| 1 | Psychiatry Res 2000 Apr 94: 43-9 |
|---|---|
| PMID | 10788676 |
| Title | Increased anti-streptococcal antibodies in patients with Tourette's syndrome. |
| Abstract | Infection or postinfectious phenomena have been postulated to play a role in the pathogenesis of children afflicted with the typical symptoms of Tourette's syndrome (TS). We investigated whether an increase of titers of antistreptococcal antibodies can be reproduced in our children with TS, and whether this increase is restricted to children. We examined the titers of two different antistreptococcal antibodies, antistreptolysin (ASL) and anitDNase B, both in children and adults. Titer s of ASO and antiDNase B were measured (1) in 13 children/adolescents suffering from TS and in an aged-matched comparison group;(2) in 23 adult patients, a comparison group of 23 aged-matched controls, and in another group of 17 aged-matched, non-medicated acute schizophrenics. ASO and antiDNase B titers were determined by laser nephelometry using a commercially available KIT. Two antistreptococcal cut-off levels were compared (> 250 U/ml and 400 U/ml). As expected, increases ASO titers (>400 IU/ml) were found in a higher portion of children/adolescents with TS compared to controls. Regarding adults, titers >250 U/ml for both antistreptococcal antigens were found in significantly more TS patients than in schizophrenic patients or healthy control subjects. The mean values of ASO and antiDNase titers were significantly higher in both groups of TS patients compared to control children/adolescents, to the comparison groups of healthy adults and to schizophrenics. No difference in antistreptococcal titers was found between schizophrenics and the group of healthy adults. TS patients exhibited higher antistreptococcal titers than age-matched comparison groups of both children/adolescents and adults using different types of calculation. Our findings support the theory that a postinfectious immune mechanism may play a role in the pathogenesis of TS. The mechanism still needs to be elucidated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Psychiatry Res 2000 Apr 94: 43-9 |
| PMID | 10788676 |
| Title | Increased anti-streptococcal antibodies in patients with Tourette's syndrome. |
| Abstract | Infection or postinfectious phenomena have been postulated to play a role in the pathogenesis of children afflicted with the typical symptoms of Tourette's syndrome (TS). We investigated whether an increase of titers of antistreptococcal antibodies can be reproduced in our children with TS, and whether this increase is restricted to children. We examined the titers of two different antistreptococcal antibodies, antistreptolysin (ASL) and anitDNase B, both in children and adults. Titer s of ASO and antiDNase B were measured (1) in 13 children/adolescents suffering from TS and in an aged-matched comparison group;(2) in 23 adult patients, a comparison group of 23 aged-matched controls, and in another group of 17 aged-matched, non-medicated acute schizophrenics. ASO and antiDNase B titers were determined by laser nephelometry using a commercially available KIT. Two antistreptococcal cut-off levels were compared (> 250 U/ml and 400 U/ml). As expected, increases ASO titers (>400 IU/ml) were found in a higher portion of children/adolescents with TS compared to controls. Regarding adults, titers >250 U/ml for both antistreptococcal antigens were found in significantly more TS patients than in schizophrenic patients or healthy control subjects. The mean values of ASO and antiDNase titers were significantly higher in both groups of TS patients compared to control children/adolescents, to the comparison groups of healthy adults and to schizophrenics. No difference in antistreptococcal titers was found between schizophrenics and the group of healthy adults. TS patients exhibited higher antistreptococcal titers than age-matched comparison groups of both children/adolescents and adults using different types of calculation. Our findings support the theory that a postinfectious immune mechanism may play a role in the pathogenesis of TS. The mechanism still needs to be elucidated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | World J. Biol. Psychiatry 2003 Oct 4: 177-83 |
| PMID | 14608589 |
| Title | Creatine kinase BB in brain in schizophrenia. |
| Abstract | Creatine kinase (CK) is responsible for the creatine/creatine phosphate level which that is known to alter in the brain of patients with schizophrenia. A comparative estimation of CK enzymatic activity and immunoreactivity of CK BB was carried out in readily soluble extracts from frontal cortex, anterior and posterior cingulate cortex, hippocampus and cerebellum from brains of individuals with schizophrenia versus normal controls. CK activity was determined using a commercial diagnostic KIT. CK BB immunoreactivity was evaluated by ECL -immunoblotting using monoclonal antibody. A drastic drop of CK activity and CK BB immunoreactivity was observed in all the examined brain areas in schizophrenia patients compared to controls (p<0.01), with the maximum drop in the cerebellum. The reduction was independent of age, postmortem interval or chlorpromazine equivalent. The decreased level of CK BB in schizophrenia was confirmed by purification of CK BB from brains of patients with schizophrenia and control brains: the yield of the purified enzyme was significantly lower in schizophrenia, wherein molecular masses of CK B-subunits were equal. Possible causes and consequences of the decrease in CK BB level observed in brain of patients with schizophrenia are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | J Psychiatr Res 2006 Oct 40: 664-8 |
| PMID | 16386272 |
| Title | Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. |
| Abstract | This study investigated serum brain-derived neurotrophic factor (BDNF) protein levels in schizophrenia patients and healthy control subjects and schizophrenia patients with various clinical phenotypes. During a 1-year period, 126 schizophrenic patients and 96 healthy control subjects were recruited. Serum BDNF protein levels were measured using an ELISA KIT. Psychiatric diagnoses were made according to DSM-IV criteria. One-way analysis of variance (ANOVA) showed no significant differences in serum BDNF protein levels between schizophrenia and healthy normals. Additionally, no significant differences existed in BDNF levels between schizophrenia patients for the following variables: with/without a suicide attempt; antipsychotic drug use, family tendency and disease onset before and after 25 years old. However, patients with catatonic schizophrenia had lower serum BDNF protein levels than patients with paranoid or residual schizophrenia. These analytical results suggested that BDNF might play an important role in the clinical subtypes of schizophrenia, but it needed further investigation in future. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | J Psychiatr Res 2006 Oct 40: 664-8 |
| PMID | 16386272 |
| Title | Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. |
| Abstract | This study investigated serum brain-derived neurotrophic factor (BDNF) protein levels in schizophrenia patients and healthy control subjects and schizophrenia patients with various clinical phenotypes. During a 1-year period, 126 schizophrenic patients and 96 healthy control subjects were recruited. Serum BDNF protein levels were measured using an ELISA KIT. Psychiatric diagnoses were made according to DSM-IV criteria. One-way analysis of variance (ANOVA) showed no significant differences in serum BDNF protein levels between schizophrenia and healthy normals. Additionally, no significant differences existed in BDNF levels between schizophrenia patients for the following variables: with/without a suicide attempt; antipsychotic drug use, family tendency and disease onset before and after 25 years old. However, patients with catatonic schizophrenia had lower serum BDNF protein levels than patients with paranoid or residual schizophrenia. These analytical results suggested that BDNF might play an important role in the clinical subtypes of schizophrenia, but it needed further investigation in future. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Schizophr Bull 2006 Oct 32 Suppl 1: S32-43 |
| PMID | 16899534 |
| Title | The Illness Management and Recovery program: rationale, development, and preliminary findings. |
| Abstract | The Illness Management and Recovery (IMR) program was developed based on a comprehensive review of research on teaching illness self-management strategies to clients with schizophrenia and other severe mental illnesses and "packaged" in a resource KIT to facilitate dissemination. Despite growing dissemination of this program, it has not yet been empirically validated. This article describes the development and theoretical underpinnings of the IMR program and presents pilot data from the United States and Australia (N = 24, 88% schizophrenia or schizoaffective) on the effects of individual-based and group-based treatment over the 9-month program and over a 3-month follow-up. High satisfaction was reported by participants. Strong improvements over treatment and at follow-up were found in clients' self-reported effectiveness in coping with symptoms and clinicians' reports of global functioning and moderate improvements in knowledge about mental illness, distress related to symptoms, hope, and goal orientation. These findings support the feasibility and promise of the IMR program and point to the need for controlled research to rigorously evaluate its effects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Biochem. Genet. 2007 Oct 45: 683-9 |
| PMID | 17690978 |
| Title | Number of STR repeats as a potential new quantitative genetic marker for complex diseases, illustrated by schizophrenia. |
| Abstract | It has proved difficult to find strong and replicable genetic linkages for complex diseases, since each susceptibility gene makes only a modest contribution to onset. This is partly because high-efficacy genetic markers are not usually available. The aim of this article is to explore the possibility that the total number of tandem repeats in one STR locus, rather than the frequencies of different alleles, is a higher efficacy quantitative genetic marker. DNA samples were collected from schizophrenic patients and from a control population. Alleles of the short tandem repeats (STR) loci D3S1358, vWA, and FGA were determined using the STR Profiler Plus PCR amplification KIT. The two groups did not differ statistically in the frequencies of alleles at the D3S1358, vWA, or FGA loci. However, a significant difference was obtained in the vWA locus when the total number of core unit repeats was compared between the schizophrenia and control groups (33.28+/-2.61 vs. 32.35+/-2.58, P<0.05). It seems that the number of STR repeats may be a new, quantitative, and higher efficacy genetic marker for directly indicating genetic predisposition to complex hereditary diseases such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | Biochem. Genet. 2007 Oct 45: 683-9 |
| PMID | 17690978 |
| Title | Number of STR repeats as a potential new quantitative genetic marker for complex diseases, illustrated by schizophrenia. |
| Abstract | It has proved difficult to find strong and replicable genetic linkages for complex diseases, since each susceptibility gene makes only a modest contribution to onset. This is partly because high-efficacy genetic markers are not usually available. The aim of this article is to explore the possibility that the total number of tandem repeats in one STR locus, rather than the frequencies of different alleles, is a higher efficacy quantitative genetic marker. DNA samples were collected from schizophrenic patients and from a control population. Alleles of the short tandem repeats (STR) loci D3S1358, vWA, and FGA were determined using the STR Profiler Plus PCR amplification KIT. The two groups did not differ statistically in the frequencies of alleles at the D3S1358, vWA, or FGA loci. However, a significant difference was obtained in the vWA locus when the total number of core unit repeats was compared between the schizophrenia and control groups (33.28+/-2.61 vs. 32.35+/-2.58, P<0.05). It seems that the number of STR repeats may be a new, quantitative, and higher efficacy genetic marker for directly indicating genetic predisposition to complex hereditary diseases such as schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | J Clin Psychiatry 2008 -1 69 Suppl 3: 25-30 |
| PMID | 18533759 |
| Title | An evidence-based strategy for remission in schizophrenia. |
| Abstract | Over the past 50 years, the therapeutic goal for schizophrenia has slowly but steadily increased, from one of modest improvement in self-care and control of aggression or self-injury in the 1950s, to effective control of both positive and negative symptoms in the 1990s. As physicians have become more equipped with a better tool KIT of pharmacologic and psychosocial interventions, the pessimistic attitude toward long-term outcome has gradually given way to cautious and guarded optimism. Remission may even be considered a potentially realistic goal. This article briefly reviews the status of remission as a therapeutic goal in the treatment of schizophrenia and summarizes available treatment research reporting remission and recovery as clinical outcomes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Adv Ther 2008 Jul 25: 703-9 |
| PMID | 18563312 |
| Title | The schizophrenia and Toxoplasma gondii connection: infectious, immune or both? |
| Abstract | Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls We used a commercially available enzyme-linked immunosorbent assay (ELISA) KIT to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n=40) and from a group of non-schizophrenic control subjects (n=37) Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Adv Ther 2008 Jul 25: 703-9 |
| PMID | 18563312 |
| Title | The schizophrenia and Toxoplasma gondii connection: infectious, immune or both? |
| Abstract | Recent research has suggested a possible link between toxoplasmic agents and schizophrenia. We aimed to assess this by measuring Toxoplasma gondii-associated antibodies in schizophrenia patients and controls We used a commercially available enzyme-linked immunosorbent assay (ELISA) KIT to measure the level of immunoglobulin G (IgG) and IgM antibodies in serum samples from schizophrenia patients (n=40) and from a group of non-schizophrenic control subjects (n=37) Among schizophrenic patients, 16 (40%) showed IgG seropositivity and two (5%) showed IgM seropositivity. Among the control group, five (13.5%) were found have IgG seropositivity and one (2.7%) showed IgM seropositivity. In our study we found that IgG T gondii antibodies were significantly higher in schizophrenia patients compared with controls This study supports the theory that toxoplasmic agents may have a role in the aetiology of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | Yonsei Med. J. 2008 Apr 49: 224-9 |
| PMID | 18452258 |
| Title | Toxocara seroprevalence in schizophrenic patients in Turkey. |
| Abstract | To investigate the seroprevalence of toxocariasis in patients diagnosed as schizophrenia. Ninety-eight schizophrenic patients hospitalized at The Elazig Psychiatric Hospital were included in the study. Anti-Toxocara IgG and/or IgM antibodies were determined by using commercial Toxocara canis IgG and/or IgM ELISA KIT. Seropositivity for T. canis was detected in 45 (45.9%) of 98 patients and 2 (2.0%) of 100 control subjects the difference was statistically significant (p<0.001). The seroprevalence was 40.4% (19 cases) and 51.0% (26 cases) for female and male subjects, respectively (p=0.3). When the seropositive and seronegative schizophrenic patients were compared with respect to the age group environment they were living in, occupation period of follow up and number of hospitalizations, there were no differences between the two groups (all, p>0.05). In conclusion, the schizophrenic state seems to present a high risk for Toxocara infection in Turkey. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Yonsei Med. J. 2008 Apr 49: 224-9 |
| PMID | 18452258 |
| Title | Toxocara seroprevalence in schizophrenic patients in Turkey. |
| Abstract | To investigate the seroprevalence of toxocariasis in patients diagnosed as schizophrenia. Ninety-eight schizophrenic patients hospitalized at The Elazig Psychiatric Hospital were included in the study. Anti-Toxocara IgG and/or IgM antibodies were determined by using commercial Toxocara canis IgG and/or IgM ELISA KIT. Seropositivity for T. canis was detected in 45 (45.9%) of 98 patients and 2 (2.0%) of 100 control subjects the difference was statistically significant (p<0.001). The seroprevalence was 40.4% (19 cases) and 51.0% (26 cases) for female and male subjects, respectively (p=0.3). When the seropositive and seronegative schizophrenic patients were compared with respect to the age group environment they were living in, occupation period of follow up and number of hospitalizations, there were no differences between the two groups (all, p>0.05). In conclusion, the schizophrenic state seems to present a high risk for Toxocara infection in Turkey. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | J Psychiatr Res 2009 Sep 43: 1078-85 |
| PMID | 19380152 |
| Title | Levels of the potential biomarker p11 in peripheral blood cells distinguish patients with PTSD from those with other major psychiatric disorders. |
| Abstract | Posttraumatic stress disorder (PTSD) is a severely debilitating anxiety disorder. Over 80% of patients with PTSD also exhibit other psychiatric condition, such as bipolar disorder (BP) or major depression (MDD). Previously, it has been found that p11 mRNA expression was significantly changed in post mortem cortex of patients with PTSD and depression. We hypothesize that p11 mRNA levels in the peripheral blood cells will be a potential biomarker for PTSD with heterogeneity in terms of type of trauma, time since trauma and duration of illness. We examined the peripheral blood mononuclear cell (PBMC) P11 mRNA of patients with PTSD (n=13), major depressive disorder (MDD, n=16), bipolar disorder (BP, n=24), and schizophrenia (SCZ, n=12) or controls (n=14) using quantitative real-time PCR and the circulating levels of cortisol in blood plasma and saliva of PTSD using radioimmunoassay KIT CORT-CT2. The Hamilton Rating Scale for Depression (HAMD) and Anxiety (HARS), the Chinese version of the Davidson Trauma Scale-Frequency (CDTS-F) and the Chinese version of the Davidson Trauma Scale-Severity (CDTS-S), and Impact of Event Scale-Revised (IES-R) were administered. We found that patients with PTSD had lower levels of p11 mRNA than control subjects, while those with MDD, BP and SCZ had significantly higher p11 levels than the controls. P11 mRNA levels were positively correlated with the scores of HAMD (r=0.62, p<0.05), CDTS-F (r=0.71, p<0.05) and CDTS-S (r=0.62, p<0.05), while they did not correlate with scores of HARS and IES-R. Basal levels of plasma and salivary cortisol of PTSD patients were not statistically different from those of controls. Our findings suggest that PBMC p11 mRNA expression levels may serve as a potential biomarker to distinguish PTSD from BP, MDD and SCZ. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | World J. Biol. Psychiatry 2009 -1 10: 27-33 |
| PMID | 19673085 |
| Title | Isoprostenes as indicators of oxidative stress in schizophrenia. |
| Abstract | Free radicals induce oxidative stress and damage to all types of biological molecules and may be involved in pathology of schizophrenia. A cell membrane dysfunction caused by lipid peroxidation can be secondary to a free radical-mediated pathology and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. The aim of our study was to estimate oxidative stress in a group of schizophrenic patients by using different biomarkers of free radicals-induced lipid peroxidation (isoprostanes, thiobarbituric acid reactive substances (TBARS)). We also determined the products of enzymatic peroxidation of arachidonic acid, such as thromboxane B2 (TXB2) and its metabolite 11-dehydrothromboxane B2. Isoprostanes (IPs) are a family of novel prostaglandin isomers and are produced in free radical-catalysed reactions from arachidonic acid. They are useful as a specific, sensitive, chemically stable, noninvasive index of free radical generation in vivo. We therefore assessed in schizophrenic patients and control subjects the level of urinary excretion of isoprostane--8-epi-prostaglandin F2 alpha, (8-isoPGF2 alpha)--a marker of lipid peroxidation induced by free radicals using an immunoassay KIT. We also studied the level of the other marker of enzymatic arachidonic acid peroxidation--11-dehydrothromboxane B2--in urine from schizophrenic patients and healthy volunteers. Moreover, we estimated the production of TBARS and TXB2 in plasma from schizophrenic patients and the control group. Patients hospitalised in the II Psychiatric Department of Medical University in Lodz, Poland, were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other EPS). According to DSM-IV criteria, all patients had diagnosis of paranoid type. All patients were treated with second-generation antipsychotic drugs (risperidone, clozapine, and olanzapine). Mean time of schizophrenia duration was about 2 years. We observed a statistically increased level of TBARS in plasma (P=0.000162) and isoprostanes (P=3.5 x 10(-12)) in urine of schizophrenic patients in comparison with the control group. The level of markers of enzymatic oxidation of arachidonic acid (TXB2 and its metabolite, 11-dehydrothromboxane B2) did not change. This indicates that free radicals induce peroxidation of unsaturated fatty acid in schizophrenic patients. Considering the data presented in this study, we suggest that non-invasive measurement of 8-isoPGF2 alpha, is a valuable and sensitive (contrary to TBARS) indicator of oxidative stress status in vivo in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | World J. Biol. Psychiatry 2009 -1 10: 27-33 |
| PMID | 19673085 |
| Title | Isoprostenes as indicators of oxidative stress in schizophrenia. |
| Abstract | Free radicals induce oxidative stress and damage to all types of biological molecules and may be involved in pathology of schizophrenia. A cell membrane dysfunction caused by lipid peroxidation can be secondary to a free radical-mediated pathology and may contribute to specific aspects of schizophrenic symptomatology and complications of its treatment. The aim of our study was to estimate oxidative stress in a group of schizophrenic patients by using different biomarkers of free radicals-induced lipid peroxidation (isoprostanes, thiobarbituric acid reactive substances (TBARS)). We also determined the products of enzymatic peroxidation of arachidonic acid, such as thromboxane B2 (TXB2) and its metabolite 11-dehydrothromboxane B2. Isoprostanes (IPs) are a family of novel prostaglandin isomers and are produced in free radical-catalysed reactions from arachidonic acid. They are useful as a specific, sensitive, chemically stable, noninvasive index of free radical generation in vivo. We therefore assessed in schizophrenic patients and control subjects the level of urinary excretion of isoprostane--8-epi-prostaglandin F2 alpha, (8-isoPGF2 alpha)--a marker of lipid peroxidation induced by free radicals using an immunoassay KIT. We also studied the level of the other marker of enzymatic arachidonic acid peroxidation--11-dehydrothromboxane B2--in urine from schizophrenic patients and healthy volunteers. Moreover, we estimated the production of TBARS and TXB2 in plasma from schizophrenic patients and the control group. Patients hospitalised in the II Psychiatric Department of Medical University in Lodz, Poland, were interviewed with a special questionnaire (treatment, course of diseases, dyskinesis and other EPS). According to DSM-IV criteria, all patients had diagnosis of paranoid type. All patients were treated with second-generation antipsychotic drugs (risperidone, clozapine, and olanzapine). Mean time of schizophrenia duration was about 2 years. We observed a statistically increased level of TBARS in plasma (P=0.000162) and isoprostanes (P=3.5 x 10(-12)) in urine of schizophrenic patients in comparison with the control group. The level of markers of enzymatic oxidation of arachidonic acid (TXB2 and its metabolite, 11-dehydrothromboxane B2) did not change. This indicates that free radicals induce peroxidation of unsaturated fatty acid in schizophrenic patients. Considering the data presented in this study, we suggest that non-invasive measurement of 8-isoPGF2 alpha, is a valuable and sensitive (contrary to TBARS) indicator of oxidative stress status in vivo in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | J Immunoassay Immunochem 2010 -1 31: 33-44 |
| PMID | 20391016 |
| Title | Competitive enzyme-linked immunosorbent assay for a selective and sensitive determination of dopamine in the presence of ascorbic acid and uric acid. |
| Abstract | Dopamine (DA) is one of the most important catecholamine neurotransmitter molecules in the central nervous system (CNS). An abnormal level of DA in vivo can cause CNS diseases such as Parkinsonism and schizophrenia. Thus, it is essential to develop an accurate and easy to use method for determining the level of DA in biological fluids such as urine and serum as a tool for clinical diagnostics as well as for pathological research. This work is the first ELISA application to detect DA in the presence of a high concentration of ascorbic acid (AA) and uric acid (UA) which are endogenous in urine. The LOD value of 1.26 x 10(-9) M and dynamic ranges of 3.16 x 10(-3) M to 3.16 x 10(-7) M were observed. It shows a good sensitivity with a broad dynamic range. Also, the competitive ELISA method for DA developed here showed no interference effect due to AA and UA, which are found in urine. The presence of AA and UA caused interference for DA determination by an electrochemical method because UA, AA, and DA have similar oxidation potential. Also, this selective and sensitive ELISA method can be made into an ELISA test KIT which can be used to quantify the level of DA with ease and simplicity in clinics and laboratories. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | Schizophr. Res. 2012 Mar 135: 51-4 |
| PMID | 22260961 |
| Title | A ticking clock for the production of sequential actions: where does the problem lie in schizophrenia? |
| Abstract | schizophrenia has been associated to a distorted time clock. By subtracting contact duration from Inter Response Interval, we report evidence for preserved internal clock in schizophrenia, with normal spontaneous tapping tempo. Contact durations were however increased in patients suggesting a specific problem in the fast integration of incoming haptic feedback with outgoing motor efferences. This integration deficit would emerge at an early phase, since Ultra High Risk patients also revealed abnormal tapping stability. Tactile screens revealed to be a simple and low cost apparatus that may constitute a suitable measuring KIT for the characterisation of sensory motor deficits in clinical settings. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | Biol. Psychiatry 2012 Jan 71: 169-77 |
| PMID | 22078303 |
| Title | Association study of nonsynonymous single nucleotide polymorphisms in schizophrenia. |
| Abstract | Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs). We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP KIT, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency >5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures. The 5 independent nsSNPs with false discovery rate q ? .25, as well as 13 additional nsSNPs at p < .01 and located in functional candidate genes, were genotyped in the replication samples. One SNP, rs13107325, located at the metal ions transporter gene SLC39A8, reached significance in the combined sample after Bonferroni correction (trend test, p = 2.7 × 10(-6), allelic odds ratio = 1.32). This SNP presents minor allele frequency of 5% to 10% in many European populations but is rare outside Europe. We also confirmed the polygenic component of susceptibility. Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 20 | J Psychiatr Res 2013 Oct 47: 1396-402 |
| PMID | 23870796 |
| Title | Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects. |
| Abstract | Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay KIT. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 21 | Psychiatry Clin. Neurosci. 2013 May 67: 228-36 |
| PMID | 23683153 |
| Title | Is T-helper type 2 shift schizophrenia-specific? Primary results from a comparison of related psychiatric disorders and healthy controls. |
| Abstract | An imbalance between T-helper type 1 (Th1) and type 2 (Th2) cytokines has been implicated in schizophrenia, although empirical evidence is rare. The aim of this study was to examine if a Th1/Th2 imbalance occurs in schizophrenia and schizophrenia-related disorder. Twenty-six subjects with schizophrenia, 26 subjects with schizophrenia-related disorders, and 26 healthy controls were recruited. The Human Th1/Th2 Cytokine Cytometric Bead Array KIT-II was utilized to assess serum Th1/Th2 cytokines and ratios simultaneously. MANOVA was used to detect differences among the three diagnostic groups in distinct Th1/Th2 cytokines/ratios. Pearson/Spearman correlations were used to examine the relationships between distinct Th1/Th2 cytokines/ratios and clinical/psychopathological data in schizophrenia. Interferon (IFN)-?/interleukin (IL)-4, IFN-?/IL-10, IL-2/IL-4, and tumor necrosis factor (TNF)-?/IL-4 ratios were significantly decreased in schizophrenia, but not in schizophrenia-related disorders compared to healthy controls. IFN-?/IL-4 and IFN-?/IL-10 in schizophrenia subjects positively correlated with age, but not in schizophrenia-related disorder subjects or in healthy controls. A clear Th2 shift was observed in schizophrenia, but not in schizophrenia-related disorders. The Th2 shift in schizophrenia appeared to be an aberrant developmental phenomenon. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 22 | Mol. Genet. Metab. 2013 Apr 108: 225-31 |
| PMID | 23422032 |
| Title | DNA methylome profiling using neonatal dried blood spot samples: a proof-of-principle study. |
| Abstract | DNA methylation is the most common DNA modification and perhaps the best described epigenetic modification. It is believed to be important for genomic imprinting and gene regulation and has been associated with the development of diseases such as schizophrenia and some types of cancer. Neonatal dried blood spot samples, commonly known as Guthrie cards, are routinely collected worldwide to screen newborns for diseases. Some countries, including Denmark, have been storing the excess neonatal dried blood spot samples in biobanks for decades. Representing a high percentage of the population under a certain age, the neonatal dried blood spot samples are a potential alternative to collecting new samples to study diseases. As such, neonatal dried blood spot samples have previously been used for DNA genotyping studies with excellent results. However, the amount of material available for research is often limited, challenging researchers to generate the most data from a limited quantity of material. In this proof-of-principle study, we address whether two 3.2mm disks punched from a neonatal dried blood spot sample contain enough DNA for genome-wide methylome profiling, measuring 27,578 loci at the same time. We selected two subjects and carried out the following with each: 1) collected an adult whole-blood sample as reference, 2) spotted a fraction of the whole-blood sample onto a similar type of filter paper as used in the newborn screening and stored it for 3years to serve as a dried blood spot reference, and 3) identified the archived neonatal dried blood spot samples, stored for 26-28years, in the Danish Newborn Screening Biobank as a representative of the archived samples. For comparison, we used two different KITs for DNA extraction. The DNA, extracted using the Extract-N-Amp Blood PCR KIT, was analyzed, and no statistically significant differences were observed (P<0.001) when we compared the methylation profile of the reference whole-blood samples to the dried blood spot references. This indicates that two 3.2mm disks contain enough material for reliable methylome profiling and that storing the whole-blood sample on neonatal dried blood spot filter paper for 3years does not interfere with the outcome of the analysis. Furthermore, we compared the adult DNA methylation profile to the neonatal dried blood spot sample profile. Approximately 50 sites in the subjects were significantly (P<0.001) different in the newborn sample compared with the adult sample. Both being healthy adults and the high quality of the DNA methylation array led to the conclusion that the archived neonatal dried blood spot samples can be used for methylome profiling, despite decades of storage and DNA degradation. In conclusion, we show that reliable methylome data can be obtained from old neonatal dried blood spot samples, by using a reasonable amount of the limited resource. This further adds to the use of neonatal dried blood spot samples in genetic research and screening and paves the way for unique population-based studies of epigenetic modifications after birth. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 23 | Mol Autism 2014 -1 5: 1 |
| PMID | 24410847 |
| Title | Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders. |
| Abstract | Autism spectrum disorders (ASDs) comprise a range of neurodevelopmental conditions of varying severity, characterized by marked qualitative difficulties in social relatedness, communication, and behavior. Despite overwhelming evidence of high heritability, results from genetic studies to date show that ASD etiology is extremely heterogeneous and only a fraction of autism genes have been discovered. To help unravel this genetic complexity, we performed whole exome sequencing on 100 ASD individuals from 40 families with multiple distantly related affected individuals. All families contained a minimum of one pair of ASD cousins. Each individual was captured with the Agilent SureSelect Human All Exon KIT, sequenced on the Illumina Hiseq 2000, and the resulting data processed and annotated with Burrows-Wheeler Aligner (BWA), Genome Analysis ToolKIT (GATK), and SeattleSeq. Genotyping information on each family was utilized in order to determine genomic regions that were identical by descent (IBD). Variants identified by exome sequencing which occurred in IBD regions and present in all affected individuals within each family were then evaluated to determine which may potentially be disease related. Nucleotide alterations that were novel and rare (minor allele frequency, MAF, less than 0.05) and predicted to be detrimental, either by altering amino acids or splicing patterns, were prioritized. We identified numerous potentially damaging, ASD associated risk variants in genes previously unrelated to autism. A subset of these genes has been implicated in other neurobehavioral disorders including depression (SLIT3), epilepsy (CLCN2, PRICKLE1), intellectual disability (AP4M1), schizophrenia (WDR60), and Tourette syndrome (OFCC1). Additional alterations were found in previously reported autism candidate genes, including three genes with alterations in multiple families (CEP290, CSMD1, FAT1, and STXBP5). Compiling a list of ASD candidate genes from the literature, we determined that variants occurred in ASD candidate genes 1.65 times more frequently than in random genes captured by exome sequencing (P?=?8.55 × 10-5). By studying these unique pedigrees, we have identified novel DNA variations related to ASD, demonstrated that exome sequencing in extended families is a powerful tool for ASD candidate gene discovery, and provided further evidence of an underlying genetic component to a wide range of neurodevelopmental and neuropsychiatric diseases. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 24 | Acta Neurobiol Exp (Wars) 2015 -1 75: 314-25 |
| PMID | 26581387 |
| Title | Biochemical and cognitive impairments observed in animal models of schizophrenia induced by prenatal stress paradigm or methylazoxymethanol acetate administration. |
| Abstract | The aim of the study was to find whether spatial memory impairment and disruption in locomotor activity were found in prenatally stressed rats (PSG) or prenatally methylazoxymethanol acetate-treated rats (MAMG). In addition to this, we examined basal plasma corticosterone level as well as brain-derived neurothropic factor (BDNF) in the PSG and MAMG rats. The effect of prenatal stress (stress paradigm between 14 and 21 day of gestation) and methylazoxymethanol acetate (MAM) administration (17 day of gestation) to the female Wistar rats were studied on the male offspring in the Morris Water Maze (spatial memory) and locomotor activity test. Through Morris Water Maze rats were injected with saline 4 times (on 1, 7, 14 and 21 day of testing) while in locomotor activity test saline was injected only once. Corticosterone level was measured using ELISA KIT while BDNF levels were assessed using ELISA Chemikine TM BDNF KIT. Results indicate that both PSG and MAMG rats deteriorate spatial memory as well as increase locomotor activity compared to the control group. Biochemical studies indicate that basal plasma corticosterone level increased in both PSG and MAMG rats compared to the control group. Analyses of the BDNF level, on the other hand, have shown decrease of the neurothropin level in both hippocampus and prefrontal cortex (PFC) in both PSG and MAMG groups of rats. As shown by the obtained results, both the prenatal stress model and prenatal MAM administration model generate a number of behavioural (e.g. spatial memory disorders, increased locomotor activity) and biochemical (e.g. increased corticosterone and decreased BDNF levels) changes in the examined offspring, Thus, these models can be successfully used in the efficacy analysis of the pharmacotherapy applied. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 25 | Eur Arch Psychiatry Clin Neurosci 2015 Mar 265: 167-70 |
| PMID | 24831601 |
| Title | Lower phosphorylated glycogen synthase kinase-3B levels in platelets of patients with schizophrenia: increment by olanzapine treatment. |
| Abstract | Glycogen synthase kinase-3B (GSK-3B) is involved with important neuronal processes such as cell survival, gene regulation, mood and cognitive performance. This enzyme is inactivated by phosphorylation at the phospho-Ser9 site. We compared GSK-3B levels in patients with schizophrenia to a health control group. The levels of phosphorylated and total GSK-3B in platelets of ten drug-free patients, ten long-term olanzapine treated patients and 20 healthy controls were determined by means of an enzyme immunoassay KIT. In drug-free patients, GSK-3B levels were accessed again after 8 weeks on treatment with olanzapine. At baseline, drug-free patients presented lower phosphorylated and total GSK-3B levels than healthy controls (p < 0.05). After 8 weeks on olanzapine treatment, phosphorylated and total GSK-3B levels were significantly increased (p < 0.01). Reduced phospho-Ser9-GSK-3B in schizophrenia may disrupt signal-transduction pathways and influence crucial cellular processes, such as transcription, apoptosis, stress response and cell proliferation. Further studies should clarify whether the increment of GSK-3B phosphorylation by olanzapine is related to its antipsychotic effects. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 26 | Int. J. Neuropsychopharmacol. 2016 Apr -1: -1 |
| PMID | 27207913 |
| Title | Serum Cytokine Profiles of Children with Obsessive-Compulsive Disorder Shows the Evidence of Autoimmunity. |
| Abstract | Previous reports have described an association between autoimmunity and primary obsessive compulsive disorder. This study aimed to investigate any differences in the levels of T helper 1, 2, and 17 effector cell cytokines between obsessive compulsive disorder patients and the control group. The study included 34 children (23 males, 11 females), aged between 7 and 17 years, with a diagnosis of obsessive compulsive disorder prior to receiving treatment. The control group consisted of age- and gender-matched children. Study participants were assessed using the Kiddie Schedule for Affective Disorders and schizophrenia, Present and Lifetime version, Children's Yale Brown Obsession Compulsion Scale, and Children's Depression Inventory. Cytokine serum concentrations were measured using the BD Cytometric Bead Array Human Th1/Th2/Th17 Cytokine KIT. Interleukin-17A, tumor necrosis factor-?, and interleukin-2 levels were significantly higher in obsessive compulsive disorder patients, However, there was no correlation between T helper 1 and 17 cytokine profiles in the obsessive compulsive disorder group. The duration and severity of obsessive compulsive disorder symptoms were not significantly associated with interleukin-17A, interferon-gamma-?, interleukin-10, interleukin-6, interleukin-4, and interleukin-2 levels. Interestingly, a negative correlation was found between tumor necrosis factor-? levels and Clinical Global Impression scores. These findings suggest, in some cases, obsessive compulsive disorder may develop on a background of autoimmunity, and interleukin-2, tumor necrosis factor-?, and interleukin-17A may play a role in these autoimmune processes. Therefore, we believe it is important to investigate for obsessive compulsive disorder symptoms in patients with autoimmune disease and, conversely, autoimmune diseases in obsessive compulsive disorder patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 27 | J. Mol. Neurosci. 2016 Mar -1: -1 |
| PMID | 27034067 |
| Title | Mitochondrial Dysfunction in Schizophrenia: Determination of Mitochondrial Respiratory Activity in a Two-Hit Mouse Model. |
| Abstract | schizophrenia is a chronic mental illness in which mitochondrial dysfunction has been suggested. Our laboratory recently developed a juvenile murine two-hit model (THM) of schizophrenia based on the combination of gestational inflammation, followed by juvenile restraint stress. We previously reported that relevant behaviors and neurochemical disturbances, including oxidative stress, were reversed by the antioxidant lipoic acid (LA), thereby pointing to the central role played by oxidative abnormalities and prompting us to investigate mitochondrial function. Mitochondrial activity was determined with the MitoXpress® commercial KIT in two schizophrenia-relevant regions (prefrontal cortex (PFC) and striatum). Measurements were performed in state 3, with substrates for complex I- and complex II-induced respiratory activity (IRA). We observed an increase in complex I IRA in the PFC and striatum in both sexes but an increase in complex II activity only in males. LA treatment prevented this increase only in complex II IRA in males. Expression levels of the different respiratory chain complexes, as well as fission/fusion proteins and protein carbonylation, were unchanged. In conclusion, our juvenile schizophrenia THM shows an increase in mitochondrial activity reversed by LA, specifically in complex II IRA in males. Further investigations are required to determine the mechanisms of these modifications. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 28 | J Neural Transm (Vienna) 2016 Mar 123: 329-38 |
| PMID | 26821981 |
| Title | Genome-wide association analysis to predict optimal antipsychotic dosage in schizophrenia: a pilot study. |
| Abstract | In recent years, several studies have investigated genetic polymorphisms of antipsychotic drug-metabolizing enzymes and receptors. However, most studies focused on drug response and very few have investigated the genetic influence on antipsychotic dosage. The aim of the present study is to test the association between antipsychotic dosages at genome-wide level. The current dosage of antipsychotic medications was collected from 79 schizophrenia patients. The dosage was standardized using three different methods: chlorpromazine equivalent (CPZe), defined daily dose (DDD), and percentage of maximum dose (PM %). The patients were then genotyped using the Illumina HumanOmni2.5-8 BeadChip KIT. All markers were screened for significance using linear regression, and the p values were visualized using a Manhattan plot. The genome-wide analysis showed that the top Single-Nucleotide Polymorphisms (SNPs) associated with dosage variation were rs981975 on chromosome 14 for CPZe, rs4470690 on chromosome 4 for PM %, and rs79323383 on chromosome 8 for DDD. However, no genome-wide significantly associated SNPs were identified. In this pilot sample, we found promising trends for pharmacodynamic targets associated with antipsychotic dosage. Therefore, studies combining large prescription databases may identify genetic predictors to adjust the dose of antipsychotic medication. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |