Predictors of response to second generation antipsychotics in drug naïve patients with schizophrenia: a 1 year follow-up study in Shanghai.

Response and remission are of great importance to patients with first-episode schizophrenia. Although previous researches have revealed characteristics related to medication response, there is rarely data over remission-related factors. We presume that factors correlated to response may also influence remission in 1 year treatment for first-episode schizophrenia. 398 drug-naïve patients met the criteria of schizophrenia using ICD-10 criteria were recruited from Shanghai Mental Health Center and treated with one of three second generation antipsychotics (risperidone, olanzapine or quetiapine). Patients were followed up for 1 year and assessed at 2 weeks, and then 2, 3, 6, 8 and 12 months. Severity of symptom was evaluated using the Chinese version of the Positive and Negative Syndrome Scale (PANSS). Response was defined as a reduction of 50% or more PANSS scores. The 8-item criteria of remission (proposed by the Remission of Schizophrenia Working Group) were used. Logistic regression analysis revealed that shorter duration of untreated psychosis (DUP), longer treatment time, higher baseline PANSS positive score and higher PANSS general pathological scores predicted response, and acute prodromal phase was the independent factor for remission. These results indicate baseline characters that related to response and those related to remission may be different for patients with schizophrenia.

Functional -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter and schizophrenia in a Chinese Han population.

OBJECTIVE: The association between a putative functional promoter polymorphism, -141C insertion/deletion (Ins/Del), in the dopamine receptor D2 gene (DRD2) and schizophrenia was investigated in a Chinese Han population. METHODS: The polymorphism was studied in unrelated schizophrenia patients and unrelated healthy controls. Linkage relationships were explored in core families of the schizophrenic patients using the transmission disequilibrium test. The Positive and Negative Syndrome Scale was used to evaluate the severity of the disorder. RESULTS: The Del allele was significantly less frequently found in patients (13/120; 11%) than in controls (18/100; 18%). In the 32 core families studied, 16 parents were Ins/Del heterozygotes. Parents transmitted the Ins and Del alleles to their children in 10 and six cases, respectively. Data from core families did not demonstrate linkage. Age, age at onset of schizophrenia and sex were not significantly different between carriers of the Ins and Del alleles. The group with the Ins allele had a significantly higher positive symptom score (75.3 ± 23.4 versus 53.9 ± 21.9) and excitement score (83.6 ± 16.8 versus 50.3 ± 24.6) than the Del group. Groups did not differ significantly in negative symptom and general psychopathology scores. CONCLUSIONS: The DRD2 -141C Ins/Del polymorphism may affect susceptibility to schizophrenia in a Chinese Han population.

Abnormal functional connectivity with mood regulating circuit in unmedicated individual with major depression: a resting-state functional magnetic resonance study.

BACKGROUND: Reports on mood regulating circuit (MRC) indicated different activities between depressed patients and healthy controls. The functional networks based on MRC have not been described in major depression disorder (MDD). Both the anterior cingulate cortex (ACC) and thalamus are all the key regions of MRC. This study was to investigate the two functional networks related to ACC and thalamus in MDD. METHODS: Sixteen patients with MDD on first episode which never got any medication and sixteen matched health controls were scanned by 3.0 T functional magnetic resonance imaging (fMRI) during resting-state. The pregenual anterior cingulate cortex (pgACC) was used as seed region to construct the functional network by cortex section. The thalamus was used as seed region to construct the functional network by limbic section. Paired-t tests between-groups were performed for the seed-target correlations based on the individual fisher z-transformed correlation maps by SPM2. RESULTS: Depressed subjects exhibited significantly great functional connectivity (FC) between pgACC and the parahippocampus gyrus in one cluster (size 923) including left parahippocampus gyrus (-21, -49, 7), left parietal lobe (-3, -46, 52) and left frontal lobe (-27, -46, 28). The one cluster (size 962) of increased FC on thalamus network overlapped the precuneus near to right parietal lobe (9, -52, 46) and right cingulate gyrus (15, -43, 43) in health controls. CONCLUSIONS: Abnormal functional networks exist in earlier manifestation of MDD related to MRC by both cortex and limbic sections. The increased functional connectivity of pgACC and decreased functional connectivity of thalamus is mainly involved in bias mood processing and cognition.

Decreased regional homogeneity in major depression as revealed by resting-state functional magnetic resonance imaging.

BACKGROUND: Functional imaging studies indicate abnormal activities in cortico-limbic network in depression during either task or resting state. The present work was to explore the abnormal spontaneous activity shown with regional homogeneity (ReHo) in depression by resting-state functional magnetic resonance imaging (fMRI). METHODS: Using fMRI, the differences of regional brain activity were measured in resting state in depressed vs. healthy participants. Sixteen participants firstly diagnosed with major depressive disorder and 16 controls were scanned during resting state. A novel method based on ReHo was used to detect spontaneous hemodynamic responses across the whole brain. RESULTS: ReHo in the left thalamus, left temporal lobe, left cerebellar posterior lobe, and the bilateral occipital lobe was found to be significantly decreased in depression compared to healthy controls in resting state of depression. CONCLUSIONS: Abnormal spontaneous activity exists in the left thalamus, left temporal lobe, left cerebellar posterior lobe, and the bilateral occipital lobe. And the ReHo may be a potential reference in understanding the distinct brain activity in resting state of depression.

[Association of cyclic adenosine monophosphate response element-binding protein gene and major depressive disorder].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD). METHODS: We recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed. RESULTS: No significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022). CONCLUSION: The rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.

[Change of cerebral metabolism rate of glucose of cerebral white matter in Alzheimer's disease: a study with statistical parametric mapping software].

OBJECTIVE: To study the change of cerebral metabolism rate of glucose (CMRglc) of cerebral white matter in Alzheimer's Disease. METHODS: Positron emission tomography (PET) was performed on 13 AD patients, 6 with behavioral and psychological symptoms of dementia (BPSD) and 7 without BPSD, and 10 healthy controls. The regional cerebral metabolism of glucose (rCMRglc) of some brain regions and nuclei were detected. RESULTS: (1) The rCMRglc of the cerebral white matter decreased extensively in the AD patients, especially in the right frontal lobe, superior gyrus of the left frontal lobe (P = 0.001). (2) The rCMRglc of subcortical white matter of the left medial prefrontal lobe and the left cuneus of occipital lobe increased in the AD patients. (3) The levels of rCMRglc of the subcortical white matter of both side middle occipital lobe, left cuneus of occipital lobe, right inferior parietal lobule, left fusiform gyrus of temporal lobe and the left medial prefrontal lobe were all significantly higher in the AD patients with BPSD than in those without BPSD (P = 0.001). While the levels of rCMRglc of the subcortical white matter of both side paracentral lobule, right superior and middle frontal lobe, and left superior temporal lobe were all significantly lower in the AD patients with BPSD than in those without BPSD (all P = 0.001). CONCLUSION: There is diffuse abnormal rCMRglc in the cerebral white matter in the AD patients: the rCMRglc decreases in the frontal-temporal-occipital association area, and the rCMRglc of the medial prefrontal lobe and cuneus of occipital lobe increases. BPSD is correlated with the abnormal metabolism of related cerebral regions.

[Expression levels of APP and PS1 genes in patients with Alzheimer's disease].

The gene expression levels of amyloid precursor protein (APP) and presenilin 1 (PS1) in the peripheral blood samples of patients with Alzheimer's disease(AD) and their association with the disease were studied. The absolute expression levels of APP and PS1 genes were quantified in 45 AD patients, 25 patients with vascular dementia (VD) and 60 healthy controls by real-time quantitative PCR using SYBR Green I. The APP expression levels in healthy controls, AD cases and VD cases are 0.026+/-0.005, 0.044+/-0.006 and 0.072+/-0.013 amol/microg cDNA, respectively; and the PS1 expression levels are 0.026+/-0.004, 0.051+/-0.011 and 0.039+/-0.005 amol/microg cDNA, respectively. Both APP and PS1 expression levels were significantly elevated in AD or in VD cases (APP, AD vs Control, t=2.639, P<0.01, VD vs Control, t=3.028P<0.01; PS1, AD vs Control, t=2.173P<0.05, VD vs Control, t=2.012P<0.05). It seems that elevated APP and PS1 gene expression is associated with dementia but not especially with AD.

[Measurement of regional cerebral metabolism rate of glucose in patients with Alzheimer's disease in different levels of severity].

OBJECTIVE: To measure the changes of regional cerebral metabolism rate of glucose (rCMRglc) in patients with Alzheimer's disease (AD) and explore their value to diagnosis of AD. METHODS: 10 patients with AD who met the diagnostic criteria of DSM-IV and 10 normal controls (NC) were assessed with (18)F-2-fluoro-deoxy-D-glucose positron emission tomography (PET). RESULTS: The two groups were matched in age, gender and education. The mean total scores of the mini-mental status examination (MMSE) were 16.5 +/- 6.1 for AD and 28.7 +/- 1.6 for NC. The mean total memory quotient of Wechsler Memory Scales (MQ) were 32.3 +/- 19.6 for AD and 93.1 +/- 9.0 for NC. Comparing to NC, the AD groups showed statistically significant decline of rCMRglc in frontal lobe, temporal lobe and the hippocampal formation with decreased rates ranged from 3.3% to 28.4% (P < 0.05, P < 0.01). The hypo-metabolism was more salient in the regions of upper and middle frontal gyri, middle temporal gyrus, orbital gyrus and anterior cingulate gyrus, in which areas the metabolism decreased over 20% compared to NC. The hypo-metabolism was correlated to the severity of dementia. Discriminant analysis demonstrated that the variables of right inferior temporal gyrus, left upper temporal gyrus, left hippocampus and right insular lobe were entered into the discriminant functions and the total discriminant accuracy reached 100%. CONCLUSIONS: (18)F-FDG PET is a very sensitive tool in measurement of the changes of rCMRglc in patients with AD. The findings show a frontal-temporal type of metabolism in AD patients and suggest that hypo-metabolism in hippocampal formation and temporal lobe is helpful in early detection of AD.

[Association of schizophrenia with a promoter polymorphism in the dopamine D2 receptor gene].

OBJECTIVE: To investigate the association of -141C insert/delete polymorphism with schizophrenia in Wuhan of Hubei province. METHODS: A case-control study was conducted to analyze the polymorphism in the D(2) receptor gene promoter region with schizophrenia. A total of 120 cases of schizophrenia diagnosed according to CCMD-II R criteria and 100 normal controls were recruited in the study. RESULTS: In this sample, the allele and genotype showed statistically significant differences between patients and normal controls (P<0.05).Especially, the frequency of -141C del was 11% in patients and 18% in control(OR 0.55, 95% CI 0.30-0.96; P<0.05). This allele was less common in schizophrenia than in normal controls (P<0.05). CONCLUSION: The -141C del polymorphism is associated with schizophrenia.The polymorphism may modify the association with other factors. Possibly -141C del in the DRD(2) promoter region is a strong candidate for a protective factor for this trait.