Open Access
Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis
(Cambridge University Press, 2023) Cuesta, Manuel J.; Papiol, S.; Ibáñez Beroiz, Berta; García de Jalón, Elena; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Moreno-Izco, Lucía; Zarzuela, Amalia; Fañanás, Lourdes; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
Background. Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. Methods. The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. Results. Our results showed that a high FLS-Sz gave greater explanatory capacity for longterm outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. Conclusions. Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.
Embargo
What does really matter in the premorbid background of psychosis leading to long-term disability? a 21-year follow-up cohort study of first-episode psychosis
(Elsevier, 2025-05-01) Peralta Martín, Víctor; García de Jalón, Elena; Moreno-Izco, Lucía; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Peralta, David; Janda-Galán, Lucía; Cuesta, Manuel J.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
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.
Open Access
Neurocognitive and social cognitive correlates of social exclusion in psychotic disorders: a 20-year follow-up cohort study
(Springer, 2024-08-02) Peralta Martín, Víctor; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; García de Jalón, Elena; Moreno-Izco, Lucía; Peralta, David; Janda-Galán, Lucía; Cuesta, Manuel J.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
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.
Open Access
Psychopathological networks in psychosis: changes over time and clinical relevance. A long-term cohort study of first-episode psychosis
(Elsevier, 2023-01-06) Gil Berrozpe, Gustavo José; Peralta Martín, Víctor; Sánchez Torres, Ana María; Moreno-Izco, Lucía; García de Jalón, Elena; Peralta, David; Janda-Galán, Lucía; Cuesta, Manuel J.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background First-episode psychosis is a critical period for early interventions to reduce the risk of poor outcomes and relapse as much as possible. However, uncertainties about the long-term outcomes of symptomatology remain to be ascertained. Methods The aim of the present study was to use network analysis to investigate first-episode and long-term stages of psychosis at three levels of analysis: micro, meso and macro. The sample was a cohort of 510 patients with first-episode psychoses from the SEGPEP study, who were reassessed at the long-term follow-up (n = 243). We used the Comprehensive Assessment of Symptoms and History for their assessments and lifetime outcome variables of clinical relevance. Results Our results showed a similar pattern of clustering between first episodes and long-term follow-up in seven psychopathological dimensions at the micro level, 3 and 4 dimensions at the meso level, and one at the macro level. They also revealed significant differences between first-episode and long-term network structure and centrality measures at the three levels, showing that disorganization symptoms have more influence in long-term stabilized patients. Conclusions Our findings suggest a relative clustering invariance at all levels, with the presence of two domains of disorganization as the most notorious difference over time at micro level. The severity of disorganization at the follow-up was associated with a more severe course of the psychosis. Moreover, a relative stability in global strength of the interconnections was found, even though the network structure varied significantly in the long-term follow-up. The macro level was helpful in the integration of all dimensions into a common psychopathology factor, and in unveiling the strong relationships of psychopathological dimensions with lifetime outcomes, such as negative with poor functioning, disorganization with high antipsychotic dose-years, and delusions with poor adherence to treatment. These results add evidence to the hierarchical, dimensional and longitudinal structure of psychopathological symptoms and their clinical relevance in first-episode psychoses.
Open Access
Effectiveness of the early intervention service for first-episode psychosis in Navarra (PEPsNa): broadening the scope of outcome measures
(Elsevier, 2023-11-25) García de Jalón, Elena; Ariz, Mari Cruz; Aquerreta, Ainhoa; Aranguren Conde, Lidia; Gutiérrez, Gerardo; Corrales, Asier; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Peralta Martín, Víctor; Cuesta, Manuel J.; PEPsNa Group; Ciencias de la Salud; Osasun Zientziak
Background This study compares the effectiveness of a new early intervention service for firstepisode psychosis (FEP) in patients under conventional treatment. Six primary and 10 secondary outcome measures are used to better characterize the comparative effectiveness between two FEP groups. Methods This study plans to enroll 250 patients aged 15-55 years with FEP from all inpatient and outpatient mental health services and primary health care from January 2020 until December 2022. The control group will be composed of 130 FEP patients treated in mental health centers in the 2 years prior to the start of PEPsNa (Programa de Primeros Episodios de Psicosis de Navarra). The primary outcome measures are symptomatic remission, functional recovery, personal recovery, cognitive performance, functional capacity in real-world settings, and costs. The secondary outcome measures are duration of untreated psychosis, substance abuse rate, antipsychotic monotherapy, minimal effective dose of antipsychotic drugs, therapeutic alliance, drop-out rate, number of relapses, global mortality and suicidality, resource use, and general satisfaction in the program. Discussion This study arises from the growing need to broaden the scope of outcome measures in FEP patients and to account for unmet needs of recovery for FEPs. It aims to contribute in the dissemination of the NAVIGATE model in Europe and to provide new evidence of the effectiveness of early intervention services for stakeholders of the National Health Service.
Open Access
Long-term trajectories of clinical staging in first-episode psychosis and their associated cognitive outcome: a 21-year follow-up study
(Elsevier, 2024-02-27) Cuesta, Manuel J.; Sánchez Torres, Ana María; Moreno-Izco, Lucía; García de Jalón, Elena; Gil Berrozpe, Gustavo José; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
Cognitive deficits are already present before psychosis onset but are a key feature of first-episode psychosis (FEP). The objective of this study was to investigate the cognitive outcomes of a cohort of FEP patients who were diagnosed using the clinical staging approach and were followed for up to 21 years. We analyzed data from 173 participants with first-admission psychosis who were followed-up for a mean of 20.9 years. The clinical staging assessment was adapted from the clinical staging framework developed by McGorry et al.1 Cognitive assessment was performed using the MATRICS Consensus Cognitive Battery (MMCB) at the end of follow-up. FEP patients who were longitudinally diagnosed in the lowest clinical stages (stages 2A and 2B) showed better performance in attention, processing speed, and MCCB overall composite score than those in the highest clinical stages (stages 4A and 4B). There was a significant linear trend association between worsening of all MCCB cognitive functions and MCCB overall composite score and progression in clinical staging. Furthermore, the interval between two and five years of follow-up appears to be associated with deficits in processing speed as a cognitive marker. Our results support the validation of the clinical staging model over a long-term course of FEP based on neuropsychological performance. A decline in some cognitive functions, such as processing speed, may facilitate the transition of patients to an advanced stage during the critical period of first-episode psychosis.
Open Access
Lifetime suicidal thoughts, attempts, and lethality of attempts as major outcome domains of psychotic disorders: a 21-year prospective cohort study after a first-episode psychosis
(Cambridge University Press, 2025-03-04) Peralta Martín, Víctor; Moreno-Izco, Lucía; García de Jalón, Elena; Sánchez Torres, Ana María; Peralta, David; Janda-Galán, Lucía; Cuesta, Manuel J.; Ansorena, X.; Ballesteros, Alejandro; Chato, J.; Fañanás, Lourdes; Gil Berrozpe, Gustavo José; Giné-Servén, Eloi; Lorente Omeñaca, Ruth; Papiol, S.; Ribeiro Fernández, María; Rosado, E.; Rosero, A.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
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.
Open Access
The network structure of cognitive deficits in first episode psychosis patients
(Elsevier, 2022-06-01) Sánchez Torres, Ana María; Peralta Martín, Víctor; Gil Berrozpe, Gustavo José; Mezquida, Gisela; Ribeiro Fernández, María; Molina-García, Mariola; Amoretti, Silvia; Lobo, Antonio; González Pinto, Ana; Merchán-Naranjo, Jessica; Corripio, Iluminada; Vieta, Eduard; Serna, Elena de la; Bergé, Daniel; Bernardo, Miguel; Cuesta, Manuel J.; PEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
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.
Open Access
Utility of the MoCA for cognitive impairment screening in long-term psychosis patients
(Elsevier, 2020) Gil Berrozpe, Gustavo José; Sánchez Torres, Ana María; García de Jalón, Elena; Moreno-Izco, Lucía; Fañanás, Lourdes; Peralta Martín, Víctor; Cuesta, Manuel J.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
Cognitive impairment is a key feature in patients with psychotic disorders. The Montreal Cognitive Assessment (MoCA) is a brief tool that has been shown to be effective in identifying mild cognitive impairment and early dementia. This study explores the usefulness of this instrument to detect cognitive impairment in long-term psychotic disorders. One hundred-forty stabilized patients were re-evaluated more than 15 years after a First Episode of Psychosis (FEP). Patients were psychopathologically assessed, and the MoCA test and MATRICS Consensus Cognitive Battery (MCCB) were administered. Two cut-off scores for cognitive impairment using the MCCB were applied (T score <40 and < 30). Concurrent validation was found between the total scores of the MoCA and MCCB. We also found significant associations between 5 out of 7 MoCA subtests (visuospatial-executive, attention, language, abstraction and delayed recall) and MCCB subtests but not for the naming and orientation MoCA subtests. Receiver operating characteristic (ROC) analysis suggested a <25 cut-off for cognitive impairment instead of the original <26. Our results suggest that the MoCA test is a useful screening instrument for assessing cognitive impairment in psychotic patients and has some advantages over other available instruments, such as its ease-of-use and short administration time.
Open Access
Assessment of cognitive impairment in psychosis spectrum disorders through self-reported and interview-based measures
(Springer, 2022) Sánchez Torres, Ana María; Moreno-Izco, Lucía; Gil Berrozpe, Gustavo José; Lorente Omeñaca, Ruth; Zandio, María; Zarzuela, Amalia; Peralta Martín, Víctor; Cuesta, Manuel J.; Ciencias de la Salud; Osasun Zientziak
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.