Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms.

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (α7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia. Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus α7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence. Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of α7 nAChR agonists for negative symptoms [standardized mean difference -0.28, 95% CI (-0.56 to -0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system. Conclusions: Current evidence is too weak to consider α7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.

Cognitive improvement of acetylcholinesterase inhibitors in schizophrenia.

BACKGROUND: Schizophrenia is a severe, persistent mental disorder, and a leading cause of disability worldwide. Cognitive impairments presented in schizophrenia lead to a worse prognostic, thus treatments targeted to enhance cognition in schizophrenia may be clinically relevant. AIMS: The purpose of this study was to assess the efficacy of acetylcholinesterase inhibitors as add-on medication to antipsychotics on cognition in patients with schizophrenia. METHODS: Search strategies were developed for Medline, Embase and Cochrane Central Register of Controlled Trials, and are current to March 2018. We included randomised controlled trials that compared antipsychotics plus acetylcholinesterase inhibitors versus antipsychotics plus placebo on prespecified cognitive domains (speed of processing, attention and working memory). Two review authors independently evaluated study eligibility, extracted data and assessed the risk of bias of included studies. We used random-effects model for meta-analyses and assessed the quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included nine randomised controlled trials. Six randomised controlled trials ( n=219) presented evidence that acetylcholinesterase inhibitors improve speed of processing (standardised mean difference -0.52, 95% confidence interval (-0.79 to -0.25); p value=0.0002). However, eight randomised controlled trials ( n=252) did find placebo was better than acetylcholinesterase inhibitors in the attention domain (-0.43, (-0.72 to -0.13); p value=0.005) and eight randomised controlled trials ( n=273) did not find differences in the working memory (-0.14, (-0.51 to 0.24), p value=0.47). CONCLUSIONS: The current evidence is too weak to base recommendations on the use of acetylcholinesterase inhibitors as adjunctive treatments to antipsychotics to improve basic cognitive functions. We have limited confidence in the effect estimates.

Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its most prevalent manifestation is neuropsychiatric SLE (NP-SLE), which is characterized by increased involvement of the nervous system, with relevant symptoms, such as marked cognitive deficits, which are directly involved in subsequent functional disability. The objective of this study is to identify and compare the profile of cognitive deficits in patients with NP-SLE and patients with non-neuropsychiatric SLE (nonNP-SLE) by means of a systematic review and meta-analysis. METHODS: We performed a systematic literature search based on the key words "cogn* OR neurocogn* AND lupus AND neuropsychiatry*" and included articles published between April 1999 and December 2016. A total of 244 articles were retrieved. We excluded reviews and meta-analyses, experiments not performed in humans, and single case reports. We included studies that used standardized cognitive measures and had included at least the subgroups NP-SLE and non NP-SLE. RESULTS: The meta-analysis was finally based on six studies, and 10 neuropsychological variables were examined. Significant differences were observed between the groups for six variables. In the remaining four variables, we observed marked heterogeneity between the groups or a low number of studies. CONCLUSIONS: The data obtained indicate greater cognitive impairment among NP-SLE patients than among nonNP-SLE patients, at least for the cognitive domains of visuomotor coordination, attention, executive function, visual learning and memory, and phonetic fluency. The identification and definition of cognitive deficits in SLE patients is necessary to develop adequate cognitive remediation programs to improve functional outcomes. (JINS, 2018, 24, 629-639).

Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional Assessment.

BACKGROUND: Studies on therapeutic drug monitoring (TDM) of second-generation antipsychotics (SGAs) have provided conflicting results regarding the association between dose, plasma concentrations, and drug effect and have focused rather on analyzing how individual drugs work. No study has attempted to process data from different SGAs globally to offer a panoramic view of the utility of TDM in clinical practice, and data on patients with first-episode psychosis (FEP) are lacking. This study aimed to assess the relationship between dose, plasma concentrations, and drug effect in a sample of patients with FEP, regardless of the SGA prescribed. METHODS: Data from 64 compliant patients treated with the same SGA during a 2-month follow-up were recorded. Clinical symptoms were assessed using the Positive and Negative Symptoms Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg für Kliniske Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents, and patients were classified into 3 different ranges according to their plasma concentrations (subtherapeutic, therapeutic, and supratherapeutic). RESULTS: Plasma concentration ranges were proportionally related to dose. Patients with supratherapeutic plasma concentrations were treated with doses significantly higher than those with subtherapeutic concentrations. Dose and plasma concentrations were not associated with early drug effect. CONCLUSIONS: TDM seems unable to accurately estimate the early effects of SGAs in FEP. Ours is the first study to categorize plasma concentrations of SGAs into ranges for joint processing of data from a larger number of patients.

A Pilot Study of the Usefulness of a Single Olanzapine Plasma Concentration as an Indicator of Early Drug Effect in a Small Sample of First-Episode Psychosis Patients.

PURPOSE/BACKGROUND: Studies analyzing concentration-effect relationships in second-generation antipsychotics have reported contradictory results in chronic schizophrenia. No data are available for the early stages of the disease. The present study aims to evaluate the association between a single olanzapine plasma concentration, clinical response, and severity of adverse effects in first-episode psychosis (FEP); to test the utility of various plasma breakpoints as markers of early response to treatment; and to identify variables affecting olanzapine concentrations. METHODS: Data from 23 compliant FEP patients receiving olanzapine monotherapy (5-30 mg/d) were evaluated 2 months after beginning treatment. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg for Kliniske Undersøgelser scale. Plasma samples were drawn at 11 (SD, 1) hours after dosing and analyzed with high-performance liquid chromatography/tandem mass spectrometry. FINDINGS: Consistent with findings on chronic disease, dose, age, sex, weight, and cigarettes/day accounted for some of the variability in olanzapine concentrations. While no relationship was found between olanzapine concentrations and adverse effects or improvement of depressive symptoms, response of psychotic symptoms was associated with concentrations between 22.56 and 77.92 ng/mL. Plasma breakpoints did not show sufficiently high specificity, resulting in a large number of false-positive results. IMPLICATIONS: Although olanzapine concentrations do not seem to be reliable indicators of early drug effect in FEP, they may still prove useful for detecting noncompliance, as well as pharmacokinetically relevant comorbidities or genetic particularities in drug metabolism.

Paliperidone reverts Toll-like receptor 3 signaling pathway activation and cognitive deficits in a maternal immune activation mouse model of schizophrenia.

The pathophysiology of psychotic disorders is multifactorial, including alterations in the immune system caused by exogenous or endogenous factors. Epidemiological and experimental studies indicate that infections during the gestational period represent a risk factor to develop schizophrenia (SZ) along lifetime. Here, we tested the hypothesis that the antipsychotic paliperidone regulates immune-related brain effects in an experimental model of SZ. A well described prenatal immune activation model of SZ in mice by maternal injection of the viral mimetic poly(I:C) during pregnancy was used. Young-adult offspring animals (60PND) received paliperidone ip (0.05 mg/kg) for 21 consecutive days. One day after last injection, animals were submitted to a cognitive test and brain frontal cortex (FC) samples were obtained for biochemical determinations. The adults showed an activated innate immune receptor TLR-3 signaling pathway, oxidative/nitrosative stress and accumulation of pro-inflammatory mediators such as nuclear transcription factors (i.e., NFκB) and inducible enzymes (i.e., iNOS) in FC. Chronic paliperidone blocked this neuroinflammatory response possibly by the synergic activation and preservation of endogenous antioxidant/anti-inflammatory mechanisms such as NRF2 and PPARγ pathways, respectively. Paliperidone administration also stimulated the alternative polarization of microglia to the M2 anti-inflammatory profile. In addition, paliperidone treatment improved spatial working memory deficits of this SZ-like animal model. In conclusion, chronic administration of paliperidone to young-adult mice prenatally exposed to maternal immune (MIA) challenge elicits a general preventive anti-inflammatory/antioxidant effect at both intracellular and cellular polarization (M1/M2) level in FC, as well as ameliorates specific cognitive deficits.

Similarities in early course among men and women with a first episode of schizophrenia and schizophreniform disorder.

The aims of this study were to analyze the presence of gender differences in the phenotypic expression of schizophrenia at the onset of illness and to explore whether these differences determine clinical and functional outcome 2 years after the initiation of treatment. Data from 231 first-episode-psychosis non-substance-dependent patients (156 men and 75 women) participating in a large-scale naturalistic open-label trial with risperidone were recorded at inclusion and months 1, 6, 12, and 24. Men presented a significant earlier age of onset (24.89 years vs. 29.01 years in women), poorer premorbid functioning, and a higher presence of prodromal and baseline negative symptoms. Women were more frequently married or lived with their partner and children and more frequently presented acute stress during the year previous to onset than men. No other significant clinical or functional differences were detected at baseline. The mean dose of antipsychotic treatment was similar for both genders during the study, and no significant differences in UKU scores were found. The number of hospitalizations was similar between groups, and adherence was more frequent among women. At the 2-year follow-up, both groups obtained significant improvements in outcome measures: PANSS, CGI severity, and GAF scores. Significant gender * time interactions were detected for negative and general PANSS subscales, with the improvement being more pronounced for men. However, no differences were detected for the mean scores obtained during the study in any outcome measure, and the final profile was similar for men and women. Our results suggest that although the initial presentation of schizophrenia can differ according to gender, these differences are not sufficient enough to determine differentiated outcome 2 years after the initiation of treatment in non-substance-dependent patients. The influence of gender on the early course of schizophrenia does not seem to be clinically or functionally decisive in this population.

Cognitive performance and smoking in first-episode psychosis: the self-medication hypothesis.

The self-medication hypothesis attempts to explain the extraordinary high levels of cigarette smoking in schizophrenia; patients may smoke in an attempt to reduce their cognitive deficits, symptoms, or the side effects of antipsychotics. In a previous report, we detected beneficial performance in attention and working memory in patients with first-episode psychosis who smoked compared to non-smoking patients soon after stabilization. In the present study, we examine differences in the course of those deficits 12 months after the initiation of antipsychotic treatment. We also explore the association between smoking and symptoms and side effects of medication. Neuropsychological assessments were performed at baseline, month 6 and month 12 using a computerized battery that included measures of sustained attention (Continuous Performance Test CPT-O), selective attention (Stroop interference task) and working memory (CPT-XO). Patients met the criterion of fitting in the same smoking category throughout the study: non-smoker (n = 15; 0 cigarettes/day) and smoker (n = 26; >15 cigarettes/day). The non-smoking patients showed significant cognitive improvements, whereas smoking patients lost their superior baseline performance, which was probably obtained through nicotinic stimulation, at the 6- and 12-month assessments due to a static course of deficits. Smokers did not obtain any cognitive benefit after instauration of treatment and worsen their symptoms over the first year. These results suggest that smoking may constitute a marker of a more severe illness. Smoking was not associated with fewer extrapyramidal side effects. Smoking might improve attention and working memory to a similarly modest extent as atypical antipsychotics and could reflect an effort to ameliorate these cognitive dysfunctions previous to treatment instauration.

Cognitive efficacy of quetiapine and olanzapine in early-onset first-episode psychosis.

The primary purpose of this study was to compare changes in cognition in early-onset psychosis after 6-months treatment with quetiapine or olanzapine. This is a randomized, single-blind, 6-month study in 50 adolescents with a diagnosis of early-onset psychosis. Patients were randomized to quetiapine (n = 24) or olanzapine (n =26). A thorough neuropsychological battery was administered at baseline and after 6-month treatment. Out of the total sample included in the study, 32 patients completed at least 6-months treatment with the assigned medication (quetiapine, n =16; olanzapine, n = 16). No changes were observed in cognitive performance after 6-month treatment with quetiapine or olanzapine. Although some trends toward cognitive improvement were observed for the olanzapine group after 6-month treatment, neither group showed statistically significant gains. Furthermore, there was no evidence of any differential efficacy of olanzapine or quetiapine on cognitive improvement in this sample of adolescents with psychosis.

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.

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.

Brain morphology and neurological soft signs in adolescents with first-episode psychosis.

BACKGROUND: Adolescents with first-episode psychosis have increased severity of neurological soft signs when compared with controls, but it is unclear whether increased severity of neurological soft signs is an expression of specific structural brain deficits. AIMS: To examine whether increased severity of neurological soft signs was associated with decreased brain volumes in adolescents with first-episode psychosis. METHOD: Brain scans were obtained for 70 adolescents (less than 18 years of age) with first-episode psychosis (duration of positive symptoms less than 6 months). Volumes were assessed using voxel-based morphometry and through segmentation of anatomical structures. RESULTS: Increased severity of sensory integration neurological soft signs correlated with smaller right and left thalamus volume, whereas increased severity of sequencing of complex motor acts neurological soft signs correlated with smaller right caudate volume. CONCLUSIONS: Neurological soft signs may be an easy-to-assess marker of region-specific structural brain deficits in adolescents with first-episode psychosis.

Gyral and sulcal cortical thinning in adolescents with first episode early-onset psychosis.

BACKGROUND: Psychosis is associated with volumetric decreases of cortical structures. Whether these volumetric decreases imply abnormalities in cortical thickness, surface, or cortical folding is not clear. Due to differences in cytoarchitecture, cortical gyri and sulci might be differentially affected by psychosis. Therefore, we examined differences in gyral and sulcal cortical thickness, surface, folding, and volume between a minimally treated male adolescent population with early-onset first-episode psychosis (EOP) and a healthy control group, with surface-based morphometry. METHODS: Magnetic resonance imaging brain scans were obtained from 49 adolescent EOP patients and 34 healthy control subjects. Subjects were younger than 18 years (age range 12 years-18 years), and EOP patients had a duration of positive symptoms of <6 months. RESULTS: Early-onset first-episode psychosis was associated with local bilateral cortical thinning and volume deficits in both the gyri and sulci of the superior temporal cortex and the inferior, middle, medial, and superior prefrontal cortex. In the pars triangularis and opercularis cortex of patients, gyral cortical thickness was thinner, whereas sulcal thickness was not. Patients exhibited cortical thinning together with a decreased degree of cortical folding in the right superior frontal cortex. CONCLUSIONS: Cortical thinning of both gyri and sulci seem to underlie most cortical volume deficits in adolescent patients with EOP. Except for the right superior frontal region, the degree of cortical folding was normal in regions showing decreased cortical thickness, suggesting that the process of cortical thinning in adolescent patients with EOP primarily takes place after the formation of cortical folds.

Olanzapine compared to quetiapine in adolescents with a first psychotic episode.

OBJECTIVE: To compare the efficacy, safety, and tolerability of olanzapine and quetiapine in adolescents with first episode psychosis. METHOD: Fifty adolescents (age 16 +/- 1.25) with a first episode of psychosis were randomized to quetiapine or olanzapine in a 6-month open label study. Efficacy and side effect scales, as well as vital signs and laboratory data were recorded at baseline, 7, 15, 30, 90, and 180 days (end of study). RESULTS: Out of the total sample included in the study, 32 patients completed the trial (quetiapine n = 16, olanzapine n = 16). Patients in both treatment groups had a significant reduction in all clinical scales with the exception of the negative scale of the Positive and Negative Symptom Scale (PANSS) for olanzapine and the general psychopathology scale of the PANSS for quetiapine. The only difference between treatment arms on the clinical scales was observed on the patients' strength and difficulties questionnaire (SDQ) scale, with greater improvement for olanzapine. Patients on olanzapine gained 15.5 kg and patients on quetiapine gained 5.5 kg. CONCLUSION: Olanzapine and quetiapine reduced psychotic symptoms in this adolescent sample. Patients on olanzapine gained significantly more weight. Side effects with both drugs seemed to be more prevalent than those reported in adult studies.

Progression of brain volume changes in adolescent-onset psychosis.

Little is known about the changes that take place in the adolescent brain over the first few years following the onset of psychosis. The present longitudinal study builds on an earlier cross-sectional report demonstrating brain abnormalities in adolescent-onset psychosis patients with a recent-onset first episode of psychosis. Magnetic resonance imaging studies were obtained at baseline and 2 years later from 21 adolescents with psychosis and 34 healthy controls matched for age, gender, and years of education. Whole-brain volumes and gray matter (GM) and cerebrospinal fluid (CSF) volumes of the frontal, parietal, temporal, and occipital lobes were measured at baseline and at 2-year follow-up. In the frontal lobe, the rate of GM volume loss was significantly higher in male patients (2.9% and 2.0%, respectively, for left and right) than in controls (1.2% and 0.7%, respectively, for left and right). In the left frontal lobe, male patients showed a significantly higher rate of CSF volume increase than controls (8.6% vs 6.4%). These differences in rates of volume change were observed in male and female patients, although only males showed significant time x diagnosis interactions. This negative finding in females should be interpreted with caution as the study was underpowered to detect change in women due to limited sample size. An exploratory analysis revealed that schizophrenia and nonschizophrenia psychotic disorders showed similar volume change patterns relative to controls. Change in clinical status was not correlated with longitudinal brain changes. Our results support progression of frontal lobe changes in males with adolescent-onset psychosis.

Cognitive performance and cigarette smoking in first-episode psychosis.

The purpose of this study is to describe possible differences in cognitive functioning between smoking and non-smoking patients with first-episode psychosis and to determine whether there is a better cognitive profile associated with smoking. We assessed 61 first-episode psychosis patients with a neuropsychological battery that included computerized measurements of attention, working memory, and executive functioning. Patients were grouped into two categories: non-smokers (0 cigarettes/day; n = 30) and smokers (>/=20 cigarettes/day; n = 31). No significant differences were detected in sociodemographic and clinical data between the two groups. For attention tasks, smokers exhibited shorter reaction times in the sustained attention test than non-smokers (P = 0.039) and needed less time to complete the Stroop interference test (P = 0.013). In the working memory task, smokers exhibited shorter reaction times (P = 0.029) and presented a significantly lower percentage of omission (P = 0.002) and commission errors (P = 0.020) than non-smokers. For executive functioning, no differences were detected between groups in performance on the Wisconsin Card Sorting Test. Results indicate that first-episode psychosis patients who are nicotine users have better cognitive functioning in the areas of attention and working memory than patients who are not nicotine users. This study supports the cognitive approach to the self-medication hypothesis, to explain the high rates of cigarette smoking among psychosis patients. These results may be relevant for developing new strategies involving nicotinic receptors for cognitive enhancement in psychosis.

Neurological soft signs in adolescents with first episode psychosis: two-year followup.

Neurological soft signs were assessed in 24 first episodes of early onset psychosis and 30 healthy adolescents over a 2-year period. Patients presented more neurological soft signs than controls and showed a significant decrease in some Neurological Evaluation Scale scores over the followup period. This decrease in the patient group was influenced by changes in symptomatology.

Regional gray matter volume deficits in adolescents with first-episode psychosis.

OBJECTIVE: The current study combined baseline voxel-based morphometry and 1-year clinical follow-up assessments to examine whether and where regional gray matter (GM) volumes differed between a control group and diagnostic subgroups of early-onset first-episode psychosis (FEP). METHOD: Magnetic resonance imaging brain scans were obtained from 70 patients with early-onset FEP, and 51 non-FEP controls. Early-onset FEP was defined as age younger than 18 years and a duration of positive symptoms of less than 6 months. The age range of the sample was 7 to 18 years. After a 1-year follow-up, patients were stratified into three subgroups: schizophrenia (n = 25), bipolar I disorder (n = 20), and other psychoses (n = 25). Regional GM volumes of each patient subgroup were compared with those of the control group. RESULTS: A follow-up diagnosis of schizophrenia was associated with GM volume deficits in the left medial and left middle frontal gyrus; bipolar I disorder was related to a GM volume deficit in the left medial frontal gyrus; and not having a follow-up diagnosis of schizophrenia or bipolar disorder was associated with smaller bilateral GM volumes in the insula and right middle occipital gyrus. CONCLUSIONS: Left medial frontal GM volume deficits were common in the groups with schizophrenia and bipolar I disorder, which may point to shared underlying pathological findings.

Course of cognitive functioning in first-episode psychosis: a comparison between schizophrenia and non schizophrenia psychosis.

AIMS: To describe the course of cognitive functioning in first-episode psychosis and to determine possible differences in the degree and trajectory of cognitive deficits between schizophrenia and non-schizophrenia first-episode psychosis. METHOD: We assessed attention, working memory, and executive functioning in 57 patients with first-episode psychosis both at baseline and at 1-year of follow-up. RESULTS: For the overall group, significant reductions were found in the percentage of omission and commission errors for the sustained attention task (p<0.001 and p=0.001, respectively), in the total time to complete the Stroop-I task (p<0.001), in the percentage of omission errors for the working memory task (p=0.001), and in the percentage of perseverative errors for the Wisconsin card sorting test (WCST; p<0.001), as well as a significant increase in the number of categories completed in the WCST (p<0.001). The remaining cognitive variables analyzed remained stable (4 of the 10 variables tested). The pattern of change was similar for patients with schizophrenia (n=20) and non-schizophrenia (n=37) in the areas of attention and working memory. For executive functioning, the non-schizophrenia group showed a more beneficial pattern of change. No significant differences were detected in cognitive performance among subgroups at baseline or at the 1-year follow-up. CONCLUSION: The course of cognitive deficits in first-episode psychosis showed significant improvements over the 1-year period in the areas of attention, working memory and executive functioning. Neuropsychological performance did not seem to be specific enough to distinguish between patients with schizophrenia and non-schizophrenia first-episode psychosis, at least during the first year.

Findings of proton magnetic resonance spectometry in the dorsolateral prefrontal cortex in adolescents with first episodes of psychosis.

Knowledge of the neurobiology of early onset psychosis is limited. We used proton magnetic resonance spectroscopy to investigate the possible existence of dorsolateral prefrontal brain biochemical abnormalities in adolescents with psychosis and to determine possible differential effects related to specific psychotic diagnoses. We measured the ratios of N-acetyl-aspartate (NAA), choline (Cho), and creatine (Cr) to water in two groups of adolescents with a first episode of psychosis (schizophrenia n=8; non-schizophrenia n=15) and in 32 healthy controls matched for age, gender, and years of education. Proton magnetic resonance spectroscopy at 1.5 T was used to study two 6.75-cc voxels placed in the left and right dorsolateral prefrontal region. The schizophrenia patients presented statistically significant reductions in NAA/water levels in the left dorsolateral prefrontal voxel as compared with non-schizophrenia patients and healthy controls. No significant differences were detected between groups for NAA/water in the right dorsolateral prefrontal voxel or for Cho/water and Cr/water levels in any hemisphere. A reduction of the NAA/water level in the left dorsolateral prefrontal region may be selectively present at the onset of psychosis during adolescence in patients who later progress to schizophrenia, but not in those who later progress to other psychotic disorders.