Increased semantic and repetition priming in schizophrenic patients.

Positive and negative priming (PP and NP) in schizophrenia were studied with a lexical-decision task. Probe words, presented 800 ms after the response to the prime (containing a word and a nonword), were either identical to, semantically related to, or unrelated to the prime target word (PP) or to the prime distractor word (NP). Schizophrenic patients displayed stronger semantic and repetition PP than controls after controlling for their slower responses. Significant NP was observed in both groups for word repetition only. The PP findings contrast with results from studies with similar prime-probe intervals but without prime responses. It is proposed that schizophrenic patients, because of impaired (controlled) processes of response selection, strongly benefit from (or rely on) the automatic retrieval of processing episodes containing response information. Related findings indicating automatic response facilitation in schizophrenia are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibitory gating of an evoked response to repeated auditory stimuli in schizophrenic and normal subjects. Human recordings, computer simulation, and an animal model

BACKGROUND: Altered sensory response is a prominent feature of schizophrenia. Inhibitory gatting mechanisms, shown by diminished P50 evoked responses to repeated auditory stimuli, seem to be deficient in schizophrenic persons. These inhibitory mechanisms usually are studied by averaging the electroencephalographic responses to many presentations of pairs of stimuli. Although averaging increases signal-to-noise ratio, it may obscure trial-to-trial differences. We compared differences between schizophrenic and normal persons in single trials and averages of P50 response. METHODS: Recordings from 10 schizophrenic patients and 10 normal subjects were analyzed using conventional averaging and single-trial measurements. A computer simulation of both methods examined their ability to extract evoked responses from background activity. Related single-neuron activity in the hippocampus in an animal model also was studied, because neuronal action potentials can be reliably identified in single trials. RESULTS: Averaged evoked potentials showed significant suppression of the P50 response to the second stimulus of the pair in normal patients, but not in schizophrenic patients. Single-trial analysis did not detect a response above background activity. Computer simulations gave similar results, suggesting that failure to detect suppression in single trials comes from inadequate differentiation of signal from noise. Recordings in animals confirmed almost complete suppression of the response of hippocampal pyramidal neurons to the second stimulus. CONCLUSIONS: The normal inhibition of response to repeated auditory stimuli seems to be compromised in schizophrenia. This loss of inhibitory gating could reflect a physiological deficit of hippocampal interneurons that is consonant with other evidence for interneuron pathologic defects in schizophrenia.     

Dependence of the peripheral blood lymphocyte reaction of schizophrenia patients to concanavalin A stimulation on the clinical parameters of the pathological process

Studies were performed on an equivalent age group of schizophrenic patients and normal donors to detect the lymphocyte reaction of the peripheral blood to concanavalin A stimulation. It was demonstrated, that in the blood of schizophrenic patients, the part of lymphocytes capable of reacting to stimulation, is 2,3 times less than in the group of normals. The studies showed that the capability of cells to react to stimulation does not depend upon the duration of the disease, the duration of the postmanifest or initial periods, but differs in patients with different forms of schizophrenia. A significant negative correlation was demonstrated between the severity of positive disorders and the lymphocyte response to stimulation.     

Neuropsychological impairment in Tardive dyskinesia.

Tardive dyskinesia (TD) is a movement disorder secondary to neuroleptic treatment. Whether TD is associated with neurocognitive dysfunction is a controversial issue. We reviewed 31 published studies evaluating neuropsychological (NP) test results in schizophrenic patients with and without TD and found that TD was generally reported to be associated with cognitive impairment. Numerous methodological limitations, however, restrict the conclusions made about the relationship between cognition and dyskinesia. We therefore undertook a study in which 143 schizophrenic patients were evaluated on a comprehensive NP test battery. On both global and learning deficit scores, TD patients demonstrated greater impairment than did a matched comparison group. Two aspects of TD (severity and topography) were related to severity of cognitive impairment. These findings suggest that dyskinesia and cognition may share some underlying mechanism in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Another look at parastichies

The conditioning-testing (S1-S2) P50 auditory evoked potential (EP) has been well-documented and accepted as an important tool for measuring sensory gating in schizophrenia research. However, the physiological mechanism of the phenomenon is not known. In this study a single-trial analysis was used to determine the influence of the latency variability of the responses in the formation of the averaged P50. Ten schizophrenic patients and 10 normal controls were tested in the dual-click EP paradigm. Using ensemble averaging analysis, we replicated the previous finding of a lower S1 P50 amplitude and higher S2/S1 ratio in schizophrenics compared with normal controls. The single-trial analysis revealed that patients had significantly higher trial-to-trial latency variability in S1 responses than normal subjects, while the S2 showed the same variability as in controls. Measured by the single-trial procedure, the arithmetic mean amplitudes of P50 responses to S1 and S2 were similar between normal and schizophrenic subjects. The same measure also eliminated the difference in averaged P50 amplitude between S1 and S2 for both groups. Temporal variability appears to be an important factor in the assessment of averaged EPs and thus contribute to the change of P50 amplitude observed in schizophrenia.     

Ribonuclease A mutant His119 Asn: the role of histidine in catalysis

BACKGROUND: We wished to investigate central serotonergic function in untreated schizophrenia. METHOD: Thirteen drug-naive, DSM-III-R schizophrenic patients were compared with sex, race, age, weight and menstrual phase matched controls. Plasma prolactin and cortisol responses to a specific serotonergic probe, d-fenfluramine, were measured along with BPRS ratings. RESULTS: Prolactin responses were enhanced in schizophrenic patients compared to controls (P < 0.05) and were correlated positively with BPRS items for depression, anxiety and guilt. Baseline cortisol was also raised in those with schizophrenia (P < 0.001). CONCLUSIONS: Central serotonergic tone may be raised in acute, drug-naive schizophrenia and may be associated with the presence of affective symptomatology.     

Proprioception and schizophrenia: a replication study with nonschizophrenic patient controls

In 3 experiments, weight discrimination, arm flexion discrimination, and a test of kinesthetic figural aftereffects were used to evaluate the proprioceptive functioning of 40 schizophrenic patients, 30 nonschizophrenic (psychotic and nonpsychotic) patients, and 10 normals. The additional variables of premorbid functioning and paranoia were also examined. Previous findings of a subtle proprioceptive deficit for schizophrenics in comparison with normals were replicated for nonparanoid schizophrenics of a weight-discrimination procedure and poor premorbid schizophrenics on an arm-flexion task. The kinesthetic-figural-aftereffects schizophrenic deficit previously reported by the author and E. Ebner (see record 1974-23243-001) was not replicated. Deficits in proprioception also were found for all nonschizophrenic patient groups on the weight-discrimination procedure and for poor premorbid nonschizophrenic psychotics and neurotics on the arm-flexion task. It is concluded that a deficit in proprioception is not unique to schizophrenia but appears to be related to chronicity and severity of pathology in both schizophrenic and nonschizophrenic hospitalized patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Response-monitoring dysfunction in schizophrenia: An event-related brain potential study.

Error-monitoring abnormalities may underlie positive symptoms of schizophrenia. Response-synchronized event-related potentials during picture-word matching yielded error- and correct-response-related negativity (ERN, CRN) and positivity (Pe, Pc) and preresponse lateralized readiness potentials (LRP) from 18 schizophrenic patients and 18 controls. Both groups responded faster to matches than nonmatches, although patients were generally slower and made more errors to nonmatches. Compared with controls, patients, particularly with paranoid subtype, had smaller ERNs and larger CRNs, which were indistinguishable. LRPs showed evidence of more response conflict before errors than before correct responses in controls but not patients. Despite ERN/CRN abnormalities, post-error slowing and Pe were normal in patients, suggesting a dissociation of ERN and error awareness. Anterior cingulate and dorsolateral prefrontal cortical dysfunction in schizophrenia are implicated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sentence verification and delusions: a content-specific deficit

BACKGROUND: A sentence verification task was developed to investigate semantic memory in schizophrenia. METHODS: The test consisted of three types of sentence (true, unlikely and nonsense) and seven different types of content (neutral, persecutory, grandiose, political, religious, relationships and somatic) representing common delusional themes present in schizophrenic patients. Sixty-three schizophrenic patients and 66 matched control subjects were asked to make true/false judgements to 143 sentences. RESULTS: Overall accuracy was similar across the two groups; sentences with some emotional themes and sentences of the unlikely type produced the most violations. Significant differences between the two subject groups were found specifically on nonsense sentences with persecutory and religious themes. Patients made significantly more incorrect responses (acceptance) to nonsense sentences that had an emotional content congruent with their delusional beliefs, past or present, and also on unlikely sentences (incorrect rejections) whose content was not congruent with their delusions. Further analysis of response bias in the patients showed, overall, that there were more incorrect rejections (a reflection of the large number of unlikely sentence errors) and more incorrect responses to sentences congruent with patients delusions. Furthermore, analysis of those patients currently experiencing delusions revealed more incorrect responses to sentences congruent with their delusional ideas compared with patients not currently deluded. CONCLUSIONS: These findings are indicative of cognitive bias in schizophrenia towards certain emotional themes that may underlie illogical semantic connections and delusions.     

A new taxane diterpenoid from Taxus mairei

OBJECTIVE: The authors examined the effect of prolonged clozapine treatment on central serotonergic (5-HT) function in schizophrenia. METHOD: Prolactin responses to the 5-HT releasing agent d-fenfluramine were measured in two groups of 10 schizophrenic subjects. The first group was tested twice, before and after a mean of 10 weeks of clozapine treatment. The second group was tested after a mean of 20 months of clozapine treatment. RESULTS: The prolactin response was significantly blunted in these 20 patients treated with clozapine. There was a significant positive correlation between d-fenfluramine-evoked prolactin release and the overall positive symptom score and the hallucination and delusion subscores of the Scale for the Assessment of Positive Symptoms. CONCLUSIONS: Blunted 5-HT-mediated prolactin responses in schizophrenic patients receiving clozapine monotherapy for up to 20 months were correlated with reductions in positive symptoms. This suggests that 5-HT antagonism is relevant to clozapine's efficacy in alleviating hallucinations and other positive schizophrenic symptoms.     

Two measures of overinclusive thinking in schizophrenia: A comparative analysis.

Compared the performance of 30 chronic schizophrenics and 30 patients with personality disorders on 2 measures of overinclusion. Consistent with previous research, schizophrenic Ss showed more overinclusion than nonschizophrenic Ss on an R. W. Payne-type test, and were more overinclusive on a Payne-type test than on an L. J. Chapman-type test. Results are interpreted within the framework of W. E. Broen and L. H. Storm's theory of partial collapse of response hierarchies in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do schizophrenic patients show a disjunctive relationship among expressive, experiential, and psychophysiological components of emotion?

Recent research has found a discrepancy between schizophrenic patients' outward expression of emotion and their reported emotional experience. In this study, which attempts to replicate and extend the findings of previous studies, participants with and without schizophrenia viewed emotional film clips while their facial expressions were videotaped and skin conductance was recorded. Participants also reported their subjective experience of emotion following each film. Those with schizophrenia were less facially expressive than controls during the emotional films and reported experiencing as much positive and negative emotion, replicating previous findings. Additionally, schizophrenic patients exhibited greater skin conductance reactivity to all films than controls. These findings suggest a disjunction among emotional response domains for schizophrenic patients; alternative explanations for the findings are considered as well as suggestions for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonergic function and negative and depressive symptomatology in schizophrenia and major depression

BACKGROUND: Serotonergic abnormalities are found in both major depressive disorder (MDD) and schizophrenia. Depressive symptoms commonly occur alongside the negative or defect symptoms in schizophrenia and antiserotonergic drugs may be particularly effective in their treatment. We wished to explore whether these symptoms could be distinguished biologically by directly comparing serotonergic function in these two illnesses. METHOD: Fifteen patients with MDD and 13 patients with schizophrenia underwent testing with the specific serotonin releasing agent D-fenfluramine (D-FEN). Prolactin and cortisol responses were measured to ascertain central serotonergic function. Individual patient results were compared with their own carefully matched control to correct for the effect of age, sex, weight and menstrual cycle, before the two patient groups were then compared. RESULTS: Prolactin responses differed significantly between the two patient groups, being lower in MDD patients and higher in schizophrenia patients than their individually matched controls. Cortisol responses did not differ. Within the schizophrenia group, increased serotonergic function correlated positively with depressive symptoms, but there was no such correlation with defect symptoms. Depressive scores were negatively correlated with the presence of negative symptoms in the schizophrenic group. CONCLUSIONS: Schizophrenia and MDD have distinct and opposite neuroendocrine responses to D-FEN. There is no evidence that depressive symptoms in these two conditions have a common serotonergic basis. Moreover, these responses distinguished between negative and depressive symptoms in our schizophrenic group.     

Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia

The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.     

Shape constancy in schizophrenic patients.

Shape constancy in visual perception of schizophrenic patients was studied. 40 chronic schizophrenic, 40 acute schizophrenic, 40 nonschizophrenic mental patients, and 40 normal controls were used as Ss. Ss matched the shape of a standard object (circle) inclined at an angle. 2 angles of inclination, 30° and 60°, were used. It was found that shape constancy was lower in schizophrenic patients than in controls when the stimulus object was inclined 60° from the horizontal plane. When the angle of inclination was 30° there was no difference between the groups. The chronic schizophrenic patients displayed greater response variability than the other groups. The relation of these findings to the theory of assimilation of percepts to the perceptual schemata in schizophrenic patients was discussed. (23 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The etiologic heterogeneity of schizophrenia

Evidence is increasing in support of the etiologic heterogeneity of schizophrenia. Five distinct diseases/disorders are suggested in this paper, and the relevant studies are reviewed. Familial forms of the disorder include a dopamine psychosis (supported by research documenting both altered dopamine activity and early neuroleptic response among some schizophrenic patients), a neurodegenerative psychosis (supported by investigations that document ongoing change in ventricular brain ratio, elevation of products of cell membrane catabolism within the central nervous system, and age-progressive third ventricle enlargement accompanied by delayed response to neuroleptics), and a neurodevelopmental psychosis (supported by evidence of static enlarged ventricles in some schizophrenic patients and neurological soft signs in high-risk offspring of schizophrenic individuals). Nonfamilial forms include a neurodevelopmental psychosis (supported by evidence of neurodevelopmental abnormalities triggered by neurotropic viruses, radiation, or anoxia) and a lithium-responsive psychosis (supported by evidence of a subgroup of psychotic patients who have low risk of either psychosis or mania in their pedigrees and respond to lithium).     

The T cell populations mediating rejection of MHC class I disparate skin grafts in mice

Numerous studies have demonstrated a lateralized impairment of attention in schizophrenia. In this study, attention in schizophrenia is investigated with a task that involves centering a rod while blindfolded. Symptoms were rated on the Brief Psychiatric Rating Scale (BPRS) for each of the 20 schizophrenic subjects. The more symptomatic patients demonstrated a right-sided hemineglect compared to the less symptomatic patients (p = 0.013). Furthermore, the difference between more and less symptomatic patients was even more distinct when they were categorized by the BPRS schizophrenia subscale alone (p = 0.0025). These findings support the hypothesis that the pathophysiology of schizophrenia involves a lateralized defect in the control of attention, and that this defect is associated with the severity of symptoms. This raises the possibility that effects of neuroleptic medication may be asymmetric, which could account for some of the inconsistencies in studies of hemispheric dysfunction in schizophrenia.     

Neurocognitive basis of impaired empathy in schizophrenia.

Patients with schizophrenia show impaired emotional and social behavior, such as lack of theory of mind and misinterpretation of social situations. However, there is a paucity of work focusing on the empathic abilities of these patients. The present study was designed to examine the degree of impairment in cognitive and affective empathy in schizophrenia and to evaluate the contribution of executive prefrontal functions to empathy in these patients. To explore the neurocognitive processes that underlie the empathic ability in schizophrenic patients, the relationship between empathy scores and the performance on a cognitive flexibility task that assesses dorsolateral and orbitofrontal functioning (set shifting and reversal, respectively) was examined in 26 patients with schizophrenia and 31 healthy control subjects. Results indicated that patients with schizophrenia were significantly impaired in both cognitive and affective empathy compared with healthy control subjects. The degree of impaired empathy related to the severity of negative symptoms. In addition, patients showed impaired performance on measures of both shifting and reversal. However, while cognitive empathy was particularly related to measurements of orbitofrontal (rather than dorsolateral) functioning, affective empathy was related to measures of social functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cortical atrophy in MRI, mental status and neuroleptic treatment effect in schizophrenia

MR imaging of the head was performed in forty schizophrenics (DSM-IV). Mental status was evaluated before and during 8-weeks of neuroleptic treatment. Cortical atrophy in frontal and temporal regions was found in 40% of subjects. They were older, had longer history of schizophrenia, were less active professionally and were more frequently hospitalized. Patients with and without cortical atrophy in MRI did not differ in the severity of schizophrenic psychopathology at baseline. During neuroleptic treatment negative schizophrenia symptoms were significantly better diminished in patients without cortical atrophy than in subjects with cortical atrophy in MRI; this regarded specially the severity of emotional blunting. Clinical improvement after 8-weeks of neuroleptic administration was less favorable in patients with cortical atrophy.     

What Is Perseverated in Schizophrenia? Evidence of Abnormal Response Plasticity in the Saccadic System.

Although perseveration is sometimes attributed to defective set switching, the authors have recently shown that set-switching is normal in schizophrenia. In this article, the authors tested for persistent states of the saccadic response system, rather than set perseveration. Schizophrenic and healthy subjects performed antisaccades and prosaccades. The authors analyzed for 3 carry-over effects. First, whereas the latency of the current saccade correlated with that of the prior saccade in both groups, the correlations under mixed-task conditions declined in healthy but not in schizophrenic subjects. Second, antisaccades in penultimate trials delayed upcoming saccades in schizophrenic but not in healthy subjects. Third, schizophrenic subjects were more likely to erroneously perseverate the direction of a prior antisaccade but not a prior prosaccade. The authors concluded that, in schizophrenia, the effects of correct antisaccades are persistent not weak. Saccades in schizophrenia are characterized by perseveration of antisaccade-induced changes in the saccadic response system rather than failures to switch task set. (PsycINFO Database Record (c) 2010 APA, all rights reserved)