Callosal dysfunction in schizophrenia and schizo-affective disorder.

Studies of corpus callosum dysfunction in schizophrenia have typically relied on measures that reveal impairment in commissurotomy patients, but measures that distinguish people with callosal agenesis may be more appropriate. Four of these indexes were included in the present study. Tests of associated movements, cross-localization of touch, interocular transfer of spiral aftereffect, and transfer of blind formboard learning were administered to 18 chronic schizophrenics, 19 schizo-affectives, and 20 normal volunteers. Both schizophrenics and schizo-affectives were impaired on all measures except transfer of blind formboard learning. Schizophrenics also made significantly more associated movements than schizo-affectives and exhibited a different pattern of cross-localization deficit. These results support the hypothesis of developmental callosal dysfunction in schizophrenia and schizo-affective disorder, although the nature of this dysfunction differs in part from that exhibited by acallosals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attentional capacity dysfunction and arousal in schizophrenia.

Criticizes 2 influential premises underlying most of current research on schizophrenia and attention: (a) belief in the existence of a specific information-processing deficit and (b) acceptance of a framework of "cold cognition." Capacity theory is proposed as an alternative theoretical framework within which the various phenotypically diverse attentional deficits in schizophrenia reflect a deficit in the control function that governs the mobilization and allocation of attention. Attentional deficits, therefore, are most manifest when effortful processing in short-term storage is required. Research on short-term memory processes in schizophrenics shows that the magnitude of the attention deficit correlates positively with the attentional requirements of the cognitive operations involved. The dysfunction is thought to reflect the high levels of arousal characteristic of schizophrenics. Parallels in the performance of schizophrenics and essentially normal but hyperaroused Ss are outlined in support of this hypothesis. The failure to consider the possible mediating effects of hyperarousal in attentional performance of schizophrenics is an omission in the research on schizophrenic cognition. Causality between arousal and information processing is addressed. (101 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Studies of brain dysfunction in schizophrenia.

The purpose of this paper is to bring to the attention of the psychologist the extensive research literature concerned with the physiological correlates of behavior. Research concerned with the electroencephalographic, histopathological, and biochemical analysis of schizophrenics receives concentrated attention. The review also includes "several psychological and physiological studies which focus specifically on the question of brain disorder in schizophrenia." The studies made within the last twenty to twenty-five years are included. 81-item bibliography. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neurocognitive dysfunction in patients diagnosed with schizophrenia and alcoholism.

The authors administered the Halstead–Reitan Neuropsychological Test Battery to schizophrenic groups with (n?=?54) and without (n?=?217) coexisting alcoholism, nonschizophrenic groups with alcoholism (n?=?231), and a patient comparison group (n?=?145) to determine the extent of additive cognitive impairment in schizophrenia associated with alcoholism and to compare cognitive function in alcoholism and schizophrenia. The additive effects of alcoholism on cognitive dysfunction in schizophrenia were subtle but were consistently identifiable. Cognitive dysfunction in alcoholism was less severe than in schizophrenia with or without alcoholism. The magnitude of additive effects of alcoholism on cognitive dysfunction in schizophrenia was age related with a significant interaction between age and presence or absence of alcoholism on a global index of cognitive dysfunction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Left hemisphere dysfunction and left hemisphere overactivation in schizophrenia.

Reports 2 experiments relating schizophrenia to functional brain asymmetry. In Exp I, 24 schizophrenics (mean age, 30.8 yrs) were compared to 24 matched controls (mean age, 37.3 yrs) on 2 tachistoscopic tasks (Syllable Test and Dot Location Test) designed to measure verbal and spatial information processing in the 2 hemispheres. Unlike the controls, the schizophrenics showed a right hemisphere superiority both on the verbal and on the spatial tests, indicating left hemisphere dysfunction in the initial processing of verbal information. In Exp II, lateral eye movements, as an index of contralateral hemispheric activation, were measured in a group of 24 paranoid schizophrenics (mean age, 28.9 yrs), 24 nonparanoid schizophrenics (mean age, 32.7 yrs), and 24 matched controls (mean age, 31.2 yrs). The eye movements were elicited by presenting the Ss with verbal neutral, verbal emotional, spatial neutral, and spatial emotional questions. The schizophrenics had significantly more rightward eye movement, compared to controls, regardless of question type, indicating left hemisphere overactivation. Results suggest that schizophrenia is associated with a pattern consisting of both left hemisphere dysfunction and overactivation. (63 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A multivariate study of attention dysfunction in schizophrenia.

Administered 5 tests purported to measure attention dysfunction to 60 schizophrenic and 60 nonschizophrenic male psychiatric patients. There was 30 chronic and 30 acute Ss in each group. The measures used were: size estimation, reaction time, and vigilance tasks, the Goldstein-Scheerer Object Sorting Test, and a proverb-interpretation task. Contrary to previous assumptions, these tests did not intercorrelate highly. In addition, individual-difference variables, as measured by staff ratings on the Psychotic Reaction Profile, failed to correlate significantly with task performance. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experimental and clinical neuropsychological measures of prefrontal dysfunction in schizophrenia.

Eighteen chronic schizophrenia patients and 14 controls were given tests that have been linked primarily to ventral (orbitofrontal) or to dorsolateral prefrontal dysfunctions in neurological patients and in nonhuman animal Ss having discrete frontal lesions. Schizophrenia patients were significantly impaired on object alternation and delayed alternation tasks but not on classical delayed response (DR). Schizophrenia patients performed well on the classical version of the DR task and their DR performance correlated significantly with measures of sustained attention. Future research is needed to interpret the contributions of attention, interference, and memory load to neuropsychological performance in schizophrenia. Additional studies are required to determine whether the frontal deficits reflect diffuse brain damage, circumscribed prefrontal damage, or damage in other brain regions having prefrontal connections. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relationship between cognitive and social dysfunction in schizophrenia

Cytogenetic monitoring was carried out on a group of 38 nurses who reconstitute antineoplastic drugs in order to determine the extent of chromosomal damage. Genotoxic activities of antineoplastic drugs are studied by chromosome aberration assay, micronucleus assay, sister chromatid exchange (SCE) frequency high frequency cells (HFC) analysis, and mitotic activity of peripheral lymphocytes. Results confirmed that occupational exposure to a mixture of antineoplastic drugs may cause genome damages. The results of this study show that biomonitoring after exposure to a mixture of antineoplastic drugs which express clastogenic and aneugenic activity should involve a battery of cytogenetic methods.     

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)     

Selective corticostriatal dysfunction in schizophrenia: Examination of motor and cognitive skill learning.

[Correction Notice: An erratum for this article was reported in Vol 22(3) of Neuropsychology (see record 2008-05020-015). Table 1 on page 102 should have included the BPRS Depression-Anxiety subscale score 9.00 (3.99) under the column heading Schiz pts. Table displays means with standard deviations in parentheses.] [Correction Notice: An erratum for this article was reported in Vol 22(2) of Neuropsychology (see record 2008-02526-002). The DOI for the supplemental materials was printed incorrectly. The correct DOI is as follows: http://dx.doi.org/10.1037/0894-4105.22.1.100.supp.] It has been suggested that patients with schizophrenia have corticostriatal circuit dysfunction (Carlsson & Carlsson, 1990). Skill learning is thought to rely on corticostriatal circuitry and different types of skill learning may be related to separable corticostriatal loops (Grafton, Hazeltine, & Ivry, 1995; Poldrack, Prabhakaran, Seger, & Gabrieli, 1999). The authors examined motor (Serial Reaction Time task, SRT) and cognitive (Probabilistic Classification task, PCT) skill learning in patients with schizophrenia and normal controls. Development of automaticity was examined, using a dual task paradigm, across three training sessions. Patients with schizophrenia were impaired at learning on the PCT compared to controls. Performance gains of controls occurred within the first session, whereas patients only improved gradually and never reached the performance level of controls. In contrast, patients were not impaired at learning on the SRT relative to controls, suggesting that patients with schizophrenia may have dysfunction in a specific corticostriatal subcircuit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The glutamatergic dysfunction hypothesis for schizophrenia

Schizophrenia is a syndrome, undoubtedly with multiple etiologies, that variably exhibits several features including positive and negative symptoms, cognitive deficits, onset in young adulthood, and deterioration from the previous level of function. This review will examine the growing evidence that dysfunction of corticolimbic glutamatergic neurotransmission may contribute to or account for the manifestations of schizophrenia. Glutamatergic neurons represent the primary excitatory afferent and efferent systems innervating the cortex, limbic regions, and striatum. The postsynaptic actions of glutamate are mediated by a family of glutamate-gated ion channels that permit the influx of sodium and calcium, thereby depolarizing (exciting) neurons. One of these receptors, the N-methyl-D-aspartate (NMDA) receptor, is the site of action of psychotomimetics such as phencyclidine and related anesthetics, which can reproduce in normal individuals most of the symptomatic features of schizophrenia. An endogenous antagonist at the NMDA receptor, N-acetyl-aspartyl glutamate, appears to have enhanced activity in the frontal cortex and hippocampal formation in persons with this disorder. Glutamatergic dysfunction may be particularly relevant to those forms of schizophrenia in which negative symptoms, cognitive deficits, and deterioration are prominent features. In support of this inference, clinical studies have shown that drugs that enhance NMDA-receptor function reduce negative symptoms and cognitive deficits in persons with chronic schizophrenia who are receiving neuroleptics. Thus, dysfunction of glutamatergic neurotransmission represents an important organizational focus for research on the complex manifestations of schizophrenia.     

Calcium signaling dysfunction in schizophrenia: a unifying approach

The present paper demonstrates a remarkable pervasiveness of underlying Ca(2+) signaling motifs among the available biochemical findings in schizophrenic patients and among the major molecular hypotheses of this disease. In addition, the paper reviews the findings suggesting that Ca(2+) is capable of inducing structural and cognitive deficits seen in schizophrenia. The evidence of the ability of antipsychotic drugs to affect Ca(2+) signaling is also presented. Based on these data, it is proposed that altered Ca(2+) signaling may constitute the central unifying molecular pathology in schizophrenia. According to this hypothesis schizophrenia can result from alterations in multiple proteins and other molecules as long as these alterations lead to abnormalities in certain key aspects of intracellular Ca(2+) signaling cascades.     

Smooth-pursuit eye movement dysfunction and liability for schizophrenia: Implications for genetic modeling.

41 nonpsychiatric Ss, 38 probands with schizophrenia, and 99 of their relatives were studied. Oculomotor functioning was bimodally distributed for probands and relatives. Oculomotor dysfunction was not present in all families with a schizophrenic proband. In those families in which it was present, there were significant phenotypic correlations between oculomotor functioning and schizophrenia-related characteristics. The patterns of familial resemblance in the families in whom oculomotor dysfunction was present were consistent with nonadditive genetic variance contributing both to oculomotor dysfunction and to the relationship between oculomotor dysfunction and clinical symptoms. These results suggest that schizophrenia may be etiologically heterogeneous and that oculomotor dysfunction may help to identify nonadditive genetic variance for this disorder. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography

BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.     

Is eye movement dysfunction a biological marker for schizophrenia? A methodological review.

There is a high prevalence of eye movement dysfunction (EMD) in persons with schizophrenia and their first-degree relatives. Studies addressing the prevalence, stability, familial transmission, and psychological correlates of EMD in persons from both psychiatric and general populations offer suggestive evidence that this abnormality may serve as a biological marker for schizophrenia. Although these findings are promising, their significance for elucidating the diagnostic bandwidth, pathophysiology, and genetics of this disorder remains to be determined. More precise characterization of ocular motility, perhaps when used in conjunction with global measures of pursuit adequacy, may be essential for clarifying the pathophysiological and genetic significance of EMD for schizophrenia. Recent research efforts are beginning to identify particular abnormalities that could serve as more specific biological markers for schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor discrimination deficits in schizophrenia: association with eye movement dysfunction

Odor discrimination deficits were found in 80% of 20 schizophrenia patients and in none of the 20 age- and sex-matched comparison subjects. Olfactory discrimination was reliably measured in the patients. Twelve patients in this study also had smooth pursuit eye movement (SPEM) qualitatively recorded. The olfactory discrimination scores were highly correlated to SPEM but not to other clinical measures. This correlation suggests a shared neurobiology, possibly involving working memory.     

Markers from event-related potential subcomponents and reaction time for information processing dysfunction in schizophrenia

Event-related potentials (ERPs) can serve as markers for cognitive processing stages. Identification of those ERPs altered in schizophrenia offer information about cognitive dysfunction. Auditory evoked potentials (AEPs) were elicited within an oddball paradigm in 35 schizophrenic patients and compared with 35 healthy controls. N100 and P200, as well as N200, frontal P300 and parietal P300 subcomponents, were separated using dipole source analysis. The amplitudes of the N100 and the parietal P300 measured in schizophrenics were diminished. The input-related processing stages (N100 and P200) were not altered, whereas later, the deviant and task-related processes (N200, frontal P300, parietal P300 and reaction time) were significantly prolonged in schizophrenia.     

Does affective blunting in schizophrenia reflect affective deficit or neuromotor dysfunction?

Schizophrenia inpatients withdrawn from all neuroleptic medication were administered measures of affective blunting, diminished affective experience, and neuromotor dysfunction. The correlations among the measures provided support for the hypothesis that measures of affective blunting reflect both neuromotor and affective deficits. Because the interpretation of such measures is therefore ambiguous, measures of diminished affective experience may have greater validity in research on affective deficits in schizophrenia than measures of blunted affective expression.     

Learning and forgetting in schizophrenia.

Recent studies of patients with schizophrenia have consistently demonstrated marked deficits on measures of initial learning. However, contradictory results have been reported concerning retention and forgetting. The present study examined the level of initial and delayed recall of stories and visual figures in a group of 76 patients with schizophrenia and 51 normal controls. Schizophrenia patients demonstrated marked impairments in initial and delayed recall as well as significantly worse percentage retention scores. However, schizophrenia patients and healthy controls individually matched on level of initial recall had nearly identical delayed recall performance. The results suggest a primary deficit in the initial acquisition of information rather than an accelerated rate of forgetting in schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)