This proof-of-concept study aimed to assess the impact of intranasal esketamine (ESK-IN) in brain volume and neurofilament light chain (sNfL) over 6-months in patients with treatment resistant depression (TDR).

Seven TRD patients received ESK-IN while continuing oral antidepressants. Clinical evaluations were conducted at baseline, 1, 3, and 6 months, with MRI scans and blood samples taken at baseline and 6 months. Brain volume was assessed using VolBrain2 and DSI studio.

Compared to controls, TRD patients initially showed lower volumes (mm3) in key cortical regions such as the insula (p = 0.0156), the frontal lobe (p = 0.0228) the superior parietal lobe (p = 0.0402), both superior (p = 0.0216) and inferior (p = 0.0437) temporal lobes and subcortical regions such as the nucleus accumbens (p = 0.0056), putamen (p = 0.0083), thalamus (p = 0.0102) and the hippocampus (p = 0.0001). Brain volume increased in the frontal cortex (p = 0.0295), the anterior cingulate (p = 0.0496), and hippocampus (p = 0.0015), as well as in the volume and fiber tracts associated with emotional regulation, such as the frontoparahippocampal (p = 0.0156 and p = 0.0313, respectively), the frontoparietal (p = 0.0496 and p = 0.0156, respectively) and the frontal aslant tract after 6 months on treatment with ESK-IN. In parallel, sNfL levels decreased post-treatment, indicating potential neuroprotective effects.

ESK-IN may promote structural changes in regions associated with mood regulation and neuroplasticity, while also reducing neuronal damage in TRD patients.

Suicide represents a significant public health concern. Suicide prevention strategies are shifting toward transdiagnostic perspectives examining interrelated risk factors, but their interrelationships remain unclear. This study investigated relationships between psychopathological dimensions, impulsivity, and childhood maltreatment in individuals with suicidal ideation (SI), comparing those with versus without intention to act using network analysis.

Data were obtained from the Suicide Prevention and Intervention Study project. Participants were categorized into two groups based on their intention to act according to the Columbia Suicide Severity Rating Scale. Psychological symptoms, impulsivity traits, and childhood maltreatment were assessed. Network analysis was performed, and centrality measures were computed.

A total of 1,265 individuals were categorized into the SI without intention to act (n = 345) and SI with intention to act (n = 920) groups. The former showed lower depression and hostility scores, and lower prevalence of major depressive and anxiety disorders. Network analyses revealed that in the SI without intention to act group, obsessive-compulsive symptoms were central, connecting to depression and anxiety, while negatively correlating with non-planning impulsivity. In contrast, the SI with intention to act group showed a more densely interconnected network where emotional abuse served as a bridge between childhood maltreatment and other psychopathological dimensions.

This study identifies symptom interaction patterns between individuals with SI without and with intention to act. Understanding these relationships may improve suicide risk assessment and inform personalized interventions, potentially reducing the transition from ideation to action. Trauma-focused approaches addressing emotional abuse may be especially relevant for individuals at high risk.

Adolescents are at a heightened risk of suicide reattempts following hospital discharge, but few evidence-based interventions exist. This study evaluated the efficacy of the self-awareness of mental health (SAM) program combined with treatment as usual (TAU) versus TAU alone in reducing reattempts among high-risk adolescents.

A randomized clinical trial was conducted across nine Spanish hospitals (January 2021–March 2024) with 261 adolescents (12–17 years) who had attempted suicide within the last 15 days. Participants were assigned to SAM + TAU (n=128) or TAU (n=133), with 12-month follow-up. The primary outcome was suicide reattempts within 12 months; secondary analyses examined time to reattempt and associated risk factors.

After 12-months, no significant differences were found in reattempt rates [22.6% (SAM) versus 27.8% (TAU); OR=0.610, 95%CI (0.321–1.151), p=0.127] or time to reattempt [HR=0.606, 95%CI (0.390–1.021), p=0.060]. In SAM, attentional impulsivity emerged as a significant risk factor [HR=1.126, 95% CI (1.004–1.263), p=0.043], while nonplanning impulsivity was protective [HR=0.878, 95%CI (0.814–0.948), p<0.001]. In TAU, increased suicide risk was linked to suicidal intentionality [HR=1.341, 95%CI (1.009–1.782), p=0.044] and more prior attempts [HR=1.230, 95%CI (1.039–1.457), p=0.016]. Conversely, fewer psychiatric diagnoses emerged as a protective factor [HR=0.821, 95%CI (0.677–0.996), p=0.045].

While no significant differences were found between groups, SAM identified important psychological factors influencing suicide risk. These findings provide a foundation for targeted interventions to prevent reattempts in adolescents.

Prolonged childhood and adolescent loneliness (CAL) is linked to various adverse mental health outcomes, yet its impact on schizophrenia spectrum disorders (SSD) has been understudied. While loneliness is associated with psychosis and worsens symptoms in SSD, few studies have explored the long-term effects of early loneliness on SSD risk. Understanding how CAL interacts with genetic liability to schizophrenia is essential for identification of high-risk individuals.

This study evaluated whether prolonged CAL is associated with increased SSD risk and examined the interaction between CAL and genetic liability for schizophrenia. Gender differences in these associations were also explored.

Data from the European Gene–Environment Interactions in Schizophrenia (EU-GEI) study were analysed, including 1261 individuals with SSD, 1282 unaffected siblings and 1525 healthy controls. CAL was retrospectively assessed for periods before age 12 years and age 12–16 years. Genetic risk was measured using polygenic risk scores for schizophrenia. Logistic regression models and the Relative Excess Risk due to Interaction (RERI) method were used to examine gene–environment interactions, with stratification by gender.

Prolonged CAL was associated with higher odds of SSD (odds ratio [95% CI] = 5.20 [3.85−7.01] for loneliness before age 12; odds ratio [95% CI] = 7.26 [5.63−9.38] for loneliness during adolescence). The interaction between CAL and genetic risk was strongest during adolescence (RERI [95% CI] = 23.46 [10.75−53.53]). Females showed a greater effect (odds ratio [95 %CI] = 10.04 [6.80−14.94]) than males (odds ratio [95% CI] = 5.50 [3.95−7.66]). Incorporating CAL and genetic interaction increased predictive values to 17% for SSD risk − rising to 22.5% in females − compared with 2.6 and 2.8%, respectively, for genetic risk alone.

Prolonged CAL significantly increases SSD risk, particularly in females. The inclusion of CAL alongside genetic risk substantially enhances predictive accuracy. Early identification of CAL could inform preventive strategies, especially in genetically vulnerable populations.

The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.

About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15–20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.

The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort.

Participants (n = 5486) aged 55–75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology.

COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15–40) weeks post-infection [fully adjusted β = 0.65 points, 95% confidence interval (CI) 0.15–1.15; p = 0.011]. This association was particularly prominent in women (β = 1.38 points, 95% CI 0.44–2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13–2.30, p = 0.008).

COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

To describe IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreaks at Galdakao University Hospital between March 2021 to December 2021.

Outbreak report.

Galdakao University Hospital is a tertiary-care hospital in the Basque Country (northern Spain).

All patients with a positive IMP-type carbapenemase producing Pseudomonas aeruginosa (IMP-PA) culture were included in this study, both colonization and infection cases.

An outbreak investigation was conducted, in which molecular epidemiology analysis [pulsed-field gel electrophoresis and whole-genome sequencing (WGS)] and environmental screenings were performed.

Between March and December 2021, 21 cases of IMP-PA were detected in Galdakao University Hospital: 18 infection cases and 3 colonization cases. In total, 4 different pulsotypes were detected belonging to 4 clones according to WGS: ST175 (n = 14), ST633 (n = 3), ST179 (n = 3), and ST348 (n = 1). IMP-13 was detected in most isolates belonging to the ST175 clone and in all ST179 and ST348 clones, whereas IMP-29 was detected in isolates belonging to the ST633 clone. Clinical isolates belonging to the ST175 clone were isolated mainly from patients admitted to the respiratory ward, and isolates belonging to the ST633 clone from patients admitted to the ICU. Two environmental isolates belonging to the ST175 clone were detected in the respiratory ward.

Molecular and genomic epidemiology revealed that there had been 2 independent IMP-PA outbreaks, one of long duration in the respiratory ward and the other more limited in the ICU.

To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms.

An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used.

Spanish older adults with metabolic syndrome (MetS).

A total of 6625 adults aged 55–75 years from the PREDIMED-Plus study with overweight or obesity and MetS.

Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v. Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v. C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v. C1 = (β = 0·70, 95 % CI (0·05, 1·35)).

According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.

A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

There is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.

We analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.

The impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).

The results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.

Data were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.

JTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.

These findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.

First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.

We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.

In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.

The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene–environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.

The Emerald project's focus is on how to strengthen mental health systems in six low- and middle-income countries (LMICs) (Ethiopia, India, Nepal, Nigeria, South Africa and Uganda). This was done by generating evidence and capacity to enhance health system performance in delivering mental healthcare.

A common problem in scaling-up interventions and strengthening mental health programmes in LMICs is how to transfer research evidence, such as the data collected in the Emerald project, into practice.

To describe how core elements of Emerald were implemented and aligned with the ultimate goal of strengthening mental health systems, as well as their short-term impact on practices, policies and programmes in the six partner countries.

We focused on the involvement of policy planners, managers, patients and carers.

Over 5 years of collaboration, the Emerald consortium has provided evidence and tools for the improvement of mental healthcare in the six LMICs involved in the project. We found that the knowledge transfer efforts had an impact on mental health service delivery and policy planning at the sites and countries involved in the project.

This approach may be valid beyond the mental health context, and may be effective for any initiative that aims at implementing evidence-based health policies for health system strengthening.