| 1 | Neuroimage 2001 Sep 14: 531-45 |
|---|---|
| PMID | 11506528 |
| Title | Statistical analysis of hippocampal asymmetry in schizophrenia. |
| Abstract | The asymmetry of brain structures has been studied inschizophreniato better understand its underlying neurobiology. Brain regions of interest have previously been characterized by volumes, cross-sectional and surface areas, and lengths. Using high-dimensional brain mapping, we have developed a statistical method for analyzing patterns of left-right asymmetry of the human hippocampus taken from high-resolution MR scans. We introduce asymmetry measures that capture differences in the patterns of high-dimensional vector fields between the left and right hippocampus surfaces. In 15 pairs of subjects previously studied (J. G. Csernansky et al., 1998,PROC. Natl. Acad. Sci. USA 95, 11406-11411). we define the difference in hippocampal asymmetry patterns between the groups. Volume analysis indicated a large normative asymmetry between left and right hippocampus (R > L), and shape analysis allowed us to visualize the normative asymmetry pattern of the hippocampal surfaces. We observed that the right hippocampus was wider along its lateral side in bothschizophreniaand control subjects. Also, while patterns of hippocampal asymmetry were generally similar in theschizophreniaand control groups, a principal component analysis based on left-right asymmetry vector fields detected a statistically significant difference between the two groups, specifically related to the subiculum. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 2 | Int J Psychophysiol 2002 May 44: 101-15 |
| PMID | 11909645 |
| Title | Cortical connectivity in high frequency beta-rhythm in schizophrenics with positive and negative symptoms. |
| Abstract | During the last decade the role of high frequency EEG activity in the 'binding phenomenon' was discovered. It was supposed that this phenomenon provided the integration between different brain structures underlying higher nervous functions and possibly even consciousness [PROC. Natl. Acad. Sci. 90 (1993) 2078; Annu. Rev. Neurosci. 18 (1995) 555; J. Neurosci. V 16 (1996) 4240; Am. Physiol. Soc. (1998) 1567; Induced Rhythms in the Brain (1992) 425; NeuroReport 8 (1997) 531;PROC. Natl. Acad. Sci. USA 94 (1997) 12198].schizophreniais considered as a disorder of the integration between different brain regions [Review of Psychiatry 18 (1999a) 29; Conceptual Advances in Russian Neuroscience: Complex Brain Functions (1999) 151; Brain Res. Rev. 31 (2000) 301], and in the present work we have studied cortical connectivity, focusing on those connections which are maintained by high frequency EEG-rhythm (20-40 Hz). The results showed a high degree of biopotential synchronisation between definite cortical areas during cognitivePROCesses in normal subjects and have evidenced significant functional connectivity disturbances inschizophreniain this EEG frequency domain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 3 | Int J Psychophysiol 2002 May 44: 101-15 |
| PMID | 11909645 |
| Title | Cortical connectivity in high frequency beta-rhythm in schizophrenics with positive and negative symptoms. |
| Abstract | During the last decade the role of high frequency EEG activity in the 'binding phenomenon' was discovered. It was supposed that this phenomenon provided the integration between different brain structures underlying higher nervous functions and possibly even consciousness [PROC. Natl. Acad. Sci. 90 (1993) 2078; Annu. Rev. Neurosci. 18 (1995) 555; J. Neurosci. V 16 (1996) 4240; Am. Physiol. Soc. (1998) 1567; Induced Rhythms in the Brain (1992) 425; NeuroReport 8 (1997) 531;PROC. Natl. Acad. Sci. USA 94 (1997) 12198].schizophreniais considered as a disorder of the integration between different brain regions [Review of Psychiatry 18 (1999a) 29; Conceptual Advances in Russian Neuroscience: Complex Brain Functions (1999) 151; Brain Res. Rev. 31 (2000) 301], and in the present work we have studied cortical connectivity, focusing on those connections which are maintained by high frequency EEG-rhythm (20-40 Hz). The results showed a high degree of biopotential synchronisation between definite cortical areas during cognitivePROCesses in normal subjects and have evidenced significant functional connectivity disturbances inschizophreniain this EEG frequency domain. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 4 | Biochim. Biophys. Acta 2004 Nov 1690: 238-49 |
| PMID | 15511631 |
| Title | A high proportion of polymorphisms in the promoters of brain expressed genes influences transcriptional activity. |
| Abstract | There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains ofschizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronicschizophrenia.PROC. Natl. Acad. Sci. 98 (2001) 4746-4751.]. We found 60 variants distributed across 31 of the genes. A total of 77 haplotypes representing 28 different putative promoters were analyzed in a reporter gene assay in two cell lines. Of a total of 54 sequence variants represented in the haplotypes, 12 (or around 22%) were functional according to a highly conservative definition. These were found in the promoters of eight genes: NPY, PCSK1, NEFL, KIAA0513, LMO4, HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 5 | Biochim. Biophys. Acta 2004 Nov 1690: 238-49 |
| PMID | 15511631 |
| Title | A high proportion of polymorphisms in the promoters of brain expressed genes influences transcriptional activity. |
| Abstract | There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains ofschizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronicschizophrenia.PROC. Natl. Acad. Sci. 98 (2001) 4746-4751.]. We found 60 variants distributed across 31 of the genes. A total of 77 haplotypes representing 28 different putative promoters were analyzed in a reporter gene assay in two cell lines. Of a total of 54 sequence variants represented in the haplotypes, 12 (or around 22%) were functional according to a highly conservative definition. These were found in the promoters of eight genes: NPY, PCSK1, NEFL, KIAA0513, LMO4, HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 6 | Ann. N. Y. Acad. Sci. 2004 Oct 1025: 84-91 |
| PMID | 15542704 |
| Title | Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression. |
| Abstract | DNA microarrays with isotope labeling from gene-specific primers enable sensitive detection of rare mRNAs, including neurotrophin and cytokine mRNAs in the brain. Using high-quality RNA from postmortem brains, gene-expression profiles covering 1373 genes were assessed in the dorsoprefrontal cortex ofschizophrenicpatients and compared with those of nonpsychiatric subjects. Statistical analysis of the DNA microarray data confirmed the findings of a previous GeneChip study by Hakak et al. (PROC. Natl. Acad. Sci. USA Vol. 98, pp. 4746-4751, 2001). The highest frequency of mRNA expression alterations occurred in oligodendrocyte- and astrocyte-related genes in the prefrontal cortex ofschizophrenicpatients, followed by the category for the genes for growth factors/neurotrophic factors and their receptors. Whether each mRNA signal represents the expression of the individual genes or homologous genes in the category remains to be determined, however. To control for potential medication effects on patients, RNA from cynomolgus monkeys that were treated with haloperidol for 3 months was also subjected to DNA microarray analysis. A few genes overlapped between the gene-expression profiles of the monkeys and patients. The present profiling study suggests a potential biological link between abnormal neurotrophic signals and impaired glial functions inschizophrenic病理 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 7 | Ann. N. Y. Acad. Sci. 2004 Oct 1025: 84-91 |
| PMID | 15542704 |
| Title | Prefrontal abnormality of schizophrenia revealed by DNA microarray: impact on glial and neurotrophic gene expression. |
| Abstract | DNA microarrays with isotope labeling from gene-specific primers enable sensitive detection of rare mRNAs, including neurotrophin and cytokine mRNAs in the brain. Using high-quality RNA from postmortem brains, gene-expression profiles covering 1373 genes were assessed in the dorsoprefrontal cortex ofschizophrenicpatients and compared with those of nonpsychiatric subjects. Statistical analysis of the DNA microarray data confirmed the findings of a previous GeneChip study by Hakak et al. (PROC. Natl. Acad. Sci. USA Vol. 98, pp. 4746-4751, 2001). The highest frequency of mRNA expression alterations occurred in oligodendrocyte- and astrocyte-related genes in the prefrontal cortex ofschizophrenicpatients, followed by the category for the genes for growth factors/neurotrophic factors and their receptors. Whether each mRNA signal represents the expression of the individual genes or homologous genes in the category remains to be determined, however. To control for potential medication effects on patients, RNA from cynomolgus monkeys that were treated with haloperidol for 3 months was also subjected to DNA microarray analysis. A few genes overlapped between the gene-expression profiles of the monkeys and patients. The present profiling study suggests a potential biological link between abnormal neurotrophic signals and impaired glial functions inschizophrenic病理 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 8 | Schizophr. Res. 2004 Jun 68: 203-16 |
| PMID | 15099603 |
| Title | Spatial working memory among middle-aged and older patients with schizophrenia and volunteers using fMRI. |
| Abstract | Goldman-Rakic and Selemon (Schizophr. Bull. 23 (1997)) hypothesized that many of the symptoms ofschizophreniacan be explained by deficits of working memory (WM) that are, in turn, caused by dysfunction of dorsolateral prefrontal cortex (DLPFC). We examined whether older patients withschizophreniawould show an aberrant neural response in the DLPFC or other brain sites when performing a spatial working memory (WM) task adapted from McCarthy et al. (PROC. Natl. Acad. Sci. U. S. A. 91 (1994)). Middle-aged and older patients withschizophrenia或分裂情感性障碍和健康志愿者performed a spatial WM task contrasted with two baselines, passive and active viewing (PV and AV, respectively), while blood oxygen level dependent (BOLD) images were acquired in a functional magnetic resonance study. Patients did not perform significantly less well on the spatial tasks compared to the volunteers. Although we found no significant group effects in spatial WM activation of DLPFC, we did observe areas in medial frontal cortex including the left anterior cingulate gyrus, parietal areas of the both hemispheres, multiple sites within the basal ganglia of the left hemisphere, and the left superior temporal gyrus where healthy volunteers showed greater BOLD response to WM. In a second pattern, patients showed a greater BOLD response to WM in left fusiform gyrus [Brodmann's Area (BA) 19], peri-rolandic areas, medial frontal area; right anterior cerebellum (culmen), middle occipital lobe, and postcentral/supramarginal gyri (BA 2/40). Middle-aged and older patients withschizophreniadisplay normal or near-normal spatial WM activation of DLPFC when thePROCessing demands of the WM task are within their performance capacity. Nonetheless, even when patients perform nearly normally, they demonstrate an aberrant pattern of brain response. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 9 | Pharmacol. Ther. 2006 Jul 111: 272-86 |
| PMID | 16574235 |
| Title | The human reelin gene: transcription factors (+), repressors (-) and the methylation switch (+/-) in schizophrenia. |
| Abstract | A recent report suggests that the down-regulation of reelin and glutamic acid decarboxylase (GAD(67)) mRNAs represents 2 of the more consistent findings thus far described in post-mortem material fromschizophrenia(SZ) patients [reviewed in. Neurochemical markers forschizophrenia, bipolar disorder amd major depression in postmortem brains. Biol Psychiatry 57, 252-260]. To study mechanisms responsible for this down-regulation, we have analyzed the promoter of the human reelin gene. Collectively, our studies suggest that SZ is characterized by a gamma-amino butyric acid (GABA)-ergic neuron pathology presumably mediated by promoter hypermethylation facilitated by the over-expression of the methylating enzyme DNA methyltransferase (Dnmt) 1. Using transient expression assays, promoter deletions and co-transfection assays with various transcription factors, we have shown a clear synergistic action that is a critical component of the mechanism of the trans-activationPROCess. Equally important is the observation that the reelin promoter is more heavily methylated in brain regions in patients diagnosed with SZ as compared to non-psychiatric control subjects [Grayson, D. R., Jia, X., Chen, Y., Sharma, R. P., Mitchell, C. P., & Guidotti, A., et al. (2005). Reelin promoter hypermethylation inschizophrenia.PROCNatl Acad Sci U S A 102, 9341-9346]. The combination of studies in cell lines and in animal models of SZ, coupled with data obtained from post-mortem human material provides compelling evidence that aberrant methylation may be part of a core dysfunction in this psychiatric disease. More interestingly, the hypermethylation concept provides a coherent mechanism that establishes a plausible link between the epigenetic misregulation of multiple genes that are affected in SZ and that collectively contribute to the associated symptomatology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 10 | Neuroscience 2006 -1 137: 37-49 |
| PMID | 16289586 |
| Title | Modeling depression: social dominance-submission gene expression patterns in rat neocortex. |
| Abstract | 基因表达谱的皮质成人瞧ng-Evans rats as a function of a stressful social loss and victory in inter-male fighting encounters were examined. This social dominance and subordination model has been postulated to simulate early changes in the onset of depression in the losers. Microarrays were fabricated containing 45mer oligonucleotides spotted in quadruplicate and representing 1178 brain-associated genes. Dynamic range, discrimination power, accuracy and reproducibility were determined with standard mRNA "spiking" studies. Gene expression profiles in dominant and subordinate animals were compared using a "universal" reference design [Churchill GA (2002) Fundamentals of experimental design for cDNA microarrays. Nat Genet 32 (Suppl):490-495]. Data were analyzed by significance analysis of microarrays using rank scores [Tusher VG, Tibshirani R, Chu G (2001) Significance analysis of microarrays applied to the ionizing radiation response.PROCNatl Acad Sci USA 98:5116-5121; van de Wiel MA (2004) Significance analysis of microarrays using rank scores. Kwantitatieve Methoden 71:25-37]. Ontological analyses were then performed using the GOMiner algorithm [Zeeberg BR, Feng W, Wang G, Wang MD, Fojo AT, Sunshine M, Narasimhan S, Kane DW, Reinhold WC, Lababidi S, Bussey KJ, Riss J, Barrett JC, Weinstein JN (2003) GoMiner: a resource for biological interpretation of genomic and proteomic data. Genome Biol 4(4):R28]. And finally, genes of special interest were further studied using quantitative reverse transcriptase polymerase chain reaction. Twenty-two transcripts were statistically significantly differentially expressed in the neocortex between dominant and subordinate animals. Ontological analyses revealed that significant gene changes were clustered primarily into functional neurochemical pathways associated with protein biosynthesis and cytoskeletal dynamics. The most robust of these were the increased expression of interleukin-18, heat shock protein 27, beta3-tubulin, ribosome-associated membrane protein 4 in subordinate animals. Interleukin-18 has been found to be over-expressed in human depression and panic disorder as well as other physiological stress paradigms [Takeuchi M, Okura T, Mori T, Akita K, Ohta T, Ikeda M, Ikegami H, Kurimoto M (1999) Intracellular production of interleukin-18 in human epithelial-like cell lines is enhanced by hyperosmotic stress in vitro. Cell Tissue Res 297(3):467-473] and heat shock proteins have been shown to be involved in the pathogenesis of many neurodegenerative and psychiatric disorders [Iwamoto K, Kakiuchi C, Bundo M, Ikeda K, Kato T (2004) Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders. Mol Psychiatry 9(4):406-416; Pongrac JL, Middleton FA, Peng L, Lewis DA, Levitt P, Mirnics K (2004) Heat shock protein 12A shows reduced expression in the prefrontal cortex of subjects withschizophrenia. Biol Psychiatry 56(12):943-950]. Thus, the gene expression changes that we have observed here are consistent with and extend the observations found in the clinical literature and link them to the animal model used here thereby reinforcing its use to better understand the genesis of depression and identify novel therapeutic targets for its treatment. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 11 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Apr 144B: 266-70 |
| PMID | 17286247 |
| Title | Positive association of the Disrupted-in-Schizophrenia-1 gene (DISC1) with schizophrenia in the Chinese Han population. |
| Abstract | Disrupted-in-schizophrenia-1 (DISC1) is located on 1q42.1, one of the most promising susceptibility loci inschizophrenialinkage studies. A non-synonymous genetic variation rs821616 (Ser704Cys) in DISC1, has recently been shown to be associated withschizophreniain family-based study [Callicott et al. (2005);PROCNatl Acad Sci USA 102: 8627-8632]. In order to further confirm this issue, we examined four single nucleotide polymorphisms (SNPs) in a chromosomal region spanning 42 kb of this gene, namely rs821616, rs821597, rs4658971, and rs843979, in Chinese sample of 313schizophreniapatients and 317 healthy controls. Our results showed that two SNPs had strong associations withschizophrenia(rs821616: Allele A > T, chi(2) = 7.8006, df = 1, P = 0.0052; Genotype, chi(2) = 7.7935, df = 2, P = 0.0203; rs821597: Allele A > G, chi(2) = 9.5404, df = 1, P = 0.0020; Genotype, chi(2) = 12.2780, df = 2, P = 0.0022). When haplotypes were constructed with two, three, and four markers, a number of haplotype combinations, especially those including rs821616 and rs821597, were significantly associated withschizophrenia. Furthermore, there was a strong evidence for association in a four-marker haplotype analysis (chi(2) = 7.686, df = 4, P = 0.005581, corrected P = 0.006199). Although the case-control and family-based association studies both suggest that DISC1 gene may play a role in genetic susceptibility toschizophrenia, the risk haplotypic combinations have subtle differences in the two studies. Our findings provide further evidence for DISC1 as a predisposing gene involved inschizophreniain the Chinese Han Population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 12 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 470-4 |
| PMID | 19302829 |
| Title | Effects of the DRD3 Ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors. |
| Abstract | Aripiprazole, a novel antipsychotic agent, has a unique pharmacological action (partial agonist) on the dopamine neurotransmission system. Aripiprazole has high affinity for dopamine D2 and D3 receptors (DRD2 and DRD3). We investigated whether the efficacy of aripiprazole can be predicted by a functional DRD3 gene polymorphism Ser9Gly (rs6280) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n=128) were given aripiprazole for up to four weeks. Patients were genotyped for DRD3 Ser9Gly polymorphism by Restriction Fragment Length Polymorphism (RFLP) method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype and medication dosage were recorded. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale (PANSS). The effects of genetic and clinical factors on PANSS performance after aripiprazole treatment were analyzed by a mixed model regression approach (SASPROC混合)。我们发现,尽管Ser运营商have numerically larger score reductions when compared with non-carriers in almost all PANSS dimensions, the difference of their effects are statically not significant. However, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype could influence PANSS performance after aripiprazole treatment. This study suggests that DRD3 Ser9Gly polymorphism may not contribute significantly to inter-individual differences in therapeutic efficacy of aripiprazole, but some clinical factors may predict treatment efficacy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 13 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2009 Apr 33: 470-4 |
| PMID | 19302829 |
| Title | Effects of the DRD3 Ser9Gly polymorphism on aripiprazole efficacy in schizophrenic patients as modified by clinical factors. |
| Abstract | Aripiprazole, a novel antipsychotic agent, has a unique pharmacological action (partial agonist) on the dopamine neurotransmission system. Aripiprazole has high affinity for dopamine D2 and D3 receptors (DRD2 and DRD3). We investigated whether the efficacy of aripiprazole can be predicted by a functional DRD3 gene polymorphism Ser9Gly (rs6280) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n=128) were given aripiprazole for up to four weeks. Patients were genotyped for DRD3 Ser9Gly polymorphism by Restriction Fragment Length Polymorphism (RFLP) method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype and medication dosage were recorded. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale (PANSS). The effects of genetic and clinical factors on PANSS performance after aripiprazole treatment were analyzed by a mixed model regression approach (SASPROC混合)。我们发现,尽管Ser运营商have numerically larger score reductions when compared with non-carriers in almost all PANSS dimensions, the difference of their effects are statically not significant. However, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype could influence PANSS performance after aripiprazole treatment. This study suggests that DRD3 Ser9Gly polymorphism may not contribute significantly to inter-individual differences in therapeutic efficacy of aripiprazole, but some clinical factors may predict treatment efficacy. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 14 | J Psychiatr Res 2009 Mar 43: 600-6 |
| PMID | 18926547 |
| Title | Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. |
| Abstract | Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors (DRD2). We investigate whether its efficacy is predictable by DRD2/ANKK1 gene polymorphisms and clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n=128) were given aripiprazole for up to 4 weeks. They were genotyped for four functional DRD2/ANKK1 polymorphisms: -141 Ins/Del, Ser311Cys, C957T, and TaqIA. Clinical factors such as gender, age, illness duration, education level, diagnostic subtype, and medication dosage were also recorded. Psychopathology was measured biweekly with the positive and negative syndrome scale (PANSS). The effects of genetic and clinical factors on PANSS performance upon aripiprazole treatment were analyzed by a mixed modeling approach (SASPROC混合)。 Compared to the patients with TaqI A2/A2 genotype, A1 carriers are associated with superior therapeutic response on positive symptoms after 4-week aripiprazole treatment. Regarding the C957T polymorphism, patients with C/C genotype were associated with poor aripiprazole response for excitement symptoms when compared with T/T patients. The other two polymorphisms, -141 Ins/Del, and Ser311Cys, have no significant effects on PANSS performance. The clinical factors including medication dosage, illness duration, and diagnostic subtype could influence PANSS performance upon aripiprazole treatment. This study suggests that DRD2/ANKK1 gene variations and some clinical factors may predict individual response to aripiprazole. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 15 | J Psychiatr Res 2009 Mar 43: 600-6 |
| PMID | 18926547 |
| Title | Effects of DRD2/ANKK1 gene variations and clinical factors on aripiprazole efficacy in schizophrenic patients. |
| Abstract | Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors (DRD2). We investigate whether its efficacy is predictable by DRD2/ANKK1 gene polymorphisms and clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n=128) were given aripiprazole for up to 4 weeks. They were genotyped for four functional DRD2/ANKK1 polymorphisms: -141 Ins/Del, Ser311Cys, C957T, and TaqIA. Clinical factors such as gender, age, illness duration, education level, diagnostic subtype, and medication dosage were also recorded. Psychopathology was measured biweekly with the positive and negative syndrome scale (PANSS). The effects of genetic and clinical factors on PANSS performance upon aripiprazole treatment were analyzed by a mixed modeling approach (SASPROC混合)。 Compared to the patients with TaqI A2/A2 genotype, A1 carriers are associated with superior therapeutic response on positive symptoms after 4-week aripiprazole treatment. Regarding the C957T polymorphism, patients with C/C genotype were associated with poor aripiprazole response for excitement symptoms when compared with T/T patients. The other two polymorphisms, -141 Ins/Del, and Ser311Cys, have no significant effects on PANSS performance. The clinical factors including medication dosage, illness duration, and diagnostic subtype could influence PANSS performance upon aripiprazole treatment. This study suggests that DRD2/ANKK1 gene variations and some clinical factors may predict individual response to aripiprazole. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 16 | Psychopharmacology (Berl.) 2009 Aug 205: 285-92 |
| PMID | 19387614 |
| Title | HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients. |
| Abstract | Aripiprazole acts as a partial agonist at dopamine D2 and D3 and serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A). Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may be important in explaining variability in response to aripiprazole. This study investigated whether the efficacy of aripiprazole can be predicted by functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n = 128) were given a 4-week course of aripiprazole. Patients were genotyped for HTR2A A-1438G/T102C polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype, and medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS). A mixed model regression approach (SASPROCMIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment. We found that the GG/CC genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole response specifically for negative symptoms. In addition, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype, were found to influence PANSS performance after aripiprazole treatment. The data suggest HTR2A A-1438G/T102C polymorphisms may predict negative symptoms performance upon aripiprazole treatment inschizophrenicpatients as modified by clinical factors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 17 | Psychopharmacology (Berl.) 2009 Aug 205: 285-92 |
| PMID | 19387614 |
| Title | HTR2A A-1438G/T102C polymorphisms predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients. |
| Abstract | Aripiprazole acts as a partial agonist at dopamine D2 and D3 and serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A). Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may be important in explaining variability in response to aripiprazole. This study investigated whether the efficacy of aripiprazole can be predicted by functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbatedschizophrenia. After hospitalization, the patients (n = 128) were given a 4-week course of aripiprazole. Patients were genotyped for HTR2A A-1438G/T102C polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype, and medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS). A mixed model regression approach (SASPROCMIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment. We found that the GG/CC genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole response specifically for negative symptoms. In addition, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype, were found to influence PANSS performance after aripiprazole treatment. The data suggest HTR2A A-1438G/T102C polymorphisms may predict negative symptoms performance upon aripiprazole treatment inschizophrenicpatients as modified by clinical factors. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 18 | >。461年。2009年9月:54-9 |
| PMID | 19477230 |
| Title | Evidence that variation in the oligodendrocyte lineage transcription factor 2 (OLIG2) gene is associated with psychosis in Alzheimer's disease. |
| Abstract | 精神病症状在患者很常见Alzheimer's disease (AD), and define a phenotype associated with more rapid cognitive and functional decline. Evidence suggests that psychotic symptoms may be influenced by genetic factors, and recent studies inschizophrenia, bipolar affective disorder (BPAD) and Alzheimer's disease with psychosis (AD+P) suggest that psychosis susceptibility or modifier genes may act across diseases. We hypothesised that oligodendrocyte lineage transcription factor 2 (OLIG2), a regulator of white matter development and a candidate gene forschizophrenia,我也可能伴有精神病症状n AD. We genotyped 11 SNPs in OLIG2 previously tested for association withschizophrenia[L. Georgieva, V. Moskvina, T. Peirce, N. Norton, N.J. Bray, L. Jones, P. Holmans, S. Macgregor, S. Zammit, J. Wilkinson, H. Williams, I. Nikolov, N. Williams, D. Ivanov, K.L. Davis, V. Haroutunian, J.D. Buxbaum, N. Craddock, G. Kirov, M.J. Owen, M.C. O'Donovan, Convergent evidence that oligodendrocyte lineage transcription factor 2 (OLIG2) and interacting genes influence susceptibility toschizophrenia,PROC. Natl. Acad. Sci. U.S.A. 103 (33) (2006) 12469-12474] and tested these for association with AD and AD+P. Significant evidence for association of psychotic symptoms within cases was identified for two SNPs, rs762237 (allelic P=0.002, OR=1.42, corrected P=0.019) and rs2834072 (allelic P=0.004, OR=1.41, corrected P=0.05). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 19 | Iran J Psychiatry 2011 -1 6: 128-32 |
| PMID | 22952537 |
| Title | Exploratory Factor Analysis of SCL90-R Symptoms Relevant to Psychosis. |
| Abstract | Inconsistent results have been reported regarding the symptom dimensions relevant to psychosis in symptoms check list revised (SCL90-R), i.e., "psychoticism" and "paranoid ideation". Therefore, some studies have suggested different factor structures for questions of these two dimensions, and proposed two newly defined dimensions of "schizotypalsigns" and "schizophrenianuclear symptoms". We conducted an exploratory factor analysis on the items of these two dimensions in a general population sample in Iran. A total of 2158 subjects residing in Southern Tehran (capital of Iran) were interviewed using the psychoticism and paranoid ideation questions in SCL90-R to assess severity of these symptom dimensions. Factor analysis was done through SAS 9.1.3PROCFACTOR using Promax rotation (power=3) on the matrix of "polychoric correlations among variables" as the input data. Two factors were retained by the proportion criterion. Considering loadings >= 0.5 as minimum criteria for factor loadings, 7 out of 10 questions from psychoticism, and 3 out of 6 questions from paranoid ideation were retained, and others were eliminated. The factor labels proposed by the questionnaire suited the extracted factors and were retained. Internal consistency for each of the dimensions was acceptable (Cronbach's alpha 0.7 and 0.74 for paranoid ideation and psychoticism respectively). Composite scores showed a half-normal distribution for both dimensions which is predictable for instruments that detect psychotic symptoms. Results were in contrast with similar studies, and questioned them by suggesting a different factor structure obtained from a statistically large population. The population in a developing nation (Iran) in this study and the socio-cultural differences in developed settings are the potential sources for discrepancies between this analysis and previous reports. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 20 | Iran J Psychiatry 2011 -1 6: 128-32 |
| PMID | 22952537 |
| Title | Exploratory Factor Analysis of SCL90-R Symptoms Relevant to Psychosis. |
| Abstract | Inconsistent results have been reported regarding the symptom dimensions relevant to psychosis in symptoms check list revised (SCL90-R), i.e., "psychoticism" and "paranoid ideation". Therefore, some studies have suggested different factor structures for questions of these two dimensions, and proposed two newly defined dimensions of "schizotypalsigns" and "schizophrenianuclear symptoms". We conducted an exploratory factor analysis on the items of these two dimensions in a general population sample in Iran. A total of 2158 subjects residing in Southern Tehran (capital of Iran) were interviewed using the psychoticism and paranoid ideation questions in SCL90-R to assess severity of these symptom dimensions. Factor analysis was done through SAS 9.1.3PROCFACTOR using Promax rotation (power=3) on the matrix of "polychoric correlations among variables" as the input data. Two factors were retained by the proportion criterion. Considering loadings >= 0.5 as minimum criteria for factor loadings, 7 out of 10 questions from psychoticism, and 3 out of 6 questions from paranoid ideation were retained, and others were eliminated. The factor labels proposed by the questionnaire suited the extracted factors and were retained. Internal consistency for each of the dimensions was acceptable (Cronbach's alpha 0.7 and 0.74 for paranoid ideation and psychoticism respectively). Composite scores showed a half-normal distribution for both dimensions which is predictable for instruments that detect psychotic symptoms. Results were in contrast with similar studies, and questioned them by suggesting a different factor structure obtained from a statistically large population. The population in a developing nation (Iran) in this study and the socio-cultural differences in developed settings are the potential sources for discrepancies between this analysis and previous reports. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 21 | J Hist Neurosci 2013 -1 22: 62-78 |
| PMID | 23323533 |
| Title | History of the discovery of the antipsychotic dopamine D2 receptor: a basis for the dopamine hypothesis of schizophrenia. |
| Abstract | The 1975 publication of Seeman et al. (PROCNat Acad Sci, USA), reporting the discovery of the antipsychotic receptor in the brain, is a classic example of translational medicine research. In searching for a pathophysiological mechanism of psychosis, the team sought to identify sites that bound the antipsychotic drug haloperidol. Their criterion was that haloperidol bound to the site at one to two nanomoles per liter, corresponding to haloperidol concentrations found in spinal fluid or plasma water in treated patients. They requested de novo synthesis of tritiated haloperidol, and it readily detected specific haloperidol binding sites in brain striatum. With dopamine binding the haloperidol-labeled sites with higher potency than other neurotransmitters, the sites were named antipsychotic/dopamine receptors (now designated dopamine D2 receptors). Most significantly, they found that all antipsychotics bound these sites at concentrations and with a rank order of potencies that were directly related to the mean daily antipsychotic dose taken by patients withschizophrenia. Their findings enabled screening for new antipsychotics, initiated D2 receptor measurements in brain of living patients, and determination of minimum occupancy (65%) of D2 receptors for antipsychotic benefit. The collective work is generally viewed as providing a fundamental basis for the dopamine hypothesis ofschizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 22 | Med. Hypotheses 2014 Mar 82: 377-81 |
| PMID | 24495565 |
| Title | Altitude is a risk factor for completed suicide in bipolar disorder. |
| Abstract | Bipolar disorder (BD) is a severe brain disease that is associated with a significant risk for suicide. Recent studies indicate that altitude of residence significantly affects overall rate of completed suicide, and is associated with a higher incidence of depressive symptoms. Bipolar disorder has shown to be linked to mitochondrial dysfunction that may increase the severity of episodes. The present study used existing data sets to explore the hypothesis that altitude has a greater effect of suicide in BD, compared with other mental illnesses. The study utilized data extracted from the National Violent Death Reporting System (NVDRS), a surveillance system designed by the Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control (NCIPC). Data were available for 16 states for the years 2005-2008, representing a total of 35,725 completed suicides in 922 U.S. counties. Random coefficient and logistic regression models in the SASPROCMIXEDPROC一些探讨被用来估计高度的影响on decedent's mental health diagnosis. Altitude was a significant, independent predictor of the altitude at which suicides occurred (F=8.28, p=0.004 and Wald chi-square=21.67, p<0.0001). Least squares means of altitude, independent of other variables, indicated that individuals with BD committed suicide at the greatest mean altitude. Moreover, the mean altitude at which suicides occurred in BD was significantly higher than in decedents whose mental health diagnosis was major depressive disorder (MDD),schizophrenia, or anxiety disorder. Identifying diagnosis-specific risk factors such as altitude may aid suicide prevention efforts, and provide important information for improving the clinical management of BD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |
| 23 | Schizophr Bull 2015 Jan 41: 233-49 |
| PMID | 24557771 |
| Title | Hippocampal volume is reduced in schizophrenia and schizoaffective disorder but not in psychotic bipolar I disorder demonstrated by both manual tracing and automated parcellation (FreeSurfer). |
| Abstract | This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-schizophreniaNetwork on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands withschizophrenia(SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3PROCMIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007-.02) and SAD (P = .003-.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18-.55). All relative groups had hippocampal volumes not different from controls (P = .12-.97) and higher than those observed in probands (P = .003-.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64-.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51-.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker forschizophreniaand schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary diseasePROCesses and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizotypal |