Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both Kraepelin [1919. Dementia Praecox and Paraphrenia, Livingston, Edinburgh.] and Bleuler [1911. Dementia Praecox or the Group of Schizophrenias. Reprinted 1950 (trans. and ed. J. Zinkin). New York: International Univ. Press.] proposed that cognitive disturbances in schizophrenia are manifestations of brain abnormality. With the advent of magnetic resonance imaging (MRI) methodology, a number of studies have attempted to determine the relationship between brain structure and neurocognition in schizophrenia. We performed a review (1991-to date) of such studies with the aim of identifying the most consistent and compelling findings. The review revealed that whole brain volume tends to correlate with the measures of general intelligence as well as with a range of specific cognitive functions in normal controls and female schizophrenia patients, but this relationship is disrupted in male patients. The enlargement of the third ventricle, relative to the whole brain volume, is associated with deficient abstraction/flexibility, language, and attention/concentration in patients, whereas disproportionally larger lateral ventricles are associated with poorer psychomotor speed and attention/concentration in women, but not in men, with schizophrenia. Archicortical, but not paleocortical, prefrontal cortex tends to associate with the measures of executive function in both sexes regardless of diagnosis. Temporal lobe, hippocampus and parahippocampal gyrus correlate with cognitive abilities such as performance speed and accuracy, memory and executive function, verbal endowment and abstraction/categorization, respectively. Some of these medial temporal lobe/neurocognition relationships appear to be specific to schizophrenia (i.e. not seen in controls). Striatal size is positively associated with goal-directed behavior, but not perseveration, in schizophrenia. Larger cerebellum is associated with higher IQ in normal controls and affected women, but this association is disrupted in affected men. Increased white matter of the vermis is associated with poorer language and immediate verbal memory in schizophrenia. Finally, the methodological limitations of the reviewed studies are discussed and suggestions for future research are offered.
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PMID:The relationship between brain structure and neurocognition in schizophrenia: a selective review. 1532 92

This study investigated the relationship of executive impairment and heart disease burden to remission of major depression among elderly patients. A total of 112 elderly subjects suffering from major depression received treatment with citalopram at a target daily dose of 40 mg for 8 weeks. Diagnosis was assigned using the Research Diagnostic Criteria and the DSM-IV Criteria after an interview with the Schedule for Affective Disorders and Schizophrenia. Executive dysfunction was assessed with the Initiation/Perseveration subscale of the Dementia Rating Scale (DRS) and the Color-Word Stroop test. Medical burden, including heart disease burden, was rated with the Cumulative Illness Rating Scale, and disability with Philadelphia Multilevel Instrument. Both abnormal initiation/perseveration and abnormal Stroop scores were associated with low remission rates of geriatric depression. Similarly, heart disease burden and baseline severity of depression also predicted low remission rates. The relationship of heart disease burden to remission was not mediated by executive dysfunction. Impairment in other DRS cognitive domains, disability, medical burden unrelated to heart disease did not significantly influence the outcome of depression in this sample. Executive dysfunction and heart disease burden constitute independent vulnerability factors that increase the risk for chronicity of geriatric depression. The findings of this study provide the rationale for investigation of the role of specific frontostriatal-limbic pathways in predisposing to geriatric depression or worsening its course.
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PMID:Executive dysfunction, heart disease burden, and remission of geriatric depression. 1534 Mar 93

The entorhinal cortex (EC) is involved in a variety of cognitive functions by virtue of its neuronal input from the neocortex and projection to the hippocampal formation and the limbic-striatal system. Neonatal lesions are increasingly considered useful models for disconnection syndromes such as schizophrenia. Therefore, we investigated the effects of neonatal EC lesions on adult rat behavior. Neonatal (postnatal day 7) lesions were inflicted by bilateral injections of ibotenate into the EC. Sham-lesioned (vehicle injection) and naive (unoperated) rats served as controls. Locomotor activity was measured in prepubertal and young adult rats. Adult rats were then tested for spatial learning in an eight-arm radial maze (reinforced delayed alternation) and for motivation (progressive ratio schedule of operant behavior). Finally, prepulse inhibition (PPI) of the acoustic startle reflex and locomotor activity were investigated with and without apomorphine (APO) challenge. Brain tissue damage was assessed using Nissl-staining. The total volume of the adult rat EC was reduced after neonatal ibotenate-injection. Neonatal EC-lesions increased perseveration only in a delayed task in the radial maze and induced a leftward-shift of breakpoints in operant responding. Lesions did not alter baseline locomotor activity, but enhanced the locomotor stimulating effect of APO. PPI was not affected by neonatal lesions of the EC with and without APO challenge. Neonatal lesions of the EC impaired the ability to hold information during delays and reduced motivation during operant behavior which reflects a state of anhedonia. Thus, they may serve as an animal model for certain aspects of schizophrenia.
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PMID:Effects of neonatal excitotoxic lesions of the entorhinal cortex on cognitive functions in the adult rat. 1535 Jun 48

Persistent paranoid symptoms are best understood as having multiple causal mechanisms. An enhanced multidimensional understanding of paranoia may result from the convergence of two distinct measurement paradigms, experimental psychopathology and social cognitive research. This study investigated the role of neurocognitive deficits and emotion misperception bias as they relate to paranoid symptoms at two different time points in a sample of individuals with severe mental illness (primarily schizophrenia spectrum disorders [N=91]) undergoing intensive psychosocial rehabilitation. Before intensive rehabilitation (but after initial stabilization), paranoid symptoms were related to a tendency to misperceive emotion as disgust. The impact of this social cognitive bias was amplified by perseveration (as measured by the COGLAB Card Sorting Task). Perseverative errors were associated with paranoid symptoms at both time points. After 6 months of treatment, there were significant reductions in paranoid symptoms and perseverative errors but no significant changes in emotion misperception biases. This study is one of few to date to evaluate the contribution of both neurocognitive deficits and social cognitive biases to paranoid symptoms. The results demonstrate how social cognitive biases can interact with neurocognitive deficits in expression of paranoid symptoms, and how these relationships change during treatment.
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PMID:Social cognitive bias and neurocognitive deficit in paranoid symptoms: evidence for an interaction effect and changes during treatment. 1547 17

Late gestational disruption of neurogenesis in rats has been shown to induce behavioral abnormalities thought to mimic aspects of positive and negative symptoms of schizophrenia. Furthermore, it has been shown that the morphological changes produced by the perturbation are relevant to schizophrenia with reduced thickness of the hippocampus, thalamus, and cortical regions. In addition to the positive and negative symptoms, schizophrenia is associated with deficits in a wide variety of cognitive domains. In the present studies, we assessed whether the cognitive deficits are modeled by disruption of neurogenesis late during gestation (gestational day 17) in the rat. In the battery of tests utilized, we describe that rats in which neurogenesis was disrupted have deficits in a reversal-learning paradigm of the Morris water maze and in object recognition, and that they exhibit perseveration in the Porsolt forced swimming test. Additionally, we found deficient associative learning in an acquisition of an active avoidance paradigm and deficits in latent inhibition. No deficits were observed in the reference memory version of the Morris water maze and in a non-match-to position experiment, showing that the deficits are limited to certain aspects of cognition.
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PMID:Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia. 1557 7

Abnormal visual scanning of faces, objects, and line drawings has been observed in patients with schizophrenia and is thought to reflect neurocognitive impairment. In this study, a simultaneous measurement approach was used to assess whether schizophrenia patients demonstrate restricted visual scanning when confronted with a complex problem-solving stimulus, and whether visual scanning deficits are predictive of inflexible thinking. Thirty-eight schizophrenia patients and 30 comparison participants were presented with Rorschach inkblots while eye movements were monitored and verbal responses to the stimuli were recorded and scored for inflexible thinking using the Rorschach Repetition and Perseveration Scale. Schizophrenia patients demonstrated fewer and longer visual fixations and shorter total scanpath relative to comparison participants but did not differ on mean scanpath length. Among patients, fewer fixations were associated with a higher frequency of verbal perseverations. Correlations between scanning measures and symptoms showed that negative symptoms were related to a minimal scanning or "staring" approach. Results support previous findings of restricted visual scanning in schizophrenia patients, are consistent with previously observed relationships between visual scanning and symptom profiles, and suggest that visual organizational deficits during complex problem-solving tasks may be related to cognitive inflexibility and frontal-executive dysfunction.
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PMID:Visual scanning deficits in schizophrenia and their relationship to executive functioning impairment. 1569 56

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.
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PMID:What is perseverated in schizophrenia? Evidence of abnormal response plasticity in the saccadic system. 1570 14

Our goal is to develop a new family of automatic tools for the diagnosis of schizophrenia, using Virtual Reality Technology (VRT). VRT is specifically suitable for this purpose, because it allows for multi-modal stimulation in a complex setup, and the simultaneous measurement of multiple parameters. In this work we studied sensory integration within working memory, in a navigation task through a VR maze. Along the way subjects pass through multiple rooms that include three doors each, only one of which can be used to legally exit the room. Specifically, each door is characterized by three features (color, shape and sound), and only one combination of features -- as determined by a transient opening rule -- is legal. The opening rule changes over time. Subjects must learn the rule and use it for successful navigation throughout the maze. 39 schizophrenic patients and 21 healthy controls participated in this study. Upon completion, each subject was assigned a performance profile, including various error scores, response time, navigation ability and strategy. We developed a classification procedure based on the subjects' performance profile, which correctly predicted 85% of the schizophrenic patients (and all the controls). We observed that a number of parameters showed significant correlation with standard diagnosis scores (PANSS), suggesting the potential use of our measurements for future diagnosis of schizophrenia. On the other hand, our patients did not show unusual repetition of response despite stimulus cessation (called perseveration in classical studies of schizophrenia), which is usually considered a robust marker of the disease. Interestingly, this deficit only appeared in our study when subjects did not receive proper explanation of the task.
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PMID:Virtual reality testing of multi-modal integration in schizophrenic patients. 1571 88

Attention disorders in schizophrenia are manifested in two different ways. On the one hand, the schizophrenia patient tends to keep a learned response even after it ceases to be relevant (perseveration). On the other hand, the schizophrenia patient tends to replace an adaptive response without being given a reason to do so (overswitching). In the present study, overswitching was investigated in relation to latent inhibition (LI), which is the normal ability to ignore nonrelevant stimuli. A new tool--the Combined Attention Test--was used for this purpose in a group of 41 unmedicated schizophrenia patients, divided into subgroups of patients with predominantly positive and negative symptoms, and 24 normal controls. The results show that positive schizophrenia patients, who exhibited high levels of overswitching, also revealed impaired LI, while the negative schizophrenia group, as well as normal controls, exhibited intact LI. These findings suggest that overswitching is a specific attention deficit in positive schizophrenia. We discuss the possibility that impaired LI is a consequence of overswitching and comment on the putative neurophysiology.
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PMID:Latent inhibition and overswitching in schizophrenia. 1595 86

Serotonin (5-HT) receptors are increasingly recognized as major targets for cognitive enhancement in schizophrenia. Several lines of evidence suggest a pathophysiological role for glutamate NMDA receptors in the prefrontal cortex in schizophrenia and associated disorders in attention and executive functioning. We investigated how the interactions between 5-HT1A and 5-HT2A and glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC) contribute to the control of different aspects of attentional performance. Rats were trained on a five-choice serial reaction time (5-CSRT) task, which provides indices of attentional functioning (percentage of correct responses), executive control (measured by anticipatory and perseverative responses), and speed. The competitive NMDA receptor antagonist CPP (50 ng/side) was infused directly into the mPFC 5 min after infusion of either 8-OH-DPAT (30 and 100 ng/side) or M100907 (100 and 300 ng/side) into the same brain area. Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907. In addition, M100907 abolished the CPP-induced anticipatory responding but had no effects on perseverative over-responding, while 8-OH-DPAT reduced the perseverative over-responding but had no effects on anticipatory responding induced by CPP. The selective 5-HT(1A) receptor antagonist WAY100635 (30 ng/side) antagonized the effects of 8-OH-DPAT (100 ng/side). 8-OH-DPAT at 30 ng/side reduced the latency of correct responses in controls and CPP-injected rats and lowered the percentage of omissions in CPP-injected rats. The data show that 5-HT1A and 5-HT2A receptors in the mPFC exert opposing actions on attentional functioning and demonstrate a dissociable contribution of 5-HT1A and 5-HT2A receptors in the mPFC to different aspects of executive control such as impulsivity and compulsive perseveration.
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PMID:Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. 1619 87


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