RESUMO
OBJECTIVES: Genetic factors play an important role in the etiology of schizophrenia (SZ). Catenin Delta 2 (CTNND2) is one of the genes regulating neuronal development in the brain. It is unclear whether CTNND2 is involved in SZ. With the hypothesis that CTNND2 may be a risk gene for SZ, we performed a case-control association analysis to investigate if CTNND2 gene single nucleotide polymorphisms (SNPs) are implicated in SZ in a Han Chinese population. MATERIALS AND METHODS: We recruited subjects from 2010 to 2022 from the Han population of northern Henan and divided them into two case-control samples, including a discovery sample (SZ = 528 and controls = 528) and replication sample (SZ = 2458 and controls = 6914). Twenty-one SNPs were genotyped on the Illumina BeadStation 500G platform using GoldenGate technology and analyzed by PLINK. The Positive and Negative Syndrome Scale (PANSS) was used to assess clinical symptoms. RESULTS: Rs16901943, rs7733427, and rs2168878 SNPs were associated with SZ (Chi2 = 7.484, 11.576, and 5.391, respectively, df = 1; p = 0.006, 0.00067, and 0.02, respectively) in the two samples. Rs10058868 was associated with SZ in male patients in the discovery sample (Chi2 = 6.264, df = 1, p = .044). Only the relationship with rs7733427 survived Bonferroni correction. Linkage disequilibrium block three haplotypes were associated with SZ in the discovery and total sample. PANSS analysis of the four SNPs implicated rs10058868 and rs2168878 in symptoms of depression and excitement, respectively, in the patients with SZ. CONCLUSION: Four SNPs of the CTNND2 gene were identified as being correlated with SZ. This gene may be involved in susceptibility to SZ.
Assuntos
Predisposição Genética para Doença , Esquizofrenia , Humanos , Masculino , Estudos de Casos e Controles , delta Catenina , Estudos de Associação Genética , Esquizofrenia/genética , População do Leste Asiático , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do GeneRESUMO
BACKGROUND: Evidence from functional and structural research suggests that abnormal brain activity plays an important role in the pathophysiology of schizophrenia (SZ). However, limited studies have focused on post-treatment changes, and current conclusions are inconsistent. STUDY DESIGN: We recruited 104 SZ patients to have resting-state functional magnetic resonance imaging scans at baseline and 8 weeks of treatment with second-generation antipsychotics, along with baseline scanning of 86 healthy controls (HCs) for comparison purposes. Individual regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and degree centrality values were calculated to evaluate the functional activity. The Positive and Negative Syndrome Scale (PANSS) and MATRICS Consensus Cognitive Battery were applied to measure psychiatric symptoms and cognitive impairment in SZ patients. RESULTS: Compared with HCs at baseline, SZ patients had higher ALFF and ReHo values in the bilateral inferior temporal gyrus, inferior frontal gyrus, and lower ALFF and ReHo values in fusiform gyrus and precuneus. Following 8 weeks of treatment, ReHo was increased in right medial region of the superior frontal gyrus (SFGmed) and decreased in the left middle occipital gyrus and the left postcentral gyrus. Meanwhile, ReHo of the right SFGmed was increased after treatment in the response group (the reduction rate of PANSS ≥50%). Enhanced ALFF in the dorsolateral of SFG correlated with improvement in depressive factor score. CONCLUSIONS: These findings provide novel evidence for the abnormal functional activity hypothesis of SZ, suggesting that abnormality of right SFGmed can be used as a biomarker of treatment response in SZ.