Estudi de ressonància magnètica funcional i estructural de la cognició social en primers episodis psicòtics : hipoactivació amigdalar durant el reconeixement emocional i dèficits prefrontals en la manca d'insight /

Descripció del recurs: 14 juliol 2011Els pacients amb esquizofrènia presenten un dèficit en àrees de la cognició social. Entre d'altres, diversos estudis han demostrat a) un dèficit en el reconeixement d'expressions facials relacionat amb un funcionament aberrant en l'amígdala cerebral i b) un dèficit a l'hora d'interpretar correctament els pensaments i les emocions dels altres que s'ha associat de forma teòrica amb la manca de consciència de malaltia i amb un funcionament anòmal en estructures prefrontals. En el moment actual hi ha encara una escassetat d'estudis en mostres de pacients en primer episodi psicòtic, que són necessaris per a aprofundir en el coneixement de les bases estructurals i funcionals de l'esquizofrènia evitant les variables de confusió del tractament i del curs deteriorant de la malaltia. El nostre treball es basa en l'estudi d'aquests dos dèficits de la cognició social a través d'un estudi de ressonància magnètica estructural i funcional en pacients en primer episodi psicòtic amb l'objectiu d'aprofundir en el coneixement de les bases estructurals i funcionals d'aquests dominis en l'esquizofrènia. El nostre estudi és el primer que avalua aquestes dues esferes mitjançant ressonància magnètica en un primer moment sense la influència del tractament, i en un segon moment un cop el tractament ha conduït a una estabilitat clínica, Els resultats de les imatges funcionals donen suport a un hipofuncionament de les estructures límbiques, incloent el complex amígdala-hipocamp, durant el reconeixement d'expressions facials en el grup de pacients durant el debut de la malaltia. Alhora, el nostre treball és el primer estudi que evidencia una milloria d'aquest funcionament després del tractament. Aquesta troballa, i els patrons d'activació davant de cada estímul emocional, suggereixen un model de relació activitat amigdalar / estímul emocional en el grup de pacients, diferent al patró del grup control. Aquest model explicaria les aparents contradiccions en la bibliografia prèvia. Els resultats de l'anàlisi estructural evidencien una relació entre manca de consciència de malaltia i estructures prefrontals, entre elles el còrtex prefrontal medial, recolzant així una connexió estructural amb els dominis de la Teoria de la Ment que tan extensament ha estat reportada de forma teòrica. En conjunt, el nostre estudi és el primer a aportar dades dels dèficits estructurals i funcionals en el reconeixement d'expressions emocionals en pacients no tractats durant el primer episodi psicòtic, així com els canvis funcionals després del tractament amb fàrmacs antipsicòtics. Per altra banda, l'estudi és el primer a aportar un coneixement de les estructures implicades en la manca d'insight en primers episodis psicòtics previ al tractament farmacològic.Los pacientes afectos de esquizofrenia presentan un déficit en diversas áreas de la cognición social. Entre otros, diversos estudios han mostrado un déficit en 1) el reconocimiento de expresiones faciales, relacionado con un funcionamiento aberrante en la amígdala cerebral y 2) un déficit en la inferencia e interpretación de los estados mentales de los demás, que se ha asociado de forma teórica con la ausencia de conciencia de enfermedad y con un funcionamiento anómalo en estructuras cerebrales prefrontales. En el momento actual existen aún pocos estudios con muestras de pacientes en primer episodio psicótico, que son necesarios para profundizar en el conocimiento de las bases estructurales y funcionales de la esquizofrenia evitando así las variables de confusión del tratamiento y del curso deteriorante de la enfermedad. Con el objetivo de profundizar en el conocimiento de las bases estructurales y funcionales de estos dos dominios de la cognición social en la esquizofrenia, estudiamos mediante resonancia magnética estructural y funcional a pacientes en primer episodio psicótico. Nuestro estudio es el primero en evaluar estas dos esferas mediante resonancia magnética funcional en un primer tiempo sin la influencia del tratamiento, y en un segundo tiempo una vez el tratamiento ha conducido a la estabilidad clínica. Los resultados de las imágenes funcionales muestran una hipoactividad de las estructuras límbicas, incluyendo el complejo amígdala-hipocampo, durante el reconocimiento de expresiones faciales en el grupo de pacientes antes de iniciar el tratamiento. Además, los resultados muestran un aumento en la actividad de la amígdala después del tratamiento. Este hallazgo, junto con los distintos patrones de activación durante cada uno de los estímulos emocionales presentados, permiten sugerir un modelo de relación entre actividad amigdalar y estímulo emocional, diferente en el grupo de pacientes que en grupo control. Este modelo explicaría las aparentes contradicciones en la bibliografía previa. Los resultados del análisis estructural evidencian una relación entre ausencia de conciencia de enfermedad y estructuras prefrontales, entre ellas la corteza prefrontal medial, apoyando así una conexión estructural con regiones implicadas en la Teoría de la Mente, que tan extensamente han sido referidas de forma teórica. En conjunto, nuestro estudio es el primero en mostrar déficits estructurales y funcionales en el reconocimiento de expresiones emocionales en pacientes aún no tratados durante el primer episodio psicótico, así como cambios funcionales después del tratamiento con fármacos antipsicóticos. Por otro lado, nuestro estudio relaciona estructuras cerebrales con la ausencia de insight en primeros episodios psicóticos previo al inicio del tratamiento.Patients with schizophrenia show a deficit in several areas of social cognition. Amongst them, previous studies have shown 1) an impairment in facial emotion recognition which has been related to abnormal amygdala activation and 2) a deficit on inference and interpretation of the emotions of others, which has been theoretically associated with a lack of insight and with a malfunction in prefrontal areas. At present there are still few studies with samples of first psychotic episode patients, which are necessary to deepen the understanding of structural and functional basis of schizophrenia avoiding the confounding effects of treatment and the course of illness. In order to study in depth the structural basis and functional domains of these two deficits in social cognition in schizophrenia we used structural and functional MRI in patients with first psychotic episode. Our study is the first to longitudinally evaluate these two areas using functional MRI in first episode subjects first, without the influence of treatment, and second, once the treatment has led to clinical stability. The functional neuroimaging results show an underactivation of limbic structures, including the amygdala, during the recognition of facial emotions in patients before starting antipsychotic drugs. At the same time, we found a trend to increase amygdala activation after antipsychotic drugs when clinical melioration was reached. These findings, together with the different patterns of activation during each emotional stimuli allow us to suggest a model of relation between amygdala activity and stimulus valence which is different for patients and controls. This model would explain the apparent contradictions in previous literature. Structural results show a relation between lack of insight and prefrontal brain structures, including medial prefrontal cortex, supporting a structural connection with regions involved in theory of mind. To sum up, our study is the first to show structural and functional deficits in the recognition of emotional expressions in untreated patients during the first psychotic episode, and related functional changes after treatment with antipsychotic drugs. On the other hand, our study links brain structures with the lack of insight in first psychotic episodes prior to initiation of treatment

Cognitive clusters in first-episode psychosis

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who will present a cognitive impairment could improve early detection and intervention. These results suggest that enhancing CR could contribute to improving the course of the illness

Estudi de ressonància magnètica funcional i estructural de la cognició social en primers episodis psicòtics: hipoactivació amigdalar durant el reconeixement emocional i dèficits prefrontals en la manca d'insight

Els pacients amb esquizofrènia presenten un dèficit en àrees de la cognició social. Entre d'altres, diversos estudis han demostrat a) un dèficit en el reconeixement d'expressions facials relacionat amb un funcionament aberrant en l'amígdala cerebral i b) un dèficit a l'hora d'interpretar correctament els pensaments i les emocions dels altres que s'ha associat de forma teòrica amb la manca de consciència de malaltia i amb un funcionament anòmal en estructures prefrontals. En el moment actual hi ha encara una escassetat d'estudis en mostres de pacients en primer episodi psicòtic, que són necessaris per a aprofundir en el coneixement de les bases estructurals i funcionals de l'esquizofrènia evitant les variables de confusió del tractament i del curs deteriorant de la malaltia. El nostre treball es basa en l'estudi d'aquests dos dèficits de la cognició social a través d'un estudi de ressonància magnètica estructural i funcional en pacients en primer episodi psicòtic amb l'objectiu d'aprofundir en el coneixement de les bases estructurals i funcionals d'aquests dominis en l'esquizofrènia. El nostre estudi és el primer que avalua aquestes dues esferes mitjançant ressonància magnètica en un primer moment sense la influència del tractament, i en un segon moment un cop el tractament ha conduït a una estabilitat clínica, Els resultats de les imatges funcionals donen suport a un hipofuncionament de les estructures límbiques, incloent el complex amígdala-hipocamp, durant el reconeixement d'expressions facials en el grup de pacients durant el debut de la malaltia. Alhora, el nostre treball és el primer estudi que evidencia una milloria d'aquest funcionament després del tractament. Aquesta troballa, i els patrons d'activació davant de cada estímul emocional, suggereixen un model de relació activitat amigdalar / estímul emocional en el grup de pacients, diferent al patró del grup control. Aquest model explicaria les aparents contradiccions en la bibliografia prèvia. Els resultats de l'anàlisi estructural evidencien una relació entre manca de consciència de malaltia i estructures prefrontals, entre elles el còrtex prefrontal medial, recolzant així una connexió estructural amb els dominis de la Teoria de la Ment que tan extensament ha estat reportada de forma teòrica. En conjunt, el nostre estudi és el primer a aportar dades dels dèficits estructurals i funcionals en el reconeixement d'expressions emocionals en pacients no tractats durant el primer episodi psicòtic, així com els canvis funcionals després del tractament amb fàrmacs antipsicòtics. Per altra banda, l'estudi és el primer a aportar un coneixement de les estructures implicades en la manca d'insight en primers episodis psicòtics previ al tractament farmacològic.Los pacientes afectos de esquizofrenia presentan un déficit en diversas áreas de la cognición social. Entre otros, diversos estudios han mostrado un déficit en 1) el reconocimiento de expresiones faciales, relacionado con un funcionamiento aberrante en la amígdala cerebral y 2) un déficit en la inferencia e interpretación de los estados mentales de los demás, que se ha asociado de forma teórica con la ausencia de conciencia de enfermedad y con un funcionamiento anómalo en estructuras cerebrales prefrontales. En el momento actual existen aún pocos estudios con muestras de pacientes en primer episodio psicótico, que son necesarios para profundizar en el conocimiento de las bases estructurales y funcionales de la esquizofrenia evitando así las variables de confusión del tratamiento y del curso deteriorante de la enfermedad. Con el objetivo de profundizar en el conocimiento de las bases estructurales y funcionales de estos dos dominios de la cognición social en la esquizofrenia, estudiamos mediante resonancia magnética estructural y funcional a pacientes en primer episodio psicótico. Nuestro estudio es el primero en evaluar estas dos esferas mediante resonancia magnética funcional en un primer tiempo sin la influencia del tratamiento, y en un segundo tiempo una vez el tratamiento ha conducido a la estabilidad clínica. Los resultados de las imágenes funcionales muestran una hipoactividad de las estructuras límbicas, incluyendo el complejo amígdala-hipocampo, durante el reconocimiento de expresiones faciales en el grupo de pacientes antes de iniciar el tratamiento. Además, los resultados muestran un aumento en la actividad de la amígdala después del tratamiento. Este hallazgo, junto con los distintos patrones de activación durante cada uno de los estímulos emocionales presentados, permiten sugerir un modelo de relación entre actividad amigdalar y estímulo emocional, diferente en el grupo de pacientes que en grupo control. Este modelo explicaría las aparentes contradicciones en la bibliografía previa. Los resultados del análisis estructural evidencian una relación entre ausencia de conciencia de enfermedad y estructuras prefrontales, entre ellas la corteza prefrontal medial, apoyando así una conexión estructural con regiones implicadas en la Teoría de la Mente, que tan extensamente han sido referidas de forma teórica. En conjunto, nuestro estudio es el primero en mostrar déficits estructurales y funcionales en el reconocimiento de expresiones emocionales en pacientes aún no tratados durante el primer episodio psicótico, así como cambios funcionales después del tratamiento con fármacos antipsicóticos. Por otro lado, nuestro estudio relaciona estructuras cerebrales con la ausencia de insight en primeros episodios psicóticos previo al inicio del tratamiento.Patients with schizophrenia show a deficit in several areas of social cognition. Amongst them, previous studies have shown 1) an impairment in facial emotion recognition which has been related to abnormal amygdala activation and 2) a deficit on inference and interpretation of the emotions of others, which has been theoretically associated with a lack of insight and with a malfunction in prefrontal areas. At present there are still few studies with samples of first psychotic episode patients, which are necessary to deepen the understanding of structural and functional basis of schizophrenia avoiding the confounding effects of treatment and the course of illness. In order to study in depth the structural basis and functional domains of these two deficits in social cognition in schizophrenia we used structural and functional MRI in patients with first psychotic episode. Our study is the first to longitudinally evaluate these two areas using functional MRI in first episode subjects first, without the influence of treatment, and second, once the treatment has led to clinical stability. The functional neuroimaging results show an underactivation of limbic structures, including the amygdala, during the recognition of facial emotions in patients before starting antipsychotic drugs. At the same time, we found a trend to increase amygdala activation after antipsychotic drugs when clinical melioration was reached. These findings, together with the different patterns of activation during each emotional stimuli allow us to suggest a model of relation between amygdala activity and stimulus valence which is different for patients and controls. This model would explain the apparent contradictions in previous literature. Structural results show a relation between lack of insight and prefrontal brain structures, including medial prefrontal cortex, supporting a structural connection with regions involved in theory of mind. To sum up, our study is the first to show structural and functional deficits in the recognition of emotional expressions in untreated patients during the first psychotic episode, and related functional changes after treatment with antipsychotic drugs. On the other hand, our study links brain structures with the lack of insight in first psychotic episodes prior to initiation of treatment

Association between neurological soft signs, temperament and character in patients with schizophrenia and non-psychotic relatives.

The heritability of schizophrenia and most personality traits has been well established, but the role of personality in susceptibility to schizophrenia remains uncertain. The aim of this study was to test for an association between personality traits and Neurological Soft Signs (NSS), a well-known biological marker of schizophrenia, in non-psychotic relatives of patients with schizophrenia. For this purpose, we evaluated the NSS scale and personality measured by the Temperament and Character inventory (TCI-R) in three groups of subjects: 29 patients with schizophrenia, 24 unaffected relatives and 37 controls. The results showed that patients with schizophrenia were more asocial (higher harm avoidance and lower reward dependence), more perseverative (higher persistence), and more schizotypal (lower self-directedness and cooperativeness, higher self-transcendence). The unaffected relatives showed higher harm avoidance, lower self-directedness and cooperativeness than the healthy controls. Higher NSS scores and sub-scores were found in patients and non-psychotic relatives compared with the controls. Among all the patients, total NSS scores were positively correlated with harm avoidance but negatively correlated with novelty seeking and persistence. Total NSS were also correlated with low scores on self-directedness and cooperativeness, which are indicators of personality disorder. Our results show that susceptibility to NSS and to schizophrenia are both related to individual differences in the temperament and character features in non-psychotic relatives of patients with schizophrenia. High harm avoidance, low persistence, low self-directedness and low cooperativeness contribute to both the risk of NSS and schizophrenia. These findings highlight the value of using both assessments to study high risk populations.We received support from the ‘‘Red de Transtornos Adictivos’’ of the Instituto de Salud Carlos III (RD12/0028/0009) and the ‘‘Centro de Investigación Biomédica en Red de Salud Mental’’ (CIBERSAM G21). LG is a recipient of the ‘‘Río Hortega’’ fellowship from the Instituto de Salud Carlos III (ISCIII-FIS, CM14/00111). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The following grant information was disclosed by the authors: Red de Transtornos Adictivos of the Instituto de Salud Carlos III: RD12/0028/0009. Centro de Investigación Biomédica en Red de Salud Mental: CIBERSAM G21. Instituto de Salud Carlos III: ISCIII-FIS, CM14/00111

The Neuroanatomical Basis of Panic Disorder and Social Phobia in Schizophrenia : A Voxel Based Morphometric Study

Objective: It is known that there is a high prevalence of certain anxiety disorders among schizophrenic patients, especially panic disorder and social phobia. However, the neural underpinnings of the comorbidity of such anxiety disorders and schizophrenia remain unclear. Our study aims to determine the neuroanatomical basis of the co-occurrence of schizophrenia with panic disorder and social phobia. Methods: Voxel-based morphometry was used in order to examine brain structure and to measure between-group differences, comparing magnetic resonance images of 20 anxious patients, 20 schizophrenic patients, 20 schizophrenic patients with comorbid anxiety, and 20 healthy control subjects. Results: Compared to the schizophrenic patients, we observed smaller grey-matter volume (GMV) decreases in the dorsolateral prefrontal cortex and precentral gyrus in the schizophrenic-anxiety group. Additionally, the schizophrenic group showed significantly reduced GMV in the dorsolateral prefrontal cortex, precentral gyrus, orbitofrontal cortex, temporal gyrus and angular/inferior parietal gyrus when compared to the control group. Conclusions: Our findings suggest that the comorbidity of schizophrenia with panic disorder and social phobia might be characterized by specific neuroanatomical and clinical alterations that may be related to maladaptive emotion regulation related to anxiety. Even thought our findings need to be replicated, our study suggests that the identification of neural abnormalities involved in anxiety, schizophrenia and schizophrenia-anxiety may lead to an improved diagnosis and management of these conditions

The effect of family environment and psychiatric family history on psychosocial functioning in first-episode psychosis at baseline and after 2 years

Altres ajuts: Fundació "La Caixa" (ID 100010434, LCF/PR/GN18/50310006); European Social Fund; Fondo Europeo de Desarrollo Regional (FEDER); CIBER of Mental Health (CIBERSAM); Generalitat de Catalunya (CERCA Programme); Departament de Salut de la Generalitat de Catalunya (PERIS SLT006/17/00357, SLT006/17/00345); Project B2017/BMD-3740 Ayudas I + D en Biomedicina de la Comunidad de Madrid.The aim of the present study was to evaluate the contribution of family environment styles and psychiatric family history on functioning of patients presenting first-episode psychosis (FEP). Patients with FEP and healthy controls (HC) were assessed at baseline and after 2 years. The Functional Assessment Short Test (FAST) was used to assess functional outcome and the Family Environment Scale (FES) to evaluate family environment. Linear regressions evaluated the effect that family environment exerts on functioning at baseline and at 2-year follow-up, when FEP patients were diagnosed according to non-affective (NA-PSYCH) or affective psychoses (A-PSYCH). The influence of a positive parents' psychiatric history on functioning was evaluated through one-way between-groups analysis of covariance (ANCOVA) models, after controlling for family environmental styles. At baseline, FEP patients presented moderate functioning impairment, significantly worse than HC (28.65±16.17 versus 3.25±7.92; p<0.001, g = 1.91). At 2-year follow-up, the functioning of NA-PSYCH patients was significantly worse than in A-PSYCH (19.92±14.83 versus 12.46±14.86; p = 0.020, g = 0.50). No specific family environment style was associated with functioning in FEP patients and HC. On the contrary, a positive psychiatric father's history influenced functioning of FEP patients. After 2 years, worse functioning in NA-PSYCH patients was associated with lower rates of active-recreational and achievement orientated family environment and with higher rates of moral-religious emphasis and control. In A-PSYCH, worse functioning was associated with higher rates of conflict in the family. Both family environment and psychiatric history influence psychosocial functioning, with important implications for early interventions, that should involve both patients and caregivers

Exploring Risk and Resilient Profiles for Functional Impairment and Baseline Predictors in a 2-Year Follow-Up First-Episode Psychosis Cohort Using Latent Class Growth Analysis

Being able to predict functional outcomes after First-Episode Psychosis (FEP) is a major goal in psychiatry. Thus, we aimed to identify trajectories of psychosocial functioning in a FEP cohort followed-up for 2 years in order to find premorbid/baseline predictors for each trajectory. Additionally, we explored diagnosis distribution within the different trajectories. A total of 261 adults with FEP were included. Latent class growth analysis identified four distinct trajectories: Mild impairment-Improving trajectory (Mi-I) (38.31% of the sample), Moderate impairment-Stable trajectory (Mo-S) (18.39%), Severe impairment-Improving trajectory (Se-I) (12.26%), and Severe impairment-Stable trajectory (Se-S) (31.03%). Participants in the Mi-I trajectory were more likely to have higher parental socioeconomic status, less severe baseline depressive and negative symptoms, and better premorbid adjustment than individuals in the Se-S trajectory. Participants in the Se-I trajectory were more likely to have better baseline verbal learning and memory and better premorbid adjustment than those in the Se-S trajectory. Lower baseline positive symptoms predicted a Mo-S trajectory vs. Se-S trajectory. Diagnoses of Bipolar disorder and Other psychoses were more prevalent among individuals falling into Mi-I trajectory. Our findings suggest four distinct trajectories of psychosocial functioning after FEP. We also identified social, clinical, and cognitive factors associated with more resilient trajectories, thus providing insights for early interventions targeting psychosocial functioning

Cognitive clusters in first-episode psychosis

Impairments in a broad range of cognitive domains have been consistently reported in some individuals with first-episode psychosis (FEP). Cognitive deficits can be observed during the prodromal stage. However, the course of cognitive deficits is still unclear. The aim of this study was to identify cognitive subgroups over time and to compare their sociodemographic, clinical and functional profiles. A total of 114 patients with Schizophrenia Spectrum Disorders were included in the present study. We assessed subjects through psychiatric scales and eight neuropsychological tests at baseline and at two-year follow-up visit. We performed the Partition Around Medoids algorithm with all cognitive variables. Furthermore, we performed a logistic regression to identify the predictors related to the different cognitive clusters at follow-up. Two distinct subgroups were found: the first cluster characterized by cognitive impairment and a second cluster had relatively intact cognition in comparison with norms. Up to 54.7% of patients with cognitive deficits at baseline tended to improve during the first two years of treatment. Patients with intact cognition at follow-up had a higher socioeconomic status, later age of onset, lower negative symptoms and a higher cognitive reserve (CR) at baseline. CR and age of onset were the baseline variables that predicted cognitive impairment. This research allows us to obtain a better understanding of the heterogeneous profile of psychotic disorders. Identifying the characteristics of patients who will present a cognitive impairment could improve early detection and intervention. These results suggest that enhancing CR could contribute to improving the course of the illness

A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood

Little is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse.This study was supported by the Carlos III Healthcare Institute, the Spanish Ministry of Science, Innovation and Universities, the European Regional Development Fund (ERDF/FEDER) (PI08/0208, PI11/00325, PI14/00612); Centro de Investigacion Biomedica en Red de Salud Mental (CIBERSAM); CERCA Program; Catalan Government, the Secretariat of Universities and Research of the Department of Enterprise and Knowledge (2017SGR1562 and 2017SGR1355); and Institut de Neurociencies, Universitat de Barcelona. The authors thank the Language Advisory Service at the University of Barcelona for manuscript revision. The authors also thank all subjects and their families for the time and effort spent on this study as well as Ana Meseguer for sample collection assistance

Epigenetic clocks in relapse after a first episode of schizophrenia

The main objective of the present study was to investigate the association between several epigenetic clocks, covering different aspects of aging, with schizophrenia relapse evaluated over a 3-year follow-up period in a cohort of ninety-one first-episode schizophrenia patients. Genome-wide DNA methylation was profiled and four epigenetic clocks, including epigenetic clocks of chronological age, mortality and telomere length were calculated. Patients that relapsed during the follow-up showed epigenetic acceleration of the telomere length clock (p = 0.030). Shorter telomere length was associated with cognitive performance (working memory, r = 0.31 p = 0.015; verbal fluency, r = 0.28 p = 0.028), but no direct effect of cognitive function or symptom severity on relapse was detected. The results of the present study suggest that epigenetic age acceleration could be involved in the clinical course of schizophrenia and could be a useful marker of relapse when measured in remission stages