Neurocognitive Deficits In Schizophrenia Research Articles

Disruption of medial prefrontal synchrony in the subchronic phencyclidine model of schizophrenia in rats

Subchronic treatment with the N-methyl-d-aspartate (NMDA) antagonist phencyclidine (PCP) produces behavioral abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2mg/kg twice daily for 7days) under urethane anesthesia. We found that this regimen reduced theta oscillations in the medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks.

La conscience des déficits neurocognitifs dans la schizophrénie : une méta-analyse

Background Schizophrenia is well-known to be associated with a lack of insight into symptoms. Comparatively, little is known on insight into neurocognitive deficits in schizophrenia, despite the fact that these dysfunctions are undoubtedly core features of the disorder. Recently, growing interest has been paid to subjective cognition, and thus far, results have been heterogeneous. The objectives of current meta-analysis were to determine the magnitude of subjective complaints in schizophrenia; to examine the association between subjective cognitive complaints and objective cognition, as well psychiatric symptoms and insight into illness. The meta-analysis also sought to determine if results are influenced by the choice of the scale used to measure subjective cognition. Methods A search was performed with PubMed, PsycInfo and EMBASE, using the following key words: schizophrenia OR psychosis AND cognition OR memory OR attention OR "executive functions" AND insight OR "subjective cognition" OR awareness. Studies involving patients with schizophrenia-spectrum disorders and measuring subjective cognition with a validated self-report scale were included. Studies using scales measuring insight into thinking processes (e.g. Beck Cognitive Insight Scale) were excluded. Statistical analyses were performed with the Comprehensive Meta-Analysis-2 software. Cognitive scores were grouped into 6 cognitive domains (as recommended by the MATRICS group): attention, problems solving, speed of processing, verbal memory, visual memory and working memory. The difference in cognitive complaints between schizophrenia patients and healthy controls was examined using Cohen's d. The associations between subjective cognition and objective cognition, psychiatric symptoms and insight into illness were examined using Pearson's correlation coefficients. Results Twenty-two studies were retrieved, including a total of 1609 patients and 294 controls. Patients reported increased subjective cognitive complaints, compared to controls (moderate effect size). A weak association was observed between subjective and objective (global) cognition. The association was larger in studies using the Subjective Scale To Investigate Cognition in Schizophrenia (SSTICS), compared to studies using other scales. The largest association was observed between subjective complaints and problem solving. The association between subjective complaints and depressive symptoms was in the same range as the association between subjective complaints (measured with the SSTICS) and objective cognition. No association was found between subjective complaints and positive / negative symptoms. Finally, a weak association was found between subjective complaints and insight into illness. Discussion Taken together, these results suggest that schizophrenia patients report significant subjective cognitive complaints. However, patients have a poor understanding of these deficits, since subjective complaints are as strongly associated with depressive symptoms as they are associated with objective cognitive deficits. Schizophrenia patients may be more aware of their problem solving deficits. However, this observation is based on a limited number of studies and will need to be replicated in future studies. Our results also show that insight into neurocognitive deficits is largely independent from insight into illness. Finally, the results of the current meta-analysis may have methodological implications, since they suggest that the SSTICS produces stronger associations between subjective and objective cognition than other scales. In the future, greater attention will need to be paid to the domains of subjective complaints, as well as to subjective cognitive complaints in other psychiatric disorders.

CDP-choline: Effects of the procholine supplement on sensory gating and executive function in healthy volunteers stratified for low, medium and high P50 suppression

Diminished auditory sensory gating and associated neurocognitive deficits in schizophrenia have been linked to altered expression and function of the alpha-7 nicotinic acetycholinergic receptor (α7 nAChR), the targeting of which may have treatment potential. Choline is a selective α7 nAChR agonist and the aim of this study was to determine whether cytidine 5'-diphosphocholine (CDP-choline), or citicoline, a dietary source of choline, increases sensory gating and cognition in healthy volunteers stratified for gating level. In a randomized, placebo-controlled, double-blind design involving acute administration of low, moderate doses (500 mg, 1000 mg) of CDP-choline, 24 healthy volunteers were assessed for auditory gating as indexed by suppression of the P50 event-related potential (ERP) in a paired-stimulus (S1, S2) paradigm, and for executive function as measured by the Groton Maze Learning Task (GMLT) of the CogState Schizophrenia Battery. CDP-choline improved gating (1000 mg) and suppression of the S2 P50 response (500 mg, 1000 mg), with the effects being selective for individuals with low gating (suppression) levels. Tentative support was also shown for increased GMLT performance (500 mg) in low suppressors. These preliminary findings with CDP-choline in a healthy, schizophrenia-like surrogate sample are consistent with a α7 nAChR mechanism and support further trials with choline as a pro-cognitive strategy.

A systematic review on improving cognition in schizophrenia: which is the more commonly used type of training, practice or strategy learning?

BackgroundThe purpose of this article was to conduct a review of the types of training offered to people with schizophrenia in order to help them develop strategies to cope with or compensate for neurocognitive or sociocognitive deficits.MethodsWe conducted a search of the literature using keywords such as “schizophrenia”, “training”, and “cognition” with the most popular databases of peer-reviewed journals.ResultsWe reviewed 99 controlled studies in total (though nine did not have a control condition). We found that drill and practice training is used more often to retrain neurocognitive deficits while drill and strategy training is used more frequently in the context of sociocognitive remediation.ConclusionsHypotheses are suggested to better understand those results and future research is recommended to compare drill and strategy with drill and practice training for both social and neurocognitive deficits in schizophrenia.

A pilot study on the effects of cognitive remediation on hemodynamic responses in the prefrontal cortices of patients with schizophrenia: A multi-channel near-infrared spectroscopy study

The regional neuronal changes taking place between before and after cognitive rehabilitation are still not characterized in schizophrenia patients. In addition, it is not known whether these regional changes are predictive or correlated with treatment response. We conducted a preliminary quasi-experimental study to investigate the effects of a Neuropsychological Educational Approach to Cognitive Remediation (NEAR), one of the cognitive remediation therapies, on neurocognitive functioning assessed by the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J), and on prefrontal and temporal hemodynamic responses during working memory (WM) task (2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS). We assessed 19 patients with schizophrenia or schizoaffective disorder twice with an interval of 6months. Moreover, taking into consideration the possible practice effect, we assessed 12 control patients twice with an interval of 6months. The NEAR group, in comparison with the control group, showed significant improvement in two subcomponents of BACS-J, that is, motor speed and executive function along with the composite scores. The NEAR group also showed a significant increase in brain activation in the bilateral cortical regions associated with WM, and in comparison with the control group the between-group differences were restricted to the right frontopolar area. In addition, the amount of enhancement in some cognitive subcomponents was positively correlated with the magnitude of an increase in hemodynamic response during WM task predominantly in the right hemispheres. These findings suggest that neurocognitive deficits in schizophrenia and their neural dysfunction may be improved by NEAR, and NIRS may be a useful tool to assess the changes of the neural activity underlying the improvement of neurocognitive functioning elicited by neurocognitive rehabilitation.

Psychopharmacological Treatment of Neurocognitive Deficits in People with Schizophrenia: A Review of Old and New Targets

Neurocognitive impairments significantly contribute to disability and the overall clinical picture in schizophrenia spectrum disorders. There has therefore been a concerted effort, guided by the discovery of neurotransmitter and synaptic systems in the central nervous system, to develop and test compounds that may ameliorate neurocognitive deficits. The current article summarizes the results of efforts to test neurocognitive-enhancing agents in schizophrenia. Overall, existing clinical trials provide little reason to be enthusiastic about the benefits of psychopharmacological agents at enhancing neurocognition in schizophrenia-a state of affairs that may reflect the inadequacy of single neurotransmitter or receptor models. The etiologic and phenomenological complexity of neurocognitive deficits in schizophrenia may be better served by psychopharmacological agents that (i) target neurotransmitter systems proximal in the causal chain to neurocognitive deficits; (ii) enhance distal survival processes in the central nervous system-neurogenesis, neuronal growth, synaptogenesis, and connectivity; and (iii) counteract the negative effects of aberrant neurodevelopment in schizophrenia, such as neuroinflammation and oxidative stress. Future efforts to develop psychopharmacological agents for neurocognitive impairment in schizophrenia should reflect the knowledge of its complex etiology by addressing aberrations along its causal chain. Clinical trials may benefit methodologically from (i) an appreciation of the phenomenological heterogeneity of neurocognitive deficits in schizophrenia; (ii) a characterization of the predictors of treatment response; and (iii) a recognition of issues of sample size, statistical power, treatment duration, and dosing.

EPA-1624 – Integrated assessment the effectiveness correction of neurocognitive deficit in schizophrenia patients

Schizophrenia is a chronic psychotic disease which occurs as a rule in young patients and often leads to their disability. The aim of our study was to show the influence of the atypical antipsychotics and drugs which have influence on sigma receptors on the neurocognitive deficit in schizophrenia patients. Material and methods For our investigation we observed 167 patients with paranoid schizophrenia according to the criteria of ICD 10. All patients received atypical antipsychotics. Patients were randomized into 3 groups. Patients of 1 st group (n=52) received sertindole monotherapy 16–20 mg per day, patients of 2 nd group (n=67) received paliperidone 9–12 mg per day and fluvoxamine in combination with zuclopenthixole depot 150–200 mg per day. Fluvoxamine was chosen because of its potential impact on sigma receptors. Results and discussion the results of the study indicate the significance of differences of dynamics of neurocognitive deficit in schizophrenia and the importance of choice of biological therapy for correction of neurocognitive deficit in patients with schizophrenia. Also the study showed the possibility of correction of components of neurocognitive deficit in schizophrenia patients which was confirmed by objective psychological tests. The use of modern atypical antipsychotics and drugs which can influence on sigma-receptors can restore the social functioning in young patients with schizophrenia.

Neurocognitive functioning in patients with first-episode schizophrenia 1 year from onset in comparison with patients 5 years from onset

Objective. The course of neurocognitive deficits in schizophrenia has not yet been established. Therefore, we followed patients with first-episode schizophrenia to verify the course of these deficits. Methods. In Study 1, tests of neurocognitive functioning were administered to patients with first-episode schizophrenia (FE group) every 6 months. Of the 26 patients who completed the baseline assessment, 19 completed a 6-month follow-up, and 13 completed a 1-year follow-up. In Study 2, 19 patients in FE group at 6-months when the neuropsychological measures was less influenced by psychotic symptoms and other patients who experienced schizophrenia 5-years earlier (5-year group) were compared. Results. In Study 1, verbal memory, motor speed, and executive functions significantly improved at the 1-year follow-up. In Study 2, patients in 5-year group performed worse in verbal memory and executive functions than patients in FE at 6-month group, but marginally but significantly better in verbal fluency. Conclusions. Verbal memory, executive functions, and verbal fluency were significantly different between 5-year group and FE at 6-month group, and may indicate progression of schizophrenia. Executive functions may reflect the state of psychosis. Working memory and processing speed which did not change significantly from onset are needed to verify the course in further research.

1247 – The role of modern antipsychotics in correction of neurocognitive deficit in schizophrenia patients

Schizophrenia is a chronic psychotic disease which occurs as a rule in young patients and often leads to their disability. A long time it was thought that a neurocognitive deficit in schizophrenia patients is unremediable but introduction of atypical antipsychotics in the therapy of schizophrenia shows us a principal possibility of its correction. It also shows that neurocognitive deficit is a plastic heteronomous phenomenon in the structure of psychopathology. The aim of our study was to show the influence of the atypical antipsychotics and drugs which have influence on sigma receptors on the neurocognitive deficit in schizophrenia patients. For our investigation we observed 167 patients with paranoid schizophrenia according to the criteria of ICD 10. Patients were randomized into 3 groups. Patients of 1 st group (n = 52) received sertindole monotherapy 16–20 mg per day, patients of 2 nd group (n = 67) received paliperidone 9–12 mg per day and fluvoxamine in combination with zuclopenthixole depot 150–200 mg per day. Social functioning in patients with schizophrenia significantly improved in all three groups especially in group №3. We suppose that it was connected with activating activity of fluvoxamine. Thus the results of the study indicate the significance of differences of dynamics of neurocognitive deficit in schizophrenia and the importance of choice of biological therapy for correction of neurocognitive deficit in patients with schizophrenia.The use of modern atypical antipsychotics and drugs which can influence on sigma-receptors can restore the social functioning in young patients with schizophrenia.

Effects of Tobacco Smoking on Neuropsychological Function in Schizophrenia in Comparison to Other Psychiatric Disorders and Non‐psychiatric Controls

Compared to the general population cigarette smoking prevalence is elevated in psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). These disorders are also associated with neurocognitive impairments. Cigarette smoking is associated with improved cognition in SZ. The effects of smoking on cognition in BD and MDD are less well studied. We used a cross-sectional design to study neuropsychological performance in these disorders as a function of smoking status. Subjects (N = 108) were SZ smokers (n = 32), SZ non-smokers (n = 15), BD smokers (n = 10), BD non-smokers (n = 6), MDD smokers (n = 6), MDD non-smokers (n = 10), control smokers (n = 12), and control non-smokers (n = 17). Participants completed a neuropsychological battery; smokers were non-deprived. SZ subjects performed significantly worse than controls in select domains, while BD and MDD subjects did not differ from controls. Three verbal memory outcomes were improved in SZ smokers compared with non-smokers; smoking status did not alter performance in BD or MDD. These data suggest that smoking is associated with neurocognitive improvements in SZ, but not BD or MDD. Our data may suggest specificity of cigarette-smoking modulation of neurocognitive deficits in SZ.

Has an Angel Shown the Way? Etiological and Therapeutic Implications of the PCP/NMDA Model of Schizophrenia

Over the last 20 years, glutamatergic models of schizophrenia have become increasingly accepted as etiopathological models of schizophrenia, based on the observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews developments in two key predictions of the model: first, that neurocognitive deficits in schizophrenia should follow the pattern of deficit predicted based on underlying NMDAR dysfunction and, second, that agents that stimulate NMDAR function should be therapeutically beneficial. As opposed to dopamine receptors, NMDAR are widely distributed throughout the brain, including subcortical as well as cortical brain regions, and sensory as well as association cortex. Studies over the past 20 years have documented severe sensory dysfunction in schizophrenia using behavioral, neurophysiological, and functional brain imaging approaches, including impaired generation of key sensory-related potentials such as mismatch negativity and visual P1 potentials. Similar deficits are observed in humans following administration of NMDAR antagonists such as ketamine in either humans or animal models. Sensory dysfunction, in turn, predicts impairments in higher order cognitive functions such as auditory or visual emotion recognition. Treatment studies have been performed with compounds acting directly at the NMDAR glycine site, such as glycine, D-serine, or D-cycloserine, and, more recently, with high-affinity glycine transport inhibitors such as RG1678 (Roche). More limited studies have been performed with compounds targeting the redox site. Overall, these compounds have been found to induce significant beneficial effects on persistent symptoms, suggesting novel approaches for treatment and prevention of schizophrenia.

Aberrant intrinsic brain activity and cognitive deficit in first-episode treatment-naive patients with schizophrenia

Given the important role of the default mode network (DMN) in cognitive function and the well-known neurocognitive deficit in schizophrenia, it is intriguing to examine systematically the relationship between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia. Method First-episode, treatment-naive patients with schizophrenia (FES) (n = 115) and healthy controls (n = 113) underwent resting-state functional magnetic resonance imaging (fMRI) scans and neurocognitive tests. Intrinsic neural activities evaluated by using the fragment amplitude of low-frequency fluctuations (fALFF) and the resting-state functional connectivity assessed by seed-based correlational analysis were compared between patients and controls. Aberrant intrinsic activities and DMN connectivity in patients were then correlated to neurocognitive performance and clinical symptoms. Compared to controls, patients with FES showed decreased fALFF in the bilateral medial prefrontal cortex (MPFC) and the orbitofrontal cortex (OFC), and increased fALFF in the bilateral putamen. Increased functional connectivity with the DMN was observed in the left insula and bilateral dorsolateral PFC (DLPFC) in patients with FES. In patients, aberrant fALFF in the bilateral OFC were correlated with cognitive processing speed; fALFF in the left OFC and right putamen were correlated with the clinical factors excited/activation and disorganization; and increased DMN functional connectivity in the left insula was correlated with the clinical factors positive, excited/activation, disorganization and neurocognitive deficit in the domain of sustained attention. These associations between neurocognitive dysfunction and aberrant intrinsic activities, and also functional connectivity, of the DMN in patients with schizophrenia may provide important insights into the neural mechanism of the disease.

NEUROPSYCHOLOGICAL CORRECTION OF COGNITIVE DISORDERS AS PART OF PSYCHOTHERAPY AT SCHIZOPHRENIA

The types of neuropsychological correction were considered and the conclusion about the effectiveness of this type of intervention and its important role in the treatment of schizophrenia was made. Cognitive impairment, observed in patients at schizophrenia are deficits of constitute executive functions, learning, memory, attention, tempo and dynamics of cognitive processes. They became the basis of the concept of neurocognitive deficits, a popular over the past twenty years. There was established interconnection between neurocognitive deficits and functional state of patients. As the awareness of the functional significance of neurocognitive deficits in schizophrenia is increasing, as interest in their correction is rising. Neuropsychological correction is a way of non-drug treatment of manifestations of neurocognitive deficits in schizophrenia.

Possible involvement of BDNF dysfunction in the synaptic loss caused by phencyclidine

Subchronic treatment with the N-methyl-d-aspartate (NMDA) antagonist phencyclidine (PCP) produces behavioral abnormalities in rodents which are considered a reliable pharmacological model of neurocognitive deficits in schizophrenia. Alterations in prefrontal neuronal firing after acute PCP administration have been observed, however enduring changes in prefrontal activity after subchronic PCP treatment have not been studied. To address this we have recorded cortical oscillations and unit responses in putative cortical pyramidal cells in subchronic PCP-treated rats (2 mg/kg twice daily for 7 days) under urethane anesthesia. We found that this regimen reduced theta oscillations in the medial prefrontal cortex. It further produced abnormal cortical synchronization in putative cortical pyramidal cells. These alterations in prefrontal cortex functioning may contribute to cognitive deficits seen in subchronic NMDA antagonist pre-treated animals in prefrontal-dependent tasks.

Standardization, Integration, and Sharing—Leveraging Research Investments

Cognitive impairment has been recognized as a significant cause of disability in schizophrenia for more than 20 years ( 1 Green M.F. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry. 1996; 153: 321-330 PubMed Google Scholar , 2 Green M.F. Kern R.S. Braff D.L. Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: Are we measuring the “Right Stuff”?. Schizophr Bull. 2000; 26: 119-136 Crossref PubMed Scopus (2398) Google Scholar ), but the development of effective treatments for cognitive impairment in schizophrenia has been slow to advance. The National Institute of Mental Health (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative ( 3 Marder S.R. Fenton W. Measurement and treatment research to improve cognition in schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res. 2004; 72: 5-9 Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar ) brought together members of academia, the pharmaceutical industry, and the US Food and Drug Administration to increase the viability of drug development by establishing consensus guidelines for study methodology, identifying promising targets for further investigation, and developing a standardized cognitive battery for use as end points in clinical trials. The resulting MATRICS Consensus Cognitive Battery (MCCB; 4 Nuechterlein K.H. Green M.F. Kern R.S. Baade L.E. Barch D.M. Cohen J.D. et al. The MATRICS Consensus Cognitive Battery, part 1: Test selection, reliability, and validity. Am J Psychiatry. 2008; 165: 203-213 Crossref PubMed Scopus (1544) Google Scholar , 5 Kern R.S. Nuechterlein K.H. Green M.F. Baade L.E. Fenton W.S. Gold J.M. et al. The MATRICS Consensus Cognitive Battery, part 2: Co-norming and standardization. Am J Psychiatry. 2008; 165: 214-220 Crossref PubMed Scopus (496) Google Scholar ) is a valuable tool that has been rapidly adopted and implemented in clinical research. However, instruments included in the MCCB are based on traditional neuropsychological measures developed more than 3 decades ago and tend to engage multiple cognitive functions simultaneously. This presents a significant disadvantage when testing treatments aimed at discrete cognitive processes, where “signal” for improved functioning might be obscured within a multi-component test of cognitive performance. With the revolution in cognitive science over the past decade ( 6 Cohen J.D. Insel T.R. Cognitive neuroscience and schizophrenia: Translational research in need of a translator. Biol Psychiatry. 2008; 64: 2-3 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ), the time is right to translate experimental cognitive neuroscience tasks into finer-grained clinical measures for use in the development of procognitive drugs. Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in SchizophreniaBiological PsychiatryVol. 70Issue 1PreviewTranscranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Full-Text PDF Using Brain Imaging Measures in Studies of Procognitive Pharmacologic Agents in Schizophrenia: Psychometric and Quality Assurance ConsiderationsBiological PsychiatryVol. 70Issue 1PreviewThe first phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICs) initiative focused on the identification of cognitive constructs from human and animal neuroscience that were relevant to understanding cognitive deficits in schizophrenia, as well as promising task paradigms that could be used to assess these constructs behaviorally. The current phase of CNTRICs has the goal of expanding this initial work by including measures of brain function that can augment these behavioral tasks as biomarkers to be used in drug development processing. Full-Text PDF Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia II: Developing Imaging Biomarkers to Enhance Treatment Development for Schizophrenia and Related DisordersBiological PsychiatryVol. 70Issue 1PreviewThe Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Full-Text PDF

Smooth pursuit and visual scanpaths: Independence of two candidate oculomotor risk markers for schizophrenia

Objectives. Smooth pursuit and visual scanpath deficits are candidate trait markers for schizophrenia. It is not clear whether eye tracking dysfunction (ETD) and atypical scanpath behaviour are the product of the same underlying neurobiological processes. We have examined co-occurrence of ETD and scanpath disturbance in individuals with schizophrenia and healthy volunteers. Methods. Eye movements of individuals with schizophrenia (N = 96) and non-clinical age-matched comparison participants (N = 100) were recorded using non-invasive infrared oculography during smooth pursuit in both predictable (horizontal sinusoid) and less predictable (Lissajous sinusoid) conditions and a free viewing scanpath task. Results. Individuals with schizophrenia demonstrated scanning deficits in both tasks. There was no association between performance measures of smooth pursuit and scene scanpaths in patient or control groups. Odds ratios comparing the likelihood of scanpath dysfunction when ETD was present, and the likelihood of finding scanpath dysfunction when ETD was absent were not significant in patients or controls in either pursuit variant, suggesting that ETD and scanpath dysfunction are independent anomalies in schizophrenia. Conclusion. ETD and scanpath disturbance appear to reflect independent oculomotor or neurocognitive deficits in schizophrenia. Each task may confer unique information about the pathophysiology of psychosis.

Lamotrigine blocks the initiation and expression of repeated high-dose methamphetamine-induced prepulse inhibition deficit in rats

Our group developed a new psychostimulant animal model reflecting some clinical aspects of schizophrenia better than the conventional model does. In this model, long-lasting prepulse inhibition (PPI) deficit at the basement state is induced via repeated administration of methamphetamine (METH, 2.5 mg/kg) without challenge injection of this psychostimulant. This study elucidates the effects of lamotrigine (LTG, 30 mg/kg) on the initiation and expression of a steady-state PPI deficit induced by the repeated METH administration. We assessed the effect of coadministration of LTG and METH on the initiation of PPI deficit. The LTG was injected 120 min after each METH injection for 5 times on every alternate day and for an additional 5 times every day, amounting to a total of 10 times. After 11–13 days of the withdrawal period, we measured PPI using the SR-LAB system. Using other animals after 20 min of LTG injection, we subsequently examined the effect of a single injection of LTG on the expression of PPI deficit caused by the repeated METH administration. The LTG blocked the initiation of PPI deficit induced by the repeated METH administration at 68 dB of prepulse intensity, but had no effect on the startle amplitude. The LTG prevented the initiation and expression of neuroplastic PPI deficit detected at the baseline state without any METH challenge injection, which was induced by the repeated administration of this psychostimulant. Results suggest that LTG is useful for blocking progressive deterioration of neurocognitive function and recovering the neurocognitive deficit in schizophrenia.

Evolution of neuropsychological dysfunction during the course of schizophrenia and bipolar disorder

Neurocognitive dysfunction in schizophrenia (SZ), bipolar (BD) and related disorders represents a core feature of these illnesses, possibly a marker of underlying pathophysiology. Substantial overlap in domains of neuropsychological deficits has been reported among these disorders after illness onset. However, it is unclear whether deficits follow the same longitudinal pre- and post-morbid course across diagnoses. We examine evidence for neurocognitive dysfunction as a core feature of all idiopathic psychotic illnesses, and trace its evolution from pre-morbid and prodromal states through the emergence of overt psychosis and into chronic illness in patients with SZ, BD and related disorders. Articles reporting on neuropsychological functioning in patients with SZ, BD and related disorders before and after illness onset were reviewed. Given the vast literature on these topics and the present focus on cross-diagnostic comparisons, priority was given to primary data papers that assessed cross-diagnostic samples and recent meta-analyses. Patients with SZ exhibit dysfunction preceding the onset of illness, which becomes more pronounced in the prodrome and early years following diagnosis, then settles into a stable pattern. Patients with BD generally exhibit typical cognitive development pre-morbidly, but demonstrate deficits by first episode that are amplified with worsening symptoms and exacerbations. Neuropsychological deficits represent a core feature of SZ and BD; however, their onset and progression differ between diagnostic groups. A lifetime perspective on the evolution of neurocognitive deficits in SZ and BD reveals distinct patterns, and may provide a useful guide to the examination of the pathophysiological processes underpinning these functions across disorders.

Behandlung kognitiver Defizite bei Schizophrenie

Cognitive dysfunction is a core feature of schizophrenia. Although cognitive deficits in the domains of attention, memory and executive functions have been described for many decades, the focus on therapeutic approaches is new. The recognition that cognitive deficits are the best known predictor of functional outcome in schizophrenic patients explains the increasing interest in the diagnosis and therapy of these impairments. Standards for the reliable evaluation of neurocognitive deficits in schizophrenia have been put forward by the MATRICS initiative (Measurement and Treatment Research to Improve Cognition in Schizophrenia). In German-speaking countries the most popular cognitive training programs for schizophrenic patients are "CogPack" and "Integrated Psychological Therapy (IPT)". Especially in Anglo-Saxon countries cognitive training has become more popular in recent years. Study outcomes can be considered encouraging. They show improvement of cognitive deficits and a positive impact on the functional outcome. Further studies are needed to optimize cognitive training for schizophrenic patients.

Specific metabolites in the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia: A preliminary study

We measured brain metabolites in the medial prefrontal cortex of 19 schizophrenic patients and 18 healthy controls by 3 T proton magnetic resonance spectroscopy (1H MRS), and examined the relationship between prefrontal cortex-related neurocognitive functions and brain metabolites in the medial prefrontal cortex. The patients with schizophrenia exhibited deficits on the verbal fluency, Wisconsin card sorting test (WCST), trail making test, Stroop test and digit span distraction test (DSDT), but not on the Iowa gambling test. The patients showed statistical significant changes in the ratio of glutamine/glutamate, the ratio of N-acetyl-l-aspartate (NAA)/glycerophosphorylcholine plus phosphorylcholine (GPC+PC) and the levels of taurine in the medial prefrontal cortex compared with normal controls. Furthermore, we found significant correlations of the ratio of glutamine/glutamate with WCST and DSDT scores, the ratio of NAA/(GPC+PC) with verbal fluency and WCST scores, and the levels of taurine with scores on the Stroop test and Trail making test A among the participants. The ratios of NAA/(GPC+PC) and (GPC+PC)/(Cr+PCr) had significant relationships with the duration of untreated psychosis of the schizophrenic patients. The glutamine/glutamate ratio and levels of taurine were significantly related to the duration of illness of the patients. These data suggest that specific metabolites of the medial prefrontal cortex are associated with the neurocognitive deficits in schizophrenia.