Cross-sectional and longitudinal studies have identified widespread and progressive grey matter volume (GMV) reductions in schizophrenia, especially in the frontal lobe. In this study, we found a progressive GMV decrease in the rostral medial frontal cortex (rMFC, including the anterior cingulate cortex) in the patient group during a 6-week follow-up of 40 patients with schizophrenia and 31 healthy controls well-matched for age, gender, and education. The higher baseline GMV in the rMFC predicted better improvement in the positive score on the Positive and Negative Syndrome Scale (PANSS), and this might be related to the improved reality-monitoring. Besides, a higher baseline GMV in the posterior rMFC predicted better remission of general symptoms, and a lesser GMV reduction in this region was correlated with better remission of negative symptoms, probably associated with ameliorated self-referential processing and social cognition. Besides, a shorter disease course and higher educational level contributed to better improvement in the general psychopathological PANSS score, and a family history was negatively associated with improvement of the negative and total PANSS scores. These phenomena might be important for understanding the neuropathological mechanisms underlying the symptoms of schizophrenia and for making clinical decisions.
Adult ; Antipsychotic Agents ; therapeutic use ; Female ; Frontal Lobe ; diagnostic imaging ; drug effects ; pathology ; Genetic Predisposition to Disease ; Gray Matter ; diagnostic imaging ; drug effects ; pathology ; Humans ; Image Processing, Computer-Assisted ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Organ Size ; Psychiatric Status Rating Scales ; Regression Analysis ; Schizophrenia ; diagnostic imaging ; drug therapy ; genetics ; pathology ; Time Factors ; Treatment Outcome

Catechol-O-methyltransferase (COMT) gene encodes catechol-O-methyltransferase, the variant of this gene may affect the expression and metabolic activity of COMT. As the result of the changes of the effective concentration of the catecholamine neurotransmitter in the central nervous system, central nervous system dysfunctions associated with schizophrenia. This review summarizes genetic polymorphism and diversity of COMT gene. It also elaborates the relation between SNP and haplotype of COMT gene and three aspects, which including schizophrenia, attacking and violent tendency, and the frontal cognitive function of the schizophreniac. The correlativity study between genetic variation of the COMT gene and schizophrenia in patients with attacking and violent tendency may be helpful for the assessment of forensic psychiatry.
Aggression/psychology* ; Brain/pathology* ; Catechol O-Methyltransferase/genetics* ; Cognition/physiology* ; Dopamine/metabolism* ; Forensic Genetics ; Gene Expression ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Prefrontal Cortex/pathology* ; Promoter Regions, Genetic ; Schizophrenia/genetics* ; Violence/psychology*

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.
Adult ; Alleles ; Case-Control Studies ; Congenital Abnormalities/*genetics ; DNA Methylation ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Middle Aged ; *Polymorphism, Single Nucleotide ; Republic of Korea ; Schizophrenia/*genetics/pathology

OBJECTIVETo explore the role of genetic factors in the brain structural variation by using magnetic resonance imaging scan in schizophrenic patients and their unaffected siblings, and to provide experimental evidence for identifying endophenotype of schizophrenia.

METHODSThe optimized voxel-based morphometry (OVBM) was used to process the brain magnetic resonance images in 15 first episode drug-naive schizophrenic patients, 19 unaffected siblings of the patients and 38 normal control subjects. The data were analyzed by using general linear model.

RESULTSCompared to the normal control subjects, significant decreases of gray matter was observed in first episode drug-naive schizophrenia in bilateral temporal lobe, bilateral occipital lobe, left insula, left frontal lobe superior frontal gyrus and right lentiform nucleus medial globus pallidus. Significant increases of gray matter in bilateral parietal lobe, bilateral limbic lobe cingulate gyrus in patients group while compared to controls were also found. In unaffected siblings, significant decreases of gray matter was observed in the right temporal lobe, bilateral occipital lobe, left insula, and left frontal lobe precentral gyrus, and significant increases of gray matter were found in left parietal lobe and bilateral cerebellum posterior lobe. Increased gray matter in left parietal lobe precuneus was found in first episode drug-naive schizophrenia when compared with their unaffected siblings.

CONCLUSIONThere were similar brain structure abnormalities between the first episode drug-naive schizophrenia and their unaffected siblings. Genetic factor may play important role in brain structural abnormality in schizophrenia, which suggested that the brain structural change might be a genetic endophenotype of schizophrenia.

Adult ; Brain ; abnormalities ; diagnostic imaging ; Case-Control Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Radiography ; Schizophrenia ; diagnostic imaging ; genetics ; pathology

Recent reports indicate that the dysbindin gene located on chromosome 6p22.3 is a major susceptibility gene for schizophrenia. In the brain, the dysbindin gene may influence glutamatergic neurotransmission by multiple post- and pr- synaptic mechanisms. This paper reviews the research progress on the dysbindin gene in schizophrenia, including the dysbindin gene and its product, the possible pathogenic mechanisms, the association study of the dysbindin gene with schizophrenia, and the cognitive decline caused by the dysbind in variations.
Brain ; metabolism ; Carrier Proteins ; genetics ; physiology ; Cognition Disorders ; genetics ; physiopathology ; Dysbindin ; Dystrophin-Associated Proteins ; Genetic Predisposition to Disease ; Genotype ; Humans ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics ; metabolism ; pathology

OBJECTIVE: To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia. METHODS: Fifty KM mice were randomly divided into 5 groups which were administered intraperitoneally with saline, clozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage (25 mg/kg), middle dosage (50 mg/kg) and high dosage (100 mg/kg) one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the clozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline. CONCLUSION Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.
Animals ; Clozapine/therapeutic use* ; Disease Models, Animal ; Dose-Response Relationship, Drug ; ErbB Receptors/metabolism* ; Hippocampus/pathology* ; Ketamine/adverse effects* ; Male ; Mice ; Neuregulin-1/metabolism* ; Neurons/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Receptor, ErbB-4 ; Reverse Transcriptase Polymerase Chain Reaction ; Schizophrenia/genetics*

OBJECTIVETo find out association mapping of loci related to schizophrenia on chromosome 1 with microsatellite markers in DNA pooling samples from schizophrenic cases and normal controls in Shandong peninsula.

METHODSA total of 31 microsatellite markers on chromosome 1 spaced at approximately 10 cM were scanned to two separated DNA pooling samples consisting of 119 schizophrenic cases and 119 normal controls respectively. Statistic analysis was performed by Chi-square test method to compare the difference between the ratio of each allele between the two pooling samples.

RESULTSSignificant statistic difference was found at D1S2878 between cases and controls, and P< 0.01 at this loci.

CONCLUSIOND1S2878 locus on chromosome 1 associates with schizophrenia in Shandong peninsula. Fine mapping and searching for candidate genes are warranted in this region.

Adult ; Case-Control Studies ; China ; Chromosome Mapping ; Chromosomes, Human, Pair 1 ; genetics ; DNA ; genetics ; Female ; Genomics ; Humans ; Male ; Microsatellite Repeats ; genetics ; Schizophrenia ; genetics ; pathology