Open Access
Motor abnormalities and cognitive impairment in first-episode psychosis patients, their unaffected siblings and healthy controls
(Elsevier, 2018) Cuesta, Manuel J.; Moreno-Izco, Lucía; Ribeiro Fernández, María; López-Ilundain, José M.; Lecumberri Villamediana, Pablo; Cabada Giadás, María Teresa; Lorente Omeñaca, Ruth; Sánchez Torres, Ana María; Gómez Fernández, Marisol; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak; Matemáticas; Matematika
Motor abnormalities (MAs) may be already evidenced long before the beginning of illness and are highly prevalent in psychosis. However, the extent to which the whole range of MAs are related to cognitive impairment in psychosis remains understudied. This study aimed to examine comparatively the relationships between the whole range of motor abnormalities and cognitive impairments in the first-episode of psychosis (FEP), their unaffected siblings and healthy control subjects. Fifty FEP patients, 21 of their healthy siblings and 24 age- and sex matched healthy controls were included. Motor assessment included catatonic, extrapyramidal and neurological soft signs (NSS) by means of standardized instruments. An exhaustive neuropsychological battery was also performed to extract the 7 cognitive dimensions of MATRICS initiative. Higher scores on NSS but not on extrapyramidal and catatonic signs showed significant associations with worse cognitive performance in the three study groups. However, the pattern of associations regarding specific cognitive functions was different among the three groups. Moreover, extrapyramidal signs showed significant associations with cognitive impairment only in FEP patients but not in their unaffected siblings and healthy controls. Catatonic signs did not show any significant association with cognitive functioning in the three study groups. These findings add evidence to the associations between motor abnormalities, particularly NSS and extrapyramidal signs, and cognitive impairment in first-episode psychosis patients. In addition, our results suggest that the specific pattern of associations between MAs and cognitive functioning is different in FEP patients from those of the unaffected siblings and healthy subjects.
Open Access
The effect of anticholinergic burden of psychiatric medications on major outcome domains of psychotic disorders: a 21-year prospective cohort study
(Elsevier, 2024) 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
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.
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
Neurocognitive correlates of the varied domains of outcomes at 20 year follow-up of first-episode psychosis
(Elsevier, 2022-11-02) Cuesta, Manuel J.; Sánchez-Torres, A. M.; Moreno-Izco, Lucía; García de Jalón, Elena; Gil Berrozpe, Gustavo José; Zarzuela, Amalia; Peralta Martín, Víctor; SEGPEPs Group; Sánchez Torres, Ana María; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Little is known about long-term outcomes of the first episode of psychosis (FEP) other than in the symptomatic domain. We hypothesised that cognitive impairment is associated with poorer multi-domain outcomes at a long-term follow-up of FEP patients. We followed-up 172 FEP patients for a mean of 20.3 years. Ten outcome dimensions were assessed (symptomatic, functional and personal recovery, social disadvantage, physical health, suicide attempts, number of episodes, current drug use, chlorpromazine equivalent doses (CPZ), and schizophrenia/schizoaffective disorder final diagnosis). Cognition was assessed at follow-up. Processing speed and verbal memory deficits showed significant associations with poor outcomes on symptomatic, social functioning, social disadvantage, higher number of episodes, and higher CPZ. Significant associations were found between visual memory impairments were significantly associated with low symptomatic and functional recovery, between attentional deficits and a final diagnosis of schizophrenia/schizoaffective disorder, and between social cognition deficits and poor personal recovery.Lower cognitive global scores were significantly associated with all outcome dimensions except for drug abuse and physical status. Using multiple outcome dimensions allowed for the inclusion of the patients¿ perspective and other commonly neglected outcome measures. Taken together, cognitive impairment in FEP patients is strongly related to poor performance on several outcome dimensions beyond symptomatic remission.
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
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.
Embargo
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
Executive functioning in schizophrenia spectrum disorder patients and their unaffected siblings: a ten-year follow-up study
(Elsevier, 2013) Sánchez Torres, Ana María; Basterra, Virginia; Moreno-Izco, Lucía; Rosa, Araceli; Fañanás, Lourdes; Zarzuela, Amalia; Peralta Martín, Víctor; Cuesta, Manuel J.; Ciencias de la Salud; Osasun Zientziak
Executive dysfunction represents a core deficit that is associated with schizophrenia spectrum disorders (SSDs). However, the longitudinal course of executive deficits in SSDs is still controversial. The aim of this study was to examine the executive performance of 34 SSD patients in relation to 34 of their unaffected siblings over a period of 10 years. Both groups completed psychopathological and executive assessments. Thirteen healthy controls were assessed using the same instruments. At baseline, the SSD patients differed significantly from siblings and controls in their performance on the Trail Making Test-B (TMT-B) and the number of categories in which they succeeded in the Wisconsin Card Sorting Test (WCST). They also differed significantly from the controls in the total number of errors in the WCST. The siblings did not differ in executive functioning from the controls over the follow-up. Longitudinally, the patients demonstrated significant improvement only for the TMT-B. However, only 14.71% of the patients showed reliable and clinically significant improvements for the TMT-B, and 8.82% made more errors on the WCST at the follow-up evaluation. Less than 3% of the patients showed either improved or worse results on the remaining measures of the WCST. A stabilisation pattern for the WCST was observed in the three groups. The patients performed worse than their siblings and controls on both executive tests. Some patients exhibited significant improvements in the TMT-B over time, but this improvement was reliable and clinically significant for less than 15% of the sample. Thus, we conclude that the patients exhibited stable impairments over time in the executive functions assessed.
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.
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.