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DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation‐expression‐pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta‐catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV‐939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.

Background Accumulating evidence has converged to suggest that childhood trauma may contribute to bipolar disorder (BD). This study aimed to investigate the patterns of childhood trauma among patients with bipolar I (BD-I) and bipolar II (BD-II) disorders, according to DSM-IV and in contrast with healthy volunteers. We also explored whether the relationship between childhood trauma and onset of bipolar disorder is mediated by immature defense mechanisms. Methods Participants were patients with BD-I (n=44) and BD-II (n = 42), and healthy controls (HCs, n = 43). Childhood traumatic experiences and defense mechanisms were assessed by the Childhood Trauma Questionnaire (CTQ) and the Defense Style Questionnaire (DSQ), respectively. Results BD patients experienced more severe childhood trauma than HCs. Physical neglect sub-score and total score of the CTQ had both direct and indirect effects on the diagnosis of BD-I, and an immature defense style mediated the indirect effects. The diagnosis of BD-II was mainly related to the physical neglect and emotional abuse subs-core and total score of the CTQ, as mediated by the immature defense mechanisms. BD-I and BD-II significantly differed in the emotional abuse sub-score of the CTQ. Conclusions Physical neglect sub-score and total score of the CTQ were associated with the diagnosis of BD (both BD-I and BD-II), as mediated by an immature defense style. Furthermore, emotional abuse might be an important risk factor for BD-II compared to BD-I. These findings may inform risk reduction and psychosocial intervention strategies to prevent and treat patients with bipolar disorders.

Individuals with attention deficit hyperactivity disorder (ADHD) show gray matter volume (GMV) reduction in the putamen. KTN1 variants may regulate kinectin 1 expression in the putamen and influence putamen structure and function. We aim to test the hypothesis that the KTN1 variants may represent a genetic risk factor of ADHD. Two independent family-based Caucasian samples were analyzed, including 922 parent-child trios (a total of 2,757 subjects with 924 ADHD children) and 735 parent-child trios (a total of 1,383 subjects with 613 ADHD children). The association between ADHD and a total of 143 KTN1 SNPs was analyzed in the first sample, and the nominally-significant (p

Background: Previous studies have implicated childhood trauma and abnormal brain-derived neurotrophic factor in the pathogenesis of schizophrenia. Here, we explored whether brain-derived neurotrophic factor levels mediated the relationship between childhood trauma and psychopathological symptoms in patients with first-episode schizophrenia. Methods: Patients with first-episode schizophrenia ( n = 192) and healthy controls ( n = 136) were enrolled. Childhood traumatic experiences and psychopathology were assessed by Childhood Trauma Questionnaire and Positive and Negative Syndrome Scale, respectively. Enzyme-linked immunosorbent assay was used to quantify brain-derived neurotrophic factor levels. Results: The patients with first-episode schizophrenia experienced more severe childhood trauma and had lower serum brain-derived neurotrophic factor levels than healthy controls. Emotional abuse and Childhood Trauma Questionnaire total score showed positive correlation with Positive and Negative Syndrome Scale positive, general psychopathological subscore and total score. Emotional neglect showed positive correlation with Positive and Negative Syndrome Scale positive subscore. Physical neglect was positively associated with Positive and Negative Syndrome Scale negative subscore. Emotional neglect and Childhood Trauma Questionnaire total score were negatively correlated with serum brain-derived neurotrophic factor levels. The serum brain-derived neurotrophic factor levels mediated the relationship between both Childhood Trauma Questionnaire total score and Positive and Negative Syndrome Scale total score and negative symptoms in the patients. The brain-derived neurotrophic factor levels also mediated the relationship between emotional neglect and Positive and Negative Syndrome Scale total score in the patients. Conclusion: Childhood trauma might contribute to the clinical symptoms of schizophrenia by affecting brain-derived neurotrophic factor levels. Perhaps we can prevent schizophrenia by reducing childhood traumatic experiences.

Background: Accumulating evidence suggests that hypothalamic-pituitary-adrenal (HPA) axis dysfunction might play an important role in the pathophysiology of schizophrenia. Cortisol secretion levels can reflect the function of the HPA axis.This study aimed to explore the cortisol response to psychological stress in patients with schizophrenia. Methods: In this cross-sectional study study, patients with schizophrenia (n = 104) and healthy volunteers (n = 59) were asked to complete psychological stress challenge tasks, which included the Paced Auditory Serial Addition Task and Mirror-Tracing Persistence Task, and then, saliva was collected to measure cortisol levels. Emotions and psychopathology were assessed by the Positive and Negative Affect Schedule (PANAS) and Positive and Negative Syndrome Scale (PANSS). Results: (1) that the cortisol stress response and negative emotions in patients with schizophrenia differed significantly from those in healthy controls; (2) there were significant interactions between sampling time and diagnosis for saliva cortisol levels; (3) there were significant interactions between scoring time and diagnosis for the negative affect score of the PANAS; and (4) the changes in salivary cortisol levels and negative affect scores before and after the psychological stress challenge tasks were not correlated with clinical symptoms in patients with schizophrenia. Conclusions: These findings indicated that an abnormal cortisol stress response might be a stable biological characteristic of schizophrenia.

The building of cabin hospitals in Wuhan has been proven to be clinically successful in curing mild-symptom COVID-19 patients shortly after the outbreak of COVID-19 in late 2019. At the same time, the psychological effect of patients being treated in cabin hospitals and the features of the psychological status of the whole society remained ambiguous. This study adopted a self-administrated questionnaire to investigate the stress, depression, and anxiety status of patients in cabin hospitals (n = 212) and healthy participants outside of Hubei province (n = 221) in a population level from February 29 to March 01, 2020. The research measured participants’ stress response, depression level, and anxiety level as well as their social support system and their resilience level. Results indicated that in this sudden outbreak of an unknown pandemic, all people (whether or not infected) showed a generally high level of stress, depression, and anxiety, regardless of age, gender, education level, and employment. It also showed that people with a lower level of psychological resilience and social support reported more severe symptoms of depression, anxiety, and stress. Moreover, the research also found a positive effect of cabin hospitals on the psychological recovery of COVID-19 patients. Stress response of patients increased after entering into cabin hospitals, while after 3–4 weeks’ treatment, patients showed a decrease in their depression and anxiety levels. This research advances the understanding of COVID-19 and gives suggestions to optimize the design and the allocation of resources in cabin hospitals and better deal with the unknown pandemics in the future.

Background: The study aimed to examine the antipsychotic treatment effect on the serum S100B and oxidative stress in patients with schizophrenia. Methods: Subjects consisted of patients with schizophrenia of first-episode drug-naive and drug-free acute phases, and met the DSM-IV diagnostic criteria for schizophrenia. All patients were treated with risperidone for eight weeks. Positive and Negative Syndrome Scale (PANSS) was evaluated, and serum levels of S100B and parameters of oxidative stress including total oxidative status (TOS) and malondialdehyde (MDA) were measured before and after antipsychotic treatment. A general linear random-effect model was used for data analysis. Results: Antipsychotic treatment with risperidone reduced the levels of S100B significantly in the first episode drug-naive patients with schizophrenia (Beta=24.89; p=0.0087) and marginally in the drug-free acute phase (Beta=15.65; p=0.093), no significant difference in the effect on S100B between patient groups (p=0.4785). In contrast, antipsychotic treatment increased the levels of MDA in drug-free acute phase schizophrenia (Beta=-6.55; p

Background The aim was to explore the associations between clinical symptoms, demographic variables, social and neurocognitive functioning in euthymic patients with bipolar disorder (BD) stratified by subgroups of DSM-IV BD (type I (BD-I) and type II (BD-II)) and occupational status (employed/unemployed), and to highlight the significance of occupational status when assessing social and neurocognitive functioning in euthymic BD patients. Methods A total of 81 euthymic BD patients were participated in the study. The severity of the depressive and manic/hypomanic symptoms was measured using the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Young Mania Rating Scale (YMRS), respectively. Social functioning and neurocognitive functioning were evaluated by the Functioning Assessment Short Test (FAST) and neurocognitive measures, respectively. Results Employed BD patients displayed greater social functioning (autonomy, occupational functioning, interpersonal relationship domain) and better verbal learning performance and speed of processing than unemployed BD patients. The correlation between neurocognitive functioning and social functioning was stronger in the employed group than in the unemployed group. There were no significant differences in neurocognitive and social functioning between the BD-I and BD-II groups, and the correlation between neurocognitive functioning and social functioning was similar between the BD-I and BD-II groups. Conclusion Employed BD patients may present greater occupational functioning and interpersonal relationships, as well as better verbal learning performance and speed of processing.

Frontline healthcare nurses devoted themselves to deal with the outbreak of COVID-19, saving many lives. However, they are under incredible unknown psychological pressures with a considerable risk of infection. In this study, a self-administered questionnaire was used to survey 593 frontline nurses in Wuhan City and non-Hubei provinces for psychological responses from March 1 to March 10, 2020. Compared with nurses outside Hubei Province, those working in Wuhan were more likely to feel physically and mentally exhausted. Their probable depression and anxiety were significantly higher than those of nurses outside Hubei province (31.2%, 18.3% vs. 13.8%, 5.9%). Correspondingly, the depressive symptoms were more often reported in the Wuhan group (70.8% vs. 41.4%). Although Wuhan received wishes, concerns, and abundant psychological and material resources from all of the world, the survey-based study found that frontline nurses in Wuhan still had higher depression and anxiety with less social support compared with nurses from non-Hubei provinces. Unexpectedly, only 4.0% of nurses have sought psychological assistance. These findings suggested that the short-term psychological impact of frontline nurses in Wuhan during the COVID-19 outbreak was extremely high compared with nurses outside Hubei Province. This research enlightened the efficient integration of psychological resources, the optimization of the nurse emergency psychological assistance system, and the mental health care of medical staff during the outbreak of epidemics.

Sleep disorders are one of the most common non-motor symptoms in Parkinson's disease (PD). It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. The most cited sleep disorders in PD included insomnia, restless legs syndrome (RLS), rapid eye movement (REM), sleep behavior disorders (RBD), excessive daytime sleepiness (EDS) and sleep disordered breathing (SDB), which can appear alone or several at the same time. In this review, we listed the recommended pharmacological treatments for common sleep disorders in PD, and discussed the recommended dosages, benefits and side effects of relative drugs. We also discussed non-pharmacological treatments to improve sleep quality, including sleep hygiene education, exercise, deep brain stimulation, cognitive behavior therapy and complementary therapies. We tried to find proper interventions for different types of sleep disorders in PD, while minimizing relative side effects.

In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease.

Reduced cortical gray matter integrity and cognitive abilities are among core deficits in schizophrenia. We hypothesized that higher allostatic load (AL) that accounts for exposure to chronic stress is a contributor to structural and cognitive deficits in schizophrenia. One hundred and sixty-seven schizophrenia patients who were on average with normal weight, normal systolic, and diastolic blood pressure and 72 healthy controls were enrolled in the study. Group differences in subclinical cardiovascular, metabolic, immune, and neuroendocrine biological markers as indexed by AL and contribution of AL components to the structural and cognitive deficits in schizophrenia were explored. Compared with controls, schizophrenia patients who were normotensive, normoweight, and had low total cholesterol levels still had significantly higher AL mainly due to lower high-density lipoprotein cholesterol and higher heart rate, waist-hip ratio, hemoglobinA1c, hypersensitive C-reactive protein, and overnight-urine cortisol levels. Patients also had decreased whole-brain mean cortical thickness, and lower cognition assessed by the MATRICS consensus cognitive battery. AL was inversely correlated with mean cortical thickness and cognition in schizophrenia, while none of these relationships existed in controls. Mediation analyses showed the effect of AL on cognitive deficits in schizophrenia was significantly mediated by cortical thinning, and the most significant mediating cortical area was the left superior frontal gyrus. Cortical thickness may act as a mediator between AL and cognitive deficits in schizophrenia. Early intervention strategies to reduce cortical thinning and cognitive dysfunction in schizophrenia should target specific aspects of their high AL in addition to weight gain, hypertension and high cholesterol levels.

Introduction Our study was designed to examine the relationship between Brain‐Derived Neurotrophic Factor (BDNF) genotypes (rs6265, Val66Met), BDNF plasma levels, and cognitive impairment in Chinese patients with panic disorder (PD). Methods Total 85 patients with PD and 91 healthy controls finally completed all assessments. The severity of panic symptoms and whole anxiety of PD was measured by Panic Disorder Severity Scale–Chinese Version (PDSS‐CV) and Hamilton Anxiety Scale (HAMA‐14). Montreal Cognitive Assessment (MoCA) and some neurocognitive measures were conducted to evaluate the cognitive performance. All participants were detected for the plasma BDNF levels and BDNF Val66Met polymorphism before assessment and treatment. Results No significant differences were found in the BDNF allele frequencies and the BDNF genotype distributions between healthy controls and PD patients. BDNF Met/Met genotype was associated with lower BDNF plasma levels in PD patients, and PD patients with BDNF Met/Met genotype had the lower scores in the attention and speed of processing domains compared to those with Val/Val and Met/Val genotype (p's, This is a study focusing on associations between Brain‐Derived Neurotrophic Factor (BDNF) single nucleotide polymorphism, plasma Levels, and cognitive impairment in Chinese patients with panic disorder (PD).We found the BDNF Met/Met genotype may be associated with lower BDNF plasma levels and some domains of cognitive impairments in PD patients.

Accumulating evidence indicates that a dysregulated kynurenine (KYN) pathway (KP) metabolism may play an important role in the pathogenesis of both schizophrenia and metabolic syndrome (MS). However, the underlying mechanisms remain poorly understood. Here, we aimed to evaluate the potential roles of KP in the pathogenesis of MS in schizophrenia. A total of 160 schizophrenia patients and 70 healthy controls were enrolled in this study. KP metabolites were quantified, and MS scores were calculated, for comparisons between patients and controls. Associations among the indices were explored in both groups. Multiple linear regression analyses were performed to investigate the effects of KP metabolites on MS factors. We observed a significantly higher MS score, lower levels of all KP metabolites, and higher nicotinamide adenine dinucleotide (NAD+)/quinolinic acid (QUNA) in patients than in controls (all p

Animal and neuroimaging studies suggest that the volume of the motor-circuit region decreases in tardive dyskinesia (TD). This study examined the differences in functional connectivity within the motor circuit of patients with schizophrenia with and without TD to further clarify how the dysfunction is related to the pathogenesis of TD.Functional magnetic resonance images were taken of 56 schizophrenic patients with TD (TD group), 64 without TD (non-TD group), and 68 healthy controls (HC group). The motor-circuit area was selected as the seed region for a whole brain resting-state functional connectivity (rsFC) analysis. Psychopathological symptoms and TD severity were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Group differences and correlations among 18 brain regions of interest (e.g., the global strength of connectivity between two regions) were analyzed.The analysis of variance results were as follows: The three groups exhibited rsFC losses in the left primary motor cortex, bilateral parietal cortices, right postcentral gyrus, right putamen, right superior parietal lobule, right supplementary motor area and bilateral thalami (false discovery rate,p0.05). The TD group showed a significant rsFC loss between the right postcentral gyrus and the inferior frontal gyrus of the left triangular part when compared with the non-TD group (AlphaSim, p0.001), which was negatively correlated with the AIMS total score (r=-0.259, p = 0.03).These findings may suggest dysfunction of the postcentral and inferior frontal gyri of the triangular part in patients with schizophrenia and TD.

Background Selective loss of dopaminergic neurons and diminished putamen gray matter volume (GMV) represents a central feature of Parkinson’s disease (PD). Recent studies have reported specific effects of kinectin 1 gene (KTN1) variants on the putamen GMV. Objective To examine the relationship of KTN1 variants, KTN1 mRNA expression in the putamen and substantia nigra pars compacta (SNc), putamen GMV, and PD. Methods We examined the associations between PD and a total of 1847 imputed KTN1 single nucleotide polymorphisms (SNPs) in one discovery sample [2,000 subjects with PD vs. 1,986 healthy controls (HC)], and confirmed the nominally significant associations (p < 0.05) in two replication samples (900 PD vs. 867 HC, and 940 PD vs. 801 HC, respectively). The regulatory effects of risk variants on the KTN1 mRNA expression in putamen and SNc and the putamen GMV were tested. We also quantified the expression levels of KTN1 mRNA in the putamen and/or SNc for comparison between PD and HC in five independent cohorts. Results Six replicable and two non-replicable KTN1-PD associations were identified (0.009 ≤ p ≤ 0.049). The major alleles of five SNPs, including rs12880292, rs8017172, rs17253792, rs945270, and rs4144657, significantly increased risk for PD (0.020 ≤ p ≤ 0.049) and putamen GMVs (19.08 ≤ β ≤ 60.38; 2.82 ≤ Z ≤ 15.03; 5.0 × 10–51 ≤ p ≤ 0.018). The risk alleles of five SNPs, including rs8017172, rs17253792, rs945270, rs4144657, and rs1188184 also significantly increased the KTN1 mRNA expression in the putamen or SNc (0.021 ≤ p ≤ 0.046). The KTN1 mRNA was abundant in the putamen and/or SNc across five independent cohorts and differentially expressed in the SNc between PD and HC in one cohort (p = 0.047). Conclusion There was a consistent, significant, replicable, and robust positive relationship among the KTN1 variants, PD risk, KTN1 mRNA expression in putamen, and putamen volumes, and a modest relation between PD risk and KTN1 mRNA expression in SNc, suggesting that KTN1 may play a functional role in the development of PD.

MicroRNA (miR)-181b-5p is considered to be involved in the pathogenesis of schizophrenia, and one of its regulatory target genes BCL-2 (B-cell lymphoma 2) is suggested to associate with cognition of schizophrenia. Cognitive deficit is a core trait of schizophrenia. However, it remains unclear whether miR-181b-5p affects cognition and its possible pathway in schizophrenia. We hypothesized that miR-181b-5p affects cognition by targeting BCL-2 mRNA and downregulating BCL-2 protein expression in schizophrenia patients. In this study, first-episode patients with schizophrenia (FEPS, n = 123) and age- and gender-matched healthy controls (HCs, n = 50) were enrolled in Chinese populations. Expression levels of miR-181b-5p and BCL-2 mRNA in peripheral whole blood were measured with quantitative real-time PCR (Q-PCR) and BCL-2 protein in plasma were measured with Enzyme Linked Immunosorbent Assay (ELISA). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Peripheral blood miR-181b-5p expression level was significantly upregulated (p = 0.001) whereas BCL-2 mRNA and BCL-2 protein levels were significantly downregulated (p = 0.002, p = 0.023 respectively) in the FEPS compared with those in the HCs. The miR-181b-5p level was negatively (p = 0.005), whereas the BCL-2 mRNA level was positively (p < 0.001), correlated with working memory in FEPS. Mediating effect analysis showed that the effect of miR-181b-5p on working memory in the FEPS was exerted via targeting BCL-2 mRNA. MiR-181b-5p in combination with BCL-2 mRNA might be suggested as potential biomarker for schizophrenia in our discovery sample. In conclusion, overexpressed miR-181b-5p may affect cognitive function in patients with schizophrenia.

Objectives: Many studies reported structural brain changes in patients with alcohol dependence (PADs). However, no studies identified structural correlates of apathy that might aggravate alcohol misuse. Here, we explored regional differences in cortical thickness in PADs relative to healthy controls (HCs), and examined the potential correlation of regional thickness with the severity of apathy. Methods: Magnetic resonance imaging data were collected from 33 male PADs and 35 male age- and education-matched HCs. We used the FreeSurfer software to investigate group differences in cortical thickness across 148 regions. Apathy was evaluated using the Lille Apathy Rating Scale-Informant (LARS-I). Regression analyses examined the relationship between cortical thickness of regions of interest and apathy score in PADs. Results: Compared to HCs, PADs significantly decreased in the cortical thickness of occipito-temporal cortex (OTC), including the left middle occipital gyrus and occipital pole, right superior occipital gyri, and bilateral lingual gyrus; bilateral superior parietal cortex (SPC), including the right intraparietal sulcus; and bilateral inferior parietal cortex (IPC). Furthermore, the cortical thickness of all of the three regions was negatively correlated with the apathy total scores. The cortical thickness of the IPC was also negatively correlated with the action initiation subscore of the LARS-I. Conclusions: The current results indicated that the thickness of bilateral parietal and occipital temporal cortices should be neural markers of apathy in PADs, which added to the literature by identifying the neural bases of a critical clinical feature of individuals with alcoholism.

The gray matter volume (GMV) of the putamen has been reported to be regulated by kinectin 1 gene (KTN1). As a hub of the dopaminergic circuit, the putamen is widely implicated in the etiological processes of substance use disorders (SUD). Here, we aimed to identify robust and reliable associations between KTN1 SNPs and SUD across multiple samples. We examined the associations between SUD and KTN1 SNPs in four independent population-based or family-based samples (n = 10,209). The potential regulatory effects of the risk alleles on the putamen GMVs, the effects of alcohol, nicotine, marijuana and cocaine on KTN1 mRNA expression, and the relationship between KTN1 mRNA expression and SUD were explored. We found that a total of 23 SNPs were associated with SUD across at least two independent samples (1.4 × 10-4 ≤ p ≤ 0.049), including one SNP (rs12895072) across three samples (8.8 × 10-3 ≤ p ≤ 0.049). Four other SNPs were significantly or suggestively associated with SUD only in European-Australians (4.8 × 10-4 ≤ p ≤ 0.058). All of the SUD-risk alleles of these 27 SNPs increased (β > 0) the putamen GMVs and represented major alleles (f > 0.5) in Europeans. Twenty-two SNPs were potentially biologically functional. Alcohol, nicotine and cocaine significantly affected the KTN1 mRNA expression, and the KTN1 mRNA was differentially expressed between nicotine or cocaine dependent and control subjects. We concluded that there was a replicable and robust relationship among the KTN1 variants, KTN1 mRNA expression, putamen GMVs, molecular effects of substances, and SUD, suggesting that some risk KTN1 alleles might increase kinectin 1 expression in the putamen, altering putamen structures and functions, and leading to SUD.

Bipolar disorder (BD) is often associated with significant functional impairment. However, there is currently no valid and reliable instrument for this variable that is both brief and easy to administer in China. We thus aimed to evaluate the psychometric properties of the Chinese version of the Functioning Assessment Short Test (FAST) in Chinese adults with BD.In this sample of adult subjects, 176 with BD and 53 healthy controls were included. The Chinese version of the FAST, the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS-17) and the Global Assessment Functioning (GAF) were administered, and the psychometric analysis of the FAST was conducted.The internal consistency (Cronbach's alpha) was 0.89 and 0.88 for the FAST at the baseline and week 1, respectively. Four domains (occupational functioning, cognitive functioning, interpersonal relationship and financial issues) at baseline had high item-total correlations. The FAST assessments at baseline and week 1 were highly correlated, indicating high test-retest reliability. The FAST total score was strongly associated with GAF total scores at week 0 (r = -0.952, p 0.001), HDRS (r = 0.575, p 0.001) and YRMS (r = 0.394, p 0.001) and at week 1 (r = -0.945, p 0.001; r = 0.582, p 0.001; r = 0.363, p 0.001), respectively, suggesting high concurrent validity. The FAST showed four dimensional measurement properties in exploratory factor analysis at baseline.The Chinese version of the FAST has satisfactory psychometric properties in terms of validity and reliability in Chinese adults with BD.

Early alcohol, tobacco and drug use prior to 18 years old are comorbid and correlated. This study included 6239 adults with major depressive disorder (MDD) in the past year and 72,010 controls from the combined data of 2013 and 2014 National Survey on Drug Use and Health (NSDUH). To deal with multicollinearity existing among 17 variables related to early alcohol, tobacco and drug use prior to 18 years old, we used principal component analysis (PCA) to infer PC scores and then use weighted multiple logistic regression analyses to estimate the associations of potential factors and PC scores with MDD. The odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The overall prevalence of MDD was 6.7%. The first four PCs could explain 57% of the total variance. Weighted multiple logistic regression showed that PC 1 (a measure of psychotherapeutic drugs and illicit drugs other than marijuana use), PC 2 (a measure of cocaine and hallucinogens), PC 3 (a measure of early alcohol, cigarettes, and marijuana use), and PC 4 (a measure of cigar, smokeless tobacco use and illicit drugs use) revealed significant associations with MDD (OR = 1.12, 95% CI = 1.08–1.16, OR = 1.08, 95% CI = 1.04–1.12, OR = 1.13, 95% CI = 1.07–1.18, and OR = 1.15, 95% CI = 1.09–1.21, respectively). In conclusion, PCA can be used to reduce the indicators in complex survey data. Early alcohol, tobacco and drug use prior to 18 years old were found to be associated with increased odds of adult MDD.

The human receptor-type protein-tyrosine phosphatase kappa ( PTPRK ) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p −6 ) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p = 4.65 × 10 −2 and 5.18 × 10 −3 , respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p = 1.02 × 10 −2 ) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p = 1.39 × 10 −4 ), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p = 4.1 × 10 −3 ), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p = 3.47 × 10 −3 ), and eight SNPs associated with total cholesterol (top SNP rs1012049 with p = 6.09 × 10 −3 ). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p = 7.3 × 10 −5 ). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.

Attention deficit hyperactivity disorder (ADHD) occurs more frequently and manifests with greater symptom severity in men than in women. Although studies have implicated basal ganglia dysfunction, the functional connectivity (FC) of the dorsal striatum (DS), particularly in terms of sex differences, has not been fully investigated in ADHD. Here, using resting state fMRI data of a large sample of adults (n = 744; 395 women; 22–36 years) curated from the Human Connectome Project, we performed seed-based correlations for caudate and lentiform nucleus (LN) FC. ADHD symptom severity was quantified with the Achenbach Adult Self-Report ADHD total score as well as inattention and hyperactivity subscores. Imaging data were processed with published routines and evaluated at a corrected threshold. Men showed significantly higher ADHD total score than women. In men, inattention was negatively associated with LN FC with the right superior frontal gyrus. In women, inattention was negatively associated with caudate FC with the right inferior parietal gyrus and positively with LN FC with the left inferior frontal gyrus, and hyperactivity was positively associated with LN FC with a cluster in the dorsal anterior cingulate cortex and supplementary motor area. Sex differences in most of these connectivity patterns were confirmed by slope tests. Further, k-means clustering of FC's identified 3 groups each in men and in women. In men, group 1 showed higher inattention and hyperactivity than both group 2 and 3, and group 2 showed higher inattention than group 3. In women, group 1 showed higher inattention and hyperactivity than group 3 and higher inattention than group 2, and group 2 showed higher hyperactivity than group 3. These findings together suggest sex differences in DS FC as neural markers of ADHD and potentially of ADHD subtypes, with men and women each showing altered FC predominantly in the executive control and ventral attention/saliency networks.

Background Major depression disorder (MDD) is often associated with cognitive impairment. The development of an accurate and effective battery to measure cognitive deficit is necessary for both research and clinical practice in MDD. Our study was designed to test the psychometric properties of the MATRICS Consensus Cognitive Battery (MCCB) in patients with MDD. Method Forty-eight patients with MDD, forty-three euthymic patients with bipolar disorder (BD) and thirty-two remitted patients with schizophrenia (SCH) were recruited from Tianjin Anding Hospital in Tianjin, China. The MCCB, the Montreal Cognitive Assessment (MoCA) and the Hamilton Depression Rating Scale-17 (HDRS-17) were administered to assess cognitive impairment and depressive symptoms at both baseline and one month later. Result Our findings showed that the MCCB had good internal consistency and acceptable reliability in Chinese MDD patients. Our findings revealed a high correlation between the MCCB and the MoCA, indicating good concurrent validity of the MCCB. Furthermore, the MCCB showed high discriminant ability between MDD patients and healthy controls, and a principal component analysis of the MCCB in MDD patients revealed four domains with acceptable internal structure. Limitations We did not consider confounding factors, such as the course, severity of symptoms and medication treatments, which might bias the cognitive assessment. In addition, the use of the MoCA as a reference scale for mild cognitive impairment could weaken the concurrent validity of the MCCB in MDD patients. Conclusion Our findings demonstrated that the MCCB may be clinically useful as a cognitive impairment rating battery in Chinese patients with MDD.

Bipolar disorder (BPD) is a common mental illness with significant morbidity and mortality.1 Although evidence have suggested changes in oxidative stress, dopamine and inflammation in BPD, it is hard to define the aetiological mechanism of BPD clearly. Recently, some but not all candidate gene association studies, family-based association studies, linkage studies, genome-wide association studies (GWASs) and meta-analyses showed that mutation of L-type voltage-gated calcium channels (LTCCs) gene CACNA1C is implicated in the mechanism of BPD.2–8 These findings support the possibility that BPD might have calcium channelopathy.9 LTCCs, which consist of a complex of alpha-1, alpha-2/delta and beta subunits in a 1:1:1 ratio, mediate the influx of calcium ions (Ca2+) into the cell on membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. Cav1.2 is crucial in modulating kinetics of the LTCCs.10 Cav1.2 is widely expressed in the heart11 12 and brain.13 So far, it is well known for its function in the heart.11 12 LTCCs are located at both presynaptic nerve terminals and postsynaptic dendrites and dendritic spines. It initiates many physiological responses, including secretion, muscle contraction and gene transcription. LTCCs have prominent roles in learning and memory processes, which might be related with the pathology of BPD.14 LTCCs might control gene expression through …

Background Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy. Methods We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits. Results We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group. Conclusion Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process.

Accumulating evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie neurodegeneration and cognitive impairment in several disorders including schizophrenia. In this study we examined the association of oxidative stress with cognitive deficits in first-episode drug-naive (FEDN) patients with schizophrenia. We recruited 54 FEDN patients and 50 age- and sex-matched healthy controls and examined the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus cognitive Battery (MCCB) and plasma total antioxidant status (TAS). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale. The results showed that plasma TAS levels were significantly lower in the patients than those in the healthy subjects (94.7 ± 25.0 U/ml vs 156.6 ± 46.7 U/ml, p

Accumulating evidence has shown that N-methyl-D-aspartate (NMDA) glutamate receptors (NMDAR) are implicated in the pathophysiology of neurological and psychiatric disorders, and that patients with NMDAR antibody encephalitis develop psychopathological symptoms. Therefore, we hypothesized that NMDAR antibodies play a key role in the etiology of schizophrenia. In this study, we enrolled 110 first-episode patients with schizophrenia (FEP) and 50 healthy controls (HC). Cognitive function and psychopathology were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) and Positive and Negative Syndrome Scale (PANSS), respectively. NMDAR antibody levels were measured using enzyme-linked immunosorbent assay. Our results showed that FEP with schizophrenia exhibited cognitive deficits in all domains of the MCCB and had elevated levels of serum anti-NMDAR antibody compared with the healthy controls (9.2 ± 3.5 vs. 7.3 ± 2.9 ng/ml, t = 3.10, p = 0.002). Furthermore, serum antibody levels were positively correlated with PANSS positive, negative and total score, and inversely correlated with performances of verbal learning and memory, working memory, speed of processing and MCCB total score in the patient group. These results indicate that elevated levels of NMDAR antibody may play a role in the pathogenesis of schizophrenia, leading to NMDAR dysfunction, thereby inducing symptoms of psychosis and cognitive impairment. Therefore, NMDAR antibodies may serve as a biomarker and provide a new avenue for treatment of schizophrenia.

BACKGROUND Accumulating evidence has shown that brain-derived neurotrophic factor (BDNF) may be involved in the pathogenesis of schizophrenia. Moreover, BDNF genetic variants, especially the Val66Met polymorphism, may influence specific aspects of human cognition. This study aimed to investigate the potential association of BDNF gene polymorphisms with susceptibility to schizophrenia and cognitive impairments in patients with schizophrenia in a Han Chinese population. METHODS Four polymorphisms (rs6265, rs12273539, rs10835210, and rs2030324) of the BDNF gene were analyzed in a case-control study of 1,887 Han Chinese individuals (844 patients meeting DSM-IV diagnosis of schizophrenia and 1,043 healthy controls). Cognitive function was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in 598 patients and 434 controls. The current study was conducted from 2008 to 2011. RESULTS Significant differences in the genotype and allele frequencies between patients and controls were observed only for rs10835210 (both P < .05). Further, we found that the rs10835210 polymorphism had a significant effect on language performance only in schizophrenia (P < .05). However, BDNF rs12273539 played a stronger role in cognitive performance among both patients and healthy controls, especially on attention (P < .001) and the RBANS total score (P < .01). CONCLUSIONS These findings suggest the role of these BDNF gene variants in susceptibility to schizophrenia and in some aspects of cognitive function.

Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Many of these lncRNAs have regulatory functions and have recently emerged as major players in governing fundamental biological processes. Here we review the definition, distribution, identification, databases, analysis, classification and functions of lncRNAs. We also discuss the potential roles of lncRNAs in the etiological processes of psychiatric disorders and the implications for clinical diagnosis and treatment.

Prepulse inhibition (PPI) of the auditory startle reflex, as an operational measurement used to evaluate the function of brain sensorimotor gating, appears to be a sensitive potential endophenotype for schizophrenia. CHRNA4 is highly expressed in the central nervous system and has been demonstrated to be significantly associated with schizophrenia by previous studies. The purpose of the current study was to evaluate the effect of CHRNA4 on PPI and acoustic startle parameters in schizophrenia.77 patients with schizophrenia and 62 controls were administered the test PPI, and 3 single nucleotide polymorphisms (SNPs) (rs3746372, rs1044396, and rs3787140) of CHRNA4 were genotyped in these subjects.Patients with schizophrenia showed significantly lower levels of PPI at the 120 ms prepulse intervals and longer peak latency than controls, and the GG genotype of rs3746372 and the TT genotype of rs1044396 were associated with decreased PPI levels in schizophrenia but not in controls.PPI may be influenced by the polymorphisms of the CHRNA4 in schizophrenia and it may be a potential endophenotype of schizophrenia. An independent replication would greatly increase the value of this study.

Major depressive disorder (MDD) is characterized by heterogeneous clinical performance and neurocognitive impairment. It is important to explore the correlation between global functioning and regional homogeneity (ReHo)/amplitude of low-frequency fluctuation (ALFF) values in MDD patients. 67 first-episode, drug naïve MDD patients and 69 healthy subjects were enrolled in the study. The MATRICS Consensus Cognitive Battery (MCCB) and the Functioning Assessment Short Test (FAST) were used to assess functional impairment in patients. Brain activity was assessed using ReHo and ALFF measurements. The relationship between the clinical features and altered brain function was evaluated using correlation analysis. There were significant differences in the ReHo and ALFF values between MDD patients and healthy subjects. The reduction in ReHo in the left calcarine/lingual gyrus/cuneus was negatively correlated with occupational functioning and the total FAST scores. The reduction in ALFF in the right calcarine/lingual gyrus was positively correlated with the verbal learning aspects of the MCCB. These findings suggest that the altered brain function in the default mode network (DMN) may be related to functional impairments in patients with first-episode, drug naïve major depressive disorder.

BackgroundThe prevalence of Alzheimer’s disease (AD) comorbid with depression is common. However, the mechanisms of AD with depression remain unclear.AimsTo investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging (rs-fMRI).Methods154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People’s Hospital from October 2014 to October 2016. According to whether the core symptoms of depression were present, patients were divided into two groups, 22 patients with AD with depression (AD-D) and 52 patients with AD without depression (AD-nD). The amplitude of low frequency fluctuations (ALFF) was compared between two groups by performing independent-samples t-test.ResultsCompared with the AD-D group, increased ALFF values in the bilateral superior frontal gyrus, left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group. The brain activity in the AD-nD group in the bilateral superior frontal gyrus, left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group.ConclusionsResting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms.

Some patients with schizophrenia do not respond to pharmacotherapy. More severe cognitive dysfunctions have been associated with treatment-resistant schizophrenia (TRS). This study examines cognitive functions and hippocampal volumes in 43 patients with TRS and compared them to 43 treatment-responsive patients (NTRS), matched on age, sex and education, as well as 53 healthy controls (HC). The results showed that there were significant deficits in all domains of cognition and hippocampal volumes in TRS as compared to HC group. However, TRS specific deficits, as indicated by comparisons with matched NTRS, were limited to poorer performance in working memory (p = 0.003) and smaller total hippocampal volume (p = 0.01). Logistic regression analysis showed that working memory deficits [OR 0.94 (95% CI 0.89–0.98), p = 0.005] and smaller hippocampal volume [OR 0.89 (95% CI 0.81–0.97), p = 0.01], but not their interactions (p = 0.68), contributed to higher risk of treatment resistance. The findings suggest that treatment-resistance to currently available antipsychotic medications may not be due to global cognitive deficits in these patients, but be associated with specific deficits in working memory and hippocampus deficits in the subgroup of schizophrenia.

Background High-altitude polycythemia (HAPC) is a chronic high-altitude disease that can lead to an increase in the production of red blood cells in the people who live in the plateau, a hypoxia environment, for a long time. The most frequent symptoms of HAPC include headache, dizziness, breathlessness, sleep disorders, and dilation of veins. Although chronic hypoxia is the main cause of HAPC, the fundamental pathophysiologic process and related molecular mechanisms responsible for its development remain largely unclear yet. Aim/methods This study aimed to explore the related hereditary factors of HAPC in the Chinese Han and Tibetan populations. A total of 140 patients (70 Han and 70 Tibetan) with HAPC and 60 healthy control subjects (30 Han and 30 Tibetan) were recruited for a case-control association study. To explore the genetic basis of HAPC, we investigated the association between HAPC and both phosphatidylinositol-4,5-bisphosphonate 3-kinase, catalytic subunit delta gene (PIK3CD) and collagen type IV α3 chain gene (COL4A3) in Chinese Han and Tibetan populations. Results/conclusion Using the unconditional logistic regression analysis and the false discovery rate (FDR) calculation, we found that eight SNPs in PIK3CD and one SNP in COL4A3 were associated with HAPC in the Tibetan population. However, in the Han population, we did not find any significant association. Our study suggested that polymorphisms in the PIK3CD and COL4A3 were correlated with susceptibility to HAPC in the Tibetan population.

Alzheimer’s disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and age at onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 single nucleotide polymorphisms (SNPs) in the HACE1 gene with the risk and the AAO of AD using 791 AD patients and 782 controls. Multiple logistic regression model identified one SNP (rs9499937 with p = 1.8×10−3) to be associated with the risk of AD. For survival analysis of AAO, both classic Cox regression model and Bayesian survival analysis using the Cox proportional hazards model were applied to examine the association of each SNP with the AAO. The hazards ratio (HR) with its 95% confidence interval (CI) was estimated. Survival analysis using the classic Cox regression model showed that 4 SNPs were significantly associated with the AAO (top SNP rs9499937 with HR=1.33, 95%CI=1.13–1.57, p=5.0×10−4). Bayesian Cox regression model showed similar but a slightly stronger associations (top SNP rs9499937 with HR=1.34, 95%CI=1.11–1.55) compared with the classic Cox regression model. Using an independent family-based sample, one SNP rs9486018 was associated with the risk of AD (p=0.0323) and the T-T-G haplotype from rs9786015, rs9486018 and rs4079063 showed associations with both the risk and AAO of AD (p=2.27×10−3 and 0.0487, respectively). The findings of this study provide first evidence that several genetic variants in the HACE1 gene were associated with the risk and AAO of AD.

Migraine without aura (MWO) is the most common among migraine group, and is mainly associated with genetic, physical and chemical factors, and hormonal changes. We aimed to identify novel non-synonymous mutations predisposing to the susceptibility to MWO in a Chinese sample using exome sequencing. Four patients with MWO from a family and four non-migraine subjects unrelated with these patients were genotyped using whole-exome sequencing. Bioinformatics analysis was used to screen possible susceptibility gene mutations, which were then verified by PCR. In four patients with MWO, six novel rare non-synonymous mutations were observed, including EDA2R (G170A), UBE2NL (T266G), GBP2 (A907G), EMR1 (C264G), CLCNKB (A1225G), and ARHGAP28 (C413G). It is worth stressing that GBP2 (A907G) was absent in any control subject. Multiple genes predispose to the susceptibility to MWO. ARHGAP28-, EMR1-, and GBP2-encoded proteins may affect angiokinesis, which supports vasogenic theory for the etiological hypothesis of this disease. CLCNKB-encoded protein may affect cell membrane potential, which is consistent with the cortical spreading depression theory. UBE2NL-encoded protein may regulate cellular responses to 5-hydroxytryptamine, which is in accordance with trigeminovascular reflex theory. EDA2R and UBE2NL are located on the X chromosome, which supports that this disease may have gender differences in genetic predisposition. Replication in larger sample size would significantly strengthen these findings.

BACKGROUND Conventional meta-analysis based on genetic markers may be less powerful for heterogeneous samples. In this study, we introduced a new meta-analysis for 4 genomewide association studies on alcohol dependence that integrated the information of putative causal variants. METHODS A total of 12,481 subjects in 4 independent cohorts were analyzed, including 1 European American cohort (1,409 cases with alcohol dependence and 1,518 controls), 1 European Australian cohort (a total of 6,438 family subjects with 1,645 probands), 1 African American cohort from SAGE + COGA (681 cases and 508 controls), and 1 African American cohort from Yale (1,429 cases and 498 controls). The genomewide association analysis was conducted for each cohort, and then, a new meta-analysis was performed to derive the combined p-values. cis-Acting expression of quantitative locus (cis-eQTL) analysis of each risk variant in human tissues and RNA expression analysis of each risk gene in rat brain served as functional validation. RESULTS In meta-analysis of European American and European Australian cohorts, we found 10 top-ranked single nucleotide polymorphisms (SNPs) (p < 10(-6) ) that were associated with alcohol dependence. They included 6 at SERINC2 (3.1 × 10(-8) ≤ p ≤ 9.6 × 10(-8) ), 1 at STK40 (p = 1.3 × 10(-7) ), 2 at KIAA0040 (3.3 × 10(-7) ≤ p ≤ 5.2 × 10(-7) ), and 1 at IPO11 (p = 6.9 × 10(-7) ). In meta-analysis of 2 African American cohorts, we found 2 top-ranked SNPs including 1 at SLC6A11 (p = 2.7 × 10(-7) ) and 1 at CBLN2 (p = 7.4 × 10(-7) ). In meta-analysis of all 4 cohorts, we found 2 top-ranked SNPs in PTP4A1-PHF3 locus (6.0 × 10(-7) ≤ p ≤ 7.2 × 10(-7) ). In an African American cohort only, we found 1 top-ranked SNP at PLD1 (p = 8.3 × 10(-7) ; OR = 1.56). Many risk SNPs had positive cis-eQTL signals, and all these risk genes except KIAA0040 were found to express in both rat and mouse brains. CONCLUSIONS We found multiple genes that were significantly or suggestively associated with alcohol dependence. They are among the most appropriate for follow-up as contributors to risk for alcohol dependence.

Previous studies have shown that the functional 511C/T polymorphism in the IL-1beta-gene may be implicated in the susceptibility for schizophrenia. Moreover, recent studies suggested that IL-1 participates in the progression of lung disease in smokers, which are overrepresented in schizophrenia. We aimed to investigate the possible relationship between the IL-1beta-511C/T polymorphism and smoking behavior in schizophrenia versus healthy controls in a Chinese population. The IL-1beta-511C/T polymorphism was genotyped in 638 male patients with chronic schizophrenia (smoker/never-smoker = 486/152) and 469 male controls (smoker/never-smoker = 243/226). The cigarettes smoked per day, the Heaviness of Smoking Index (HSI) and the Fagerstrom Test for nicotine dependence (FTND) were assessed. Patients were also rated on the Positive and Negative Syndrome Scale (PANSS). The results showed no significant differences in genotype and allele distribution between patients and controls, and between smokers and never-smokers in either the patient or control group. However, in patients, smokers with the C/C genotype had significantly higher HSI (p

Some recent studies show an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to nicotine dependence and we hypothesized that this polymorphism was associated with smoking in both schizophrenia patients and healthy controls. The BDNF Val66Met gene polymorphism was genotyped in 690 chronic male schizophrenia patients (smoker/nonsmoker = 522/169) and 628 male controls (smoker/nonsmoker = 322/306) using a case-control design. Nicotine dependence (ND) was assessed by the cigarettes smoked per day (CPD), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). Patients also were rated on the Positive and Negative Syndrome Scale (PANSS). The results showed no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. In patient groups, however, the smokers with the Met allele had significantly higher HSI scores (Met/Met: 2.8 ± 1.7 vs. Met/Val: 2.2 ± 1.7 vs. Val/Val: 2.0 ± 1.6, p < 0.01) and a trend toward a significantly higher FTND score (p = 0.09) than those with the Val/Val genotype. In addition, the smokers showed significantly lower PANSS negative symptom and total scores, longer duration of illness and more hospitalizations (all p < 0.05). In the control group, the smokers with the Met allele started smoking significantly earlier than those with the Val/Val genotype (both p < 0.05). These results suggest that the BDNF Val66Met polymorphism may affect a smoker's response to nicotine in both schizophrenia and healthy controls from a Chinese Han population, but with differential effects in different aspects of smoking behaviors.

There is little understanding of how unipolar major depressive disorder (UMDD) symptoms evolve in response to antidepressant treatment. The present research examined the associations between symptom trajectories and clinical remission in Chinese patients with UMDD. A total of 165 outpatients with UMDD received treatment of fluoxetine (20 mg/day) for 6 weeks and were assessed for symptom severity at weeks 1, 2, 4, and 6. We found that patients with UMDD show heterogeneity in treatment response to fluoxetine. Psychomotor retardation is a prominent symptom during the 6 weeks of assessment, and its severity at baseline is negatively associated with clinical remission. © 2016 John Wiley & Sons Australia, Ltd