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
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
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.
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
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.
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
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
Familial liability to schizophrenia and mood disorders and cognitive impairment in psychosis
(Elsevier, 2015) Cuesta, Manuel J.; Zarzuela, Amalia; Sánchez Torres, Ana María; Lorente Omeñaca, Ruth; Moreno-Izco, Lucía; Sanjuán, Julio; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak
Schizophrenia and other psychoses are complex disorders with high rates of cognitive impairment and a considerable degree of genetic and environmental influence on its etiology. Whether cognitive impairment is related to dimensional scores of familial liability is still matter of debate. We conducted a cross-sectional study including 169 patients with psychotic disorders and 26 healthy controls. Attention, memory and executive functions were assessed, and familial loading scores for schizophrenia and mood disorders were calculated. The relationships between familial liability and neuropsychological performance were examined with Spearman's correlation coefficients. In addition, patients were classified into three groups by family loading tertiles, and comparisons were performed between the patients in the top and bottom tertiles. Low familial loading scores for schizophrenia showed a significant association with poor executive functioning and delayed visual memory. And these results were also achieved when the subset of psychotic patients in the two extreme tertiles of family loadings of schizophrenia and mood disorders were compared. Low familial liability to schizophrenia seems to be a contributing factor for the severity of cognitive impairment in patients with a broad putative schizophrenia spectrum diagnosis.