Open Access
Additive effects of a family history of schizophrenia spectrum disorders and an environmental risk score for the outcome of patients with non-affective first-episode psychosis
(Cambridge University Press, 2024) Cuesta Zorita, Manuel Jesús; García de Jalón, Elena; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Aranguren Conde, Lidia; Gutiérrez, Gerardo; Corrales, Asier; Zarzuela, Amalia; Ibáñez Beroiz, Berta; Peralta Martín, Víctor; PEPsNa Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). Methods: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. Results: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. Conclusions: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.
Open Access
20-Year trajectories of six psychopathological dimensions in patients with first-episode psychosis: could they be predicted?
(Elsevier, 2024) Cuesta, Manuel J.; Gil Berrozpe, Gustavo José; Sánchez Torres, Ana María; Moreno-Izco, Lucía; García de Jalón, Elena; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
Patients with first-episode psychoses (FEP) exhibit heterogeneity in clinical manifestations and outcomes. This study investigated the long-term trajectories of six key psychopathological dimensions (reality-distortion, negative, disorganization, catatonia, mania and depression) in patients diagnosed with FEP. A total of 243 patients were followed up for 20 years and the trajectories of the dimensions were analysed using growth mixture modelling. These dimensions showed varied course patterns, ranging from two to five trajectories. Additionally, the study examined the predictive value of different factors in differentiating between the long-term trajectories. The exposome risk score showed that familial load, distal and intermediate risk factors, acute psychosocial stressors and acute onset were significant predictors for differentiating between long-term psychopathological trajectories. In contrast, polygenic risk score, duration of untreated psychosis and duration of untreated illness demonstrated little or no predictive value. The findings highlight the importance of conducting a multidimensional assessment not only at FEP but also during follow-up to customize the effectiveness of interventions. Furthermore, the results emphasize the relevance of assessing premorbid predictors from the onset of illness. This may enable the identification of FEP patients at high-risk of poor long-term outcomes who would benefit from targeted prevention programs on specific psychopathological dimensions.
Open Access
Empirical validity of Leonhard's psychoses: a long-term follow-up study of first-episode psychosis patients
(Elsevier, 2023-12-18) Cuesta, Manuel J.; Sánchez Torres, Ana María; García de Jalón, Elena; Moreno-Izco, Lucía; Gil Berrozpe, Gustavo José; Zarzuela, Amalia; Papiol, S.; Fañanás, Lourdes; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
The validation of nosological diagnoses in psychiatry remains a conundrum. Leonhard's (1979) nosology seems to be one of the few acceptable alternative categorical models to current DSM/ICD systems. We aimed to empirically validate Leonhard's four classes of psychoses: systematic schizophrenia (SSch), unsystematic (USch), cycloid psychosis (Cyclo), and manic-depressive illness (MDI) using a comprehensive set of explanatory validators. 243 patients with first-episode psychosis were followed between 10 and 31 years. A wide-ranging assessment was carried out by collecting data on antecedent, illness-related, concurrent, response to treatment, neuromotor abnormalities, and cognitive impairment variables. Compared with USch, Cyclo, and MDI, SSch displayed a pattern of impairments significantly larger across the seven blocks of explanatory variables. There were no significant differences between Cyclo and MDI in explanatory variables. Except for the majority of illness-onset features, USch displayed more substantial abnormalities in the explanatory variables than Cyclo and MDI. SSch and MDI showed higher percentages of correctly classified patients than USch and Cyclo in linear discriminant analyses. Partial validation of Leonhard's classification was found. SSch showed differences in explanatory variables with respect to Cyclo and MDI. USch showed also significant differences in explanatory variables regarding Cyclo and MDI, although with a lower strength than SSch. There was strong empirical evidence of the separation between both Leonhard's schizophrenia subtypes; however, the distinction between the Cyclo and MDI groups was not empirically supported. A mild to moderate discriminative ability between Leonhard's subtypes on the basis of explanatory blocks of variables was observed.
Open Access
Small area variations in non-affective first-episode psychosis: the role of socioeconomic and environmental factors
(Springer, 2023) Gutiérrez, Gerardo; Goicoa Mangado, Tomás; Ugarte Martínez, María Dolores; Aranguren Conde, Lidia; Corrales, Asier; Gil Berrozpe, Gustavo José; Librero, Julián; Sánchez Torres, Ana María; Peralta Martín, Víctor; García de Jalón, Elena; Cuesta, Manuel J.; Martínez, Matilde; Otero, María; Azcárate, Leire; Pereda, Nahia; Monclús, Fernando; Moreno, Laura; Fernández, Alba; Ariz, Mari Cruz; Sabaté, Alba; Aquerreta, Ainhoa; Aguirre, Izaskun; Lizarbe, Tadea; Begué, María José; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Institute for Advanced Materials and Mathematics - INAMAT2
Background: There is strong evidence supporting the association between environmental factors and increased risk of non-affective psychotic disorders. However, the use of sound statistical methods to account for spatial variations associated with environmental risk factors, such as urbanicity, migration, or deprivation, is scarce in the literature. Methods: We studied the geographical distribution of non-affective first-episode psychosis (NA-FEP) in a northern region of Spain (Navarra) during a 54-month period considering area-level socioeconomic indicators as putative explanatory variables. We used several Bayesian hierarchical Poisson models to smooth the standardized incidence ratios (SIR). We included neighborhood-level variables in the spatial models as covariates. Results: We identified 430 NA-FEP cases over a 54-month period for a population at risk of 365,213 inhabitants per year. NA-FEP incidence risks showed spatial patterning and a significant ecological association with the migrant population, unemployment, and consumption of anxiolytics and antidepressants. The high-risk areas corresponded mostly to peripheral urban regions; very few basic health sectors of rural areas emerged as high-risk areas in the spatial models with covariates. Discussion: Increased rates of unemployment, the migrant population, and consumption of anxiolytics and antidepressants showed significant associations linked to the spatial-geographic incidence of NA-FEP. These results may allow targeting geographical areas to provide preventive interventions that potentially address modifiable environmental risk factors for NA-FEP. Further investigation is needed to understand the mechanisms underlying the associations between environmental risk factors and the incidence of NA-FEP.
Open Access
Long-term diagnostic stability, predictors of diagnostic change, and time until diagnostic change of first-episode psychosis: a 21-year follow-up study
(Cambridge University Press, 2023-11-21) Peralta, David; Janda-Galán, Lucía; García de Jalón, Elena; Moreno-Izco, Lucía; Sánchez Torres, Ana María; Cuesta, Manuel J.; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
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.
Open Access
Long-term outcomes of first-admission psychosis: a naturalistic 21-year follow-up study of symptomatic, functional and personal recovery and their baseline predictors
(Oxford University Press, 2022) Peralta Martín, Víctor; García de Jalón, Elena; Moreno-Izco, Lucía; Peralta, David; Janda-Galán, Lucía; Sánchez Torres, Ana María; Cuesta, Manuel J.; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
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.
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
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
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
Treatment response of neurological soft signs in drug-naïve patients with a first psychotic episode
(Elsevier, 2012) Cuesta, Manuel J.; Campos, María S.; García de Jalón, Elena; Sánchez Torres, Ana María; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Neurological soft signs (NSS) are intrinsic features of psychosis that appear years before beginning a drug treatment. However, whether NSS respond to antipsychotics and whether these changes are clinically reliable and significant remains to be seen. Objective: We sought to determine the effect of antipsychotics on NSS in a first-episode psychosis (FEP) sample who had never exposed to antipsychotics. Methods: We included 100 antipsychotic-naïve patients with FEP in this study. 77 patients completed the study assessments at baseline, 1 month and 6 months. The Neurological Evaluation Scale (NES) evaluated NSS. Patients were alternatively selected to receive risperidone or olanzapine treatments and continued participation in their mental health setting during follow-up with one of four treatment groups: risperidone, olanzapine, mixed antipsychotics or no medication. We also included a control group of 28 healthy volunteers. Results: Treatment groups showed a statistically significant improvement on total NES scores and most NES subscales except for ‘frontal signs’, regardless of antipsychotic allocation. NSS changes were reliable; however, there was great variation in the total NES scores between treatment groups, ranging from 4% to 24%. Clinically meaningful changes (CMCs) on total NES scores ranged from 25% to 50%. Six patients (7.8%) demonstrated a reliable change (RC) and CMC on total NES scores. Conclusions: NSS improved significantly over follow up regardless of the treatment regimen assigned to antipsychotic-naïve patients with a FEP. However, only 6 (7.8%) achieved a reliable and clinically meaningful improvement. The pattern of response of NSS to antipsychotic drugs evidenced both state and trait characteristics.