Neurocognition In Schizophrenia Research Articles

The association between plasma thyroxine levels and neurocognitive impairment in early-onset schizophrenia and other psychosis spectrum disorders

Background/aimLimited studies have delved into the association between thyroid hormones and neurocognition in schizophrenia. We aimed to evaluate the relationship between thyroid hormone levels and neurocognitive functions in patients with schizophrenia and other psychosis spectrum disorders (SSD). MethodA total of 135 patients with early-onset SSD were included in the study. The participants underwent a cognitive assessment. Blood samples were collected to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). Subgroup analyses were conducted based on the severity of the psychosis. FindingsThe results revealed a significant association between fT4 levels and various cognitive domains, including processing speed, verbal fluency, working memory, verbal learning, verbal memory, and visual memory. However, serum TSH and fT3 levels exhibited no significant association with neurocognitive impairment in adjusted linear regression models. Specifically, the correlation between fT4 levels and global cognition was more pronounced in patients with higher scores. ConclusionsSerum fT4 levels were associated with the performance across various cognitive domains in cases of early-onset psychotic disorders. This correlation was accentuated among patients with higher illness severity. Future studies could focus on the effects of specific pathways that can affect the course and progression of psychosis.

Negative symptoms and neurocognition in drug-naïve schizophrenia: moderating role of plasma neutrophil gelatinase-associated lipocalin (NGAL) and interferon-gamma (INF-γ).

Previous studies reported that peripheral inflammation was associated with cognitive performance and brain structure in schizophrenia. However, the moderating effect of inflammation has not been extensively studied. This study investigated whether inflammation markers moderated the association between negative symptoms and neurocognition in schizophrenia. This cross-sectional study included 137 drug-naïve schizophrenia patients (DNS) and 67 healthy controls (HC). We performed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for cognitive assessment and the Positive and Negative Syndrome Scale (PANSS) for psychiatric symptoms. Plasma concentrations of interferon-gamma (IFN-γ), neutrophil gelatinase-associated lipocalin (NGAL), and nuclear factor kappa B (NF-κB) were measured. The MCCB neurocognition score, social cognition score, and total score; the plasma concentrations of NGAL, IFN-γ, and NF-κB were significantly decreased in DNS than in HC (all P's < 0.001). PANSS negative subscale (PNS), PANSS reduced expressive subdomain (RES) negatively correlated with neurocognition score (P = 0.007; P = 0.011, respectively). Plasma concentrations of IFN-γ and NGAL positively correlated with neurocognition score (P = 0.043; P = 0.008, relatively). The interactions of PNS × NGAL; PNS × IFN-γ; RES × IFN-γ accounted for significant neurocognition variance (P = 0.025; P = 0.029, P = 0.007, respectively). Simple slope analysis showed that all the above moderating effects only occurred in patients with near normal IFN-γ and NGAL levels. Plasma concentrations of IFN-γ and NGAL moderated the relationship between negative symptoms (especially RES) and neurocognition in schizophrenia. Treatment targeting inflammation may contribute to neurocognition improvement in schizophrenia.

Neurocognition and its association with adverse childhood experiences and familial risk of mental illness

Environmental factors such as adverse childhood experiences (ACEs) may affect neurocognition, an endophenotype for several mental illnesses. This study examines the effect of ACEs on neurocognitive performance in first-degree relatives (FDRs) of patients with severe mental illness to determine whether familial risk has a moderating effect on the relationship between ACEs and neurocognition. Unaffected FDRs from multiplex families with severe mental illnesses (schizophrenia, bipolar disorder, obsessive-compulsive disorder, or alcohol use disorder) (n = 324) and healthy controls (with no familial risk) (n = 188) underwent neurocognitive tests for processing speed, new learning, working memory and Theory of Mind. ACEs were measured using the WHO ACE-International Questionnaire (ACE-IQ). Regression models were done to predict each neurocognitive domain by the effect of familial risk, ACE-IQ Score and their interaction (familial risk*ACE-IQ score). The main effect of familial risk predicted poor performance in all domains of neurocognition (p < 0.01), and the interaction had a negative association with global neurocognition (β = −0.093, p = 0.009), processing speed (β = −0.109, p = 0.003) and working memory (β = −0.092, p = 0.01). Among the ACEs sub-domains, only maltreatment (specifically the main effect of physical neglect and the interaction effect of sexual abuse with familial risk) predicted poorer neurocognition. In FDRs of schizophrenia and bipolar disorder, only the main effects of familial risk were significantly associated with poorer neurocognition. We conclude that there is a relationship between ACEs (especially maltreatment) and neurocognitive functioning, which is moderated by the familial risk of mental illnesses. Genetic/familial vulnerability may have a stronger association with neurocognition in schizophrenia and bipolar disorder.

The Impact of Sleep on Neurocognition and Functioning in Schizophrenia-Is It Time to Wake-Up?

People with schizophrenia (SZ) display substantial neurocognitive deficits that have been implicated as major contributors to poor daily functioning and disability. Previous reports have identified a number of predictors of poor neurocognition in SZ including demographics, symptoms, and treatment adherence, as well as body mass index, aerobic fitness, and exercise activity. However, the putative impact of sleep has received relatively limited consideration, despite sleep disturbances, which are pervasive in this population, resulting in symptoms that are strikingly similar to the neurocognitive deficits commonly observed in SZ. Here we argue for the consideration of the impact of sleep on neurocognition in people with SZ and propose recommendations for future research to elucidate the links between sleep parameters, neurocognition and daily functioning.

High-intensity interval training and active video gaming improve neurocognition in schizophrenia: a randomized controlled trial.

There is a need for treatments targeting neurocognitive dysfunctions in schizophrenia. The aim of this study was to investigate the neurocognitive effect of aerobic high-intensity interval training (HIIT). A comparison group performed sport simulating active video gaming (AVG). We anticipated that HIIT would improve neurocognition beyond any effect of AVG, due to engagement in higher intensity cardiorespiratory demands. Recent research on the beneficial neurocognitive effect of AVG challenges this expectation but added new relevance to comparing the two interventions. This is an observer-blinded randomized controlled trial. Eighty-two outpatients diagnosed with schizophrenia were allocated to HIIT (n = 43) or AVG (n = 39). Both groups received two supervised sessions per week for 12weeks. The attrition rate was 31%, and 65% of the participants were defined as protocol compliant study completers. Intention-to-treat analyses showed significant improvements in the neurocognitive composite score from baseline to post-intervention and from baseline to 4months follow-up in the total sample. The same pattern of results was found in several subdomains. Contrary to our hypothesis, we found no interaction effects of time and group, indicating equal effects in both groups. Separate within-group analysis unexpectedly showed trends of differential effects in the learning domain, as HIIT showed post-intervention improvement in verbal but not visual learning, while AVG showed improvement in visual but not verbal learning. HIIT and AVG improve neurocognition equally, suggesting that both interventions may be applied to target neurocognition in schizophrenia. Future research should investigate trends towards possible differential effects of exercise modes on neurocognitive subdomains. NCT02205684, 31.07.14.

Adjunctive Raloxifene and Isradipine Improve Cognitive Functioning in Patients With Schizophrenia: A Pilot Study.

Cognitive impairment is the most important feature of schizophrenia leading to severe functional disability. To identify pathways that improve pathophysiological neurocognition in schizophrenia is a current challenge for the development of goal-directed clinical interventions. In the present study, we investigated the effects of raloxifene (a selective estrogen modulator) and isradipine (a voltage-gated L-type calcium channel blocker) on cognitive deficits in patients with schizophrenia. We designed a double-blind, randomized, parallel, placebo-controlled trial. We randomized 60 patients with schizophrenia into 3 groups including isradipine 5 mg, raloxifine 60 mg, and placebo for 6 consequent weeks, all in the same shape capsules, 2 times a day, along with treatment as usual. The initial and final results of blood tests, electrocardiograms, and cognitive tests in specific domains, such as attention, processing speed, executive function, and verbal memory were evaluated. Our findings revealed a remarkable association between adjunctive raloxifene treatment and the alleviation of verbal memory deficits. Isradipine treatment significantly improved the verbal memory and attention dysfunction in some variables of the Stroop test, compared with the placebo. However, no effect was observed in processing speed and executive function deficits. To the best of our knowledge, this study provides the first evidence that isradipine is a novel therapy option improving verbal memory and attention, both related to its activity in the hippocampus and the cerebellum. Further investigations are necessary to elucidate the mechanisms of action for both drugs in schizophrenia.

O4.3. SHARED AND DIFFERENTIAL NEUROCOGNITIVE EFFECTS COMPARING HIGH-INTENSITY INTERVAL TRAINING AND ACTIVE VIDEO-GAMING IN SCHIZOPHRENIA – RESULTS FROM AN RCT

BackgroundStudies on the efficiency and efficacy of aerobic exercise (AE) as a neurocognitive intervention in schizophrenia are promising, but there is a need for larger and well-designed randomized controlled trials (RCT) to draw more certain conclusions. The aim of this RCT was to study the effect of high-intensity interval training (HIIT), on neurocognitive functions in schizophrenia. A comparison group performed active video-gaming (AVG) using Nintendo WII sport. We hypothesized some effect in both groups, but anticipated that the effect of HIIT would reach beyond AVG. However, in recent studies AVG interventions with perceptual and motor-coordination demands were found to have neurocognitive effects equivalent to AE, challenging our hypothesis and adding new relevance to our study. To our knowledge, this is the first study to compare the effects of HIIT and AVG on neurocognition in schizophrenia.MethodsThe current study was a single-blinded RCT. Eighty-two participants (61% males, median age 32 (24.3)) diagnosed with schizophrenia were recruited from outpatient clinics at Vestfold Hospital Trust and randomly allocated to HIIT (n=43) or AVG (n=39). Both interventions consisted of 45 minutes supervised sessions two times per week for 12 weeks. The primary outcome neurocognition was measured with the MATRICS consensus cognitive battery by blinded assessors at baseline, post-intervention and follow-up. In sum 88% were protocol-compliant and attrition rate was 30.5%, resulting in 65% protocol-compliant study-completers (HIIT n=25/AVG n=28).Intervention effects were estimated using repeated linear mixed model analysis (LMM): Intention-to-treat (ITT) analyses of all randomized participants and per-protocol (PP) analyses of protocol-compliant study-completing participants. Per-protocol between-group effect sizes (Cohen’s d) and within-group pretest-posttest effect sizes were calculated.ResultsWe present post-intervention results. In the between-group analysis (ITT and PP) there was a main effect of time (EST 2.71, 95% CI: 1.45–3.98, p <.001), but no significant interaction effect of group and time (EST 0.36, 95% CI: -1.45–2.17, p=.696), for the neurocognitive composite T-score. The same pattern of results was found in the subdomains, indicating an increase in functioning over time for both groups on several subdomains. Per-protocol effect-sizes indicated a small to medium effect on verbal learning favoring HIIT (Cohen’s d =.46).Within-group analysis (PP) and pre-post effect sizes (PP) indicated small effects from both interventions on the neurocognitive composite score and the subdomains attention and working memory. There was a small effect on speed from HIIT. In the learning domain, HIIT had significant medium effect on verbal learning while AVG had a significant small effect on visual learning.DiscussionContrary to our hypothesis, the main analyses did not indicate superiority of HIIT compared to AVG on neurocognitive functions. Despite this, effect sizes indicated a small/moderate effect on verbal learning favoring HIIT.Within-group analysis showed increase in the neurocognitive composite score and the subdomains attention and working memory following both interventions. There was a small increase in speed following HIIT. Differential effects within the learning domain as indicated by increased verbal learning following HIIT and increased visual learning following AVG was unexpected, but replicate studies showing differential neurocognitive effects from different training modes. Our results show shared and differential positive effects from the two exercise modes HIIT and AVG on neurocognition. Both show potential as clinical interventions targeting neurocognition in schizophrenia.

A meta-analysis of the associations between theory of mind and neurocognition in schizophrenia

Theory of mind (ToM) refers to the ability to infer the mental states of others. ToM is impaired in schizophrenia and these deficits seem to hinder functional recovery. ToM is thus an important, but complex treatment target, supported by several processes. A large number of studies report significant associations between ToM and neurocognition (e.g. memory, attention), but the neurocognitive domains that are most closely linked to ToM remain to be identified. A meta-analysis was conducted to estimate the magnitude of the associations between ToM and neurocognition in people with schizophrenia. Correlations were extracted from the relevant literature, transformed into effect sizes Zr and pooled as weighted means. Focused-tests were employed to test for differences between neurocognitive domains and for differences linked to the characteristics of ToM tasks. Ninety-one studies (N = 5462) were included. Moderate associations emerged between ToM and each neurocognitive domain (Zrs 0.27–0.43), with no significant difference between domains (χ2(8) = 11.89, p = 0.156). Within the domain of executive functions, abstraction showed a stronger association with ToM (χ2(4) = 18.93, p = 0.001). Several ToM tasks characteristics (e.g. modality of stimuli, type of mental state), were significantly related to the magnitude of the associations between ToM and executive functions, visuospatial/problem solving, attention and episodic memory. These results suggest that ToM is linked to a wide range of neurocognitive abilities in schizophrenia, and that ToM tasks are a significant moderator of these associations. The assessment and treatment of ToM should consider the neurocognitive profile of each patient to understand his difficulties and to tailor interventions.

Endogenous oxytocin levels are associated with impaired social cognition and neurocognition in schizophrenia

Intranasal administration of the neuropeptide oxytocin (OT) has yielded inconsistent effects on social cognition and general cognition in individuals with schizophrenia (SZ). Few studies have examined whether endogenous peripheral OT levels are also associated with social and general cognition in SZ. The current study examined whether plasma OT levels are associated with performance on a higher-order social cognition measure (i.e., a task that requires inferential processes and knowledge not directly presented in social stimuli), as well as domains of general cognition. Participants included 30 individuals with SZ and 21 demographically matched healthy controls (CN). The MATRICS Consensus Cognitive Battery was administered to assess neuropsychological impairment in relation to 7 domains (processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving, and social cognition). Plasma OT levels were measured via radioimmunoassay. SZ had significantly lower endogenous OT levels and poorer MCCB performance on all 7 domains than CN. In CN and SZ, lower endogenous OT was associated with poorer social cognition. In SZ, lower endogenous OT was also associated with poorer processing speed and working memory. The significant association between OT and social cognition in both CN and SZ highlights the importance of endogenous OT levels as a biological predictor of social cognition, irrespective of clinical status. Significant associations between plasma OT and general neurocognition may reflect either an anxiolytic effect of plasma OT that results in better neurocognitive performance, or OT's action on dopamine and enhancement of dopamine tone that results in improved cognition.

Social Cognition and Neurocognition in Schizophrenia and Healthy Controls: Intercorrelations of Performance and Effects of Manipulations Aimed at Increasing Task Difficulty.

Social cognition (SC) and neurocognition appear to predict different aspects of functional outcome in people with schizophrenia. However, the correlations between performance on these domains have not been tested extensively and compared cross-diagnostically with healthy controls. Further, some social cognitive measures appeared to have potential ceiling effects, particularly for healthy people, in previous research, so increasing their difficulty is of interest. In this paper we report on two studies wherein we examined the correlations between neurocognitive ability and performance on SC tests. In the first study the correlations between measures of social perception, emotion processing, and theory of mind and performance on a brief neuropsychological (NP) assessment were examined in 179 schizophrenia (SCZ) patients and 104 healthy controls (HC). In the second study, we instructed participants to perform a subset of the tasks as rapidly as possible in order to increase task difficulty, and we examined the effects of those instructions on task difficulty, task psychometrics, and correlations between SC and NP tests in 218 SCZ patients and 154 HC. In the first study, both HC and SCZ manifested a domain specific pattern of correlation between NP and SC test performance. Controlling for group differences in NP performance did not eliminate SC performance differences between the groups. In the second study, no differences in task performance, intercorrelations other SC tests, or test-retest stability were induced by the difficulty manipulation in the samples who performed the tasks with speed demands compared to the performance of the previous sample. These data suggest that simple manipulations aimed at increasing task difficulty may not have the desired effect and that despite consistent correlations between SC and NP test performance, impairments in social cognitive functioning are not fully explained by NP performance deficits.

S240. Intact Motor Plasticity in Schizophrenia as Assessed by Transcranial Magnetic Stimulation With Paired Associative Stimulation

Deficient synaptic plasticity, including deficits in long term potentiation (LTP), may underlie impaired neurocognition in schizophrenia (SZ). LTP-like plasticity can be assessed non-invasively using the transcranial magnetic stimulation-paired associative stimulation (TMS-PAS) paradigm, involving repeated pairings of median nerve stimulation with a TMS pulse delivered over contralateral motor cortex.

Relationship between effortful motivation and neurocognition in schizophrenia

Effortful motivation and reward valuation learning deficits are associated with negative symptoms and impaired cognition in schizophrenia (SZ) patients. Whereas clinical assessments of motivation and reward value typically rely upon clinician ratings or self-report scales, behavioral measures often confound these constructs. Simple reverse-translated behavioral tasks that independently quantify motivation and reward valuation—which could then be linked to cognition—may facilitate the development of pro-cognitive therapeutics by bridging the “preclinical-to-clinical” gap. This study determined whether novel behavioral measures of effortful motivation and reward valuation are associated with impaired cognition in SZ patients (n=36). Patients completed the Progressive Ratio Breakpoint task (PRBT; physical effort motivation) and the Probabilistic Learning Task (PLT; reward learning/valuation) in conjunction with the MATRICS Consensus Cognitive Battery (MCCB). SZ patients exhibited statistically significant deficits in global cognition and all individual MCCB subdomains. Significant correlations were observed between PRBT and MCCB global cognition (r=0.52), speed of processing (r=0.56) and attention vigilance (r=0.48) subdomains, but not with PLT or clinical symptoms. Results indicate that effort and reward learning deficits are dissociable targets that can improve our understanding of cognitive impairments associated among patients with SZ. More importantly, the results support the long-standing notion that the measurement of cognitive impairments in SZ is highly linked to a willingness to expend effort. The availability of a PRBT designed for use in both rodents and humans could improve our understanding of the nature of cognitive impairments in neuropsychiatric disorders and accelerate the development of novel pro-cognitive therapeutics.

Intranasal Oxytocin May Improve High-Level Social Cognition in Schizophrenia, But Not Social Cognition or Neurocognition in General: A Multilevel Bayesian Meta-analysis.

While there is growing interest in the potential for intranasal oxytocin (IN-OT) to improve social cognition and neurocognition (ie, nonsocial cognition) in schizophrenia, the extant literature has been mixed. Here, we perform a Bayesian meta-analysis of the efficacy of IN-OT to improve areas of social and neurocognition in schizophrenia. A systematic search of original research publications identified randomized controlled trials (RCTs) of IN-OT as a treatment for social and neurocognitive deficits in schizophrenia for inclusion. Standardized mean differences (SMD) and corresponding variances were used in multilevel Bayesian models to obtain meta-analytic effect-size estimates. Across a total of 12 studies (N = 273), IN-OT did not improve social cognition (SMD = 0.07, 95% credible interval [CI] = [-0.06, 0.17]) or neurocognition (SMD = 0.12, 95% CI = [-0.12, 0.34]). There was moderate between study heterogeneity for social cognition outcomes(τs=0.12). Moderator analyses revealed that IN-OT had a significantly larger effect on high-level social cognition (ie, mentalizing and theory of mind) compared to low-level social cognition (ie, social cue perception) (b = 0.19, 95% CI = [0.05, 0.33]). When restricting our analysis to outcomes for high-level social cognition, there was a significant effect of IN-OT (SMD = 0.20, 95 % CI = [0.05, 0.33]) but the effect was not robust to sensitivity analyses. The present analysis indicates that IN-OT may have selective effects on high-level social cognition, which provides a more focused target for future studies of IN-OT.

Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills?

Most original studies and all meta-analyses conducted to date converge on the conclusion that patients with schizophrenia display rather generalized neurocognitive deficits. For the present study, we reopen this seemingly closed chapter and examine whether important influences, such as lack of motivation and negative attitudes towards cognitive assessment, result in poorer secondary neuropsychological performance. A sample of 50 patients with an established diagnosis of schizophrenia were tested for routine neurocognitive assessment and compared to 60 nonclinical volunteers. Before and after the assessment, subjective momentary influences were examined (e.g. motivation, concerns about assessment, fear about poor outcome) for their impact on performance using a new questionnaire called the Momentary Influences, Attitudes and Motivation Impact (MIAMI) on Cognitive Performance Scale. As expected, patients performed significantly worse than controls on all neurocognitive domains tested (large effect size, on average). However, patients also displayed more subjective momentary impairment, as well as more fears about the outcome and less motivation than controls. Mediation analyses indicated that these influences contributed to (secondary) poorer neurocognitive performance. Differences in neurocognitive scores shrank to a medium effect size, on average, when MIAMI scores were accounted for. The data argue that performance on measures of neurocognition in schizophrenia are to a considerable extent due to secondary factors. Poor motivation, fears and momentary impairments distinguished patients from controls and these variables heavily impacted performance. Before concluding that neurocognitive deficits in psychiatric patients are present, clinicians should take these confounding influences into account. Although patients with schizophrenia achieved, on average, worse test scores than controls, a large subgroup displayed spared performance.

The pro-cognitive mechanisms of physical exercise in people with schizophrenia.

Schizophrenia is associated with pervasive cognitive deficits which are unresponsive to antipsychotic medications. Physical exercise has been shown to improve cognitive functioning in people with schizophrenia, although the mechanisms for this are unclear. We conducted a systematic review of all exercise intervention studies which reported changes in brain structure, connectivity or peripheral biomarkers which could underlie cognitive improvements from exercise in schizophrenia. An electronic database search was conducted on 22 September 2016 using keywords relevant to exercise and neurocognition in schizophrenia. The search returned 2342 articles. Sixteen were eligible for inclusion, reporting data from 14 independent trials of 423 patients with schizophrenia. Seven studies used neuroimaging to examine the impact of exercise on brain structure and connectivity in schizophrenia, whereas seven other studies examined peripheral biomarkers to assess the effects of exercise. Imaging studies collectively indicated that exercise can increase brain volume in people with schizophrenia, although the regions which responded to exercise varied across studies. Most biomarker studies assessed the effects of exercise on serum levels of BDNF. Several studies found significant increases from exercise along with positive correlations between BDNF and cognitive enhancements (indicating a mechanistic link), although other studies did not observe this relationship. In conclusion, the cognitive benefits of exercise in schizophrenia may be due to exercise stimulating neurogenesis, perhaps by up-regulating BDNF, although current evidence is insufficient to draw definitive conclusions. Further exploration of the pro-cognitive mechanisms of exercise in schizophrenia would inform the development of optimal interventions for reducing cognitive impairments in this population. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

Do better communication skills promote sheltered employment in schizophrenia?

Alongside various psychopathological symptoms and neurocognitive dysfunctions, communication skill impairments may be considered core feature of schizophrenia. Although many studies examined the relation between employment status and neurocognition in schizophrenia, we still know very little about the role of communication skills in vocational status among people with schizophrenia. The purpose of this study is to identify the most characteristic communication, neurocognitive and social cognition differences which separate the employed schizophrenia outpatients from those who do not work. The study included three groups: 33 schizophrenia outpatients employed in social firms, 29 unemployed schizophrenia outpatients participating in occupational therapy and sex & age matched 31 healthy controls. We assessed communication skills, global cognitive functioning, executive functions, memory, social cognition as well as severity of psychopathology. Our results indicate that the most characteristic differences between employed and unemployed schizophrenia outpatients are associated with selective language and communication skills, i.e. paralinguistic aspects of communication, understanding of discrete meaning of linguistic context and figurative meaning of language. We find no significant differences between both clinical groups with regard to neurocognition and social cognition. Moreover, unemployed group had more severe psychopathology than the employed group, so we re-analyzed results controlling for symptom severity. The only differences that endured were related to general communication skills and explanation of pictured metaphors, but only when controlling solely for positive or negative syndrome. In conclusion, the present study indicates that employment in schizophrenia is associated with better symptomatic remission and communication skills, but not with better neurocognition and social cognition.

Effects of caffeine intake and smoking on neurocognition in schizophrenia

Although most studies support the beneficial effects of caffeine on neurocognition, its effects have never been assessed in psychiatric patients. In addition, results from studies in smokers are contradictory. Moreover, there are no data available about the neurocognitive effects of caffeine and tobacco together. We explored the concomitant effects of regular caffeine and tobacco intake on neurocognition in 52 schizophrenic patients and 61 healthy controls. Verbal fluency, processing speed, and working, visual and verbal memory were assessed. For each measurement, two tasks with two levels of complexity were administered. Our results showed that caffeine intake had beneficial effects on male schizophrenic patients only in complex tasks requiring deeper cognitive processing (semantic fluency, cognitive speed, working memory, and visual memory). Female patients and controls were unaffected. In contrast, smoking had a negative effect on male, but not on female, schizophrenic patients in semantic fluency. The effects of smoking in controls were inconsistent. In conclusion, our data showed, for the first time, beneficial effects of caffeine intake on neurocognition in male schizophrenic patients. These data suggest that further research of therapeutics based on caffeine is needed, as this could be beneficial for schizophrenic patients. In contrast, smoking appears to be detrimental.

Neurocognitive normality in schizophrenia revisited

The validity and significance of normal range neurocognition in schizophrenia remain unclear and controversial. We assessed whether normal range patients and controls demonstrate evidence of decline relative to premorbid ability and differ in performance profiles across measures, including those external to the normality criterion. In addition, we compared below normal range healthy control participants with patients at the same ability level. Performance normality was defined as a MATRICS Consensus Cognitive Battery (MCCB) composite T score between 40 and 60. Patients (n=17) and controls (n=24) meeting the criterion were compared on MCCB domain scores and on independent measures of reading ability, probabilistic and social reasoning. Patients (n=19) and controls (n=20) scoring below 40 on the MCCB composite were compared on the same set of measures. Cognitively normal range patients and controls did not differ on estimated premorbid ability or decline and differed only on the Processing Speed domain of the MCCB. Performance did not differ across other domains or on social and probabilistic reasoning tasks. Cognitively below normal range patients and controls showed marked discrepancies between premorbid and current ability, but there were no group differences. In addition, below normal range groups did not differ on any MCCB domain score or in terms of external cognitive measures. Cognitively normal range schizophrenia patients may be largely indistinguishable from normal range controls, with the exception of processing speed performance. More typical schizophrenia patients below the normal range may be indistinguishable from low-performing controls even in terms of processing speed.

Oxidative stress in schizophrenia: a case-control study on the effects on social cognition and neurocognition.

BackgroundSchizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia.MethodsWe assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty–one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group.ResultsWe found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress.ConclusionsWe propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

C-14 * Plasma Oxytocin Levels are Associated with Impaired Social Cognition and Neurocognition in Schizophrenia

C-14 * Plasma Oxytocin Levels are Associated with Impaired Social Cognition and Neurocognition in Schizophrenia