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Literature Search Results for Gene CIT
| CIT | ||
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| 1 |
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| PMID | 10770574 | |
| Title | Applications of SPECT imaging of dopaminergic neurotransmission in neuropsychiatric disorders. | |
| Abstract | Single photon emission computed tomography (SPECT) tracers selective for pre- and post-synaptic targets have allowed measurements of several aspects of dopaminergic (DA) neurotransmission. In this article, we will first review our DA transporter imaging in Parkinson's disease. We have developed the in vivo dopamine transporter (DAT) imaging with [123I]beta-CIT ((1R)-2beta-Carbomethoxy-3beta-(4-iodophenyl)tropane). This method showed that patients with Parkinson's disease have markedly reduced DAT levels in striatum, which correlated with disease severity and disease progression. Second, we applied DA imaging techniques in patients with schizophrenia. Using amphetamine as a releaser of DA, we observed the enhanced DA release, which was measured by imaging D2 receptors with [123I]IBZM (iodobenzamide), in schizophrenics. Further we developed the measurement of basal synaptic DA levels by AMPT (alpha-methyl-paratyrosine)-induced unmasking of D2 receptors. Finally, we expanded our techniques to the measurement of extrastriatal DA receptors using [123I]epidepride. The findings suggest that SPECT is a useful technique to measure DA transmission in human brain and may further our understanding of the pathophysiology of neuropsychiatric disorders. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 2 |
| |
| PMID | 10770574 | |
| Title | Applications of SPECT imaging of dopaminergic neurotransmission in neuropsychiatric disorders. | |
| Abstract | Single photon emission computed tomography (SPECT) tracers selective for pre- and post-synaptic targets have allowed measurements of several aspects of dopaminergic (DA) neurotransmission. In this article, we will first review our DA transporter imaging in Parkinson's disease. We have developed the in vivo dopamine transporter (DAT) imaging with [123I]beta-CIT ((1R)-2beta-Carbomethoxy-3beta-(4-iodophenyl)tropane). This method showed that patients with Parkinson's disease have markedly reduced DAT levels in striatum, which correlated with disease severity and disease progression. Second, we applied DA imaging techniques in patients with schizophrenia. Using amphetamine as a releaser of DA, we observed the enhanced DA release, which was measured by imaging D2 receptors with [123I]IBZM (iodobenzamide), in schizophrenics. Further we developed the measurement of basal synaptic DA levels by AMPT (alpha-methyl-paratyrosine)-induced unmasking of D2 receptors. Finally, we expanded our techniques to the measurement of extrastriatal DA receptors using [123I]epidepride. The findings suggest that SPECT is a useful technique to measure DA transmission in human brain and may further our understanding of the pathophysiology of neuropsychiatric disorders. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 3 |
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| PMID | 10704949 | |
| Title | Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [(123)I]beta-CIT. | |
| Abstract | Several lines of evidence derived from imaging and postmortem studies suggest that schizophrenia is associated with hyperactivity of dopamine function and deficiency in serotonin (5-HT) function. The aim of this study was to investigate potential alterations of striatal dopamine transporters (DAT) and brainstem serotonin transporters (SERT) density in schizophrenia. Striatal DAT and brainstem SERT were measured in 24 patients with schizophrenia and 22 matched healthy control subjects using single photon emission computed tomography and [(123)I]beta-CIT. In this cohort of subjects, we previously reported an increase in striatal amphetamine-induced dopamine release, measured as the displacement of the D(2) receptor radiotracer [(123)I]IBZM. No differences were observed between patients and control subjects in the equilibrium uptake ratio (V(3)") of [(123)I]beta-CIT in the striatum, indicating that schizophrenia is not generally associated with an alteration of striatal DAT density; however, a trend level association (p =.07) was observed in patients with schizophrenia between low striatal [(123)I]beta-CIT V(3)" and severity of negative symptoms. After controlling for age, striatal [(123)I]beta-CIT V(3)" in patients was not associated with duration of illness, suggesting that this relative deficit was not secondary to a neurodegenerative process. No correlation was observed between DAT density and amphetamine-induced dopamine release, either in the patients or in the controls. Brainstem [(123)I]beta-CIT V(3)" was unaffected in patients with schizophrenia, and was unrelated to symptomatology. Schizophrenia is generally not associated with alterations of DAT in the striatum or SERT in the brainstem. In some patients, a relative deficit in dopamine nerve terminals might play a role in the pathophysiology of negative symptoms. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 4 |
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| PMID | 11282255 | |
| Title | The variable number of tandem repeats polymorphism of the dopamine transporter gene is not associated with significant change in dopamine transporter phenotype in humans. | |
| Abstract | A 40 base polymorphism of a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). Despite being located in the untranslated region of the gene, this polymorphism has been associated with clinical phenotypes associated with dysregulation of dopamine transmission, such as attention deficit hyperactivity disorder and cocaine-induced paranoia. To examine the neurochemical phenotype associated with this polymorphism, we compared amphetamine-induced dopamine release (measured as displacement of the radiotracer [123I]IBZM) and DAT expression (measured with [123I]beta-CIT) in the striatum with Single Photon Computerized Emission Tomography (SPECT). Our sample included 59 subjects, 31 healthy controls and 29 patients with schizophrenia. No significant association was found between VNTR polymorphism and amphetamine-induced dopamine release or DAT density in the total sample, nor when each diagnostic group was considered separately. Thus, we did not replicate the findings of two previous studies, which had suggested that the 9 repeat allele was associated with either an increased or decreased DAT expression, albeit in different patient populations. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 5 |
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| PMID | 11163545 | |
| Title | Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT. | |
| Abstract | Disturbances in the dopamine (DA) system are thought to play a major role in schizophrenia. Amphetamine-induced release of endogenous DA is shown to be enhanced in schizophrenia, as is striatal [18F]FDOPA uptake in the striatum. It is not clear if the density of DA neurons is altered in schizophrenia. By studying the DA transporter with [123I]FP-CIT single photon emission computed tomography (SPECT), the density of nigrostriatal dopaminergic cells can be studied. Using [123I]FP-CIT SPECT, DA transporter density in the striatum was studied in 36 young patients with schizophrenia. Ten patients were antipsychotic (AP)-naive, 15 were treated with olanzapine, eight with risperidone and three were AP-free. A control group of 10 age-matched volunteers was included. Striatal [123I]FP-CIT binding was not significantly different between AP-naive patients (2.87), patients treated with olanzapine (2.76), patients treated with risperidone (2.76), AP-free patients (2.68) and controls (2.82) (F=0.07,p=0.98). Unexpectedly, striatal [123I]FP-CIT binding in females was significantly higher than in males (3.29 and 2.70, respectively; t=-2.56, p=0.014).Concluding, functional changes in the dopaminergic system in schizophrenia are not likely to be reflected in a change in DA transporter density. Moreover, DA transporter density does not seem to be altered by AP medication. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 6 |
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| PMID | 11374328 | |
| Title | Dopamine transporter density in patients with tardive dyskinesia: a single photon emission computed tomography study. | |
| Abstract | Tardive dyskinesia occurs frequently in schizophrenic patients chronically treated with classical antipsychotic medication. It may be caused by loss of dopaminergic cells, due to free radicals as a product of high synaptic dopamine levels. To evaluate dopamine transporter density in the striatum in patients with tardive dyskinesia. Striatal [123I]FP-CIT binding was measured with SPECT in seven schizophrenic patients with tardive dyskinesia and eight healthy controls. No significant difference was found between striatal [123I]FP-CIT binding ratios in patients with tardive dyskinesia and controls. This preliminary study indicates no change in striatal dopamine transporter density in schizophrenic patients with tardive dyskinesia. This finding does not support the hypothesis that tardive dyskinesia is caused by dopaminergic cell loss. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 7 |
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| PMID | 12478878 | |
| Title | Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology. | |
| Abstract | Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-naïve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-naïve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-naïve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-naïve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 8 |
| |
| PMID | 12478878 | |
| Title | Receptor and transporter imaging studies in schizophrenia, depression, bulimia and Tourette's disorder--implications for psychopharmacology. | |
| Abstract | Considerable progress has been achieved over the past 15 years in uncovering the biological basis of major psychiatric disorders. To determine patterns of brain dysfunction and to uncover the mechanism of action of centrally active compounds we used single photon emission computerized tomography (SPECT) as well as positron emission tomography (PET) in patients diagnosed with schizophrenia, depression, bulimia and Tourette's disorder. Striatal D2 and 5-HT1A receptors were studied in schizophrenia and 5-HT transporters (5-HTT) in depression and bulimia. Patients were either drug-naïve or drug free, or we studied the influence of specifically acting compounds on receptor/transporter occupancy. We could demonstrate that atypical antipsychotics have a dose-dependent (with the exception of clozapine and quetiapine) lower striatal D2 receptor occupancy rate compared with typical neuroleptics, paralleling the more favourable extrapyramidal side effects of atypical antipsychotics. However, no association between striatal D2 receptor occupancy rates and antipsychotic efficacy has been found. The measurement of 5-HT1A receptors in drug-naïve schizophrenic patients using the in vivo PET methodology revealed an increase of cortical 5-HT1A receptor binding potential in schizophrenia. beta-CIT as a ligand for measurement of 5-HT transporter densities (5-HTT) revealed lower rates in depression compared to age- and sex-matching healthy controls, a measurement that has also been obtained for bulimia. We also documented seasonal variations in brain serotonergic function by our finding of reduced brain 5-HTT availability in winter (compared to summer) in healthy controls. Furthermore, displaceable [123I] beta-CIT binding in the area corresponding to the left striatum (representing predominantly the density of dopamine transporters) was significantly reduced in SAD patients compared to healthy controls. In depression as well as in bulimia, selective serotonin reuptake inhibitors significantly decreased the beta-CIT binding potential, however, no significant dose relationship has been obtained in depression. Genotyping depressed patients for the serotonin transporter promoter gene region (5-HTTLPR) did not provide evidence for in vivo functional regulation of 5-HTT availability by 5-HTTLPR in the thalamus-hypothalamus and mesencephalon-pons of healthy subjects. In patients suffering from Tourette's disorder (TD) we were unable to detect differences of dopamine transporter densities between psychotropic drug-naïve TD patients and controls. Furthermore, no difference could be found between currently treated (with antipsychotics) and psychotropic drug-naïve TD patients. Our data provide insight into the pathophysiology of neuropsychiatric disorders and may guide future psychopharmacological drug developments. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 9 |
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| PMID | 14712338 | |
| Title | 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia. | |
| Abstract | The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 10 |
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| PMID | 14712338 | |
| Title | 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia. | |
| Abstract | The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 11 |
| |
| PMID | 14712338 | |
| Title | 123I-beta-CIT SPECT demonstrates increased presynaptic dopamine transporter binding sites in basal ganglia in vivo in schizophrenia. | |
| Abstract | The dopamine hypothesis for schizophrenia postulates overactivity of dopamine transmission in the basal ganglia. Most effective antipsychotic drugs block postsynaptic dopamine receptors, but in-vivo imaging studies have not been able to show changes in these receptors in drug-naive schizophrenics. The presynaptic dopamine transporter (DAT) is thought to be an important regulator of synaptic dopamine concentration. We have used SPECT with (123)I-beta-CIT, which has a high affinity for DAT, in order to further examine the dopamine hypothesis for schizophrenia. Six patients with chronic schizophrenia treated with classic dopamine D(2)-receptor blocking neuroleptics were investigated. The number of DAT binding sites in the basal ganglia was calculated and compared with five healthy volunteers and ten parkinsonian patients. The schizophrenic patients showed a 36-63% increase in DAT binding sites compared with the volunteers, whereas the parkinsonian patients showed a 57-96% decrease. The differences between the groups were highly significant (even after correction for different age composition within the groups). There was an increased number of DAT binding sites in the schizophrenic patients treated with dopamine D(2)-receptor blocking neuroleptics. This fits well with several recent reports that have shown increased volumes of basal ganglia in this patient category. It thus appears that there is an increased number of presynaptic dopamine releasing nerve terminals in the basal ganglia, possibly as a biological adaptation to counteract the postsynaptic dopamine D(2)-receptor blockade. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 12 |
| |
| PMID | 15974500 | |
| Title | Psychiatric disposition of patients brought in by crisis intervention team police officers. | |
| Abstract | As part of an effort to improve police interactions with mentally ill citizens, and improve mental health care delivery to subjects in acute distress, the University of Louisville, in conjunction with the Louisville Metro Police, established the crisis intervention team (CIT). CIT is composed of uniformed officers who receive extensive training in crisis intervention and psychiatric issues and who are preferentially called to investigate police calls that may involve a mentally ill individual. In an effort to determine the characteristics of the individuals brought to the emergency psychiatric service (EPS) by CIT officers, a comparative (CIT vs. mental inquest warrant [MIW, a citizen-initiated court order to bring someone for psychiatric evaluation because of concerns regarding dangerousness] vs non-CIT/non-MIW), descriptive evaluation was performed. With the exception of a higher rate of schizophrenic subjects brought in by CIT (43.0% vs. 22.1%, non-CIT, P = .002), the demographics, diagnosis, and disposition of CIT-referred subjects were not different in any way from non-CIT patients. Subjects referred on MIWs were more likely to be admitted to a psychiatric hospital than non-MIW patients (71.6% vs. 34.8%, P < .0001), but CIT-referred hospitalization rates were not different from hospitalization rates of self-referred subjects (20.7% vs. 33.3%, ns). CIT officers appear to do a good job at identifying patients in need of psychiatric care. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 13 |
| |
| PMID | 15830229 | |
| Title | Decreased striatal dopamine transporter binding assessed with [123I] FP-CIT in first-episode schizophrenic patients with and without short-term antipsychotic-induced parkinsonism. | |
| Abstract | Drug-induced parkinsonism (DIP) is one of the main causes of treatment drop-out in schizophrenic patients causing a high incidence of relapse that leads patients to a bad clinical prognosis. The dopaminergic nigrostriatal pathway is involved in the movement control, so the study of the dopamine transporter (DAT) could be of great value to determine its implication in the appearance of DIP. The goal of the study is to determine the striatal DAT binding assessed with [(123)I] FP-CIT SPECT in first-episode neuroleptic-naive schizophrenic in-patients with DIP after short-term antipsychotic treatment. The [(123)I] FP-CIT binding ratios of ten schizophrenic in-patients who developed DIP during the first 4-week period of risperidone treatment (6+/-2 mg/day) were compared with ten schizophrenic in-patients treated with the same doses of risperidone and who do not developed DIP and with ten age-matched healthy subjects. Quantitative analyses of SPECTs were performed using regions of interest located in caudate, putamen and occipital cortex. Parkinsonism was assessed by the Simpson-Angus Scale and the psychopathological status by the Clinical General Impression and Positive and Negative Syndrome Scales. Whole striatal [(123)I] FP-CIT binding ratios were significantly lower in patients with and without DIP than in healthy subjects (p<0.001). This was also observed in whole putamen (p<0.001) and caudate nucleus (p<0.001). Females showed higher whole striatal [(123)I] FP-CIT binding ratios than males (p<0.05). No differences in psychopathological scales were observed between patients with and without DIP. Our first-episode schizophrenic patients with and without DIP after short-term risperidone treatment have a decreased striatal DAT binding assessed with [(123)I] FP-CIT. This alteration could be related to the schizophrenic disease or may be secondary to the antipsychotic treatment. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 14 |
| |
| PMID | 16870973 | |
| Title | Brief reports: crisis intervention team training: changes in knowledge, attitudes, and stigma related to schizophrenia. | |
| Abstract | Crisis intervention team (CIT) training provides police officers with knowledge and skills to improve their responses to individuals with mental illnesses. This study determined changes in knowledge, attitudes, and social distance related to schizophrenia among police officers after CIT training. A survey was administered to 159 officers immediately before and after a 40-hour CIT training program in Georgia. Pre- and posttest data were gathered from surveys taken between December 2004 and July 2005. After the training, officers reported improved attitudes regarding aggressiveness among individuals with schizophrenia, became more supportive of treatment programs for schizophrenia, evidenced greater knowledge about schizophrenia, and reported less social distance toward individuals with schizophrenia. This study supports the hypothesis that an educational program for law enforcement officers may reduce stigmatizing attitudes toward persons with schizophrenia. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 15 |
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| PMID | 16768017 | |
| Title | The development of a culturally informed, family-focused treatment for schizophrenia. | |
| Abstract | With the changing demographics in the United States, there is an increasing need for psychotherapy interventions that have been tailored for and empirically evaluated with culturally diverse groups. This article discusses the development and evaluation of a family-focused, culturally informed therapy for schizophrenia (CIT-S) that is currently being pilot tested at the University of Miami. Case examples of CIT-S with participating families are provided, along with a discussion of interesting and challenging cultural issues that we have encountered during the pilot phase of this treatment study. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 16 |
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| PMID | 16916074 | |
| Title | Social-cognitive functioning and schizotypal characteristics. | |
| Abstract | The authors examined the relationship between social cognition and a feature of schizotypal personality referred to as magical ideation, defined broadly as the presence and intensity of illogical beliefs about causality and the nature of reality. The measures of social cognition used in this study were the Character Intention Task (CIT) and the adult version of the Reading the Mind in the Eyes Test. Regression analyses indicated that understanding of character intentions, as measured by CIT scores, and ability to identify emotions on the Eyes test were related to non-realistic beliefs. Principal components analysis of the Magical Ideation Scale generated 3 factors: Occult Beliefs, Non-Realism, and New Age Ideas. Results indicated that impaired understanding of character intentions and ability to identify emotions on the Eyes test were related to non-realistic beliefs. Understanding the cognitive impairments associated with schizotypal characteristics can facilitate development of more targeted therapeutic interventions. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 17 |
| |
| PMID | 17150335 | |
| Title | Dopamine transporter (DAT) genotype (VNTR) and phenotype in extrapyramidal symptoms induced by antipsychotics. | |
| Abstract | Impaired dopamine transporter (DAT) function may be involved in antipsychotic (AP)-induced extrapyramidal symptoms (EPS). A polymorphism involving a variable number of tandem repeats (VNTR) has been described in the DAT gene (SLC6A3). We studied whether the SLC6A3 VNTR polymorphism is a risk or protection factor for AP-induced EPS. We also investigated the relationship between the polymorphism and DAT availability in the schizophrenic patient's brain. Sixty-one patients receiving AP therapy participated in the EPS study. Of these, thirty-two cases presented EPS (Simpson-Angus >3) and twenty-nine without EPS (Simpson-Angus < or =3). The DAT expression was studied in fifteen AP-naive patients by [(123)I] FP-CIT SPECT. No significant differences were observed for the more common alleles ((*)9R and (*)10R) or for genotype frequencies between patients with EPS and those without EPS. The frequency of the (*)9R and (*)10R alleles was similar to that described in other European populations. There were no significant differences in striatal DAT binding among the three major VNTR genotype groups. Our results suggest that the VNTR polymorphism did not influence AP-induced EPS and did not affect DAT gene expression or protein function. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 18 |
| |
| PMID | 17294064 | |
| Title | Chorea-acanthocytosis in monozygotic twins: clinical findings and neuropathological changes as detected by diffusion tensor imaging, FDG-PET and (123)I-beta-CIT-SPECT. | |
| Abstract | We report on two 33 years old monozygotic twins with chorea-acanthocytosis (ChAc) misdiagnosed as schizophrenia and Tourette syndrome, respectively. Although the patients shared several clinical similarities, there were also some clear differences: twin 1 presented initially with an acute episode of a paranoid schizophrenia, while twin 2 suffered from generalized epileptic seizures. In both twins, MRI demonstrated caudate nucleus atrophy and an increased apparent diffusion coefficient (ADC) in the striatum bilaterally with right sided predominance. (18)F-FDG PET showed bilaterally reduced glucose utilization in the striatum with clearly pronounced reduction on the right side compared to the left and in twin 1 compared to twin 2. Ratios of binding to striatal dopamine transporters (DAT) and serotonin transporters in the hypothalamus midbrain area as determined using (123)I-beta-CIT-SPECT fell within the normal ranges. However, in twin 1 a significant difference in binding to presynaptic DAT with marked reduction on the right hemisphere was observed. Right hemispheric accentuated changes measured by MRI, FDG-PET, and (123)I-beta-CITSPECT correspond to more severe hyperkinetic movements on the left part of the body in both twins. Different neuro-psychiatric features in this monocygotic twin pair suggest that not only genetic but also environmental factors contribute to the clinical symptomatology. Our findings suggest that the main neuropathological process in ChAc is located in the striatum, involving microstructural alterations, and disturbance of metabolism and dopaminergic neurotransmission. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 19 |
| |
| PMID | 17019564 | |
| Title | Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait. | |
| Abstract | Drug induced parkinsonism (DIP) is directly related to dopamine D2 receptor blockade. However, there are many references describing parkinsonian signs (PS) in naive-patients. In our previous study, we observed lower DAT binding in a group of first-episode schizophrenic patients after short-term treatment with risperidone, compared with age-matched healthy controls. To clarify if DAT decrease could be an illness trait, excluding the effect of antipsychotics on DAT availability, and to determine whether DAT availability before treatment with antipsychotics may predict subsequent development of PS. A new series of 20 neuroleptic-naive schizophrenic patients and 15 healthy subjects was recruited. SPECT with [(123)I] FP-CIT (DaTSCAN(R)) was performed before starting antipsychotics and after 4 weeks of treatment. PS and psychopathological status were assessed by the Simpson-Angus (SAS), CGI and PANSS scales. Quantitative analyses of SPECTs were performed using ROIs placed in the caudate, putamen and occipital cortex. Schizophrenic patients showed lower DAT binding compared with the healthy subjects at baseline (p<0.001) and after a 4-week-treatment period (p=0.001). Six out of eight schizophrenic patients of the DIP group were symptomatic for PS at baseline, in comparison to two out of 12 in the NoDIP group. Nonetheless, no differences were observed on DAT between DIP and NoDIP, neither at baseline (p=0.360) nor at endpoint (p=0.984). Finally, no differences between baseline-endpoint DAT binding were observed, neither in the DIP group (p=0.767) nor in the NoDIP group (p=0.093). Our new series of first-episode naive-schizophrenic patients (1) points out DAT dysfunction as an illness trait due to the significantly lower DAT binding in schizophrenic patients in comparison to healthy subjects; (2) supports the results of other authors who describe PS in never-treated patients; (3) confirms that [(123)I] FP-CIT does not allow us to predict which patients will develop parkinsonism due to the lack of differences between DIP and NoDIP patients; and (4) confirms a null effect of antipsychotics on DAT due to the lack of differences in [(123)I] FP-CIT before and after a 4-week-treatment period. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 20 |
| |
| PMID | 18040771 | |
| Title | Preliminary evidence of effects of crisis intervention team training on self-efficacy and social distance. | |
| Abstract | The Crisis Intervention Team (CIT) program is a collaborative model involving mental health professionals and law enforcement officers that is being implemented in a multitude of localities across the country. This study had two main objectives: (1) To assess perceptions of self-efficacy and desired social distance of control officers and officers entering CIT training with regard to individuals with psychiatric syndromes (depression and schizophrenia) and individuals with substance dependence (alcohol and cocaine), and (2) To examine the effects, if any, of CIT training on self-efficacy and social distance. Between March and July 2006, a survey was administered to 34 control police officers, 58 officers just before a 40-h CIT training program, and 40 of these officers upon completion of the training. At baseline, pre-CIT officers did not differ from control non-CIT officers in terms of self-efficacy or social distance relating to the four disorders. Officers trained in CIT demonstrated enhanced self-efficacy for interacting with individuals with depression, cocaine dependence, schizophrenia, and alcohol dependence. Additionally, CIT-trained officers reported reduced social distance regarding individuals with these four psychiatric conditions. Regarding the schizophrenia vignette, there was a significant interaction between pre-CIT/post-CIT status and family history of psychiatric treatment in the prediction of social distance. Enhancements in self-efficacy and reductions in social distance may have important implications in terms of improving officers' interactions with people with mental illnesses and substance use disorders. Given the importance of the problem of law enforcement/criminal justice involvement among people with such illnesses, and the dearth of research on this growing collaborative service model, further research is needed on officer-level outcomes of the CIT program. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 21 |
| |
| PMID | 19408116 | |
| Title | Beliefs about causes of schizophrenia among police officers before and after crisis intervention team training. | |
| Abstract | This study examined the ways in which beliefs about the causes of schizophrenia change after crisis intervention team (CIT) training of police officers. Comparisons of pre- and post-training scores from 159 officers revealed a decrease in endorsement of items pertaining to personal/family/social stressors and items inconsistent with contemporary conceptions of risk, as well as an increase in endorsement of items consistent with modern biological conceptions of the causation of schizophrenia. Changes in causal beliefs were associated with personal and family history of psychiatric treatment among officers. Findings indicate a need for further research in this area, and suggest that some characteristics of officers may be associated with an increased capacity for knowledge/attitudinal change during CIT training. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 22 |
| |
| PMID | 20179754 | |
| Title | Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. | |
| Abstract | Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 23 |
| |
| PMID | 20084519 | |
| Title | Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging. | |
| Abstract | The etiology of schizophrenia likely involves genetic interactions. DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis. We tested for epistasis between these genes in a schizophrenia case-control study using machine learning algorithms (MLAs: random forest, generalized boosted regression andMonteCarlo logic regression). Convergence of MLAs revealed a subset of seven SNPs that were subjected to 2-SNP interaction modeling using likelihood ratio tests for nested unconditional logistic regression models. Of the 7C2 = 21 interactions, four were significant at the ? = 0.05 level: DISC1 rs1411771-CIT rs10744743 OR = 3.07 (1.37, 6.98) p = 0.007; CIT rs3847960-CIT rs203332 OR = 2.90 (1.45, 5.79) p = 0.003; CIT rs3847960-CIT rs440299 OR = 2.16 (1.04, 4.46) p = 0.038; one survived Bonferroni correction (NDEL1 rs4791707-CIT rs10744743 OR = 4.44 (2.22, 8.88) p = 0.00013). Three of four interactions were validated via functional magnetic resonance imaging (fMRI) in an independent sample of healthy controls; risk associated alleles at both SNPs predicted prefrontal cortical inefficiency during the N-back task, a schizophrenia-linked intermediate biological phenotype: rs3847960-rs440299; rs1411771-rs10744743, rs4791707-rs10744743 (SPM5 p < 0.05, corrected), although we were unable to statistically replicate the interactions in other clinical samples. Interestingly, the CIT SNPs are proximal to exons that encode theDISC1 interaction domain. In addition, the 3' UTR DISC1 rs1411771 is predicted to be an exonic splicing enhancer and the NDEL1 SNP is ~3,000 bp from the exon encoding the region of NDEL1 that interacts with the DISC1 protein, giving a plausible biological basis for epistasis signals validated by fMRI. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 24 |
| |
| PMID | 20600460 | |
| Title | Delusional infestation: neural correlates and antipsychotic therapy investigated by multimodal neuroimaging. | |
| Abstract | In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging. In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM). In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy. Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 25 |
| |
| PMID | 20600460 | |
| Title | Delusional infestation: neural correlates and antipsychotic therapy investigated by multimodal neuroimaging. | |
| Abstract | In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging. In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM). In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy. Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 26 |
| |
| PMID | 22103308 | |
| Title | Pharmacological challenge and synaptic response - assessing dopaminergic function in the rat striatum with small animal single-photon emission computed tomography (SPECT) and positron emission tomography (PET). | |
| Abstract | Disturbances of dopaminergic neurotransmission may be caused by changes in concentrations of synaptic dopamine (DA) and/or availabilities of pre- and post-synaptic transporter and receptor binding sites. We present a series of experiments which focus on the regulatory mechanisms of the dopamin(DA)ergic synapse in the rat striatum. In these studies, DA transporter (DAT) and/or D(2) receptor binding were assessed with either small animal single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after pharmacological challenge with haloperidol, L-DOPA and methylphenidate, and after nigrostriatal 6-hydroxydopamine lesion. Investigations of DAT binding were performed with [(123)I]N-?-fluoropropyl-2?-carbomethoxy-3?-(4-iodophenyl)nortropane ([(123)I]FP-CIT). D(2) receptor bindingd was assessed with either [(123)I](S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([(123)I]IBZM) or [(18)F]1[3-(4'fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1-benzimidazolinyl)piperidine ([(18)F]FMB). Findings demonstrate that in vivo investigations of transporter and/or receptor binding are feasible with small animal SPECT and PET. Therefore, tracers that are radiolabeled with isotopes of comparatively long half-lives such as (123)I may be employed. Our approach to quantify DAT and/or D(2) receptor binding at baseline and after pharmacological interventions inducing DAT blockade, D(2) receptor blockade, and increases or decreases of endogenous DA concentrations holds promise for the in vivo assessment of synaptic function. This pertains to animal models of diseases associated with pre- or postsynaptic DAergic deficiencies such as Parkinson's disease, Huntington's disease, attention-deficit/hyperactivity disorder, schizophrenia or drug abuse. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 27 |
| |
| PMID | 21831607 | |
| Title | A 4-year dopamine transporter (DAT) imaging study in neuroleptic-naive first episode schizophrenia patients. | |
| Abstract | Alterations in the dopaminergic system have long been implicated in schizophrenia. A key component in dopaminergic neurotransmission is the striatal dopamine transporter (DAT). To date, there have been no longitudinal studies evaluating the course of DAT in schizophrenia. A 4-year follow-up study was therefore conducted in which single photon emission computed tomography was used to measure DAT binding in 14 patients and 7 controls. We compared the difference over time in [(123)I] FP-CIT striatal/occipital uptake ratios (SOUR) between patients and controls and the relationship between this difference and both symptomatology and functional outcome at follow-up. We also calculated the relationship between baseline SOUR, symptoms and functional outcome at follow-up. There were no statistically significant differences between patients' SOUR changes over time and those of controls. A significant negative correlation was observed between patients' SOUR changes over time and negative symptomatology at follow-up. A significant negative correlation was also found between baseline SOUR in patients and negative symptomatology, and there was a significant association between lower SOUR at baseline and poor outcome. Although the study found no overall differences in DAT binding during follow-up between schizophrenia patients and controls, it demonstrated that differences in DAT binding relate to patients' characteristics at follow-up. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 28 |
| |
| PMID | 19933714 | |
| Title | Use of force preferences and perceived effectiveness of actions among Crisis Intervention Team (CIT) police officers and non-CIT officers in an escalating psychiatric crisis involving a subject with schizophrenia. | |
| Abstract | Few studies have examined police officers' use of force toward individuals with schizophrenia, despite the widely disseminated Crisis Intervention Team (CIT) model of partnership between mental health and law enforcement that seeks to reduce use of force and enhance safety of officers and individuals with mental illnesses. This study tested the hypotheses that CIT-trained officers would select a lower level of force, identify nonphysical actions as more effective, and perceive physical force as less effective in an escalating psychiatric crisis, compared with non-CIT-trained officers. Police officers (n = 135)-48 CIT trained and 87 non-CIT trained-completed a survey containing 3 scenario-based vignettes depicting an escalating situation involving a subject with psychosis. Data were analyzed using repeated-measures analyses of variance. Officers escalated their preferred actions across the scenarios. A significant scenario by group interaction indicated that CIT-trained officers chose less escalation (ie, opting for less force at the third scenario) than non-CIT-trained officers. Officers reported decreasing perceived effectiveness of nonphysical action across the 3 scenarios. A significant scenario by group interaction indicated that CIT-trained officers reported a lesser decline in perceived effectiveness of nonphysical actions at the third scenario. CIT-trained officers consistently endorsed lower perceived effectiveness of physical force. Efforts are needed to reduce use of force toward individuals with psychotic disorders. These findings suggest that CIT may be an effective approach. In addition to clinical and programmatic implications, such findings demonstrate a role for clinicians, advocates, and schizophrenia researchers in promoting social justice through partnerships with diverse social sectors. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 29 |
| |
| PMID | 21947317 | |
| Title | Association of the ZFPM2 gene with antipsychotic-induced parkinsonism in schizophrenia patients. | |
| Abstract | Antipsychotic-induced parkinsonism (AIP) is a severe adverse affect of antipsychotic drug treatment. Recently, our group performed a genome-wide association study (GWAS) for AIP severity, and identified several potential AIP risk variants. The aim of this study was to validate our original AIP-GWAS susceptibility variants and to understand their possible function. We conducted a validation study of 15 single-nucleotide polymorphisms (SNPs) in an independent sample of 178 US schizophrenia patients treated for at least a month with typical or atypical antipsychotics. Then, a sample of 49 Jewish Israeli Parkinson's disease (PD) patients with available neuroimaging ([(123)I]-FP-CIT-SPECT) data was analyzed, to study association of confirmed AIP SNPs with level of dopaminergic deficits in the putamen. Using logistic regression and controlling for possible confounders, we found nominal association of the intronic SNP, rs12678719, in the Zinc Finger Protein Multitype 2 (ZFPM2) gene with AIP (62 affected/116 unaffected), in the whole sample (p?=?0.009; P?=?5.97?×?10(-5) in the GWAS), and in the African American sub-sample (N?=?111; p?=?0.002). The same rs12678719-G AIP susceptibility allele was associated with lower levels of dopaminergic neuron related ligand binding in the contralateral putamen of PD patients (p?=?0.026). Our preliminary findings support association of the ZFPM2 SNP, rs12678719, with AIP. At the functional level, this variant is associated with deficits in the nigrostriatal pathway in PD patients that may be related to latent subclinical deficits among AIP-prone individuals with schizophrenia. Further validation studies in additional populations are required. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 30 |
| |
| PMID | 22727453 | |
| Title | [¹²³I]FP-CIT single photon emission computed tomography findings in drug-induced Parkinsonism. | |
| Abstract | Drug-induced parkinsonism (DIP) in patients treated with antipsychotic drugs is considered a form of post-synaptic parkinsonism, caused by D2-receptor blockade. Recent studies, however, carried out on small and heterogeneous patient samples, have shown that DIP may be associated with [(123)I]FP-CIT single photon emission computed tomography (SPECT) abnormalities, which are markers of dopamine nigrostriatal terminal defect. In the present study, outpatients fulfilling the DSM-IV criteria for schizophrenia and treated with antipsychotics for at least 6 months, were enrolled in order to estimate the prevalence of DIP and, among patients with DIP, the prevalence of [(123)I]FP-CIT SPECT abnormalities. Socio-demographic and clinical variables associated with the presence of DIP and SPECT abnormalities were also assessed. DIP was diagnosed in 149 out of 448 patients with schizophrenia (33%). Age, use of long-acting antipsychotics and a positive family history of parkinsonism were the only demographic variables significantly associated with the development of DIP. Neuroimaging abnormalities were found in 41 of 97 patients who agreed to undergo [(123)I]FP-CIT SPECT (42%). Only age differentiated this group of patients from those with normal imaging. These preliminary findings suggest that D2-receptor blockade may coexist with a dopamine nigrostriatal terminal defect, as assessed by [(123)I]FP-CIT SPECT abnormalities, in a relevant proportion of DIP patients. Longitudinal studies should be designed with the aim of improving our understanding of the mechanisms of pre-synaptic abnormalities in DIP patients and identifying specific treatment strategies. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 31 |
| |
| PMID | 23602339 | |
| Title | Human brain imaging studies of DISC1 in schizophrenia, bipolar disorder and depression: a systematic review. | |
| Abstract | Disrupted-in-Schizophrenia 1 (DISC1) is a well researched candidate gene for schizophrenia and affective disorders with a range of functions relating to neurodevelopment. Several human brain imaging studies investigating correlations between common and rare variants in DISC1 and brain structure and function have shown conflicting results. A meta-analysis of case/control data showed no association between schizophrenia and any common SNP in DISC1. Therefore it is timely to review the literature to plan the direction of future studies. Twenty-two human brain imaging studies have examined the influence of DISC1 variants in health, schizophrenia, bipolar disorder or depression. The most studied common SNPs are Ser704Cys (rs821616) and Leu607Phe (rs6675281). Some imaging-genomic studies report effects on frontal, temporal and hippocampal structural indices in health and illness and a volumetric longitudinal study supports a putative role for these common SNPs in neurodevelopment. Callosal agenesis is described in association with rare deletions at 1q42 which include DISC1 and rare sequence variants at DISC1 itself. DISC1 interactions with translin-associated factor X (TRAX) and neuregulin have been shown to influence several regional volumes. In the first study involving neonates, a role for Ser704Cys (rs821616) has been highlighted in prenatal brain development with large clusters of reduced grey matter reported in the frontal lobes. Functional MRI studies examining associations between Ser704Cys (rs821616) and Leu607Phe (rs6675281) with prefrontal and hippocampal activation have also given inconsistent results. Prefrontal function was reported to be associated with interaction between DISC1 and CITRON (CIT) in health. Preliminary magnetic resonance spectroscopy and diffusion tensor data support the influence of Ser704Cys (rs821616) status on grey and white matter integrity. The glutamate system remains uninvestigated. Associations between rare sequence variants and structural changes in brain regions including the corpus callosum and effects of gene-gene interactions on brain structure and function are promising areas for future study. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 32 |
| |
| PMID | 24369987 | |
| Title | Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study. | |
| Abstract | Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 33 |
| |
| PMID | 24369987 | |
| Title | Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study. | |
| Abstract | Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 34 |
| |
| PMID | 25286175 | |
| Title | A randomized clinical trial to test the efficacy of a family-focused, culturally informed therapy for schizophrenia. | |
| Abstract | Research strongly suggests that family interventions can benefit patients with schizophrenia, yet current interventions often fail to consider the cultural context and spiritual practices that may make them more effective and relevant to ethnic minority populations. We have developed a family focused, culturally informed treatment for schizophrenia (CIT-S) patients and their caregivers to address this gap. Sixty-nine families were randomized to either 15 sessions of CIT-S or to a 3-session psychoeducation (PSY-ED) control condition. Forty-six families (66.7%) completed the study. The primary aim was to test whether CIT-S would outperform PSY-ED in reducing posttreatment symptom severity (controlling for baseline symptoms) on the Brief Psychiatric Rating Scale. Secondary analyses were conducted to test whether treatment efficacy would be moderated by ethnicity and whether patient-therapist ethnic match would relate to efficacy and patient satisfaction with treatment. Patients included 40 Hispanic/Latinos, 14 Whites, 11 Blacks, and 4 patients who identified as "other." In line with expectations, results from an ANCOVA indicated that patients assigned to the CIT-S condition had significantly less severe psychiatric symptoms at treatment termination than did patients assigned to the PSY-ED condition. Patient ethnicity and patient-therapist ethnic match (vs. mismatch) did not relate to treatment efficacy or satisfaction with the intervention. Results suggest that schizophrenia may respond to culturally informed psychosocial interventions. The treatment appears to work equally well for Whites and minorities alike. Follow-up research with a matched length control condition is needed. Further investigation is also needed to pinpoint specific mechanisms of change. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 35 |
| |
| PMID | 27239468 | |
| Title | Copy Number Variations in DISC1 and DISC1-Interacting Partners in Major Mental Illness. | |
| Abstract | Robust statistical, genetic and functional evidence supports a role for DISC1 in the aetiology of major mental illness. Furthermore, many of its protein-binding partners show evidence for involvement in the pathophysiology of a range of neurodevelopmental and psychiatric disorders. Copy number variants (CNVs) are suspected to play an important causal role in these disorders. In this study, CNV analysis of DISC1 and its binding partners PAFAH1B1, NDE1, NDEL1, FEZ1, MAP1A, CIT and PDE4B in Scottish and Northern Swedish population-based samples was carried out using multiplex amplicon quantification. Here, we report the finding of rare CNVs in DISC1, NDE1 (together with adjacent genes within the 16p13.11 duplication), NDEL1 (including the overlapping MYH10 gene) and CIT. Our findings provide further evidence for involvement of DISC1 and its interaction partners in neuropsychiatric disorders and also for a role of structural variants in the aetiology of these devastating diseases. | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
| 36 |
| |
| PMID | 26654115 | |
| Title | The effect of a culturally informed therapy on self-conscious emotions and burden in caregivers of patients with schizophrenia: A randomized clinical trial. | |
| Abstract | Caring for a family member with schizophrenia often results in high degrees of self-conscious emotions (shame and guilt/self-blame), burden, and other serious mental health consequences. Research suggests that ethnic and cultural factors strongly influence the manner in which family members respond to mental illness. Research further indicates that certain cultural practices and values (spirituality, collectivism) may assist family members in coping with the self-conscious emotions and burden associated with caregiving. With this in mind, the authors have developed a family-focused, culturally informed treatment for schizophrenia (CIT-S). Using a sample of 113 caregivers of patients with schizophrenia (60% Hispanic, 28.2% Caucasian, 8% African American, and 3.8% other), the authors assessed the ability of CIT-S to reduce self-conscious emotions and caregiver burden above and beyond a 3-session psychoeducation (PSY-ED) control condition. They further examined whether self-conscious emotions mediated the relationship between treatment type and caregiver burden. In line with expectations, CIT-S was found to outperform PSY-ED in reducing guilt/self-blame and caregiver burden. Furthermore, consistent with hypotheses, reductions in guilt/self-blame were found to mediate the changes observed between treatment type and caregiver burden. Although caregivers in both treatment groups demonstrated significant posttreatment reductions in shame, CIT-S was not found to outperform PSY-ED in reducing levels of this construct. Results suggest that caregivers of patients with schizophrenia may respond well to a treatment that specifically taps in to their cultural beliefs, values, and behaviors in helping them cope with schizophrenia in a loved one. Study implications and future directions are discussed. (PsycINFO Database Record | |
| SCZ Keywords | schizophrenia,schizophrenic,schizophrenics,schizotypal | |
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