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)

Among new-generation antipsychotics, quetiapine was found to be associated with a partial 'normalization' of reduced functional activation in prefrontal and temporal areas and studies conducted by our group found a clinical improvement in negative symptoms in addition to restoration of frontal activation in schizophrenia patients with blunted affect after treatment with quetiapine. Here we investigated the parallelism between improved clinical symptoms and grey mater density (GMD) changes in the frontal region after quetiapine treatment in 15 schizophrenia patients. We hypothesize that improvement in clinical symptoms will be associated with change in GMD in prefrontal regions of interest. By using voxel-based morphometry, paired t-test random-effect analysis showed a significant increase in GMD bilaterally in the inferior frontal cortex/orbitofrontal gyrus and anterior cingulate cortex after 5.5 months of treatment with quetiapine. This GMD increase was associated with a significant improvement in negative symptoms. When GMD was correlated with psychiatric assessment scores, there was a negative correlation between GMD in the anterior cingulate cortex and the Rating Scale for Emotional Blunting score (r=-665, P=0.008) and between the orbitofrontal gyrus and the total Positive and Negative Syndrome Scale negative score (r=-764, P=0.001). Results suggest that increased GMD in some frontal regions are associated with an improvement of negative symptoms. Although not unique to quetiapine, it would be reasonable to attribute the GMD changes in the study to treatment.
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PMID:Increased grey matter densities in schizophrenia patients with negative symptoms after treatment with quetiapine: a voxel-based morphometry study. 1907 76

Negative symptoms of schizophrenia, such as social withdrawal and blunted affect, usually persist for a long period, making rehabilitation difficult. Many studies have demonstrated a close relationship between function of the amygdala and social behavior. Normal social behavior is disturbed in animals administered phencyclidine (PCP), which is now considered a reliable pharmacological model of schizophrenia. Recent studies have reported that disruption of social behavior in PCP-treated rats involved dysfunction of the amygdala. Disturbance of function of the amygdala has also been reported in schizophrenic patients. However, no study has yet examined the effects of PCP on the firing activity of amygdala neurons. In the present study, we recorded the unit activity of basolateral amygdala neurons while rats engaged in socially interactive behavior. After identifying the response properties of recorded neurons, we then recorded the same neurons with systemic PCP administration. Approximately half of the neurons recorded from exhibited an increase in spontaneous discharge rate during social interaction. Only a few neurons exhibited suppression of discharge rate during social interaction. Systemic administration of PCP induced long-lasting activation in half of the neurons that exhibited an increase in firing rate during social interaction. PCP activated half of basolateral amygdala neurons related to socially interactive behavior, and might in this fashion produce dysfunction of social behavior.
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PMID:Phencyclidine affects firing activity of basolateral amygdala neurons related to social behavior in rats. 1916 35

In schizophrenia, blunted affect has been argued to reflect difficulties with the amplification of emotion expressive behavior. The aim of the present study was to assess whether ostensibly healthy individuals vulnerable to schizophrenia present with similar difficulties. In the first component of the study, 843 non-clinical participants completed the Schizotypal Personality Questionnaire, of which 27 scoring in the upper 15% (high schizotypy group) and 27 scoring in the lower 15% (low schizotypy group) were asked to watch amusing film clips, whilst engaging in different emotion regulatory strategies, and specifically, amplify the expression of an experienced emotion ('amplification') or suppress the expression of an experienced emotion ('suppression'). The results indicate that highly schizotypal participants present with specific difficulties with the amplification (but not suppression) of emotion expressive behavior. These difficulties are significantly correlated with total negative schizotypy, particularly blunted affect. In the second component of the study, an individual differences approach was used to assess the interrelationship between self-reported use of suppression and schizotypy in an independent sample of 204 community volunteers. The results suggest that, although blunted affect is associated with increased use of suppression, it cannot be regarded as the primary mechanism underpinning this disturbance. Implications for understanding blunted affect in schizophrenia and related disorders are discussed.
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PMID:Emotion dysregulation and schizotypy. 1926 64

Dysfunctional emotional processing affects social functioning in patients with schizophrenia. However, the relationship between emotional perception and response in social interaction has not been elucidated. Twenty-seven patients with schizophrenia and 27 normal controls performed a virtual reality social encounter task in which they introduced themselves to avatars expressing happy, neutral, or angry emotions while verbal response duration and onset time were measured and perception of emotional valence and arousal, and state anxiety were rated afterwards. Self-reported trait-affective scale scores and the Positive and Negative Syndrome Scale (PANSS) ratings were also obtained. Patient group significantly underestimated the valence and arousal of angry emotions expressed by an avatar. While valence and arousal ratings of happy avatars were comparable between groups, patient group reported significantly higher state anxiety in response to happy avatars. State anxiety ratings significantly decreased from encounters with neutral to happy avatars in normal controls while no significant decrease was observed in the patient group. The Social Anhedonia Scale and PANSS negative symptom subscale scores (blunted affect, emotional withdrawal, and passive/ apathetic social withdrawal items) were significantly correlated with state anxiety ratings of the encounters with happy avatars. These results suggest that patients with schizophrenia have interference with the experience of pleasure in social interactions which may be associated with negative symptoms.
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PMID:Characteristics of social anxiety from virtual interpersonal interactions in patients with schizophrenia. 1936 96

Schizophrenia is a complex neuropsychiatric disorder in which symptoms can be classified as either positive, such as delusions and hallucinations, or negative, such as blunted affect and social withdrawal. However, the mechanisms underlying this disease are poorly understood. There is evidence that reactive oxygen species (ROS) play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. Ketamine has been used to induce a schizophrenia-like condition as an animal model in which to study this condition. In the present study we tested the effects of sub-anesthetic doses of ketamine on various parameters of oxidative stress in the brain of rats. Our results indicate that lipid peroxidation and tissue protein oxidation were affected by varying sub-anesthetic doses of ketamine in multiple cerebral structures. Additionally, the activity of the antioxidant enzymes CAT and SOD was measured and was also found to be altered in most of the structures tested. In conclusion, we observe an increase in oxidative damage marked by an increase in lipid peroxidation, oxidative protein damage and a decrease in enzymatic defenses, in an animal model of schizophrenia. Given that oxidative stress could be related to schizophrenia, these findings may explain, at least in part, the mechanisms underlying in this disease.
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PMID:Different sub-anesthetic doses of ketamine increase oxidative stress in the brain of rats. 1945 99

Communicating with individuals who express delusions they believe are real is not easy. And nor is reaching out to engage individuals who present with severely blunted affect. But, those who live with schizophrenia need nurses' to understand their illness and help by monitoring medication compliance and asking questions about hallucinations, suicide and substance abuse.
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PMID:Schizophrenia: a brief review of what nurses can do and say to help. 1971 97

Deficits in everyday living skills and social skills are associated with the pervasive disability seen in schizophrenia. Cognitive impairments are determinants of these skills deficits and it is known that positive and negative symptoms add to the influence of cognitive impairments for prediction of real-world outcomes. This study examined the relative importance of cognitive impairments measured with a neuropsychological battery, performance-based measures of social and everyday living skills, and positive and negative symptoms for the prediction of real-world outcomes in social and residential domains. In contrast to most previous studies, we examined the importance of individual symptoms, as well as total subscale scores, for predicting clinician rated outcomes in 194 older outpatients with schizophrenia. Symptoms were rated with the Positive and Negative Syndrome Scale; everyday living skills were measured by the UCSD Performance-based Skills Assessment; and social skills were measured with the Social Skills Performance Assessment. For prediction of real-world social outcomes, blunted affect and passive-apathetic social withdrawal accounted for all of the predicted variance, while social competence and cognitive impairments did not enter the final equation. For residential functioning, everyday living skills were the most important predictor, followed by lack of spontaneity. The positive symptoms of hallucinatory behavior and suspiciousness also predicted real-world residential outcomes. These results suggest that real-world disability is the product of a complex array of ability deficits and symptoms, indicating interventions will need to be carefully targeted. For social and everyday living outcomes, variance accounted for by the entire array of predictive variables was less than 40%, suggesting that other factors, such as social and cultural influences, are involved as well.
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PMID:Determinants of everyday outcomes in schizophrenia: the influences of cognitive impairment, functional capacity, and symptoms. 1977 69

Deficits in odor identification have been most frequently described in schizophrenia (SZ). A relationship between dysfunction in odor identification and negative symptoms of SZ has also been reported. Furthermore, deficit SZ (a subtype of the illness with primary, enduring negative symptoms) has been found to be associated with a particularly poor performance on odor identification tests indicating that deficits in smell identification could be differentially expressed in some subtypes of SZ. We describe correlations of performance on smell identification with positive and negative symptoms of SZ. Patients with SZ (n=15) and normal controls (n=19) were tested by the University of Pennsylvania Smell Identification Test (UPSIT). Psychopathology was assessed with the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS). SZ patients performed more poorly on the UPSIT test than did normal controls. Consistent with previous findings, we observed a correlation of SANS with UPSIT performance. In particular, specific subdomains of SANS, such as blunted affect, apathy and anhedonia, were associated with odor identification deficits. Furthermore, UPSIT score predicts these subdomains of negative symptoms. No correlation was observed between positive symptom and odor identification deficits. Our study further reinforces a relation between olfactory identification deficit and negative symptoms in SZ and suggests that smell identification could be a candidate endophenotype relevant to negative symptoms of SZ.
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PMID:Negative symptoms of schizophrenia correlate with impairment on the University of Pennsylvania smell identification test. 1981 72

Negative symptoms commonly seen in chronic schizophrenia are related to prefrontal hypodopaminergia. Dysfunction of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The present study is an attempt to perform a quantitative trait test for genetic association between the COMT gene and negative symptoms in a Chinese population. A total of 290 unrelated individuals with schizophrenia patients were recruited and their symptoms were assessed through the Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED programme to examine the correlation between the scored negative symptoms and the coding single nucleotide polymorphisms (SNPs) present in the COMT gene. The rs4633-rs4680 haplotype showed significant association with the overall score of negative symptoms, and four individual negative symptoms, including blunted affect, emotional withdrawal, poor rapport and passive/apathetic social withdrawal. SNP rs4680 (Val/Met) showed significant association with blunted affect. The present finding suggests that the COMT gene may a etiologically contribute to the severity of negative symptoms in schizophrenia, but its precise mechanism needs further investigating.
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PMID:Analysis of association between the catechol-O-methyltransferase (COMT) gene and negative symptoms in chronic schizophrenia. 2048 79

Effective social interactions necessary for getting affiliative and instrumental needs met require the smooth integration of social skills, including verbal, non-verbal, and paralinguistic behaviors. Schizophrenia is characterized by prominent impairments in social and role functioning, and research on younger individuals with the illness has shown that social skills deficits are both common and distinguish the disease from other psychiatric disorders. However, less research has focused on diagnostic differences and correlates of social skills in older persons with schizophrenia. To address this question, we examined diagnostic and gender differences in social skills in a community-dwelling sample of 183 people older than age 50 with severe mental illness, and the relationships between social skills and neurocognitive functioning, symptoms, and social contact.Individuals with schizophrenia had worse social skills than those with bipolar disorder or major depression, with people with schizoaffective disorder in between. Social contact and cognitive functioning, especially executive functions and verbal fluency, were strongly predictive of social skills in people with schizophrenia and schizoaffective disorder, but not those with mood disorder. Other than blunted affect, symptoms were not predictive of social skills in either the schizophrenia spectrum or the mood disorder group. Older age was associated with worse social skills in both groups, whereas female gender was related to better skills in the mood disorder group, but not the schizophrenia group. The findings suggest that poor social skills, which are related to the cognitive impairment associated with the illness, are a fundamental feature of schizophrenia that persists from the onset of the illness into older age.
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PMID:Neurocognition and social skill in older persons with schizophrenia and major mood disorders: An analysis of gender and diagnosis effects. 2111 3


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