Search

Objective To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L (n = 98); Q2 group: 358.23 ± 14.03 μmol/L (n = 99); Q3 group: 405.50 ± 14.59 μmol/L (n = 98) and Q4 group: 499.14 ± 56.97μmol/L (n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan–Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. Results During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN (P = 0.747) was shown in the Kaplan–Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621–2.992; P = 0.439), 1.518 (0.768–3.002; P = 0.230) and 1.411 (0.706–2.821; P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P = 0.652). Conclusions No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.

Background Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear. Methods This retrospective study enrolled 218 adult patients with type 2 diabetes mellitus and biopsy-proven DKD, and without known cardiovascular diseases. These patients were followed up at least 1 year. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was further analyzed with logistic regression and Cox proportional hazard analysis. Results Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively (P = 0.268). Compared with patients with lower ASCVD risk(༜14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk(> 14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis(odds ratio [OR], 3.997; 95% confidence interval [CI], 1.385–11.530;P = 0.010). However, univariate and multivariate COX proportional hazard analysis showed the 10-year ASCVD risk score failed to be an independent risk factor for ESRD in patients with type 2 diabetes mellitus. Conclusions PCE can estimate ASCVD risk in patients with DKD, and DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.

Linghong Guo,1,2,* Honghong Ren,2,* Lutong Pu,2 Xingyu Zhu,2 Yin Liu,1,3,4 Xuelei Ma1 1Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 3Department of Pharmacology, West China School of Basic Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Anesthesiology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuelei MaDepartment of Biotherapy, Cancer Center West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan 610041, People’s Republic of ChinaTel/ Fax +86-28-85475576Email drmaxuelei@gmail.comBackground: Hepatic artery interventional therapy has been recognized as the first choice for advanced liver cancer. However, reliable prognostic markers are still lacking. In the present study, we aimed to evaluate the prognostic value of inflammation factors including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) in hepatocellular carcinoma (HCC) patients with hepatic artery interventional treatments.Methods: Patients undergoing hepatic artery interventional therapy after being diagnosed with HCC between 2007 and 2014 were enrolled. Pre-treatment NLR, PLR and MLR were calculated, and all factors including gender, age, TNM stage, BCLC staging, inflammation factors, LDH, ALP, CEA, AFP, hepatitis, liver cirrhosis, portal vein involvement, surgical history and hepatic artery interventional treatment on overall survival (OS) were evaluated by the univariate and multivariate Cox proportional hazards analyses.Results: Overall, 407 patients were included. The optimal cutoff values determined by receiver operating characteristic (ROC) curve analyses for NLR, PLR and MLR were 3.82, 140.00 and 0.27, respectively. High NLR was associated with worse OS (median survival time: high NLR group 9 vs low NLR group 19 months, HR 1.842, 95% CI: 1.457– 2.329, P< 0.001). Elevated PLR was negatively correlated with OS (8 vs 18 months, HR 1.677, 95% CI: 1.302– 2.161, P< 0.001). Patients in high MLR group had a worse OS (10 vs 21 months, HR 1.626, 95% CI: 1.291– 2.048, P< 0.001). In multivariate analysis, NLR, LDH, ALP and portal vein involvement were independent prognostic factors for OS of HCC patients after hepatic artery interventional therapy. In addition, for patients in BCLC stage A and B, higher NLR, PLR and MLR were all significantly negatively correlated to median survival time (NLR: 17 vs 26 months, HR: 1.739 (95% CI: 1.279– 2.365), P< 0.001; PLR: 18 vs 26 months, HR: 1.681 (95% CI: 1.245– 2.271), P=0.001; MLR: 20 vs 26 months, HR: 1.589 (95% CI: 1.185– 2.129), P=0.002).Conclusion: Elevated pre-treatment NLR, PLR and MLR were associated with worse survival time in HCC patients after hepatic artery interventional therapy. Among them, NLR was an independent prognostic factor for OS.Keywords: hepatocellular carcinoma, neutrophils, platelets, lymphocytes, inflammation, prognosis

Objective: To characterize the relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in Chinese patients and to determine whether the severity of DR predicts end-stage renal disease (ESRD). Methods: Bilateral fundic photographs of 91 Chinese type 2 diabetic patients with biopsy-confirmed DN, not in ESRD stage, were obtained at the time of renal biopsy in this longitudinal study. The baseline severity of DR was determined using the Lesion-aware Deep Learning System (RetinalNET) in an open framework for deep learning and was graded using the Early Treatment Diabetic Retinopathy Study severity scale. Cox proportional hazard models were used to estimate the hazard ratio (HR) for the effect of the severity of diabetic retinopathy on ESRD. Results: During a median follow-up of 15 months, 25 patients progressed to ESRD. The severity of retinopathy at the time of biopsy was a prognostic factor for progression to ESRD (HR 2.18, 95% confidence interval 1.05 to 4.53, P = .04). At baseline, more severe retinopathy was associated with poor renal function, and more severe glomerular lesions. However, 30% of patients with mild retinopathy and severe glomerular lesions had higher low-density lipo-protein-cholesterol and more severe proteinuria than those with mild glomerular lesions. Additionally, 3% of patients with severe retinopathy and mild glomerular changes were more likely to have had diabetes a long time than those with severe glomerular lesions. Conclusion: Although the severity of DR predicted diabetic ESRD in patients with type 2 diabetes mellitus and DN, the severities of DR and DN were not always consistent, especially in patients with mild retinopathy or microalbuminuria. Abbreviations: CI = confidence interval; DM = diabetic mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = hemoglobin A1c; HR = hazard ratio; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus; VEGF = vascular endothelial growth factor.

The human gut microbiome plays an important role in the basic neurodevelopmental processes of the central nervous system and has been implicated in several neuropsychiatric disorders. However, the connection between the gut microbiome and the underlying pathogenesis of schizophrenia (SCZ) is poorly defined. Here we analyzed the faecal samples from 40 first-episode drug-naïve SCZ (FSCZ) patients, 85 chronically antipsychotic-treated SCZ (TSCZ) patients and 69 healthy controls (HCs) using 16S rRNA gene sequence to determine whether the alterations of the gut microbiome were associated with SCZ or antipsychotic treatment. In addition, we acquired the T1-weighted brain imaging data by using structural magnetic resonance imaging to test whether microbial composition correlated with structural brain signatures. Our analyses revealed low microbiome alpha-diversity indexes in TSCZ patients but not in FSCZ patients as compared to HCs. Importantly, both FSCZ and TSCZ patients had distinct changes in gut microbial composition at certain taxa including Christensenellaceae, Enterobacteriaceae, Pasteurellaceae, Turicibacteraceae at the family level and Escherichia at genus level as compared to HCs. We also found significant disturbances of gut microbial composition in TSCZ versus FSCZ patients (eg. Enterococcaceae and Lactobacillaceae). Most interestingly, our exploratory analyses found specific SCZ-associated microbiota to be correlated with the right middle frontal gyrus (rMFG) volume which was aberrant in SCZ patients. Our findings extend prior work and suggest a possible link between the gut microbiome and brain structure which may be implicated in the pathology of SCZ.

Introduction: Wernicke's encephalopathy (WE) is a severe neurological syndrome often associated with alcoholism. Clinicians tend to ignore WE in other non-alcoholic clinical settings related to malnutrition and thiamine deficiency, resulting in delayed diagnosis. The diagnosis becomes more difficult when WE is secondary to psychiatric illnesses as symptoms can be masked by the primary disease.Case Presentation: We present a case of a 56-year-old female patient with schizophrenia who was admitted to the hospital for mental and behavioral disorder, without history of alcohol. She presented symptoms of ophthalmoplegia and high muscular tension, and the brain MRI showed symmetric lesions in the bilateral basal ganglia and third ventricle. She responded well to thiamine and was discharged on hospital day 22.Conclusion: The psychiatrists should be on the alert for starvation-induced WE, especially for patients suffering from malnutrition. WE is a preventable and treatable disease, so once suspected of WE, patients ought to take adequate supplements of thiamine immediately.

BackgroundTo investigate the association between sex differences and end-stage kidney disease (ESKD) in patients with biopsy-confirmed diabetic kidney disease (DKD).MethodWe performed a retrospective cohort study. A total of 336 patients with biopsy-confirmed DKD who were followed up for at least 12 months were enrolled. Baseline clinical and pathological data at the time of biopsy were collected. ESKD was defined by an estimated glomerular filtration rate of 2or initiation of renal replacement therapy. The association between sex differences and ESKD was assessed using the log-rank test and Cox regression.ResultThere were 239 (71%) male and 97 (29%) female patients in our cohort. Female patients had higher systolic blood pressure, total cholesterol and low-density lipoprotein cholesterol levels compared with male. There were a lower proportion of female patients in the very high risk grade according to the chronic kidney disease categories (37% of female vs. 44% of male). During a median follow-up time of 20 months, 101 (57.7%) male and 43 (44.3%) female entered into ESKD, with no significant difference by the log-rank test (P >0.05). Univariate [male: hazard ratio (HR) [95% confidence interval (CI)], 1.005, (0.702–1.439)] and multivariable ([male: HR (95%CI), 1.164, (0.675–2.007)]. Cox regression further showed that sex difference was not significantly associated with ESKD.ConclusionFemale patients had the higher systolic blood pressure, total cholesterol, LDL-C, compared with male patients. However, there was no significant association observed between sex difference and ESKD in our study.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Background To address the prognostic value of combining tubular basement membrane (TBM) and glomerular basement membrane (GBM) thickness in diabetic nephropathy (DN). Methods This retrospective study enrolled 110 patients with type 2 diabetes and biopsy‐proven DN from 2011 to 2018. The pathological findings were confirmed according to the Renal Pathology Society classifications. GBM and TBM thicknesses were determined using the Haas' direct measurement/arithmetic mean method and orthogonal intercept method, respectively. Cox proportional hazard models were used to investigate the hazard ratios (HRs) for the influence of combined GBM and TBM thickness for predicting end‐stage renal disease (ESRD). Results Patients were assigned to three groups according to the median GBM and TBM thickness: GBMloTBMlo (GBM, Highlights The prognostic value of combining tubular basement membrane (TBM) and glomerular basement membrane (GBM) in diabetic nephropathy (DN) was lacking.TBM thickness was strongly correlated with GBM thickness, baseline estimated glomerular filtration rate, and proteinuria.The degree of TBM thickness provided additional value to GBM thickness for predicting end‐stage renal disease progression in patients with type 2 diabetes and biopsy‐proven DN.

Zhao, Lijun, Xi Wang, Tingli Wang, Wenxin Fan, Honghong Ren, Rui Zhang, Yutong Zou, Huan Xu, Jie Zhang, Yunhong Wu, and Fang Liu. Associations between high-altitude residence and end-stage kidney disease in Chinese patients with type 2 diabetes.

The glutamatergic system has previously been shown to be involved in the pathophysiology of schizophrenia and the mechanisms of action of antipsychotic treatment. The present study aimed to investigate the relationship between the levels of glutamate (Glu) or Glu/total creatine (Glu/Cr+PCr) in the anterior cingulate cortex (ACC) and psychiatric symptoms as well as the response to antipsychotic treatment. We performed proton magnetic resonance spectroscopy (1H–MRS) to measure Glu and Glu/Cr+PCr in the ACC of 35 drug-naïve first-episode schizophrenia (FES) patients and 40 well-matched healthy controls (HCs). After scanning, we treated the patients with risperidone for eight weeks. Remission status was based on the Positive and Negative Syndrome Scale (PANSS) scores at week 8. At baseline, there were no significant differences in the levels of Glu or Glu/Cr+PCr in the ACC between drug-naïve FES patients and HCs. Lower baseline levels of Glu/Cr+PCr but not Glu in the ACC were associated with more severe negative symptoms of schizophrenia. Compared to the remission group (RM), the non-remission group (NRM) had lower baseline ACC Glu levels (P < 0.05). Our results suggest that ACC Glu levels may be related to the severity of symptoms in the early stages of schizophrenia and therefore may be a marker with which to evaluate the treatment effect of antipsychotics in schizophrenia patients.

This retrospective study included 299 patients with type 2 diabetes mellitus and biopsy-confirmed diabetic nephropathy (DN) to investigate the prognostic value of alkaline phosphatase (ALP) for renal outcome. Cox proportional hazards models were used to estimate the hazard ratios (HRs) for the serum ALP level on renal outcome, which was defined as end-stage renal disease (ESRD) or a 50% decline in estimated glomerular filtration rate (eGFR) from baseline. The median baseline ALP was 80 IU/L with an interquartile range of 64–97 IU/L. Serum ALP was negatively associated with eGFR but positively associated with proteinuria and renal interstitial fibrosis. During a median follow-up period of 23 months, ESRD or a 50% declined in the eGFR occurred in 156 (52.2%) patients. The highest quartile of ALP was significantly associated with poor renal outcome, as defined above (HR 2.38, 95% confidence interval [CI] 1.09–5.17), when adjusted for sociodemographics, baseline eGFR, proteinuria, liver function parameters, parathyroid hormone levels, and renal pathological findings. Each standard deviation higher in the natural log-transformed ALP was associated with a 25% increased risk for poor renal outcome. Additionally, there was a graded increase in the risk for poor renal outcome with higher ALP in patients with nephrotic-range proteinuria. However, no significant associations were observed between serum ALP levels and renal outcome in patients with non-nephrotic-range proteinuria. In conclusion, an elevated ALP level was independently associated with poor renal outcome in patients with type 2 diabetes mellitus and nephrotic-range proteinuria after multivariate adjustment.

The older population has increased sharply in China. However, renal clinical and histopathological data in this population are lacking. This study investigated the clinicopathologic features and the related risk factors for long-term renal survival in older patients with diabetic nephropathy (DN). In this retrospective observational study, 74 older patients (≥ 60 years old) with type 2 diabetes mellitus and biopsy-proven DN from 2007 to 2019 were included. Clinical data were extracted from electronic records. Renal biopsy specimens were semiquantitatively evaluated using the Renal Pathology Society (RPS) classification system. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for progression to end-stage renal disease (ESRD). During the median follow-up period of 22 months, 24 (32%) older patients progressed to ESRD. Older patients who progressed to ESRD had poorer renal function, lower hemoglobin and albumin concentrations, more severe glomerular lesions, and higher percentages of Kimmelstiel–Wilson lesions than those who did not progress to ESRD. After adjusting for age, sex, baseline renal function, and pathological parameters, multivariate Cox proportional hazard analysis showed that RPS glomerular classification (HR 2.49, 95% confidence interval [CI] 1.03–6.04), estimated glomerular filtration rate (eGFR) (HR 0.76, 95% CI 0.58–0.99), and proteinuria (HR 3.85, 95% CI 1.44–10.27) were independent risk factors for progression to ESRD. Lower eGFR, heavier proteinuria, and more severe RPS glomerular lesions were associated with ESRD in older patients with type 2 diabetes mellitus and DN.

To investigate the relationships between hematuria, clinicopathological features and renal outcomes in patients with biopsy-proven diabetic nephropathy (DN). This cohort study included 261 patients with DN. Participants were divided into two groups according to number of red blood cells per high-power field (RBC/hpf) in urine sediment: the hematuria (−) group (≤ 3 RBC/hpf) and the hematuria (+) group (> 3 RBC/hpf). Basic clinical parameters were measured at the time of renal biopsy; relationships between hematuria and clinicopathological features and renal outcomes were analyzed. Patients in the hematuria (+) group often had overt proteinuria. Interstitial inflammation was more severe in the hematuria (+) group than in the hematuria (−) group. Glomerular arteriolar hyalinosis, interstitial fibrosis and tubular atrophy were comparable between groups. For patients with early DN (eGFR ≥ 60 ml/min/1.73 m2), urinary RBC/hpf at baseline was positively correlated with glomerular classification, interstitial fibrosis/tubular atrophy scores and interstitial inflammation scores. In prognostic analysis, hematuria was associated with a higher risk of progression to end-stage renal disease. Hematuria remained an independent predictor after adjustment for confounding factors such as sex, age, duration of diabetes, serum glucose level, hypertension, cholesterol, eGFR and urine protein excretion, especially in patients with early DN and in male patients. In this study, hematuria was associated with more severe renal pathologic lesions in patients with DN. The presence of hematuria could be an independent predictor of renal outcome in patients with early DN.

Background: Dopaminergic and serotonergic systems play crucial roles in the pathophysiology of schizophrenia and modulate response to antipsychotic treatment. However, previous studies of dopaminergic and serotonergic genes expression are sparse, and their results have been inconsistent. In this longitudinal study, we aim to investigate the expressions of Catechol-O-methyltransferase (COMT), serotonin 2A receptor (5-HTR2A), and serotonin transporter gene (SLC6A4) mRNA in first-episode antipsychotic-naive schizophrenia and to test if these mRNA expressions are associated with cognitive deficits and treatment outcomes or not. Method: We measured COMT, 5-HTR2A, and SLC6A4 mRNA expressions in 45 drug-naive first-episode schizophrenia patients and 38 health controls at baseline, and repeated mRNA measurements in all patients at the 8-week follow up. Furthermore, we also assessed antipsychotic response and cognitive improvement after 8 weeks of risperidone monotherapy. Results: Patients were divided into responders (N = 20) and non-responders groups (N = 25) according to the Remission criteria of the Schizophrenia Working Group. Both patient groups have significantly higher COMT mRNA expression and lower SLC6A4 mRNA expression when compared with healthy controls. Interestingly, responder patients have significantly higher levels of COMT and 5-HTR2A mRNA expressions than non-responder patients at baseline. However, antipsychotic treatment has no significant effect on the expressions of COMT, 5-HTR2A, and SLC6A4 mRNA over 8-week follow up. Conclusion: Our findings suggest that dysregulated COMT and SLC6A4 mRNA expressions may implicate in the pathophysiology of schizophrenia, and that COMT and 5-HTR2A mRNA may be potential biomarkers to predict antipsychotic response.

Both post-mortem and neuroimaging studies have identified abnormal white matter (WM) microstructure in patients with schizophrenia. However, its genetic underpinnings and relevant biological pathways remain unclear. In order to unravel the genes and the pathways associated with abnormal WM microstructure in schizophrenia, we recruited 100 first-episode, drug-naïve patients with schizophrenia and 140 matched healthy controls to conduct genome-wide association analysis of fractional anisotropy (FA) value measured using diffusing tensor imaging (DTI), followed by multivariate association study and pathway enrichment analysis. The results showed that one intergenic SNP (rs11901793), which is 20 kb upstream of CXCR7 gene on chromosome 2, was associated with the total mean FA values with genome-wide significance (p = 4.37 × 10−8), and multivariate association analysis identified a strong association between one region-specific SNP (rs10509852), 400 kb upstream of SORCS1 gene on chromosome 10, and the global trait of abnormal WM microstructure (p = 1.89 × 10−7). Furthermore, one pathway that is involved in cell cycle regulation, REACTOME_CHROMOSOME _MAINTENANCE, was significantly enriched by the genes that were identified in our study (p = 1.54 × 10−17). In summary, our study provides suggestive evidence that abnormal WM microstructure in schizophrenia is associated with genes that are likely involved in diverse biological signals and cell-cycle regulation although further replication in a larger independent sample is needed.