| 1 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2005 Feb 133B: 1-5 |
|---|---|
| PMID | 15645418 |
| Title | Assessing the validity of blood-based gene expression profiles for the classification of schizophrenia and bipolar disorder: a preliminary report. |
| Abstract | Recent advances have facilitated the use of blood-derived RNA to conduct genomic analyses of human diseases. This emerging technology represents a rigorous and convenient alternative to traditional tissue biopsy-derived RNA, as it allows for larger sample sizes, better standardization of technical procedures, and the ability to non-invasively profile human subjects. In the present pilot study, we have collected RNA from blood of patients diagnosed with schizophrenia or bipolar disorder (BPD), as well as normal control subjects. Using microarray analysis, we found that each disease state exhibited a unique expressed genome signature, allowing us to discriminate between the schizophrenia, BPD, and control groups. In addition, we validated changes in several potential biomarker genes for schizophrenia and BPD by RT-PCR, and some of these were found to code to chromosomal loci previously linked to schizophrenia. Linear and non-linear combinations of eight putative biomarker genes (APOBEC3B, ADSS, ATM, CLC, CTBP1, DATF1, CXCL1, and S100A9) were able to discriminate between schizophrenia, BPD, and control samples, with an overall accuracy of 95%-97% as indicated by receiver operating characteristic (ROC) curve analysis. We therefore propose that blood cell-derived RNA may have significant value for performing diagnostic functions and identifying disease biomarkers in schizophrenia and BPD. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 2 | BMC Med. Genet. 2008 -1 9: 119 |
| PMID | 19115993 |
| Title | Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population. |
| Abstract | The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 3 | J. Parasitol. 2008 Jun 94: 757-8 |
| PMID | 18605805 |
| Title | Effects of high pressure processing on Toxoplasma gondii oocysts on raspberries. |
| Abstract | Oocysts are the environmentally resistant life stage of Toxoplasma gondii. Humans can become infected by accidentally ingesting the oocysts in water or from contaminated produce. Severe disease can occur in immunocompromised individuals, and nonimmune pregnant women can infect their offspring. Chronic infection is associated with decreased mental functions, vision and hearing problems, and some mental disorders such as schizophrenia. High pressure processing (HPP) is a commercial method used to treat food to eliminate pathogens. TreATMent of produce to eliminate viable T. gondii oocysts would provide a means to protect consumers. The present study was done to better define the effects of HPP on oocysts placed on raspberries. Raspberries were chosen because they are a known source of a related human intestinal parasite, Cyclospora cayetanensis. Raspberries were inoculated with 5 x 10(4) oocysts of the VEG strain of T. gondii for 20 hr prior to HPP. Individual raspberries were exposed to 500 MPa, 400 MPa, 340 MPa, 300 MPa, 270 MPa, 250 MPa, 200 MPA, 100 MPa, or no MPa treATMent for 60 sec in a commercial HPP unit (1 MPa = 10 ATM = 147 psi). TreATMent of raspberries with 340 MPa for 60 sec was needed to render oocysts spot inoculated on the raspberries noninfectious for mice. TreATMent of raspberries with 200 MPa or less for 60 sec was not effective in rendering oocysts noninfectious for mice. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 4 | BMC Med. Genet. 2008 -1 9: 119 |
| PMID | 19115993 |
| Title | Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population. |
| Abstract | The blood-derived RNA levels of the adenylosuccinate synthase (ADSS) and ataxia telangiectasia mutated (ATM) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and ADSS and ATM were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes. Six SNPs in the ADSS gene and three SNPs in the ATM gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform. There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the ADSS gene and rs227061 and rs664143 in the ATM gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10. These findings suggest that the combined effects of the polymorphisms in the ADSS and ATM genes may confer susceptibility to the development of SZ in a Chinese population. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 5 | Psychiatry Res 2008 Apr 158: 324-34 |
| PMID | 18262656 |
| Title | Attitudes toward medication in inpatients with schizophrenia: a cluster analytic approach. |
| Abstract | Attitudes toward medication (ATM) exert an influential role on compliance. Ninety-nine inpatients with schizophrenia were administered the Rating of Medication Influences scale (ROMI). Patients were also rated using: i) the Health of the Nation Outcome Scales, ii) the Global Assessment of Functioning scale, iii) the Clinical Global Impression, Severity scale, and iv) the WHO Quality Of Life assessment, Brief Version. Seventy-seven subjects (77.8%) completed the ROMI interview. Cluster analysis identified the following four clusters: i) Ambivalence (n=17; 22%); ii) Problems with Patient, Family, Alliance (n=11; 14.3%); iii) Medication Affinity, Positive Influence from Others (n=30; 39%); and iv) Illness, Medication, Label Distress (n=19; 24.7%). Clusters did not differ in demographic or clinical variables except for depressed mood and physical well-being, which were, respectively, lower and higher in patients with mostly negative ATM. Based on rater assessment, psychotic symptoms were related to negative ATM independently of their severity, and the family played a central role in the expression of negative attitudes. ATM were relatively independent of clinical and psychosocial variables. The existence, in each cluster, of both external and inner motivations underpinning ATM suggests that therapeutic interventions must take into account both patients and their broader living contexts. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 6 | PLoS ONE 2013 -1 8: e68361 |
| PMID | 23861893 |
| Title | Cell cycle checkpoint abnormalities during dementia: A plausible association with the loss of protection against oxidative stress in Alzheimer's disease [corrected]. |
| Abstract | Increasing evidence suggests an association between neuronal cell cycle (CCL) events and the processes that underlie neurodegeneration in Alzheimer's disease (AD). Elevated levels of oxidative stress markers and mitochondrial dysfunction are also among early events in AD. Recent studies have reported the role of CCL checkpoint proteins and tumor suppressors, such as ATM and p53 in the control of glycolysis and oxidative metabolism in cancer, but their involvement in AD remains uncertain. In this postmortem study, we measured gene expression levels of eight CCL checkpoint proteins in the superior temporal cortex (STC) of persons with varying severities of AD dementia and compare them to those of cognitively normal controls. To assess whether the CCL changes associated with cognitive impairment in AD are specific to dementia, gene expression of the same proteins was also measured in STC of persons with schizophrenia (SZ), which is also characterized by mitochondrial dysfunction. The expression of CCL-checkpoint and DNA damage response genes: MDM4, ATM and ATR was strongly upregulated and associated with progression of dementia (cognitive dementia rating, CDR), appearing as early as questionable or mild dementia (CDRs 0.5-1). In addition to gene expression changes, the downstream target of ATM-p53 signaling - TIGAR, a p53-inducible protein, the activation of which can regulate energy metabolism and protect against oxidative stress was progressively decreased as severity of dementia evolved, but it was unaffected in subjects with SZ. In contrast to AD, different CCL checkpoint proteins, which include p53, CHEK1 and BRCA1 were significantly downregulated in SZ. These results support the activation of an ATM signaling and DNA damage response network during the progression of AD dementia, while the progressive decrease in the levels of TIGAR suggests loss of protection initiated by ATM-p53 signaling against intensifying oxidative stress in AD. |
| SCZ Keywords | schizophrenia, schizophrenics |
| 7 | Clin Schizophr Relat Psychoses 2015 Jul -1: -1 |
| PMID | 26218237 |
| Title | Attitudes Toward Medications and The Relationship To Outcomes in Patients with Schizophrenia. |
| Abstract | The determinants of attitudes toward medication (ATM) are not well elucidated. In particular, literature remains equivocal regarding the influence of cognition, adverse events, and psychiatric symptomatology. This study evaluated relationships between those outcomes in schizophrenia and ATM. This is a retrospective analysis of data collected during the Texas Medication Algorithm Project (TMAP, n=307 with schizophrenia-related diagnoses), in outpatient clinics at baseline and every 3 months for ?1 year (for cognition: 3rd and 9th month only). The Drug Attitude Inventory (DAI-30) measured ATM, and independent variables were: cognition (Trail Making Test [TMT], Verbal Fluency Test, Hopkins Verbal Learning Test), adverse events (Systematic Assessment for TreATMent-Emergent Adverse Events, Barnes Akathisia Rating Scale), psychiatric symptomatology (Brief Psychiatric Rating Scale, Scale for Assessment of Negative Symptoms [SANS]), and medication adherence (Medication Compliance Scale). Analyses included binary logistic regression (cognition, psychiatric symptoms) and chi-square (adverse events, adherence) for baseline comparisons, and linear regression (cognition) or ANOVA (adverse events, adherence) for changes over time. Mean DAI-30 scores did not change over 12 months. Odds of positive ATM increased with higher TMT Part B scores (p=0.03) and lower SANS scores (p=0.02). Worsening of general psychopathology (p<0.001), positive symptoms (p<0.001), and negative symptoms (p=0.007) correlated with negative changes in DAI-30 scores. Relationships between cognition, negative symptoms, and ATM warrant further investigation. Studies evaluating therapies for cognitive deficits and negative symptoms should consider including ATM measures as endpoints. Patterns and inconsistencies in findings across studies raise questions about whether some factors thought to influence ATM have non-linear relationships. |
| SCZ Keywords | schizophrenia, schizophrenics |