Ten-year course of cognition in first-episode non-affective psychosis patients: PAFIP cohort.

BACKGROUND: A large body of research states that cognitive impairment in schizophrenia is static. Nevertheless, most previous studies lack a control group or have small study samples or short follow-up periods. METHOD: We aimed to address these limitations by studying a large epidemiological cohort of patients with first-episode schizophrenia spectrum disorders and a comparable control sample for a 10-year period. RESULTS: Our results support the generalized stability of cognitive functions in schizophrenia spectrum disorders considering the entire group. However, the existence of a subgroup of patients characterized by deteriorating cognition and worse long-term clinical outcomes must be noted. Nevertheless, it was not possible to identify concomitant factors or predictors of deterioration (all Ps > 0.05). CONCLUSIONS: Cognitive functions in schizophrenia spectrum disorder are stable; however, a subgroup of subjects that deteriorate can be characterized.

Diagnosis and neurocognitive profiles in first-episode non-affective psychosis patients.

This study explored whether there are distinguishable neurocognitive profiles in diagnostic subgroups of first-episode non-affective psychosis (FEP) patients. Four hundred and eighty-seven individuals with diagnoses of non-affective psychosis disorders were evaluated 6 months after first contact with psychiatric services. Individuals with schizophrenia (n = 257), schizophreniform (n = 141), brief psychotic disorder (n = 54), and psychosis not otherwise specified (n = 35) were compared on baseline neuropsychological variables using analyses of variance and covariance with potential clinical, premorbid, and sociodemographic confounders. The brief psychotic disorder subgroup was the least impaired on global cognitive function, in particular when compared to the schizophrenia subgroup, and specifically on executive function, processing speed, and motor dexterity domains. However, with the exception of the processing speed domain, profile differences could be explained by sex, age, psychotic and negative symptoms, years of education, and premorbid IQ. These results suggest processing speed as a diagnostic marker for brief psychotic disorder in FEP patients. Further, there are quantitative and qualitative differences across the schizophrenia spectrum disorders subgroups, indicating different profiles with varying degrees of deficit.

Dysbindin gene variability is associated with cognitive abnormalities in first-episode non-affective psychosis.

INTRODUCTION: Dystrobrevin-binding protein 1 gene (dysbindin or DTNBP1) has been associated with schizophrenia and cognitive performance. Its expression in areas implicated in cognition such as the dorsolateral prefrontal cortex, as well as its role in dopaminergic and glutamatergic system, has been replicated by several studies. The main aim of this study was to examine the association between DTNBP1 variability and cognitive performance in a sample of 238 patients with a first episode of a non-affective psychosis. METHODS: Patients, and a comparison sample of 47 healthy subjects, completed an extensive neuropsychological battery. Five single nucleotide polymorphisms (SNPs) within DTNBP1 (rs2619528, rs2619538, rs3213207, rs2619539 and rs760761) and three haplotypes (GACAC, GAGAC and GTGAC) were analysed. RESULTS: In the group of patients, we found a significant association between two of the DTNBP1 SNPs and one of the haplotypes (rs2619539, rs3213207 and GACAC) and a measure of premorbid IQ [Wechsler Adult Intelligence Scale-3rd Edition (WAIS-III) Vocabulary subtest]. Moreover, one of these SNPs, rs2619539, was also associated with our measure of working memory (WAIS-III Backward digits subtest) and two haplotypes, GAGAC and GTGAC, with our measure of verbal memory (Rey Auditory Verbal Learning Test), of visual memory (Rey Complex Figure Test) in the case of GAGAC, and of speed of processing (WAIS-III Digit Symbol-coding) in the case of GTGAC. CONCLUSIONS: Our findings add further evidence suggesting an association between dysbindin gene variability and cognitive abnormalities in schizophrenia, providing preliminary evidence of this association since the time of illness onset among minimally medicated patients.

Effect of long-acting antipsychotic treatment on psychiatric hospitalization rate in early psychosis patients: a naturalistic study.

Background: The effectiveness of long-acting injectable (LAI) antipsychotics in preventing relapses of first-episode psychosis is currently debated. Objectives: The study aimed to investigate the number of psychiatric hospitalizations comparing the LAI cohort versus the oral cohort during different phases of the illness, pre-LAI treatment, during LAI treatment, and after LAI treatment. Design: A naturalistic study was conducted on two independent cohorts of early psychosis patients receiving treatment from a specific early intervention service. The first cohort comprised 228 patients who received LAIs, while the second cohort comprised 667 patients who had never received LAIs. Methods: This study was designed as a longitudinal observational study conducted within a naturalistic clinical setting in two cohorts of early psychosis patients. Repeated series ANCOVA (ANCOVA-r) was used to study the number of hospitalizations in the different study periods (T1 = from the date of the first psychiatric record to the beginning of the mirror period; T2 = the mirror period; T3 = from the LAI implementation to the LAI discontinuation; and T4 = from the LAI discontinuation to the end). In all cases, discontinuation of LAI involved the return to oral treatment. In all, 35 patients had not T4 as they were still on LAI treatment at the time of database closing (September 2020), and their data were not included in the analysis of the effect of the LAI discontinuation. Results: The patients in the LAI cohort were younger, more frequently males, presented more schizophrenia diagnoses, and had a higher number of hospitalizations (2.50 ± 2.61 versus 1.19 ± 1.69; p < 0.001) than the oral cohort. The number of hospitalizations at the end of the follow-up was higher in the LAI cohort [0.20 (standard deviation (SD)) = 0.79] versus 0.45 [SD = 0.45 (SD = 1.13); F(23.90), p < 0.001]. However, after the introduction of LAIs, the differences in hospitalization rates between the two cohorts became less pronounced. Once LAI treatment was ceased, the hospitalization rate increased again. Conclusion: In our study, early psychosis patients receiving LAIs experienced a greater decrease in hospitalizations after introducing the LAI treatment than those treated solely with oral medication. These findings support using LAIs as a viable strategy for preventing rehospitalization and improving the overall course of treatment for individuals with early psychosis.

Homocysteine and cognition in first-episode psychosis patients.

In the last years, there has been growing evidence linking elevated homocysteine levels with cognitive dysfunction in several neurological and neuropsychiatric diseases. The aim of the present study was to investigate the potential relationship between elevated homocysteine levels and cognitive deficits in first-episode psychosis patients. Plasma levels and cognitive performance of 139 patients and 99 healthy volunteers were compared. Patients were classified as elevated homocysteine (>90 percentile for controls) and normal and compared on 22 cognitive outcome measures grouped into cognitive domains known to be impaired in schizophrenia. Patients had a statistically significant increase in plasmatic homocysteine levels. In addition, they presented with significantly increased cognitive deficits. However, no relationship between homocysteine levels and cognitive impairment was detected. These results suggest the need for further studies to clarify the role of homocysteine in the etiology and prognosis of psychosis.

Identifying attentional deficits in people with first-episode psychosis with the Scale for the Assessment of Negative Symptoms attention subscale: is it possible?

OBJECTIVE: The aim of this study was to examine the correspondence between clinical ratings of inattention problems in the early course of a psychotic disorder and concurrent neuropsychological data for sustained attention and speed of processing/executive functioning (SP/EF) derived from a comprehensive neuropsychological test battery. METHOD: A sample of 131 patients with first-episode psychosis (FEP) was clinically rated after clinical stabilization with the attention subscale of the Scale for the Assessment of Negative Symptoms (SANS) and a completed neuropsychological test battery, which included measurements of sustained attention and SP/EF. To test the associations of the clinical ratings and objective data, correlations and regression analyses were conducted. RESULTS: Clinical ratings of inattention showed only weak correlations with the global score of SP/EF and with the clinical ratings of negative symptoms (ρ < 0.25). None of the independent variables entered in the logistic regression model were significant (all P values > .05). Percentages of agreement between clinical judgment and neuropsychological measures were unacceptably low (ranged from 53% to 68%). κ values indicate only slight agreement (κ < 0.2). CONCLUSIONS: Clinical ratings based on the SANS attention subscale do not reliably match neuropsychological test measures of attention or other related cognitive processes in FEP. Even for those cognitive domains more pronouncedly impaired, mental health professionals will likely need to rely on psychometric testing or, alternatively, specific guidelines and also, probably, to collect data from different sources to adequately identify cognitive impairments.

Neuropsychological functioning in early-onset first-episode psychosis: comparison of diagnostic subgroups.

The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

Cognitive functioning in children and adolescents in their first episode of psychosis: differences between previous cannabis users and nonusers.

To investigate the relationship between cognition and prior cannabis use in children and adolescents presenting a first episode of psychosis. A total of 107 patients with first episode of psychosis and 96 healthy controls, aged 9 to 17 years, were interviewed about their previous substance use and to assess their cognitive functions. Patients were assessed while not using cannabis by means of a comprehensive neuropsychological battery. They were divided into 2 groups depending on the history of prior cannabis use: cannabis users (CU) and cannabis nonusers (CNU). Significant differences were found in all areas evaluated between the 3 groups. Both CU and CNU patients obtained lower scores than controls on verbal learning and memory and working memory. Patients with prior cannabis use performed better on some tests of attention (Continuous performance test (CPT) number of correct responses, p = 0.002; CPT average reaction time, p < 0.001) and executive functions (Trail Making Test, part B (TMT-B) number of mistakes, p < 0.001; Wisconsin Card Sorting Test (WCST) number of categories completed, p < 0.001) than CNU patients. CU patients performed better than CNU subjects on some cognitive measures. This may indicate lower individual vulnerability for psychosis in CU patients in whom cannabis use can be a precipitating factor of psychotic episodes.

Effects of family psychoeducation on expressed emotion and burden of care in first-episode psychosis: a prospective observational study.

The present study aimed to examine the levels and interactions of family burden (FB) and expressed emotion (EE) in first episode psychosis (FEP) patients and, secondly, to observe the potential change after a brief psychoeducational group intervention implemented in a real world clinical setting. Twenty-three key relatives of FEP patients received a brief psychoeducational group intervention. FB and EE were assessed before and after the intervention. EE-change and correlations between variables were examined. Half of the sample of key-relatives showed high levels of EE. No severe family burden was observed. FB and EE did not change after the intervention. Family subjective and objective burden were correlated with emotional overinvolvement, but not with criticism. Brief psychoeducational groups may not be sufficient to reduce FB and EE associated to the experience of caregiving for a family member with a first-episode psychotic disorder.

Verbal memory and voxel based morphometry in first episode non-affective psychosis: A process oriented approach.

OBJECTIVE: The present study aimed to comprehensively study the specific neurocognitive constructs underlying verbal memory deficits and their neuroanatomical correlates in first episode psychosis (FEP) patients. METHOD: A total of 218 FEP patients and 145 healthy participants were examined with the Rey Auditory Verbal Learning Test (a widely used verbal memory measure that provides a range of performance indexes to evaluate memory) and voxel-based morphometry (a neuroimaging analysis technique that allows investigation of focal differences in brain anatomy). RESULTS: The analyses showed that the FEP group presented significantly lower scores on acquisition/learning, F(1, 566) = 40.7; p < .001, and delayed recall, F(1, 570) = 74.12; p < .001, as well as higher rates of forgetting, F(1, 566) = 20.03; p < .001. They also exhibited a significant sensitivity to retroactive, F(1, 554) = 8.74; p = .003, but not to proactive interference. Neuroimaging analyses found significant interactions between bilateral frontal lobe morphometry and proactive interference (ρFWE = 0.023). Rate of forgetting also significantly interacted with right occipital cortex morphometry (ρFWE = 0.033). Patients with higher rates of forgetting, proactive and retroactive interference demonstrated further gray matter reductions in frontal and occipital cortical areas. CONCLUSIONS: These findings emphasize the anterior orbitofrontal cortex as the brain region that contributes to verbal memory deficits in FEP patients, and suggest specific relationships between different neuroanatomical structures and discrete verbal memory processes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Lack of influence of COMT Val158Met genotype on cognition in first-episode non-affective psychosis.

COMT gene is a logical candidate gene for schizophrenia. Moreover, variations in the COMT Val158Met functional polymorphism have been associated with prefrontal cognitive abnormalities among patients with schizophrenia, healthy relatives and controls. In this study, using an epidemiologically-based sample of 130 patients experiencing a first-episode of a non-affective psychosis, we examined whether COMT Val158Met genotype influenced cognitive performance on the phenotypic expression of psychosis. We found no significant differences in any cognitive measure according to COMT genotype. These findings, together with previously published research, put the relationship between COMT genotype and cognitive performance in doubt.

Antipsychotic-induced weight gain in chronic and first-episode psychotic disorders: a systematic critical reappraisal.

Antipsychotic-induced weight gain is an important issue in the treatment of psychotic illnesses, and affects 80% of individuals being treated with antipsychotic drugs. However, the true dimension of weight gain and many accepted 'facts' in this area remain unclear as most research has been conducted in short-term trials and has included individuals receiving prolonged antipsychotic treatment. This review aims to systematically and critically review the evidence on weight gain induced by the two leading second-generation antipsychotics (olanzapine and risperidone) and the most widely researched first-generation antipsychotic (haloperidol) in patients with chronic and first-episode psychotic disorders. Weight gain was 3- to 4-fold greater in studies that included young patients with limited previous exposure to antipsychotic agents in both short-term studies (7.1-9.2 kg for olanzapine, 4.0-5.6 kg for risperidone and 2.6-3.8 kg for haloperidol vs 1.8-5.4 kg, 1.0-2.3 kg and 0.01-1.4 kg, respectively, in studies that included patients with chronic psychotic disorders) and long-term trials (10.2-15.4 kg for olanzapine, 6.6-8.9 kg for risperidone and 4.0-9.7 kg for haloperidol vs 2.0-6.2 kg, 0.4-3.9 kg and -0.7 to 0.4 kg, respectively). The same disparity was observed regarding the proportion of patients increasing their baseline weight by > or =7% (the cut-off for clinically significant weight gain). Recent studies carried out in young patients with first-episode psychosis (FEP), along with methodological artefacts in studies of chronic populations, suggest that the magnitude of weight gain reported by much of the literature could in fact be an underestimation of the true magnitude of this adverse effect. Although antipsychotics present idiosyncratic patterns of weight gain, they may also generate similar absolute gains.

Cognitive functioning and negative symptoms in first episode schizophrenia: different patterns of correlates.

Negative symptoms of schizophrenia have been related to disturbances of executive functions, memory, attention and motor functioning. The executive functions dimension comprises a variety of cognitive subprocesses, including speed of processing, flexibility and working memory. We independently analysed the relationship between different cognitive tasks and clinical symptoms (negative, positive and disorganized) in a sample of 126 first-episode patients with schizophrenia spectrum disorders. Negative symptoms were significantly associated with performance on executive-functions and motor coordination tasks. Within the executive functions domain only those tests that required speeded performance showed a significant association with the negative dimension. The widely described relationship between negative symptoms and executive impairments in schizophrenia appears to be mediated by likely dysfunctions in the speed of processing instead of by working memory impairment.

Preserved orbitofrontal function in first-episode schizophrenia: further evidence from the object alternation paradigm.

Neuropsychological literature indicates that performance on Object Alternation Task (OAT) can be linked to the orbitofrontal cortex (OFC). Patients with chronic schizophrenia perform poorly on behavioral and neuropsychological tasks related to OFC functions. In a previous study using the Iowa Gambling Task, we found unimpaired performance in a sample of individuals with first-episode schizophrenia (FES) spectrum disorders. In this study, we aimed to extend our study of OFC functions by using the OAT paradigm, to determine whether there are abnormalities in the early phases of schizophrenia. We examined the performance of 70 patients with FES and 21 healthy controls on a computerized version of OAT. There were no significant differences between patients and control subjects with respect to the OAT. This finding suggests that the OFC function, as measured by decision-making tasks, is preserved in the early phases of schizophrenia.

Cognitive dimensions in first-episode schizophrenia spectrum disorders.

BACKGROUND: The severity and pattern of cognitive deficits in epidemiological cohorts of patients with first-episode schizophrenia spectrum disorders still remains unclear. We aimed to characterize the basic cognitive functioning of a representative sample of patients with a first-episode schizophrenia spectrum disorders. METHOD: One hundred thirty-one patients experiencing first-episode psychosis and 28 healthy volunteers were administered a comprehensive neuropsychological evaluation. To reduce the number of cognitive test measures into meaningful cognitive dimensions, before analyzing differences between patient and healthy volunteer samples, exploratory factor analysis was carried out on data collected in patients group. The method of extraction was Principal Components Analysis with oblique rotation. RESULTS: An eight-factor model including verbal learning/memory, verbal comprehensive abilities, speed of processing/executive functioning, motor dexterity, motor speed, sustained attention, and impulsivity emerged. A significant below average performance in all cognitive dimensions, except impulsivity, was found. Patient's performance in speed of processing/executive functioning, motor dexterity and sustained attention dimensions exceeded one standard deviation below healthy comparison subjects. CONCLUSIONS: At early stages of the illness, patients display a marked impairment in several functionally relevant cognitive domains.

Cognitive dysfunction in first-episode psychosis: the processing speed hypothesis.

BACKGROUND: Speed of processing is a cognitive process underlying cognitive dysfunction in people with chronic schizophrenia. AIMS: To investigate the contribution of speed of processing to the cognitive deficits observed in a representative large sample with first-episode schizophrenia. METHOD: People with a diagnosis of first-episode schizophrenia-spectrum disorders (n=26) and healthy controls (n=28) were compared on several cognitive measures before and after controlling for speed of processing. RESULTS: Before controlling for speed of processing, patients and controls differed significantly on all cognitive measures. All significant differences in cognitive functioning disappeared when the result of the Digital Symbol Substitution Test was included as an additional covariate. CONCLUSIONS: Speed of information processing may be considered a core cognitive deficit in schizophrenia and might be mediating a broader diversity of cognitive disturbances.

Prefrontal cognitive functions in stabilized first-episode patients with schizophrenia spectrum disorders: a dissociation between dorsolateral and orbitofrontal functioning.

Specific prefrontal cognitive impairments have been reported in first-episode and chronic schizophrenia. We sought to investigate potential impairments in specific prefrontal cortical cognitive functions among stabilized patients with a first-episode of schizophrenia. A sample of 80 individuals with a first-episode of schizophrenia spectrum disorders and 22 healthy volunteers underwent a neurocognitive battery assessing orbitofrontal (OFC) [The Iowa Gambling Task (GT)], and dorsolateral prefrontal (DLPFC) functions (WAIS III Backward digits, verbal fluency test (FAS), and Trail Making Test). Cognitive data were obtained following stabilization of acute psychotic symptoms. Clinical symptoms after six weeks of treatment were assessed by using the SAPS and SANS scales. While there were no significant group differences in overall scores and in the profile of progress of performance along periods on the GT, patient group showed a significant impairment when performing DLPFC tasks. Only FAS score was correlated to the severity of negative symptomatology. The OFC functions are unimpaired at the early phases of psychosis and in contrast there is a significant deficit in DLPFC functions in first-episode of schizophrenia.

No sex differences in neuropsychological performance in first episode psychosis patients.

OBJECTIVE: The purpose of this study was to verify whether male patients with psychosis have greater neurocognitive impairment than female patients at illness onset. METHOD: Participants with a first episode of psychosis (74 women/86 men) and healthy controls (62 women/97 men) were assessed with an extensive neuropsychological test battery. RESULTS: Women in the clinical group were older at illness onset and had achieved higher formal education than men. This trend was the same for the control group. The patient group presented with lower premorbid IQ compared to healthy controls, and performed below for most neuropsychological tests. Women scored higher than men on a test of verbal memory, whereas men scored higher than women on a test of reaction time, visual memory, and a planning task. There were no group-by-sex interactions for any of the neuropsychological tests. CONCLUSION: The present study shows that at the onset of psychosis there are no differences between males and females in neuropsychological performance. The differential pattern of cognitive performance observed is similar to that in healthy males and females. Furthermore, females with a late onset of psychosis may represent a subgroup with specific visuospatial and problem solving impairments.

Lack of insight 3 years after first-episode psychosis: an unchangeable illness trait determined from first presentation?

BACKGROUND: Lack of insight is recognized as a symptom that predisposes the individuals with psychosis to noncompliance with the treatment, leading to poorer course of illness. This study aimed to explore baseline predictors of disturbances on insight at follow-up. METHODS: Three insight dimensions (insight of: 'mental illness', 'need for treatment' and 'the social consequences of the disorder') were measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) in a cohort of 224 first-episode psychosis (FEP) patients at 3-year follow-up. Subgroups, good vs. poor insight, were compared on baseline clinical, neuropsychological, premorbid and sociodemographic characteristics. Regression models tested baseline predictors for each insight dimension. RESULTS: At 3-year follow-up a high percentage of patients, 45%, 36% and 33% for each dimension, were found to remain lacking insight. Poor insight into having an illness was predicted by a diagnosis of schizophrenia and poor baseline insight of the social consequences; insight into the need for treatment was predicted by adolescent adjustment and depression at baseline; and insight into the social consequences of the disorder was determined by late adolescent adjustment and baseline insight of mental illness. CONCLUSIONS: Our findings support the hypothesis that long-term insight in psychosis seems to be, to some extent, determined from first presentation, showing trait-like properties. A subgroup of 'lacking insight' patients, which is characterized by a diagnosis of schizophrenia, lower levels of premorbid adjustment and less severe depressive symptoms at baseline might benefit from special interventions targeted at enhancing insight from their first contact with psychiatric services.

Long-term (3-year) neurocognitive effectiveness of antipsychotic medications in first-episode non-affective psychosis: a randomized comparison of haloperidol, olanzapine, and risperidone.

INTRODUCTION: The initially postulated superior neurocognitive effectiveness of second-generation antipsychotics is currently under debate. METHODS: A prospective, randomized, open-label study was carried out to compare the long-term neurocognitive effectiveness of haloperidol, olanzapine, and risperidone in the first episode of schizophrenia spectrum disorders. A final sample of 79 patients randomized to haloperidol (N = 28), olanzapine (N = 23), or risperidone (N = 28) who completed clinical and cognitive evaluations at baseline and 3-year follow-up was included in the final analysis. Forty-one healthy individuals were also included in the final analysis. The main outcome measure was cognitive changes at 3-year follow-up. Due to the fact that some of the patients had switched their initially prescribed antipsychotic medication during the course of the study (6 out of 28 in haloperidol group, 18 out of 23 in olanzapine group, and 24 out of 28 in risperidone group continued with the initial study drug at 3-year assessment), we have also conducted a per protocol analysis. RESULTS: Overall, cognitive changes were similar in the three treatment groups and controls, although a greater improvement in Rey Auditory Verbal Learning Test, Digit Symbol, and Iowa Gambling Test was found in the treatment groups. The better performance observed on Rey Auditory Verbal Learning Test and Digit Symbol in olanzapine treatment group was likely explained by the lower prevalence of use of antimuscarinic drugs. These results were essentially similar to those found in the intention-to-treat analysis. CONCLUSIONS: The major conclusion of this study is that haloperidol, olanzapine, and risperidone have not demonstrated substantial neurocognitive effectiveness, improving cognitive deficits present in the early phases of the illness. The study also underscores the importance of exploring new drugs for the treatment of cognitive impairments and associated functional disabilities in schizophrenia.