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
Premorbid adjustment and clinical correlates of cognitive impairment in first-episode psychosis: the PEPsCog study
(Elsevier, 2015) Cuesta, Manuel J.; Sánchez Torres, Ana María; Cabrera, Bibiana; Bioque, Miquel; Merchán-Naranjo, Jessica; Corripio, Iluminada; González Pinto, Ana; Lobo, Antonio; Bombín, Igor; Serna, Elena de la; Sanjuán, Julio; Parellada, Mara; Sáiz-Ruiz, Jerónimo; Bernardo, Miguel; PEPs Group; Ciencias de la Salud; Osasun Zientziak
Background: The extent to which socio-demographic, clinical, and premorbid adjustment variables contribute to cognitive deficits in first-episode schizophrenia spectrum disorders remains to be ascertained. Aims: To examine the pattern and magnitude of cognitive impairment in first-episode psychosis patients, the profile of impairment across psychosis subtypes and the associations with premorbid adjustment. Methods: 226 first-episode psychosis patients and 225 healthy controls were assessed in the PEPsCog study, as part of the PEPs study. Results: Patients showed slight to moderate cognitive impairment, verbal memory being the domain most impaired compared to controls. Broad affective spectrum patients had better premorbid IQ and outperformed the schizophrenia and other psychosis groups in executive function, and had better global cognitive function than the schizophrenia group. Adolescent premorbid adjustment together with age, gender, parental socio-economic status, and mean daily antipsychotic doses were the factors that best explained patients' cognitive performance. General and adolescent premorbid adjustment, age and parental socio-economic status were the best predictors of cognitive performance in controls. Conclusions: Poorer premorbid adjustment together with socio-demographic factors and higher daily antipsychotic doses were related to a generalized cognitive impairment and to a lower premorbid intellectual reserve, suggesting that neurodevelopmental impairment was present before illness onset.
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
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
Cognitive intraindividual variability, cognitive impairment and psychosocial functioning in first-episode psychosis patients
(Elsevier, 2023-09-08) Sánchez Torres, Ana María; García de Jalón, Elena; Gil Berrozpe, Gustavo José; Peralta Martín, Víctor; Cuesta Zorita, Manuel Jesús; PEPsNa Group; Ciencias de la Salud; Osasun Zientziak
Cognitive intraindividual variability (IIV) refers to fluctuations in performance across tasks (i.e. dispersion) or in a single task on multiple occasions (i.e. inconsistency). Little is known about IIV in patients with first-episode psychosis (FEP). We aimed to explore the association between IIV and both global cognitive performance and psychosocial functioning in a sample of 103 FEP patients. Patients were recruited at discharge from the PEPsNa program, a FEP follow-up intervention program lasting 24 months. The Social and Occupational Functioning Scale (SOFAS) and the Cognitive Assessment Interview (CAI-Sp) were employed for assessing psychosocial functioning. Cognitive assessments were performed using the MATRICS Cognitive Assessment Battery (MCCB), and the variability in the cognitive functions assessed with the MCCB was used to calculate the IIV. Significant correlations were obtained between IIV and global MCCB scores, the CAI-Sp and the SOFAS. We found significant differences in psychosocial functioning and cognitive performance between patients with high and low IIV. A higher IIV in FEP patients was related both to worse psychosocial functioning and worse global cognitive performance. Unlike global cognitive performance, IIV was not related to clinical characteristics, suggesting that it could be an indicator of cognitive impairment even in the absence of global impairment.
Open Access
From genetics to psychosocial functioning: unraveling the mediating roles of cognitive reserve, cognition, and negative symptoms in first-episode psychosis
(Wiley, 2024-12-25) Forte, María Florencia; Clougher, Derek; Segura, Àlex G.; Sánchez Torres, Ana María; Vieta, Eduard; Garriga, Marina; Lobo, Antonio; González Pinto, Ana; Díaz-Caneja, Covadonga M.; Roldán, Alexandra; Martínez-Aran, Anabel ; Serna, Elena de la; Mané, Anna; Mas, Sergi; Torrent, Carla; Allot, Kelly; Bernardo, Miguel; Amoretti, Silvia; PEPs Group; Iris Rodríguez, Corina; Ciencias de la Salud; Osasun Zientziak
Background: Studies have shown associations between polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), cognition, negative symptoms (NS), and psychosocial functioning in first-episode psychosis (FEP). However, theirspecific interactions remain unclear. This study aimed to investigate the mediating roles of CR, cognition, and NS in the relationship between PRSEA and psychosocial functioning one year after a FEP. Additionally, we sought to explore the impact of two NSsubtypes on this relationship: diminished Expression (EXP-NS) and Motivation and Pleasure (MAP-NS). Methods: A total of 138 FEP participants, predominantly male (70%), with a mean age of 24.77 years (SD = 5.29), underwent genetic, clinical, and cognitive assessments two months after study enrollment. Functioning evaluation followed at one-year follow-up. To investigate the mediating role of CR, cognition, and NS in the relationship between PRSEA and functioning, a serial mediation model was employed. Two further mediation models were tested to explore the differential impact of EXP-NS and MAP-NS. Mediation analysis was performed using the PROCESS macro version 4.1 within SPSS version 26. Results: The serial mediation model revealed a causal chain for PRSEA > CR > cognition > NS > Functioning (β = −3.08, 95%CI[−5.73, −0.43], p = 0.023). When differentiating by type of NS, only EXP-NS were significantly associated in the casual chain (β = −0.17, 95% CI [−0.39, −0.01], p < 0.05). Conclusions: CR, cognition and NS -specifically EXP-NS- mediate the association between PRSEA and psychosocial functioning at one-year follow-up in FEP patients. These results highlight the potential for personalized interventions based on genetic predisposition.
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.
Open Access
Spontaneous parkinsonism is associated with cognitive impairment in antipsychotic-naive patients with first-episode psychosis: a 6-month follow-up study
(Oxford University Press, 2014) Cuesta, Manuel J.; Sánchez Torres, Ana María; García de Jalón, Elena; Campos, María S.; Ibáñez Beroiz, Berta; Moreno-Izco, Lucía; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak
There is now growing evidence that parkinsonism and other extrapyramidal signs are highly prevalent in patients with first-episode psychosis who have never been exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis were enrolled on the study and followed up for 6 months. Seventy-seven completed assessments at 3 time points (baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor abnormalities. The Simpson-Angus Scale (SAS) was used for the assessment of extrapyramidal signs, and each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore the longitudinal relationships between parkinsonism scores and cognitive impairment. Parkinsonism scores showed significant strong longitudinal associations with deficits in memory, executive functioning, and attention. Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high 6-month predictive values for cognitive impairment. In addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia, akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor subscores on the SAS scale. These results emphasize the relevance of the assessment of parkinsonism signs prior to starting to administer antipsychotic drugs, as core manifestations of psychotic illness with a high predictive value for cognitive impairment.
Open Access
Relapse, cognitive reserve and their relationship with cognition in first episode schizophrenia: a 3-year follow-up study
(Elsevier, 2023) Sánchez Torres, Ana María; Amoretti, Silvia; Enguita Germán, Mónica; Mezquida, Gisela; Moreno-Izco, Lucía; Panadero-Gómez, Rocío; Rementería, Lide; Toll, Alba; Rodríguez-Jiménez, Roberto; Roldán, Alexandra; Pomarol-Clotet, Edith; Ibáñez, Ángela; Usall, Judith; Contreras, Fernando; Vieta, Eduard; López-Ilundain, José M.; Merchán-Naranjo, Jessica; González Pinto, Ana; Berrocoso, Esther; Bernardo, Miguel; Cuesta, Manuel J.; Forte, María Florencia; González-Díaz, Jairo M.; Parellada, Mara; Abrokwa, Hayford; Sans Segura, María; González, Judtih Selma; Zorrilla, Iñaki; González-Ortega, Itxaso; Legido, Teresa; Mané, Anna; Sanchez-Pastor, Luis; Rentero, David; Sarró, Salvador; García-León, María Ángeles; Butjosa, Anna; Pardo, Marta; Zarzuela, Amalia; Ribeiro Fernández, María; Sáiz-Ruiz, Jerónimo; León-Quismondo, Leticia; Hernández, Miguel; Cámara, Concepción de la; Gutiérrez-Fraile, Miguel; González-Blanco, Leticia; Ciencias de la Salud; Osasun Zientziak
Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness.
Open Access
Individual trajectories of cognitive performance in first episode psychosis: a 2-year follow-up study
(Springer, 2018) Sánchez Torres, Ana María; Moreno-Izco, Lucía; Lorente Omeñaca, Ruth; Cabrera, Bibiana; Lobo, Antonio; González Pinto, Ana; Merchán-Naranjo, Jessica; Corripio, Iluminada; Vieta, Eduard; Serna, Elena de la; Butjosa, Anna; Contreras, Fernando; Sarró, Salvador; Mezquida, Gisela; Ribeiro Fernández, María; Bernardo, Miguel; Cuesta, Manuel J.; PEPs Group; Ciencias de la Salud; Osasun Zientziak
Individual changes over time in cognition in patients with psychotic disorders have been studied very little, especially in the case of frst episode psychosis (FEP). We aimed to establish whether change in individual trajectories in cognition over 2 years of a sample of 159 FEP patients was reliable and clinically signifcant, using the reliable change index (RCI) and clinically signifcant change (CSC) methods. We also studied a sample of 151 matched healthy controls. Patients and controls were assessed with a set of neuropsychological tests, as well as premorbid, clinical and functionality measures. We analysed the course of cognitive measures over time, using analysis of variance, and the individual trajectories in the cognitive measures with the regression-based RCI (RCISRB) and the CSC. The RCISRB showed that between 5.4 and 31.2% of the patients showed deterioration patterns, and between 0.6 and 8.8% showed improvement patterns in these tests over time. Patients showing better cognitive profles according to RCISRB (worsening in zero to two cognitive measures) showed better premorbid, clinical and functional profles than patients showing deterioration patterns in more than three tests. When combining RCISRB and CSC values, we found that less than 10% of patients showed improvement or deterioration patterns in executive function and attention measures. These results support the view that cognitive impairments are stable over the frst 2 years of illness, but also that the analysis of individual trajectories could help to identify a subgroup of patients with particular phenotypes, who may require specifc interventions.