Information Processing In Schizophrenia Research Articles

Oxidative stress and role of antioxidant and ω-3 essential fatty acid supplementation in schizophrenia

Mahadik, Sahebarao P., Denise Evans and Harbans Lal: Oxidative Stress and Role of Antioxidant and ω3 Essential Fatty Acid Supplementation in Schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiat. 1. Schizophrenia is a major mental disorder that has a lifetime risk of 1% and affects at young age (average age at the onset 24 ± 4.6 years) in many cultures around the world. The etiology is unknown, the pathophysiology is complex, and most of the patients need treatment and care for the rest of their lives. 2. Cellular oxidative stress is inferred from higher tissue levels of reactive oxygen species (ROS, e.g., O 2 — , OH , OH —, NO and ONOO —) than its antioxidant defense that cause peroxidative cell injury, i.e., peroxidation of membrane phospholipids, particularly esterified essential polyunsaturated fatty acids (EPUFAS), proteins and DNA. 3. Oxidative stress can lead to global cellular with predominantly neuronal peroxidation, since neurons are enriched in highly susceptible EPUFAs and proteins, and damages DNA is not repaired effectively. 4. Such neuronal peroxidation may affect its function (i.e., membrane transport, loss of mitochondrial energy production, gene expression and therefore receptor-mediated phospholipid-dependent signal transduction) that may explain the altered information processing in schizophrenia. 5. It is possible that the oxidative neuronal injury can be prevented by dietary supplementation of antioxidants (e.g., vitamins E, C and A; β-carotene; Q-enzyme, flavons, etc.) and that membrane phospholipids can be corrected by dietary supplementation of EPUFAs. 6. It may be that the oxidative stress is lower in populations consuming a low caloric diet rich in antioxidants and EPUFAs, and minimizing smoking and drinking. 7. Oxidative stress exists in schizophrenia based on altered antioxidant enzyme defense, increased lipid peroxidation and reduced levels of EPUFAs. The life style of schizophrenic patients is also pro-oxidative stress, i.e., heavy smoking, drinking, high caloric intake with no physical activity and treatment with pro-oxidant drugs. 8. The patients in developed countries show higher levels of lipid peroxidation and lower levels of membrane phospholipids as compared to patients in the developing countries. 9. Initial observations on the improved outcome of schizophrenia in patients supplemented with EPUFAs and antioxidants suggest the possible beneficial effects of dietary supplementation. 10. Since the oxidative stress exists at or before the onset of psychosis the use of antioxidants from the very onset of psychosis may reduce the oxidative injury and dramatically improve the outcome of illness.

Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia.

In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.

Misattribution of sensory input reflected in dysfunctional target:non-target ERPs in schizophrenia.

While numerous studies have found disturbances in the Event-Related Potentials (ERPs) of patients with schizophrenia linked to task relevant target stimuli (most notably a reduction in P300 amplitude), few have examined ERPs to task irrelevant non-targets. We hypothesize, from current models of dysfunction in information processing in schizophrenia, that there will be less difference between ERPs to targets and non-targets in patients with schizophrenia than in controls. EEGs were recorded for 40 subjects with schizophrenia and 40 age and sex matched controls during an auditory oddball reaction time task. ERPs to the targets and non-targets immediately preceding the targets were averaged separately. There was a disturbance in ERPs to targets but also to non-targets (reduced N100 amplitude and earlier P200 latency) and the difference between target and non-target ERP components (N100 and P200 amplitude and P200 latency), was significantly reduced in the schizophrenic group compared with controls. These findings suggest a disturbance in processing task relevant and irrelevant stimuli, consistent with Gray's (1998) hypothesis of misattributions in the 'match:mismatch' of novel (target) and familiar (non-target) sensory input compared with stored information.

The effect of clozapine on the speed and accuracy of information processing in schizophrenia

1. 1. The study aimed to investigate the effects of clozapine on the speed and accuracy of information processing in patients with schizophrenia. Data are reported from 13 subjects with schizophrenia, treated with clozapine for 6.8 (± 1.8) months. 2. 2. Reaction time and accuracy of target detection on a tone detection task were measured before and during clozapine treatment, and these results were compared with a matched control group. 3. 3. Symptom severity and performance on three timed tests of cognitive function were also measured prior to clozapine treatment in the schizophrenia group, and these measures were repeated during treatment with clozapine. 4. 4. Treatment with clozapine was found to significantly improve reaction time and the accuracy of target detection in patients with schizophrenia. Despite this improvement their performance remained significantly inferior to that of a matched control group. Both positive and negative symptoms improved with clozapine treatment, as did performance on the WAIS-R digit symbol substitution test. 5. 5. Improved performance on the WAIS-R digit symbol substitution test correlated with reduction in negative symptoms, and faster reaction time showed some correlation with reduction in positive symptoms. 6. 6. The results of this pilot study indicate that treatment with clozapine can produce limited improvement in cognitive function in schizophrenia.

Schizophrenia-like deficits in auditory P1 and N1 refractoriness induced by the psychomimetic agent phencyclidine (PCP)

Objectives: The amplitude of the cortically generated auditory event-related potential (ERP) components P1 and N1 decreases as the interval between successive stimuli (ISI) decreases. Although the phenomenon of P1 and N1 refractoriness is well established, the underlying mechanisms are poorly understood. The present study investigates P1 and N1 refractoriness in the awake monkey in order to investigate underlying mechanisms.Methods: Auditory ERP were obtained in response to repetitive auditory stimuli presented at 5 levels of ISI between 150 ms and 9 s, prior to and following administration of the selective N-methyl-d-aspartate (NMDA) antagonist phencyclidine (PCP).Results: P1 and N1 amplitude declined in monkeys with decreasing ISI, with similar temporal characteristics to that observed in humans. PCP inhibited P1 and N1 generation at long, but not short, ISI producing a pattern similar to that recently observed in schizophrenic subjects.Conclusions: The present findings suggest that the primate P1/N1 model may be useful for investigating mechanisms underlying impaired information processing in schizophrenia, and that NMDA receptor dysfunction may play a key role in information processing dysfunction associated with schizophrenia.

85. Disturbances of auditory information processing in schizophrenia reflected by MMN

Cognitive dysfunction in schizophrenia is associated with disturbances of working memory systems. The mismatch negativity (MMN), a short latency event-related potential, can be used as an objective measure of echoic memory. Reduction of MMN in schizophrenia patients has been shown in several studies. Effects of the antipsychotic medication are discussed controversely.

567. NMDA-mediated neurophysiologic deficits in schizophrenia

Deficits in auditory event-related potential (aERP) generation are among the most consistent and robust indices of impaired cortical information processing in schizophrenia. Deficits in P300 generation were first demonstrated over 30 years ago. More recently, deficits have been demonstrated as well in earlier aERP components, including mismatch negativity (MMN) and N1. Both MMN and N1 are obtained under passive attention conditions. Nevertheless, deficits in MMN and N1 generation are as robust as those observed in attentionally demanding paradigms, and reflect impaired ERP generation at the level of auditory sensory cortex. MMN is elicited to deviant stimuli in an auditory oddball paradigm and reflects integrity of auditory sensory (echoic) memory system. N1, in contrast, is observed even to repetitive standard stimuli and reflects stimulus registration within auditory cortex. N1 normally increases with increasing interstimulus interval. In schizophrenia, N1 generation is significantly reduced in amplitude at long, but not short, ISI, reflecting a failure of normal augmentation. Monkeys generate MMN- and N1-like ERP components and can thus be used to evaluate mechanisms underlying cortical information processing. In monkeys, phencyclidine (PCP) and other N-methyl-D-aspartate (NMDA) antagonists induce aERP deficits closely resembling those of schizophrenia. Deficits are associated with decreased NMDA-dependent current flow within supragranular layers of auditory cortex, whereas input to auditory cortex remains intact. These findings indicate that NMDA receptors play a crucial role in cortical response amplification and that deficits in NDMA receptor-mediated neurotransmission may contribute significantly to cortical information processing deficits in schizophrenia.

Genetic influence on auditory information processing in schizophrenia: P300 in monozygotic twins

Background: It is widely accepted that schizophrenia is to some extent genetically determined. Abnormalities of the P300 component are one of the most robust biological findings in schizophrenia. They outlast clinical impairment and are present also in relatives of schizophrenic patients. In the present study on schizophrenic twins, the heritability of auditory P300 abnormalities and the influence of task difficulty on heritability was examined. Methods: Twenty-two monozygotic twin pairs were included into this study (eight pairs discordant, five pairs concordant for schizophrenia or schizoaffective psychosis according to ICD-10 criteria, and nine control pairs). Two different versions of the auditory oddball paradigm were used to control for deficient stimulus perception. Results: Compared to healthy controls, P300 amplitudes were significantly smaller in affected twins as well as in the non-affected co-twins of the discordant pairs. Conclusions: Our results suggest that P300 amplitude reduction is a genetically transmitted vulnerability marker for schizophrenia. Because the findings were independent of the difficulty of the task and could be demonstrated even when pitch disparity was adjusted to the subjects’ ability to discriminate tones, the findings can not be explained by deficient perception and may rather be related to the genetic influence on higher information processing.

Facial affect recognition and information processing in schizophrenia and bipolar disorder

This study assessed facial affect recognition and visual attention in a sample of 40 individuals with schizophrenia, at hospitalization and 3 months later during an out-patient phase of relative remission. Secondly, at the out-patient phase the performance of the individuals with schizophrenia on tasks of visual attention, facial affect recognition and facial recognition was compared to the performances of a non-psychiatric control group and a bipolar group on these tasks. Attention was measured with the Continuous Performance Test and the Span of Apprehension task. Facial affect recognition was measured with a discrimination task and an identification task. A measure of facial recognition was also used. The schizophrenia patients performed more poorly on measures of facial affect recognition and facial recognition than both control groups. Despite a significant improvement in symptoms over time, there was no change in facial affect recognition for the schizophrenia subjects. For the schizophrenia subjects there were significant associations between attention tasks and the facial tasks. These results suggest that for individuals with schizophrenia, deficits in facial affect recognition are stable deficits that are related to other impairments in neurocognition. This has implications for psychosocial treatments.

Increased repetition blindness in schizophrenia patients and first-degree relatives of schizophrenia patients

This study investigated the phenomenon of repetition blindness in schizophrenia patients and first-degree relatives of schizophrenia patients. Twelve schizophrenia patients, 13 siblings of schizophrenia patients and 26 normal controls were tested on their ability to detect the repetitions within rapidly presentated visual word lists. Schizophrenics and their relatives showed increased repetition blindness compared with normal controls. This suggests a deficit in rapid information processing in schizophrenia.

51-5 - The effect of clozapine on information processing in schizophrenia

51-5 - The effect of clozapine on information processing in schizophrenia

A left temporal lobe impairment of auditory information processing in schizophrenia: an event-related potential study

A measure of auditory prepulse inhibition (PPI) is the reduction of the scalp-recorded P1 event-related potential (ERP) after a sound that is preceded by 100–300 ms by a click as prepulse. This measure of sensory gating was adapted to study the effect of a prepulse on processing tones that were part of a `go no-go' discrimination. ERPs were recorded at right and left, frontal and temporal sites in groups of patients with schizophrenia (SCH) or obsessive compulsive disorder (OCD) and healthy controls (CON). A prepulse 100 ms but not 500 ms before either tone reduced the P1 ERP amplitude in healthy and OCD subjects but not SCH patients. At frontal and temporal recording sites the P1 amplitude was similar bilaterally in controls but showed a right temporal shift in the SCH patients. If the tone was the `no-go' tone, the prepulse reduced the N1 amplitude in both the CON and SCH groups. The N1 was similar, bilaterally in controls but again showed a right temporal shift in the SCH group. These results show a reduction of a PPI-like effect on early processing (P1) that is more marked in the left hemisphere of SCH patients and may affect channel selection for processing information (N1) about task-relevant sounds.

Oxidative injury and potential use of antioxidants in schizophrenia

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, β-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.

Analysis of reaction time in post-acute schizophrenia using electrophysiologic variables

20 postacute schizophrenic patients with predominantly negative symptoms and 21 age and sex matched normal controls were investigated in a P300 paradigm with simultaneous measurement of EP, EMG and behavioural reaction time. The steps of central information processing were operationalized by the following measures: input processing time (IPT): N1-latency; central processing time (CPT): N1-latency until EMG-onset; motor execution time (MET): EMG-onset until onset of target behaviour. For the schizophrenic group we found a pattern of significant deviations with reduction of the N1-, N2- and P3-amplitude, prolongation of the central processing, motor execution and behavioural termination time. The largest loss of time however was found for the central information processing time (203.1 +/- 72.9 vs. 113.1 vs. 20.2 ms, p = 0.000). In the control group the EMG reaction started 12.4 ms before the N2 peak, in the schizophrenic group 63.5 ms after the N2 peak (p = 0.02). Summing up, these findings are compatible with the assumption of a multiple functional deficit of central information processing in schizophrenia.

Abnormally high neuronal density in the schizophrenic cortex. A morphometric analysis of prefrontal area 9 and occipital area 17.

In the past two decades, gross morphologic changes have been uncovered in the schizophrenic brain, eg, increased ventricular width and decreased cortical volume; however, relatively little is known about the area-specific and laminar density of cells in the schizophrenic cortex, particularly in prefrontal areas. A direct, three-dimensional counting method was used to determine cell density in 16 brains from patients with schizophrenia, 19 from normal subjects, six from patients with schizoaffective disorder, and nine from patients with advanced-stage Huntington's disease. Increased neuronal density was found in prefrontal area 9 (17%) and occipital area 17 (10%) in the schizophrenic brains. In area 9, neuronal density was increased in layers III to VI; cell packing of pyramidal and nonpyramidal neurons was elevated. Cortical thickness in the schizophrenic brains was slightly but not significantly reduced in both areas, with a disproportionate reduction in layer V in area 9. In contrast, brains with Huntington's disease exhibited markedly higher glial density (50%) and drastically reduced cortical thickness (28%). Abnormally high density in the cerebral cortices of schizophrenics suggests that neuronal atrophy is the anatomic substrate for deficient information processing in schizophrenia.

Perceptual and Conceptual Information Processing in Schizophrenia and Depression

Schizophrenic patients (n = 20), depressive patients (n = 20), and normal adults (n = 20) were compared on global vs local analyses of perceptual information using tachistoscopic tasks and on top-down vs bottom-up conceptual processing using card-sort tasks. The schizophrenic group performed more poorly on tasks requiring either global analyses (counting lines when distracting circles were present) or top-down conceptual processing (rule learning) than they did on tasks requiring local analyses (counting heterogeneous lines) or bottom-up processing (attribute identification). The schizophrenic group appeared not to use conceptually guided processing. Normal adults showed the reverse pattern. The depressive group performed similarly to the schizophrenic group on perceptual tasks but closer to the normal group on conceptual tasks, thereby appearing to be less dependent on a particular information-processing strategy. These deficits in organizational strategy may be related to the use of available processing resources as well as the allocation of attention.

Thought disorder and semantic memory information processing in schizophrenia

Thought disorder and semantic memory information processing in schizophrenia

A neural network model of cortical information processing in schizophrenia. II--Role of hippocampal-cortical interaction: a review and a model.

This paper considers the relevance of hippocampal dysfunction to symptom production in schizophrenia with the help of an integrative computational model of cortical processing. First, evidence for involvement of the hippocampus was systematically reviewed. Then, a neural network model of hippocampal-cortical interaction was proposed. The effects of a dysfunction in hippocampal-cortical interaction were explored through simulation experiments. Neural network simulation demonstrated that when the hippocampal function of classification and reduction of overlap in input is sub-optimal, increasing correlation among input patterns compromised storage capacity of the cortical network. Hippocampal dysfunction predisposes to the emergence of spurious retrieval states in cortical information processing. This provides a model for psychotic symptom formation in schizophrenia.

Clozapine increases EEG photic driving in clinical responders.

Photically driven electroencephalography was tested in 17 chronic schizophrenia patients who were treated with clozapine for 5 weeks. Eight of the 17 patients showed clinical improvement on the Brief Psychiatric Rating Scale (delta BPRS > 30%) while the other 9 patients remained unchanged (delta BPRS < 15%). In comparison with the nonresponders, clozapine responders had a significantly greater increase in photic driving in the electroencephalogram (EEG), primarily in the low-frequency range of alpha band (7.2 hertz [Hz], 8.3 Hz, 9.0 Hz, and 9.6 Hz, but not 12.0 Hz). The difference in the resting EEG between the responders and nonresponders did not reach statistical significance. These findings suggested that EEG photic driving might be more sensitive than the resting EEG in detecting the central nervous system drug effect. Further analysis revealed that the increase of EEG photic driving was positively correlated with patients' clinical improvement. Combined with our previous observation in the drug-free schizophrenia patients who had lower EEG photic driving, present results supported the hypothesis that the amount of EEG alpha activity, particularly its synchronization to the external stimuli, could reflect the thalamic function in sensory information processing in schizophrenia.

Selective Attention and Intention in Schizophrenia

Behavioral studies in humans have suggested that each hemisphere is important for mediating selective attention and response preparation (intention) in contralateral hemispace. In addition, there is evidence that the medial frontal lobe has a major role in response preparation. The aims of this study were to provide an experimental neuropsychological assessment of response preparation and selective attention in schizophrenia and to evaluate the hypotheses of medial frontal lobe dysfunction and/or hemispheric asymmetry in this disorder. Age and sex matched group of 21 chronic schizophrenic patients and 21 normal subjects were tested on a choice reaction time task in which they were given preliminary information about where a target stimulus would occur (selective attention) and which hand to use for responding (response preparation). Schizophrenic patients provided longer reaction times than normal controls (F=64.3; df=1,40; p<0.0001), which effect was more prominent when the target stimuli was presented in the right hemispace (F=4.1; df=1,40; p<0.05). All subjects, controls and patients, benefited from preparatory information regarding subsequent responses. The results of the attentional paradigm indicate, that the deficit of information processing in schizophrenia may affect left hemispheric mechanisms to a larger extent. According to the response preparation model, there was no evidence of medial frontal lobe impairment.