Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), but initial outcomes can be modest.

To compare SSRI dose optimisation with four alternative second-line strategies in MDD patients unresponsive to an SSRI.

Of 257 participants, 51 were randomised to SSRI dose optimisation (SSRI-Opt), 46 to lithium augmentation (SSRI+Li), 48 to nortriptyline combination (SSRI+NTP), 55 to switch to venlafaxine (VEN) and 57 to problem-solving therapy (SSRI+PST). Primary outcomes were week-6 response/remission rates, assessed by blinded evaluators using the 17-item Hamilton Depression Rating Scale (HDRS-17). Changes in HDRS-17 scores, global improvement and safety outcomes were also explored. EudraCT No. 2007-002130-11.

Alternative second-line strategies led to higher response (28.2% v. 14.3%, odds ratio = 2.36 [95% CI 1.0–5.6], p = 0.05) and remission (16.9% v. 12.2%, odds ratio = 1.46, [95% CI 0.57–3.71], p = 0.27) rates, with greater HDRS-17 score reductions (−2.6 [95% CI −4.9 to −0.4], p = 0.021]) than SSRI-Opt. Significant/marginally significant effects were only observed in both response rates and HDRS-17 decreases for VEN (odds ratio = 2.53 [95% CI 0.94–6.80], p = 0.067; HDRS-17 difference: −2.7 [95% CI −5.5 to 0.0], p = 0.054) and for SSRI+PST (odds ratio = 2.46 [95% CI 0.92 to 6.62], p = 0.074; HDRS-17 difference: −3.1 [95% CI −5.8 to −0.3], p = 0.032). The SSRI+PST group reported the fewest adverse effects, while SSRI+NTP experienced the most (28.1% v. 75%; p < 0.01), largely mild.

Patients with MDD and insufficient response to SSRIs would benefit from any other second-line strategy aside from dose optimisation. With limited statistical power, switching to venlafaxine and adding psychotherapy yielded the most consistent results in the DEPRE'5 study.

One of the most relevant risk factors for suicide is the presence of previous attempts. The symptomatic profile of people who reattempt suicide deserves attention. Network analysis is a promising tool to study this field.

To analyze the symptomatic network of patients who have attempted suicide recently and compare networks of people with several attempts and people with just one at baseline.

1043 adult participants from the Spanish cohort “SURVIVE” were part of this study. Participants were classified into two groups: single attempt group (n = 390) and reattempt group (n = 653). Different network analyses were carried out to study the relationships between suicidal ideation, behavior, psychiatric symptoms, diagnoses, childhood trauma, and impulsivity. A general network and one for each subgroup were estimated.

People with several suicide attempts at baseline scored significantly higher across all clinical scales. The symptomatic networks were equivalent in both groups of patients (p > .05). Although there were no overall differences between the networks, some nodes were more relevant according to group belonging.

People with a history of previous attempts have greater psychiatric symptom severity but the relationships between risk factors show the same structure when compared with the single attempt group. All risk factors deserve attention regardless of the number of attempts, but assessments can be adjusted to better monitor the occurrence of reattempts.

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.

A wide variety of traits is heritable and has genetic loading, including schizophrenia spectrum disorders (SSDs) and its associated neurocognitive features. The genetic architecture of SSDs is polygenic, with the contribution of thousands of single nucleotide polymorphisms of small effect with an estimated SNP-heritability of 24%. The same occurs with neurocognitive phenotypes such as intelligence or educational attainment. Therefore, the method of polygenic risk scores (PRS) is useful in estimating the genetic burden of such traits. Moreover, the use of PRS in a sample of genetically related individuals would allow analyzing the contribution of genetic and environmental factors involved in the development of the disorder and its candidate endophenotypes.

To estimate PRS for schizophrenia, and polygenic scores for intelligence and educational attainment in patients with First Episode Psychosis (FEP), their first-degree relatives (siblings and parents), and a group of healthy controls.

The sample is comprised of 579 participants of the PAFIP-FAMILIAS project in Santander, Spain (133 FEP patients, their 244 first-degree relatives, and 202 healthy controls). All provided sociodemographic information and completed the same neuropsychological battery. Participants’ DNA was extracted from venous blood samples, and genotyping was performed at the Centro Nacional de Investigaciones Oncológicas (CeGen) by the Global Screening Array v.3.0 panel (Illumina). Data quality control, imputation, calculation of PRS, and genetic association analysis are being performed using PLINK, SHAPEIT, IMPUTE2, SPSS and R.

Data analysis is currently in progress, at the quality analysis stage, in collaboration with the Institute of Psychiatric Phenomics and Genomics (IPPG) in Munich, Germany. We expect to find higher PRS for schizophrenia in FEP patients, while their first-degree relatives will potentially show intermediate risk scores between patients and healthy controls. A similar finding is expected regarding intelligence and educational attainment, as FEP patients may show more genetic burden for low intelligence and education.

The estimation of PRS has demonstrated to be valuable in studying complex traits such as schizophrenia. We believe that by applying this method in a family design can provide interesting insights on the development of SSDs and its potential endophenotypes, and potentially useful in their prevention.

None Declared

The evidence on the course of the intelligence quotient (IQ) at the long term in individuals with schizophrenia spectrums disorders is inconclusive.

We aimed to analyse whether IQ improves, declines, or remains stable over 10 years in a sample of patients with First Episode Psychosis (FEP) and healthy controls (HCs).

The FEP patients participated in a Program of First Episode Psychosis in Spain called PAFIP. At baseline, FEP patients provided demographic and clinical data, and completed a neuropsychological assessment that included an estimation of premorbid IQ trough the WAIS vocabulary subtest. At 10-year follow-up, the participants were invited to complete the same evaluation and 10-year IQ was estimated. The group of HCs underwent the same neuropsychological battery at both moments. Cluster analysis was performed separately in the FEP patients and the HCs to determine their profiles of intellectual change.

FEP patients (n=137) were grouped into five clusters (see Figure 1): “Improved low IQ” (9.49% of patients), “Improved average IQ” (14.6%), “Preserved low IQ” (17.52%), “Preserved average IQ” (43.06%), and “Preserved high IQ” (15.33%). Ninety HCs were grouped into three clusters: “Preserved low IQ” (32.22% of the HC), “Preserved average IQ” (44.44%), and “Preserved high IQ” (23.33%). Demographic data of FEP patients are presented in Table 1.Table 1.Sociodemographic data of FEP patients

The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HCs over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancement.

None Declared

Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes.

To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories.

We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases.

Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data.

Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

Family studies provide the opportunity to investigate endophenotypes as a powerful neurobiological platform to better understand the underlying neurobiological mechanisms of schizophrenia spectrum disorders. Shared features between the patients and their first-degree relatives may shed some light on the path to identify potential causes of psychosis, and to implement preventive and therapeutic interventions.

This study aimed to explore and compare neuropsychological measures in first episodes of psychosis (FEP) patients, their first-degree relatives and healthy controls (HC), participants on the PAFIP-FAMILIES project.

Statistical analyses were performed using one-way ANOVA, followed by multiple comparisons test where appropriate. Age, sex and years of education were introduced as covariates.

From 387 eligible FEP patients enrolled in a previous cohort, 133 were included. In addition, 244 of their first-degree relatives (146 parents and 98 siblings) and 202 HC participated in this study (see Figure 1). In general, relatives showed an intermediate neuropsychological performance between the HC and the FEP patients (see Figure 2). Specifically, siblings performed similar to HC in the domains verbal memory, visual memory, working memory, motor dexterity and theory of mind, since their values practically overlap those of HC. The parents presented significant deficits, similar to that of the affected individuals, in executive functions and attention domains.

These findings suggest that executive and attention dysfunction might have a greater family aggregation and could be a relevant cognitive endophenotype for psychotic disorders. The study shows the potential of exploring intra-family neuropsychological performance supporting neurobiological and genetic research in schizophrenia.

No significant relationships.

Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders.

Education achievement was explored in a large sample (n = 659) of FEP patients enrolled in programa de atención a fases iniciales de psicosis (PAFIP), a research and assistance program conducted in Spain. Patients were stratified according to the Spanish educational system according to their attendance in primary (low), secondary (medium) or university studies (high). The three groups were compared on available premorbid, clinical and neuropsychological variables. A subgroup of patients (n = 209), comprising the 10-year follow-up PAFIP cohort, were again compared.

Overall, 49% and 37% of FEP patients had low and medium levels of education, respectively. In total, 13% of the patients with a higher level of education were more frequently women (64%) and older at illness onset (36 years old), reported better premorbid adjustment, presented less severe positive symptoms and better functioning; and showed higher premorbid intelligence quotient and better performance on all the explored cognitive domains. Ten years later the FEP patients in the medium- and high-education groups had good global functioning and a neurocognitive performance within the normal limits.

Higher education is associated with better initial conditions and more favourable outcomes after an FEP. Sharing this information with the world's educational systems is essential to targeting resources and designing innovative programs or strategies to compensate for student difficulties.