Schizophrenic Process Research Articles

Phenotypic markers as risk factors in schizophrenia: neurocognitive functions.

To review the literature on neurocognitive measures as risk markers for schizophrenia and to present data from the Perth family study of schizophrenia. Of all the risk markers that have been identified, the most promising are deficits in sustained attention. Inclusion in the review was determined by whether the research addressed a number of key questions: methods of assessing sustained attention; evidence of sustained attention deficits in patients and first-degree relatives including children; the importance of attentional dysfunction in the schizophrenic process and functional outcome; and the biological basis of sustained attention deficits. Sustained attention deficits are evident in both patients and a proportion of their first-degree relatives, a finding replicated in preliminary data from the Perth family study. The literature suggests that the attention deficit is a stable enduring trait that is independent of clinical state. The neural basis of the deficit may be a functional disconnection between prefrontal and parietal cortex. Attention impairment is an important predictor of functional outcome in patients and the development of social dysfunction in adulthood in the at-risk offspring of patients. However, sustained attention deficits that are measured in childhood results in an unacceptable high false-positive rate (21%) when predicting which at-risk offspring of parents with schizophrenia will develop a schizophrenia spectrum disorder, although the overall classification accuracy (78%) is impressive. The main findings are that sustained attention deficits are important risk markers for schizophrenia but need to be supplemented by other neurocognitive risk markers to improve predictive accuracy.

Differences between patients with schizophrenia within and without a high security psychiatric hospital

To report and discuss differences between schizophrenic patients in the community and those in maximum security care. Comparison of 193 community schizophrenic patients with 169 in high security care. Data included case notes, interviews and cognitive tests. Compared to high security patients, community patients tended to be female and married. They had higher school achievement, higher premorbid IQ and better occupational levels, were less likely to have a family history of alcohol abuse, to have had police contact and to have attempted suicide. They had more frequent shorter psychiatric admissions and fewer current and lifetime schizophrenic symptoms. Logistic regression models discriminated the groups with considerable accuracy. Patients needing high security care may be recognizable when schizophrenia is first diagnosed. Progression to the State Hospital seems to result from schizophrenia together with other factors such as deprivation rather than from a worse schizophrenic process per se.

Schizophrenia: reduced signal-to-noise ratio and impaired phase-locking during information processing

Objective: This study was performed in order to clarify the mechanisms which underlie the reduced signal-to-noise of event-related potentials in schizophrenic patients. Specifically, we wanted to find out, whether it is reduced activation and/or synchronization (phase-locking) in specific frequency bands of the ongoing EEG which is related to the decreased signal amplitude and signal-to-noise ratio in schizophrenics.Methods: We investigated 41 unmedicated schizophrenics (10 of them drug-naı̈ve) and compared them with healthy control subjects (n=233) as well as unmedicated subjects with schizotypal personality (n=21), who were considered to be high-risk subjects for schizophrenia, and unmedicated depressive patients (n=71). We measured event-related activity during an acoustical choice reaction paradigm and calculated the signal-to-noise ratio, signal power and noise for a time interval of 50–200 ms after stimulus presentation. Signal-to-noise ratio was calculated from the power of the averaged trials (signal power) divided by the mean power of the single trials minus the power of the average (noise power). Also, we performed a frequency analysis of the pre- and poststimulus EEG based on a factor analytical approach. Group comparisons were performed with ANCOVA.Results: As expected, a decreased signal-to-noise ratio of evoked activity was found in the schizophrenic and a non-significant trend in the schizotypal subjects and the depressive patients. We were able to show that the observed decrease is due to a reduced signal power and an increase of absolute noise power. Frequency analysis of the evoked activity revealed that normals, schizophrenics schizotypal subjects and depressive patients increased theta/delta activity between pre- and poststimulus interval to a similar extend. However, this theta/delta-augmentation does not correlate with signal power in schizophrenics. Also, normals and depressive subjects augment coherence between both temporal lobes during information processing, which is not found in schizophrenics and schizotypal subjects. In contrast, these two groups augment frontal lobe coherence, which goes along with an increase of noise.Conclusions: Reduced stimulus-induced phase-locking and bitemporal coherence of cortically evoked activity but not a failure to activate the cortex may be responsible for the observed low signal-to-noise ratio during information processing in schizophrenics. Accordingly, schizophrenics increase noise after stimulus presentation instead of building up a signal. This is discussed in the framework of the theory of stochastic resonance.

Phenotypic Markers as Risk Factors in Schizophrenia: Neurocognitive Functions

Objective To review the literature on neurocognitive measures as risk markers for schizophrenia and to present data from the Perth family study of schizophrenia. Of all the risk markers that have been identified, the most promising are deficits in sustained attention. Method Inclusion in the review was determined by whether the research addressed a number of key questions: methods of assessing sustained attention; evidence of sustained attention deficits in patients and first-degree relatives including children; the importance of attentional dysfunction in the schizophrenic process and functional outcome; and the biological basis of sustained attention deficits. Results Sustained attention deficits are evident in both patients and a proportion of their first-degree relatives, a finding replicated in preliminary data from the Perth family study. The literature suggests that the attention deficit is a stable enduring trait that is independent of clinical state. The neural basis of the deficit may be a functional disconnection between prefrontal and parietal cortex. Attention impairment is an important predictor of functional outcome in patients and the development of social dysfunction in adulthood in the at-risk offspring of patients. However, sustained attention deficits that are measured in childhood results in an unacceptable high false-positive rate (21%) when predicting which at-risk offspring of parents with schizophrenia will develop a schizophrenia spectrum disorder, although the overall classification accuracy (78%) is impressive. Conclusions The main findings are that sustained attention deficits are important risk markers for schizophrenia but need to be supplemented by other neurocognitive risk markers to improve predictive accuracy.

Contextual insensitivity in schizophrenic language processing: evidence from lexical ambiguity.

The authors investigated whether contextual failures in schizophrenia are due to deficits in the detection of context or the inhibition of contextually irrelevant information. Eighteen schizophrenia patients and 24 nonpsychiatric controls were tested via a cross-modal semantic priming task. Participants heard sentences containing homonyms and made lexical decisions about visual targets related to the homonyms' dominant or subordinate meanings. When sentences moderately biased subordinate meanings (e.g., the animal enclosure meaning of pen), schizophrenia patients showed priming of dominant targets (e.g., paper) and subordinate targets (e.g., pig). In contrast, controls showed priming only of subordinate targets. When contexts strongly biased subordinate meanings, both groups showed priming only of subordinate targets. The results suggest that inhibitory deficits rather than context detection deficits underlie contextual failures in schizophrenia.

Cerebrospinal fluid angiotensin-converting enzyme (ACE) correlates with length of illness in schizophrenia

The aim of the study was to evaluate a possible progression with time of cerebrospinal fluid (CSF) angiotensin-converting enzyme (ACE) levels in treated schizophrenia patients. CSF ACE was determined in duplicate by a sensitive inhibitor-binding assay (IBA) from morning CSF samples of 56 acute and chronic in-patients with schizophrenic psychoses diagnosed according to DSM-IV. CSF ACE correlated significantly with length of schizophrenic psychosis ( r=0.39, p=0.003). There was also a positive significant correlation between CSF ACE and duration of current psychotic episode ( r=0.39, p=0.003) as well as duration of current hospitalization ( r=0.66, p<0.001). These significances were maintained even when patients who were not treated with antipsychotics at the time of sampling were excluded. The correlations also remained significant when controlling for current neuroleptic dose in chlorpromazine equivalents. Serum ACE did not correlate with any clinical variable. No significant correlations between serum or CSF ACE and age, diagnostic subgroup, gender, serum ACE, CSF to serum albumin ratios, or neuroleptic dose in chlorpromazine equivalents were detected. The elevation of CSF ACE seemed to be confined to a subgroup of chronic patients with few positive symptoms. Elevated CSF ACE may reflect an increased solubilization of ACE from cell membranes in the central nervous system or constitute an increased expression of the ACE gene in response to some stimuli. This may be a function of treatment or a result of the deteriorating schizophrenic process.

Cortical brain dysfunction in early schizophrenia: secondary pathogenetic hierarchy of neuroplasticity, psychopathology and social impairment.

Schizophrenia has the quality of a 'top-down' disorder with perturbation of self, and malattuned appraisal of basic experience of the outside world, and of intentionality. There is dissonance between the faculties of consciousness. The neuronal cortical network displays distributed activation of the sensory cortices during perception, and retroactivation during recall. This multimodal organization is sensitive to aberrations of structure and informational content during the metabolically dynamic phases of expansion and pruning in childhood and adolescence. There is substantial evidence of deviant function of the cortical network in schizophrenia. This includes increased neuronal density, reduced prefrontal capacity for activation, impaired fronto-temporal interaction during language production, defect monitoring of inner speech, activation of secondary sensory cortices during hallucinations, reduced cortical and thalamic volume, reduced thalamic activation (filtering) and sensitization of dopaminergic modulation. As a hypothesis the cortical defects lead to secondary causation of abnormalities at the levels of neuroplasticity, symptomatology and social competence. Suggestions for empirical testing are presented for the hypothesis that neocortical defects are primary, thalamic defects secondary and dopaminergic aberrations tertiary in the schizophrenic process. This testing of hypotheses involves prospective studies of patient groups at various ages of onset, as well as comparison of neurobiological measures in remitting vs. treatment-resistant cases.

Abnormal visual scan paths: a psychophysiological marker of delusions in schizophrenia

The role of the visual scan path as a psychophysiological marker of visual attention has been highlighted previously (Phillips and David, 1994). We investigated information processing in schizophrenic patients with severe delusions and again when the delusions were subsiding using visual scan path measurements. We aimed to demonstrate a specific deficit in processing human faces in deluded subjects by relating this to abnormal viewing strategies. Scan paths were measured in six deluded and five non-deluded schizophrenics (matched for medication and negative symptoms), and nine age-matched normal controls. Deluded subjects had abnormal scan paths in a recognition task, fixating non-feature areas significantly more than controls, but were equally accurate. Re-testing after improvement in delusional conviction revealed fewer group differences. The results suggest state-dependent abnormal information processing in schizophrenics when deluded, with reliance on less-salient visual information for decision-making.

Tumbling Dice: Gilles Deleuze and the Economy of Repetition

Tumbling Dice: Gilles Deleuze and The Economy of Répétition Daniel W. Conway (bio) The schizo is not revolutionary, but the schizophrenic process—in terms of which the schizo is merely the interruption, or the continuation in the void—is the potential for revolution. . . Courage consists, however, in agreeing to flee rather than live tranquilly and hypocritically in false refuges. —Deleuze and Guattari, Anti-Oedipus In his 1962 classic Nietzsche et la philosophie, Gilles Deleuze proposes a beguiling figure for Nietzsche’s enigmatic teaching of eternal recurrence: the dicethrow. By means of this figure, Deleuze attempts to capture the double movement that governs the economy of repetition, whereby necessity and chance, being and becoming, are simultaneously affirmed in their constitutive difference. Hence the centrifugal economy of the teaching of eternal recurrence, at least on Deleuze’s interpretation of it: any genuine affirmation of the possibility of reactive forces already involves (and in fact presupposes) the necessity of active forces. In this essay I apply the figure of the dicethrow to Deleuze’s own thought. The figure of the dicethrow serves, I contend, not only as the master trope of his political thinking, but also as a model for his account of the economy of repetition. Most importantly, the figure of the dicethrow provides us with a blueprint for putting Deleuze himself to work, as a desiring machine in his own right. Here the [End Page 7] influence of Nietzsche is doubly useful to us: we may map outbreaks of Deleuze’s own schizophrenia by charting his use and abuse of Nietzsche; and we may employ Deleuze’s experimentation with Nietzsche as a model for our own experimentation with Deleuze. On the Use and Abuse of Eternal Recurrence Gilles Deleuze situates his thought along an unexplored seismic rift, which threatens to shift the tectonic plates that undergird the unstable metaphysical landscape of post-Kantian philosophy. Having egregiously mismeasured the Richter magnitude of the Copernican revolution, Kant and his successors have systematically ignored the ramifying cracks and fissures that fault the foundation of their metaphysical projects. They consequently have failed to meet the calamitous demand placed upon philosophy by this earth-quaking critique of metaphysics: the production of difference. Positioned at a historical remove from the epicenter of Kant’s Copernican revolution, Deleuze investigates a seismic vortex in which the aftershocks of this critique reverberate with heightened severity. It is the peculiar business of metaphysics, he believes, to misplace relations of difference behind relations of binary opposition, which are weighted toward one of the two terms in accordance with the precepts of (fabricated) first principles. Metaphysicians characteristically codify the lifeworld of human experience by enforcing a farrago of standard binary oppositions: order is preferred to chaos, stability to change, unity to multiplicity, mind to body, reason to passion, and so on. While one might have thought that Kant’s leveling critique of metaphysics had cleared the way for an exploration of difference, metaphysicians continue to ply their trade, albeit now in disguised form. Deleuze’s designation for the metaphysical recidivism of post-Kantian philosophy is “the dialectic,” a term that captures under its umbrella any attempt to derive a productive result from the clash of binary opposites (Deleuze 1983, 8–10). The dialectic thus functions to redeem the oppositional nature of traditional metaphysics, by teasing from its obfuscatory operations a “higher” synthesis or truth. According to Deleuze, however, practitioners of the dialectic succeed merely in compounding the swindle perpetrated by pre-Kantian metaphysicians. By enshrining binary opposition as the preferred model for all relationships between attributes (irrespective of any productive syntheses that opposition might magically yield), the dialectic perpetuates the signature prejudices of metaphysical thinking. The dialectic thus rehabilitates metaphysics following the devastating blow dealt it by Kant, but only at the expense of [End Page 8] postponing indefinitely the investigation of difference. As Deleuze sees it, the enduring appeal of the dialectic trades on an egregious confusion of cause and effect: affirmation is not the effect of the negation of negation, but its cause or precondition. The negation of the negation, which dialecticians claim to orchestrate through the clash of binary opposites, thus presupposes affirmation as its ground and provenance...

Event-related potential correlates of linguistic information processing in schizophrenics

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.

Cholecystokinin and Psychiatric Disorders

Cholecystokinin (CCK) is one of the most abundant neuropeptides in the brain. It is found in the highest levels in cortical and limbic structures and also in the basal ganglia. Two subtypes of CCK receptors have been described in the brain and gastrointestinal tissues. CCK(A) (alimentary subtype) receptors are mainly located in the gastrointestinal tract, regulating secretion of enzymes from the pancreas and emptying of the gallbladder. However, CCK(A) receptors are also found in several brain regions, with the highest densities in structures poorly protected by the haematoencephalic barrier (the area postrema, nucleus tractus solitarius and hypothalamus). The distribution of CCK(B) (brain subtype) receptors overlaps with the localisation of CCK and its mRNA in different brain areas, with the highest densities in the cerebral cortex, basal ganglia, nucleus accumbens and forebrain limbic structures.Both subtype of CCK receptor belong to the guanine nucleotide-binding protein-(G protein)-linked receptor superfamily containing 7 transmembrane domains. Signal transduction at CCK receptors is mediated via G(q) protein-related activation of phospholipase C and the formation of inositol 1,4,5-triphosphate (IP(3)) and 1,2-diacylglycerol (DAG). Recent cloning of CCK(A) and CCK(B) receptors has shown that mRNA for both receptors is distributed in the same tissues as established in radioligand binding and receptor autoradiography studies, with few exceptions.The existence of multiple CCK receptors has fuelled the development of selective CCK(A) and CCK(B) receptor antagonists. These antagonists belong to distinct chemical groups, including dibutyryl derivatives of cyclic nucleotides, amino acid derivatives, partial sequences and derivatives of the -COOH terminal sequence heptapeptides of CCK, benzodiazepine derivatives, 'peptoids' based on fragments of the CCK molecule, and pyrazolidinones. At the present time, the compounds of choice for blockade of the CCK(A) receptor are lorglumide, devazepide and lintitript (SR27897). L-365,260, CI-988, L-740,093 and LY288513 are the drugs most widely used to block CCK(B) receptors.Studies with CCK antagonists (and agonists) in animals and humans suggest a role for CCK in the regulation of anxiety and panic. The administration of CCK agonists [ceruletide (caerulein), CCK-4, pentagastrin] has an anxiogenic action in various animal models and in different animal species. However, the anxiogenic action of CCK agonists is restricted to nonconditioned (ethological) models of anxiety, with very limited activity in the 'classical' conditioned models. Pharmacological studies have revealed that CCK(B) receptors are the key targets in the anxiogenic action of CCK agonists. Nevertheless, CCK(B) antagonists displayed very little activity, if any at all, in these models, but strongly antagonised the effects of CCK(B) agonists. The anxiogenic/panicogenic action of CCK(B) agonists (CCK-4, pentagastrin) is even more pronounced in human studies, but the effectiveness of CCK(B) antagonists as anxiolytics remains unclear. Clinical trials performed to date have provided inconclusive data about the anxiolytic potential of CCK(B) receptor antagonists, probably because of limiting pharmacokinetic factors.The results of some animal experiments suggest a role for CCK in depression. The administration of CCK(B) antagonists causes antidepressant-like action in mouse models of depression. However, human studies replicating this result have yet to be carried out.A prominent biochemical alteration in schizophrenia is a reduction of CCK levels in the cerebral cortex. This change may be related to the loss of cortical neurons, due to the schizophrenic process itself. In animal studies (mainly in mice), administration of CCK agonists and antagonists has been shown to be effective in several models, reflecting a possible antipsychotic activity of these drugs. However, the data obtained in human studies suggest that CCK agonists and antagonists do not improve the symptoms of schizophrenia. Taking into account the reduced levels of CCK and its receptors found in schizophrenia, treatments increasing, but not blocking, brain CCK activity may be more appropriate.

23-6 - Stuctural and functional changes of auditory sensory processing in schizophrenics

23-6 - Stuctural and functional changes of auditory sensory processing in schizophrenics

Comparative affective reactivity of different types of communication disturbances in schizophrenia.

Twenty-nine schizophrenic outpatients provided speech samples on affectively positive and negative topics. These samples were assessed for several different types of communication failures by using the Communication Disturbances Index. Frequencies of overinclusive references, ambiguous word meanings, and ambiguous referents increased in the affectively negative condition; frequencies of missing referents and instances of syntactic unclarity did not change across affective conditions. Degree of overall affective reactivity of speech was associated with severity of the core positive schizophrenic syndrome. These findings support the idea that different types of schizophrenic communication disturbances are associated with different underlying pathophysiological processes, that some are more reactive to affect than others, and that affective reactivity of these symptoms is associated with the positive schizophrenic process.

Rhythmic finger-tapping task and fast segmentation of neural processing in schizophrenics

Rhythmic finger-tapping task and fast segmentation of neural processing in schizophrenics

Processing of contextual syntactic information in a decision making task in schizophrenic subjects

This research report studies how schizophrenic subjects process contextual syntactic information using a double-decision lexical task (deciding whether or not strings of letters form French words). Given the automatic nature of syntax, we are assuming the preservation of syntactical information processing in all the schizophrenic subjects, including those presenting thought disorder (TFP), which we name schizophrenic TPF+. Twenty control subjects and 20 schizophrenic subjects (including 10 TFP+ schizophrenic subjects) participated in a double-decision lexical task containing syntactic errors. The results confirm our hypothesis because we show that all subjects (control and schizophrenic) are hampered in recognizing words when they contain grammatical errors. The results contrast with data on the processing of contextual semantic information by schizophrenic subjects, since the data in the literature conclude that there is an information-processing anomaly on the part of these patients. As a result, our study refutes the hypothesis of a generalized difficulty in the processing context by schizophrenic subjects.

Reduced susceptibility to oxidative damage of erythrocyte membranes from medicated schizophrenic patients

Susceptibility to non-enzymatic peroxidation of erythrocyte membranes from medicated schizophrenic patients relative to healthy control subjects was investigated by measuring internalization into erythrocytes of ethylene glycol, cellobiotol or mannitol, with or without preincubation with cumene hydroperoxide or with chlorpromazine. The main finding was that erythrocytes from schizophrenic patients were less susceptible than those from control subjects to non-enzymatic oxidative damage from cumene hydroperoxide, as measured by internalization of cellobiotol and mannitol. At baseline before incubation, there was reduced internalization of cellobiotol and mannitol and this was reduced even further by preincubation with chlorpromazine. It is suggested that previous findings of fatty acid deficits in erythrocyte membranes from neuroleptic-treated schizophrenic patients are unlikely to have resulted from non-enzymatic oxidative damage of the membrane. Furthermore, it is suggested that depleted erythrocyte membrane essential fatty acids are more likely to be the result of the schizophrenic process rather than antipsychotic drug treatment, and that antipsychotic drugs may even offer protection against membrane lipid peroxidation.

Auditory processing in schizophrenics and controls using fMRI

Auditory processing in schizophrenics and controls using fMRI

Memory and intellectual functioning in familial and non familial schizophrenic subjects

The National Adult Reading Test (NART) has achieved popularity as a measure of pre-morbid intellectual ability, based on the premises that pronunciation of irregular words is unaffected in many clinical disorders and that performance is highly correlated with general intellectual ability. Recently, schizophrenia research studies have begun to appear in the literature, where the NART has been used to estimate pre-morbid ability. However, this use has preceded the basic required demonstration that, in fact, NART performance is unaffected by the schizophrenic process. In the present study, NART performance was compared across three groups; 20 acutely ill unmedicated DSM-IIIR schizophrenics, 10 other unmedicated acute psychotics, and 20 control subjects. When demographic variability between the groups was controlled for, there were no group differences in terms of NART performance. NART performance was not correlated with Brief Psychiatric Rating Scale scores, and in all three groups, no significant differences emerged when demographically predicted intelligence quotients were compared with NART estimated intelligence quotients. NART performance (predicted on the basis of demographic variables) was not significantly different from observed NART performance in any of the three experimental groups. However, within the sample with schizophrenia, NART estimated pre-morbid IQ was significantly higher than currently measured intellectual abilities. These results suggest that the National Adult Reading Test provides a reasonable estimate of pre-morbid ability in acutely ill, unmedicated schizophrenic patients.

Schizophrenia and postmodern philosophy.

Abstract This essay examines the postmodern idea that the schizophrenic process can be seen as a strategy of disruption, to be directed against the stability and productive forces of modern capitalism. The modern idea that schizophrenia itself is a correctable form of mental illness is also examined, and this assumption is related to issues about power and control encountered in cultural, social and psychological studies. These issues center around the different ways that modernist and postmodernist thinkers approach schizophrenic experience. Issues pertaining to social control and its connection to the nature of personal identity are examined, as are modernist and postmodernist responses to the double bind experience. Strategies of modernist control and postmodernist disruption are compared and contrasted.

Prevalence and clinical correlates of extrapyramidal signs and spontaneous dyskinesia in never-medicated schizophrenic patients.

This study assessed the prevalence of extrapyramidal signs and spontaneous dyskinesia in neuroleptic-naive, first-episode schizophrenic patients and examined the clinical correlates. In a prospective study of the psychobiology of schizophrenia, the authors examined 89 neuroleptic-naive patients for the presence of extrapyramidal signs by using the Simpson-Angus Rating Scale and for dyskinesia by using the Tardive Dyskinesia Rating Scale. Fifteen patients (16.9%) had extrapyramidal signs, but only one had spontaneous dyskinesia at baseline. Presence of extrapyramidal signs was correlated with more negative symptoms and poorer treatment outcome that was reflected in a longer time to and lower level of remission. There was no correlation of spontaneous extrapyramidal signs with age of patient, age at onset of psychotic symptoms, or baseline psychopathology. There was no difference between patients with and without spontaneous extrapyramidal signs in terms of the subsequent development of persistent tardive dyskinesia, but the patients with spontaneous extrapyramidal signs were more likely to develop parkinsonian side effects after 8 weeks of antipsychotic treatment. Extrapyramidal signs are present in a proportion of neuroleptic-naive, first-episode schizophrenic patients, which suggests an involvement of these signs in the schizophrenic process that probably reflects basal ganglia pathology. The presence of spontaneous extrapyramidal signs seems to have prognostic significance insofar as it is linked to a poorer outcome and longer time to remission. Spontaneous dyskinesia appears to be a relatively rare finding.