Comparison of the touch-screen and traditional versions of the Corsi block-tapping test in patients with psychosis and healthy controls

Background: Working memory (WM) refers to the capacity system for temporary storage and processing of information, which is known to depend on the integrity of the prefrontal cortex. Impairment in working memory is a core cognitive deficit among individuals with psychotic disorders. The Corsi block-tapping test is a widely-used instrument to assess visuospatial working memory. The traditional version is composed of 9 square blocks positioned on a physical board. In recent years, the number of digital instruments has increased significantly; several advantages might derive from the use of a digital version of the Corsi test. Methods: This study aimed to compare the digital and traditional versions of the Corsi test in 45 patients with psychotic disorders and 45 healthy controls. Both groups completed a neuropsychological assessment involving attention and working memory divided into the two conditions. Results: Results were consistent between the traditional and digital versions of the Corsi test. The digital version, as well as the traditional version, can discriminate between patients with psychosis and healthy controls. Overall, patients performed worse with respect to the healthy comparison group. The traditional Corsi test was positively related to intelligence and verbal working memory, probably due to a more significant effort to execute the test. Conclusions: The digital Corsi might be used to enhance clinical practice diagnosis and treatment.The digital version can be administered in a natural environment in real-time. Further, it is easy to administer while ensuring a standard procedure

Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients

A better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia

Prodromal symptoms and the duration of untreated psychosis in first episode of psychosis patients: what differences are there between early vs. adult onset and between schizophrenia vs. bipolar disorder?

To assess the role of age (early onset psychosis-EOP < 18 years vs. adult onset psychosis-AOP) and diagnosis (schizophrenia spectrum disorders-SSD vs. bipolar disorders-BD) on the duration of untreated psychosis (DUP) and prodromal symptoms in a sample of patients with a first episode of psychosis. 331 patients with a first episode of psychosis (7–35 years old) were recruited and 174 (52.6%) diagnosed with SSD or BD at one-year follow-up through a multicenter longitudinal study. The Symptom Onset in Schizophrenia (SOS) inventory, the Positive and Negative Syndrome Scale and the structured clinical interviews for DSM-IV diagnoses were administered. Generalized linear models compared the main effects and group interaction. 273 AOP (25.2 ± 5.1 years; 66.5% male) and 58 EOP patients (15.5 ± 1.8 years; 70.7% male) were included. EOP patients had significantly more prodromal symptoms with a higher frequency of trouble with thinking, avolition and hallucinations than AOP patients, and significantly different median DUP (91 [33–177] vs. 58 [21–140] days; Z = − 2.006, p = 0.045). This was also significantly longer in SSD vs. BD patients (90 [31–155] vs. 30 [7–66] days; Z = − 2.916, p = 0.004) who, moreover had different profiles of prodromal symptoms. When assessing the interaction between age at onset (EOP/AOP) and type of diagnosis (SSD/BD), avolition was significantly higher (Wald statistic = 3.945; p = 0.047), in AOP patients with SSD compared to AOP BD patients (p = 0.004). Awareness of differences in length of DUP and prodromal symptoms in EOP vs. AOP and SSD vs. BD patients could help improve the early detection of psychosis among minors

Cortical thinning over two years after first-episode psychosis depends on age of onset

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15–35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe

Combining MRI and clinical data to detect high relapse risk after the first episode of psychosis

Detecting patients at high relapse risk after the first episode of psychosis (HRR-FEP) could help the clinician adjust the preventive treatment. To develop a tool to detect patients at HRR using their baseline clinical and structural MRI, we followed 227 patients with FEP for 18–24 months and applied MRIPredict. We previously optimized the MRI-based machine-learning parameters (combining unmodulated and modulated gray and white matter and using voxel-based ensemble) in two independent datasets. Patients estimated to be at HRR-FEP showed a substantially increased risk of relapse (hazard ratio = 4.58, P < 0.05). Accuracy was poorer when we only used clinical or MRI data. We thus show the potential of combining clinical and MRI data to detect which individuals are more likely to relapse, who may benefit from increased frequency of visits, and which are unlikely, who may be currently receiving unnecessary prophylactic treatments. We also provide an updated version of the MRIPredict software

The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

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

Influence of clinical and neurocognitive factors in psychosocial functioning after a first episode non-affective psychosis: differences between males and females

BackgroundDeficits in psychosocial functioning are present in the early stages of psychosis. Several factors, such as premorbid adjustment, neurocognitive performance, and cognitive reserve (CR), potentially influence functionality. Sex differences are observed in individuals with psychosis in multiple domains. Nonetheless, few studies have explored the predictive factors of poor functioning according to sex in first-episode psychosis (FEP). This study aimed to explore sex differences, examine changes, and identify predictors of functioning according to sex after onset.Materials and methodsThe initial sample comprised 588 individuals. However, only adults with non-affective FEP (n = 247, 161 males and 86 females) and healthy controls (n = 224, 142 males and 82 females) were included. A comprehensive assessment including functional, neuropsychological, and clinical scales was performed at baseline and at 2-year follow-up. A linear regression model was used to determine the predictors of functioning at 2-year follow-up.ResultsFEP improved their functionality at follow-up (67.4% of both males and females). In males, longer duration of untreated psychosis (β = 0.328, p = 0.003) and worse premorbid adjustment (β = 0.256, p = 0.023) were associated with impaired functioning at 2-year follow-up, while in females processing speed (β = 0.403, p = 0.003), executive function (β = 0.299, p = 0.020) and CR (β = −0.307, p = 0.012) were significantly associated with functioning.ConclusionOur data indicate that predictors of functioning at 2-year follow-up in the FEP group differ according to sex. Therefore, treatment and preventative efforts may be adjusted taking sex into account. Males may benefit from functional remediation at early stages. Conversely, in females, early interventions centered on CR enhancement and cognitive rehabilitation may be recommended

Stressful life events and first-episode psychosis

[eng] Nowadays, advances in affective and social neuroscience have shown how the exposure to environmental factors has an impact on the structure and functioning of the brain being thus, active agents in the formation of an individual’s level of vulnerability. There is an increasing interest in the influence of stress on many diseases including a first-episode psychosis (FEP). From the stress-vulnerability model (Zubin & Spring, 1977) to the current models of neural diathesis-stress (Pruessner et al., 2017), schizophrenia is conceptualised as an episodic disorder in which there is vulnerability and stress due to biological and/or environmental factors. This suggests that patients are likely predisposed to manifesting psychotic episodes induced by the impact of precipitating factors, such as stressful life events (SLEs). In FEP, the role of stressors, specifically SLEs, as predisposing factors or adjuvants to the onset of the disease is relevant. These events are circumstances that occur in the lives of people with an identifiable beginning and end which have the potential to alter their current mental or physical status. However, there are very few studies on SLEs in patients with schizophrenia - and even fewer in patients with FEP-, thereby emphasising the need for such studies. SLEs can be treated as prodromal events, which together with other events, contribute to the appearance of later psychotic symptomatology. Indeed, it is likely that the diversity of environmental factors associated with schizophrenia may be linked to an equal number of different underlying mechanisms. Several studies have evaluated the role of SLEs, but most of the studies include these events as trauma, what makes their research and evaluation more difficult and complicated. This thesis was aimed at achieving adequate and effective early intervention in psychotic disorders since: i) in general, few studies have specifically evaluated SLEs; ii) no studies have analysed the age of onset of FEP in relation to SLEs; iii) no studies have been found about gender differences, family history and psychotic symptomatology in relation to SLEs; and iv) no instruments are available to assess SLEs along the life cycle. The main objective of this thesis was to evaluate the relationship between SLEs and the development of FEP. This objective was developed under three specific objectives: 1) to systematically review the literature available on SLEs and FEP, 2) to evaluate the impact of SLEs and the influence of sociodemographic and clinical variables on the appearance of FEP, and 3) to validate an instrument to measure SLEs in FEP and in a healthy population. The data obtained in this thesis provide more in depth knowledge regarding SLEs and their evaluation and detection as well as the relationship of these events with clinical variables and symptoms in a sample of patients with FEP and healthy controls. The objective of identifying SLEs across the stress-vulnerability model psychosis phenotype continuum may provide insights into the aetiology of this disorder and may lead to the development of strategies for its prevention and treatment. We provide further corroboration that rather than being a correlate of frank psychosis, the variability of SLEs may play an important role in FEP populations and this is of great relevance to the practice of professionals dedicated to detecting, caring for, and treating people with this disease. The work presented in this thesis is framed within the stress-vulnerability model and the clinical staging model, which considers the phenotypic continuum reflecting a shared interactive set of diathesis, psychosocial and sociocultural factors. Currently, few studies have evaluated SLEs in these sample types and there is a need to obtain more in depth information on the influence of SLEs in these populations in which genetics and stress play a relevant role.[cat] Actualment, els avenços en la neurociència afectiva i social han demostrat com l’exposició als factors ambientals influeix en l’estructura i la funció del cervell, essent agents actius en la formació del nivell de vulnerabilitat de l’individu. A més, hi ha un interès creixent en la influència de l’estrès en moltes malalties, incloent un primer episodi psicòtic (PEP). Des del model de vulnerabilitat-estrès (Zubin i Spring, 1977) fins als models actuals de diàtesi- estrès neural (Pruessner et al., 2017), l’esquizofrènia es conceptualitza com un trastorn episòdic en què hi ha vulnerabilitat i estrès a causa de factors biològics i/o ambientals. Això suggereix que probablement els pacients estiguin predisposats a manifestar episodis psicòtics induïts per l’impacte dels factors precipitants, com els esdeveniments vitals estressants (EVEs). En el PEP, és rellevant el paper dels estressors, específicament EVEs, com a factors predisponents o adjuvants a l’aparició de la malaltia. Aquesta tesi tenia com a objectiu aconseguir una intervenció primerenca adequada i efectiva en trastorns psicòtics ja que: i) en general, pocs estudis han avaluat específicament els EVEs; ii) cap estudi ha analitzat l’edat d’aparició de PEP en relació amb els EVEs; iii) no hi ha estudis sobre diferències de gènere, historia familiar i simptomatologia psicòtica en relació amb els EVEs; i per últim, iv) no hi ha instruments disponibles per avaluar els EVEs durant el cicle vital. L’objectiu principal d’aquesta tesi va ser avaluar la relació entre els EVEs i el desenvolupament del PEP. Aquest objectiu es va desenvolupar en tres objectius específics: 1) revisar de forma sistemàtica la literatura disponible dels EVEs i PEP, 2) avaluar l’impacte dels EVEs i la influència de les variables sociodemogràfiques i clíniques sobre l’aparició de PEP, i 3) validar un instrument per mesurar els EVEs en pacients amb PEP i en població sana. Les dades obtingudes en aquesta tesi proporcionen un coneixement més profund sobre els EVEs i la seva avaluació i detecció, així com la relació d’aquests esdeveniments amb variables i símptomes clínics en una mostra de pacients amb PEP i controls sans

Relation between self-perceived stress, psychopathological symptoms and the stress hormone prolactin in emerging psychosis

Psychosocial stress and the stress hormone prolactin are assumed to play an important role in the pathogenesis of schizophrenia and related psychoses, and have been frequently observed to be increased in antipsychotic-naïve patients with a clinical high risk for psychosis (CHR-P) or first episode of psychosis (FEP). The aim of this study was to further elucidate the relationships between self-perceived stress, psychopathological symptoms and prolactin levels in these patients.; In this cross-sectional study, 45 healthy controls, 31 CHR-P patients and 87 FEP patients were recruited from two different study centers. Prolactin was measured under standardized conditions between 8 and 10 am. All patients were antipsychotic-naïve and not taking any prolactin influencing medication. Self-perceived stress during the last month was measured with the perceived stress scale (PSS-10) immediately before blood taking.; Both CHR-P and FEP patients showed significantly higher levels of self-perceived stress and prolactin than controls. Hyperprolactinemia (i.e. prolactin levels above the reference range) was observed in 26% of CHR-P and 45% of FEP patients. Self-perceived stress was significantly positively associated with affective symptoms, but not with other symptoms. There was no significant association between self-perceived stress and prolactin levels.; Our results confirm that CHR-P and FEP patients have higher stress levels than healthy controls and frequently have hyperprolactinemia, independent of antipsychotic medication. However, although it is well established that prolactin increases in response to stress, our results do not support the notion that increased prolactin levels in these patients are due to stress