| 1 | Seishin Shinkeigaku Zasshi 2001 -1 103: 622-9 |
|---|---|
| PMID | 11692394 |
| Title | [Neural correlates of memory organization deficits in schizophrenia--a single photon emission computed tomography study with 99mTc-ECD during a verbal learning task]. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Int J Geriatr Psychiatry 2002 Apr 17: 383-7 |
| PMID | 11994894 |
| Title | Negative symptoms, depression and Alzheimer's disease. |
| Abstract | To apply the negative symptoms (NS) concept used in schizophrenia to patients with AD, to compare the results with the frontal lobe perfusion in ethyl cysteinate dimmer (ECD) single-photon emission computed tomography (SPECT) and with the apolipoprotein E genotype. 32 patients with a diagnosis of probable AD were assessed by the Positive and Negative Symptoms Scale (PANSS-N), the Montgomery and Asberg Depression Scale (MADRS), the NeuroPsychiatric Inventory (NPI), and the Mini-Mental Status Examination (MMSE). Each patient underwent ECD SPECT and APO E genotyping. PANSS-N, MADRS, NPI, and MMSE were administered to 19 normal elderly control subjects. The mean PANSS-N score for AD patients (20.56, SD: 8, range: 7-40) was significantly higher (p < 0.001) than that of controls (7, SD: 0). MADRS scores were not significantly different (p = 0.75) between AD patients (9.03, SD: 6.14, range: 0-25) and controls (6.2, SD: 3.61, range: 1-15). The NPI apathy score (0-12) was correlated with PANSS-N (p < 0.001). Correlation between prominent frontal hypoperfusion (six cases) and NS was at the limit of significance. No relation was found between epsilon E4 and NS. This consideration is important in distinguishing between depression and AD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Schizophr Bull 2002 -1 28: 467-74 |
| PMID | 12645678 |
| Title | Impaired temporal lobe processing of preattentive auditory discrimination in schizophrenia. |
| Abstract | Feature-specific stimulus discrimination related to short-term auditory sensory memory can be studied electrophysiologically using a specific event-related potential (ERP) component termed mismatch negativity (MMN), which is generated in the auditory cortex, indexing automatic comparison of the existing memory trace to incoming novel stimuli. Previous results with electroencephalography (EEG) and magnetoencephalography (MEG) suggest that schizophrenia patients have attenuated MMN response and that preattentive auditory processing preceding MMN appears to be functionally asymmetric in schizophrenia. Here we studied parallel MMN activity of the hemispheres using a whole-head MEG by presenting stimulus blocks consisting of frequent standard and infrequent deviant tones to 15 schizophrenia patients and 19 healthy control subjects. Auditory evoked fields (AEFs) were recorded simultaneously over both auditory cortices. The equivalent current dipole (ECD) modeling revealed that patients had significant MMNm reduction (magnetic counterpart of MMN) in both temporal lobes. In addition, patients had significantly delayed MMNm in the left but not in the right hemisphere to ipsilateral auditory stimuli. These results suggest that patients with schizophrenia have impaired auditory processing in the temporal lobes underlying preattentive stimulus discrimination that is also selectively delayed in the left hemisphere. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Schizophr. Res. 2003 Feb 59: 253-60 |
| PMID | 12414082 |
| Title | Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity. |
| Abstract | The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics (n = 15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics (chi(2) test = 16.13, p < 0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) (r = -0.673, p = 0.008), especially with the hallucinatory behavior subscale (r = -0.677, p = 0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Schizophr. Res. 2003 Feb 59: 253-60 |
| PMID | 12414082 |
| Title | Altered hemispheric asymmetry and positive symptoms in schizophrenia: equivalent current dipole of auditory mismatch negativity. |
| Abstract | The abnormality of mismatch negativity (MMN) in schizophrenia is thought to be associated with perceptional disturbance and cognitive dysfunction. The purpose of the present study was to investigate the change of the normal functional hemispheric lateralization in schizophrenia by employing the equivalent current dipole (ECD) model of auditory MMN with individual MRI and high-density electroencephalography (EEG). The MMNs resulting from auditory stimuli with passive oddball paradigm in a group of schizophrenics (n = 15), and also a group of age-, sex-, and handedness-matched normal controls, were recorded by 128 channel EEG. The location and power of ECD sources at the peak point were calculated. Individual 3-D brain magnetic resonance images (MRI) were used for realistic head modeling and for source localization. For both groups, the MMN source was determined to be located in the superior temporal gyrus (STG). However, the normal functional hemispheric asymmetry of ECD power was significantly altered in the schizophrenics (chi(2) test = 16.13, p < 0.001). Left MMN ECD power and the asymmetry coefficient (AC) were negatively correlated with the positive scores from Positive and Negative Syndrome Scale (PANSS) (r = -0.673, p = 0.008), especially with the hallucinatory behavior subscale (r = -0.677, p = 0.008). These findings support the deficits in preattentive automatic processing of auditory stimuli, especially in the left hemisphere, and indicate the correlation between positive symptoms, especially auditory hallucination, and left temporal lobe dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Psychol Med 2004 Oct 34: 1157-63 |
| PMID | 15697042 |
| Title | High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study. |
| Abstract | Repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions is under study as a non-invasive method in the treatment of affective disorders. Recent publications provide increasing evidence that rTMS may be useful in treating schizophrenia. Results are most intriguing, demonstrating a reduction of negative symptoms following high-frequency rTMS. In this context, disentangling of negative and depressive symptoms is of the utmost importance when understanding specific rTMS effects on schizophrenic symptoms. Using a sham-controlled parallel design, 20 patients with schizophrenia were included in the study. Patients were treated with high-frequency 10 Hz rTMS over 10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single photon emission computed tomography) imaging was performed before and after termination of rTMS treatment. High-frequency rTMS leads to a significant reduction of negative symptoms combined with a trend for non-significant improvement of depressive symptoms in the active stimulated group as compared with the sham stimulated group. Additionally, a trend for worsening of positive symptoms was observed in the actively treated schizophrenic patients. In both groups no changes in regional cerebral blood flow could be detected by ECD-SPECT. Beneficial effects of high-frequency rTMS on negative and depressive symptoms were found, together with a trend for worsening positive symptoms in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Psychol Med 2004 Oct 34: 1157-63 |
| PMID | 15697042 |
| Title | High-frequency repetitive transcranial magnetic stimulation in schizophrenia: a combined treatment and neuroimaging study. |
| Abstract | Repetitive transcranial magnetic stimulation (rTMS) of frontal brain regions is under study as a non-invasive method in the treatment of affective disorders. Recent publications provide increasing evidence that rTMS may be useful in treating schizophrenia. Results are most intriguing, demonstrating a reduction of negative symptoms following high-frequency rTMS. In this context, disentangling of negative and depressive symptoms is of the utmost importance when understanding specific rTMS effects on schizophrenic symptoms. Using a sham-controlled parallel design, 20 patients with schizophrenia were included in the study. Patients were treated with high-frequency 10 Hz rTMS over 10 days. Besides clinical ratings, ECD-SPECT (technetium-99 bicisate single photon emission computed tomography) imaging was performed before and after termination of rTMS treatment. High-frequency rTMS leads to a significant reduction of negative symptoms combined with a trend for non-significant improvement of depressive symptoms in the active stimulated group as compared with the sham stimulated group. Additionally, a trend for worsening of positive symptoms was observed in the actively treated schizophrenic patients. In both groups no changes in regional cerebral blood flow could be detected by ECD-SPECT. Beneficial effects of high-frequency rTMS on negative and depressive symptoms were found, together with a trend for worsening positive symptoms in schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | Biol. Psychiatry 2005 Apr 57: 743-51 |
| PMID | 15820231 |
| Title | Amphetamine sensitization impairs cognition and reduces dopamine turnover in primate prefrontal cortex. |
| Abstract | Amphetamine (AMPH) sensitization in monkeys produces long-lasting behavioral changes that model positive (hallucinatory-like behaviors) and negative (psychomotor depression) symptoms of schizophrenia. The extent to which this model produces the core deficit in schizophrenia--working memory impairment--is unknown. Two groups of rhesus monkeys were sensitized to AMPH over 6 weeks. In one group, acquisition of cognitive tasks (delayed response, visual discrimination, delayed nonmatch-to-sample) was examined beginning 6+ months postsensitization. The second group was pretrained to stability on delayed response before sensitization. Regional postmortem concentrations of dopamine and its metabolites were examined in tissue from age-matched AMPH-naive and AMPH-sensitized monkeys using high-performance liquid chromatography with electrochemical detection (HPLC-ECD). The AMPH-sensitized monkeys were profoundly impaired in their ability to acquire cognitive tasks compared with AMPH-naïve monkeys. Pretrained monkeys showed impaired delayed response performance for several months following sensitization. Analysis by HPLC revealed that AMPH sensitization significantly reduced dopamine turnover in prefrontal cortex and striatum. Impairments in the acquisition and performance of spatial delayed response in association with reduced dopamine turnover in prefrontal cortex following AMPH sensitization provide further support for the relevance of this model to both the etiology and the treatment of cognitive dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | Neuro Endocrinol. Lett. 2005 Dec 26: 685-9 |
| PMID | 16380684 |
| Title | Early effects of treatment on regional cerebral blood flow in first episode schizophrenia patients evaluated with 99Tc-ECD-SPECT. |
| Abstract | Altered regional cerebral blood flow (r-CBF) is mentioned as one of possible etiological factors or as a consequence of schizophrenia. Perfusion scintigraphic brain studies with SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) can detect areas of the brain with altered perfusion during the disease. Conflicting data exist on follow-up after treatment. The aim of our study was to evaluate r-CBF in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF. Clinical criteria for schizophrenia were met according to International Classification of Diseases-10th Edition (ICD-10). Psychic status and severity of the disease in each patient were evaluated with psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed 20 minutes after 99mTc-ECD application. R-CBF was measured in 9 first-episode schizophrenic male patients 2-7 (median 6) days after the beginning of antipsychotic treatment and 8-15 (median 9) weeks later. Semiquantitative analysis of r-CBF was performed with cerebellum as the reference region. R-CBF was evaluated for 12 regions in each study. Decrease in perfusion in comparison to cerebellum was detected in left (90%) and right (93%) frontal lobes. Increase in perfusion between the first (t1) and the second (t2) investigation was significant (p<0.05) for both frontal regions (left 94%, right 97%). Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with the increase of r-CBF. Our findings implicate that patients with first-episode schizophrenia have significant left hypoperfusion relative to the right in dorsolateral frontal lobes. Increased blood flow was observed bilaterally in dorsolateral frontal lobes after 10 weeks of antipsychotic medication. Significant amelioration of r-CBF correlated with clinical improvement. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Neuro Endocrinol. Lett. 2005 Dec 26: 685-9 |
| PMID | 16380684 |
| Title | Early effects of treatment on regional cerebral blood flow in first episode schizophrenia patients evaluated with 99Tc-ECD-SPECT. |
| Abstract | Altered regional cerebral blood flow (r-CBF) is mentioned as one of possible etiological factors or as a consequence of schizophrenia. Perfusion scintigraphic brain studies with SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) can detect areas of the brain with altered perfusion during the disease. Conflicting data exist on follow-up after treatment. The aim of our study was to evaluate r-CBF in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF. Clinical criteria for schizophrenia were met according to International Classification of Diseases-10th Edition (ICD-10). Psychic status and severity of the disease in each patient were evaluated with psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed 20 minutes after 99mTc-ECD application. R-CBF was measured in 9 first-episode schizophrenic male patients 2-7 (median 6) days after the beginning of antipsychotic treatment and 8-15 (median 9) weeks later. Semiquantitative analysis of r-CBF was performed with cerebellum as the reference region. R-CBF was evaluated for 12 regions in each study. Decrease in perfusion in comparison to cerebellum was detected in left (90%) and right (93%) frontal lobes. Increase in perfusion between the first (t1) and the second (t2) investigation was significant (p<0.05) for both frontal regions (left 94%, right 97%). Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with the increase of r-CBF. Our findings implicate that patients with first-episode schizophrenia have significant left hypoperfusion relative to the right in dorsolateral frontal lobes. Increased blood flow was observed bilaterally in dorsolateral frontal lobes after 10 weeks of antipsychotic medication. Significant amelioration of r-CBF correlated with clinical improvement. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Int J Med Sci 2005 -1 2: 79-86 |
| PMID | 15968344 |
| Title | Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging. |
| Abstract | Many neuroimaging studies of schizophrenia have shown abnormalities in the frontal cortex, limbic system, basal ganglia, temporal and parietal lobes. These findings are not specific or consistent enough to build up a coherent theory of the origin of the brain abnormality in schizophrenia. This paper describes a state-of-the-art approach of SPECT to correlate neuropsychological evaluation. PANSS scores and different brain focal abnormalities of two groups of patients receiving Clozapine and classical antipsychotic treatments were observed. A total of 20 drug-free patients, actively psychotic schizophrenic, were selected according to the DSM-IV criteria. Pre-Post-treatment was designed using PANSS and 99mTc- ECD-SPECT to assess regional Cerebral Blood Flow (rCBF). The results showed that after treatment, differences in PANSS scores were significant in both groups, with superior scores resulting from the Clozapine therapy. Results were supported by SPECT, which showed a greater improvement in the Clozapine group. Both positive and negative symptoms were improved with Clozapine as well. Before treatment, hypofrontality was the most common (85%) finding, whereas after treatment hypofrontality was mostly cleared. However, in some areas like temporal and caudate, hyperfrontality was induced. Negative symptoms showed linkage to hypofrontality in both groups before and after treatment, and both positive and negative symptoms were improved more with Clozapine therapy than with classical treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | Int J Med Sci 2005 -1 2: 79-86 |
| PMID | 15968344 |
| Title | Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging. |
| Abstract | Many neuroimaging studies of schizophrenia have shown abnormalities in the frontal cortex, limbic system, basal ganglia, temporal and parietal lobes. These findings are not specific or consistent enough to build up a coherent theory of the origin of the brain abnormality in schizophrenia. This paper describes a state-of-the-art approach of SPECT to correlate neuropsychological evaluation. PANSS scores and different brain focal abnormalities of two groups of patients receiving Clozapine and classical antipsychotic treatments were observed. A total of 20 drug-free patients, actively psychotic schizophrenic, were selected according to the DSM-IV criteria. Pre-Post-treatment was designed using PANSS and 99mTc- ECD-SPECT to assess regional Cerebral Blood Flow (rCBF). The results showed that after treatment, differences in PANSS scores were significant in both groups, with superior scores resulting from the Clozapine therapy. Results were supported by SPECT, which showed a greater improvement in the Clozapine group. Both positive and negative symptoms were improved with Clozapine as well. Before treatment, hypofrontality was the most common (85%) finding, whereas after treatment hypofrontality was mostly cleared. However, in some areas like temporal and caudate, hyperfrontality was induced. Negative symptoms showed linkage to hypofrontality in both groups before and after treatment, and both positive and negative symptoms were improved more with Clozapine therapy than with classical treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Hum Psychopharmacol 2005 Jun 20: 243-8 |
| PMID | 15830401 |
| Title | An open study of risperidone liquid in the acute phase of schizophrenia. |
| Abstract | An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | Hum Psychopharmacol 2005 Jun 20: 243-8 |
| PMID | 15830401 |
| Title | An open study of risperidone liquid in the acute phase of schizophrenia. |
| Abstract | An open-label study was performed to investigate the clinical efficacy and mechanisms of risperidone liquid in ameliorating positive symptoms in the acute phase of schizophrenia. Eighty-eight patients (M/F: 50/38; age: 18-74 years;, mean +/- SD =32 +/- 16 years) meeting DSM-IV criteria for schizophrenia and treated with risperidone liquid (14 patients also used lorazepam) were evaluated with regard to their clinical improvement and extrapyramidal side effects using the positive and negative syndrome scale (PANSS) and the Simpson and Angus scale (SAS), while plasma concentrations of HVA and MHPG were analysed by HPLC-ECD before and 4 weeks after risperidone liquid administration. Patients showing a 50% or greater improvement in PANSS scores were defined as responders. An improvement in the PANSS scores related to excitement, hostility and poor impulse control was seen within 7 days after administration of risperidone liquid, and an improvement with regard to hallucinatory behaviour and uncooperativeness was seen within 14 days after its administration. Finally, 68% of patients were classified as responders 4 weeks after risperidone liquid administration. The scores of SAS were not changed after risperidone liquid administration. Pretreatment plasma homovanillic acid (HVA) levels in the responders (8.1 +/- 2.9 ng/ml) were higher than those in nonresponders (5.9 +/- 1.9 ng/ml). In addition, a negative correlation was seen between the changes in plasma HVA levels and the percentage of improvement in PANSS scores. On the other hand, there were no differences between pretreatment plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and those of nonresponders. These results suggest that risperidone liquid is effective and well tolerated for the treatment of acute phase schizophrenic patients, and that efficacy is related to its affects on dopaminergic activity, not noradrenergic activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | J. Mol. Graph. Model. 2008 Jun 26: 1333-7 |
| PMID | 18329305 |
| Title | Model of the extracellular domain of the human alpha7 nAChR based on the crystal structure of the mouse alpha1 nAChR extracellular domain. |
| Abstract | Neuronal nicotinic acetylcholine receptors (nAChRs) are important therapeutic targets for various diseases, including Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for cessation of smoking. Based on the recently determined crystal structure of the extracellular domain (ECD) of the mouse nAChR alpha1 subunit complexed with alpha-bungarotoxin at 1.94A resolution, we have constructed three-dimensional models of the ECD of the monomer, homodimer, and homopentamer of the human alpha7 nAChR and investigated in detail the interface between the two alpha7 subunits. The docking of the agonist in the ligand-binding pocket of the human alpha7 dimer was also performed and found consistent with results from labeling and mutagenesis experiments. Since the nAChR ligand-binding site is a useful target for mutagenesis studies and the rational design of drugs against diseases, these models provide useful information for future work. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | Eur. Psychiatry 2010 Oct 25: 361-5 |
| PMID | 20615670 |
| Title | Characteristic brain hypoperfusion by 99mTc-ECD single photon emission computed tomography (SPECT) in patients with the first-episode schizophrenia. |
| Abstract | In this study, we evaluated brain perfusion in patients with first-episode medicated schizophrenia using the new analytical method, statistical parametric mapping (SPM) applied to single photon emission computed tomography (SPECT). We performed SPECT with 99-Tc-ethyl cysteinate dimer (99mTc-ECD) of the brain and magnetic resonance imaging (MRI) in patients with schizophrenia (n=30) and control subjects matched for age and gender (n=37). A voxel-by-voxel group analysis was performed using SPM2 (Z>3.0, P<0.001, uncorrected for multiple comparisons). In comparison with control subjects, the volumes of the bilateral frontal areas were found to be decreased on MRI. Blood flow was found to be reduced in the bilateral temporal areas in the patients with schizophrenia on SPECT. In this study, patients with first-episode schizophrenia appeared to have significant bilateral temporal hypoperfusion, although temporal volumes were not significantly decreased in comparison with control subjects. Abnormality of temporal lobe blood flow in schizophrenia may show that functional changes occur earlier than structural changes, and may assist in the diagnosis of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | Neuropharmacology 2010 Jun 58: 1199-205 |
| PMID | 20211191 |
| Title | Hyperactivity of the dopaminergic system in NTS1 and NTS2 null mice. |
| Abstract | Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors, NTS1 and NTS2. The functional-anatomical interactions between NT, the mesotelencephalic dopamine system, and structures targeted by dopaminergic projections have been studied. The present study was conducted to determine the effects of NT receptor subtypes on dopaminergic function with the use of mice lacking either NTS1 (NTS1(-/-)) or NTS2 (NTS2(-/-)). Basal and amphetamine-stimulated locomotor activity was determined. In vivo microdialysis in freely moving mice, coupled with HPLC-ECD, was used to detect basal and d-amphetamine-stimulated striatal extracellular dopamine levels. In vitro radioligand binding and synaptosomal uptake assays for the dopamine transporters were conducted to test for the expression and function of the striatal pre-synaptic dopamine transporter. NTS1(-/-) and NTS2(-/-) mice had higher baseline locomotor activity and higher basal extracellular dopamine levels in striatum. NTS1(-/-) mice showed higher locomotor activity and exaggerated dopamine release in response to d-amphetamine. Both NTS1(-/-) and NTS2(-/-) mice exhibited lower dopamine D(1) receptor mRNA expression in the striatum relative to wild type mice. Dopamine transporter binding and dopamine reuptake in striatum were not altered. Therefore, lack of either NTS1 or NTS2 alters the dopaminergic system. The possibility that the dysregulation of dopamine transmission might stem from a deficiency in glutamate neurotransmission is discussed. The data strengthen the hypothesis that NT receptors are involved in the pathogenesis of schizophrenia and provide a potential model for the biochemical changes of the disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | J. Neurochem. 2011 Jun 117: 1066-74 |
| PMID | 21517849 |
| Title | Systemic administration of neuregulin-1?1 protects dopaminergic neurons in a mouse model of Parkinson's disease. |
| Abstract | Neuregulin-1 (Nrg1) is genetically linked to schizophrenia, a disease caused by neurodevelopmental imbalance in dopaminergic function. The Nrg1 receptor ErbB4 is abundantly expressed on midbrain dopaminergic neurons. Nrg1 has been shown to penetrate blood-brain barrier, and peripherally administered Nrg1 activates ErbB4 and leads to a persistent hyperdopaminergic state in neonatal mice. These data prompted us to study the effect of peripheral administration of Nrg1 in the context of Parkinson's disease, a neurodegenerative disorder affecting the dopaminergic system in the adult brain. We observed that systemic injections of the extracellular domain of Nrg1?(1) (Nrg1?(1)-ECD) increased dopamine levels in the substantia nigra and striatum of adult mice. Nrg1?(1)-ECD injections also significantly protected the mouse nigrostriatal dopaminergic system morphologically and functionally against 6-hydroxydopamine-induced toxicity in vivo. Moreover, Nrg1?(1)-ECD also protected human dopaminergic neurons in vitro against 6-hydroxydopamine. In conclusion, we have identified Nrg1?(1)-ECD as a neurotrophic factor for adult mouse and human midbrain dopaminergic neurons with peripheral administratability, warranting further investigation as therapeutic option for Parkinson's disease patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | Neuropharmacology 2011 Dec 61: 1413-8 |
| PMID | 21903113 |
| Title | Biodistribution and brain permeability of the extracellular domain of neuregulin-1-?1. |
| Abstract | Neuregulin-1 (NRG1) belongs to a large family of growth and differentiation factors with a key role in the development and maintenance of the brain. Genetic association of NRG1 within brain disorders such as Alzheimer's disease, schizophrenia and neuroprotective properties of certain NRG1 isoforms have led to a variety of studies in corresponding disease models. In the present work, we investigated NRG1 with regard to its peripheral and central biodistribution after systemic application. We first-time radiolabeled the entire biologically active extracellular domain of NRG1 isotype-?1 (NRG1-?1 ECD; aa 2-246) with iodine-125 and administered it peripherally to healthy adult C57Bl6 mice. Blood kinetics and relative organ distribution of (125)I-labeled NRG1-?1 ECD were determined. The blood level of NRG1-?1 ECD peaked within the first hour after intraperitoneal (i.p.) application. The brain-blood ratios of (125)I-labeled NRG1-?1 ECD were time-dependently 150-370% higher compared to the brain impermeable control, (131)I-labeled bovine serum albumin. Autoradiographs of brain slices demonstrated that (125)I-labeled NRG1-?1 ECD accumulated in several regions of the brain e.g. frontal cortex, striatum and ventral midbrain containing the substantia nigra. In addition we found histochemical and biochemical evidence that phosphorylation of the NRG1 prototype receptor ErbB4 was increased in these regions after systemic application of NRG1-?1 ECD. Our data suggest that NRG1-?1 ECD passes the blood-brain barrier and activates cerebral ErbB4 receptors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 20 | Psychiatry Res 2012 May 202: 155-60 |
| PMID | 22698762 |
| Title | Functional involvement of superior temporal sulcus in quality of life of patients with schizophrenia. |
| Abstract | The aim of this study was to investigate the neural substrate underlying quality of life (QoL) in patients with schizophrenia. Thirty-one right-handed patients were included. Patients were grouped according to 'high' and 'low' QoL levels. Whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD), for the measurement of voxel-based regional cerebral blood flow (rCBF), was used to compare these two groups with Statistical Parametric Mapping. Correlations of rCBF with QoL scores were secondarily explored. Nineteen of the 31 patients had a high QoL level. There was no significant difference in demographic and clinical characteristics between patients with high and low QoL levels. In comparison to patients with low QoL, those with high QoL exhibited significant bilateral temporal hypoperfusions, primarily in the superior temporal sulcus (STS). In the total group of patients, perfusion in the left STS was negatively correlated with psychological well-being, self-esteem, and sentimental life, as well as with the global index of the questionnaire. This study shows that perfusion of the STS, a brain area thought to contribute to self/other awareness and metacognition, is involved in the functional substrate underlying QoL. Our findings contribute to clarifying the scientific foundation required for a better clinical use of QoL questionnaires by suggesting that the recognition of illness-related impairment is associated with alteration of QoL. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 21 | Psychoneuroendocrinology 2014 Dec 50: 95-105 |
| PMID | 25199983 |
| Title | Neurophysiological correlates of metabolic syndrome and cognitive impairment in schizophrenia: a structural equation modeling approach. |
| Abstract | We aimed to investigate the brain functional substrate underlying relationships between metabolic syndrome (MetS) and cognitive impairment in schizophrenia. In this cross-sectional study, we collected socio-demographic, clinical, anthropometric, blood, and cognition data and performed brain 99mTc-ECD-SPECT imaging of cerebral blood flow in patients with schizophrenia. Patients were grouped according to the absence or presence of MetS. Whole-brain perfusion SPECTs were compared at voxel level between these two groups, and voxel-wise interregional correlation was performed to compare functional connectivity (voxel level significance of p<0.005, uncorrected; p<0.05 for the cluster, uncorrected; using SPM8). A structural equation model (SEM) was applied to examine the relationships between brain perfusion, connectivity between brain areas, and cognition. Of the 55 patients, 17 had MetS. They performed significantly worse than patients without MetS on tests of executive functions (processing speed p=0.005 for TMT-A; and reactive flexibility p=0.014 for TMT-B), attention (D2 attention task p=0.007), and memory (California Verbal Learning Test p=0.039). In comparison to patients without MetS, those with MetS exhibited significant hypoperfusion within the left orbital prefrontal cortex and greater functional connectivity from this left frontal cluster within the left insula and middle/superior frontal gyrus. SEM confirmed the effect on executive functions of brain hypoperfusion and of increased connectivity, suggesting possible compensatory networks in patients with MetS. Our study identifies the brain functional impact of MetS on cognition, with orbital prefrontal impairment and possible compensatory networks. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 22 | J. Alzheimers Dis. 2014 -1 39: 809-22 |
| PMID | 24284366 |
| Title | Dementia in middle-aged patients with schizophrenia. |
| Abstract | Although numerous studies have assessed cognitive dysfunction in patients with schizophrenia, very few have focused on the diagnosis of dementia. Our objectives were to accurately diagnose dementia in a cohort of middle-aged patients with schizophrenia and to assess the type of dementia. 96 patients with schizophrenia (46 inpatients and 50 outpatients), aged 50 to 70 years, underwent a psychiatric, neurological, and neuropsychological evaluation at baseline and after a 20-month follow-up. We established a 3-step procedure: 1) diagnose dementia according to the DSM-IV criteria, using the Mattis Dementia Rating and Activities of Daily Living scales; 2) characterize dementia using brain imaging, perfusion by 99mTc-ECD-SPECT and laboratory tests including Alzheimer's disease cerebrospinal fluid biomarkers; and 3) search for genetic determinants. Fourteen patients fulfilled the diagnostic criteria of dementia. Four were diagnosed with possible or probable behavioral-variant frontotemporal dementia (bvFTD), two with probable Alzheimer's disease, two with probable vascular dementia (including one due to CADASIL), one with CNS inflammatory disease, and six could not be fully characterized. The diagnosis of dementia in middle-aged patients with schizophrenia is challenging but possible, using a multistep procedure. The most frequent condition, bvFTD, could reflect the presence of an evolutive neurodegenerative process in some patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 23 | Schizophr. Res. 2015 Feb 161: 439-45 |
| PMID | 25497439 |
| Title | Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia. |
| Abstract | Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [(99m)Tc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 24 | Eur Arch Psychiatry Clin Neurosci 2016 Feb 266: 13 |
| PMID | 26078259 |
| Title | Erratum to: Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-ECD. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 25 | Eur Arch Psychiatry Clin Neurosci 2016 Feb 266: 3-12 |
| PMID | 26015391 |
| Title | Regional cerebral blood flow in late-onset schizophrenia: a SPECT study using 99mTc-ECD. |
| Abstract | Progressive disability in schizophrenia has been considered to be associated with onset-age. The objective of this study was to evaluate age onset-related degeneration in rCBF in patients with schizophrenia. We evaluated characteristic changes in brain perfusion by age, gender, medication and clinical symptoms in medicated patients with early-onset (EOS: developed at younger than 40 years old: n = 44) and late-onset (LOS: developed at older than 40 years old: n = 19) schizophrenia and control subjects matched for age and gender (n = 37) using statistical parametric mapping (SPM8) applied to 99mTc-ECD SPECT. We performed SPECT with 99mTc-ECD on the brains of subjects. A voxel-by-voxel group analysis was performed using SPM 8 and ANOVA. rCBF in EOS was found to be reduced in the precentral and inferior frontal gyri; on the other hand, rCBF was reduced in the bilateral postcentral gyrus in LOS. This study revealed a significant difference in brain perfusion between EOS and LOS. The present study might suggest that the characteristic changes in rCBF are related to onset-age in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 26 | Psychiatry Res 2016 Mar 249: 67-75 |
| PMID | 27000309 |
| Title | Functional brain substrate of quality of life in patients with schizophrenia: A brain SPECT multidimensional analysis. |
| Abstract | The aim of this study was to investigate the functional brain substrate of quality of life (QoL) in patients with schizophrenia. Participants comprised 130 right-handed patients with schizophrenia who underwent whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD) for exploring correlations of regional cerebral blood flow (rCBF) with the eight dimensions score of the schizophrenia Quality of Life questionnaire (S-QoL 18). A significant positive correlation was found between the global index of the S-QoL 18 and rCBF in the right superior temporal sulcus and between psychological well-being dimension and rCBF in Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem dimension and rCBF in striatum and between family relationship dimension and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and between relationship with friends dimension and rCBF in BA44 and between physical well-being dimension and rCBF in parahippocampal gyrus, and finally between autonomy dimension and rCBF in cuneus and precuneus. A significant negative correlation was found between resilience dimension and rCBF in precuneus and between sentimental life dimension and rCBF in BA10. Our findings provide neural correlates of QoL. Brain regions involved in cognitions, emotional information processing and social cognition underlie the different QoL dimensions. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |