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Abstract Background Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism. Methods We genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software. Results We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values. Conclusions Our study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.

Background: Little is known about the effect of persistent depressive symptoms on the trajectory of cognitive decline.AimsWe aimed to investigate the longitudinal association between the duration of depressive symptoms and subsequent cognitive decline over a 10-year follow-up period.Method: The English Longitudinal Study of Ageing cohort is a prospective and nationally representative cohort of men and women living in England aged ≥50 years. We examined 7610 participants with two assessments of depressive symptoms at wave 1 (2002-2003) and wave 2 (2004-2005), cognitive data at wave 2 and at least one reassessment of cognitive function (wave 3 to wave 7, 2006-2007 to 2014-2015).Results: The mean age of the 7610 participants was 65.2 ± 10.1 years, and 57.0% were women. Of these, 1157 (15.2%) participants had episodic depressive symptoms and 525 participants (6.9%) had persistent depressive symptoms. Compared with participants without depressive symptoms at wave 1 and wave 2, the multivariable-adjusted rates of global cognitive decline associated with episodic depressive symptoms and persistent depressive symptoms were faster by -0.065 points/year (95% CI -0.129 to -0.000) and -0.141 points/year (95% CI -0.236 to -0.046), respectively (P for trend < 0.001). Similarly, memory, executive and orientation function also declined faster with increasing duration of depressive symptoms (all P for trend < 0.05).Conclusions: Our results demonstrated that depressive symptoms were significantly associated with subsequent cognitive decline over a 10-year follow-up period. Cumulative exposure of long-term depressive symptoms in elderly individuals could predict accelerated subsequent cognitive decline in a dose-response pattern.Declaration of interestNone. [ABSTRACT FROM AUTHOR]

Background: High-sensitivity C-reactive protein (hs-CRP) has been suggested to be involved in the process of cognitive decline. However, the results from previous studies exploring the relationship between hs-CRP concentration and cognitive decline are inconsistent. Method: We employed data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing. Cognitive function was assessed at baseline (wave 2) and reassessed biennially at waves 3–7. Results: A total of 5257 participants (54.9% women, mean age 65.4 ± 9.4 years) with baseline hs-CRP levels ranged from 0.2 to 210.0 mg/L (median: 2.0 mg/L, interquartile range: 0.9–4.1 mg/L) were studied. The mean follow-up duration was 8.1 ± 2.8 years, and the mean number of cognitive assessment was 4.9 ± 1.5. Linear mixed models show that a one-unit increment in natural log-transformed hs-CRP was associated with faster declines in global cognitive scores [−0.048 points/year, 95% confidence interval (CI) −0.072 to −0.023], memory scores (−0.022 points/year, 95% CI −0.031 to −0.013), and executive function scores (−0.025 points/year, 95% CI −0.043 to −0.006), after multivariable adjustment. Compared with the lowest quartile of hs-CRP, the multivariable-adjusted rate of global cognitive decline associated with the second, third, and highest quartile was faster by −0.043 points/year (95% CI −0.116 to 0.029), −0.090 points/year (95% CI −0.166 to −0.015), −0.145 (95% CI −0.221 to −0.069), respectively (p for trend <0.001). Similarly, memory and executive function also declined faster with increasing quartiles of hs-CRP. Conclusions: A significant association between hs-CRP concentration and long-term cognitive decline was observed in this study. Hs-CRP might serve as a biomarker for cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Autism is a neurodevelopmental disorder with a high estimated heritability. ATP2B2, located on human chromosome 3p25.3, encodes the plasma membrane calcium-transporting ATPase 2 which extrudes Ca2+ from cytosol into extracellular space. Recent studies reported association between ATP2B2 and autism in samples from Autism Genetic Resource Exchange (AGRE) and Italy. In this study, we investigated whether ATP2B2 polymorphisms were associated with autism in Chinese Han population. Methods: We performed a family based association study between five SNPs (rs35678 in exon, rs241509, rs3774180, rs3774179, and rs2278556 in introns) in ATP2B2 and autism in 427 autism trios of Han Chinese descent. All SNPs were genotyped using the Sequenom genotyping platform. The family-based association test (FBAT) program was used to perform association test for SNPs and haplotype analyses. Results: This study demonstrated a preferential transmission of T allele of rs3774179 to affected offsprings under an additive model (T>C, Z = 2.482, p = 0.013). While C allele of rs3774179 showed an undertransmission from parents to affected children under an additive and a dominant model, respectively (Z = −2.482, p = 0.013; Z = −2.591, p = 0.0096). Haplotype analyses revealed that three haplotypes were significantly associated with autism. The haplotype C-C (rs3774180–rs3774179) showed a significant undertransmission from parents to affected offsprings both in specific and global haplotype FBAT (Z = −2.037, p = 0.042; Global p = 0.03). As for the haplotype constructed by rs3774179 and rs2278556, C-A might be a protective haplotype (Z = −2.206, p = 0.027; Global p = 0.04), while T-A demonstrated an excess transmission from parents to affected offsprings (Z = 2.143, p = 0.032). These results were still significant after using the permutation method to obtain empirical p values. Conclusions: Our research suggested that ATP2B2 might play a role in the etiology of autism in Chinese Han population. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine whether baseline atherosclerosis was associated with subsequent short-term domain-specific cognitive decline., Methods and Results: This research was based on the BRAVE (Beijing Research on Aging and Vessel) study, a population-based prospective cohort study of adults aged 40 to 80 years, free of dementia. At baseline (wave 1, 2019), cognitive assessments and atherosclerosis measures, including carotid intima-media thickness, carotid plaques, coronary artery calcification, and brachial-ankle pulse wave velocity were conducted. Cognitive function was reassessed in wave 2 (2022-2023) using linear mixed models for analysis. A total of 932 participants (63.7% women; mean age, 60.0±6.9 years) were included. Compared with the lowest tertile of carotid intima-media thickness, carotid plaques, and brachial-ankle pulse wave velocity, or a coronary artery calcification score=0, the highest tertile of carotid intima-media thickness (β=-0.065 SD/y [95% CI, -0.112 to -0.017]; P =0.008), carotid plaques (β=-0.070 SD/y [95% CI, -0.130 to -0.011]; P =0.021), and brachial-ankle pulse wave velocity (β=-0.057 SD/y [95% CI, -0.105 to -0.010]; P =0.018), and a coronary artery calcification score≥400 (β=-0.081 SD/y [95% CI, -0.153 to -0.008]; P =0.029) were significantly associated with a faster decline in semantic fluency after multivariable adjustment. Moreover, greater carotid intima-media thickness, coronary artery calcification, and brachial-ankle pulse wave velocity were significantly associated with a faster decline in global cognition., Conclusions: More significant atherosclerosis was associated with faster semantic fluency and global cognition declines.

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer., Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed., Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer., Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases., Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466)., Competing Interests: JL, YP, WZ, DG, YW, WX, FZ No competing interests declared, (© 2024, Liang et al.)

The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a 6-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in schizophrenia patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Various brain structural and functional features such as cytoarchitecture, topographic mapping, gyral/sulcal anatomy, and anatomical and functional connectivity have been used in human brain parcellation. However, the fine-grained intrinsic genetic architecture of the cortex remains unknown. In the present study, we parcellated specific regions of the cortex into subregions based on genetic correlations (i.e., shared genetic influences) between the surface area of each pair of cortical locations within the seed region. The genetic correlations were estimated by comparing the correlations of the surface area between monozygotic and dizygotic twins using bivariate twin models. Our genetic subdivisions of diverse brain regions were reproducible across 2 independent datasets and corresponded closely to fine-grained functional specializations. Furthermore, subregional genetic correlation profiles were generally consistent with functional connectivity patterns. Our findings indicate that the magnitude of the genetic covariance in brain anatomy could be used to delineate the boundaries of functional subregions of the brain and may be of value in the next generation human brain atlas., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)