BUSCADOR RECOLECTA

Psychopathological manifestations and cognitive impairments are core features of psychotic disorders. Polygenic risk scores (PRS) offer insights into the relationships between genetic vulnerability, symptomatology, and cognitive impairments. This study used a network analysis to explore the connections between PRS, cognition, psychopathology, and overall functional outcomes in individuals experiencing a first episode of psychosis (FEP). The study sample comprised 132 patients with FEP. Genetic data were used to construct PRS for mental disorders and cognitive traits via PRS-continuous shrinkage. We conducted comprehensive clinical and neuropsychological assessments at 2 months post-diagnosis and again at a 2-year follow-up. A network analysis was performed to generate two distinct networks and their centrality indices, encompassing 19 variables across domains such as symptoms, cognition, functioning, and PRS. Variables were grouped within related domains, and stronger relationships were observed within domains than between them. PRS for schizophrenia showed weak negative associations with attention, working memory, and verbal memory, while PRS for cognitive performance showed weak positive associations with attention. Negative symptoms were negatively associated with functioning and verbal memory at both the 2-month and 2-year assessments, as well as with social cognition at 2 years. Poor functioning was moderately related to greater severity of Positive and Negative Syndrome Scale dimensions. This study identified pathways linking PRS, cognition, symptoms, and functioning, suggesting that genetic risk may serve as a marker of vulnerability and disorder progression. The findings also highlight the importance of considering genetic predispositions alongside clinical and cognitive factors to better understand the heterogeneity of psychotic disorders.

Background: The dimensional symptom structure of classes of affective psychoses, and more specifically the relationships between affective and mood symptoms, has been poorly researched. Here, we examined these questions from a network analysis perspective.
Methods: Using Exploratory Graph Analysis (EGA) and network centrality parameters, we examined the dimensionality and network structure of 28 mood and psychotic symptoms in subjects diagnosed with schizoaffective disorder (n=124), psychotic bipolar disorder (n=345) or psychotic depression (n=245), such as in the global sample of affective psychoses.
Results: EGA identified four dimensions in subjects with schizoaffective or bipolar disorders (depression, mania, positive and negative) and three dimensions in subjects with psychotic depression (depression, psychosis and activation). The item composition of dimensions and the most central symptoms varied substantially across diagnoses. The most central (i.e., interconnected) symptoms in schizoaffective disorder, psychotic bipolar disorder and psychotic depression were hallucinations, delusions and depressive mood, respectively. Classes of affective psychoses significantly differed in terms of network structure but not in network global strength.
Limitations: The cross-sectional nature of this study precludes conclusions about the causal dynamics between affective and psychotic symptoms.
Conclusion: EGA is a powerful tool for examining the dimensionality and network structure of symptoms in affective psychoses showing that both the interconnectivity pattern between affective and psychotic symptoms and the most central symptoms vary across classes of affective psychoses. The findings outline the value of specific diagnoses in explaining the relationships between mood and affective symptoms., The study was funded by the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitiveness (grant number PI16/02148) and the Regional Government of Navarra (grant number 31/17).

This study was aimed at characterizing long-term outcomes of first-admission psychosis and examining their baseline predictors. Participants were assessed at baseline for 38 candidate predictors and re-assessed after a median follow-up of 21 years for symptomatic, functional, and personal recovery. Associations between the predictors and the outcomes were examined using univariate and multivariate Cox regression models. At baseline, 623 subjects were assessed for eligibility, 510 met the inclusion/exclusion criteria and 243 were successfully followed-up (57.3% of the survivors). At follow-up, the percentages of subjects achieving symptomatic, functional, and personal recovery were 51.9%, 52.7%, and 51.9%, respectively; 74.2% met at least one recovery criterion and 32.5% met all three recovery criteria. Univariate analysis showed that outcomes were predicted by a broad range of variables, including sociodemographics, familial risk, early risk factors, premorbid functioning, triggering factors, illness-onset features, neurological abnormalities, deficit symptoms and early response to treatment. Many of the univariate predictors became nonsignificant when entered into a hierarchical multivariate model, indicating a substantial degree of interdependence. Each single outcome component was independently predicted by parental socioeconomic status, family history of schizophrenia spectrum disorders, early developmental delay, childhood adversity, and mild drug use. Spontaneous dyskinesia/parkinsonism, neurological soft signs and completion of high school remained specific predictors of symptomatic, functional, and personal outcomes, respectively. Predictors explained between 27.5% and 34.3% of the variance in the outcomes. In conclusion, our results indicate a strong potential for background and first-episode characteristics in predicting long-term outcomes of psychotic disorders, which may inform future intervention research., The study was funded by the Carlos III Health Institute
(FEDER Funds) from the Spanish Ministry of Economy
and Competitiveness (grant number PI16/02148) and the
Regional Government of Navarra (grant number 31/17).

Background
The long-term stability of neuromotor domains assessed at the first episode of psychosis (FEP) and their ability for predicting a number of outcomes remains largely unknown, and this study addressed these issues.
Methods
This was a longitudinal study of 243 participants with FEP who were assessed at baseline for background variables and parkinsonism, dyskinesia, neurological soft signs (NSS) and catatonia, and reassessed 21 years later for the same neuromotor variables, psychopathology, functioning, personal recovery, cognitive performance and medical comorbidity. Stability of neuromotor ratings was assessed using the intraclass correlations coefficient and associations between the predictors and outcomes were examined using univariate and multivariate statistics.
Results
Baseline dyskinesia and NSS ratings showed excellent stability over time whereas that for parkinsonism and catatonia was relatively low. Neuromotor dysfunction at follow-up was independently predicted by a family history of schizophrenia, obstetric complications, neurodevelopmental delay, low premorbid IQ and baseline ratings of dyskinesia and NSS. Moreover, baseline dyskinesia and NSS ratings independently predicted more positive and negative symptoms, poor functioning and less personal recovery; catatonia predicted less personal recovery and more medical comorbidity. Baseline neuromotor ratings explained between 4% (for medical comorbidity) and 34% (for neuromotor dysfunction) of the variance in the outcomes. Lastly, neuromotor dysfunction at baseline highly predicted clinical staging at follow-up.
Conclusion
Baseline neuromotor domains show variable stability over time and relate distinctively to very long-term outcomes. Both baseline dyskinesia and NSS are trait markers of the disease process and robust predictors of the outcomes., The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness (grant PI16/02148 and 19/01698) and the Regional Government of Navarra (grant 31/17 and 41/18).

Background: clinicians are currently unable to predict which patients are at higher risk of long-term disability based on premorbid factors. We aimed to determine the extent to which premorbid factors could prospectively predict long-term disability in patients with first-episode psychosis.
Methods: we assessed 12 potential premorbid risk factors in 243 individuals with first-episode psychosis reassessed 21 years later for several domains of psychosocial disability. Hierarchical multivariate regression and Directed Acyclic Graphs (DAGs) were used sequentially to investigate independent and causal associations between risk factors and long-term disability.
Results: the familial load of schizophrenia, lower parental SES, obstetric complications, early neurodevelopmental delay, childhood adversity, and poor adolescence social networks were independent predictors of long-term disability, accounting for 40.6 % of the variability. The DAGs analysis showed that both familial risk of schizophrenia and lower SES had statistically significant direct and indirect effects on later disability. The indirect effects were mediated by the variables indexing impaired development, although childhood adversity and poor adolescence social networks also had significant direct effects on disability. Early neurodevelopmental delay was the only developmental marker present in all statistically significant indirect paths from familial background factors to long-term disability, suggesting that it is a key component of the causal chain that leads to later disability.
Conclusions: in individuals with psychotic disorders, familial background factors appear to trigger a complex and multidetermined cascade of risk factors across developmental stages that interact iteratively, leading to long-term disability., This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness (VP, grant numbers PI16/02148 ; EGJ and MJC, 19/01698), and the Regional Government of Navarra (VP, grant number 31/17), (LMI, grant number 41/18).

Purpose: Little is known about the relationship between social exclusion and cognitive impairment in psychosis. We conducted a long-term cohort study of first-episode psychosis to examine the association between comprehensive measures of cognitive impairment and social exclusion assessed at follow-up. Methods: A total of 173 subjects with first-episode psychosis were assessed after a 20-year follow-up for 7 cognitive domains and 12 social exclusion indicators. Associations between sets of variables were modeled using multivariate regression, where social exclusion indicators were the dependent variables, cognitive domains were the independent variables, and age, gender, and duration of follow-up were covariates. Results: The total scores on the measures of cognition and social exclusion were strongly associated (β =  −.469, ∆R2 = 0.215). Participants with high social exclusion were 4.24 times more likely to have cognitive impairment than those with low social exclusion. Verbal learning was the cognitive function most related to social exclusion domains, and legal capacity was the exclusion domain that showed the strongest relationships with individual cognitive tests. Neurocognition uniquely contributed to housing, work activity, income, and educational attainment, whereas social cognition uniquely contributed to neighborhood deprivation, family and social contacts, and discrimination/stigma. Neurocognition explained more unique variance (11.5%) in social exclusion than social cognition (5.5%). Conclusion: The domains of cognitive impairment were strongly and differentially related to those of social exclusion. Given that such an association pattern is likely bidirectional, a combined approach, both social and cognitive, is of paramount relevance in addressing the social exclusion experienced by individuals with psychotic disorders., The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness (Grant PI16/02148 and 19/01698) and the Regional Government of Navarra (Grant 31/17 and 41/18). The authors have no relevant financial or non-financial interests to disclose.

Negative symptoms are a core dimension of schizophrenia and other psychoses that account for a large degree of the poor functional outcomes related to these disorders. Newer assessment scales for negative symptoms, such as the Clinical Assessment Interview for Negative Symptoms (CAINS), provide evidence for separate dimensions of motivational and pleasure (MAP) and expression (EXP) dimensions. This study was aimed at extending the analysis of the clinical, functional and cognitive correlates of CAINS dimensions in a sample of patients with psychotic disorders (n=98) and 50 healthy controls. A psychopathological evaluation was conducted by using the Comprehensive Assessment of Symptoms and History (CASH). To assess the extrapyramidal signs, the UKU scale was used. Community functioning was evaluated by means of real-world and functional attainment measures. Additionally, a full neuropsychological test battery was administered. Pearson correlation and hierarchical multiple linear regression analyses were performed to identify the infuencing and predictive factors associated with the CAINS dimensions. The MAP and EXP dimensions showed strong associations with the Scale for the Assessment of Negative Symptoms (SANS) items and were not signifcantly associated with extra-pyramidal or cognitive defcits. The MAP and EXP CAINS dimensions revealed good predictive validity for real-world functioning and functional attainment measures. These fndings suggest that the CAINS scale endorses good convergent validity for the assessment of negative symptoms and is very useful in the prediction of psychosocial functioning. In addition, the CAINS dimensions might provide advantages over old assessment scales on disentangling the complex associations between negative symptoms and cognitive impairment., This work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148).

Self-reported and interview-based measures can be considered coprimary measures of cognitive performance. We aimed to ascertain to what extent cognitive impairment in psychotic disorders, as assessed with a neuropsychological battery, is associated with subjective cognitive complaints compared to difficulties in daily activities caused by cognitive impairment. We assessed 114 patients who had a psychotic disorder with a set of neuropsychological tests and two additional measures: the Cognitive Assessment Interview-Spanish version (CAI-Sp) and the Frankfurt Complaint Questionnaire (FCQ). Patients also underwent a clinical assessment. The CAI-Sp correlated significantly with all the clinical dimensions, while the FCQ correlated only with positive and depressive symptoms. The CAI-Sp correlated significantly with all cognitive domains, except for verbal memory and social cognition. The FCQ was associated with attention, processing speed and working memory. The combination of manic and depressive symptoms and attention, processing speed, working memory and explained 38–46% of the variance in the patients’ CAI-Sp. Education and negative symptoms, in combination with attention, processing speed, and executive functions, explained 54–59% of the CAI-Sp rater’s variance. Only negative symptoms explained the variance in the CAI-Sp informant scores (37–42%). Depressive symptoms with attention and working memory explained 15% of the FCQ variance. The ability to detect cognitive impairment with the CAI-Sp and the FCQ opens the possibility to consider these instruments to approximate cognitive impairment in clinical settings due to their ease of application and because they are less time-consuming for clinicians., This work was supported by the Government of Navarra
(grants 17/31 and 18/41) and the Carlos III Health Institute (FEDER
Funds) from the Spanish Ministry of Economy and Competitivity
(16/02148 and 19/1698).

Fe de erratas en https://academica-e.unavarra.es/handle/2454/54500, Background. Suicidal thoughts and behaviors (STBs) are a major concern in people with psychotic disorders. There is a need to examine their prevalence over long-term follow-up after first-episode psychosis (FEP) and determine their early predictors.
Methods. Of 510 participnts with FEP evaluated on 26 risk factors for later outcomes, 260 were reassessed after 21 years of follow-up for lifetime ratings of most severe suicidal ideation, number of suicide attempts, and lethality of the most severe attempt. Risk factors and STB outcomes were modeled using hierarchical linear regression analysis.
Results. Over the 21-year follow-up period, 62.7% of participants experienced suicidal thoughts, 40.8% attempted suicide, and 18 died of suicide (3.5% case fatality and 20.6% proportionate mortality). Suicidal ideation was independently predicted by parental socioeconomic status, familial load of major depression, neurodevelopmental delay, poor adolescence social networks, and suicidal thoughts/behavior at FEP. The number of suicide attempts was independently predicted by years of follow-up, familial load of major depression, obstetric complications, childhood adversity, and suicidal thoughts/behavior at FEP. Lethality was independently predicted by familial load of major depression, obstetric complications, neurodevelopmental delay, and poor adolescence social networks. The proportion of variance in suicidal ideation, attempts, and lethality explained by the independent predictors was 29.3%, 21.2%, and 18.1%, respectively.
Conclusions. STBs are highly prevalent in psychotic disorders and leads to substantial morbidity and mortality. They were predicted by a number of early risk factors, whose clinical recognition should contribute to improved prediction and prevention in people with psychotic disorders., This work was funded by the Instituto de Salud Carlos III, the Spanish Ministry of Science, Innovation and Universities, the European Regional Development Fund (ERDF/FEDER) (VP, gran numbers PI16/02148; EGJ and MJC, PI19/01968), and the Regional Government of Navarra (VP, grant number 31/17; LMI, grant number 41/18). Open access funding provided by Universidad Pública de Navarra.

Network analysis is an important conceptual and analytical approach in mental health research. However, few studies have used network analysis to examine the structure of cognitive performance in psychotic disorders.
We examined the network structure of the cognitive scores of a sample of 207 first-episode psychosis (FEP) patients and 188 healthy controls. Participants were assessed using a battery of 10 neuropsychological tests. Fourteen cognitive scores encompassing six cognitive domains and premorbid IQ were selected to perform the network analysis.
Many similarities were found in the network structure of FEP patients and healthy controls. Verbal memory, attention, working memory and executive function nodes were the most central nodes in the network. Nodes in both groups corresponding to the same tests tended to be strongly connected.
Verbal memory, attention, working memory and executive function were central dimensions in the cognitive network of FEP patients and controls. These results suggest that the interplay between these core dimensions is essential for demands to solve complex tasks, and these interactions may guide the aims of cognitive rehabilitation. Network analysis of cognitive dimensions might have therapeutic implications that deserve further research., This work was supported by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - Fondo Europeo de Desarrollo Regional, and European Union, Una manera de hacer Europa - FEDER Funds (grant numbers PI08/1026; 11/02831; 14/1621; 16/02148) and by the Health Department of the Government of Navarra (grant numbers 87/2014; 17/031; 41/18).

We examined the empirical validity of a staging model of psychotic disorders primarily based on their long-term course. The model distinguished 6 consecutive stages (2A, 2B, 3A, 3B, 4A, 4B) based on symptom recurrence, persistence and progression, such as functional decline. We analyzed data from 243 participants with first-admission psychosis who were followed-up for a mean of 20.9 years and assessed for 22 baseline variables, 23 construct-related variables and 31 outcome variables. Later stages scored significantly poorer than early stages on most validators by showing generally medium to large effect sizes and a dose-response pattern, thus confirming the validity of the model. For each set of validators, differences between consecutive stages were especially evident for stages 2 and 3A, although many variables from each validation realm also differentiated between the consecutive stages 3A and above. Baseline predictors including familial load of schizophrenia, neurodevelopmental impairment, childhood adversity, treatment delay, negative symptoms, neurological impairment and poor early response to treatment, independently accounted for 49.9% of the variance of staging. A staging model of psychosis based primarily on its long-term course has sound construct, outcome and predictive validity, which may inform about stage indicators and predictors of clinical stages from psychosis onset., The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness (grant PI16/02148 and 19/01698) and the Regional Government of Navarra (grant 31/17 and 41/18).

Background: Most medications used to treat psychotic disorders possess anticholinergic properties. This may
result in a considerable anticholinergic burden (ACB), which may have deleterious effects on long-term outcomes. The extent to which cumulative ACB over years of treatment with psychotropic medications impacts
different outcome domains remains unknown.
Methods: This was a naturalistic study of 243 subjects with first-episode psychosis aimed at examining the cumulative effect of ACB of psychotropic medications administered over the illness course (ACB-years exposure) on
several outcome domains assessed after a mean 21-year follow-up. Associations between ACB and the outcomes
were modelled accounting for relevant confounding factors by using hierarchical linear regression analysis.
Results: Over the study period, 81.9 % of the participants were dispensed at least one drug with strong anticholinergic effects for at least 1 year; at the follow-up visit, 60.5 % of the participants continued to take medications with strong ACB. ACB-years exposure was uniquely related to severity of negative symptoms (β = 0.144,
p = 0.004), poor psychosocial functioning (β = 0.186, p < 0.001) and poor cognitive performance (β = − 0.273, p
< 0.001). This association pattern was independent of a schizophrenia diagnosis. Most of the associations between ACB at the follow-up visit and the outcomes were accounted for ACB-years exposure.
Conclusion: Lifetime ACB of psychotropic medications has deleterious effects on the outcome of psychotic disorders. Clinicians should avoid prescribing medications with strong ACB, since there are numerous alternatives
within each psychotropic drug group for prescribing medications with low ACB., The study was funded by the Spanish Ministry of Economy, Industry
and Competitiveness (grant PI16/02148 and 19/01698) and the
Regional Government of Navarra (grant 31/17 and 41/18).

Background
Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change.

Methods
This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories.

Results
The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed.

Conclusions
FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions., The study was funded by the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitiveness (grant number PI16/02148 and 19/01698) and the Regional Government of Navarra (grant number 31/17 and 41/18).

Phenotype validation of endogenous psychosis is a problem that remains to be solved. This study investigated the neuropsychological performance of endogenous psychosis subtypes according to Wernicke–Kleist–Leonhard’s classification system (WKL). The participants included consecutive admissions of patients with schizophrenia spectrum disorder or mood disorder with psychotic symptoms (N = 98) and healthy comparison subjects (N = 50). The patients were assessed by means of semi-structured interviews and diagnosed through the WKL system into three groups: a manic-depressive illness and cycloid psychosis group (MDC), unsystematic schizophrenia (USch) and systematic schizophrenia (SSch). All the participants completed a comprehensive neuropsychological battery. The three Leonhard’s psychosis subtypes showed a common neuropsychological profile with differences in the severity of impairment relative to healthy controls. MDC patients showed better performance on premorbid intelligence, verbal memory and global cognitive index than USch and SSch patients, and they showed better performance on processing speed, and working memory than SSch patients. USch patients outperformed SSch patients in verbal memory, working memory and global cognitive index. Neuropsychological performance showed a modest accuracy for classification into the WKL nosology. Our results suggest the existence of a common profile of cognitive impairment cutting across WKL subtypes of endogenous psychosis but with significant differences on a severity continuum. In addition, classification accuracy in the three WKL subtypes by means of neuropsychological performance was modest, ranging between 40 and 64% of correctly classified patients., This work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148).

Background
Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.

Methods
Two hundred and forty-three patients were assessed at their first episode of psychosis for CA and re-assessed after a mean of 21 years of follow-up for several outcome domains, including symptoms, functioning, quality of life, cognitive performance, neurological dysfunction, and comorbidity. The unique predictive ability of CA exposure for outcomes was examined using linear regression analysis controlling for relevant confounders, including socioeconomic status, family risk of schizophrenia, and obstetric complications.

Results
There were 54% of the patients with a documented history of CA at mild or higher levels. CA experiences were more prevalent and severe in schizophrenia than in other psychotic disorders (p < 0.001). Large to very large effect sizes were observed for CA predicting most role functioning variables and negative symptoms (¿R2 between 0.105 and 0.181). Moderate effect sizes were observed for positive symptoms, personal functioning, impaired social cognition, impaired immediate verbal learning, poor global cognition, internalized stigma, poor personal recovery, and drug abuse severity (¿R2 between 0.040 and 0.066). A dose¿response relationship was observed between levels of CA and severity of outcome domains.

Conclusion
Our results suggest a strong and widespread link between early adversity exposure and outcomes of psychotic disorders. Awareness of the serious long-term consequences of CA should encourage better identification of those at risk and the development of effective interventions., The study was funded by the Spanish Ministry of Economy, Industry and Competitiveness (grant PI16/02148 and 19/01698) and the Regional Government of Navarra (grant 31/17 and 41/18).

Background Few studies have examined the long-term outcomes of first-episode psychosis (FEP) among patients beyond symptomatic and functional remission. This study aimed to broaden the scope of outcome indicators by examining the relationships between 12 outcomes of FEP patients at 20.9 years after their initial diagnosis. Methods At follow-up, 220 out of 550 original patients underwent a new assessment. Twelve outcomes were assessed via semistructured interviews and complementary scales: symptom severity, functional impairment, personal recovery, social disadvantage, physical health, number of suicide attempts, number of episodes, current drug use, dose-years of antipsychotics (DYAps), cognitive impairment, motor abnormalities, and DSM-5 final diagnosis. The relationships between these outcome measures were investigated using Spearman's correlation analysis and exploratory factor analysis, while the specific connections between outcomes were ascertained using network analysis. Results The outcomes were significantly correlated; specifically, symptom severity, functioning, and personal recovery showed the strongest correlations. Exploratory factor analysis of the 12 outcomes revealed two factors, with 11 of the 12 outcomes loading on the first factor. Network analysis revealed that symptom severity, functioning, social disadvantage, diagnosis, cognitive impairment, DYAps, and number of episodes were the most interconnected outcomes. Conclusion Network analysis provided new insights into the heterogeneity between outcomes among patients with FEP. By considering outcomes beyond symptom severity, the rich net of interconnections elucidated herein can facilitate the development of interventions that target potentially modifiable outcomes and generalize their impact on the most interconnected outcomes., Funding for the study came from the Gobierno de Navarra (grants 31/17 and 41/18), Ministerio de Economía, Industria y Competitividad de España (grants PI16/02148 and 19/01698), and Instituto de Salud Carlos III (ISCIII) (grant RD21/0009/0001),

Background: Our current ability to predict the long-term course and outcome of subjects with a first-episode of psychosis (FEP) is limited. To improve our understanding of the long-term outcomes of psychotic disorders and their determinants, we designed a follow-up study using a well-characterized sample of FEP and a multidimensional approach to the outcomes. The main goals were to characterize the long-term outcomes of psychotic disorders from a multidimensional perspective, to address the commonalities and differential characteristics of the outcomes, and to examine the common and specific predictors of each outcome domain. This article describes the rationale, methods, and design of a longitudinal and naturalistic study of subjects with epidemiologically defined first-admission psychosis.

Methods: Eligible subjects were recruited from consecutive admissions between January 1990 and December 2009. Between January 2018 and June 2021, we sought to trace, re-contact, and re-interview the subjects to assess the clinical course, trajectories of symptoms and functioning, and the different outcomes of psychotic disorders. Since this is a naturalistic study, the research team will not interfere with the subjects' care and treatment. Predictors include antecedent variables, first-episode characteristics, and illness-related variables over the illness course. We assess eight outcome domains at follow-up: psychopathology, psychosocial functioning, self-rated personal recovery, self-rated quality of life, cognitive performance, neuromotor dysfunction, medical and psychiatric comorbidities, and mortality rate. The range of the follow-up period will be 10–31 years with an estimated mean of 20 years. We estimate that more than 50% of the baseline sample will be assessed at follow-up.

Discussion: The study design was driven by the increasing need to refine the ability to predict the different clinical outcomes in FEP, and it aims to close current gaps in knowledge, with a broad approach to both the definition of outcomes and their determinants. To the best of our knowledge, this study is one of the few attempting to characterize the very long-term outcome of FEP and the only study addressing eight major outcome domains. We hope that this study helps to better characterize the long-term outcomes and their determinants, enabling better risk stratification and individually tailored, person-based interventions., This study was funded by the Carlos III Health Institute (FEDER Funds) fromthe Spanish Ministry of Economy and Competitivity (grant PI16/02148) and the Regional Government of Navarra (grant 31/17).

Schizophrenia and other psychoses display a common profile of mild to moderate cognitive deficits that are associated with poor functional outcomes.
Cognitive impairment is usually evaluated by neuropsychological assessment, and interview-based measures with good psychometric properties and high utility for clinical practice are now available. However, the extent to which a set of clinical criteria can be used as proxy measures of cognitive deficits in this population has not been tested.
This study aimed to examine the empirical validity of a set of clinical criteria for cognitive impairment associated with psychosis (CIAPs).
Ninety-eight patients with non-pure affective psychosis and 50 healthy-matched controls were included.
The CIAPs criteria were empirically tested against antecedent, concurrent and outcome validators and by means of a neuropsychological evaluation based on MATRICS Consensus Cognitive Battery (MCCB).
The CIAPs criteria showed strong associations with outcomes and certain antecedent validators and moderate associations with concurrent validators. The CIAPs criteria achieved superior neuropsychological validity compared to current DSM 5 criteria for schizophrenia, the B-criterion of DSM 5 schizophrenia or a combination of both criteria.
Cognitive impairment associated with psychosis can be clinically assessed and is a useful tool for clinical practice and predicting outcomes of schizophrenia and related psychosis., This work was supported by the Government of Navarra (grants 17/31, 18/41, 87/2014) and the Carlos III Health Institute (FEDER Funds) from the Spanish Ministry of Economy and Competitivity (14/01621 and 16/02148).