| 1 | World J. Biol. Psychiatry 2009 -1 10: 809-18 |
|---|---|
| PMID | 19707957 |
| Title | Stroop and emotional Stroop interference in unaffected relatives of patients with schizophrenic and bipolar disorders: distinct markers of vulnerability? |
| Abstract | Reduced inhibition has been demonstrated in both schizophrenic and bipolar patients through the findings of increased interference on the Stroop Colour-Word Task (SCWT) and increased emotional interference on specific versions of the Emotional Stroop Task (EST). Despite previous findings of enhanced interference in unaffected RELatives of schizophrenic and bipolar patients, it remains unclear whether interference might be a candidate endophenotype to both disorders. Moreover, data regarding emotional interference in unaffected RELatives are critically lacking. In the present study, we aimed to compare unaffected RELatives of patients with schizophrenia (SZ-REL, N = 30) and bipolar disorder (BD-REL, N= 30) with normal controls (N = 60) when performing the SCWT and an EST designed with neutral, depressive, paranoid and manic words. SZ-REL exhibited greater interference effect on both the SCWT and the EST as compared to either BD-REL or normal controls. BD-REL, and by contrast to SZ-REL and controls, showed increased emotional interference effect on the EST that was specifically associated to the disease-RELated words. The findings support the hypothesis of different markers of vulnerability to schizophrenic and bipolar disorders; impairment in cognitive inhibition could characterize high-risk individuals for schizophrenia whereas an emotional bias towards mood-RELated information could be a trait marker of bipolar disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | World J. Biol. Psychiatry 2009 -1 10: 809-18 |
| PMID | 19707957 |
| Title | Stroop and emotional Stroop interference in unaffected relatives of patients with schizophrenic and bipolar disorders: distinct markers of vulnerability? |
| Abstract | Reduced inhibition has been demonstrated in both schizophrenic and bipolar patients through the findings of increased interference on the Stroop Colour-Word Task (SCWT) and increased emotional interference on specific versions of the Emotional Stroop Task (EST). Despite previous findings of enhanced interference in unaffected RELatives of schizophrenic and bipolar patients, it remains unclear whether interference might be a candidate endophenotype to both disorders. Moreover, data regarding emotional interference in unaffected RELatives are critically lacking. In the present study, we aimed to compare unaffected RELatives of patients with schizophrenia (SZ-REL, N = 30) and bipolar disorder (BD-REL, N= 30) with normal controls (N = 60) when performing the SCWT and an EST designed with neutral, depressive, paranoid and manic words. SZ-REL exhibited greater interference effect on both the SCWT and the EST as compared to either BD-REL or normal controls. BD-REL, and by contrast to SZ-REL and controls, showed increased emotional interference effect on the EST that was specifically associated to the disease-RELated words. The findings support the hypothesis of different markers of vulnerability to schizophrenic and bipolar disorders; impairment in cognitive inhibition could characterize high-risk individuals for schizophrenia whereas an emotional bias towards mood-RELated information could be a trait marker of bipolar disease. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Schizophr. Res. 2009 Apr 109: 24-37 |
| PMID | 19223268 |
| Title | Endophenotypes in schizophrenia: a selective review. |
| Abstract | Given the wealth of data in the literature on schizophrenia endophenotypes, it is useful to have one source to reference their frequency data. We reviewed the literature on disease-liability associated variants in structural and functional magnetic resonance images (MRI), sensory processing measures, neuromotor abilities, neuropsychological measures, and physical characteristics in schizophrenia patients (SCZ), their first-degree RELatives (REL), and healthy controls (HC). The purpose of this review was to provide a summary of the existing data on the most extensively published endophenotypes for schizophrenia. We searched PubMed and MedLine for all studies on schizophrenia endophenotypes comparing SCZ to HC and/or REL to HC groups. Percent abnormal values, generally defined as >2 SD from the mean (in the direction of abnormality) and/or associated effect sizes (Cohen's d) were calculated for each study. Combined, the articles reported an average 39.4% (SD=20.7%; range=2.2-100%) of abnormal values in SCZ, 28.1% (SD=16.6%; range=1.6-67.0%) abnormal values in REL, and 10.2% (SD=6.7%; range=0.0-34.6%) in HC groups. These findings are reviewed in the context of emerging hypotheses on schizophrenia endophenotypes, as well as a discussion of clustering trends among the various intermediate phenotypes. In addition, programs for future research are discussed, as instantiated in a few recent large-scale studies on multiple endophenotypes across patients, RELatives, and healthy controls. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Neuropsychopharmacology 2011 Aug 36: 1921-31 |
| PMID | 21593732 |
| Title | Variants of the RELA gene are associated with schizophrenia and their startle responses. |
| Abstract | The pathogenesis of schizophrenia is thought to involve aberrant immune and inflammatory responses. Nuclear factor kappa B (NF-?B) has important roles in the immune and inflammatory responses. The v-REL avian reticuloendotheliosis viral oncogene homolog A (RELA) gene encodes the major component of the NF-?B complex. We genotyped four single-nucleotide polymorphisms (SNPs) in the RELA gene and performed a gene-based association analysis using 1224 patients with schizophrenia and 1663 controls. We found significant associations of three SNPs (rs11820062: p=0.00011, rs2306365: p=0.0031, and rs7119750: p=0.0080) with schizophrenia and stronger evidence for association in a multi-marker sliding window haplotype analysis (the lowest p=0.00006). The association between this gene and schizophrenia was evident in male subjects but not in female subjects, when separately analyzed by gender. In silico genotype-gene expression analysis using web database and the WGAViewer software revealed that these three schizophrenia-associated SNPs might be RELated to RELA mRNA expression in immortalized B-lymphocytes. In silico analysis also suggested the putative promoter SNP, rs11820062, might disrupt the consensus transcription factor binding sequence of the androgen receptor. The impact of four RELA polymorphisms on pre-pulse inhibition (PPI) was investigated in 53 patients with schizophrenia. We provided evidence that at risk genotypes of three SNPs were associated with deficits in PPI; however, there was no effect of the one non-risk SNP on PPI. These findings suggest that variants of the RELA gene are associated with risk for schizophrenia and PPI deficits in a Japanese population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | J Abnorm Psychol 2012 Aug 121: 784-94 |
| PMID | 22708888 |
| Title | Working memory encoding and false memory in schizophrenia and bipolar disorder in a spatial delayed response task. |
| Abstract | Working memory (WM) impairment is a core feature of schizophrenia, but the contributions of different WM components are not yet specified. Here, we investigated the potential role of inefficient encoding in reduced WM performance in patients with schizophrenia (PSZ). Twenty-eight PSZ, 16 patients with bipolar disorder (PBP), 16 unaffected and unmedicated RELatives of PSZ (REL), and 29 demographically matched healthy controls (HC) performed a spatial delayed response task with either low or high WM demands. The demands on attentional selection were also manipulated by presenting distractor stimuli during encoding in some of the trials. After each trial, participants rated their level of response confidence. This allowed us to analyze different types of WM responses. WM was seveRELy impaired in PSZ compared to HC; this reduction was mainly due to an increase in the amount of false memory responses (incorrect responses that were given with high confidence) rather than an increase in the amount of incorrect and not-confident responses. Although PBP showed WM impairments, they did not have increased false memory errors. In contrast, reduced WM in REL was also accompanied by an increase in false memory errors. The presentation of distractors led to a decline in WM performance, which was comparable across groups indicating that attentional selection was intact in PSZ. These findings suggest that inefficient WM encoding is responsible for impaired WM in schizophrenia and point to differential mechanisms underlying WM impairments in PSZ and PBP. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 6 | J. Pharmacol. Exp. Ther. 2015 Sep 354: 340-9 |
| PMID | 26109678 |
| Title | Discovery of D1 Dopamine Receptor Positive Allosteric Modulators: Characterization of Pharmacology and Identification of Residues that Regulate Species Selectivity. |
| Abstract | The present studies represent the first published report of a dopamine D1 positive allosteric modulator (PAM). D1 receptors have been proposed as a therapeutic target for the treatment of cognitive deficits associated with schizophrenia. However, the clinical utility of orthosteric agonist compounds is limited by cardiovascular side effects, poor pharmacokinetics, lack of D1 selectivity, and an inverted dose response. A number of these challenges may be overcome by utilization of a selective D1 PAM. The current studies describe two chemically distinct D1 PAMs: Compound A [1-((REL-1S,3R,6R)-6-(benzo[d][1,3]dioxol-5-yl)bicyclo[4.1.0]heptan-3-yl)-4-(2-bromo-5-chlorobenzyl)piperazine] and Compound B [REL-(9R,10R,12S)-N-(2,6-dichloro-3-methylphenyl)-12-methyl-9,10-dihydro-9,10-ethanoanthracene-12-carboxamide]. Compound A shows pure PAM activity, with an EC50 of 230 nM and agonist activity at the D2 receptor in D2-expressing human embryonic kidney cells. Compound B shows superior potency (EC50 of 43 nM) and selectivity for D1 versus D2 dopamine receptors. Unlike Compound A, Compound B is selective for human and nonhuman primate D1 receptors, but lacks activity at the rodent (rat and mouse) D1 receptors. Using molecular biology techniques, a single amino acid was identified at position 130, which mediates the species selectivity of Compound B. These data represent the first described D1-selective PAMs and define critical amino acids that regulate species selectivity. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 7 | 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-schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (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 (SAS9.3 Proc MIXED); 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 for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes 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 |
| 8 | Philos Trans A Math Phys Eng Sci 2015 Feb 373: -1 |
| PMID | 25548266 |
| Title | High-resolution joint symbolic analysis to enhance classification of the cardiorespiratory system in patients with schizophrenia and their relatives. |
| Abstract | schizophrenia as a mental illness is one of the most serious in the world. Patients with schizophrenia have an increased cardiac mortality rate, but the reasons for this remain unclear. In addition to other factors, the role of impaired autonomic regulation during acute psychosis has become more evident in different studies applying heart rate (HR) variability analyses. But, until now, respiration and cardiorespiratory regulation, which are important for homeostatic control, have not been considered. In this study, short-term cardiorespiratory couplings (CRCs) of 23 unmedicated patients with paranoid schizophrenia (SZO), 20 of their healthy first-degree RELatives (REL) and 20 healthy subjects (CON) matched according to age and sex of SZO and REL were investigated by applying high-resolution joint symbolic dynamics (HRJSD) analysis. We found a significantly (p<0.0061) altered HR pattern, respiratory pattern and CRCs in SZO and only marginal alterations for the REL group in comparison with the CON group when we applied HRJSD. These results might be an indication of decreased vagal activity within the brainstem, an altered or suppressed interaction of the brainstem and higher regulatory centres, or panic- and anxiety-RELated changes in the brainstem associated with the acute psychosis of these patients. |
| SCZ Keywords | schizophrenia, schizophrenic |