An association study of ADSS gene polymorphisms with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Adenylosuccinate synthase (ADSS) catalyzes the first committed step of AMP synthesis. It was suggested that the blood-derived RNA of ADSS was down-regulated in schizophrenia (SZ) and one of the eight putative biomarker genes to discriminate SZ from normal controls. However, it remains unclear whether the reduction of ADSS RNA is due to the polymorphisms of the gene or not.</p> <p>Methods</p> <p>We attempted to examine the association of ADSS gene with schizophrenia in a Chinese population of 480 schizophrenics and 502 normal controls. Genotyping was performed by the Sequenom platform.</p> <p>Results</p> <p>The 6 marker SNPs (rs3102460, rs3127459, rs3127460, rs3127465, rs3006001, and rs3003211) were genotyped. The frequencies of alleles, genotypes, and haplotypes were tested between cases and controls. There was no significant difference of genotypic, allelic, or haplotypic distributions of the 6 SNPs between the two groups.</p> <p>Conclusion</p> <p>Our data did not support ADSS gene as a susceptibility gene for SZ in Chinese Han population. Large sample size study is needed to validate or replicate our association study, especially from other ethnic populations.</p

Characteristics of prefrontal activity during emotional and cognitive processing in patients with bipolar disorder: A multi-channel functional near-infrared spectroscopy study

Bipolar disorder (BD) is a recurrent chronic mental disorder with a broad profile of functional deficits including disturbed emotional processing and cognitive impairments. The goal of the current study was to further explore the underlying neural mechanism of dysfunction in patients with BD from a comprehensive perspective of both cognition and emotion. Forty-six clinical patients with BD and forty-five healthy controls performed emotion induction task and verbal fluency task (VFT), with frontal activity measured by functional near-infrared spectroscopy (fNIRS). Our results show distinct hemodynamic activity in the prefrontal region during emotional and cognitive processing between patients with BD and healthy controls. Patients with BD exhibit valence-dependent prefrontal cortex (PFC) hemodynamic response to emotional stimuli, with bilateral frontal hypoactivity indicating decreased positive reactivity and left frontal hyperactivity indicating increased negative reactivity. On the other hand, patients with BD showed impaired performance with bilateral frontal hypoactivity during VFT. Taken together, frontal dysfunction of cognition and emotionality in patients with BD probed by fNIRS would be a potential biomarker in clinical assessment

Association analyses of the interaction between the ADSS and ATM genes with schizophrenia in a Chinese population

<p>Abstract</p> <p>Background</p> <p>The blood-derived RNA levels of the adenylosuccinate synthase (<it>ADSS</it>) and ataxia telangiectasia mutated (<it>ATM</it>) genes were found to be down- and up-regulated, respectively, in schizophrenics compared with controls, and <it>ADSS </it>and <it>ATM </it>were among eight biomarker genes to discriminate schizophrenics from normal controls. ADSS catalyzes the first committed step of AMP synthesis, while ATM kinase serves as a key signal transducer in the DNA double-strand breaks response pathway. It remains unclear whether these changes result from mutations or polymorphisms in the two genes.</p> <p>Methods</p> <p>Six SNPs in the <it>ADSS </it>gene and three SNPs in the <it>ATM </it>gene in a Chinese population of 488 schizophrenics and 516 controls were genotyped to examine their association with schizophrenia (SZ). Genotyping was performed using the Sequenom platform.</p> <p>Results</p> <p>There was no significant difference in the genotype, allele, or haplotype distributions of the nine SNPs between cases and controls. Using the Multifactor Dimensionality Reduction (MDR) method, we found that the interactions among rs3102460 in the <it>ADSS </it>gene and rs227061 and rs664143 in the <it>ATM </it>gene revealed a significant association with SZ. This model held a maximum testing accuracy of 60.4% and a maximum cross-validation consistency of 10 out of 10.</p> <p>Conclusion</p> <p>These findings suggest that the combined effects of the polymorphisms in the <it>ADSS </it>and <it>ATM </it>genes may confer susceptibility to the development of SZ in a Chinese population.</p

Cortical structural changes of morphometric similarity network in early-onset schizophrenia correlate with specific transcriptional expression patterns

BACKGROUND: This study aimed to investigate the neuroanatomical subtypes among early-onset schizophrenia (EOS) patients by exploring the association between structural alterations and molecular mechanisms using a combined analysis of morphometric similarity network (MSN) changes and specific transcriptional expression patterns. METHODS: We recruited 206 subjects aged 7 to 17 years, including 100 EOS patients and 106 healthy controls (HC). Heterogeneity through discriminant analysis (HYDRA) was used to identify the EOS subtypes within the MSN strength. The differences in morphometric similarity between each EOS subtype and HC were compared. Furthermore, we examined the link between morphometric changes and brain-wide gene expression in different EOS subtypes using partial least squares regression (PLS) weight mapping, evaluated genetic commonalities with psychiatric disorders, identified functional enrichments of PLS-weighted genes, and assessed cellular transcriptional signatures. RESULTS: Two distinct MSN-based EOS subtypes were identified, each exhibiting different abnormal MSN strength and cognitive functions compared to HC. The PLS1 score mapping demonstrated anterior–posterior gradients of gene expression in EOS1, whereas inverse distributions were observed in EOS2 cohorts. Genetic commonalities were identified in autistic disorder and adult schizophrenia with EOS1 and inflammatory bowel diseases with EOS2 cohorts. The EOS1 PLS1- genes (Z &lt; -5) were significantly enriched in synaptic signaling-related functions, whereas EOS2 demonstrated enrichments in virtual infection-related pathways. Furthermore, the majority of observed associations with EOS1-specific MSN strength differences contributed to specific transcriptional changes in astrocytes and neurons. CONCLUSIONS: The findings of this study provide a comprehensive analysis of neuroanatomical subtypes in EOS, shedding light on the intricate relationships between macrostructural and molecular aspects of the EOS disease

Lessons from a Canada-China cross-national qualitative suicide research collaboration

A cross-national qualitative suicide study was conducted by Tsinghua University and the University of Toronto with two samples of Chinese women in Beijing and Toronto. The aim of this article is to reflect on lessons learned from this collaborative study. A literature review guided the analysis. A focus group was conducted with members of both research teams. A semi-structured interview guide was developed to explore the researchers’ experiences of participating in the cross-national study. Focus group transcript data and observations from authors informed the analysis, situated in the existing literature on cross-national qualitative health research and guided by Baistow’s cross-national research frame. Our study highlights how cross-national research involves conceptual and practical challenges that require negotiation. Such research also holds many opportunities, including (1) using a different cultural lens to understand differences and clarify similarities cross-culturally; (2) co-constructing knowledge through collaboration; (3) deconstructing one’s own assumptions; and (4) engaging in an inspiring and empowering experience in collaboration