Towards personalized medicine in psychosis: the roles of social cognition and metacognition

[eng] People with psychosis experience a range of symptoms and impairments that significantly impact their lives and often concur with disability. The best predictors of functional outcome are social cognition and metacognition, which are often impaired in psychosis. Interventions to improve both domains are effective, but this efficacy does not always translate into better functioning. Delivering early, and targeted social cognitive or metacognitive interventions to patients with psychosis could be instrumental in preventing poor functional outcome and preventing relapse, but the grounds on how to personalize these interventions are unknown. Although it has been suggested that the approach should take sex differences, the refining of measurement instruments and the use of sophisticated statistical models, these have not been explored yet. Under this rationale, the present doctoral dissertation aims to: 1) validate a test of facial emotion recognition (Baron Cohen’s Face Test) in healthy population, with the aim of detecting whether it is an appropriate tool to use in clinical research, 2) detect whether patients with first episode psychosis have different, clinically meaningful profiles of performance in social cognition and metacognition, 3) explore the sociodemographic, clinical, and neurocognitive characteristics of each profile, 4) examine if males and females with first episode psychosis are similar in their heterogeneity in social cognition and metacognition, 5) explore the role of social cognition and sex in functional outcome in people with established psychosis (schizophrenia). This broad aim yielded four research articles. The main findings of this doctoral dissertation are a) Baron Cohen’s Face Test is an adequate and reliable instrument to measure facial emotion recognition in Spanish population but it presents a ceiling effect, b) People with first-episode psychosis have distinct profiles of social cognition and metacognition that have specific clinical and neurocognitive correlates. Having worse social cognition is associated with worse clinical presentation, even if metacognition is preserved, c) Men and women with first-episode psychosis have similar configurations of social cognition and metacognition. However, there are sex- specific profiles that should be considered when delivering treatment. Sex-specific profiles seem to be associated with more severity of the disorder than the common profiles. These results suggest that people with psychosis can receive social cognitive or metacognitive targeted treatment as early as after the first episode, but these should be chosen considering the profile of each individual and their biological sex. Thus, patients with psychosis should always be carefully assessed for social cognitive and metacognitive performance.[spa] Las personas con psicosis experimentan una serie de síntomas y déficits que afectan significativamente a sus vidas y que a menudo concurren con la discapacidad. Los mejores predictores de funcionamiento son la cognición social y la metacognición, que a menudo presentan deterioro en personas con psicosis. Diversas intervenciones para mejorar ambos dominios son eficaces, pero esto no siempre se traduce en un mejor funcionamiento. Para ello, se ha propuesto que intervenciones en cognición social y metacognición tempranas y dirigidas podrían maximizar su efecto sobre el funcionamiento y la prevención de recaídas. No obstante, se desconocen los fundamentos que debería guiar su personalización. Aunque se ha sugerido que el enfoque debería tener en cuenta las diferencias de sexo, el perfeccionamiento de los instrumentos de medida y el uso de modelos estadísticos sofisticados, éstos aún no se han explorado en la literatura. Bajo este razonamiento, la presente tesis doctoral pretende: 1) validar una prueba de reconocimiento facial de emociones (Test de Caras de Baron Cohen) en población sana, con el objetivo de detectar si es un instrumento adecuado para utilizar en la investigación clínica, 2) detectar si los pacientes con primer episodio de psicosis tienen perfiles diferentes y clínicamente significativos de rendimiento en cognición social y metacognición, 3) explorar las características sociodemográficas, clínicas y neurocognitivas de cada perfil, 4) examinar si los hombres y las mujeres con primer episodio psicótico son similares en su heterogeneidad en la cognición social y la metacognición, 5) explorar el papel de la cognición social y el sexo en el resultado funcional en personas con psicosis establecida (esquizofrenia). Este amplio objetivo dio lugar a cuatro artículos de investigación. Los principales hallazgos de esta tesis doctoral son: a) El Test de Caras de Baron Cohen es un instrumento adecuado y fiable para medir el reconocimiento de emociones faciales en población española, pero presenta un efecto techo, b) Las personas con primer episodio psicótico tienen perfiles distintos de cognición social y metacognición, con correlatos clínicos y neurocognitivos específicos asociados. Tener una peor cognición social se asocia con una peor presentación clínica, incluso si la metacognición está preservada, c) Los hombres y las mujeres con primer episodio psicótico tienen configuraciones similares de cognición social y metacognición. Sin embargo, existen perfiles específicos de cada sexo que deben tenerse en cuenta a la hora de aplicar el tratamiento, ya que éstos parecen estar asociados a una mayor gravedad del trastorno que los perfiles comunes. Estos resultados sugieren que las personas con psicosis pueden recibir tratamiento en cognición social o metacognición específico desde el primer episodio psicótico, pero éste debe elegirse teniendo en cuenta el perfil de cada individuo y su sexo biológico. Para ello, se pone de manifiesto la necesidad de una correcta evaluación de sus habilidades cognitivo-sociales y metacognitivas

Application of the unified protocol for the transdiagnostic treatment of comorbid emotional disorders in patients with ultra-high risk of developing psychosis: A randomized trial study protocol

Cognitive Behavioral Therapy is delivered in most of the early intervention services for psychosis in different countries around the world. This approach has been demonstrated to be effective in decreasing or at least delaying the onset of psychosis. However, none of them directly affect the comorbidity of these types of patients that is often the main cause of distress and dysfunctionality. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders (UP) is a psychological intervention that combines cognitive-behavioral and third-generation techniques that address emotional dysregulation as an underlying mechanism that these disorders have in common. The application of this intervention could improve the comorbid emotional symptoms of these patients.Materials and methodsThe study is a randomized controlled trial in which one group receives immediate UP plus standard intervention and the other is placed on a waiting list to receive UP 7 months later, in addition to standard care in one of our early psychosis programs. The sample will be 42 patients with UHR for psychosis with comorbid emotional symptoms. The assessment is performed at baseline, at the end of treatment, and at 3-months’ follow-up, and includes: general psychopathology, anxiety and depression, positive and negative emotions, emotional dysregulation, personality, functionality, quality of life, cognitive distortions, insight, and satisfaction with the UP intervention.DiscussionThis will be the first study of the efficacy, acceptability, and viability of the UP in a sample of young adults with UHR. The results of this study may have clinical implications, contributing to improving the model of care for young people who consult for underlying psychotic, anxiety, and/or depressive symptoms that can lead to high distress and dysfunctionality.Clinical trial registration[https://clinicaltrials.gov/], identifier [NCT04929938]

The effect of sex on social cognition and functioning in schizophrenia

Social cognitive impairment is a core feature of schizophrenia and plays a critical role in poor community functioning in the disorder. However, our understanding of the relationship between key biological variables and social cognitive impairment in schizophrenia is limited. This study examined the effect of sex on the levels of social cognitive impairment and the relationship between social cognitive impairment and social functioning in schizophrenia. Two hundred forty-eight patients with schizophrenia (61 female) and 87 healthy controls (31 female) completed five objective measures and one subjective measure of social cognition. The objective measures included the Facial Affect Identification, Emotion in Biological Motion, Self-Referential Memory, MSCEIT Branch 4, and Empathic Accuracy tasks. The subjective measure was the Interpersonal Reactivity Index (IRI), which includes four subscales. Patients completed measures of social and non-social functional capacity and community functioning. For objective social cognitive tasks, we found a significant sex difference only on one measure, the MSCEIT Branch 4, which in both patient and control groups, females performed better than males. Regarding the IRI, females endorsed higher empathy-related items on one subscale. The moderating role of sex was found only for the association between objective social cognition and non-social functional capacity. The relationship was stronger in male patients than female patients. In this study, we found minimal evidence of a sex effect on social cognition in schizophrenia across subjective and objective measures. Sex does not appear to moderate the association between social cognition and functioning in schizophrenia

Heterogeneity in Response to MCT and Psychoeducation: A Feasibility Study Using Latent Class Mixed Models in First-Episode Psychosis

Primer episodi de psicosi; Cognició social; PsicoeducacióFirst episode psychosis; Social cognition; PsychoeducationPrimer episodio de psicosis; Cognición social; PsicoeducaciónMetacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatmentsThis study was funded by the Instituto de Salud Carlos III, Spanish Government, (PI11/01347, PI14/00044 and PI18/00212); the Fondo Europeo de Desarrollo Regional (FEDER), Health Department of Catalonia, PERIS call (SLT006/17/00231); Progress and Health Foundation of the Andalusian Regional Ministry of Health (PI-0634/2011 and PI-0193/2014); Obra Social La Caixa (RecerCaixa call 2013), Obra Social Sant Joan de Déu, BML (RTI2018-100927-J-I00) administrated by Ministerio de Ciencia e Innovación (MCI, Spain), by the Agencia Estatal de Investigación (AEI, Spain), and by the European Regional Development Fund (FEDER, UE); Daniel Fernández has been supported by grant 2017 SGR 622 (GRBIO) administrated by the Departament d’Economia i Coneixement de la Generalitat de Catalunya (Spain) and by the Ministerio de Ciencia e Innovación (Spain) [PID2019-104830RB-I00/ DOI (AEI): 10.13039/501100011033]; and CIBER, Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación

Heterogeneity in response to MCT and psychoeducation: a feasibility study using latent class mixed models in first-episode psychosis

Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatments.Daniel Fernández has been supported by grant 2017 SGR 622 (GRBIO) administrated by the Departament d’Economia i Coneixement de la Generalitat de Catalunya (Spain) and by the Ministerio de Ciencia e Innovación (Spain) [PID2019-104830RB-I00/ DOI (AEI): 10.13039/501100011033]; and CIBER, Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e InnovaciónPostprint (published version

Males and females with first episode psychosis present distinct profiles of social cognition and metacognition

Deficits in social cognition and metacognition impact the course of psychosis. Sex differences in social cognition and metacognition could explain heterogeneity in psychosis. 174 (58 females) patients with first-episode psychosis completed a clinical, neuropsychological, social cognitive, and metacognitive assessment. Subsequent latent profile analysis split by sex yielded two clusters common to both sexes (a Homogeneous group, 53% and 79.3%, and an Indecisive group, 18.3% and 8.6% of males and females, respectively), a specific male profile characterized by presenting jumping to conclusions (28.7%) and a specific female profile characterized by cognitive biases (12.1%). Males and females in the homogeneous profile seem to have a more benign course of illness. Males with jumping to conclusions had more clinical symptoms and more neuropsychological deficits. Females with cognitive biases were younger and had lower self-esteem. These results suggest that males and females may benefit from specific targeted treatment and highlights the need to consider sex when planning interventionsDF has been supported by Marsden (E2987-3648) administered by the Royal Society of New Zealand, by grant 2017 SGR 622 (GRBIO) administrated by the Departament d'Economia i Coneixement de la Generalitat de Catalunya (Spain) and by Ministerio de Ciencia e Innovación (Spain) [PID2019-104830RB-I00/ DOI (AEI): 10.13039/501100011033]Peer ReviewedAutors: M. Ferrer-Quintero, D. Fernández, R. López-Carrilero, I. Birulés, A. Barajas, E. Lorente-Rovira, A. Luengo, L. Díaz-Cutraro, M. Verdaguer, H. García-Mieres, A. Gutiérrez-Zotes, E. Grasa, E. Sousa, E. Huerta-Ramos, T. Pélaez, M. L. Barrigón, J. Gómez-Benito, F. González-Higueras, I. Ruiz-Delgado, J. Cid, S. Moritz, J. Sevilla-Llewellyn-Jones, Spanish Metacognition Group & S. OchoaPostprint (published version

Persons with first episode psychosis have distinct profiles of social cognition and metacognition

Subjects with first-episode psychosis experience substantial deficits in social cognition and metacognition. Although previous studies have investigated the role of profiles of individuals in social cognition and metacognition in chronic schizophrenia, profiling subjects with first-episode psychosis in both domains remains to be investigated. We used latent profile analysis to derive profiles of the abilities in 174 persons with first-episode psychosis using the Beck’s Cognitive Insight Scale, the Faces Test, the Hinting Task, the Internal, Personal and Situational Attributions Questionnaire, and the Beads Task. Participants received a clinical assessment and a neuropsychological assessment. The best-fitting model was selected according to the Bayesian information criterion (BIC). We assessed the importance of the variables via a classification tree (CART). We derived three clusters with distinct profiles. The first profile (33.3%) comprised individuals with low social cognition. The second profile (60.9%) comprised individuals that had more proneness to present jumping to conclusions. The third profile (5.7%) presented a heterogeneous profile of metacognitive deficits. Persons with lower social cognition presented worse clinical and neuropsychological features than cluster 2 and cluster 3. Cluster 3 presented significantly worst functioning. Our results suggest that individuals with FEP present distinct profiles that concur with specific clinical, neuropsychological, and functional challenges. Each subgroup may benefit from different interventionsPeer ReviewedArticle signat per 22 articles: "M. Ferrer-Quintero, D. Fernández, R. López-Carrilero, I. Birulés, A. Barajas, E. Lorente-Rovira, L. Díaz-Cutraro, M. Verdaguer, H. García-Mieres, J. Sevilla-Llewellyn-Jones, A. Gutiérrez-Zotes, E. Grasa, E. Pousa, E. Huerta-Ramos, T. Pélaez, M. L. Barrigón, F. González-Higueras, I. Ruiz-Delgado, J. Cid, S. Moritz, Spanish Metacognition Group & S. Ochoa"Postprint (published version

Are There Gender Differences in Social Cognition in First-Episode Psychosis?

Altres ajuts: This research was funded by the Instituto de Salud Carlos III (Spanish Government, PI11/01347, PI14/00044, and PI18/00212) by the Fondo Europeo de Desarrollo Regional (FEDER), Health Department of Catalonia, PERIS call (SLT006/17/00231), Progress and Health Foundation of the Andalusian Regional Ministry of Health, grant PI-0634/2011 and PI-0193/ 2014, Obra Social La Caixa (RecerCaixa call 2013), CERCA Programme/Generalitat de Catalunya, Obra Social Sant Joan de Déu (BML) and by FI19/00062 (Ayudas para la contratación de personal predoctoral, Luciana Díaz-Cutraro is a beneficiary of a Predoctoral Training Grant in Health Research).The aim of this study was to explore gender differences in social cognition in a sample of first-episode psychosis (FEP). An observational descriptive study was performed with 191 individuals with FEP. Emotion perception was assessed using the Faces Test, theory of mind was assessed using the Hinting Task, and attributional style was assessed using the Internal, Personal and Situational Attributions Questionnaire. No gender differences were found in any of the social cognitive domains. Our results suggest that men and women with FEP achieve similar performances in social cognition. Therefore, targeting specific needs in social cognition regarding gender may not be required in early interventions for psychosis

The relationship between jumping to conclusions and social cognition in first-episode psychosis

Altres ajuts: Obra Social La Caixa (RecerCaixa call 2013), and Obra Social Sant Joan de Déu (BML), Generalitat de Catalunya, Health Department, PERIS call (SLT006/17/00231), and the CERCA Programme/Generalitat de Catalunya. Andalusian Regional Ministry of Health, grant PI-0634/2011Jumping to conclusions (JTC) and impaired social cognition (SC) affect the decoding, processing, and use of social information by people with psychosis. However, the relationship between them had not been deeply explored within psychosis in general, and in first-episode psychosis (FEP) in particular. Our aim was to study the relationship between JTC and SC in a sample with FEP. We conducted a cross-sectional study with 121 patients with FEP, with measures to assess JTC (easy, hard, and salient probability tasks) and SC (emotional recognition, attributional style, and theory of mind). We performed Student's t-test and logistic regression in order to analyse these associations.We found a statistically significant and consistent relationship of small-moderate effect size between JTC (all three tasks) and impaired emotional recognition. Also, our results suggest a relationship between JTC and internal attributions for negative events. Relationships between JTC and theory of mind were not found. These results highlight the importance of psychological treatments oriented to work on a hasty reasoning style and on improving processing of social information linked to emotional recognition and single-cause attributions

Influence of Menstrual Cycle Length and Age at Menarche on Symptoms, Cognition, Social Cognition, and Metacognition in Patients with First-Episode Psychosis

Altres ajuts: PERIS call (grant no. SLT006/17/00231); the Progress and Health Foundation of the Andalusian Regional Ministry of Health (grant no. PI-0634/2011 and PI-0193/2014); Obra Social La Caixa (RecerCaixa call 2013); CERCA Programme/Generalitat de Catalunya; Obra Social Sant Joan de Déu (BML); and FI19/00062 (Ayudas para la Contratación de Personal Predoctoral).A protective effect has traditionally been attributed to estrogen in psychotic disorders. The aim of this study was to investigate cumulative lifetime estrogen by assessing the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and the age of menarche, measuring their effects on symptoms, cognition, social cognition, and metacognition. As it was not possible to directly measure cumulative estrogen levels over the lifetime of a patient, the study sample was composed of 42 women with first-episode psychosis; estrogen levels were inferred by the menstrual cycle length, age at menarche, and years of difference between the onset of psychotic symptoms and menarche. All patients were assessed with a battery of questionnaires using the BDI, PSYRATS, PANSS, STROOP, TAVEC, WSCT, IPSAQ, and BCIS questionnaires. The results related to menstrual cycle length showed a relationship with memory; specifically, shorter cycles with semantic strategies (p = 0.046) and longer cycles with serial strategies in the short term (p = 0.005) as well as in the long term (p = 0.031). The results also showed a relationship with perseverative errors (p = 0.035) and self-certainty (p = 0.049). Only personalized bias (p = 0.030) was found to be significant in relation to the age at menarche. When analyzing the differences in years of difference between the age at menarche and the onset of psychotic symptoms, the results indicated lower scores in women with a smaller difference between both events in memory (short-term (p = 0.050), long-term (p = 0.024), intrusions (p = 0.013), and recognition (p = 0.043)) and non-perseverative errors (p = 0.024). No relationship was found between symptoms and menstrual characteristics. The investigatory outcomes seem to indicate a relationship between estrogen cumulative effects and the memory domain. More in-depth investigations in the field are necessary in order to improve personalized treatment in women with psychosis