Identification of Enolase 1 as a Potential Target for Magnaporthe oryzae: Integrated Proteomic and Molecular Dynamics Simulation.

Rice blast is an essential factor affecting rice yield and quality, which is caused by Magnaporthe oryzae (M. oryzae). Isobavachalcone (IBC) is a botanical fungicide derived from the seed extract of the Leguminosae plant Psoralea corylifolia L. and has shown an excellent rice blast control effect in field applications. To explore the potential targets of rice blast control, the analysis of the differentially expressed proteins (DEPs) between the liquid culture medium of mycelium treated by 10 mg/L of IBC for 2 h and the control group indicated that Enolase 1 (ENO1) was the most significantly down-regulated DEP with a fold change value of 0.305. In vitro experiments showed that after treating liquid culture mycelium with 10 mg/L of IBC for 0.5, 1, 2, 4, and 8 h, the enzymatic activity of ENO1 in the IBC experimental groups was 0.97, 0.75, 0.52, 0.44, and 0.39 times as much as in the control groups, respectively. To further explore the molecular interaction and binding mode between IBC and ENO1, the three-dimensional structure of ENO1 was established based on homology modeling. Molecular docking and molecular dynamics simulation showed that IBC had a pi-pi stacking effect with the residue TYR_365, a hydrogen bond interaction with the residue ARG_393, and hydrophobic interactions with non-polar residues ALA_361, LYS_362, and VAL_371 of ENO1. These findings indicated that ENO1 is a potential target of M. oryzae, which would pave the way for screening novel effective fungicides targeting ENO1.

A novel chromosome 2q24.3-q32.1 microdeletion in a fetus with multiple malformations.

BACKGROUND: Terminal or interstitial deletion of chromosome 2q is rarely reported but clinically significant, which can result in developmental malformations and psychomotor retardation in humans. In the present study, we analyzed this deletion to comprehensively clarify the relationship between phenotype and microdeletion region. METHODS: We collected clinical records of the fetus and summarized patient symptoms. Subsequently, genomic DNA was extracted from fetal tissue or peripheral blood collected from parents. In addition, whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. RESULTS: The fetus presented a previously unreported interstitial deletion of 2q24.3-q32.1. WES and CNV-seq revealed a de novo 18.46 Mb deletion at 2q24.3-q32.1, a region involving 94 protein-coding genes, including HOXD13, MAP3K20, DLX1, DLX2, SCN2A, and SCN1A. The fetus had upper and lower limb malformations, including camptodactyly and syndactyly, along with congenital cardiac defects. CONCLUSION: Herein, we report a fetus with a novel microdeletion of chromosome 2q24.3-q32.1, likely a heterozygous pathogenic variant. Haploinsufficiency of HOXD13 might be related to limb deformity in the fetus.

Identification of Pyruvate Dehydrogenase E1 as a Potential Target against Magnaporthe oryzae through Experimental and Theoretical Investigation.

Magnaporthe oryzae (M. oryzae) is a typical cause of rice blast in agricultural production. Isobavachalcone (IBC), an active ingredient of Psoralea corylifolia L. extract, is an effective fungicide against rice blast. To determine the mechanism of IBC against M. oryzae, the effect of IBC on the metabolic pathway of M. oryzae was explored by transcriptome profiling. In M. oryzae, the expression of pyruvate dehydrogenase E1 (PDHE1), part of the tricarboxylic acid (TCA cycle), was significantly decreased in response to treatment with IBC, which was verified by qPCR and testing of enzyme activity. To further elucidate the interactions between IBC and PDHE1, the 3D structure model of the PDHE1 from M. oryzae was established based on homology modeling. The model was utilized to analyze the molecular interactions through molecular docking and molecular dynamics simulation, revealing that IBC has π-π stacking interactions with residue TYR139 and undergoes hydrogen bonding with residue ASP217 of PDHE1. Additionally, the nonpolar residues PHE111, MET174, ILE 187, VAL188, and MET250 form strong hydrophobic interactions with IBC. The above results reveal that PDHE1 is a potential target for antifungal agents, which will be of great significance for guiding the design of new fungicides. This research clarified the mechanism of IBC against M. oryzae at the molecular level, which will underpin further studies of the inhibitory mechanism of flavonoids and the discovery of new targets. It also provides theoretical guidance for the field application of IBC.

Aberrant brain structural-functional connectivity coupling in euthymic bipolar disorder.

Aberrant structural (diffusion tensor imaging [DTI]) and resting-state functional magnetic resonance imagining connectivity are core features of bipolar disorder. However, few studies have explored the integrity agreement between structural and functional connectivity (SC-FC) in bipolar disorder. We examine SC connectivity coupling index whether could potentially provide additional clinical predictive value for bipolar disorder spectrum disorders besides the intramodality network measures. By examining the structural (DTI) and resting-state functional network properties, as well as their coupling index, among 57 euthymic bipolar disorder patients (age 13-28 years, 18 females) and 42 age- and gender-matched healthy controls (age 13-28 years, 16 females), we found that compared to controls, bipolar disorder patients showed increased structural rich-club connectivity as well as decreased functional modularity. Importantly, the coupling strength between structural and functional connectome was decreased in patients compared to controls, which emerged as the most powerful feature discriminating the two groups. Our findings suggest that structural-functional coupling strength could serve as a valuable biological trait-like feature for bipolar disorder over and above the intramodality network measures. Such measure can have important clinical implications for early identification of bipolar disorder individuals, and inform strategies for prevention of bipolar disorder onset and relapse.

Contribution of genes in the GABAergic pathway to bipolar disorder and its executive function deficit in the Chinese Han population.

In this study, we investigated the association between bipolar I disorder (BDI) and between cognitive deficits therein and SNPs in GABAergic receptor genes. The sample comprised 477 patients with BDI and 438 healthy controls, with three neurocognitive tests being administered in 123 patients and 164 controls. For three SNPs, rs505474, rs1398175, and rs4868029 in the GABRA2, GABRA4, and GABRP genes, respectively, their allele frequencies were significantly different between patients and controls (Bonferroni-adjusted p = values 3.84 × 10-4 , 9.92 × 10-3 , and 1.22 × 10-2 , respectively). Four haplotypes were significantly associated with BDI (TA and AG for rs3815762 and rs4868029 in GABRP, GG for rs11636988 and rs8024256 in GABRB3 and GAGG for rs2197414, rs4921195, rs13188991, and rs11956731 in GABRA6, with p values of 0.0038, 0.044, 0.0176, and 0.0267, respectively, on 10,000 permutations). Furthermore, the SNP (rs2912585) within 250 kb upstream of the GABRB3 gene displayed a strong association with the Tower of Hanoi (TOH) executive time in the patient group (p = 2.844 × 10-6 ). One other SNP (rs754661), which is located at the intronic region of the same gene, was associated with the global trait of the executive function and post hoc analysis showed significant SNP by group effect (p = 0.0094). Our study supports previous findings that GABAA receptor genes are associated with bipolar disorder; it also suggests that the GABAA genes, especially the GABRB3 gene, might play a role in the executive function deficit in bipolar disorder, although future replication with a larger sample size is needed.

Association analysis of genes in serotonin pathway with attention and executive function in patients with bipolar affective disorder.

BACKGROUND: The reason why it is difficult to identify susceptibility genes attributed to bipolar disorder (BPD) is the phenotypic heterogeneity. The use of endophenotypes has been advocated as one possible strategy to discovery cause variants of BPD. METHODS: A total of 164 patients with BPD and 164 matched controls were employed in the present research. Fifty-two single nucleotide polymorphisms (SNPs) within the genes in serotonin pathway were selected for genotyping using the GoldenGate genotyping assay. All participants completed three neurocognitive tests including the tower of Hanoi (TOH), the Wisconsin card sorting test (WCST) and Trail making tests (TMTA and TMTB-M). RESULTS: Patients with BPD demonstrated a wide range of deficits in mental activities of attention and speed of information processing, and executive function. Significant interactions between rs2760347 in 5HTR2A gene and diagnosis were found for the executive time of TOH, with ß=11.82 and P=0.002 (adjusted P=0.03 after Bonferroni correction). CONCLUSIONS: Cognitive impairments existing in BPD may be particularly notable in certain domains of attention and executive function, and 5HTR2A gene may be involved in modulating executive function of BP-I patients.

[Association study of LIS1 and TSNAX genes with bipolar disorder in Chinese Han population].

OBJECTIVE: To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population. METHODS: Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software. RESULTS: Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms. CONCLUSION: Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.

Exploring the impact of social capital, institutional quality and political stability on environmental sustainability: New insights from NARDL-PMG.

The social aspect of sustainable development is often considered the least strong component, particularly in terms of its analytical and theoretical foundations. Although there has been a recent increase in focus on social sustainability, the relationship between the environmental aspect and social capital is still not well understood. This research seeks to explore initial concepts on frameworks for analyzing the interface between environmental and social capital. However, to demonstrated the core connection of social capital, institutional quality, income and renewable energy consumption with sustainability level (CO2 emissions) in the BRICS economies from 1996 to 2021. Specifically, this study uses advanced techniques such as Non-ARDL, Pooled Mean Group, the Augmented Mean Group and Common Correlated Effect Mean Group. However, under the linear outcomes, social capital, law & order, government stability, political stability and income decline the emissions levels. However, renewable energy consumption shows the positive association with rising emissions in BRICS countries. Interestingly, under the non-linear form, study outcomes describe social capital, and law & order contribute to environmental quality, while government & political stability spur the level of emissions in the long-run. Also, this study provides some core implications to meet the desired sustainability level.

Aerobic exercise impacts the anterior cingulate cortex in adolescents with subthreshold mood syndromes: a randomized controlled trial study.

Aerobic exercise is effective in alleviating mood symptoms while the mechanism is poorly understood. There are limited clinical trials that investigated the effect of exercise on the anterior cingulate cortex (ACC), a key brain region involved in mood regulations, in adolescents with subthreshold mood syndromes. This randomized controlled trial (RCT) of aerobic exercise was undertaken in a middle school in Guangzhou, China. Participants were adolescents aged 12-14 with subthreshold mood syndromes including depressive and manic symptoms and were randomly assigned to an aerobic exercise intervention or a psychoeducation control group. Participants in the exercise group received moderate-intensity exercise intervention, consisting of 30 mins running, 4 days per week for 3 months. The primary outcome in this study was structural changes in the ACC from baseline to post intervention. The trial was registered with ClinicalTrial.gov (NCT03300778). Of 56 participants who met the criteria for subthreshold mood syndromes, 39 (41.03% males) had complete MRI data, with 20 and 19 subjects in the exercise and control group, respectively. At baseline, demographic information (e.g., age and sex), clinical symptoms, and the gray matter volume and cortical thickness of ACC were matched between the two groups. After 12 weeks of treatment, participants in the exercise group displayed increased gray matter volume of the left rostral ACC (F1,30 = 5.73, p = 0.02) and increased cortical thickness of the right rostral ACC (F1,30 = 7.83, p = 0.01) when compared with the control group. No significant differences were found for caudal ACC cortical thickness and gray matter volume. Our data demonstrate that 12-week, moderate-intensity aerobic exercise can induce structural changes in the rostral ACC in adolescents with subthreshold mood syndromes.

Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes.

The effects of intrahepatic cholestasis of pregnancy (ICP) on hepatic function, changes of inflammatory cytokines and fetal outcomes were studied. In total, 663 pregnant women admitted to Daqing Longnan Hospital from July 2016 to December 2017 were selected. There were, 40 cases with ICP enrolled in the observation group, and 40 normal pregnant women were recruited in the normal group. They were also grouped according to hepatic function and inflammatory cytokines, with 40 cases in each group. Neonatal Apgar scores were recorded. The correlations of serum cholylglycine (CG) in pregnant women with umbilical artery systolic-to-diastolic (S/D) ratio in the third trimester of pregnancy, the alanine aminotransferase level, the high-sensitivity C-reactive protein (hs-CRP) level, neonatal Apgar score and gestational week were analyzed. The birth weight in the observation group was lighter than that in the normal group (P<0.05); the gestational week at birth was earlier than that in the normal group (P<0.05); Apgar score at birth was lower than that in the normal group (P<0.05), and the levels of inflammatory cytokines were higher than those in the control group (P<0.05). Apgar scores of newborns at birth and at 1 and 5 min after birth in the normal hepatic function and normal inflammatory cytokine groups were higher than those in the abnormal hepatic function group (P<0.05). The serum CG level in pregnant women was positively correlated with umbilical artery S/D ratio, the alanine aminotransferase level and the hs-CRP level in the third trimester of pregnancy, but negatively correlated with neonatal Apgar score and gestational week. Among patients with ICP, the higher the GG level in the body is, the higher the alanine aminotransferase, inflammatory cytokine and umbilical artery S/D ratio will be, which may cause lower neonatal Apgar score, neonatal asphyxia and premature delivery.

Identification of isobavachalcone as a potential drug for rice blast disease caused by the fungus Magnaporthe grisea.

The rice blast disease caused by the fungus Magnaporthe grisea is one of the most devastating rice diseases, but there is no effective fungicide toward chitinase which is a key enzyme of M. grisea. In this study, we observed that distortion and cell-wall damage of M. grisea hyphae were significantly under the scanning electron micrograph after a 24-h treatment with 10 mg/L isobavachalcone (IBC) extracted from Psoralea corylifolia L. To further explore the effect of IBC on the cell wall of M. grisea, we examined changes in enzymes associated with cell wall degradation by enzyme activity experiments, treated liquid culture mycelia with 10 mg/L IBC for 1 h. Results displayed that chitinase was obviously more active than control group. To illustrate the interactions between IBC and chitinase, the studies of homology modeling and molecular docking were carried out successively. The results revealed that IBC had hydrogen bonds with residues ASP267 and ARG276 of chitinase. Besides, these nonpolar residues TYR270, PRO271, VAL272, LEU310, PRO311, TYR316, and LEU317 were able to form strong hydrophobic interactions. Binding energies of the chitinase-IBC complexes were calculated by MM-GBSA showed that the ΔGbind score of molecular dynamics had lower binding energy and more stable than docking complexes. All above, IBC owns significant agonistic activity in chitinase and would be a potent fungicide to inhibit the growth of M. grisea. We hope the above information provides an important insight for understanding the interactions between IBC and chitinase, which may be useful in the discovery of a novel potent agonist. Communicated by Ramaswamy H. Sarma.

Abnormal Degree Centrality Associated With Cognitive Dysfunctions in Early Bipolar Disorder.

Delayed diagnosis of bipolar disorder (BD) is common. However, diagnostic validity may be enhanced using reliable neurobiological markers for BD. Degree centrality (DC) is one such potential marker that enables researchers to visualize neuronal network abnormalities in the early stages of some neuropsychiatric disorders. In the present study, we measured resting-state DC abnormalities and cognitive deficits in order to identify early neurobiological markers for BD. We recruited 23 patients with BD who had recently experienced manic episodes (duration of illness <2 years) and 46 matched healthy controls. Our findings indicated that patients with BD exhibited DC abnormalities in frontal areas, temporal areas, the right postcentral gyrus, and the posterior lobe of the cerebellum. Moreover, correlation analysis revealed that psychomotor speed indicators were associated with DC in the superior temporal and inferior temporal gyri, while attention indicators were associated with DC in the inferior temporal gyrus, in patients with early BD. Our findings suggest that DC abnormalities in neural emotion regulation circuits are present in patients with early BD, and that correlations between attention/psychomotor speed deficits and temporal DC abnormalities may represent early markers of BD.

Illness, at-risk and resilience neural markers of early-stage bipolar disorder.

BACKGROUND: Current knowledge on objective and specific neural markers for bipolar risk and resilience-related processes is lacking, partly due to not subdividing high-risk individuals manifesting different levels of subclinical symptoms who possibly possess different levels of resilience. METHODS: We delineated grey matter markers for bipolar illness, genetic high risk (endophenotype) and resilience, through comparing across 42 young non-comorbid bipolar patients, 42 healthy controls, and 72 diagnosis-free, medication-naive high-genetic-risk individuals subdivided into a combined-high-risk group who additionally manifested bipolar risk-relevant subsyndromes (N = 38), and an asymptomatic high-risk group (N = 34). Complementary analyses assessed the additional predictive and classification values of grey matter markers beyond those of clinical scores, through using logistic regression and support vector machine analyses. RESULTS: Illness-related effects manifested as reduced grey matter volumes of bilateral temporal limbic-striatal and cerebellar regions, which significantly differentiated bipolar patients from healthy controls and improved clinical classification specificity by 20%. Reduced bilateral cerebellar grey matter volume emerged as a potential endophenotype and (along with parieto-occipital grey matter changes) separated combined-high-risk individuals from healthy and high-risk individuals, and increased clinical classification specificity by approximately 10% and 27%, respectively, while the relatively normalized cerebellar grey matter volumes in the high-risk sample may confer resilience. LIMITATIONS: The cross-validation procedure was not performed on an independent sample using independently-derived features. The BD group had different age and sex distributions than some other groups which may not be fully addressable statistically. CONCLUSIONS: Our framework can be applied in other measurement domains to derive complete profiles for bipolar patients and at-risk individuals, towards forming strategies for promoting resilience and preclinical intervention.

CACNA1C polymorphisms Impact Cognitive Recovery in Patients with Bipolar Disorder in a Six-week Open-label Trial.

Cognitive impairments in bipolar patients deteriorate as the disorder progresses. Little is known about whether genetic risks impact cognitive recovery during the course from depression to remission. In this six-week open-label trial, we shed light on the impacts of six single nucleotide polymorphisms (SNPs) in the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene on cognitive recovery in 192 bipolar patients suffering a major depressive episode (MDE). The primary outcome measures were changes in a battery of neuropsychological tests following 6-week treatment. Carriers with rs10466907 GT genotype did not significantly improve their executive function total scores on the Wisconsin Card Sorting Test after six weeks of treatment compared to the TT genotypes (ß = -0.944, 95% Confidence Interval (CI) = -1.482--0.405). Moreover, during a MDE carriers with rs58619945 GG and GA genotypes performed significantly worse than those with AA genotype on the categories completed (p = 0.013 and p = 0.001), total errors (p = 0.039 and p = 0.009), and random errors (p = 0.055 and p = 0.014, respectively). Our data suggest that the tested CACNA1C SNPs may have impacts on cognitive recovery from depression.

Association study of dopamine receptor genes polymorphism with cognitive functions in bipolar I disorder patients.

OBJECTIVE: To determine the correlation among the polymorphisms of dopamine receptor genes, cognitive function of Bipolar disorder (BD) patients, and BD. METHODS: Twenty-three Single Nucleotide Polymorphisms (SNPs) of dopamine receptor genes were genotyped using Illumina GoldenGate genotyping assay in 375 patients with bipolar I disorder (BD-I) (patients group) and 475 healthy controls (control group). Cognitive function tests were performed in 158 patients who were clinically stable and 307 healthy controls who were matched with the patients in age, sex, and education. RESULTS: The allele frequencies of rs3758653 in the promoter region of the DRD4 gene were significantly different between patients group and control group (χ(2)=9.386, Corrected P=0.046). This significant difference was also observed between BD-I patients with psychotic symptoms and healthy controls (χ(2)=9.27, Corrected P=0.049). Patients with BD-I performed significantly worse than healthy controls in all cognitive domains (p<0.01) except TMTA errors and illegal time. Significant interactions between polymorphisms of rs5326 in DRD1 gene and phenotype (affected or unaffected with BD-I) were found in non-perseverative errors (ß=3.20 and Corrected P=0.0034) on the Wisconsin Card Sorting Test (WCST). The allele of this SNP denoted the positive effect on the WCST non-perseverative errors in BD-I patients group (ß=2.80 and Corrected P=0.017). The genotypic association analyses also supported the findings (F=4.24 and P=0.007), but this effect was not found in controls. LIMITATIONS: The sample size was relatively small and the SNP coverage was limited, making it very important to be cautious when drawing a conclusion. CONCLUSIONS: DRD4 gene may play an important role in psychotic symptomatology rather than in unique diagnosis, BD, for example. A genetic association exists between DRD1 gene and impaired cognition in BD.

Methionine sulfoxide reductase A (MsrA) associated with bipolar I disorder and executive functions in A Han Chinese population.

BACKGROUND: The oxidative stress hypothesis proposed to explain bipolar I disorder (BD I) pathogenesis has gained growing attention based on its association with cognitive impairment. The aim of the present study was to explore the association of the methionine sulfoxide reductase A (MsrA) gene with BD I as well as executive functions of BD I patients. METHODS: A total of 44 tagging single-nucleotide polymorphisms within the MsrA gene were selected to analyze gene association with BD I in 375 BD I patients and 475 controls in a Han Chinese population. The association of MsrA haplotypes with executive functions was analyzed in 157 clinically stable BD I patients and 210 controls. RESULTS: Allele frequencies of the rs4840463 polymorphism were significantly different between BD I patients and controls, and between patients with psychotic symptoms and controls. BD I patients performed more poorly in 11 of the 13 neurocognitive measurements compared with controls. Three MsrA haplotypes showed significant associations with different executive functions. LIMITATIONS: The limited sample size requires a cautious conclusion, and further comprehensive approaches are needed to explore the mechanism of MsrA's effect on BD I. CONCLUSIONS: The rs4840463 polymorphism in the MsrA gene may be associated with the increased risk of BD I in a Chinese population. The association of MsrA haplotypes with executive functions indicated that MsrA is associated with executive function defects in BD I patients.

Completely reversed flow in the vertebral artery does not always indicate subclavian steal phenomenon.

We evaluated the causes, differential diagnosis and clinical significance of completely reversed flow (CRF) in the vertebral artery (VA). Twenty-three patients diagnosed with CRF in the VA by Doppler ultrasound were studied retrospectively. CRF was divided into intermittent CRF and continuous CRF. The peak reversed velocity (PRV) and ratio of time in intermittent CRF to one cardiac cycle (tICRF/CC) were calculated. Causes of CRF were determined on the basis of previous angiography results. The results indicated that subclavian steal phenomenon (SSP) caused all cases of continuous CRF (n = 8). Intermittent CRF was caused by SSP (n = 6) or proximal VA occlusion (n = 9). PRV and tICRF/CC were increased in SSP as compared with VA occlusion (p < 0.05). Using a cutoff of tICRF/CC = 0.30, we achieved excellent accuracy in predicting the cause of intermittent CRF (100%) and posterior circulatory infarction (91%). Thus, analysis of CRF patterns and measurements of VA parameters can be used in differential diagnosis of the causes of CRF and in prediction of posterior circulatory infarction.

Genes in the serotonin pathway are associated with bipolar affective disorder in a Han Chinese population.

Serotonin plays an important role in mood regulation, but the involvement of serotonin pathway genes in the development of bipolar I disorder (BP-I), a mood disorder, is not clear. We selected 21 single-nucleotide polymorphisms (SNPs) within the HTR2A gene, 8 within the SLC6A4 gene and 23 within the TPH2 gene for genotyping using the GoldenGate genotyping assay. A total of 375 patients with BP-I and 475 normal controls were recruited. Two out of 21 SNPs (rs1475196 and rs9567747) in the HTR2A gene and 1/23 SNPs (rs17110566) in the TPH2 gene were significantly associated with BP-I, both genotype-wise and allele-wise. Furthermore, a specific haplotype in the HTR2A gene showed a significant association with BP-I. Our results indicate that the HTR2A and TPH2 genes in the serotonin pathway play important roles in susceptibility to BP-I.

Association of the 3' region of the neuregulin 1 gene with bipolar I disorder in the Chinese Han population.

BACKGROUND: Based on the function of neuregulin 1 (NRG1) in neurodevelopment, susceptibility to bipolar disorder presumably involves this gene. The 3' region of NRG1 contains the majority of the coding exons, and transcripts from this region encode 8 of the 9 known NRG1 isoforms; therefore, this region is likely to be predominant versus the 5' region in terms of their relative contributions to NRG1 function. We investigated the association between the 3' region of the NRG1 gene and bipolar I disorder (BPI) in the Chinese Han population and performed further analyses depending on the presence or absence of psychotic features. METHODS: A total of 385 BPI patients and 475 healthy controls were recruited for this study. Thirty tag single nucleotide polymorphisms (SNPs) across the 3' region of the NRG1 gene were genotyped for allelic and haplotypic associations with BPI and subgroups with psychotic features (BPI-P) or without psychotic features (BPI-NP). RESULTS: Individual marker analysis showed that 2 SNPs (rs12547858 and rs6468121) in this region were significantly associated with BPI. Moreover, subgroup analyses showed significant but marginal associations of rs6468121 with BPI-P and rs3757933 with BPI-NP. Haplotype analyses showed that 6 haplotypes were associated with BPI only. LIMITATIONS: The sample size was relatively small. The investigated tag SNPs only represented 83% of the information on the targeted region. There might be a retrospective bias in the subgroup analyses. CONCLUSION: The results suggest that the 3' region of the NRG1 gene plays a role in BPI susceptibility in the Chinese Han population. In addition, the preliminary results show that BPI with psychotic features and BPI without psychotic features may constitute different sub-phenotypes; however, this finding should be confirmed in a larger population sample.