Search

BackgroundCognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes.MethodsPremorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups.ResultsThe FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning.ConclusionsCR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

Objective To evaluate the ten-year stability of schizophrenia diagnosis in a cohort of first-episode psychosis (FEP) patients and the factors associated with it. Methods Changes in diagnosis of 209 FEP patients were described during ten years of follow-up. Related factors with maintenance or change of schizophrenia diagnosis were evaluated in prospective and retrospective approaches through Binary Logistic Regressions, ROC and survival curves. Results Out of the 209 patients, 126 were diagnosed of schizophrenia six months after their inclusion in the clinical program. Prospective analyses showed that eight of those 126 schizophrenia patients had changed to a different diagnosis after ten years, and predictors of change were better childhood premorbid adjustment, less severity of clinical global impression at baseline, and diagnosis of comorbid personality disorder during follow-up. Retrospectively, out of the 154 patients with schizophrenia in the ten-year assessment, 36 had a different diagnosis at baseline, and those factors related with a different prior diagnosis than schizophrenia were better socioeconomic status and shorter duration of untreated psychosis (DUP). A survival analysis on the timing of schizophrenia diagnosis showed that male gender and longer DUP were predictors of earlier definite diagnosis. Conclusions Diagnostic stability of schizophrenia in our FEP sample is high, especially prospective stability, and the group of patients with diagnostic change corresponded to a milder psychopathological profile before and at the onset of disease. Moreover, we observed a cautious attitude in the diagnosis of schizophrenia in patients with shorter DUP who had schizophrenia diagnosis after ten years.

Special Issue: The ENIGMA Consortium: the first 10 years., Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia., Center for Integrated Healthcare, U.S. Department of Veterans Affairs, Grant/Award Number: I01 CX000497; Commonwealth Health Research Board, Grant/Award Number: HRA_POR/2011/100; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grant/Award Numbers: 478466/2009, 480370/2009; Department of Energy, Labor and Economic Growth, Grant/Award Number: DE-FG02-99ER62764; Forskningsrådet om Hälsa, Arbetsliv och Välfärd, Grant/Award Numbers: K2009-62X-15077-06-3, K2012-61X-15077-09-3, 523-2014-3467, 2009-7053, 2013-2838; Fundação Amazônia Paraense de Amparo à Pesquisa, Grant/Award Numbers: 2009/14891-9, 2010/18672-7, 2012/23796-2, 2013/039; Instituto de Salud Carlos III, Grant/Award Numbers: FIS 00/3095, 01/3129, PI020499, PI060507, PI10/001; National Health and Medical Research Council, Grant/Award Numbers: 1009064, 496682; National Institutes of Health, Grant/Award Numbers: 1RC1MH089257, MH 60722, MH019112, MH064045, MH085096, MH098130, MO1 RR025758, P41RR14075, P50 MH071616, R01 DA053028, R01 EB020062, R01 HD050735, R01 MH056584, R01 MH084803, R01 MH116147, R01 MH117601, R01EB005846, R01EB015611, R01MH074797, R21 MH097196, R21MH097196, R37MH43375, S10 OD023696, T32 AG058507, T32 MH073526, TR000153, U01 MH097435, U24 RR021382A, U24 RR021992, U24 RR025736, U24 RR21992, U24RR021992, U54 EB020403, U54EB020403, UL1 TR000153; National Science Foundation, Grant/Award Numbers: 1636893, 1734853; Norges Forskningsråd, Grant/Award Numbers: 213837, 217776, 223273; Science Foundation Ireland, Grant/Award Numbers: 08/IN.1/B1916, 12/IP/1359; Wellcome Trust, Grant/Award Number: 072894/2/03/Z.

[Background] Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up., [Method] From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy., [Results] The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea., [Conclusions] Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis., The study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant supports: Plan Nacional de Drogas Research (2005-Orden sco/3246/2004); SENY Fundació (CI 2005–0308007); and Fundación Marqués de Valdecilla (API07/011); Gerencia Regional de Salud de Castilla y León (INT/M/04/17).

BackgroundNeuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples.MethodsStructural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons.ResultsFEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms.ConclusionsThis study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.

Background Prevention of symptom relapse and promotion of functional recovery are the two main goals of early intervention following a first episode of non-affective psychosis (FEP). The identification of patterns of recovery is important in developing and implementing recovery focused interventions at set time interval. Method Patterns of recovery course, in terms of symptomatic and functional remission, were explored at 1 and 3-year follow-up in a sample of 373 consecutive FEP patients. Relapses during this period were considered. Results Four patterns of recovery course were defined: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery were more likely have less severe baseline negative symptoms (OR = 2.092; 95% CI = 0.99–4.419) and to not be diagnosed with schizophrenia (OR = 2.242; 95% CI = 1.015–4.954). Short DUP (OR = 2.152; 95% CI = 0.879–5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954–5.457) increased the likelihood of good unstable recovery. Less severe baseline negative symptoms (OR = 3.851; 95% CI = 1.422–10.435) and single status (OR = 4.307; 95% CI = 1.014–18.293) increased the likelihood of a poor unstable recovery. Poor unstable pattern was significantly associated with a high relapse rate (73%). Conclusions Our results shed light on identifying different recovery patterns in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly in reference to the role of timing in the design of interventions.

OBJECTIVE To determine possible progressive changes of the grey matter at the first stages of the schizophrenia spectrum disorders, and to determine what regions are involved in these changes. METHODS We searched the literature concerning studies on longitudinal changes in grey matter in first-episode psychosis using magnetic resonance imaging, especially studies with an interval between scans of more than a year. Only articles published before 2018 were searched. We selected 19 magnetic resonance imaging longitudinal studies that used different neuroimaging analysis techniques to study changes in cerebral grey matter in a group of patients with a first episode of psychosis. RESULTS Patients with first episode of psychosis showed a decrease over time in cortical grey matter compared with a group of control subjects in frontal, temporal (specifically in superior regions), parietal, and subcortical regions. In addition to the above, studies indicate that patients showed a grey matter decrease in cerebellum and lateral ventricles volume. CONCLUSION The results suggest a decrease in grey matter in the years after the first episode of psychosis. Furthermore, the results of the studies showed consistency, regardless of the methods used in their analyses, as well as the time intervals between image collections.

[Background] Selecting the most effective treatment represents a critical challenge with the potential of modifying the long-term prognosis of individuals suffering a first break of psychosis. Head-to-head clinical trials comparing effectiveness among antipsychotic drugs in individuals with a first-episode of non-affective psychosis (FEP) are scarce., [Methods] The rationale and design of a 3 phases clinical trial (PAFIP-3, NCT02305823) comparing the effectiveness of aripiprazole and risperidone, and to additionally assess the benefits of an early use of clozapine in primary treatment-resistant patients is reported. The design encompasses of 5 work packages (medication algorithm, cognitive functioning, psychoeducation/vocational functioning, imaging and biological markers) addressing critical issues and needs of first episode psychosis individuals and their cares. The primary outcome measure was treatment effectiveness assessed by all-cause treatment discontinuation rate., [Results] 266 individuals have been included in the randomization study phase I (risperidone vs. aripiprazole). At 3 months, the retention rate was of 94% (249/266), 48(19.3%) patients have gone through phase II (olanzapine treatment), and 7(2.8%) entered the clozapine phase (phase III)., [Discussion] The PAFIP 3 clinical trial may provide relevant information about clinical guidelines to optimally treat patients with a first episode of non-affective psychosis and the benefits and risks of an early use of clozapine in treatment resistant patients., [Clinicaltrials.gov] NCT02305823.

Cognitive deficits have been recognized as a central feature of schizophrenia spectrum disorders. These deficits are often related to more severe negative symptoms, as well as a poorer adjustment in social functioning. Therefore, it is important to improve cognitive performance from the onset of the disease. In this study, we compared the effects of two atypical antipsychotics, risperidone and aripiprazole, on cognition. The data used in the present investigation were obtained from a large epidemiological cohort of patients with a first episode of psychosis who were treated in a longitudinal intervention programme. The patients included in the program were randomized to treatment with risperidone or aripiprazole and were assessed for cognitive function at baseline and 3 years later. The final sample consisted of 115 patients, 55 of whom were initially assigned to risperidone and 60 to aripiprazole. The groups did not show significant differences in their sociodemographic or clinical characteristics at intake. Longitudinal analyses showed that risperidone-treated patients improved in the processing speed domain at the 3-year follow-up, while the aripiprazole group showed better scores for the executive function domain. Our study shows slight differences between the effects of risperidone and aripiprazole on cognition, suggesting different patterns of efficacy on cognitive function that may warrant more thorough research to determine the beneficial effects of these drugs on cognition. Future studies should evaluate the effects of these treatments over longer follow-up periods using standardized tools for the assessment of cognitive function., Dr. Ayesa-Arriola is funded by a Miguel Servet contract from the Carlos III Health Institute (CP18/00003), carried out on Fundación Instituto de Investigación Marqués de Valdecilla.

AIM To explore if the entire duration of active psychosis (DAP) is related to neurocognitive performance at baseline and at 3-year follow-up in patients with first episode psychosis (FEP). METHODS DAP was estimated for 481 FEP patients. A neuropsychological battery was administered to measure neurocognitive specific domains, and a global indicator of neurocognitive impairment (global deficits score, GDS) was calculated. According to the DAP quartiles, four subgroups were formed, and these were compared. In addition, a logistic regression analysis was carried out to predict neurocognitive impairment at 3-year follow-up. RESULTS FEP patients with the longest DAP (more than 18.36 months) presented a more severe global neurocognitive impairment evidenced in their GDS, both at baseline (F = 5.53; p˂ .01) and at 3-year follow-up (F = 4.16; p˂ .01). Moreover, a subgroup of participants with DAP between 7.40 and 18.36 months showed a specific attentional decline over the 3-year follow-up (F = 3.089; p˂ .05).The logistic regression model showed that sex (Wald = 7.29, p

PAFIP Group Study., Cortical thickness has been widely studied in individuals with schizophrenia and, in particular, first-episode psychosis. Abnormalities have been described, although there is, to date, a lack of consensus regarding changes across time and correlations with clinical and functional outcomes of the illness. One hundred and twenty-three first-episode psychosis patients and 74 healthy volunteers were subjected to magnetic resonance imaging scans and clinical and functional assessments by different scales at four consecutive visits during a 10 year follow-up period. Linear mixed effects models were applied to our data to compute cortical thickness changes over time in (1) schizophrenia patients versus healthy controls and (2) in patients with good versus poor functional outcome. The associations between cortical thickness percentage changes and clinical and functional status at 10 years were also assessed. The patients presented a thinner cortex than the controls at baseline (b's = −0.06; q ≤ 0.00023) with non-significant coefficients for the interaction term (follow-up time x group) (b's = −0.001; q ≥ 0.681). Poor functioning patients presented statistically significant coefficients for the interaction term (follow-up time x functionality) (left: b = −0.005, q = 0.019; right: b = −0.005, q = 0.022). In contrast, no correlations were found between cortical thickness measurements and clinical variables at 10 years. Overall, there were widespread thickness anomalies in first-episode psychosis patients across cortical regions that remained stable across time. Progressive thickness changes were related to patient functional outcomes, with progressive and steeper cortical thinning in patients with worse functional outcomes and a stabilization in those with better outcomes., This work was supported by the Instituto de Salud Carlos III, Spain (PI14/00639 and PI14/00918).

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions., This work was supported by the Instituto de Salud Carlos III (PI14/00639 andPI14/00918). No pharmaceutical company has financially supported the study. Dr. Ayesa-Arriola is funded by a Miguel Servet contract from the Carlos III Health Institute (CP18/00003), carried out on Fundación Instituto de Investigación Marqués de Valdecilla.

In recent years, the effects of cannabis use on cognitive functions in patients with psychosis have been widely studied. Recently, special emphasis has been placed on the impact of age at the onset of consumption on cognition in these patients.349 patients with a first episode of non-affective psychosis were studied. Patients were classified as cannabis users and non-users. Users were divided, according to their age when they began using cannabis, into: early-onset (age 16) and late-onset (age ≥ 16) users. Differences between groups at baseline were studied based on sociodemographic, clinical, and cognitive variables. The groups were longitudinally (3-year) compared on cognitive variables.Out of the 349 patients included in this study, 38.7% (N = 135) were cannabis users. Of them, 39.3% (N = 53) were early-onset and 60.7% (N = 82) were late-onset cannabis users. No baseline differences were found between the early-onset and late-onset groups on cognitive domains. Longitudinally, only patients who had withdrawn from cannabis use during follow-up showed a significant improvement in verbal memory.Our results did not show differences between the early-onset group and the other two groups in long-term cognitive performance, even if they kept consuming cannabis during the first three years of disease progression. Further studies are needed to elucidate the true relationship between early-onset cannabis use and cognitive function in patients with a first episode of psychosis.

[EN] Background: Schizophrenia spectrum disorders (SSD) are mental diseases caused by a combination of genetic susceptibility and a number of environmental factors. Among these factors, the role of traumatic events suffered in childhood, as well as that of substance use, have been of particular research interest. Objectives: To conduct a systematic review to clarify whether there is an interaction between childhood trauma and substance use related to the diagnosis or symptoms of SSD. It was also the objective of this review to collate the associations that may exist between the three variables of the study (trauma, substance use and psychosis). Methods: We conducted a systematic search resulting in 240 articles. We considered all of the original articles that explored childhood trauma and substance use in patients suffering from SSD. Results: Twenty-three articles were selected for this review. Several of the reviewed papers found associations between childhood trauma and substance use with SSD, as well as interactions between trauma and drug use on SSD. Conclusions: The results suggest that childhood trauma and substance use may be present at the basis of psychosis. This double hit on the pathogenesis could have clinical implications, since each of these impacts could be considered a window of opportunity for the primary prevention of SSD., [ES] Introducción: Los trastornos del espectro de la esquizofrenia (SSD) son enfermedades mentales que parecen estar provocadas por una combinación de múltiples factores genéticos y ambientales. Entre los factores ambientales desencadenantes, el papel de los eventos traumáticos sufridos en la infancia y el consumo de sustancias resultan de particular interés para la investigación. Objetivos: Aclarar si existe una interacción entre el trauma infantil y el uso de sustancias relacionadas con el diagnóstico o los síntomas de las SSD. También fue el objetivo de esta revisión cotejar las asociaciones que pueden existir entre las tres variables del estudio (trauma, consumo de sustancias y psicosis). Métodos: Se realizó una búsqueda sistemática que resultó en 240 artículos. Consideramos todos los artículos originales que exploraron el trauma infantil y el consumo de sustancias en pacientes que presentaban trastornos psicóticos. Resultados: 23 artículos fueron seleccionados a los efectos de esta revisión. Varios de los artículos revisados encontraron asociaciones entre el trauma infantil y el consumo de sustancias con SSD, además de interacciones entre trauma y consumo en los trastornos psicóticos. Conclusiones: El doble impacto que representan el trauma en la infancia y el consumo de sustancias en la patogénesis de la enfermedad podría tener implicaciones clínicas por la ventana de oportunidad que supone la intervención en estos factores en la prevención primaria de los trastornos psicóticos.

BACKGROUND: A higher incidence of childhood trauma (CT) has been reported in first episode of psychosis (FEP). There is, however, a lack of knowledge about the synergetic effect between CT and recent stressful events (RSE). METHODS: Information on specific types of CT (under 17 years) and RSE (within the past 3 years) was available for 290 FEP patients and 52 healthy controls (HC). Cognitive function at baseline was assessed through a comprehensive neuropsychological test battery. RESULTS: While 45.2% of FEP patients and 25% of HC reported at least one CT event, 62.7% of FEP and 21.2% of HC reported an RSE. Meanwhile, 36.2% of FEP patients and 9.6% of HC encountered both childhood and recent stressful events. The patients that just reported CT showed normality in all but the verbal memory cognitive domain; those with additive CT and RSE presented worse general cognitive function, specifically on working memory, processing speed, and executive function. RSE and general cognitive dysfunction were significant determinants of psychosis onset. CONCLUSIONS: These results support a synergetic influence of trauma and stressful events on brain function and allow a better understanding of mediators for psychotic disorders useful in the design of specific strategies based on stress-targeted therapies.

PAFIP research group., This work was supported by the Instituto de Salud Carlos III (PI14/00639 and PI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363). No pharmaceutical company has financially supported the study.

BackgroundThe aim of the current study was to examine the heterogeneity of functional outcomes in first episode psychosis (FEP) patients and related clinical, neurocognitive and sociodemographic factors using a cluster analytic approach.MethodA large sample of FEP patients (N = 209) was functionally reassessed 10 years after the first contact with an early intervention service. Multiple baseline, 3-year and 10-year follow-up variables were explored.ResultsThe cluster analysis emphasized the existence of six independent clusters of functioning: one cluster was normal overall (42.16%), two clusters showed moderate interpersonal (9.63%) or instrumental (12.65%) deficits, two clusters showed more severe interpersonal (12.05%) or interpersonal and instrumental (13.85%) deficits and there was a significantly overall impaired cluster (9.63%). Cluster comparisons showed that several baseline and follow-up factors were differentially involved in functional outcomes.ConclusionsThe current study demonstrated that distinct clusters of functioning in FEP patients can be identified. The fact that a variety of profiles was observed contributes to a better understanding of the nature of the heterogeneity characterizing FEP patients and has clinical implications for developing individualized treatment plans.

Objective To examine the long-term (up to 10 years) patterns related to cannabis use in a sample of patients with first episode of psychosis (FEP) and the effect that consumption might have on clinical, functioning, and neurocognition at long-term. Methods Cannabis use was described in 209 FEP patients. Patients were divided into three groups according to cannabis use: persistent users, ex-users, and never-users. Groups were longitudinally (baseline and 10-year follow-up) compared on clinical, functional, and cognitive variables. Results Clinical differences at 10-year follow-up were observed between persistent cannabis users and the other two groups (ex-users and never-users), showing persistent users more severe symptoms (BPRS: x2 = 15.583, P ≤ 0.001; SAPS: x2 = 12.386, P = 0.002) and poorer functionality (DAS: x2 = 6.067, P = 0.048; GAF: x2 = 6.635, P = 0.033). Patients who stopped cannabis use prior to the reassessment showed a similar pattern to those who had never consumed. Conclusion The use of cannabis could negatively affect the evolution of the psychotic disorder. Perhaps the negative effects caused by cannabis use could be reversed with the cessation of consumption. It is necessary to make an effort in the intervention toward an early withdrawal from the use of cannabis, since this could play an important role in the prognosis of the disease.

BACKGROUND: Scarce research has focused on Visual Memory (VM) deficits as a possible neurocognitive endophenotype of bipolar disorder (BD). The main aim of this longitudinal, family study with healthy controls was to explore whether VM dysfunction represents a neurocognitive endophenotype of BD. METHODS: Assessment of VM by Rey-Osterrieth Complex Figure Test (ROCF) was carried out on a sample of 317 subjects, including 140 patients with BD, 60 unaffected first-degree relatives (BD-Rel), and 117 genetically-unrelated healthy controls (HC), on three occasions over a 5-year period (T1, T2, and T3). BD-Rel group scores were analyzed only at T1 and T2. RESULTS: Performance of BD patients was significantly worse than the HC group (p < 0.01). Performance of BD-Rel was also significantly different from HC scores at T1 (p < 0.01) and T2 (p?=?0.05), and showed an intermediate profile between the BD and HC groups. Only among BD patients, there were significant differences according to sex, with females performing worse than males (p?=?0.03). Regarding other variables, education represented significant differences only in average scores of BD-Rel group (p?=?0.01). LIMITATIONS: Important attrition in BD-Rel group over time was detected, which precluded analysis at T3. CONCLUSIONS: BD patients show significant deficits in VM that remain stable over time, even after controlling sociodemographic and clinical variables. Unaffected relatives also show stable deficits in VM. Accordingly, the deficit in VM could be considered a potential endophenotype of BD, which in turn may be useful as a predictor of the evolution of the disease. Further studies are needed to confirm these findings. VB-M is supported by the national grant PI16/01770 (PROBILIFE Study), from the ISCIII. RTS was supported in part by grant PROMETEOII/2015/021 from Generalitat Valenciana and the national grands PI14/00894, PI17/00719 and PIE14/00031 from ISCIII-FEDER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The presented article describes data from secondary analyses, related to the research article entitled “Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients” [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking. Keywords: Cannabis, Psychosis, Liver, Liver steatosis, NAFLD, Antipsychotic treatment, Mental health

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-na&iuml, ve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1&ndash, 9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1&ndash, 9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-&alpha, ) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

[Background]: Cannabis smoking is highly prevalent among patients with psychotic disorders. Its use has been found to be related to clinical characteristics and the prognosis of the disorder. Recent evidence indicates a protective effect of cannabis on weight gain and related metabolic alterations. However, there are no previous studies on the long-term longitudinal effects of cannabis on first-episode drug-naïve patients, which would thereby avoid the confounding effects of chronicity and previous treatment exposure. We aimed to explore the effect of cannabis smoking on weight and lipid/glycaemic metabolic measures in a sample of first-episode non-affective psychosis patients., [Method]: Anthropometric measurements and glycaemic and lipid parameters were obtained at baseline and three years after initiation of treatment. Patients self-reported their cannabis use at both time points. To explore the longitudinal effect of cannabis, patients were divided into three groups: continuers, discontinuers and non-users., [Results]: Cannabis users at baseline presented a lower weight (F=14.85, p, [Conclusions]: The study suggests that cannabis use may produce a protective effect against weight gain and related metabolic alterations in psychosis. However, these results need to be replicated in a larger sample size.

Background:Suicide has been recognised as one of the major causes of premature death in psychosis. However, predicting suicidal behaviour (SB) is still challenging in the clinical setting and the association of neurocognition with SB in psychosis remains poorly understood. This study aimed to investigate the role of neurocognitive performance as predictor of SB. Also, we sought to explore differences in the evolution of clinical and neurocognitive functioning between participants with/without history of suicide attempts (SA) over follow-up period.Methods:The sample of the study is composed by 517 patients. Sociodemographic, clinical, functional and neurocognitive measures were evaluated at baseline as well as 1-year and 3 years after first episode of psychosis. Bivariate and multivariate analyses explored the influence of these variables as putative baseline predictors of SB. Repeated measures analyses of variance tested differences in clinical and neurocognitive outcomes at 1- and 3-year follow-up.Results:Global cognitive functioning (GCF) (OR = 1.83, 95% CI = 1.25–2.67) and severe depressive symptoms (OR = 1.17, 95% CI = 1.07–1.28) predicted SB. Longitudinal analyses revealed that patients with SB at follow-up presented with higher levels of remission in terms of positive psychotic symptoms and depression. In addition, those with a history of SB had worse GCF and visual memory than those without such antecedents.Conclusions:GCF was found to be the most robust predictor of SB along with severe depressive symptomatology. Hence, poorer cognitive performance in FEP appears to emerge as a risk factor for suicidal behaviour from early stages of the illness and a comprehensive neurocognitive assessment may contribute to risk assessment.

Studies have established the high risk of suicide in first episode psychosis (FEP). Between 15% and 26% of FEP patients attempt suicide at least once before their first contact with psychiatric services and 2-5% die from suicide. Also, many patients with schizophrenia spectrum disorders lack insight into having a mental disorder. However, the relationship between insight changes and suicidal behavior in FEP remains poorly understood. In the present study information about suicidal behavior over a 3 years period was available on a cohort of 397 FEP patients, of whom 270 were assessed in the three dimensions of insight (into mental illness, the need for treatment, and the social consequences) at baseline, 1 and 3 years after treatment initiation. Survival analyses examined time to suicidal behavior in relation to (i) insight at baseline, (ii) the closest insight measure to the suicide attempt, and (iii) changes in insight during the follow-up. No associations were found between baseline insight dimensions and time to suicidal behavior. However, poor insight at the evaluation closest to the suicide attempt was associated with an increased risk of suicide. Stability of insight did not affect the risk of suicidal behavior, while changes in either direction were linked with an increased risk of suicidal behavior, particularly worsening insight. Insight in psychosis is a dynamic concept and we demonstrated the relationship between insight and suicide risk to be equally dynamic. Poor insight seems to increase the risk, especially when insight levels change. Repeated insight assessment to detect change from early psychosis may play a role in suicide prevention.

Objectives: Our aims were to confirm the relationship between lipid and lipoprotein concentrations and suicidal behaviour in first-episode psychosis (FEP) patients. Methods: Suicidal behaviour was explored in a large FEP sample (N?=?383). Baseline lipid profile was compared between those who attempted or completed suicide and those who not presented suicidal behaviour. Results: Low-density lipoprotein cholesterol (LDL-c) (OR?=?0.99, 95% CI=?0.98?1.00) and depressive symptoms (OR?=?1.15, 95% CI?=?1.06?1.24) were significantly related with suicidal behaviour. Conclusions: Lipid profile test may be considered in the assessment of suicide risk in psychosis and LDL-c an important biological marker. Funding Sources: This work was supported by the Instituto de Salud Carlos III (PI14/00639 and PI14/00918) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363). No pharmaceutical company has financially supported the study.

Background Low IQ has been associated with schizophrenia, even to the point of being posited as a possible causal factor for psychosis. However, individuals with normal and high IQ also develop psychotic illnesses. The aim of this study was to characterize premorbid IQ subgroups at first episode of psychosis (FEP). Methods The study sample comes from a large epidemiological, 3-year longitudinal, intervention program on psychosis containing individuals living in a catchment area in Spain. Estimated premorbid IQ (epIQ) scores were used to build low ( 110) epIQ subgroups in samples of FEP patients (N = 292) and healthy controls (N = 199). The epIQ subgroups were compared in sociodemographic, neuropsychological, clinical and premorbid characteristics. Long-term functional and cognitive outcome, with a focus on sex differences, were also explored. Results Low-epIQ was more frequently found in FEP patients (28.8%) than in healthy controls (14.6%). Low-epIQ patients were more likely to have worse premorbid adjustment, belong to low socioeconomic status families, have less years of education, and to be single, unemployed, and younger. They presented more severe impairments in processing speed, executive and global cognitive function. Female patients with low-epIQ showed better baseline function and more stable outcome than males. Conclusions Our results indicate that low premorbid IQ is a morbid manifestation, easily detected in a subgroup of FEP patients that predicts poorer outcome particularly in males. This perspective provides important information for the tailoring of subgroup-specific early intervention programs for psychosis.

INTRODUCTION: Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS: A total of 390 patients were evaluated at baseline and after 3?years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS: At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F?=?13.874; p?.001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2?=?7.97, p?=?.019). Longitudinally, patients maintaining cannabis consumption after 3?years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p?=?.022) and never-users (p?=?.016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS: Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain. Funding sources: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Next-Val 2017 (ref.: NVAL17/24) and Inn-Val 2018 (ref.: INNVAL18/30) IDIVAL grants; Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011.

Background Structural abnormalities in first episode psychosis (FEP) tend to be subtle and widespread. Most studies investigating structural abnormalities in this clinical population have used small samples, and therefore may be under-powered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, findings from existing studies have often been heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP relative to healthy controls that are expressed consistently across five independent datasets. Methods Structural Magnetic Resonance Imaging data were acquired from a total of 572 patients with FEP and 502 age and gender comparable healthy controls (HC) at five sites - London (UK), Utrecht (Netherlands), Chengdu (China) and two independent sites at Santander (Spain). Voxel-based morphometry (VBM) as implemented in Statistical Parametric Mapping software (SPM12) was used to investigate differences in gray matter volume (GMV) between the two groups. The statistical analysis was carried out using an analysis of variance (ANCOVA), with diagnostic group and scanning site as factors, and age and gender as covariates of no interest. Neuroanatomical alterations in patients with FEP relative to HC common to the five datasets were identified by comparing the total FEP group against the total HC group, and then using the inclusive masking option (at p

Background Studies have established the high risk of suicide in first episode psychosis (FEP). Between 15%-26% of FEP patients attempt suicide at least once before their first contact with psychiatric services and 2–5% die from suicide. Also, many patients with schizophrenia spectrum disorders lack insight into having a mental disorder. However, the relationship between insight changes and suicidal behaviour in FEP remains poorly understood. Methods Information about suicidal behaviour was available on a cohort of 397 FEP patients. Three dimensions of insight (into mental illness, the need for treatment, and the social consequences) were measured at: baseline, 1 and 3 years after the initiation of treatment. Survival analyses examined time to suicidal behavior in relation to i) insight at baseline, ii) the closest insight measure to the suicide attempt, and iii) changes in insight during the follow-up. Results No associations were found between baseline insight dimensions and time to suicidal behaviour. However, poor insight at the evaluation closest to the suicide attempt was associated with an increased risk of suicide. Stability of insight did not affect the risk of suicidal behaviour, while changes in either direction were linked with an increased risk of suicidal behaviour, particularly worsening insight. Discussion Insight in psychosis is a dynamic concept and we demonstrated the relationship between insight and suicide risk to be equally dynamic. Poor insight seems to increase the risk, especially when insight levels change. Repeated insight assessment to detect change from early psychosis may play a role in suicide prevention.

Background In recent years, the effect of cannabis use on cognitive functions in patients with psychosis has been widely studied, but results are somewhat contradictory. On the other hand, it has also been studied the relevance of the age of onset of consume, suggesting that the early age of onset of consumption may be related to a greater cognitive impairment. Methods 349 patients with a first episode of non-affective psychosis were studied. Patients were classified in cannabis users and non-users. Users were divided according to their age at the beginning of use of cannabis in: early-onset (age

Background Deficits in auditory-verbal memory have been reported by the vast majority of published research in schizophrenia and also detected in first episode psychosis (FEP), confirming they are already present at the early stages of the illness. However, the specific neurocognitive constructs underlying defective verbal memory and their neuroanatomical correlates remains poorly understood in schizophrenia spectrum disorders patients. Methods Data on the Rey Auditory Verbal Learning Test (RAVLT), a widely used verbal memory measure that provides a range of performance indexes to evaluate distinct memory processes including: a) acquisition/learning b) sensitivity to interference c) retrieval; d) retention or rate of forgetting; e) and retrieval efficiency was available for 388 FEP patients and 184 healthy controls (HC). In 218 FEP patients and 146 HC, structural magnetic resonance imaging data were analysised using Voxel based morphometry (VBM) toolbox. Results The FEP group showed significantly lower results on acquisition/learning, delayed recall as well as higher rates of forgetting. They also exhibited a significant sensitivity to retroactive but not proactive interference. We also found significant correlations between bilateral frontal lobe morphometry and proactive interference as well as between right frontal lobe morphometry and retroactive interference. Rate of forgetting was significantly correlated with right occipital cortex morphometry. Those with higher rates of forgetting and proactive and retroactive interference demonstrated further gray matter reductions in frontal and occipital cortical areas. Discussion The application of a process oriented approach to the neuropsychological evaluation of verbal memory allows a finer-grained analysis of the neurocognitive constructs underlying defective verbal memory in FEP. The results suggest specific relationships between different neuroanatomical structures and discrete memory processes with these structures playing an important role in verbal memory deficits found in FEP.

Background Prevent symptom relapse and promote functional recovery are the two main goals of early intervention services in first episode of psychosis. Identify patterns of recovery will be important in developing and implementing targeted recovery focused interventions. The goal of this study was to explore trajectories of recovery following a first episode of psychosis. Methods A sample of 373 FEP patients was followed over 3 years. Recovery profiles in terms of symptomatic and functional remission were explored. Relapses during follow-up were considered. Results Four recovery trajectories were identified: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery more likely have less severe baseline negative symptoms (OR= 2.092; 95% CI = 0.99–4.419) and not be diagnosed with schizophrenia (OR= 2.242; 95% CI = 1.015–4.954); short DUP (OR= 2.152; 95% CI = 0.879–5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954–5.457) increased the likelihood of good unstable recovery; less severe baseline negative symptoms (OR= 3.851; 95% CI = 1.422–10.435) and single status (OR= 4.307; 95% CI = 1.014–18.293) increased the likelihood of a poor unstable recovery when these three trajectories were compared with a poor stable recovery. Poor unstable trajectory was significantly associated with a high relapse rate (73%). Discussion Our results shed light on identifying different recovery profiles in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly attending the role of timing in the design of interventions.

Background Metabolic alterations are common in patients suffering from psychosis. The rise in glycemic lipids may be related to and observed increased in the prevalence of hepatic steatosis measured by the Fatty Liver Index. However, we have recently reported a probable protective effect of cannabis smoking on weight gain and related metabolic alterations in a sample of patients drug-naïve suffering from a first episode of psychosis. We aimed to explore the effect of cannabis smoking on hepatic steatosis in a sample of first-episode non-affective psychosis patients. Methods Anthropometric measurements, glycemic and lipid parameters, and liver steatosis index (FLI), were obtained at baseline and after 3 years of having initiated treatment. Patients were divided into two groups depending on self-reported cannabis use (cannabis users and non-users). Results Cannabis users presented at baseline lower FLI (F=4.26, p=0.040) than non-users. These differences were also observed after 3 years of treatment (F=6.61, p=0.011). Discussion Our results support the hypothesis that cannabis has a protective effect against hepatic steatosis. However, before being transferred to clinical practice, this study should be replicated, using larger samples.

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not.