Activin B: detection by an immunoenzymometric assay in human serum during ovarian stimulation and late pregnancy

Cerebral 1H MR spectra were recorded in 13 children and adolescents with schizophrenia and 12 healthy children and adolescents. Stimulated echo acquisition mode (STEAM) sequence was used to localize an 8-ml voxel bilaterally in the frontal gray matter. The frontal gray matter metabolite ratios for NAA/Cr, Ch/Cr, Glx/Cr, and mI/Cr in schizophrenic children and adolescents were 1.08 +/- .28, .64 +/- .23, 1.09 +/- .30, and .60 +/- .24, respectively. In comparison, these ratios were 1.59 +/- .35, .74 +/- .27, 1.23 +/- .36, and .58 +/- .29 in healthy children and adolescents. Decrease in the frontal lobe NAA/Cr of schizophrenic children and adolescents was statistically significant (P < .001). In contrast, the MR spectra localized bilaterally in the occipital gray matter (8 ml) showed no significant changes between the patients and the controls. In the occipital gray matter, the metabolite ratios were 1.21 +/- .26,.52 +/- .08, 1.00 +/- .11, and.55 +/- .12 inpatients versus 1.30 +/- .23, .45 +/- .10, 1.15 +/- .20, and .48 +/- .19 in controls. Our preliminary finding of reduced NAA/Cr ratio in the frontal gray matter is consistent with the neurodevelopmental models emphasizing dysfunction of frontal lobe areas in patients with schizophrenia.     

Increased density of microtubule associated protein 2-immunoreactive neurons in the prefrontal white matter of schizophrenic subjects

Recent studies have suggested that schizophrenia may be related to prenatal disturbances in the cortical subplate, a transient but essential structure in the formation of cerebral cortical circuitry. Although most subplate neurons die during later development, some remain as the interstitial neurons of the adult white matter. In this study we used a monoclonal antibody against the cytoskeletal protein, microtubule associated protein-2 (MAP2), to quantify the density and distribution of labeled neurons in postmortem brain specimens containing the prefrontal white matter from five schizophrenic cases and matched controls. In both schizophrenics and matched controls, the density of white matter neurons decreased with increasing white matter depth. However, the mean density of MAP2-immunoreactive neurons was greater in the superficial white matter of the schizophrenic subjects compared to the matched controls. In contrast, no difference in the density of labeled neurons was seen in the deeper white matter. These findings are consistent with an abnormality in the development of the cortical subplate in at least some cases of schizophrenia.     

Deficits in gray matter volume are present in schizophrenia but not bipolar disorder

Studies using magnetic resonance (MR) imaging have provided strong evidence that patients with schizophrenia as a group have structural brain abnormalities, including enlarged ventricles and sulci as well as smaller cortical gray matter volumes. This study was undertaken to investigate whether the brain abnormalities found in schizophrenia could be distinguished from those seen in bipolar disorder. The MR scans of 23 patients with schizophrenia were compared to those of 17 healthy community volunteers and 14 patients with bipolar disorder. Images were processed using computer-based image processing techniques to generate quantitative measures of cerebrospinal fluid (CSF), gray matter and white matter volumes. Compared to the community volunteers, the schizophrenia group had larger total CSF volumes while the bipolar group had larger ventricles. Smaller cortical gray matter volumes were found in the schizophrenia group, but not in the bipolar group. The schizophrenia group had regional deficits in gray matter volumes in comparison with both the community volunteers and the bipolar group. These findings suggest that the brain tissue abnormalities found in schizophrenia and bipolar disorder may be distinguishable using MR imaging.     

Value of beat-to-beat blood pressure changes, detected by pulse transit time, in the management of the obstructive sleep apnoea/hypopnoea syndrome

BACKGROUND: Previous studies of oculomotor dysfunction in schizophrenia have tended to concentrate on abnormalities of smooth pursuit eye tracking in chronic medicated patients. We report the results of a study of smooth pursuit, reflexive and antisaccade performance in drug naive and antipsychotic treated first-episode schizophrenic patients. METHODS: Smooth pursuit and saccadic eye movements were recorded in 36 first-episode schizophrenic patients and 36 controls matched for age and estimated IQ. The schizophrenic patients were divided into drug-naive (N = 17) and antipsychotic treated groups (N = 19). RESULTS: Smooth pursuit velocity gain was significantly lower than controls only in the drug-naive patients. The treated patients did not differ significantly from either the controls or the untreated group. In an antisaccade paradigm both treated and drug-naive schizophrenic patients demonstrated an increased number of errors, but only drug-naive patients also demonstrated an increased latency in initiating correct antisaccades. CONCLUSIONS: These impairments are unlikely to be due to a generalized deficit in oculomotor function in the schizophrenic groups, as there were no differences between the groups in saccadic metrics on a reflexive saccade task. The results show that both smooth pursuit and saccadic abnormalities are present at the onset of schizophrenia and are integral to the disorder.     

Potency assay of diphtheria antitoxin in Vero cell microcultures

A slowly rising cortical potential shift with negative polarity following the imperative stimulus of a forewarned reaction time task, the 'post-imperative negative variation' (PINV), is regularly observed in schizophrenic patients but not in controls. The topography of the PINV suggests that it may originate in frontal cortical regions. We used a task designed to test two putative prefrontal cortical functions: working memory and processing of ambiguity. Nineteen patients with a chronic schizophrenic disorder and 19 control subjects matched for age, sex, and education participated in two experimental sessions. The EEG was recorded from frontal, central, temporal, and parietal leads over both hemispheres using a DC amplifier. PINV amplitudes were generally larger in patients than in controls. If the result of comparing physical features of the two successively presented stimuli (warning and imperative stimulus) was ambiguous rather than clear, an augmentation of the PINV amplitudes was seen in both groups. If this comparison required high rather than low involvement of working memory functions, PINV amplitudes were augmented in schizophrenic patients only. Scalp distribution of the PINV indicated a left-hemisphere fronto-central PINV maximum in patients, and a right-hemisphere predominance in controls, which was larger following ambiguous stimulus comparisons. These results suggest that ambiguity during the comparison of physical features of successively presented stimuli may be a general factor of the PINV in schizophrenic patients and healthy controls. Augmented involvement of working memory functions, presumably subserved by the prefrontal cortex, specifically affected the fronto-centrally predominant PINV in schizophrenic patients. This result is compatible with the hypothesis of prefrontal cortical dysfunctions in schizophrenia.     

Residual performance deficit in clinically remitted schizophrenics: A marker of schizophrenia?

The study of remitted schizophrenic outpatients is proposed as a way of minimizing the effects of the "nuisance variables" that confound the study of hospitalized schizophrenics. 20 hospitalized acutely disturbed schizophrenics (mean age, 37.0 yrs), 20 schizophrenic outpatients in clinical remission (mean age, 42.8 yrs) and 20 normal controls (mean age, 35.1 yrs) were administered a span of apprehension test and the Continuous Performance Test (CPT). All Ss were controlled for sex and WAIS scores and schizophrenics were rated with Phillips Prognostic Rating Scale. On the CPT, both acute and remitted schizophrenics made significantly more errors of omission and commission than did the normal controls. On the span of apprehension, both groups of schizophrenics showed a significantly greater decrement in accuracy of detection of the target stimuli than did normal controls. The same pattern of results has been observed in children at risk for schizophrenia, which suggests that the span of apprehension may be sensitive to core schizophrenic processes that are independent of clinical state. The cross-sectional study of the 3 stages of schizophrenia—the premorbid, acute, and remitted—is proposed as a way of identifying "core" schizophrenic processes and markers of vulnerability to schizophrenia. The adequacy of a general "attentional impairment" interpretation of schizophrenic deficit is questioned. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Second-order facial information processing in schizophrenia.

This study investigated the processing of second-order relational face information in schizophrenia. Twenty-eight schizophrenic patients and 28 controls were asked to say whether the space between the eyes was the same in 2 side-by-side faces. The 2 faces were derived from the same original face, but the spacing between the eyes was either the same or differed by various distances. The results showed that schizophrenic patients needed a space that was twice as great as controls to see a difference. The authors conclude that schizophrenic patients have a deficit in processing second-order relational face information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The backward masking red light effect in schizophrenia: Relationship to clinical features and neurocognitive performance.

The “backward masking red light effect” involves a change in visual backward masking performance with a red (compared with a green or gray) background that is in the opposite direction relative to nonpsychiatric controls. This effect has been previously reported in individuals with schizophrenia, their first-degree relatives, and a schizotypy sample. The current study provides the first examination of the relationship of this effect with clinical and neurocognitive measures in a new sample of higher functioning patients with schizophrenia. A location backward masking by pattern task was administered to 16 outpatients with schizophrenia and 21 nonpsychiatric controls. The task was presented on red, green, and gray backgrounds. There was a significant group by color interaction at the 60-ms stimulus onset asynchrony: Participants with schizophrenia tended to decrease accuracy with a red (compared with a gray) background, whereas controls tended to increase accuracy. This interaction remained significant after covarying for baseline (gray) backward masking accuracy. In the schizophrenia patients, a decrease in backward masking accuracy to the red background was correlated with more negative symptoms, lower estimated premorbid IQ, and greater color–word Stroop interference but was not related to positive or disorganized symptoms, age of onset, duration of illness, digit symbol coding performance, or baseline (gray) backward masking accuracy. In contrast, there was no relationship between the red light change score and any of the neurocognitive variables in the control group. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

More evidence for generalized poor performance in facial emotion perception in schizophrenia.

Previous studies showing that schizophrenic patients have a deficit in the ability to perceive facial expressions of emotion in others often have not used a differential deficit design and standardized measures of emotion perception. Using standardized and cross-validated measures in a differential deficit design, S. L. Kerr and J. M. Neale (see record 1993-29687-001) found no evidence for a deficit specific to emotion perception among unmedicated schizophrenic patients. The present study replicated and extended the findings of Kerr and Neale in a sample of medicated schizophrenic patients. Results showed that medicated patients performed more poorly than controls overall; however, they performed no worse on facial emotion perception tasks than on a matched control task. These findings support Kerr and Neale's conclusion that schizophrenic patients do not have a differential deficit in facial emotion perception ability. Future research should examine the nature of schizophrenic patients generalized poor performance on tests of facial emotion perception. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Factor structure of the Wisconsin Card Sorting Test: Dimensions of deficit in schizophrenia.

The aim of this study was to explore the factorial structure of the Wisconsin Card Sorting Test (WCST) and to identify the dimensions of deficit in schizophrenia. WCST scores in patients with schizophrenia and schizophrenia-related psychosis (n?=?292), 1st degree relatives of schizophrenic patients (n?=?91), and normal controls (n?=?141) were subjected to a principal factor analysis followed by orthogonal rotation. This led to 3 factors, perseveration, failure to maintain set, and idiosyncratic sorting. The detected factor structure was found to be invariant across the schizophrenic and control subsamples. Moreover, it replicated previous findings from 2 smaller samples. Only perseverations and, to a lesser degree, idiosyncratic sorting appeared to differentiate schizophrenic patients from comparisons. Only perseveration had good sensitivity and specificity, as well as the most robust significant correlations with estimates of IQ, attention, and other measures of executive functioning. Thus, perseveration appears to be the most diagnostically useful and characteristic WCST feature of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired generation and use of strategy in schizophrenia: evidence from visuospatial and verbal tasks

BACKGROUND: The aim of this study was to investigate mnemonic strategic deficits in schizophrenic patients. METHODS: Analogous tasks were used that required the self-generation of an efficient strategy and its implementation in two domains: visuospatial and verbal. The tasks were given to 20 IQ preserved schizophrenics and 20 matched normal controls. A number of different scores was derived from each task including strategy, short-term memory capacity and perseveration. RESULTS: Overall, the schizophrenic patients were significantly impaired in their ability to generate effective mnemonic strategies on both tasks. In addition, on the visuospatial task there was no difference between the groups on the memory scores, but the schizophrenic patients made significantly more perseverative errors than controls. They were disproportionately worse on the verbal strategy task, showing impairment on memory as well as on strategy scores and were also impaired at semantically classifying the words. Performance was similar to the deficit seen in patients with frontal lobe excisions and Parkinson's disease, in terms of the inability to generate an effective strategy. The deficit on the verbal task was similar to patients with temporal lobe excisions who show impaired verbal memory. However, the pattern differed in the sense that the temporal lobe patients were able to generate effective strategies, unlike the patients with schizophrenia. CONCLUSIONS: High functioning schizophrenic patients are impaired in utilizing visuospatial and verbal mnemonic strategies. By comparing the results with those of neurosurgical excision patients, further evidence is provided for both frontal and temporal lobe involvement in schizophrenia.     

Semantic memory is impaired in schizophrenia

Memory is emerging as a key area of neuropsychological deficit in schizophrenia, with evidence suggesting that the impairment is restricted to long-term memory. Semantic memory, the component of long-term memory containing stored representations of the meanings of words and knowledge about the world, was examined in 46 schizophrenic patients and 40 normal controls using a recently devised battery of tests. Evidence of semantic memory impairment was found which was wide ranging and substantial; in some cases it approached the levels seen in a group of 22 patients with mild-to-moderate Alzheimer's disease. Both group analysis and a more detailed examination of two single cases suggested that semantic memory impairment represents a disproportionate and possibly specific neuropsychological deficit 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.     

Maintenance of grip-induced muscle tension: A behavioral marker of schizophrenia.

A grip-induced muscle tension maintenance task distinguished between schizophrenic patients, regardless of medication or hospitalization status, and both normals and controls with affective (unipolar and bipolar) disorders. Unaffected 1st-degree relatives of schizophrenic patients also showed a grip deficit. Coupling the grip task with a visual discrimination task that divided attention through instruction or reinforcement contingency increased grip error times for all groups. No group differences appeared on the discrimination task, regardless of difficulty level, and the tone used to provide corrective feedback was not implicated in the grip deficit. The results suggest that the grip task is tapping, in a systematic and reliable manner, a motor-control abnormality that may be useful as a behavioral marker of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls

Twenty-six patients with RDC bipolar disorder were compared with a previously reported group of 48 RDC schizophrenics and 34 healthy controls, using volumetric MRI measurements of cerebral, cortical and sulcal volumes. The bipolar group appeared no different from the controls, and both of these groups had significantly larger cerebral and cortical volumes than the schizophrenics. Our previous report of a significantly reduced cortical volume in the schizophrenic group, with a corresponding increase in the volume of sulcal fluid is, therefore, not a generalized feature of psychotic illness but may be more specific to schizophrenia.     

Exploratory factor analysis of MRI brain structure measures in schizophrenia

Much of the literature shows various regional structural brain abnormalities in schizophrenia, but the complexity and variability of brain makes it difficult to determine how these regions are related. Statistical methods which estimate factors underlying patterns of covariance have not been widely used, but could be useful for analyzing such complex data. We applied exploratory and confirmatory factor analysis procedures to specific cortical and subcortical regional brain volume measures from MRI data in 60 normal and 44 schizophrenic subjects. Basal ganglia, heteromodal cortical gray, and medial temporal lobe factors were present in both the normal and the schizophrenia groups. The factor structure observed in the normal group showed a high degree of bilateral symmetry which is present but disrupted in the schizophrenia group. In the bilateral data, the disruption is most pronounced with medial and lateral temporal lobe structures including entorhinal cortex and anterior and posterior superior temporal gyri. There was a significant correlation between the basal ganglia factor and the heteromodal cortical gray factor in the normal group that was not present in the schizophrenia group. In the unilateral data, left posterior superior temporal gyrus did not load onto any factor in the schizophrenia group. Confirmatory factor analyses showed significant differences between the two groups in factor structure. A number of specific brain regions are affected in schizophrenia, and structural relationships between groups of regions also are abnormal. The results suggest that heteromodal dorsolateral prefrontal and superior temporal cortical gray regions are structurally related, whereas inferior parietal cortical gray is less so. These results should be viewed as preliminary as the ratio of parameters to subjects was relatively low, and replication is needed. However, the results demonstrate the potential utility of latent structure methods such as factor analysis in study of complex relationships in neuropsychiatric data.     

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)     

Synthesis and pharmacological study of some new beta-(dialkylaminomethyl)- gamma-butyrolactones and their tetrahydrofuran analogues

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy (1H-MRS) in 21 medicated schizophrenic patients and 21 gender and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline containing compounds (Cho) (t = 2.60, p < 0.05) and ratio of Cho to N-acetylaspartate (NAA) (t = 2.46, p < 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine equivalent neuroleptic dosage was positively correlated with the level of NAA (r = 0.38, p < 0.05) and negatively correlated with the Cho/NAA ratio (r = -0.34, p < 0.05). These findings suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.     

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)     

P50 suppression in recent-onset schizophrenia: Clinical correlates and risperidone effects.

Chronic schizophrenic patients often do not suppress the auditory P50 component of the event-related potential to the second of 2 clicks, presented 500 ms apart, suggesting a loss of normal inhibition. This study attempted to replicate the P50 suppression deficit in patients with recent-onset schizophrenia and to examine whether P50 is related to clinical symptoms or is affected by an atypical antipsychotic medication. Data from 22 recent-onset schizophrenia patients and 11 normal controls revealed that disruption in P50 suppression is present during the early stages of illness. In addition, impaired P50 suppression covaried with clinical ratings of anxiety, depression, and anergia; results also suggested that the P50 inhibitory deficit may be related to the degree of patients' attentional impairment. Finally, risperidone, compared with a typical antipsychotic medication, improved inhibition of P50 to the second click. These results support P50 suppression as a measure of disordered neurocognition in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)