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
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
Duration of untreated negative and positive symptoms of psychosis and cognitive impairment in first episode psychosis
(Elsevier, 2012) Cuesta, Manuel J.; García de Jalón, Elena; Campos, María S.; Ibáñez, Berta; Sánchez Torres, Ana María; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Duration of untreated psychosis (DUP) has been significantly associated with poor clinical and social outcomes in First Episode Psychosis (FEP) patients, but an association with cognitive outcomes has not been clearly established. Method: Seventy-seven consecutively admitted, drug-naïve patients with FEP were assessed at baseline and at 1 month and 6 months. Underlying dimensions of DUP (general prodrome and positive, negative and disorganisation symptoms) were assessed using the Symptom Onset in Schizophrenia (SOS) inventory (Perkins et al., 2000). To assess the effect of DUP on the neuropsychological status of the patients, a linear mixed-effect model was fitted to each neuropsychological dimension. These models included a dichotomised version of DUP (short versus long duration) as a fixed effect, several adjusting variables to account for patient differences, and a random effect to incorporate the longitudinal structure of the data. Results: Patients with a short duration of untreated negative symptoms (DUNS) or a short duration of untreated positive symptoms (DUPS) outperformed patients with a long duration of untreated symptoms on memory tasks and a pre-attentional visual task but not on measures of verbal fluency, attention, reaction time, visual processing and executive functions. Conclusions: This study provides additional support for an early intervention to shorten DUP to facilitate a better outcome in memory and attentional domains of FEP patients.
Open Access
Controversies surrounding the diagnosis of schizophrenia and other psychoses
(Taylor and Francis, 2009) Cuesta, Manuel J.; Basterra, Virginia; Sánchez Torres, Ana María; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak
The diagnosis of schizophrenia and other psychotic disorders in current psychiatric classifications identifies individuals who are severely ill but who have few clinical characteristics in common. The usual picture of psychotic patients is a mixture of mood and psychotic symptoms. Fortunately, clinicians do not base their therapeutic strategies exclusively on diagnosis, but also on symptom predominance. Thus, clinicians’ treatments have been dimensional in nature for years, although, until recently, their psychiatric classifications had been mainly categorical. The main principle in psychosis classification has been the Kraepelinian dichotomy, despite its lack of enduring empirical validation. Without doubt, current psychiatric classifications have made great strides in reliability and clinical utility, although these advantages have not been enough to compensate for their shortcomings concerning validity. It has recently been suggested that the Kraepelinian dichotomy may be hindering progress in neurobiological research within psychosis. Mounting evidence is now fuelling a paradigm shift in the ongoing process of review of psychiatric classifications toward the introduction of complementary dimensional indicators of psychiatric categorical diagnoses. This new approach will allow us to understand psychosis as prototypical extremes of a severity continuum. The gradients of this continuum may begin with subtle expressions in the general population, continue with milder forms in relatives of psychotic patients and subclinical cases and finally reach the prototypical forms of psychosis at the other extreme. Future complementary dimensional indicators will require sound instruments capable of reflecting a multidimensional assessment of psychopathological symptoms, polydiagnostic interviews and the assessment of a wide range of nonsymptomatic domains. These new methods of assessment merging created by the shift toward a dimensional paradigm will be applied in the forthcoming new diagnostic criteria and may allow for a phenome-wide scanning for psychosis.
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
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.