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

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

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

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

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

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

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

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

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

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 (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.

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

Current antidepressants (SSRIs/SNRIs) face limitations including delayed onset (4–6 weeks) and modest efficacy (~50% response rates), while serotonergic psychedelics show rapid antidepressant potential via 5-HT2A agonism and synaptic plasticity but are hindered by hallucinogenic activity and 5-HT2B-mediated cardiotoxicity.

To address these challenges, we characterize HJ-006, a novel synaptogenic agent, designed to promote neuroplasticity without hallucinogenic or safety liabilities, and antidepressant efficacy.

Efficacy was evaluated with head twitch response (HTR) in mice (predictive of hallucinogenic activity), and established in vivo models (Forced Swim Test [FST], Tail Suspension Test [TST], Sucrose Preference Test [SPT] in Chronic Unpredictable Mild Stress [CUMS] and corticosterone-induced depression). Safety was evaluated via Conditioned Place Preference (CPP), neurite outgrowth/synaptogenesis assays, multielectrode array (MEA) recordings in CORT-damaged hippocampal neurons, cardiovascular monitoring (non-human primate ECG), and pharmacokinetic profiling.

HJ-006 is an orally active, brain penetrant, small molecule. In vitro, HJ-006 showed significant effects on neurite-outgrowth and synaptogenesis in primary cultures of rat cortical neurons. It demonstrated rapid (30 min post-single dose) FST antidepressant effects in corticosterone-induced depression and reversed CUMS-induced deficits in FST, TST, and SPT, with efficacy sustained ≥8 days, with no hallucinogenic behavior (HTR-negative). Safety profiles included no CPP rewarding effects, enhanced dendritogenesis/synaptogenesis in cortical neurons, rescued CORT-impaired hippocampal activity (30 nM, 15 min post-treatment), 5-HT2B antagonist activity (Ki = 2.18 nM, IC50 = 272.8 nM), favorable brain penetration, CYP3A4 metabolism, no cardiovascular signals in primates, and a 40× safety margin in 14-day toxicity studies.

HJ-006 is a first-in-class non-hallucinogenic neuroplastogen with rapid, sustained antidepressant-like efficacy and improved safety, supporting its potential as a transformative depression treatment.

None Declared

Depression is a major contributor to global disability, with profound personal, social, and economic costs. In Singapore, while cross-sectional studies have provided valuable insights into the prevalence of depression, data on the long-term trajectory, outcomes, and determinants of depression remain scarce.

This protocol describes the PREDICT study, which seeks to address this gap by launching the nation’s first longitudinal cohort dedicated to major depressive disorder (MDD) and subsyndromal depression (SD). The objectives include examining disease prognosis, relapse, comorbidity, suicidality, treatment response, healthcare utilization, and mortality, identifying biopsychosocial determinants, quantifying economic burden, and understanding progression from SD to MDD.

The study will recruit 3,201 participants aged 18–75 years, including those with first-episode depression, those with a longer history of depression, individuals with SD, and matched controls without psychiatric illness. Recruitment will be conducted at primary and tertiary care settings as well as from population cohorts. Participants will undergo comprehensive baseline and annual follow-up assessments for up to five years, capturing socio-demographic, psychosocial, physical, and biological data.

We hypothesize that sociocultural factors, such as accessible mental healthcare, social support, strong intergenerational relationships may confer protective effects leading to better outcomes compared with international cohorts, and that individuals with SD will incur higher resource use, poorer quality of life, and increased risk of progression to major depressive disorder as compared to controls.

Findings will provide the first comprehensive longitudinal evidence on depression trajectories in Singapore. Results will guide clinical protocols, inform national mental health strategies (including Singapore’s Healthier SG initiative), and strengthen early detection and management of depression at the population level.

None Declared

Aggressive behaviours affect approximately two-thirds of autistic individuals, with significant consequences for their own quality of life and that of their families. Risperidone is among the most frequently prescribed medications for managing aggression in autism. However, prior systematic reviews have pooled heterogeneous study designs, limiting the strength of their conclusions.

This systematic review and meta-analysis synthesises evidence from randomised controlled trials (RCTs) on risperidone’s efficacy in reducing aggression in autism and its safety profile.

Five databases (Embase, Ovid Medline, PsycInfo, Global Health, and PubMed) were systematically searched from inception to 2025. Eligible studies were randomised controlled trials (RCTs) assessing risperidone for the treatment of aggression in autistic children, adolescents, or adults. Risk of bias was evaluated using the Cochrane RoB tool. Random-effects models with standardised mean differences (SMDs) were applied to compare risperidone with placebo.

Thirteen studies met the inclusion criteria for the systematic review; eight RCTs (N = 445; age range 2.5–56 years) were included in the meta-analysis. Risperidone was significantly more effective than placebo in reducing aggression, with a large effect size (SMD = –0.96, 95% CI [–1.37, –0.55], Z = 4.62, p < .00001). Substantial heterogeneity was observed (I² = 73%). The most frequently reported adverse effects were weight gain, increased appetite, sedation, somnolence, and fatigue.

Risperidone reduces aggression in autistic individuals but is associated with adverse side effects that restrict its long-term clinical use. Further research is needed to evaluate safer pharmacological alternatives and to develop more targeted treatments for aggression in autism.

None Declared

Childhood-Onset Schizophrenia Spectrum Disorder (COSS) represent a very early-onset subtype of schizophrenia spectrum disorders, typically manifesting before age 13. Although interest in COSS has grown in recent years, studies exploring its clinical characteristics remain scarce.

This study aimed to analyze clinical differences within the COSS group based on the presence of psychiatric or neurodevelopmental comorbidities to delineate distinct psychopathological profiles of childhood psychosis. We hypothesized that COSS presents variable symptomatology depending on the presence of comorbid psychiatric disorders, neurodevelopmental disorders, or the absence of comorbidities.

Seventy children diagnosed with COSS were selected at the onset of psychotic symptoms from admission to a specialized very early-onset psychosis clinical service. Participants were assessed and divided into three subgroups based on comorbidity profiles: COSS with neurodevelopment disorder comorbidity, COSS with psychiatric disorder comorbidity, COSS without psychiatric or neurodevelopmental disorder comorbidities. Psychotic symptoms were indexed using the Structured Interview for Psychosis-Risk Syndrome.

The Statistical analysis of the subgroups revealed that COSS with neurodevelopmental disorder comorbidity exhibited a distinct profile, characterized by earlier onset of psychotic symptoms, lower intelligence quotient, greater disorganization symptoms, and fewer negative symptoms compared to COSS with psychiatric disorder comorbidity. COSS with psychiatric disorder comorbidity and COSS without comorbidities showed more similarities with each other than with COSS with neurodevelopmental disorder comorbidity, suggesting a significant influence of neurodevelopmental comorbidities on clinical presentation.Image 1:

Identifying specific psychopatological profiles within COSS may enhance personalized treatment approaches for COSS, as well as for early-onset and adult-onset schizophrenia spectrum disorders.

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Although both nonsuicidal self-injury (NSSI) and cyberbullying (CB) are very common among adolescents, there are only a few studies examining the relationship between the two phenomena.

The aim of our study was to explore the relationship between CB and NSSI, and to examine the potential mediating effects of anxiety and depression.

119 Hungarian adolescents (70% female, 13–18-year-olds) were involved in the study. A self-report questionnaire about CB, the Inventory of Statements About Self-injury, and the Mini International Neuropsychiatric Interview – Kid were administered. Regression and network analysis were conducted to analyze the interrelationships among CB, NSSI, and anxiety/depression.

The prevalence of NSSI was significantly higher among those who were involved in CB, compared to those who were not, χ2(1) = 5.62, p = 0.02. CB and NSSI were mediated by anxiety, and anxiety disorder was directly related to NSSI. Conversely, depression was not directly related to CB, only to anxiety. Victimization was positively related to anxiety, which, in turn, was positively associated with NSSI.

Our results draw attention to the importance of focusing on comorbid anxiety disorders and to both those who are involved in CB and those who witness CB in NSSI prevention strategies.

None Declared

The prescription of antipsychotics in children and adolescents has increased significantly over the past decade, primarily for managing challenging behaviour and irritability in neurodevelopmental conditions such as ADHD and ASD (Radojčić et al. Lancet Psychiatry 2023; 10 119–128). Risperidone and aripiprazole are commonly used, but these drugs carry the risk of serious side-effects, particularly metabolic, cardiovascular, and hormonal. The NICE Quality Standard (QS102) recommends regular biochemical monitoring, but compliance with these guidelines in local practice remains unclear.

To evaluate adherence to the NICE-recommended biochemical monitoring protocols for children and adolescents prescribed antipsychotics in Maltese Child and Adolescent Mental Health Services (CAMHS).

A retrospective case-note review of 350 patients attending CAMHS was conducted. One hundred patients prescribed antipsychotics for ≥9 consecutive months were included. Data was extracted from the iCM system to determine whether HbA1c or fasting glucose, lipid profile, and serum prolactin were assessed at baseline, 12 weeks, and 9 months, in line with the NICE Quality Standard.

No patient underwent all recommended monitoring at the specified intervals. Baseline monitoring occurred in 0%, 12-week monitoring in 1%, and 9-month monitoring in 2% of patients. At least two-thirds of the recommended tests were completed at any time point in 28% of cases. Risperidone (56%) and aripiprazole (42%) were the most commonly prescribed agents, with quetiapine (2%) being prescribed for the remainder. The majority of patients were diagnosed with ADHD (47%) or ASD (37%). Regarding biological sex, females accounted for 16% of the sample, while males accounted for 84%.Table 1.

Diagnostic Characteristics of Patients Prescribed Antipsychotics (n = 100)

Biochemical monitoring of antipsychotic use in Maltese CAMHS does not align with international standards. Interventional strategies including the creation of evidence-based protocols, clinician teaching, and integration of monitoring reminders into electronic systems should be considered. Improving surveillance of side-effects, not just biochemical, will strengthen patient safety and the quality of care; however, any overarching reasons why biochemical tests were not monitored should also be considered, including the risk/benefit profile and the potential psychological ramifications of blood-letting in young people. Opportunities exist for further research, including a re-audit in one year, and surveilling the monitoring of all side-effects.

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Suicide is a leading cause of death among adolescents, representing a major global health concern (World Health Organization, 2024). While psychosocial risk factors are widely studied, less is known about the role of cognitive functioning. Evidence indicates that poor cognitive performances, particularly in executive functions (EF) and memory, are linked to suicidal concern (SC)(Burton et al., 2011). Research has shown deficits in attention, cognitive flexibility, working memory and inhibitory control among individuals with SC (Bredemeier & Miller, 2015; Keilp et al., 2013; Richard-Devantoy et al., 2023). However, studies in adolescents using standardized intelligence measures remain limited.

This study aimed to compare cognitive functioning between adolescents with and without SC, examine associations between cognitive indices and suicidal ideation/behaviors and explore the role of cognitive vulnerabilities in risk stratification.

In this cross-sectional study, 261 adolescents aged 12–18 admitted to Child Neuropsychiatry Services in Northern Italy (2020–2024) were included after excluding cases with cognitive impairment (IQ ≤ 70), insufficient knowledge of Italian, or no written consent. SC was assessed with the Columbia-Suicide Severity Rating Scale (C-SSRS), and cognitive functioning with WISC-IV or WAIS-IV. Participants were classified as SC (n = 200) or non-suicidal concern (NSC; n = 61). Independent t-tests compared Wechsler scales indices; Pearson’s correlations examined associations between cognitive scores and C-SSRS dimensions.

Adolescents with SC were more often female and showed poorer social relationships and higher rates of NSSI. Our analysis showed lower total IQ, Working Memory Index (WMI), and Perceptual Reasoning Index (PRI) in the SC group compared to NSC, while no differences emerged in Verbal Comprehension or Processing Speed. Correlational analyses showed that reduced WMI and PRI were consistently linked to greater severity, frequency, and behavioral expression of suicidal ideation and attempts. Total IQ also correlated negatively with several suicidal ideation and behavior subscales.

Adolescents with suicidal concern display distinct cognitive vulnerabilities, particularly in WMI and PRI. These deficits may impair problem-solving, cognitive flexibility, and regulation of intrusive thoughts, thereby increasing vulnerability to suicidal ideation and behaviors. Cognitive screening, combined with psychosocial assessment, may enhance risk stratification and guide early interventions. Bearing in mind these findings, it is essential to view suicidal concern and cognitive vulnerabilities as a bidirectional relationship. Given the cross-sectional design of the study and the possibility that cognitive deficits may also arise because of sustained psychological distress future longitudinal research is needed to clarify directionality and further investigate these associations.

None Declared

Auditory hallucinations are a debilitating manifestation of trauma in children. Voice-hearing is common among youth exposed to multiple traumatic experiences and is associated with cognitive mechanisms that contribute to the persistence of symptoms [1]. These experiences can cause severe distress, disrupt development, and may increase risk of self-harm mediated by hallucinatory symptoms [5]. Children often attempt to manage these experiences through coping strategies such as humming, listening to music, engaging in play, or externalizing the voices into objects or characters—techniques aligned with distraction, self-generated competing stimuli, and externalization described in coping-strategy-enhancement frameworks [2]. While antipsychotic medications remain an option in severe cases [3], creative coping strategies can be integrated into structured trauma-focused therapies [2,4].

This study explores coping mechanisms for trauma-induced hallucinations in children, with emphasis on idiosyncratic strategies such as puppet play, and evaluates psychiatric treatment management including psychopharmacology and trauma-focused psychotherapies.

A clinical and literature review was conducted, drawing on Thomas et al (2014), Adetunji et al (2005), and Reid et al (2024). Findings were contextualized through a case illustration of a 9-year-old girl with trauma-related hallucinations who used puppets to act out and externalize frightening voices.

The patient’s puppet play reflected key CSE principles—distraction, externalization, and normalization—demonstrating how spontaneous coping aligns with structured interventions [2]. Pharmacological evidence supports risperidone when hallucinations remain severe [3]; however, in this case, medication was reserved given her adaptive strategy. Trauma-focused therapies such as TF-CBT and EMDR could incorporate puppet play to facilitate safe narrative reprocessing and emotional regulation [1,4].Image 1:

Children may naturally generate innovative coping strategies for trauma-induced hallucinations. Clinicians should recognize and support these behaviors within a multimodal treatment framework that integrates psychosocial techniques, judicious pharmacotherapy, and trauma-focused psychotherapies.

None Declared