Wen Zhang

Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

This pilot study evaluated the effects of supplementation with PUFA on blood FA composition and behavior in children with Attention-Deficit/Hyperactivity Disorder (AD/HD)-like symptoms also reporting thirst and skin problems. Fifty children were randomized to treatment groups receiving either a PUFA supplement providing a daily dose of 480 mg DHA, 80 mg EPA, 40 mg arachidonic acid (AA), 96 mg GLA, and 24 mg alpha-tocopheryl acetate, or an olive oil placebo for 4 mon of double-blind parallel treatment. Supplementation with the PUFA led to a substantial increase in the proportions of EPA, DHA, and alpha-tocopherol in the plasma phospholipids and red blood cell (RBC) total lipids, but an increase was noted in the plasma phospholipid proportions of 18:3n-3 with olive oil as well. Significant improvements in multiple outcomes (as rated by parents) were noted in both groups, but a clear benefit from PUFA supplementation for all behaviors characteristic of AD/HD was not observed. For most outcomes, improvement of the PUFA group was consistently nominally better than that of the olive oil group; but the treatment difference was significant, by secondary intent-to-treat analysis, on only 2 out of 16 outcome measures: conduct problems rated by parents (-42.7 vs. -9.9%, n = 47, P = 0.05), and attention symptoms rated by teachers (-14.8 vs. +3.4%, n = 47, P = 0.03). PUFA supplementation led to a greater number of participants showing improvement in oppositional defiant behavior from a clinical to a nonclinical range compared with olive oil supplementation (8 out of 12 vs. 3 out of 11, n = 33, P = 0.02). Also, significant correlations were observed when comparing the magnitude of change between increasing proportions of EPA in the RBC and decreasing disruptive behavior as assessed by the Abbreviated Symptom Questionnaire (ASQ) for parents (r = -0.38, n = 31, P < 0.05), and for EPA and DHA in the RBC and the teachers' Disruptive Behavior Disorders (DBD) Rating Scale for Attention (r = -0.49, n = 24, P < 0.05). Interestingly, significant correlations were observed between the magnitude of increase in alpha-tocopherol concentrations in the RBC and a decrease in scores for all four subscales of the teachers' DBD (Hyperactivity, r = -0.45; Attention, r= -0.60; Conduct, r = -0.41; Oppositional/Defiant Disorder, r = -0.54; n = 24, P < 0.05) as well as the ASQ for teachers (r = -0.51, n = 24, P < 0.05). Thus, the results of this pilot study suggest the need for further research with both n-3 FA and vitamin E in children with behavioral disorders.

// Wen Zhang 1 , Yan Ge 1, 2 , Qian Cheng 1 , Qi Zhang 1 , Lin Fang 1 and Junnian Zheng 1, 2, 3 1 Cancer Institute, Xuzhou Medical University, Xuzhou, China 2 Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China 3 Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China Correspondence to: Junnian Zheng, email: fl@xzhmu.edu.cn Lin Fang, email: fanglinzhqf@163.com Keywords: anti-fibrosis; anti-tumour; decorin; pro-inflammatory; proteoglycan Received: July 21, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: December 27, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: January 03, 2018 ABSTRACT Decorin (DCN), an extracellular matrix (ECM) protein, belongs to the small leucine-rich proteoglycan family. As a pluripotent molecule, DCN regulates the bioactivities of cell growth factors and participates in ECM assembly. Accumulating evidence has shown that DCN acts as a ligand of various cytokines and growth factors by directly or indirectly interacting with the corresponding signalling molecules involved in cell growth, differentiation, proliferation, adhesion and metastasis and that DCN especially plays vital roles in cancer cell proliferation, spread, pro-inflammatory processes and anti-fibrillogenesis. The multifunctional nature of DCN thus enables it to be a potential therapeutic agent for a variety of diseases and shows good prospects for clinical and research applications. DCN, an extracellular matrix (ECM) protein that belongs to the small leucine-rich proteoglycan family, is widely distributed and plays multifunctional roles in the stroma and epithelial cells. Originally, DCN was known as an effective collagen-binding partner for fibrillogenesis [ 1 ] and to modulate key biomechanical parameters of tissue integrity in the tendon, skin and cornea [ 2 ]; thus, it was named decorin (DCN). Since being initially cloned in 1986, DCN was discovered to be a structural constituent of the ECM [ 3 ]. However, the paradigm has been shifted; it has become increasingly evident that in addition to being a matrix structural protein, DCN affects a wide range of biological processes, including cell growth, differentiation, proliferation, adhesion, spread and migration, and regulates inflammation and fibrillogenesis [ 4 &ndash; 7 ]. Two main themes for DCN functions have emerged: maintenance of cellular structure and regulation of signal transduction pathways, culminating in anti-tumourigenic effects. Here, we review the interaction network of DCN and emphasize the biological correlations between these interactions, some of which are expected to be therapeutic intervention targets.

Adolescent idiopathic scoliosis (AIS) is a structural deformity of the spine affecting millions of children. As a complex disease, the genetic aetiology of AIS remains obscure. Here we report the results of a four-stage genome-wide association study (GWAS) conducted in a sample of 4,317 AIS patients and 6,016 controls. Overall, we identify three new susceptibility loci at 1p36.32 near AJAP1 (rs241215, Pcombined=2.95 × 10(-9)), 2q36.1 between PAX3 and EPHA4 (rs13398147, Pcombined=7.59 × 10(-13)) and 18q21.33 near BCL-2 (rs4940576, Pcombined=2.22 × 10(-12)). In addition, we refine a previously reported region associated with AIS at 10q24.32 (rs678741, Pcombined=9.68 × 10(-37)), which suggests LBX1AS1, encoding an antisense transcript of LBX1, might be a functional variant of AIS. This is the first GWAS investigating genetic variants associated with AIS in Chinese population, and the findings provide new insight into the multiple aetiological mechanisms of AIS.

OBJECTIVE: Large numbers of people with type 2 diabetes are obese. However, changes in cognition and related brain function in obese people with diabetes have not been characterized. Here, we investigated cognition, olfactory function, and odor-induced brain alterations in these patients and therapeutic effects of glucagon-like peptide 1 receptor agonists (GLP-1Ras) on their psychological behavior and olfactory networks. RESEARCH DESIGN AND METHODS: Cognitive, olfactory, and odor-induced brain activation assessments were administered to 35 obese and 35 nonobese people with type 2 diabetes and 35 control subjects matched for age, sex, and education. Among them, 20 obese individuals with diabetes with inadequate glycemic control and metformin monotherapy received GLP-1Ra treatment for 3 months and were reassessed for metabolic, cognitive, olfactory, and neuroimaging changes. RESULTS: Obese subjects with diabetes demonstrated lower general cognition and olfactory threshold scores, decreased left hippocampal activation, and disrupted seed-based functional connectivity with right insula compared with nonobese subjects with diabetes. Negative associations were found between adiposity and episodic memory and between fasting insulin and processing speed test time in diabetes. Mediation analyses showed that olfactory function and left hippocampus activation mediated these correlations. With 3-month GLP-1Ra treatment, obese subjects with diabetes exhibited improved Montreal Cognitive Assessment (MoCA) score, olfactory test total score, and enhanced odor-induced right parahippocampus activation. CONCLUSIONS: Obese subjects with type 2 diabetes showed impaired cognition and dysfunctional olfaction and brain networks, the latter of which mediated adiposity in cognitive impairment of diabetes. GLP-1Ras ameliorated cognitive and olfactory abnormalities in obese subjects with diabetes, providing new perspectives for early diagnosis and therapeutic approaches for cognitive decrements in these patients.