| 1 | J Anal Toxicol 2000 Oct 24: 638-41 |
|---|---|
| PMID | 11043672 |
| Title | Loxapine intoxication: case report and literature review. |
| Abstract | Loxapine is a dibenzoxazepine tricyclic compound used to treat schizophrenia in the United States since 1976. Metabolism includes demethylation to its primary metabolite, amoxapine. There are few documented reports of the disposition of loxapine in deaths due to overdose. This report discusses the overdose suicide of a 69-year-old white female found dead in her home by her husband. A prescription for loxapine (50-mg capsules) was found near the body. An autopsy was performed and heart blood, bile, vitreous humor, and gastric contents were submitted for toxicological analysis. The blood specimen was subjected to comprehensive testing that included volatile analysis by headspace gas chromatography (GC); acidic/neutral and basic drug screening by GC; benzodiazepine screening by high-performance liquid chromatography; opiate screening by modified immunoassay; and acetaminophen, salicylate, and ethchlorvynol screening by colorimetry. Loxapine and amoxapine were detected in the basic drug screen. No other drugs were detected in the case specimens. The respective concentrations of loxapine and amoxapine in each specimen were as follows: heart blood, 9.5 and 0.6 mg/L; bile, 28.8 and 4.7 mg/L; gastric, 278 mg/L and negative; and vitreous, 1.5 mg/L and negative. A review of the literature showed that the heart blood concentration of loxapine measured in this case was the highest reported to date. Based on the autopsy findings, patient history, and toxicology results, the cause of death was determined to be acute intoxication of loxapine and the manner, suicide. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 2 | Mol. Psychiatry 2001 Mar 6: 168-72 |
| PMID | 11317218 |
| Title | An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. |
| Abstract | alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 3 | Mol. Psychiatry 2001 Mar 6: 168-72 |
| PMID | 11317218 |
| Title | An in-frame deletion in the alpha(2C) adrenergic receptor is common in African--Americans. |
| Abstract | alpha(2) adrenergic receptors are activated by adrenaline and noradrenaline, and three subtypes (ie, A, B, C) have differential affinities for antagonists and medications. The alpha(2c) adrenergic receptor (ADRA2C), located on chromosome 4p16.3, is a candidate gene for schizophrenia because it binds clozapine, an atypical neuroleptic useful for treatment-resistant schizophrenia. In addition, ADRA2C binds clonidine which is prescribed for three psychiatric diseases. This report communicates the findings of the genetic scanning of this gene of very tough GC content. The complete coding sequences and splice junctions were scanned with [DOVAM]-S in 104 schizophrenics, and pilot probes of patients with alcoholism (41 patients), cocaine abuse (25 patients), puerperal psychosis (30 patients), attention deficient/hyperactivity disorder (25 patients) and autism (25 patients). Six sequence variants were found, including five silent polymorphisms (allele frequencies 0.6--25%) and an in-frame deletion of a homologous repeat at nucleotides 967--978 (ie, TIDRU(1)). Genotyping of the normal two repeat unit of the Third Intracytoplasmic Domain Repeat Unit (TIDRU(2)) and the deleted variant (TIDRU(1)) revealed that TIDRU(1) had allelic frequencies of 39% (11/28) and 3.5% (6/172) in African-American and Caucasian schizophrenics, respectively, and it occurred with equal frequency in controls (44%, 31/70 and 3.0%, 6/198). TIDRU(1) occurs at a location similar to the third intracytoplasmic 48-nucleotide repeat unit in the DRD4 that is associated with ADHD. Although these data do not suggest an association of TIDRU(1) with schizophrenia, additional studies are needed to see whether TIDRU(1) confers a clinical phenotype. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 4 | Forensic Sci. Int. 2001 Nov 123: 13-6 |
| PMID | 11731191 |
| Title | Acute intoxication with orphenadrine and clozapine. |
| Abstract | This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 5 | Ross Fiziol Zh Im I M Sechenova 2002 Nov 88: 1388-93 |
| PMID | 12587266 |
| Title | [Correlation between cataleptic freezing and prestimulation inhibition of the startle reflex in rats]. |
| Abstract | In rats of GC strain bred for predisdposition to cataleptic freezing, a significant negative correlation between the duration of freezing and the level of prepulse inhibition (PPI) of the startle reflex, has been found. Besides, in a group of GC rats specific by their "nervousness" and jumpiness, there was also a negative correlation between the duration of freezing and the habituation to the startle reflex. None of this correlation have been found in Wistar rats. Since impairment of the PPI and habituation of the startle reflex is considered to be characteristic of schizophrenia, it is believed than cataleptic freezing in the GC rats may be used as a model of schizophrenic psychopathology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 6 | Ross Fiziol Zh Im I M Sechenova 2002 Nov 88: 1388-93 |
| PMID | 12587266 |
| Title | [Correlation between cataleptic freezing and prestimulation inhibition of the startle reflex in rats]. |
| Abstract | In rats of GC strain bred for predisdposition to cataleptic freezing, a significant negative correlation between the duration of freezing and the level of prepulse inhibition (PPI) of the startle reflex, has been found. Besides, in a group of GC rats specific by their "nervousness" and jumpiness, there was also a negative correlation between the duration of freezing and the habituation to the startle reflex. None of this correlation have been found in Wistar rats. Since impairment of the PPI and habituation of the startle reflex is considered to be characteristic of schizophrenia, it is believed than cataleptic freezing in the GC rats may be used as a model of schizophrenic psychopathology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 7 | Acta Psychiatr Scand 2002 Nov 106: 351-7 |
| PMID | 12366469 |
| Title | Does guilt proneness predict acute and long-term distress in relatives of patients with schizophrenia? |
| Abstract | The aim of the study was to improve our understanding of guilt proneness as predictor of acute and long-term stress responses in relatives of acutely admitted patients. Forty-nine relatives in close contact with 36 patients suffering from schizophrenia DSM-III-R, completed Hostility Guilt (HG) and Guilt Conscience (GC) scales (Revised Mosher Guilt Inventory), and Levenson's Locus of Control Scale (LOC) at the patient's admission to hospital, and the General Health Questionnaire (GHQ) at the patient's admission and at 9 months after discharge. Acute distress (GHQ) was positively related to HG, but not when controlling for LOC. GC was positively associated with acute and long-term distress, GHQ-depression and coping-failure, and long-term GHQ-anxiety. When controlling for LOC, GC was still positively related to long-term distress. HG, GC and LOC explained 32% variance of GHQ at 9 months. GC seems to be an important predictor of long-term distress in relatives. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 8 | Mol. Cell. Probes 2002 Oct 16: 379-84 |
| PMID | 12477442 |
| Title | Reduced amplification efficiency of KIAA0027/MLC1 alleles: implications for the molecular diagnosis of megalencephalic leukoencephalopathy with subcortical cysts. |
| Abstract | Autosomal recessive megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare childhood-onset spongiform leukodystrophy with macrocephaly and slowly progressive deterioration of motor functions. Mutations in KIAA0027/MLC1 have recently been found associated with MLC, and a high degree of allelic heterogeneity has been observed. In addition, initial reports suggested that a rare variant in exon 11 (L309M) is involved in the etiology of schizophrenia, but recent studies have brought forward compelling arguments that genetic variants of MLC1 are not associated with schizophrenia. Using DHPLC-analysis, reproduction of previous findings on L309M revealed homoduplex resolution patterns among individuals, who had been described to be heterozygous for the variant, which was further confirmed by sequencing the respective PCR products. Cumulative effects of high GC content, secondary folding structures due to incomplete intronic tandem-repeats, and a complicated insertion polymorphism at the 3-end of exon 11 may be the cause of preferential amplification of specific alleles of exon 11. Consistent amplification was obtained only when we employed exonic primers directly adjacent to the L309M variant. For mutational screening, we propose a two-step test: (1) testing for the 33 bp insertion polymorphism of exon 11, and (2) amplification of the exon using different primer sets depending on the presence or absence of the insertion. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 9 | Biochem. Biophys. Res. Commun. 2003 Dec 312: 1123-31 |
| PMID | 14651989 |
| Title | Cloning and cell type-specific regulation of the human tyrosine hydroxylase gene promoter. |
| Abstract | Tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine biosynthesis, is predominantly expressed in several cell groups within the brain, including the dopaminergic (DA) neurons of the substantia nigra and ventral tegmental area, and the noradrenergic neurons of the locus coeruleus. To investigate the regulation of cell type-specific TH expression, we cloned and sequenced a 5.5kb fragment of human genomic DNA immediately 5(') of the TH coding region. This 5(')-flanking region does not contain either a CAAT box or a GC-rich region, but does contain a TATA box and consensus binding sequences for basal (TATA and CRE), and DA neuron-specific (NBRE, Gli, and BBE) transcription factors. Sequence analysis showed low overall homology with the rat and mouse TH promoter regions, with the exception of two high-homology domains, which encompassed -2384 to -2323 and -123 to -65, respectively. Interestingly, these distal and proximal domains contained NBRE, BBE, CRE, and TATA boxes, which are known to play important roles in DA neurogenesis. To further localize the TH promoter region responsible for transcriptional activity, we fused a 3301-bp human TH promoter fragment (-3174 to +127) to a luciferase reporter gene, and used this to assess promoter activity in neuronal and non-neuronal cell lines. Consistent with endogenous TH expression, this promoter construct was active in SH-SY5Y human neuroblastoma cells but not F3 human neural stem cells (NSCs). Deletion analysis of TH promoter/luciferase constructs revealed the presence of the repressor element in -1232 to -1210 upstream of transcription initiation site. While this region repressed 85% of promoter activity when transfected into F3 cells, it was not active in SH-SY5Y cells. These data suggest that the repressor element may play an important role in neuron cell-specific expression of the TH gene. Our results may provide insight into neuronal cell-specific expression of the human TH gene and allow a better understanding of catecholaminergic neuron disorders such as Parkinson's disease and schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 10 | Amino Acids 2003 Jul 25: 49-57 |
| PMID | 12836058 |
| Title | Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. |
| Abstract | We applied proteomics technologies to analyze the cerebrospinal fluid of patients with schizophrenia. Such an analysis can result in the identification of proteins, which may play a role in the disease progress and thus lead to the discovery of clues of the etiology of schizophrenia. Cerebrospinal fluid from patients and controls was analyzed by two-dimensional gels and the proteins were identified by matrix-assisted laser desorption ionization mass spectrometry (MS) in the MS and MS/MS mode. 54 different gene products were identified, which were mainly plasma proteins. The level of apolipoprotein A-IV was significantly decreased in the schizophrenic patients compared to that in the controls. Little is known about the function of this apolipoprotein in the central nervous system. The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and GC-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 11 | Amino Acids 2003 Jul 25: 49-57 |
| PMID | 12836058 |
| Title | Proteomic analysis of the cerebrospinal fluid of patients with schizophrenia. |
| Abstract | We applied proteomics technologies to analyze the cerebrospinal fluid of patients with schizophrenia. Such an analysis can result in the identification of proteins, which may play a role in the disease progress and thus lead to the discovery of clues of the etiology of schizophrenia. Cerebrospinal fluid from patients and controls was analyzed by two-dimensional gels and the proteins were identified by matrix-assisted laser desorption ionization mass spectrometry (MS) in the MS and MS/MS mode. 54 different gene products were identified, which were mainly plasma proteins. The level of apolipoprotein A-IV was significantly decreased in the schizophrenic patients compared to that in the controls. Little is known about the function of this apolipoprotein in the central nervous system. The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and GC-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 12 | Neurosci. Behav. Physiol. 2004 May 34: 413-6 |
| PMID | 15341220 |
| Title | Correlation between cataleptic freezing and prepulse inhibition of the startle reflex in rats. |
| Abstract | GC rats, bred for a predisposition to cataleptic freezing, were found to show a significant negative correlation between the duration of freezing and the level of prepulse inhibition of the startle reflex. In addition, a group of GC rats characterized by increased "nervousness" also showed a negative correlation between the duration of freezing and the extent of habituation of the startle reflex. These correlations were not seen in Wistar rats. Since decreases in the level of prepulse inhibition and habituation of the startle reflex are regarded as characteristic of schizophrenia, it is suggested that cataleptic freezing in GC rats might be used as a model of schizophrenic pyschopathology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 13 | Neurosci. Behav. Physiol. 2004 May 34: 413-6 |
| PMID | 15341220 |
| Title | Correlation between cataleptic freezing and prepulse inhibition of the startle reflex in rats. |
| Abstract | GC rats, bred for a predisposition to cataleptic freezing, were found to show a significant negative correlation between the duration of freezing and the level of prepulse inhibition of the startle reflex. In addition, a group of GC rats characterized by increased "nervousness" also showed a negative correlation between the duration of freezing and the extent of habituation of the startle reflex. These correlations were not seen in Wistar rats. Since decreases in the level of prepulse inhibition and habituation of the startle reflex are regarded as characteristic of schizophrenia, it is suggested that cataleptic freezing in GC rats might be used as a model of schizophrenic pyschopathology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 14 | Psychiatry Clin. Neurosci. 2004 Aug 58: 359-63 |
| PMID | 15298647 |
| Title | Lack of association between sigma receptor gene variants and schizophrenia. |
| Abstract | Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 15 | Psychiatry Clin. Neurosci. 2004 Aug 58: 359-63 |
| PMID | 15298647 |
| Title | Lack of association between sigma receptor gene variants and schizophrenia. |
| Abstract | Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 16 | Genetika 2004 Jun 40: 827-34 |
| PMID | 15341273 |
| Title | [Catatonia or depression: the GC rat strain as an animal model of psychopathology]. |
| Abstract | The utility of "incomplete" genetic animal models of human diseases, in particular, psychoses, is discussed. The GC rat strain selected for predisposition to cataleptic reactions is described. It is shown that in many of their characteristics, GC rats are similar to schizophrenic and depressive patients. A possibility that akinetic catatonic states and depressions, hyperkinetic catatonic states and mania share common mechanisms is discussed. It is hypothesized that the GC strain may be an incomplete model of the common genetic and pathogenetic core of schizophrenic substuporous states and depression, which suggests the importance of returning to the issue of a unitary psychosis (Einheitpsychosis). |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 17 | Neurosci. Lett. 2005 Dec 389: 173-7 |
| PMID | 16115734 |
| Title | Quetiapine and venlafaxine synergically regulate heme oxygenase-2 protein expression in the hippocampus of stressed rats. |
| Abstract | HO-2 is a constitutive isoform of heme oxygenase (HO), a microsomal enzyme that catalyzes the cleavage of the heme ring to form ferrous iron, carbon monoxide, and biliverdin. In contrast to HO-1, which is inducible, HO-2 is not responsive to stimuli tested to date except for prolonged exposure to the adrenal glucocorticoids (GCs). Previous studies have shown that high GC concentrations or stress damage or kill hippocampal neurons. In the present study, it was found that chronic restraint stress decreased HO-2 protein levels in hippocampal neurons, as demonstrated by immunohistochemistry and Western blot analysis. Moreover, our results showed that the combination of 2.5mg/kg of venlafaxine and 5mg/kg of quetiapine effectively prevented the HO-2 protein decrease in hippocampal neurons of stressed rats, whereas either of the drugs alone did not show any effect. At higher dose levels, both quetiapine (10mg/kg) and venlafaxine (5mg/kg) produced significant effects comparable to that of their combination. Quetiapine is an atypical antipsychotic and venlafaxine an antidepressant. In previous studies, these two drugs have been shown to prevent or protect against the stress-induced decrease in hippocampal neurogenesis and BDNF expression. These data suggest that both quetiapine and venlafaxine share the hippocampus as their common target by enhancing hippocampal resilience, which may be impaired in patients with schizophrenia or depression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 18 | Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 42-7 |
| PMID | 16252386 |
| Title | [Dopamine receptor DRD4 gene polymorphism and its association with schizophrenia spectrum disorders and personality traits of patients]. |
| Abstract | A vast body of associative studies reported a role of highly polymorphic dopamine receptor DRD4 gene in regulation of emotional processes and development of mental disorders. The present study addresses allele, genotype and haplotype distribution of 3 polymorphic DRD4 markers (-809G/A, -616G/C N -521C/T) in Russian patients with schizophrenia spectrum disorders and their relation to the disease and personality traits. A sample included 151 patients with iCD-10 diagnosis of schizophrenia, schizoaffective psychosis and schizotypal personality disorders, 89 their first-degree non-psychotic relatives and 131 mentally healthy individuals. No differences in allele and genotype frequency was found between the patients and the controls. Transmission disiquilibrium test (TDT) did not reveal a preferential transmission of either allele from parents to proband. The 521C/T N -616G/C markers were linked to the disease when the EH program has been used in the analysis. Patients with the GG (-809G/A) and GG (-616G/C) genotypes had higher scores on the Hypomania scale (MMPI) comparing to the GA(-809G/A)+AA(-809G/A) and GC(-616G/C)+CC(-616G/C) genotypes but the association did not reach a level of significance (p = 0.06). The results confirmed the literature reports on the relation of the DRD4 gene to schizophrenia and personality traits related to social activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 19 | Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 42-7 |
| PMID | 16252386 |
| Title | [Dopamine receptor DRD4 gene polymorphism and its association with schizophrenia spectrum disorders and personality traits of patients]. |
| Abstract | A vast body of associative studies reported a role of highly polymorphic dopamine receptor DRD4 gene in regulation of emotional processes and development of mental disorders. The present study addresses allele, genotype and haplotype distribution of 3 polymorphic DRD4 markers (-809G/A, -616G/C N -521C/T) in Russian patients with schizophrenia spectrum disorders and their relation to the disease and personality traits. A sample included 151 patients with iCD-10 diagnosis of schizophrenia, schizoaffective psychosis and schizotypal personality disorders, 89 their first-degree non-psychotic relatives and 131 mentally healthy individuals. No differences in allele and genotype frequency was found between the patients and the controls. Transmission disiquilibrium test (TDT) did not reveal a preferential transmission of either allele from parents to proband. The 521C/T N -616G/C markers were linked to the disease when the EH program has been used in the analysis. Patients with the GG (-809G/A) and GG (-616G/C) genotypes had higher scores on the Hypomania scale (MMPI) comparing to the GA(-809G/A)+AA(-809G/A) and GC(-616G/C)+CC(-616G/C) genotypes but the association did not reach a level of significance (p = 0.06). The results confirmed the literature reports on the relation of the DRD4 gene to schizophrenia and personality traits related to social activity. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 20 | Med. Sci. Monit. 2005 Aug 11: CR366-75 |
| PMID | 16049378 |
| Title | Identification of schizophrenic patients by examination of body odor using gas chromatography-mass spectrometry and a cross-selective gas sensor array. |
| Abstract | Previous findings have shown that the body odor of patients affected by schizophrenia contains some specific compounds. Chemical sensor technology has proved to be able to classify different odours. We investigated the possibility of using a chemical sensor array to detect body odor alteration in schizophrenic patients. The sweat of subjects was sampled and analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and by an array of cross-selective gas sensors. A total of 27 individuals were involved in the experiment: 9 schizophrenics, 9 with other mental disorders, and 9 controls. GC-MS analysis showed a richer composition for the sweat of schizophrenic patients. Nevertheless, the individuation of specific markers was unsuccessful. On the other hand, statistical analysis of cross-selective gas sensor data provided a complete classification of schizophrenic patients with respect to the other three groups. The alteration of body odor in schizophrenic patients was confirmed by GC-MS and chemical sensor array. Results show that the alteration is complex and cannot be limited to a single compound, but rather to a global variation of the body odor. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 21 | Med. Sci. Monit. 2005 Aug 11: CR366-75 |
| PMID | 16049378 |
| Title | Identification of schizophrenic patients by examination of body odor using gas chromatography-mass spectrometry and a cross-selective gas sensor array. |
| Abstract | Previous findings have shown that the body odor of patients affected by schizophrenia contains some specific compounds. Chemical sensor technology has proved to be able to classify different odours. We investigated the possibility of using a chemical sensor array to detect body odor alteration in schizophrenic patients. The sweat of subjects was sampled and analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and by an array of cross-selective gas sensors. A total of 27 individuals were involved in the experiment: 9 schizophrenics, 9 with other mental disorders, and 9 controls. GC-MS analysis showed a richer composition for the sweat of schizophrenic patients. Nevertheless, the individuation of specific markers was unsuccessful. On the other hand, statistical analysis of cross-selective gas sensor data provided a complete classification of schizophrenic patients with respect to the other three groups. The alteration of body odor in schizophrenic patients was confirmed by GC-MS and chemical sensor array. Results show that the alteration is complex and cannot be limited to a single compound, but rather to a global variation of the body odor. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 22 | Med. Sci. Monit. 2005 Aug 11: CR366-75 |
| PMID | 16049378 |
| Title | Identification of schizophrenic patients by examination of body odor using gas chromatography-mass spectrometry and a cross-selective gas sensor array. |
| Abstract | Previous findings have shown that the body odor of patients affected by schizophrenia contains some specific compounds. Chemical sensor technology has proved to be able to classify different odours. We investigated the possibility of using a chemical sensor array to detect body odor alteration in schizophrenic patients. The sweat of subjects was sampled and analysed by Gas Chromatography-Mass Spectrometry (GC-MS) and by an array of cross-selective gas sensors. A total of 27 individuals were involved in the experiment: 9 schizophrenics, 9 with other mental disorders, and 9 controls. GC-MS analysis showed a richer composition for the sweat of schizophrenic patients. Nevertheless, the individuation of specific markers was unsuccessful. On the other hand, statistical analysis of cross-selective gas sensor data provided a complete classification of schizophrenic patients with respect to the other three groups. The alteration of body odor in schizophrenic patients was confirmed by GC-MS and chemical sensor array. Results show that the alteration is complex and cannot be limited to a single compound, but rather to a global variation of the body odor. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 23 | Biol. Psychiatry 2005 Jul 58: 16-22 |
| PMID | 15992519 |
| Title | MLC1 gene is associated with schizophrenia and bipolar disorder in Southern India. |
| Abstract | Chromosome 22q13 has shown linkage with schizophrenia (SCZ) and bipolar affective disorder (BPAD). A missense mutation in MLC1 (putative cation-channel gene on 22q13) co-segregating with periodic catatonic schizophrenia has been reported. We have investigated the relationship of MLC1 with SCZ and BPAD in Southern India. All exons and flanking intronic sequences of MLC1 were screened for novel variations. Case-control (216 BPAD, 193 SCZ, 116 control subjects) and family-based analyses (113 BPAD, 107 SCZ families) were performed to evaluate association of MLC1 with these disorders. We found 33 MLC1 sequence variations, including three novel mutations: Val210Ile, Leu308Gln, and Arg328His in six BPAD cases and Val210Ile in one control individual. Minor allele of a common variation, ss16339182 (in approximately 6 Kb Linkage-Disequilibrium [LD]-block) was associated with BPAD in case-control (p = .03) and family-based analyses (transmitted/nontransmitted [T/NT]-44/20; p = .003). Association was observed for rs2235349 and rs2076137 with SCZ and ss16339163 with BPAD in case-control study. Using Block 2 haplotype tagging single nucleotide polymorphisms (htSNPs), GC haplotype revealed association (p = .02) and excess transmission (p = .002) with BPAD. Association of MLC1 with SCZ and BPAD suggests involvement of a common pathway. Rare missense mutations and common variants associated with BPAD favors hypothesis about likely involvement of both rare and common polymorphisms in etiology of this complex disorder. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 24 | Mol. Psychiatry 2006 May 11: 479-87 |
| PMID | 16402132 |
| Title | Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations. |
| Abstract | Recently, the nested genes G72 and G30 on chromosome 13q32-q33 have been implicated in the etiology of schizophrenia. We genotyped six single-nucleotide polymorphisms (SNPs: rs3916965, rs3916967, rs2391191, rs778294, rs779293 and rs3918342), which span approximately 82.5 kb in the region encompassing the G72/G30 genes in 1176 Han Chinese subjects (588 cases and 588 controls) and 365 Scottish subjects (183 cases and 182 controls). Significant association between an allele of marker rs778293 and schizophrenia was found in our Chinese samples (P = 0.0013), and was replicated in the Scottish samples (P = 0.022). LD analysis revealed that four SNPs between rs3916965 and rs778294 were in LD, called block I, and the two distal SNPs (rs778293 and rs3918342) constituted a block II in both the Chinese and Scottish samples. We selected one SNP from each block (rs778294 from block I and rs778293 from block II), and then analyzed the haplotypes. A significant difference was observed for the common haplotype GC in the Chinese sample (P = 0.0145), and was replicated in the Scottish sample (P = 0.003). On meta-analysis, we separately analyzed the studies in Asian and European populations because of significant heterogeneity in the homogeneity test. We found a statistically significant association between rs778293 and schizophrenia in Asian populations, but no difference was found between cases and controls in the European populations. Overall, our data give further support to the existing evidence that G72/G30 genes are involved in conferring susceptibility to schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 25 | PLoS ONE 2007 -1 2: e817 |
| PMID | 17786189 |
| Title | Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. |
| Abstract | The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. mRNA of Sp1 and of mitochondrial complex I subunits (NDUFV1, NDUFV2) was analyzed in three postmortem brain regions obtained from the Stanley Foundation Brain Collection, and in lymphocytes of schizophrenic patients and controls. Sp1 role in the transcription of these genes was studied as well. Sp1 was abnormally expressed in schizophrenia in both brain and periphery. Its mRNA alteration pattern paralleled that of NDUFV1 and NDUFV2, decreasing in the prefrontal cortex and the striatum, while increasing in the parieto-occipital cortex and in lymphocytes of schizophrenic patients as compared with controls. Moreover, a high and significant correlation between these genes existed in normal subjects, but was distorted in patients. Sp1 role in the regulation of complex I subunits, was demonstrated by the ability of the Sp1/DNA binding inhibitor, mithramycin, to inhibit the transcription of NDUFV1 and NDUFV2, in neuroblastoma cells. In addition, Sp1 activated NDUFV2 promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin. These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 26 | PLoS ONE 2007 -1 2: e817 |
| PMID | 17786189 |
| Title | Sp1 expression is disrupted in schizophrenia; a possible mechanism for the abnormal expression of mitochondrial complex I genes, NDUFV1 and NDUFV2. |
| Abstract | The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. mRNA of Sp1 and of mitochondrial complex I subunits (NDUFV1, NDUFV2) was analyzed in three postmortem brain regions obtained from the Stanley Foundation Brain Collection, and in lymphocytes of schizophrenic patients and controls. Sp1 role in the transcription of these genes was studied as well. Sp1 was abnormally expressed in schizophrenia in both brain and periphery. Its mRNA alteration pattern paralleled that of NDUFV1 and NDUFV2, decreasing in the prefrontal cortex and the striatum, while increasing in the parieto-occipital cortex and in lymphocytes of schizophrenic patients as compared with controls. Moreover, a high and significant correlation between these genes existed in normal subjects, but was distorted in patients. Sp1 role in the regulation of complex I subunits, was demonstrated by the ability of the Sp1/DNA binding inhibitor, mithramycin, to inhibit the transcription of NDUFV1 and NDUFV2, in neuroblastoma cells. In addition, Sp1 activated NDUFV2 promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin. These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 27 | J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2007 Sep 856: 57-61 |
| PMID | 17602901 |
| Title | Detection and quantification of aripiprazole and its metabolite, dehydroaripiprazole, by gas chromatography-mass spectrometry in blood samples of psychiatric patients. |
| Abstract | Aripiprazole is a novel antipsychotic drug for the treatment of schizophrenia and schizoaffective disorders. In this study, a new method using gas chromatography-mass spectrometry (GC-MS) was developed and validated for the detection of aripiprazole and its main metabolite, dehydroaripiprazole, in plasma. Blood samples from seven psychiatric patients treated with aripiprazole (10-20 mg/day) underwent a solid-phase extraction (SPE) and N-methyl-N-trimethylsilytrifluoroacetamide (MSTFA) derivatization. The characteristic ions of mass spectra for aripiprazole and dehydroaripiprazole were m/z 306, 292, 218 and 304, 290, 218, respectively. Extraction recoveries from this method were 75.4% (n=5) for aripiprazole and 102.3% (n=5) for dehydroaripiprazole. The calibration curves of aripiprazole and dehydroaripiprazole were linear from 16 to 500 ng/ml (r(2)=0.999) and 8 to 250 ng/ml (r(2)=0.999), respectively. The respective limits of quantification (LOQs) for aripiprazole and dehydroaripiprazole evaluated in 0.5 ml of serum were 14.4 ng/ml and 6.9 ng/ml. Intra-assay and interassay precision and accuracy were within acceptable ranges. In this study, we also found that the mean trough concentrations in plasma at steady-state were 128.9 microg/l for aripiprazole and 30.1 microg/l for dehydroaripiprazole. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 28 | J. Neurochem. 2008 Mar 104: 1450-65 |
| PMID | 18028338 |
| Title | Cholecystokinin-2 receptor mediated gene expression in neuronal PC12 cells. |
| Abstract | Cholecystokinin (CCK) is abundantly expressed in the CNS, in which it regulates feeding behavior and long-term memory. Moreover, CCK has been implicated in mental disorders, such as anxiety and schizophrenia. Despite its manifest physiological and pathophysiological role, the molecular targets of neuronal CCK are incompletely understood. To identify genes regulated by neuronal CCK, we generated neuronal PC12 cells stably expressing the CCK-2 receptor (CCK-2R) and treated the cells with sulphated CCK-8 for 2-16 h, before the global expression profile was examined. The changes in gene expression peaked after 2 h, with 67 differentially expressed transcripts identified. A pathway analysis indicated that CCK was implicated in the regulation of the circadian clock system, the plasminogen system and cholesterol metabolism. But transcripts encoding proteins involved in dopamine signaling, ornithine decarboxylase (ODC) regulation, memory and epidermal growth factor receptor (EGFR) signaling were also found. Several target genes contained cAMP response elements (CREs), serum response elements (SREs), activator protein 1 (AP1) elements and GC-rich regions, but otherwise no common regulatory promoter element could be identified. Comparison with forskolin- and nerve growth factor (NGF)-treated PC12 cells showed that CCK induced a separate set of target genes. Taken together, we propose that neuronal CCK may have a role in the regulation of the circadian rhythm, the metabolism of cerebral cholesterol and in the regulation of the plasminogen system. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 29 | Biol. Psychiatry 2008 Dec 64: 1093-6 |
| PMID | 18708184 |
| Title | Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese population. |
| Abstract | The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population. Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis. In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype-transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed. The result supports that the NRG3 gene is a susceptibility gene for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 30 | Biol. Psychiatry 2008 Dec 64: 1093-6 |
| PMID | 18708184 |
| Title | Neuregulin 3 genetic variations and susceptibility to schizophrenia in a Chinese population. |
| Abstract | The study investigated the possible association of NRG3 gene and schizophrenia in a Han Chinese population. Of a total of 1345, 270 unrelated schizophrenia inpatients, 235 normal control subjects, and 280 nuclear families (trios) with schizophrenia probands were studied. Nine single nucleotide polymorphisms (SNPs) spanning intron 1 to exon 9 of the NRG3 gene were analyzed, starting with the case-control samples. The SNPs showing significant association with schizophrenia in the case-control samples were subsequently studied in the independent trio samples with family-based association analysis. In case-control samples, two SNPs (rs1937970 and rs677221) showed significant genotypic and allelic association with schizophrenia (all p < .05) with rs677221-C being the risk allele for schizophrenia (uncorrected p = .001, odds ratio = 1.439, 95% confidence interval = 1.115-1.858). Haplotypes GC constructed by the two SNPs was also significantly associated with schizophrenia (permutation p value = .0047). In the independent trio samples, rs1937970-A and rs677221-G consistently showed significant under-transmission to schizophrenic offspring (unadjusted p = .003 and p = .004, respectively). In the haplotype-transmission disequilibrium test (TDT) for allelic combination of rs1937970-rs677221, significant under-transmission for haplotype AG (uncorrected p = .006) and over-transmission for haplotype GC (uncorrected p = .004) to the affected schizophrenia offspring were observed. The result supports that the NRG3 gene is a susceptibility gene for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 31 | Pharmacogenomics 2009 Jun 10: 989-95 |
| PMID | 19530966 |
| Title | Development of a new genotyping assay for detection of the BDNF Val66Met polymorphism using melting-curve analysis. |
| Abstract | Brain-derived neurotrophic factor (BDNF) plays a critical role in the growth, differentiation and survival of neurons in the CNS. Recent research has suggested that BDNF may be implicated in the etiology of mood disorders and schizophrenia, as well as in the therapeutic action of some drugs, such as antidepressants and antipsychotics. This study aimed to develop a simple, fast and accurate new method for detecting the Val66Met polymorphism of the BDNF gene in schizophrenia patients using melting-curve analysis and a DNA-specific dye, SYBR Green I. A group of 30 schizophrenia patients were analyzed to detect the BDNF Val66Met polymorphism (rs6265) using the new genotyping method based on the analysis of fluorescence melting curves of PCR products that were labeled with SYBR Green I. The genotype results were confirmed for all 30 samples using the specific BDNF TaqMan allele discrimination assay. This new method allows the analysis of both alleles in the same reaction tube using SYBR Green I, with no need for additional steps. The addition of a GC clamp makes this method universally applicable, since the melting temperature of one allele can be adjusted as necessary to give the distinctive separation of melting curves. Therefore, this new method is simple, fast and accurate for determining the presence of the BDNF Val66Met polymorphism. It may also be useful for the analysis of other SNPs in pharmacogenetic studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 32 | Chem. Pharm. Bull. 2009 Nov 57: 1251-6 |
| PMID | 19881277 |
| Title | Effects of formulation parameters on encapsulation efficiency and release behavior of risperidone poly(D,L-lactide-co-glycolide) microsphere. |
| Abstract | A 4-week sustained release risperidone biodegradable poly(D,L-lactide-co-glycolide) (PLGA) microsphere for the therapy of schizophrenia, the effects of formulation parameters on encapsulation efficiency and release behavior were studied. The risperidone PLGA microspheres were prepared by O/W solvent evaporation method and characterized by HPLC, SEM, laser particle size analysis, GC and HPLC-MS. The results indicated that the morphology of the risperidone PLGA microspheres presented a spherical shape with smooth surface, the particle size was distributed from 32 to 92 microm and the drug encapsulation efficiency was influenced by homogeneous rotation speed, intrinsic viscosity, carboxylic terminal group, the polymer concentration in the oil phase and the molecular weight of the polymer. These changes were also reflected in drug release. When the Mw of the polymers increased from ca. 28000 to ca. 90000, the initial burst release of risperidone PLGA microspheres decreased from 13 to 0.8% and the sustained-release could be extended to 4 weeks. Pharmacokinetic study on beagle dogs showed that the 4-week sustained release profile of the risperidone loaded microspheres prepared with 75253A was verified. The PLGA 75253A and 75255A show the potential as excipients for the monthly sustained release risperidone PLGA microspheres due to higher encapsulation efficiency and almost zero-order release kinetics of release profile. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 33 | Schizophr. Res. 2009 Sep 113: 259-67 |
| PMID | 19502010 |
| Title | Two complex genotypes relevant to the kynurenine pathway and melanotropin function show association with schizophrenia and bipolar disorder. |
| Abstract | Prior studies of mRNA expression, protein expression, and pathway metabolite levels have implicated dysregulation of the kynurenine pathway in the etiology of schizophrenia and bipolar disorder. Here we investigate whether genes involved in kynurenine pathway regulation might interact with genes that respond to kynurenine metabolites, to enhance risk for these psychiatric phenotypes. Candidate genes were selected from prior studies of genetic association, gene expression profiling and animal models. A single nucleotide polymorphism (SNP) in each of six genes, TDO2, HM74, HM74A, MCHR1, MCHR2 and MC5R, was tested for association with phenotype (475 Caucasians, 88 African Americans with schizophrenia; 97 Caucasians, 3 African Americans with bipolar disorder; 191 Caucasian, 49 African American controls). An A allele in HM74 was significantly associated with schizophrenia and with schizophrenia plus bipolar disorder combined, odds ratios (OR) of 1.48, p=0.011 and 1.50, p=0.007, respectively. Augmentation of disease risk was found for the complex genotype HM74[A,any]+MCHR1[T,any]+MCHR2[C,any] which conferred an OR maximal for the combined diagnostic category of schizophrenia plus bipolar disorder (1.70, p=0.003), carried by 30% of the cases. TDO2[CC]+MC5R[G, any]+MCHR2[GC] conferred an OR maximal for schizophrenia alone (4.84, p=0.005), carried by 8% of schizophrenia cases. The combined risk posed by these related, complex genotypes is greater than any identified single locus and may derive from co-regulation of the kynurenine pathway by interacting genes, a lack of adequate melanotropin-controlled sequestration of the kynurenine-derived pigments, or the production of melanotropin receptor ligands through kynurenine metabolism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 34 | J. Mol. Neurosci. 2010 Sep 42: 112-9 |
| PMID | 20393813 |
| Title | Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. |
| Abstract | schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 35 | J. Mol. Neurosci. 2010 Sep 42: 112-9 |
| PMID | 20393813 |
| Title | Functional polymorphism in the interleukin-6 and interleukin-10 genes in patients with paranoid schizophrenia--a case-control study. |
| Abstract | schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 36 | Hum Psychopharmacol 2010 Apr 25: 253-9 |
| PMID | 20373477 |
| Title | Association study of polymorphisms in insulin induced gene 2 (INSIG2) with antipsychotic-induced weight gain in European and African-American schizophrenia patients. |
| Abstract | Atypical antipsychotic drugs, in particular clozapine and olanzapine, influence cellular lipogenesis and are associated with metabolic side effects including weight gain. Insulin induced gene 2 (INSIG2) mediates feedback control of lipid synthesis and polymorphisms in the gene (rs17587100, rs10490624 and rs17047764) have been associated with antipsychotic induced weight gain. In this study we intended to replicate these findings in an independent patient population. All three polymorphisms as well as an additional polymorphism (rs7566605) were genotyped in 154 patients who underwent treatment for chronic schizophrenia with one of four antipsychotics (clozapine, olanzapine, haloperidol or risperidone). Patients were evaluated for antipsychotic induced weight gain during treatment for up to 14 weeks. We did not observe any significant allelic, genotypic or haplotypic association of the polymorphisms with antipsychotic induced weight gain in the patients of European ancestry (p > 0.05). In the patients of African ancestry, no haplotypic association was observed but a trend of allelic association with the C allele of rs7566605 and genotypic association with the 'GC' genotype in rs17047764 was observed (p = 0.02; p(Bonferroni) = 0.225). We were unable to replicate significant associations in patients of European ancestry. However, we observed a marginal effect of the rs17047764 and rs7566605 in the African-American sample. Since the latter observations were generated in a relatively small sample set, further replication studies are warranted. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 37 | Biochem. Biophys. Res. Commun. 2011 Nov 415: 519-25 |
| PMID | 22079628 |
| Title | Sigma-1Rs are upregulated via PERK/eIF2?/ATF4 pathway and execute protective function in ER stress. |
| Abstract | Sigma-1 receptors (Sig-1Rs) are the ER resident proteins. Sig-1Rs in the brain have been reported to be significantly reduced in patients with schizophrenia. The impediment of regulating Sig-1Rs expression levels increases the risk for schizophrenia. Thus elucidating the mechanism regulating Sig-1Rs expression might provide the strategy to prevent mental disorders. In this study, we have demonstrated that Sig-1Rs were transcriptionally upregulated by ATF4 in ER stress. Moreover, ATF4 directly bounds to the 5' flanking region of Sig-1R gene. The reporter activities using this region were enhanced in ER stress, or by ATF4 alone. The reporter activities with the pathogenic polymorphisms (GC-241-240TT, T-485A) were reduced. In addition, the processing of Caspase-4 was inhibited by Sig-1Rs. These results indicate that Sig-1Rs are transcriptionally upregulated via the PERK/eIF2?/ATF4 pathway and ameliolate cell death signaling. This study is the first report identifying the transcription factor regulating Sig-1Rs expression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 38 | Science 2011 Sep 333: 1642-6 |
| PMID | 21835979 |
| Title | Role for the membrane receptor guanylyl cyclase-C in attention deficiency and hyperactive behavior. |
| Abstract | Midbrain dopamine neurons regulate many important behavioral processes, and their dysfunctions are associated with several human neuropsychiatric disorders such as attention deficit hyperactivity disorder (ADHD) and schizophrenia. Here, we report that these neurons in mice selectively express guanylyl cyclase-C (GC-C), a membrane receptor previously thought to be expressed mainly in the intestine. GC-C activation potentiates the excitatory responses mediated by glutamate and acetylcholine receptors via the activity of guanosine 3',5'-monophosphate-dependent protein kinase (PKG). Mice in which GC-C has been knocked out exhibit hyperactivity and attention deficits. Moreover, their behavioral phenotypes are reversed by ADHD therapeutics and a PKG activator. These results indicate important behavioral and physiological functions for the GC-C/PKG signaling pathway within the brain and suggest new therapeutic targets for neuropsychiatric disorders related to the malfunctions of midbrain dopamine neurons. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 39 | J Mass Spectrom 2011 May 46: 502-7 |
| PMID | 21500319 |
| Title | Simultaneous determination of serine enantiomers in plasma using Mosher's reagent and stable isotope dilution gas chromatography-mass spectrometry. |
| Abstract | D-Serine is a co-agonist of the N-methyl-D-aspartate receptor in glutamate neurotransmission and has been proposed as a potential therapeutic agent for schizophrenia. However, D-serine also acts as a nephrotoxic substance in rats at high doses. To investigate the pharmacokinetics and toxicokinetics of D-serine, a method for the stereoselective determination of serine enantiomers in rat plasma was developed using GC-MS with selected ion monitoring (GC-MS-SIM). DL-[(2)H(3)]Serine was used as an internal standard to account for losses associated with the extraction, derivatization and chromatography. Serine enantiomers were purified by cation-exchange chromatography using BondElut SCX cartridge and derivatized with HCl in methanol to form methyl ester followed by subsequent N,O-diacylation with optically active (+)-?-methoxy-?-trifluoromethylphenylacetyl chloride to form epimeric amide. Quantitation was performed by SIM of the molecular-related ions of the epimers in the chemical ionization mode. The intra- and inter-day reproducibility of the assay was less than 5% for D-serine and 3% for L-serine. The method was successively applied to study the pharmacokinetics of D-serine in rats. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 40 | Pharmacol. Biochem. Behav. 2011 Apr 98: 234-40 |
| PMID | 21236294 |
| Title | Effects of the alpha- and gamma-polymorphs of glycine on the behavior of catalepsy prone rats. |
| Abstract | Glycine is used to treat various health problems and is efficient in the treatment of the negative symptoms of schizophrenia. Since glycine exists as a few polymorphs, the aim of this work is to compare the effects of the alpha- and gamma-forms of glycine on the behavior of the genetic catalepsy (GC) strain of rats. Both polymorphs of glycine have been administered to rats orally as pure solid chemicals, and cataleptic behavior and behaviors in the open-field, elevated plus-maze, and light-dark box tests were studied. Both the alpha- and gamma-polymorphs of glycine increased exploratory activity in the open-field test, but only the gamma-polymorph had beneficial effects on catalepsy and exploratory activity in the light-dark box and reduced anxiety in the elevated plus-maze. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 41 | Genome Med 2011 -1 3: 19 |
| PMID | 21429189 |
| Title | Metabolome in schizophrenia and other psychotic disorders: a general population-based study. |
| Abstract | Persons with schizophrenia and other psychotic disorders have a high prevalence of obesity, impaired glucose tolerance, and lipid abnormalities, particularly hypertriglyceridemia and low high-density lipoprotein. More detailed molecular information on the metabolic abnormalities may reveal clues about the pathophysiology of these changes, as well as about disease specificity. We applied comprehensive metabolomics in serum samples from a general population-based study in Finland. The study included all persons with DSM-IV primary psychotic disorder (schizophrenia, n = 45; other non-affective psychosis (ONAP), n = 57; affective psychosis, n = 37) and controls matched by age, sex, and region of residence. Two analytical platforms for metabolomics were applied to all serum samples: a global lipidomics platform based on ultra-performance liquid chromatography coupled to mass spectrometry, which covers molecular lipids such as phospholipids and neutral lipids; and a platform for small polar metabolites based on two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC × GC-TOFMS). Compared with their matched controls, persons with schizophrenia had significantly higher metabolite levels in six lipid clusters containing mainly saturated triglycerides, and in two small-molecule clusters containing, among other metabolites, (1) branched chain amino acids, phenylalanine and tyrosine, and (2) proline, glutamic, lactic and pyruvic acids. Among these, serum glutamic acid was elevated in all psychoses (P = 0.0020) compared to controls, while proline upregulation (P = 0.000023) was specific to schizophrenia. After adjusting for medication and metabolic comorbidity in linear mixed models, schizophrenia remained independently associated with higher levels in seven of these eight clusters (P < 0.05 in each cluster). The metabolic abnormalities were less pronounced in persons with ONAP or affective psychosis. Our findings suggest that specific metabolic abnormalities related to glucoregulatory processes and proline metabolism are specifically associated with schizophrenia and reflect two different disease-related pathways. Metabolomics, which is sensitive to both genetic and environmental variation, may become a powerful tool in psychiatric research to investigate disease susceptibility, clinical course, and treatment response. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 42 | Indian J Hum Genet 2012 May 18: 222-5 |
| PMID | 23162299 |
| Title | Lack of association between the G-660C polymorphism in the dopamine transporter gene (SLC6A3) and schizophrenia in the Iranian population. |
| Abstract | Dopaminergenic system plays an essential role in the plasticity of the human brain. The dopamine transporter gene (SLC6A3) mediates active reuptake of dopamine from synapsis, terminates dopamine signals, and therefore, is implicated in a number of dopamine-related disorders like psychosis. Variations in the form of single nucleotide polymorphisms in the core promoter of the SLC6A3 gene are reported to be involved in the pathogenesis of schizophrenia. In this study, we also attempted to establish the possible role of the polymorphism G-660C in the SLC6A3 gene promoter in schizophrenia in a case-control study. The allele and genotype frequency were analyzed in an Iranian cohort of 200 unrelated patients and 200 controls using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequency for case and control groups was GG 100%, GC 0%, CC 0%, and GG 100%, GC 0%, CC 0%, respectively. The C allele was failed in both groups. Our data suggest clearly that there is no association between the -660G/C polymorphism and outcome of schizophrenia in the Iranian population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 43 | Am. J. Hum. Genet. 2012 Oct 91: 597-607 |
| PMID | 23040492 |
| Title | Discovery and statistical genotyping of copy-number variation from whole-exome sequencing depth. |
| Abstract | Sequencing of gene-coding regions (the exome) is increasingly used for studying human disease, for which copy-number variants (CNVs) are a critical genetic component. However, detecting copy number from exome sequencing is challenging because of the noncontiguous nature of the captured exons. This is compounded by the complex relationship between read depth and copy number; this results from biases in targeted genomic hybridization, sequence factors such as GC content, and batching of samples during collection and sequencing. We present a statistical tool (exome hidden Markov model [XHMM]) that uses principal-component analysis (PCA) to normalize exome read depth and a hidden Markov model (HMM) to discover exon-resolution CNV and genotype variation across samples. We evaluate performance on 90 schizophrenia trios and 1,017 case-control samples. XHMM detects a median of two rare (<1%) CNVs per individual (one deletion and one duplication) and has 79% sensitivity to similarly rare CNVs overlapping three or more exons discovered with microarrays. With sensitivity similar to state-of-the-art methods, XHMM achieves higher specificity by assigning quality metrics to the CNV calls to filter out bad ones, as well as to statistically genotype the discovered CNV in all individuals, yielding a trio call set with Mendelian-inheritance properties highly consistent with expectation. We also show that XHMM breakpoint quality scores enable researchers to explicitly search for novel classes of structural variation. For example, we apply XHMM to extract those CNVs that are highly likely to disrupt (delete or duplicate) only a portion of a gene. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 44 | Neurosci Bull 2012 Aug 28: 435-48 |
| PMID | 22833041 |
| Title | Using optogenetics to translate the "inflammatory dialogue" between heart and brain in the context of stress. |
| Abstract | Inflammatory processes are an integral part of the stress response and are likely to result from a programmed adaptation that is vital to the organism's survival and well-being. The whole inflammatory response is mediated by largely overlapping circuits in the limbic forebrain, hypothalamus and brainstem, but is also under the control of the neuroendocrine and autonomic nervous systems. Genetically predisposed individuals who fail to tune the respective contributions of the two systems in accordance with stressor modality and intensity after adverse experiences can be at risk for stress-related psychiatric disorders and cardiovascular diseases. Altered glucocorticoid (GC) homeostasis due to GC resistance leads to the failure of neural and negative feedback regulation of the hypothalamic-pituitary-adrenal axis during chronic inflammation, and this might be the mechanism underlying the ensuing brain and heart diseases and the high prevalence of co-morbidity between the two systems. By the combined use of light and genetically-encoded light-sensitive proteins, optogenetics allows cell-type-specific, fast (millisecond-scale) control of precisely defined events in biological systems. This method is an important breakthrough to explore the causality between neural activity patterns and behavioral profiles relevant to anxiety, depression, autism and schizophrenia. Optogenetics also helps to understand the "inflammatory dialogue", the inflammatory processes in psychiatric disorders and cardiovascular diseases, shared by heart and brain in the context of stress. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 45 | J Chromatogr Sci 2012 Sep 50: 727-32 |
| PMID | 22595261 |
| Title | Development and validation of a stability-indicating gas chromatographic method for quality control of residual solvents in blonanserin: a novel atypical antipsychotic agent. |
| Abstract | Blonanserin is a novel atypical antipsychotic agent for the treatment of schizophrenia. Ethyl alcohol, isopropyl alcohol and toluene are utilized in the synthesis route of this bulk drug. A new validated gas chromatographic (GC) method for the simultaneous determination of residual solvents in blonanserin is described in this paper. Blonanserin was dissolved in N, N-dimethylformamide to make a sample solution that was directly injected into a DB-624 column. A postrun oven temperature at 240°C for approximately 2 h after the analysis cycle was performed to wash out blonanserin residue in the GC column. Quantitation was performed by external standard analyses and the validation was carried out according to International Conference on Harmonization validation guidelines Q2A and Q2B. The method was shown to be specific (no interference in the blank solution), linear (correlation coefficients ?0.99998, n = 10), accurate (average recoveries between 94.1 and 101.7%), precise (intra-day and inter-day precision ?2.6%), sensitive (limit of detection ?0.2 ng, and limit of quantitation ?0.7 ng), robust (small variations of carrier gas flow, initial oven temperature, temperature ramping rate, injector and detector temperatures did not significantly affect the system suitability test parameters and peak areas) and stable (reference standard and sample solutions were stable over 48 h). This extensively validated method is ready to be used for the quality control of blonanserin. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 46 | Tissue Antigens 2012 Aug 80: 136-42 |
| PMID | 22571276 |
| Title | Interleukin-6 promoter polymorphism and plasma levels in patients with schizophrenia. |
| Abstract | schizophrenia is a severe psychiatric disease with inflammatory component. Several studies indicated the increased blood levels of proinflammatory interleukin-6 cytokine in schizophrenia. However, only limited studies explored the relationship between excess production and genetic variations of this cytokine in schizophrenia, and the results were controversial. Here, we investigated possible association of the interleukin-6 gene (IL6) rs1800795 (-174G/C) polymorphism with schizophrenia and relationship between this polymorphism and interleukin-6 protein (IL-6) blood levels. This polymorphism was found by other researchers to associate with different transcription rates and different plasma levels of IL-6. A total of 208 unrelated Armenians were genotyped by polymerase chain reaction with sequence-specific primers, and IL-6 levels were assessed by enzyme-linked immunosorbent assay. The IL6 rs1800795 alleles and genotypes in both groups were in Hardy-Weinberg (H-W) equilibrium. We found that rs1800795*C allele [38% vs 24%, P = 0.002, odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.18-2.14] and its carriers (62% vs 42%, P = 0.003, OR = 2.28, 95% CI: 1.13-1.94) were more frequent in patients than in controls. IL-6 in patients was 1.5-fold higher than in controls (mean ± SD: 6.41 ± 2.47 pg/ml vs 4.15 ± 1.42 pg/ml, P = 1.9E-19). In both groups, higher IL-6 in rs1800795 GG compared to rs1800795*C allele carriers was observed (GG vs GC + CC, patients: 7.02 ± 2.83 pg/ml vs 5.39 ± 1.2 pg/ml, P = 0.0006; controls: 5.21 ± 1.17 pg/ml vs 3.38 ± 1.03 pg/ml, P = 1.6E-15). In conclusion, we report an association of IL6 rs1800795 and higher IL-6 with schizophrenia. We also conclude that IL6 rs1800795*C allele is linked to increased IL-6 blood levels and may be a risk factor for schizophrenia development at least in Armenian population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 47 | Anal Bioanal Chem 2012 Jun 403: 1823-30 |
| PMID | 22349337 |
| Title | Development and validation of a GC-EI-MS method with reduced adsorption loss for the quantification of olanzapine in human plasma. |
| Abstract | A simple and sensitive GC-EI-MS method using solvent extraction and evaporation was developed for the determination of olanzapine concentrations in plasma samples. Because olanzapine and promazine, which was used as the internal standard (IS), are nitrogenous bases, they can adsorb to the weakly acidic silanol groups on the surfaces of glass centrifuge tubes during solvent extraction and evaporation. Silylation of the glass tubes, addition of triethylamine (TEA), and use of a sample solution with a basic pH could prevent adsorption loss. The extraction method involved mixing plasma (500 ?L) in a silylated glass tube with a promazine solution (2 ?g/mL, 25 ?L) in methanol containing 1% TEA. After addition of aqueous sodium carbonate (0.5 mol/L, pH 11.1, 1 mL) and extraction into 3 mL of dichloromethane/n-hexane (1:1, v/v) containing 1% TEA, the organic phase was evaporated to dryness in a silylated glass tube. The residue was dissolved in ethyl acetate containing 1% TEA (50 ?L). For GC-EI-MS analysis, the calibration curves of olanzapine in human plasma were linear from 0.5 to 100 ng/mL. Intra- and interday precisions in plasma were both less than 7.36% (coefficient of variation), and the accuracy was between 94.6 and 110% for solutions with concentrations greater than 0.5 ng/mL. The limit of quantification was 0.5 ng/mL in plasma. The assay was applied to therapeutic drug monitoring in samples from three schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 48 | Neurosci. Res. 2013 Dec 77: 247-50 |
| PMID | 24120685 |
| Title | Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders. |
| Abstract | Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a good surrogate system to address brain disease-associated molecular changes. Nonetheless, whether use of this experimental strategy is justified remains unclear. Here we compared expression profiles of olfactory cells systematically with those from the brain tissues and other cells. Principal component analysis indicated that the expression profiles of olfactory cells are very different from those of blood cells, but are closer to those of stem cells, in particular mesenchymal stem cells, that can be differentiated into the cells of the central nervous system. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 49 | Neuroscience 2013 Sep 249: 31-42 |
| PMID | 23022220 |
| Title | The interaction of disrupted type II neuregulin 1 and chronic adolescent stress on adult anxiety- and fear-related behaviors. |
| Abstract | The incidence of anxiety, mood, substance abuse disorders and schizophrenia increases during adolescence. Epidemiological evidence confirms that exposure to stress during sensitive periods of development can create vulnerabilities that put genetically predisposed individuals at increased risk for psychiatric disorders. Neuregulin 1 (NRG1) is a frequently identified schizophrenia susceptibility gene that has also been associated with the psychotic features of bipolar disorder. Previously, we established that Type II NRG1 is expressed in the hypothalamic-pituitary-adrenal (HPA) axis neurocircuitry. We also found, using a line of Nrg1 hypomorphic rats (Nrg1(Tn)), that genetic disruption of Type II NRG1 results in altered HPA axis function and environmental reactivity. The present studies used the Nrg1(Tn) rats to test whether Type II NRG1 gene disruption and chronic stress exposure during adolescence interact to alter adult anxiety- and fear-related behaviors. Male and female Nrg1(Tn) and wild-type rats were exposed to chronic variable stress (CVS) during mid-adolescence and then tested for anxiety-like behavior, cued fear conditioning and basal corticosterone secretion in adulthood. The disruption of Type II NRG1 alone significantly impacts rat anxiety-related behavior by reversing normal sex-related differences and impairs the ability to acquire cued fear conditioning. Sex-specific interactions between genotype and adolescent stress also were identified such that CVS-treated wild-type females exhibited a slight reduction in anxiety-like behavior and basal corticosterone, while CVS-treated Nrg1(Tn) females exhibited a significant increase in cued fear extinction. These studies confirm the importance of Type II NRG1 in anxiety and fear behaviors and point to adolescence as a time when stressful experiences can shape adult behavior and HPA axis function. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 50 | J Anal Toxicol 2013 Oct 37: 559-64 |
| PMID | 24009049 |
| Title | Asenapine (Saphris®): GC-MS method validation and the postmortem distribution of a new atypical antipsychotic medication. |
| Abstract | Asenapine (Saphris®) is an atypical antipsychotic approved in the USA in 2009 for the treatment of schizophrenia and bipolar disorder. The Los Angeles County Department of Coroner Toxicology Laboratory developed an analytical method for the detection and quantitation of asenapine by gas chromatography-mass spectroscopy in multiple specimens of postmortem casework. Asenapine was isolated from specimens through a basic, liquid-liquid extraction procedure and quantitated utilizing D5-fentanyl as an internal standard. Method validation for asenapine was conducted utilizing the Scientific Working Group Toxicology (SWGTOX) method validation draft proposal and the tissue distribution of four case studies was determined. The authors believe that these are the first cases to be reported in the literature and are intended to assist other forensic toxicologists with interpreting their casework. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 51 | Pharmacogenet. Genomics 2013 Dec 23: 666-74 |
| PMID | 24141736 |
| Title | Next-generation sequencing of pharmacogenes: a critical analysis focusing on schizophrenia treatment. |
| Abstract | Because of the unmet needs of current pharmacotherapy for schizophrenia, antipsychotic pharmacogenetic research is of utmost importance. However, to date, few clinically applicable antipsychotic pharmacogenomic alleles have been identified. Nonetheless, next-generation sequencing technologies are expected to aid in the identification of clinically significant variants for this complex phenotype. The aim of this study was therefore to critically examine the ability of next-generation sequencing technologies to reliably detect variation present in pharmacogenes. Candidate antipsychotic pharmacogenes and very important pharmacogenes were identified from the literature and the Pharmacogenomics Knowledgebase. Thereafter, the percentage sequence similarity observed between these genes and their corresponding pseudogenes and paralogues, as well as the percentage low-complexity sequence and GC content of each gene, was calculated. These sequence attributes were subsequently compared with the 'inaccessible' regions of these genes as described by the 1000 Genomes Project. It was found that the percentage 'inaccessible genome' correlated well with GC content (P=9.96×10), low-complexity sequence (P=0.0002) and the presence of pseudogenes/paralogues (P=8.02×10). In addition, it was found that many of the pharmacogenes were not ideally suited to next-generation sequencing because of these genomic complexities. These included the CYP and HLA genes, both of which are of importance to many fields of pharmacogenetics. Current short read sequencing technologies are unable to comprehensively capture the variation in all pharmacogenes. Therefore, until high-throughput sequencing technologies advance further, it may be necessary to combine next-generation sequencing with other genotyping strategies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 52 | J Genet Couns 2013 Oct 22: 625-32 |
| PMID | 23604904 |
| Title | "Nothing is absolute in life": understanding uncertainty in the context of psychiatric genetic counseling from the perspective of those with serious mental illness. |
| Abstract | No genetic tests are currently clinically available for serious mental illnesses such as schizophrenia and bipolar disorder. Rather, the full spectrum of genetic variants that confer susceptibility remain unknown, and estimates of probability of condition recurrence typically have the form of ranges rather than single absolute numbers. Genetic counselors have been shown to feel that the information that can be provided for patients with serious mental illness could be more confusing than helpful. However, how those with serious mental illness perceive this uncertainty remains unknown. So, to investigate this, individuals with serious mental illness participated in a psychiatric genetic counseling (GC) session and responded to a single open ended question about their reactions towards the uncertainty that they encountered in their GC session immediately and one month post-counseling (from which themes were identified), and completed the Genetic Counseling Satisfaction Scale immediately post-session (descriptive statistics applied). While some of the 37 participants were disappointed with the uncertainty, twice as many were unconcerned. Overall, responses from immediately and one month after GC were very similar; participants were very satisfied with, and found value in GC despite uncertainty, and four approaches to coping with uncertainty emerged. Ultimately, these findings offer insight into providing GC for those with serious mental illness, and potentially could be applied to other areas of GC where uncertainty lies, with downstream impact on GC practice and future research. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 53 | Genet. Mol. Res. 2014 -1 13: 1609-18 |
| PMID | 24668635 |
| Title | Relationship between genetic polymorphisms in the DRD5 gene and paranoid schizophrenia in northern Han Chinese. |
| Abstract | Dopamine (DA) has been implicated in the pathophysiol-ogy of several psychiatric disorders, including schizophrenia. Thus, genes related to the dopaminergic (DAergic) system are good candidate genes for schizophrenia. One of receptors of the DA receptor system is dopa-mine receptor 5 (DRD5). Single nucleotide polymorphisms (SNPs) in the regulatory regions of DRD5 gene may affect gene expression, influence biosynthesis of DA and underlie various neuropsychiatric disorders re-lated to DA dysfunction. The present study explored the association of SNPs within the DRD5 gene with paranoid schizophrenia in Han Chinese. A total of 176 patients with schizophrenia and 206 healthy controls were genotyped for four DRD5 SNPs (rs77434921, rs2076907, rs6283, and rs1800762). Significant group differences were observed in the allele and genotype frequencies of rs77434921 and rs1800762 and in the frequen-cies of GC haplotypes corresponding to rs77434921-rs1800762. Our find-ings suggest that common genetic variations of DRD5 are likely to con-tribute to genetic susceptibility to paranoid schizophrenia in Han Chinese. Further studies in larger samples are needed to replicate this association. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 54 | Curr Psychiatry Rep 2014 Oct 16: 483 |
| PMID | 25135782 |
| Title | Circadian clock and stress interactions in the molecular biology of psychiatric disorders. |
| Abstract | Many psychiatric disorders are characterized by circadian rhythm abnormalities, including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders, including post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 55 | Mol Biosyst 2014 Jul 10: 2398-406 |
| PMID | 24975926 |
| Title | GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells. |
| Abstract | schizophrenia is a debilitating mental disorder. Currently, the lack of disease biomarkers to support objective laboratory tests constitutes a bottleneck in the clinical diagnosis of schizophrenia. Here, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was applied to characterize the metabolic profile of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia. Multivariate statistical analysis was used to visualize group discrimination and to identify differentially expressed metabolites in schizophrenia subjects relative to healthy controls. The multivariate statistical analysis demonstrated that the schizophrenia group was significantly distinguishable from the control group. In total, 18 metabolites responsible for the discrimination between the two groups were identified. These differential metabolites were mainly involved in energy metabolism, oxidative stress and neurotransmitter metabolism. A simplified panel of PBMC metabolites consisting of pyroglutamic acid, sorbitol and tocopherol-? was identified as an effective diagnostic tool, yielding an area under the receiver operating characteristic curve (AUC) of 0.82 in the training samples (45 schizophrenia subjects and 50 healthy controls) and 0.71 in the test samples (24 schizophrenic patients and 35 healthy controls). Taken together, these findings help to develop diagnostic tools for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 56 | Mol Biosyst 2014 Jul 10: 2398-406 |
| PMID | 24975926 |
| Title | GC-MS based metabolomics identification of possible novel biomarkers for schizophrenia in peripheral blood mononuclear cells. |
| Abstract | schizophrenia is a debilitating mental disorder. Currently, the lack of disease biomarkers to support objective laboratory tests constitutes a bottleneck in the clinical diagnosis of schizophrenia. Here, a gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was applied to characterize the metabolic profile of schizophrenia subjects (n = 69) and healthy controls (n = 85) in peripheral blood mononuclear cells (PBMCs) to identify and validate biomarkers for schizophrenia. Multivariate statistical analysis was used to visualize group discrimination and to identify differentially expressed metabolites in schizophrenia subjects relative to healthy controls. The multivariate statistical analysis demonstrated that the schizophrenia group was significantly distinguishable from the control group. In total, 18 metabolites responsible for the discrimination between the two groups were identified. These differential metabolites were mainly involved in energy metabolism, oxidative stress and neurotransmitter metabolism. A simplified panel of PBMC metabolites consisting of pyroglutamic acid, sorbitol and tocopherol-? was identified as an effective diagnostic tool, yielding an area under the receiver operating characteristic curve (AUC) of 0.82 in the training samples (45 schizophrenia subjects and 50 healthy controls) and 0.71 in the test samples (24 schizophrenic patients and 35 healthy controls). Taken together, these findings help to develop diagnostic tools for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 57 | Biochem. Biophys. Res. Commun. 2015 May 460: 678-83 |
| PMID | 25817788 |
| Title | Functional magnetic resonance imaging reveals abnormal brain connectivity in EGR3 gene transfected rat model of schizophrenia. |
| Abstract | schizophrenia is characterized by the disorder of "social brain". However, the alternation of connectivity density in brain areas of schizophrenia patients remains largely unknown. In this study, we successfully created a rat model of schizophrenia by the transfection of EGR3 gene into rat brain. We then investigated the connectivity density of schizophrenia susceptible regions in rat brain using functional magnetic resonance imaging (fMRI) in combination with multivariate Granger causality (GC) model. We found that the average signal strength in prefrontal lobe and hippocampus of schizophrenia model group was significantly higher than the control group. Bidirectional Granger causality connection was observed between hippocampus and thalamic in schizophrenia model group. Both connectivity density and Granger causality connection were changed in prefrontal lobe, hippocampus and thalamus after risperidone treatment. Our results indicated that fMRI in combination with GC connection analysis may be used as an important method in diagnosis of schizophrenia and evaluation the effect of antipsychotic treatment. These findings support the connectivity disorder hypothesis of schizophrenia and increase our understanding of the neural mechanisms of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 58 | Nat. Genet. 2015 Dec 47: 1385-92 |
| PMID | 26523775 |
| Title | Contrasting genetic architectures of schizophrenia and other complex diseases using fast variance-components analysis. |
| Abstract | Heritability analyses of genome-wide association study (GWAS) cohorts have yielded important insights into complex disease architecture, and increasing sample sizes hold the promise of further discoveries. Here we analyze the genetic architectures of schizophrenia in 49,806 samples from the PGC and nine complex diseases in 54,734 samples from the GERA cohort. For schizophrenia, we infer an overwhelmingly polygenic disease architecture in which ?71% of 1-Mb genomic regions harbor ?1 variant influencing schizophrenia risk. We also observe significant enrichment of heritability in GC-rich regions and in higher-frequency SNPs for both schizophrenia and GERA diseases. In bivariate analyses, we observe significant genetic correlations (ranging from 0.18 to 0.85) for several pairs of GERA diseases; genetic correlations were on average 1.3 tunes stronger than the correlations of overall disease liabilities. To accomplish these analyses, we developed a fast algorithm for multicomponent, multi-trait variance-components analysis that overcomes prior computational barriers that made such analyses intractable at this scale. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 59 | Clin. Genet. 2015 Mar 87: 218-24 |
| PMID | 24773225 |
| Title | Evaluating a unique, specialist psychiatric genetic counseling clinic: uptake and impact. |
| Abstract | People with psychiatric disorders and their family members have expressed interest in receiving genetic counseling (GC). In February 2012, we opened the first (to our knowledge) specialist psychiatric GC clinic of its kind, for individuals with non-syndromic psychiatric disorders and their families. Prior to GC and at a standard 1-month follow-up session, clinical assessment tools are completed, specifically, the GC outcomes scale (GCOS, which measures empowerment, completed by all clients) and the Illness Management Self Efficacy scale (IMSES, completed by those with mental illness). Consecutive English-speaking clients attending the clinic between 1 February 2012 and 31 January 2013 who were capable of consenting were asked for permission to use their de-identified clinical data for research purposes. Descriptive analyses were conducted to ascertain demographic details of attendees, and paired sample t-tests were conducted to assess changes in GCOS and IMSES scores from pre- to post-GC. Of 143 clients, seven were unable to consent, and 75/136 (55.1%) consented. Most were female (85.3%), self-referred (76%), and had personal experience of mental illness (65.3%). Mean GCOS and IMSES scores increased significantly after GC (p?GC increases empowerment and self-efficacy in this population. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 60 | Neuropharmacology 2015 Aug 95: 252-60 |
| PMID | 25842242 |
| Title | Neurotensinergic augmentation of glutamate release at the perforant path-granule cell synapse in rat dentate gyrus: Roles of L-Type Ca²? channels, calmodulin and myosin light-chain kinase. |
| Abstract | Neurotensin (NT) serves as a neuromodulator in the brain where it is involved in modulating a variety of physiological functions including nociception, temperature, blood pressure and cognition, and many neurological diseases such as Alzheimer's disease, schizophrenia and Parkinson's disease. Whereas there is compelling evidence demonstrating that NT facilitates cognitive processes, the underlying cellular and molecular mechanisms have not been fully determined. Because the dentate gyrus expresses high densities of NT and NT receptors, we examined the effects of NT on the synaptic transmission at the synapse formed between the perforant path (PP) and granule cells (GC) in the rats. Our results demonstrate that NT persistently increased the amplitude of the AMPA receptor-mediated EPSCs at the PP-GC synapse. NT-induced increases in AMPA EPSCs were mediated by presynaptic NTS1 receptors. NT reduced the coefficient of variation and paired-pulse ratio of AMPA EPSCs suggesting that NT facilitates presynaptic glutamate release. NT increased the release probability and the number of readily releasable vesicles with no effects on the rate of recovery from vesicle depletion. NT-mediated augmentation of glutamate release required the influx of Ca(2+) via L-type Ca(2+) channels and the functions of calmodulin and myosin light chain kinase. Our results provide a cellular and molecular mechanism to explain the roles of NT in the hippocampus. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 61 | Int J Anal Chem 2015 -1 2015: 972480 |
| PMID | 26236337 |
| Title | Development and Validation of a GC-MS Method for the Detection and Quantification of Clotiapine in Blood and Urine Specimens and Application to a Postmortem Case. |
| Abstract | Introduction. Clotiapine is an atypical antipsychotic of the dibenzothiazepine class introduced in a few European countries since 1970, efficient in treatment-resistant schizophrenic patients. There is little published data on the therapeutic and toxic concentrations of this drug. Aims. The aim of the present study is the development and validation of a method that allows the detection and quantification of clotiapine in blood and urine specimens by gas chromatography-mass spectrometry (GC-MS). Methods. Validation was performed working on spiked postmortem blood and urine samples. Samples were extracted with liquid-liquid extraction (LLE) technique at pH 8.5 with n-hexane/dichloromethane (85/15 v/v) and analysis was followed by GC-MS. Methadone-d9 was used as internal standard. Results. The limit of detection (LOD) was 1.2 and 1.3?ng/mL for urine and blood, respectively, while the lower limit of quantification (LLOQ) was 3.9 and 4.3?ng/mL, respectively. Linearity, precision, selectivity, accuracy, and recovery were also determined. The method was applied to a postmortem case. The blood and urine clotiapine concentrations were 1.32 and 0.49??g/mL, respectively. Conclusions. A reliable GC-MS method for the detection and quantification of clotiapine in blood and urine samples has been developed and fully validated and then applied to a postmortem case. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 62 | PLoS ONE 2016 -1 11: e0150574 |
| PMID | 26949964 |
| Title | Effect of Acacia catechu (L.f.) Willd. on Oxidative Stress with Possible Implications in Alleviating Selected Cognitive Disorders. |
| Abstract | In human body, several categories of degenerative processes are largely determined by free radicals originating in cell. Free radicals are also known to have correlated with a variety of cognitive disorders (CDs) resulting in neuronal injury and eventually to death. Alzheimer's disease (AD) and Parkinson's disease (PD) are such kind of killer CDs that occur due to dysfunction of cholinergic and dopaminergic neurons. Plant parts of Ginkgo biloba, Bacopa monnieri etc. are being used for the treatment of cognitive disorders in several countries. The present study was aimed to explore the detailed antioxidant and anti-cholinesterase activity of Acaciacatechu leaf (ACL) over CDs. Gas chromatography-Mass spectroscopy (GC-MS) analysis and Nuclear Magnetic Resonance (NMR) were employed to identify the bioactive components present in ACL. Furthermore, the extract was evaluated to check the cytotoxic effects of ACL on normal cells. Amongst several antioxidant assays, DPPH assay, hydroxyl radical, nitric oxide radical and hypochlorous acid inhibitory activities were found to be greater in ACL than that of the respective standards while other assays exhibited a moderate or at per inhibitory activity with standards. Total phenolic and flavonoid content were also found to be present in decent amount. In addition, we found, a greater acetylcholinesterase (AChE) inhibitory activity of ACL when compared to other medicinally important plants, indicating its positive effect over CDs. Forty one bioactive components were explored through GC-MS. Of these, gallic acid, epicatechin, catechin, isoquercitrin etc. were found, which are potent antioxidant and a few of them have anti-neurodegenerative properties. Eventually, ACL was found to be nontoxic and safer to consume. Further studies with animal or human model however, would determine its efficacy as a potential anti-schizophrenic drug. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 63 | Brain Struct Funct 2016 Jun 221: 2459-75 |
| PMID | 25944572 |
| Title | Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment. |
| Abstract | The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 64 | Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016 Mar 160: 39-53 |
| PMID | 26757776 |
| Title | Quantification of selected antidepressants and antipsychotics in clinical samples using chromatographic methods combined with mass spectrometry: A review (2006-2015). |
| Abstract | Psychiatric disorders contribute significantly to worldwide morbidity and mortality. In the case of depression and schizophrenia, effective drug therapy is available but 30-50% of patients do not respond sufficiently to the initial treatment regimen. Apart from the development of new molecules, it is desirable to optimize treatment outcomes with agents that are currently available. Therapeutic drug monitoring (TDM) is a suitable and widely accepted approach for improving the efficacy and safety of these drugs. A review of the relevant literature published between 2006 and January 2015. This review describes major advances and drawbacks in the field of chromatography coupled with single or tandem mass spectrometry (LC-MS, LC-MS/MS and GC/MS) of selected antidepressants (agomelatine, vilazodone) and antipsychotics (iloperidone, asenapine, amisulpride, aripiprazole, melperone, zotepine, ziprasidone). The high specificity in combination with high sensitivity makes these techniques an attractive complementary method to traditional procedures used in routine practice for TDM. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 65 | J Affect Disord 2016 May 195: 75-81 |
| PMID | 26874244 |
| Title | Metabolite signature for diagnosing major depressive disorder in peripheral blood mononuclear cells. |
| Abstract | Major depressive disorder (MDD) is a serious debilitating psychiatric disorder. However, the molecular mechanisms of MDD remain largely unknown, and no objective laboratory-based tests are available to diagnose this disorder. A gas chromatography-mass spectrometry (GC-MS) based metabolomic approach was used to compare peripheral blood mononuclear cells (PBMC) metabolic profiling of 50 first onset drug-naïve MDD subjects and 50 healthy controls (training samples), to identify potential metabolite biomarkers for MDD. An independent sample cohort including 58 MDD patients, 40 schizophrenia (SCZ) patients and 56 healthy controls (test samples) was used to validate diagnostic generalizability and specificity of identified biomarkers. 17 PBMC metabolites responsible for discriminating MDD group from healthy control group were identified. These metabolites were mainly involved in disturbances of energy and neurotransmitter metabolism. This PBMC metabolite signature could effectively discriminate MDD subjects from the healthy controls with an AUC of 0.926 in training samples and 0.870 in test samples. Moreover, this metabolite signature enabled distinguishing MDD subjects from schizophrenia subjects with an AUC of 0.899. This study was limited by potential confounding effects of different drug treatments in some MDD and schizophrenia subjects, and lack of animal studies to further validate the identified metabolite pathways in MDD. These findings suggest that early disturbances of PBMC energy and neurotransmitter metabolism may be associated with the onset of MDD. This PBMC metabolite signature may facilitate development of a laboratory-based diagnostic test for MDD. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 66 | Schizophr. Res. 2016 Jan 170: 226-31 |
| PMID | 26706197 |
| Title | An emerging role of cGMP in the treatment of schizophrenia: A review. |
| Abstract | schizophrenia is a progressive psychotic disorder with devastating effects on the broad aspects of human emotion, perception, thought, and psychosocial interactions. Although treatment with antipsychotic drugs, the mainstay in the treatment of schizophrenia, the large number of patients with schizophrenia respond poorly to the pharmacological and, the large number of patients with schizophrenia poorly respond to the pharmacological treatment. Although a variety of novel therapeutics have long been tested, to date, no drugs clinically efficacious for schizophrenia are available. The multiple lines of evidence strongly suggest that the modulation of cyclic guanosine monophosphate (cGMP) is a promising target in promoting the novel therapeutic strategies of schizophrenia beyond the "receptor-dependent" psychopharmacology. cGMP is modulated via regulating its synthesis by N-methyl-d-aspartate receptor (NMDAR) and nitric oxide (NO), which regulate guannylyl cyclase (GC), the enzyme producing cGMP. cGMP is also regulated by phosphodiesterase (PDE), the enzyme hydrolyzing cGMP. In this review, we critically evaluate the therapeutic potential of agents modulating cGMP activity by regulating cGMP synthesis including NMDAR enhancers, NO enhancers, NO inhibitors including minocycline with anti-inflammatory properties and PDE inhibitors in improving the negative, cognitive and positive symptoms of schizophrenia. We also discuss the possible mechanisms by which these agents produce therapeutic effects on schizophrenia including cGMP signaling pathways, oxidative stress, and neuroinflammation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |
| 67 | Biomed. Chromatogr. 2016 Mar 30: 440-6 |
| PMID | 26194341 |
| Title | Recognition and identification of active components from Radix Bupleuri using human neuroblastoma SH-SY5Y cells. |
| Abstract | The aim of the study was to screen active components of Radix Bupleuri (a traditional Chinese herb) and discover novel anti-schizophrenic candidate drugs using human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were used for preparation of the stationary phase in the cell membrane chromatography model. Retention components by the SH-SY5Y/CMC model were collected and then analyzed by GC/MS under the optimized conditions in offline conditions. After investigating the suitability and reliability of the SH-SY5Y/CMC method using amisulpride and haloperidol as standard compounds, this method was applied to screening active components from the extracts of Radix Bupleuri. Retention components of SH-SY5Y/CMC model were saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D, which were identified by the GC/MS method. In vitro pharmacological trials-MTT, saikosaponin B1, saikosaponin B2 and saikosaponin C could protect SY5Y cells. The protective effects of saikosaponin B1 and saikosaponin C were concentration dependent. Saikosaponin A and saikosaponin D inhibited cell viability at concentrations >30?µg/mL (p?schizophrenic candidate drugs. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics, schizophrenias, schizotypal |