron, Novartis, Organon, Orion Corporation, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, Speakers bureau of: Johnson & Johnson, Lundbeck, B. T. Baune Grant / Research support from: AstraZeneca, BMBF (Germany), BMG (Germany), DFG (Germany), ERA PerMed, Fay Fuller Foundation, Horizon Europe (European Union), James & Diana Ramsay Foundation (Adelaide), Johnson & Johnson, Lundbeck, La Marató de TV3, National Health and Medical Research Council (Australia), Sanofi-Synthélabo, and Wellcome Trust (UK), Consultant of: National Health and Medical Research Council (Australia). Advisory boards – Biogen, Boehringer, GH Research, Ingelheim, Janssen-Cilag, LivaNova, Lundbeck, Medscape, Novartis, Otsuka, Teva, and Viatris, Speakers bureau of: Angelini, AstraZeneca, Biogen, BMS, Boehringer Ingelheim, Johnson & Johnson, LivaNova, Lundbeck, Medscape, Novartis, Otsuka, Pfizer, Roche, Servier, Sumitomo Pharma, Sunovion, Takeda, Teva, Viatris, and Wyeth, N. Cardoner Grant / Research support from: Ministry of Health, Ministry of Science and Innovation (CIBERSAM), Strategic Plan for Research and Innovation in Health (PERIS, 2016–2020), Recercaixa, Marató TV3, Consultant of: Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer, Viatris, Employee of: Hospital de la Santa Creu i Sant Pau; Universitat Autònoma de Barcelona, Speakers bureau of: Adamed, Elsevier, Exeltis, Janssen, Lundbeck, Pfizer, Servier; medical conferences hosted by Boston, Janssen, Lundbeck, and Pfizer, R. M. Dueñas Herrero Grant / Research support from: COMP 006 Subinvestigator. BPL 201: PI, L. Janů: None Declared, J. R. Kelly Grant / Research support from: Health Research Board (ILP-POR-2022-030, DIFA-2023-005, HRB KTA-2024-002), S. J. McInerney Grant / Research support from: Principal investigator – GH Research and Transcend Therapeutics, Speakers bureau of: Janssen and Lundbeck, A. Nawka Grant / Research support from: Principal Investigator - GH Research, T. Páleníček Shareholder of: Psychedelická klinika s.r.o., Společnost pro podporu neurovědního výzkumu s.r.o., and AVI-X Aviation Experts s.r.o. Founder – PSYRES (Psychedelic Research Foundation), Grant / Research support from: Principal investigator – Compass, GH Research, MAPS, and Ketabon, Consultant of: CB21 Pharma and GH Research, V. Pérez Sola Consultant of: Consultant, honoraria, or grants – AB-Biotics, AstraZeneca, Bristol Myers Squibb, CIBERSAM, FIS-ISCiii, Janssen Cilag, Lundbeck, Medtronic, Otsuka, and Servier, A. Reif Grant / Research support from: Medice and Janssen, Consultant of: Janssen/Johnson & Johnson, Boehringer Ingelheim, Compass, GH Research, SAGE/Biogen, LivaNova, Medice, Shire/Takeda, Newron, MSD, AbbVie, cyclerion and Polpharma, Speakers bureau of: Janssen/Johnson & Johnson, Boehringer Ingelheim, Compass, GH Research, SAGE/Biogen, LivaNova, Medice, Shire/Takeda, Newron, MSD, AbbVie, cyclerion and Polpharma, M. E. Thase Grant / Research support from: Acadia, Alkermes, Axsome, Intra-Cellular Therapies, Janssen, National Institute of Mental Health, Otsuka, Patient-Centered Outcomes Research Institute (PCORI), and Takeda, Consultant of: Autobahn Therapeutics, Axsome, Clexio Biosciences, Gerson Lehrman Group, GH Research, Lundbeck, Janssen, Johnson & Johnson, Luye Pharma, Merck, Object Pharma, Otsuka, Pfizer, Sage, Seelos Therapeutics, Sunovion, and Takeda, V. Valcheva Shareholder of: Stock option holder of GH Research, Employee of: GH Research, W. J. Cubala Grant / Research support from: Acadia, Angelini, Beckley Psytech, GH Research, HMNC Brain Health, Intra-Cellular Therapies, Janssen, MSD, Neumora, Novartis, Otsuka, Recognify Life Sciences, Consultant of: Douglas Pharmaceuticals, GH Research, Janssen, MSD, and Novartis, Speakers bureau of: Angelini, GH Research, Janssen, and Novartis.

Substantial evidence confirms a linear relationship between low-density lipoprotein and depression. However, findings on the association of abnormal high-density lipoprotein cholesterol (HDLc) with depression are inconclusive, with both low and high levels of HDLc implicated in severe symptoms and suicidality. Additionally, gender differences in this association remain underexplored.

This study evaluated the association between abnormal serum HDLc and depressive symptom severity and investigated whether the association varied by gender in a sample of multi-ethnic adults in Singapore.

Descriptive and multivariable analyses were conducted on data collected from participants of a longitudinal cohort - The PREDICT study. Participants were aged 18-75 years, of Chinese, Malay, or Indian ethnicity, with major depressive disorder (MDD) or general population without any psychiatric diagnosis. The primary outcome was depressive symptom score assessed with the Patient Health Questionnaire (PHQ)-9. Its association with abnormal serum HDLc levels (categorised into ordinal variable for abnormal low (AL), normal (N), and abnormal high (AH) HDL) and gender differences were investigated after adjusting for age, race, and known confounders of lipid abnormality (body mass index, mental health treatment, and history of chronic conditions).

The study sample comprised 212 participants with a mean age of 38.1 (SD 13) years. In all, 59.4% were women, 76.9% were Chinese, and 51.4% were diagnosed with MDD. Total PHQ-9 score ranged from 1- 34, with a mean score of 7.8 (SD 7); 19.8% met criteria for moderately severe to severe depression. The prevalence of abnormal HDLc was 58% with AL-HDLc and AH-HDLc observed in 11.8% and 46.2% of the sample, respectively. Compared to persons with N-HDLc, AL-HDLc was significantly and directly associated with symptom severity (β = 4.4, 95% CI:1.2 to 7.7, p = 0.008), while an inverse association was observed with AH-HDLc (β = −2.6, 95% CI:‒4.7 to −0.5, p = 0.015). The significant direct association between AL-HDLc and symptom severity was observed only among men, whereas AH-HDLc showed a significant inverse relationship only in women. The association between AL-HDLc remained significant after adjusting for confounders in the overall sample and among men.

Study results indicate that low HDLc is linked to more severe depressive symptoms, whereas high levels of HDLc have an inverse relationship. The latter contrasts with emerging literature on adverse outcomes of depression associated with high HDLc. Gender differences exist in these associations, which need to be investigated further and replicated in a larger sample. Nevertheless, these preliminary findings underscore the importance of maintaining healthy HDLc levels, which may lower morbidity in depressive disorders.

None Declared

Treatment-resistant depression is a major concern, though there has been significant advancement in antidepressant therapy. The therapeutic outcome for patients with depressive disorder is achieving a treatment response with remission. Predictions based on genetic markers may have the potential to increase the treatment response through a personalised approach. Norepinephrine neurotransmission is a major pathophysiological concern.

To investigate the association of single-nucleotide polymorphisms (SNPs) in the norepinephrine transporter (SLC6A2) as predictive pharmacogenetic biomarkers with antidepressant response in the Indian population, by comparing treatment responders and non-responders to SSRI/SNRI monotherapy.

Two hundred thirty-eight patients suffering from depressive disorder were selected and enrolled for this study. The patients were treated with SSRI/SNRI over a period of 3 months. Standardised questionnaires were used for assessment, including the severity of depression assessed by the Hamilton Depression Rating Scale (HDRS) and the Centre for Epidemiologic Studies Depression Scale (CES-D), social cognition assessment using SOCRATIS, and side effects evaluation with the UKU Side Effect Rating Scale. Genetic variations SLC6A2 with their SNPs (rs5569 and rs36029) were genotyped. The genetic data of the responders and non-responders were compared to evaluate the role of genetic variants in therapeutic outcome.

Out of the total patients, 136 (57.14%) showed a positive treatment response, with 32 (23.52%) achieving complete remission. Analysis of SNP rs36029 (A/G) revealed no significant association with responder/non-responder or remitter/non-remitter groups, nor with the eight most common side effects, except memory loss, which showed a significant (p = 0.029). For SNP rs5529 (G/A/C), the wild-type allele (G) was predominant among responders (56 patients, 37.3%), while mutant alleles A (19 patients, 12%) and C (1 patient, 0.7%) were less common. In non-responder groups, the G allele was less frequent (34 patients, 12.5%), with higher prevalence of A (29 patients, 17.3%) and C (11 patients, 7.3%). These findings suggest that mutant alleles, especially C, may reduce treatment efficacy. Notably, the NET rs5569 allele C has not been previously reported in the Indian population.Image 1:

This study suggests that while SNP rs36029 (A/G) showed no association with treatment response, it was significantly linked to memory loss. In contrast, SNP rs5529 (G/A/C) indicated that mutant alleles, particularly allele C—reported for the first time in the Indian population—may contribute to reduced antidepressant efficacy. Studies with larger samples are required to find out the genetic basis of antidepressant response in Indian patients.

None Declared

Depression often shows suboptimal outcomes with antidepressants, with ~66% response and ~37% remission after 6 weeks of treatment (MDD-1 India study). Renin–angiotensin–aldosterone system (RAAS) has been implicated in mood regulation through its effects on neuroplasticity, inflammation, and stress. While ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely prescribed for cardiovascular disease, their influence on antidepressant response and RAAS-related mechanisms remains underexplored.

To evaluate influence of ACEI/ARBs on antidepressant treatment response and correlate them with RAAS and depression related biomarkers.

This prospective observational study included patients with depression who were going to receive antidepressants for 6 weeks. They were divided into two groups: a. AD group: only antidepressants, b. AD+ACEI/ARBs group: antidepressants with ongoing ACEI/ARBs treatment for ≥ 3 months. Depression severity was assessed using Hamilton Depression Rating Scale (HDRS-17) at baseline and 6 weeks. Serum biomarkers (ACE, Ang II, Ang 1–7, renin, BDNF, cortisol) were quantified by ELISA, and gene expression (ACE, AT1R, AT2R, MasR) was analysed in peripheral blood by qRT-PCR. Safety of medications was evaluated through routine laboratory tests.

This study included 186 patients with depression (AD group: n=102; AD+ACEI/ARB group: n=64) and 20 healthy controls. Reduction in HDRS-17 score was greater within the AD+ACEI/ARB group (22.19 ± 7.15 to 10.61 ± 4.00) compared with AD group (21.97 ± 7.54 to 13.24 ± 6.50; p=0.001). Responder rate (≥ 50% reduction in HDRS score from baseline) was higher in AD+ACEI/ARBs (p=0.001) compared to AD group. At baseline AD+ACEI/ARB group had significantly lower serum ACE (p=0.022) compared to AD group. At 6 weeks of follow-up there was significant reduction in Ang II level (p = 0.002) in AD+ACEI/ARBs group compared to AD group. At baseline gene expression analysis showed upregulation of MasR (p = 0.022) and downregulation of ACE (p = 0.049) in the AD+ACEI/ARB group (with ≥ 3 months ACEI/ARB treatment) vs AD group. However, at follow-up there was no significant change among AD vs AD+ACEI/ARBs group in serum Ang 1–7, renin, BDNF, cortisol levels, and gene expression of AT1 and AT2 receptors.

Adjunctive ACEI/ARB therapy improves antidepressant treatment response, which may be ascribed to the modification of RAAS-related biomarkers. This was reflected through reduction in serum ACE and Ang II levels, downregulation of ACE and upregulation of MasR expression.

None Declared

The glutamatergic system is implicated in the pathogenesis of Treatment Resistant Depression (TRD), evidenced by the efficacy of ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist. This hypothesis suggests that NMDAR inhibition promotes glutamate release via suppression of NMDAR GABAergic interneurons (1). Studies report reduced plasmatic Gamma AminoButiric Acid (pGABA) (2) and altered plasmatic glutamate (pGlu) levels in depressed patients vs. healthy controls (HC) (3). Single nucleotide polymorphisms (SNPs) in the GRIN2B gene, encoding the NMDAR 2B subunit (rs1806201, rs890, rs1805502) have been associated with TRD (4).

1. To evaluate the distribution of GRIN2B haplotypes formed by these SNPs (rs1806201-rs890-rs1805502) in TRD and HC. 2. To analyze the relationship between pGABA or pGlu levels and haplotypes in all participants as well as differences by diagnosis.

38 TRD patients (non-responders to 3 different antidepressants including potentiation strategies) prior to esketamine initiation and 55 HCs were recruited. pGABA and pGLu levels were analysed by HPLC. Haplotypes were inferred using PLINK toolset. Associations with diagnosis were assessed by PLINK toolset and Fisher’s test. General Linear models (GLM) were used to evaluate haplotype effects on pGABA or pGlu levels in all participants as well as differences by diagnosis, considering age and sex were covariates.

No differences in GRIN2B haplotype distribution between TRD and HC were observed. In GLM analysis, only ACG haplotype (rs1806201-rs890-rs1805502) showed effect on pGABA (Wald’s X2 = 11.77, df:5 p = 0.038). While no overall association was found between AGC-haplotype presence and pGABA levels (B = 0.153, p = 0.166), a diagnosis-haplotype interaction was observed (B = -0.110, p = 0.033). Among TRD patients, AGC carriers had higher pGABA levels than non-AGC carriers, whereas no difference was observed in HCs. Moreover, TRD patients had lower pGABA levels than HCs (B = 0.125, p = 0.006) and pGABA levels increase with age in the study population (B = 0.002, p = 0.043). Sex had no effect. In pGlu no relevant findings were observed

While GRIN2B haplotypes seemed to be not associated with TRD diagnosis, the pGABA levels are related to TRD and are influenced by ACG-haplotype in TRD. Our findings suggest a potential role of the AGC-haplotype (rs1806201-rs890-rs1805502) modulating pGABA levels among TRD patients. These results could improve treatment selection in these patients. Nonetheless, given our limited sample size, larger samples are necessary to confirm these results.

1. Zanos P, Gould TD. Mol Psychiatry. 2018;23(4):801-11.

2. Gammoh O, et al. XCLI J. 2024 Jan 4;23:62–78.

3. Romeo B, et al. J Psychiatry Neurosci JPN. 2018;43(1):58-66.

4. Zhang C, et al. Psychopharmacology. 2014; 231: 685-693.

Supported by the Basque Government Health Department, 2023111045

None Declared

Multiple clinician-rated and self-report measures are widely used to assess depression symptom severity. (Ma et al., 2021; Uher et al., 2012) show moderate to strong correlations, but also systematic differences. The extent to which these measures can be used interchangeably in clinical practice remains debated.

To evaluate the degree of agreement between commonly used clinician-rated (Montgomery–Åsberg Depression Rating Scale [MADRS], Hamilton Depression Rating Scale [HDRS-17]) and self-report (Patient Health Questionnaire-9 [PHQ-9], Beck Depression Inventory-II [BDI-II]) depression symptom severity measures in a clinical sample of patients with major depressive disorder, and to explore whether self-report instruments systematically differ from clinician ratings across severity levels.

Data was analyzed from 108 patients with major depressive disorder who participated in The DiSCoVeR Trial: ‘Examining the synergistic effects of a cognitive control videogame and a self-administered non-invasive brain stimulation on alleviating depression’. At screening and baseline assesments they completed both clinician-rated scales (MADRS, HDRS-17) and self-report scales (PHQ-9, BDI-II). Pearson correlations were computed among measures, and agreement patterns were visualized with scatterplots.

All measures were significantly correlated (p < .001). Clinician-rated scales correlated moderately with each other (MADRS–HDRS-17: r = 0.59). Self-reported scales showed the strongest association (PHQ-9–BDI-II: r = 0.66). Cross-method correlations were moderate (r = 0.38–0.55), with stronger alignment for MADRS–PHQ-9 (r = 0.55) than for HDRS-17–BDI-II (r = 0.38). Scatterplots revealed variability: patients with identical clinician ratings reported a wide range of self-reported severity. Visual inspection suggested that self-report scores tended to be higher than clinician ratings.

Clinician and self-report depression measures are moderately correlated but not interchangeable. Self-report instruments appear to capture broader variance in symptom perception, while clinician scales show greater consistency with each other. These findings highlight the importance of integrating both perspectives in clinical assessment and research.

None Declared

Depression is a globally prevalent mental health condition and a leading cause of disability, frequently managed within UK primary care. The National Institute for Health and Care Excellence (NICE) NG 222 provides guidance for diagnosing and managing depression. This audit is underscored by the discontinuation of national supervision for depression care, a scarcity of audits on the updated guidelines, and the need to assess adherence in a rural setting where patients may face unique barriers to accessing healthcare.

To assess and improve the adherence to NICE guideline NG222 “Depression in adults: treatment and management” by auditing the management of newly diagnosed depression, focusing on the documentation of suicide risk assessment and first-line treatment for less-severe depression, therefore to improve patient outcomes.

A retrospective audit was conducted at a general practice (GP) in rural England. Patients newly diagnosed with depression between June 2022 and May 2025 were identified using an Egton Medical Information Systems (EMIS) search. For the first criterion, a random sample of 20 patients was reviewed for documented suicidal ideation enquiry. For the second, 11 patients with less-severe depression (PHQ-9<16) were assessed to determine if antidepressants were offered as a first-line treatment without documented patient preference. The data extracted was compared to set standards of 95% and 90% respectively.

The practice did not meet the set standards (Table 1). For criterion 1, 85% (17/20 cases) had documented enquiry of suicidal ideation, falling short of the 95% standard (Figure 1). For criterion 2, adherence was 81.8% (9/11 cases), below the 90% standard for offering non-pharmacological treatment first for less-severe depression (Figure 2).Table 1.

Results

This audit reveals that adherence to NICE NG222 guidelines for depression management was suboptimal, highlighting a significant gap between guidance and practice. Contributing factors may include challenges in remote consultations, inconsistent documentation, and long waiting times for psychological services. While the study’s findings are limited by a small sample size from a single practice and a retrospective design, the identified pitfalls point to areas for improvement. To address this, targeted interventions were proposed: implementing mandatory EMIS prompts and templates to standardise documentation, alongside specific staff training on guideline adherence and shared decision-making. These practical steps aim to improve care and patient safety, with a re-audit planned in 12 months to evaluate their impact.

None Declared

Treatment-resistant depression (TRD) is a severe condition associated with high suicide risk and limited response to conventional antidepressants. Intranasal esketamine has shown rapid efficacy in reducing depressive symptoms and suicidal ideation.

This observational study assessed the real-world effectiveness of esketamine in reducing suicidal ideation, self-harm behaviors, and depressive symptoms in TRD patients, with a focus on potential gender differences in treatment response.

We retrospectively analyzed the clinical records of 26 adults with TRD treated with intranasal esketamine at a specialized outpatient service between January 2023 and October 2024. Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), while suicidal ideation and behavior were evaluated with the Columbia Suicide Severity Rating Scale (C-SSRS). Assessments were performed at baseline, week 2, and week 4. Gender-based response patterns were also analyzed.

Esketamine treatment resulted in significant reductions in suicidal ideation (C-SSRS: t = 12.36; p<.001) and depressive symptoms (MADRS: t = 10.87; p<.001) within four weeks. Non-suicidal self-injury decreased more rapidly in female patients (t = 2.71; p = 0.01), whereas male patients exhibited a slower but significant improvement in suicidal behaviors. A significant correlation was observed between reductions in depressive symptoms and suicidal ideation (τb = 0.419; p = 0.002), suggesting a close interaction between these domains.

Esketamine demonstrated rapid effectiveness in reducing suicidality and depressive symptoms in TRD patients in a real-world setting. The observed gender-specific patterns in response highlight the need for personalized treatment approaches. Larger, prospective studies are warranted to confirm these findings and explore underlying mechanisms.

None Declared

The presence of a bidirectional relationship between low folate and depression has long been demonstrated. Folate deficiency has been shown to be associated with worse depressive symptoms, worse outcomes of treatment, and increased chance of relapse. Conversely, patients with depression have been shown to be more likely to have a lower than normal folate. The idea of providing folate supplementation as an adjuvant therapy for depression has been suggested, even discounting the physical health benefits of folate replacement in deficiency. In September 2015, it was published that 14.7% of adults in the UK have a serum folate lower than ~4.5ug/L (Buttriss, J.L. Nutrition Bulletin 2015; 40(3),153–157.), while staff at our service noted anecdotally that prevalence seemed to be higher in our patient population.

To assess the proportion of the patients within a secondary care adult mental health service that have a folate deficiency, compare this to other measures of diet to review whether this is as a result of dietary deficiencies, and to assess whether there is an association between a diagnosis of depression, and a decreased folate level, within our patient population.

Data was manually collected via the electronic records of patients included (all patients aged 18-65 seen in the service physical health clinic between 20/09/24 and 25/04/25 who had blood haematinics taken and a valid folate level result. Their blood tests were recorded, including folate, B12, sodium, potassium, and ferritin). Their letters and records were searched to collect the mental health diagnoses of each patient.

In our patient population, we found that 37% of our patients had a folate deficiency, and a further 10% had a borderline deficiency (defined as <3.0μg/L and <4.0μg/L respectively, n=90). Mean serum folate was 5.91μg/L. There was no association found between folate deficiency and deficiencies of sodium, potassium, or vitamin B12. Pearson’s Rank Correlation Coefficient between folate levels and ferritin levels returned a p value of -0.05. Mean folate in patients with depression was 5.55μg/L against 6.23μg/L for patients without depression. Folate levels in patients with and without a depression diagnosis returned a point biserial correlation one-tailed p value of 0.31.

Despite a lack of data on folate deficiency prevalence and average folate levels in the UK and globally, as well as inconsistent use of methods or units to measure folate levels in existing data, these results suggest a higher prevalence of folate deficiency within our patient population. There is no suggestion from this data that this higher prevalence is due to overall malnutrition. Finally, there is a weak to moderate correlation between depression and lower serum folate levels, consistent with the observed difference in group means, and in line with some of the previous literature.

None Declared

Postpartum depression is a significant mental health disorder that can have profound and detrimental effects on both the mother and child. Early intervention, facilitated by a comprehensive understanding of the risk factors associated with this condition, is crucial for mitigating the onset of postpartum depressive symptoms.

The aim of this study was to investigate the effect of time perspective and circadian rhythm disturbances on postpartum depressive symptoms.

Participants were 126 women. They were examined in the first trimester of pregnancy and during the first 3 months after delivery. At each stage, the women completed questionnaires—the Zimbardo Time Perspective Inventory, the Dark Future Scale, the Biological Rhythms Interview for Assessment in Neuropsychiatry, and the Edinburgh Postpartum Depression Scale. The participants also wore an actigraphy monitor for 1 week.

The results showed that fatalistic time perspective, subjectively perceived disturbances of circadian rhythms, and a tendency to focus on a negative future in the first trimester were associated with increased symptoms of postpartum depression. Moreover, the association of fatalistic and future negative perspectives with symptoms of postpartum depression was explained by the perception of disturbances of circadian rhythms. There were no significant relationships between objective and self-report measures of circadian rhythm disturbances.

Our findings indicate that minimizing a negative time perspective during the first trimester may contribute to a reduced sense of circadian rhythm disturbances, thereby potentially alleviating postpartum depressive symptoms.

E. Plucińska Grant / Research support from: Malgorzata Sobol reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., M. Sobol Grant / Research support from: Grant / Research support from: Malgorzata Sobol reports financial support was provided by National Science Centre Poland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., A. Błachnio: None Declared, A. Wdowiak: None Declared, I. Hryhorchuk: None Declared, P. Szczepaniak: None Declared, J. Stasiniewicz: None Declared

Ketamine therapy for treatment-resistant depression has a well-established rapid antidepressant effect for acute symptom management. However, there is far less research on the efficacy of long-term maintenance therapy for relapse prevention.

To examine the utility of long-term maintenance therapy with ketamine infusions delivered in a naturalistic treatment setting.

We conducted a retrospective chart review of data from 56 outpatients with treatment-resistant depression receiving intravenous ketamine therapy in Saskatchewan, Canada. Depressive symptoms were assessed before each treatment session with the 17-item Hamilton Depression Rating Scale (HAM-D). The lowest HAM-D score after 3-6 infusions marked the start of maintenance therapy. From this point forward, Kaplan-Meier survival curves were used to estimate the probability of relapse (i.e., HAM-D score increase ≥ 25%, for two consecutive visits) over the next 365 days.

Patients received, on average, 14 maintenance infusions over 253 days. The average number of days between infusions, per patient, was 25.5 (SD = 8.86). Average HAM-D scores at the start of maintenance (M = 17.2, SD = 7.31) did not increase by the final session (M = 16.5, SD = 8.81; t = -0.94, p = .35). After 365 days, the estimated relapse rate was 21-36% depending on the minimum HAM-D score required to define a relapse. The average time to the start of a relapse was approximately 6 months, but individual times ranged from 14 to 328 days.

Long-term maintenance therapy with intravenous ketamine can be continued for up to a year alongside conventional treatment. During this time, roughly a third of patients may experience a persistent depressive symptom exacerbation of unknown clinical significance. More research is needed to determine the nature of these symptom exacerbations.

None Declared

Major depression is one of the leading causes of disability worldwide and is closely associated with physical comorbidities such as cardiometabolic diseases. Comorbidity with type 2 diabetes mellitus (T2DM) is particularly significant. Analysis of the literature shows that adult patients with depression have a 37-60% higher risk of developing T2DM than patients without depressive disorder and that depression in people with T2DM is associated with a more chronic course and a higher frequency of relapses. Insulin resistance (IR), the pathophysiological mechanism underlying T2DM, has been found to be associated with the severity of depressive symptoms in individuals with major depressive episodes. To date, no study has investigated whether the presence of IR/T2DM is associated with a poorer response to psychopharmacological treatment.

The aim of the study, therefore, was to identify the impact of IR/DM2 on the response to drug therapy for major depression.

Patients diagnosed with current major depressive episode not undergoing drug treatment with antidepressants were recruited, and the presence of IR/DM2 was assessed based on HOMA index values. The prospective study lasted 6 months, and all patients recruited in the cross-sectional study were offered SSRI antidepressant therapy. The change in depressive symptoms was assessed after 4, 8, 12, and 18 weeks of drug therapy using the Montgomery Asberg Depression Rating Scale (MADRS). In order to assess the remission rate (MADRS score < 10), Cox regression was used, including IR, gender, age, and severity of depressive symptoms as covariates.

Fifty patients diagnosed with current major depressive episode were recruited, 28 of whom had IR/DM2. The groups did not differ significantly in terms of age, gender, and severity of depressive symptoms. The median remission time was 12 weeks for the control group and 24 weeks for the IR/DM2 group. The results suggest that the presence of IR/DM2 is associated with a longer remission time in response to first-line drug treatment (p = 0.003).

In accordance with the initial hypothesis, it emerged that the presence of dysmetabolic conditions, represented by IR/DM2, negatively influences the response to antidepressant drug treatment. These results could support the existence of an immuno-metabolic subtype of major depression, related to the presence of IR/DM2.

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Forced migration is a traumatic experience that heightens vulnerability to depression, with refugee women being particularly susceptible due to multiple stressors. Psychiatric assessment in this population is often constrained by language and cultural barriers, underscoring the need for accessible diagnostic tools. Voice analysis offers a promising approach, as depression is associated with measurable changes in acoustic features such as pitch, intensity, and timing.

To evaluate whether acoustic analysis of free speech can distinguish depressed refugee women from healthy controls, and to explore the potential of voice-based models as tools for mental health assessment of migrants. This pilot study also aimed to generate early evidence to guide future large-scale and validated research.

Thirty-second free speech samples were recorded from 72 Arabic-speaking refugee women, including 31 with depression and 41 healthy controls, all aged 18–65 years and not using psychiatric medication. Recordings were acquired at 16 kHz and pre-processed with silence removal and data augmentation. The acoustic parameters included energy measures, spectral features (spectral centroid, bandwidth, roll-off, flatness, contrast), prosodic markers (pitch, voiced frame ratio, tempo), Mel-Frequency Cepstral Coefficients with derivatives, and chroma features. High-level embeddings were obtained using YAMNet and combined with acoustic features through feature-level fusion. Classification was conducted using support vector machines with radial basis kernel and XGBoost classifiers. Model performance was assessed with 10-fold cross-validation, reporting accuracy, recall, precision, F1 score, ROC-AUC, and precision–recall metrics.

The ensemble model achieved an accuracy of 0.594 (±0.174), precision of 0.618 (±0.135), recall of 0.755 (±0.204), and F1 score of 0.674 (±0.149). The overall discrimination performance was reflected by an ROC-AUC of 0.599 (±0.195) and an average precision of 0.726 (±0.127), based on 10-fold cross-validation.

This pilot study focuses on Arabic-speaking refugee women, a population that is difficult to reach and relatively underrepresented in mental health research, and uses short free speech samples for the detection of depression. The findings highlight the feasibility and potential of voice-based assessment, which is non-invasive and scalable and can potentially overcome cultural and linguistic barriers inherent to traditional approaches. Nonetheless, our findings are preliminary, and larger, externally validated datasets, potentially incorporating multimodal features, are required prior to any clinical application.

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The role of dissociation in mediating antidepressant response to intranasal esketamine remains debated. While dissociative experiences are often observed during treatment, their predictive value for clinical outcomes is uncertain.

We aimed to assess whether (i) baseline dissociative traits (DES-II) and (ii) early changes in dissociation (ΔDES T0→T2) predict short-term antidepressant response, and to explore whether dissociation mediates depressive symptom improvement across 6 months of follow-up.

This multicenter naturalistic cohort included 31 patients with treatment-resistant depression (mean age 44.7±11.6) treated at academic community clinics in Pavia and Milan. Clinical assessments included MADRS at baseline (T0), 2 weeks (T1), 1 month (T2), 2 months (T3), 3 months (T4), and 6 months (T5) (Montgomery & Åsberg, Br J Psychiatry 1979). Dissociation was measured with DES-II at T0 and T2 (Carlson & Putnam, Dissociation 1993). Outcomes: % MADRS change and responder status (≥50% reduction). Predictors: DES-II at baseline and ΔDES T0→T2. Covariates: baseline MADRS, age, RMET (Baron-Cohen et al., J Child Psychol Psychiatry 2001), Psychache . Analyses included linear/logistic regressions and exploratory mediation (Preacher & Hayes, Behav Res Methods 2008).

Mean MADRS decreased from 31.9±7.9 to 16.7±9.6 at T2 (−47%, responders 48%). Baseline DES-II (mean 0.185±0.12) showed no independent association with response (OR 0.18; 95%CI 0.00–15.5; p = 0.38). ΔDES T0→T2 did not predict response (OR 0.01; 95%CI 0.00–80.5; p = 0.36) nor % improvement (β = 12.7; p = 0.33). Mediation analysis revealed no significant indirect effect (a*b ≈ 10.7%; 95%CI −21.7–79.9). By DES tertiles, % improvement was comparable (Low 42.6%; Mid 51.0%; High 46.5%). Longitudinal follow-up (T1–T5) confirmed sustained MADRS reduction independent of dissociation. (Figure 1 Madrs reduction across timepoints, Figure 2 %madrs improvement by baseline DES, Figure 3 mediation model)Image 1:

In this real-world cohort, dissociative traits and early changes in dissociation did not predict or mediate antidepressant response to intranasal esketamine. However, in clinical practice patients frequently report intense dissociative experiences, and psychotherapists describe esketamine as facilitating emotional processing of unelaborated traumatic memories (DeCou et al., Behav Ther 2019). This suggests that standard trait-based measures such as DES-II may introduce bias and fail to capture clinically meaningful dissociative phenomena. Future studies should employ session-level state measures (e.g., CADSS, ASC-5), cumulative dosing parameters, and longitudinal mixed-effects models to disentangle trait versus state contributions and clarify the therapeutic relevance of dissociation.

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Long-term treatment is crucial for achieving favorable outcomes in mood disorders. However, the prolonged treatment process can be stressful, and the ways in which patients cope with stress may influence whether they adhere to or discontinue treatment.

This study aimed to investigate the associations between stress-coping strategies and treatment discontinuation in patients with mood disorders.

A total of 321 patients diagnosed with mood disorders were included. Dropout rates were estimated at 1, 2, and 3 years. The associations between stress-coping strategies and treatment discontinuation were analyzed using a Cox regression model.

The cumulative discontinuation rates were 31.2%, 40.5%, and 47.0% at 1, 2, and 3 years, respectively. Younger age (p = 0.043), emotional coping (p = 0.020), and compulsive coping behaviors (p = 0.043) were significantly associated with treatment discontinuation.

Despite the clinical importance of sustained treatment in mood disorders, nearly half of patients discontinued care within three years. The findings suggest that specific stress-coping strategies may contribute to treatment discontinuation, and that addressing maladaptive coping behaviors could improve adherence and long-term treatment outcomes.

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Major depressive disorder (MDD) is one of the most prevalent psychiatric conditions worldwide and is strongly associated with early adverse experiences. While the impact of childhood abuse has been extensively studied, the specific contribution of neglect, encompassing physical, emotional, and unspecified subtypes, has historically received less attention. Given its potential to disrupt attachment and emotion regulation, quantifying its association with MDD is crucial.

This study aimed to investigate the association between childhood neglect and MDD by estimating pooled Odds Ratios (ORs) for unspecified, physical, and emotional neglect. A secondary objective was to examine moderators of these associations through meta-regression analyses.

Following PRISMA guidelines, PubMed, Scopus, and Web of Science were systematically searched in September 2024. Eligible studies included adults with a diagnosis of MDD and documented exposure to childhood neglect assessed with validated instruments.

Random-effects model based on the inverse variance method was applied to calculate pooled ORs and between-study heterogeneity was quantified using Cochran’s Q and I² statistics. Meta-regression models were performed to explore potential moderators influencing the outcomes across studies.

Twenty-two studies were included. Childhood neglect was significantly associated with MDD across all subtypes: unspecified neglect (OR = 4.14, 95% CI [1.73–9.89]; I² = 67.7%, p = 0.015), emotional neglect (OR = 3.71, 95% CI [2.33–5.88]; I² = 85.1%, p < 0.001), and physical neglect (OR = 3.30, 95% CI [2.22–4.91]; I² = 79.7%, p < 0.001). High heterogeneity was observed, particularly for emotional and physical neglect, reflecting variability across studies.

These results are consistent with previous meta-analyses reporting strong associations between neglect and depression (Mandelli et al. Eur Psychiatry 2015; 30:665–680; Nelson et al. Br J Psychiatry 2017; 210:96–104; Norman et al. PLoS Med 2012; 9:e1001349), although the ORs in the present study were higher. Prior evidence indicates that neglect, especially emotional neglect, is more strongly linked to depressive outcomes than other forms of maltreatment (Humphreys et al. Child Abuse Negl 2020; 102:104361; Infurna et al. J Affect Disord 2016; 190:47–55).

The consistency and strength of these associations support the role of childhood neglect as a key vulnerability factor for MDD and underscore the importance of systematic screening and trauma-informed therapeutic strategies in clinical practice.

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Treatment-resistant depression (TRD) poses a significant clinical challenge, with limited evidence guiding long-term pharmacological strategies. Esketamine, a glutamatergic modulator, has demonstrated short-term efficacy in TRD, but data on its extended use in real-world settings remains scarce

This study aimed to evaluate the long-term effectiveness and tolerability of intranasal esketamine in adults with TRD over more than 100 treatment sessions.

We conducted a retrospective, single-arm pre-post study of 20 patients with TRD at a private psychiatric clinic in the United Arab Emirates. All participants received ≥100 sessions of intranasal esketamine alongside oral antidepressants. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scales. Tolerability was monitored through blood pressure, sedation, dissociation, urinary symptoms, and psychiatric side effects.

After an average of 129 esketamine sessions (mean duration 2.5 years), PHQ-9 and GAD-7 scores significantly decreased (p<0.001). 85% of patients improved in depressive severity, with 25% achieving remission. 65% improved in anxiety severity, and 20% reached remission. Esketamine was generally well-tolerated; side effects were mild and transient, with no serious adverse events. No clinical or demographic factors significantly predicted response.

Intranasal esketamine demonstrated sustained effectiveness and acceptable tolerability in a real-world TRD cohort with extensive psychiatric comorbidity. These findings support its long-term use in complex clinical populations and underscore the need for further prospective, multi-site studies.

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Post-stroke depression, a prevalent and persistent neuropsychiatric complication, adversely affects stroke recovery outcomes. Almost half of stroke survivors experience social isolation. Yet the contribution of social isolation to post- stroke depression development remains unclear.

We investigate the association between social isolation and incident depression in stroke survivors.

We included 7,267 UK Biobank participants with prior stroke (mean±SD age =60.5 ±6.9 years, 55.6% male) without baseline depression. Degree of social isolation was assessed with three questions: 1) “Including yourself, how many people are living together in your household? (Include those who usually live in the house such as students living away from home during term, partners in the armed forces, or professions such as pilots)” (1 point for living alone); 2) “How often do you visit friends or family or have them visit you?” (1 point for answering rarely, never, or monthly); and 3) “Which of the following [leisure/social activities] do you engage in once a week or more often? You may select more than one” (1 point for none of the above). Incident post-stroke depression was ascertained from hospital records and death registries. We used Cox cause-specific hazards models to estimate hazard ratios (HRs) adjusted for demographics, socioeconomic status, comorbidities, health behaviours and physiological covariates. We also performed a relative importance analysis to rank risk factors. We calculated the Percentage of Excess Risk Mediated (PERM) by grouping explanatory covariates into categories, such as medication, behaviors, and comorbidities.

Over a median 10.2-year follow-up, 591 stroke survivors developed depression. Compared with the least isolated participants, the most isolated group showed a significantly higher risk of depression (HR: 1.35, 95% CI: 1.07-1.70). In a risk-factor ranking, social isolation ranks higher than traditional risk factors, including hypertension and obesity, as a predictor of post-stroke depression. Health behaviors mediated the association between social isolation and elevated depression risk most strongly, accounting for 32-44% (PERM) of the effect. This mediating effect was significantly greater than that explained by medication, comorbidities, and other covariates.

In this population-based cohort study of UK Biobank participants with stroke, social isolation was significantly associated with an increased risk of post-stroke depression. These findings suggest that interventions targeting social connectivity may improve clinical outcomes in stroke survivors.

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Postpartum depression has emerged as one of the most socially significant medical concerns, exerting a profound impact on maternal health, family relations, and child development (McNab et al. BMC Pregnancy and Childbirth 2022, 22(1):342; Slomian et al., Women’s Health 2019, 15:55). Exploring associations between the prevalence of depressive symptoms and various clinical and sociodemographic factors may provide valuable insights for the development of targeted screening strategies, thereby ensuring appropriate care and support for women in fulfilling their role as mothers.

Our study aimed to provide the first systematic assessment of postpartum depressive symptom prevalence, associated sociodemographic and clinical characteristics of women in outpatient care in Latvia.

All women aged 18 years and older who consecutively attended the country’s largest Riga Maternity Hospital’s outpatient unit 4-6 weeks postpartum were screened with the Patient Health Questionnaire-9 (PHQ-9). Based on sensitivity and specificity analysis, a cut-off score of 8 was identified as the optimal threshold for the PHQ-9. Sociodemographic data were collected via self-administered questionnaires; clinical data were extracted from medical records. Group differences in PHQ-9 score distributions were analyzed using chi-square tests.

Over one year, 272 women aged 18-49 (mean 30.66 ± 5.59) were assessed. Depressive symptoms (PHQ-9 ≥8) were observed in 18.01%. Birth complications were significantly associated with higher PHQ-9 scores (p=0.031), and self-reported sleep problems showed a strong association (p=0.010). Mode of delivery (p=0.184), infant health problems (p=0.172), difficult infant temperament (p=0.124), and stressful events during pregnancy (p=0.100) showed non-significant trends. No significant differences were observed with respect to age, residence, ethnicity, education, marital and employment status, income, or other clinical factors (all p>0.05).

Postpartum depressive symptoms were present in nearly one-fifth of women, underscoring the relevance of mental health in perinatal care. Birth complications and sleep problems emerged as significant associated factors, while other perinatal and psychosocial variables showed non-significant trends. These findings underscore the importance of systematic screening and early identification of women at risk, as well as the need for further studies to elucidate causal pathways and inform effective prevention and intervention strategies.

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