Hypoconnectivity within the cingulo-opercular network in patients with mild cognitive impairment in Chinese communities.

INTRODUCTION: At rest, the brain's higher cognitive systems engage in correlated activity patterns, forming networks. With mild cognitive impairment (MCI), it is essential to understand how functional connectivity within and between resting-state networks changes. This study used resting-state functional connectivity to identify significant differences within and between the cingulo-opercular network (CON) and default mode network (DMN). METHODS: We assessed cognitive function in patients using the Chinese version of the Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog). A group of MCI subjects (ages 60-83 years, n = 45) was compared to age-matched healthy controls (n = 70). Resting-state functional connectivity was used to determine functional connectivity strength within and between the CON and DMN. RESULTS: Compared to healthy controls, the MCI group showed significantly lower functional connectivity within the CON (F = 10.76, df = 1, p = 0.001, FDR adjusted p = 0.003). Additionally, the MCI group displayed no distinct differences in functional connectivity within DMN (F = 0.162, df = 1, p = 0.688, FDR adjusted p = 0.688) and between CON and DMN (F = 2.270, df = 1, p = 0.135, FDR adjusted p = 0.262). Moreover, we found no correlation between ADAS-Cog and within- or between-connectivity metrics among subjects with MCI. CONCLUSIONS: Our findings indicate that specific patterns of hypoconnectivity within CON circuitry may characterize MCI relative to healthy controls. This work improves our understanding of network dysfunction underlying MCI and could inform more targeted treatment.

Association of plasma brain-derived neurotrophic factor with Alzheimer's disease and its influencing factors in Chinese elderly population.

Objective: To explore the association of plasma brain-derived neurotrophic factor (BDNF) levels with Alzheimer's disease and its influencing factors. Materials and methods: A total of 1,615 participants were included in the present study. Among all subjects, 660 were cognitive normal controls (CNCs), 571 were mild cognitive impairment (MCI) patients, and 384 were dementia with Alzheimer's type (DAT) patients. BDNF in blood samples collected from these subjects was analyzed via the Luminex assay. Additionally, DNA extraction and APOE4 genotyping were performed on leukocytes using a blood genotyping DNA extraction kit. All data were processed with SPSS 20.0 software. Analysis of variance (ANOVA) or analysis of covariance (ANCOVA) was used to compare differences among groups on plasma BDNF. Pearson and Spearman correlation analysis examined the correlation between BDNF and cognitive impairment, and linear regression analysis examined the comprehensive effects of diagnosis, gender, age, education, and sample source on BDNF. Results: BDNF levels in DAT patients were higher than those in CNC and MCI patients (P < 0.01). BDNF levels were significantly correlated with CDR, MMSE, and clinical diagnosis (P < 0.001). Age, education, occupation, and sample source had significant effects on BDNF differences among the CNC, MCI, and DAT groups (P < 0.001). BDNF first decreased and then increased with cognitive impairment in the ApoE4-negative group (P < 0.05). Conclusion: Plasma BDNF levels decreased in the MCI stage and increased in the dementia stage and were affected by age, education, occupation, and sample source. Unless the effects of sample heterogeneity and methodological differences can be excluded, plasma BDNF is difficult to become a biomarker for the early screening and diagnosis of AD.

Association Plasma Aß42 Levels with Alzheimer's Disease and Its Influencing Factors in Chinese Elderly Population.

Background and Purpose: Intracerebral Aß protein deposition is an important pathological mechanism of Alzheimer's disease (AD) and is one of the indicators of early diagnosis of AD. However, invasive lumbar puncture and Aß PET are difficult to perform in primary units, resulting delays in early diagnosis of AD. In recent years, it has been found that plasma Aß can reflect the pathological state of AD in early stage, but the results are not consistent. The objective of this study was to explore the association between plasma Aß42 levels and AD cognitive impairment and its influencing factors in Chinese elderly population, so as to provide guidance for the clinical application of plasma Aß42 as a blood biomarker of AD. Methods: This is a cross-sectional study based on the community population. Plasma samples were collected from 604 healthy controls (HC), 508 mild cognitive impairment (MCI) and 202 dementia with Alzheimer's type (DAT) patients from three cities. We analyzed the correlation between plasma Aß42 levels and cognitive function and the influence of confounding factors on the relationship between plasma Aß42 levels and AD. The independent influencing factors of plasma Aß42 levels were determined by covariance and linear regression analysis. Results: Our results suggest that there is a special linear relationship between plasma Aß42 and cognitive impairment of AD in Chinese elderly population, with Aß42 levels slightly decreased in early AD and significantly increased in moderate-to-severe AD (P<0.01). There are many factors influencing the association between plasma Aß42 levels and AD cognitive impairment, and sample source, gender and BMI are independent influencing factors of plasma Aß42. Conclusion: This indentifies that plasma Aß42 may be a peripheral biomarker for AD screening in Chinese elderly population, but it is necessary to establish standardized detection methods and establish different demarcation criteria for various influencing factors.

Altered Metabolic Characteristics in Plasma of Young Boys with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder with no clinical biomarker. This study used untargeted metabolomic analysis to identify metabolic characteristics in plasma that can distinguish ASD children. 29 boys with ASD (3.02 ± 0.67 years) and 30 typically developing (TD) boys (3.13 ± 0.46 years) were recruited. Developmental and behavioral assessments were conducted in ASD group. Samples of plasma were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between metabolite concentration and scale score was assessed by Spearman rank correlation. Altered metabolic characteristics were found in boys with ASD. In Receiver Operating Characteristic (ROC) analysis, ornithine had the highest AUC (Area under ROC) value. Furthermore, the concentration of choline and ornithine was negatively correlated with ABC-language score in ASD group.

Association Analysis of Polymorphisms in BIN1, MC1R, STARD6 and PVRL2 with Mild Cognitive Impairment in Elderly Carrying APOE ε4 Allele.

BACKGROUND: Apolipoprotein (APOE) ε4 is recognized as an independent risk factor for mild cognitive impairment (MCI). However, not everyone with the ε4 allele develops MCI, suggesting that other susceptibility genes exist. This study aimed to identify MCI susceptibility genes, including BIN1, MC1R, STARD6, and PVRL2, in elderly Han Chinese and to verify their association with APOE ε4 allele in MCI onset. METHODS: To determine whether polymorphisms in BIN1 (rs6733839, rs7561528), MC1R (rs2228479), STARD6 (rs10164112), and PVRL2 (rs6859) occurred in elderly MCI patients carrying APOE ε4 allele, we carried out a case-control study including 285 MCI patients and 326 healthy controls. RESULTS: Statistically significant differences in the proportion of APOE ε4 carriers, and BESCI, ADAS-cog, and CNT scores existed between the NC and MCI groups (all P < 0.01). Frequencies of the rs10164112 T and rs6859 A alleles were significantly higher in the latter than in the former (P = 0.01; 0.029). However, no significant differences in allele and genotype distribution of BIN1 (rs6733839, rs7561528) and MC1R (rs2228479) existed between samples in our two groups (all P > 0.05). When stratified by APOE ε4 status (carriers/non-carriers), genotype frequencies of BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 among the four groups (NCε4+, NCε4-, MCIε4+, MCIε4-) were significantly different. Additionally, our results suggest a significant association between MCI and BIN1 rs7561528, STARD6 rs10164112, and PVRL2 rs6859 (all P<0.05) in elderly carriers. CONCLUSION: This suggests that among the Han Chinese, MCI in elderly APOE ε4 carriers may be related to the BIN1 (rs7561528), STARD6 (rs10164112) and PVRL2 (rs6859). Genotype AA of rs7561528 and TT of rs10164112 might be protective factors against MCI in elderly APOE ε4 carriers.

Plasma Protein Panels for Mild Cognitive Impairment Among Elderly Chinese Individuals with Different Educational Backgrounds.

To explore plasma protein panels as potential biomarkers to screen for mild cognitive impairment (MCI) among elderly Chinese individuals with different educational backgrounds. Forty-four illiterate, 36 lower education (1-6 years), and 55 higher education (7 years or more) elderly individuals were included in the present study. Among all subjects, 67 were healthy individuals and 68 were diagnosed with MCI. Fifty plasma proteins in blood samples collected from these subjects were analyzed via the Luminex assay. Binary logistic regression was utilized to explore diagnostic models for MCI among the three educational subgroups. Then, receiver operating characteristic (ROC) curves were conducted for the clinical validity of the MCI models. Among the analyzed proteins, clusterin was used in the model of MCI among the total sample with a sensitivity (se) of 67.6%, a specificity (sp) of 59.7%, and a classification rate of 63.68%. The MCI model for the illiterate group included cystatin C, plasminogen activator inhibitor-1, and apolipoprotein A-I (se: 71.4%, sp.: 82.6%, accuracy: 77.25%). The sensitivity, specificity, and classification rate of the diagnostic model of MCI in elderly adults with lower education (human serum albumin) were each 75.0%. Additionally, the sensitivity, specificity, and accuracy rate of the diagnostic model for MCI elderly individuals with higher education (alpha-acid glycoprotein + soluble intercellular adhesion molecule-1 + pancreatic polypeptide) were 77.8%, 89.3%, and 83.60%, respectively. The performance of diagnostic models for MCI based on different educational levels is superior to that of diagnostic models for MCI without grouping by educational level.

Reliability and concurrent validity of Alzheimer's disease assessment scale - Cognitive subscale, Chinese version (ADAS-Cog-C) among Chinese community-dwelling older people population.

OBJECTIVE: To evaluate reliability and concurrent validity of the Alzheimer's Disease Assessment Scale - Cognitive Subscale, Chinese Version (ADAS-Cog-C) among Chinese community older adults. METHOD: Three groups, comprising of 1,276 community-dwelling older adults, were included in this study: a normal control (NC), a mild cognitive impairment (MCI), and an Alzheimer's disease (AD) group. All participants were assessed through ADAS-Cog-C, clinical interviews, physical examinations, Mini Mental State Examination (MMSE), and the Clinical Dementia Rating Scale (CDR). Internal consistency was assessed to evaluate the reliability of ADAS-Cog-C. Pearson and Spearman correlation coefficients were calculated to evaluate the concurrent validity between ADAS-Cog-C, MMSE, and CDR. RESULTS: Overall, the Cronbach's alpha coefficients of ADAS-Cog-C for the AD and MCI groups were 0.843 and 0.554, respectively. The split-half reliability coefficients for the AD and MCI groups were 0.860 and 0.539, respectively. ADAS-Cog-C scores were negatively correlated with MMSE scores (r = -0.706, p < 0.001) and positively associated with CDR scores (r = 0.546, p < 0.001). After excluding the MCI group from the analysis, the internal consistency of ADAS-Cog-C for the total population improved (α = 0.813, rhh = 0.852, all p < 0.001), as did the correlation between ADAS-Cog-C and MMSE (r = -0.828, p < 0.001) and CDR (r = 0.429, all p < 0.001) scores. CONCLUSIONS: ADAS-Cog-C has good internal consistency and concurrent validity for assessing Chinese community older adults with AD, but poor consistency, good concurrent validity with the MMSE while moderate concurrent validity with the CDR for MCI.

Abnormal Default-Mode Network Homogeneity in Patients With Mild Cognitive Impairment in Chinese Communities.

Background and Objective: Current evidence suggests that abnormalities within the default-mode network (DMN) play a key role in the broad-scale cognitive problems that characterize mild cognitive impairment (MCI). However, little is known about the alterations of DMN network homogeneity (NH) in MCI. Methods: Resting-state functional magnetic resonance imaging scans (rs-fMRI) were collected from 38 MCI patients and 69 healthy controls matched for age, gender, and education. NH approach was employed to analyze the imaging dataset. Cognitive performance was measured with the Chinese version of Alzheimer's disease assessment scale-Cognitive subscale (ADAS-Cog). Results: Two groups have no significant differences between demographic factors. And mean ADAS-Cog score in MCI was 12.02. MCI patients had significantly lower NH values than controls in the right anterior cingulate cortex and significantly higher NH values in the ventral medial prefrontal cortex(vmPFC) than those in healthy controls. No significant correlations were found between abnormal NH values and ADAS-Cog in the patients. Conclusions: These findings provide further evidence that abnormal NH of the DMN exists in MCI, and highlight the significance of DMN in the pathophysiology of cognitive problems occurring in MCI.

Validation study of the Alzheimer's Disease Assessment Scale-Cognitive Subscale for people with mild cognitive impairment and Alzheimer's disease in Chinese communities.

OBJECTIVE: Our study aimed to verify the validity of the Chinese version of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) for the community-dwelling older people in China. METHODS: A total of 1276 individuals composed by 628 normal controls (NCs), 572 people living with mild cognitive impairment (MCI), and 76 people living with Alzheimer's disease (AD) were recruited for the current study. All of the participants underwent ADAS-Cog, clinical interview and examination, Quick Cognitive Screening Scale for the Elderly, and Activities of Daily Living Scale. The sensitivity and specificity of ADAS-Cog were calculated, and a receiver operating characteristic curve (ROC curve) was drawn to decide the optimal cutoff points of ADAS-Cog for screening MCI and AD. RESULTS: Statistically significant differences were observed among the three groups (P <. 001, NC < MCI

hsa_circRNA_104597: a novel potential diagnostic and therapeutic biomarker for schizophrenia.

Aim: To assess whether expression of circular RNAs (circRNAs) in peripheral blood mononuclear cells can serve as a biomarker for diagnosis and/or therapeutic response in people living with schizophrenia (SZ). Materials & methods: Differentially expressed circRNAs were screened via microarray in nine individuals living with SZ and nine healthy controls, then quantified using real-time quantitative reverse transcription PCR in SZ (n = 102) and healthy control (n = 103) groups. CircRNAs were re-assessed twice in 30 randomly selected individuals living with SZ after 4- and 8-week antipsychotic treatments. Results: Five circRNAs were differentially expressed between groups. Only hsa_circRNA_104597, which was downregulated in the SZ group, was significantly upregulated after 8-week treatment. Conclusion: Dysregulation of hsa_circRNA_104597 may serve as a novel potential diagnostic and therapeutic biomarker for SZ.

Association analysis of polymorphisms in STARD6 and near ECHDC3 in Alzheimer's disease patients carrying the APOE ε4 Allele.

BACKGROUND AND PURPOSE: Lipid metabolism plays an important role in Alzheimer's disease (AD), and recent evidence suggests that single nucleotide polymorphisms (SNPs) in the StAR-related lipid transfer domain 6 (STARD6) and near the enzyme enoyl CoA hydratase domain containing 3 (ECHDC3) gene are related to plasma lipid levels or lipid traits in AD. MATERIALS AND METHODS: To identify whether the variants in or near the STARD6 and ECHDC3 genes contribute to AD susceptibility, we carried out an association analysis of STARD6 rs10164112 and ECHDC3 rs7920721 in combination with the apolipoprotein E (APOE) ε4 allele in a case-control study (278 cases, 509 controls) in China. RESULTS: We identified that SNP rs10164112 in the STARD6 gene was a risk factor associated with AD and the APOE ε4 carriers (all P<0.05) after Bonferroni correction. However, multivariate logistic regression analysis indicated that only the minor T allele of STARD6 rs10164112 combined with the APOE ε4 allele increased the risk of AD under the additive and dominant models (additive model: P=0.0078, OR=1.988, 95 % CI: 1.198-3.298; dominant model: P=0.0172, OR=2.169, 95% CI: 1.147-4.102). CONCLUSION: These results suggest that the rs10164112-T allele is not an independent risk factor for AD patients. However, in combination with the APOE ε4 allele, the rs10164112-T allele has been found to be a risk factor for AD in the Han Chinese population reported in this study.

Efficacy of Acupuncture Therapy for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients.

BACKGROUND Chemotherapy can cause adverse effects such as chemotherapy-related cognitive impairment (CRCI). In this prospective study, the efficacy of traditional Chinese medicine acupuncture therapy in relieving CRCI and its impact on serum brain-derived neurotrophic factor (BDNF) are evaluated. MATERIAL AND METHODS Eighty patients were randomly divided into a treatment group and a control group with 40 patients in each group. The treatment group was treated at the following acupuncture points: Baihui (DU20), Sishencong (EX-HN1), Shenting (DU24), Zusanli (ST36), Taixi (K13), Dazhong (K14), and Juegu (GB39). Cognitive function was assessed using the functional assessment of cancer treatment cognition test (FACT-COG, version 3), the auditory-verbal learning test (AVLT), the verbal fluency test (VFT), the symbol digit modality test (SDMT), the clock-drawing test (CDT), and the trail-making test part B (TMT-B). In addition, blood serum levels of BDNF were measured before and after treatment. Correlations between change in BDNF levels and cognitive function were also analyzed. RESULTS CRCI was ameliorated in the acupuncture treatment group, with scores on FACT-COG, AVLT-recognition and CDT assessments all significantly increased (P<0.05 in all cases). In addition, serum BDNF levels after acupuncture treatment were significantly higher than before treatment ([i]t[/i]=3.242, [i]P[/i]<0.01). Moreover, the level of BDNF was positively correlated with the total score of FACT-COG, AVLT-recognition, and CDT ([i]r[/i]=0.694, 0.628, and 0.532, respectively; all P<0.05). The control group showed no statistically significant difference in any measures over the same period. CONCLUSIONS Acupuncture therapy is effective in the treatment of CRCI in breast cancer patients through a mechanism that may be related to an increase of BDNF.

Amyloid ß causes excitation/inhibition imbalance through dopamine receptor 1-dependent disruption of fast-spiking GABAergic input in anterior cingulate cortex.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. At the early stages of AD development, the soluble ß-amyloid (Aß) induces synaptic dysfunction, perturbs the excitation/inhibition balance of neural circuitries, and in turn alters the normal neural network activity leading to cognitive decline, but the underlying mechanisms are not well established. Here by using whole-cell recordings in acute mouse brain slices, we found that 50 nM Aß induces hyperexcitability of excitatory pyramidal cells in the cingulate cortex, one of the most vulnerable areas in AD, via depressing inhibitory synaptic transmission. Furthermore, by simultaneously recording multiple cells, we discovered that the inhibitory innervation of pyramidal cells from fast-spiking (FS) interneurons instead of non-FS interneurons is dramatically disrupted by Aß, and perturbation of the presynaptic inhibitory neurotransmitter gamma-aminobutyric acid (GABA) release underlies this inhibitory input disruption. Finally, we identified the increased dopamine action on dopamine D1 receptor of FS interneurons as a key pathological factor that contributes to GABAergic input perturbation and excitation/inhibition imbalance caused by Aß. Thus, we conclude that the dopamine receptor 1-dependent disruption of FS GABAergic inhibitory input plays a critical role in Aß-induced excitation/inhibition imbalance in anterior cingulate cortex.

Blood-Derived Plasma Protein Biomarkers for Alzheimer's Disease in Han Chinese.

It is well known that Alzheimer's disease (AD) is one of the most common progressive neurodegenerative diseases; it begins gradually, and therefore no effective medicine is administered in the beginning. Thus, early diagnosis and prevention of AD are crucial. The present study focused on comparing the plasma protein changes between patients with AD and their healthy counterparts, aiming to explore a specific protein panel as a potential biomarker for AD patients in Han Chinese. Hence, we recruited and collected plasma samples from 98 AD patients and 101 elderly healthy controls from Wuxi and Shanghai Mental Health Centers. Using a Luminex assay, we investigated the expression levels of fifty plasma proteins in these samples. Thirty-two out of 50 proteins were found to be significantly different between AD patients and healthy controls (P < 0.05). Furthermore, an eight-protein panel that included brain-derived neurotrophic factor (BDNF), angiotensinogen (AGT), insulin-like growth factor binding protein 2 (IGFBP-2), osteopontin (OPN), cathepsin D, serum amyloid P component (SAP), complement C4, and prealbumin (transthyretin, TTR) showed the highest determinative score for AD and healthy controls (all P = 0.00). In conclusion, these findings suggest that a combination of eight plasma proteins can serve as a promising diagnostic biomarker for AD with high sensitivity and specificity in Han Chinese populations; the eight plasma proteins were proven important for AD diagnosis by further cross-validation studies within the AD cohort.

Correlation of DRD2 mRNA expression levels with deficit syndrome severity in chronic schizophrenia patients receiving clozapine treatment.

Schizophrenia is a complex, severe, chronic psychiatric disorder, and the associated deficit syndrome is widely regarded as an important clinical aspect of schizophrenia. This study analyzed the relationship of deficit syndrome severity with the mRNA levels of members of signaling pathways that associate with the pathophysiology of schizophrenia, including the dopamine D2 receptor (DRD2), protein kinase B (AKT1), and phosphoinositide-3 kinase (PI3KCB), in peripheral blood leukocytes (PBLs) of 20 healthy controls and 19 chronic schizophrenia patients with long-term clozapine treatment. The DRD2 expression levels in chronic schizophrenia group were statistically higher than those in controls (t=2.168, p=0.037). Moreover, in chronic schizophrenia group, correlations were observed between the expression levels of DRD2 and PI3KCB (r=0.771, p<0.001), DRD2 and AKT1 (r=0.592, p=0.008), and PI3KCB and AKT1 (r=0.562, p=0.012) and between the DRD2 mRNA levels and the Proxy for the Deficit Syndrome score (r=0.511, p=0.025). In control group, the correlation between PI3KCB expression levels and DRD2 expression levels was only observed (r=0.782, p<0.001). In conclusion, a correlation was observed between increased deficit syndrome severity and elevated expression levels of DRD2 in PBLs of chronic schizophrenia patients receiving long-term clozapine treatment.

An Integrative Computational Approach to Evaluate Genetic Markers for Bipolar Disorder.

Studies to date have reported hundreds of genes connected to bipolar disorder (BP). However, many studies identifying candidate genes have lacked replication, and their results have, at times, been inconsistent with one another. This paper, therefore, offers a computational workflow that can curate and evaluate BP-related genetic data. Our method integrated large-scale literature data and gene expression data that were acquired from both postmortem human brain regions (BP case/control: 45/50) and peripheral blood mononuclear cells (BP case/control: 193/593). To assess the pathogenic profiles of candidate genes, we conducted Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analyses, with 4 metrics proposed and validated for each gene. Our approach developed a scalable BP genetic database (BP_GD), including BP related genes, drugs, pathways, diseases and supporting references. The 4 metrics successfully identified frequently-studied BP genes (e.g. GRIN2A, DRD1, DRD2, HTR2A, CACNA1C, TH, BDNF, SLC6A3, P2RX7, DRD3, and DRD4) and also highlighted several recently reported BP genes (e.g. GRIK5, GRM1 and CACNA1A). The computational biology approach and the BP database developed in this study could contribute to a better understanding of the current stage of BP genetic research and assist further studies in the field.

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study.

BACKGROUND: Overgeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. METHODS: Twenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. RESULTS: Patients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. LIMITATIONS: The sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. CONCLUSIONS: These results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD.

Association between MKL1 rs6001946 and schizophrenia in a Han Chinese population.

Megakaryoblastic leukemia 1 (MKL1) is highly expressed in the nervous system and plays a potentially principal role in neuronal migration and morphology. A recent study showed that some genetic loci within the MKL1 gene, especially single nucleotide polymorphism (SNP) rs6001946, may increase schizophrenia susceptibility. Here, we sought to determine whether the polymorphism rs6001946 was associated with schizophrenia in a Han Chinese population using the ligase detection reaction-polymerase chain reaction method to genotype SNP rs6001946 in the MKL1 gene. We observed that there was a marginally significant association between SNP rs6001946 and the risk of schizophrenia (P=0.077). Our results indicated that SNP rs6001946 of the MKL1 gene is likely a risk factor for schizophrenia, but the role of SNP rs6001946 in the development of schizophrenia in Han Chinese should be interpreted cautiously. Further studies with larger sample sizes are needed to determine the involvement of the MKL1 polymorphism in schizophrenia susceptibility.

The mRNA expression of DRD2, PI3KCB, and AKT1 in the blood of acute schizophrenia patients.

The phosphoinositide 3 kinase - protein kinase B (PI3K-Akt) signaling pathway plays an important role in the dopamine D2 receptor (DRD2) pathway and in the pathophysiology of schizophrenia. This study measured the mRNA levels of DRD2, PI3KCB, and AKT1 in peripheral blood samples from 24 acute schizophrenia patients and 20 healthy controls using real-time quantitative reverse transcription polymerase chain reaction (real-time qRT-PCR). We found that in the acute schizophrenia patients, the mRNA expression levels of DRD2 and PI3KCB were significantly lower than those in the healthy controls, while the AKT1 mRNA levels were significantly higher than those in the healthy controls. A significant relationship between the mRNA levels of DRD2 and PI3KCB was found only in the controls. In conclusion, the gene expression state of the DRD2-PI3K-AKT signaling cascade differed significantly between acute schizophrenia patients and healthy controls.