Association between increased serum interleukin-8 levels and improved cognition in major depressive patients with SSRIs.

BACKGROUND: The effect of neuroinflammatory cytokines on cognitive deficits in patients with major depressive disorder (MDD) can be altered by selective serotonin reuptake inhibitors (SSRIs). This study aimed to examine serum interleukin-8 (IL-8) levels, cognitive function, and their associations in MDD patients with SSRIs. METHODS: Thirty SSRI-treated MDD patients and 101 healthy controls were recruited for this study. We examined cognitive performance using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum IL-8 levels using the Human Inflammatory Cytokine Cytometric Bead Array in both cases and controls. RESULTS: The RBANS test scores were significantly lower in MDD patients with SSRIs than in healthy controls after controlling for covariates (all p < 0.001). Serum levels of IL-8 were higher in MDD patients with SSRIs than in healthy controls after adjusting for covariates (F = 3.82, p = 0.05). Serum IL-8 levels were positively correlated with sub-scores of delayed memory (r = 0.37, p = 0.04) and visuospatial/constructional (r = 0.43, p = 0.02) in MDD patients with SSRIs but not in in healthy controls (delayed memory score: r = -0.12, p = 0.24; visuospatial/constructional score: r = 0.02, p = 0.81). CONCLUSIONS: Our findings suggested that increased serum IL-8 level might not only be involved in the MDD psychopathology or the use of SSRIs but also correspond to improving MDD delayed memory and visuospatial/constructional function.

The type 2 diabetes mellitus susceptibility gene CDKAL1 polymorphism is associated with depressive symptom in first-episode drug-naive schizophrenic patients.

BACKGROUND: Patients with schizophrenia have an increased prevalence of type 2 diabetes mellitus that has shown a significant association with the rs7754840 polymorphism in the gene encoding the cyclin-dependent kinase 5 (CDK5) regulatory subunit-associated protein 1-like 1 (CDKAL1). OBJECTIVE: To examine whether this polymorphism was involved in the susceptibility in first-episode drug-naive schizophrenic patients (FDSP), and further influenced their clinical symptoms. METHODS: This polymorphism was genotyped in 239 FDSP and 368 healthy controls. The clinical symptoms in FDSP were assessed using the Positive and Negative Syndrome Scale (PANSS) five-factor models. RESULTS: There was no significant difference in the allelic and genotypic frequencies of this polymorphism between two groups (both p > 0.05) after adjusting for covariates. However, the PANSS depressive score significantly differed by genotype in FDSP after adjusting for covariates (F = 5.25, p = 0.006). This significant difference also persisted after Bonferroni correction (p < 0.05). FDSP with C/C genotype had significantly higher PANSS depressive score than those with C/G genotype (p = 0.007) and those with G/G genotype (p = 0.005). Moreover, further stepwise multivariate regression analysis showed the significant association between the rs7754840 polymorphism and PANSS depressive score in FDSP (ß = -1.07, t = -2.75, p = 0.007). CONCLUSIONS: Our findings demonstrated that although the CDKAL1 rs7754840 polymorphism did not contribute to the susceptibility to FDSP, it might be implicated in depressive symptoms in this patient group.

Association between dopamine beta-hydroxylase polymorphism and attention function in suicide attempters with chronic schizophrenia.

BACKGROUND: Patients with schizophrenia are at a higher risk for suicide compared with the general population. Dopamine beta-hydroxylase (DßH) plays a key role in the conversion of dopamine to norepinephrine, which is related to suicidal behavior and cognitive regulation. OBJECTIVE: To examine whether there is the effect of DßH 5'-insertion/deletion (Ins/Del) polymorphism on cognitive performance in suicide attempters with chronic schizophrenia. METHODS: This polymorphism was detected in 114 suicide attempters and 617 non-suicide attempters with chronic schizophrenia. Cognitive performance was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The allelic and genotypic frequencies of this polymorphism between two groups did not differ after controlling for covariates (both, p > .05). There were no differences in RBANS scores between two groups after adjusting for covariates (all, p > .05). However, based on the genotype grouping in suicide attempters and non-attempters, the attention score significantly differed after adjusting for covariates (both, p < .05). Further analysis indicated that this polymorphism was associated with attention score in suicide attempters (p < .05), but not in non-suicide attempters (p > .05). CONCLUSIONS: DßH 5'-Ins/Del polymorphism was not a risk locus of suicide attempters, but it was implicated in attention regulation in suicide attempters with chronic schizophrenia.

Cognitive Impairments in First-Episode Drug-Naïve Versus Medicated Depressive Patients: RBANS in a Chinese Population.

Cognitive deficits are a core feature of major depressive disorder (MDD). However, there are no previous studies that directly compare cognitive performance between first-episode drug-naive depressive patients (FDDP) and medicated depressive patients (MDP). Therefore, the aim of this study was to investigate whether there were the differences in cognitive functions between FDDP and MDP. Sixty-two FDDP, 111 MDP and 90 healthy controls were enrolled in a Chinese population. Cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were the differences in the RBANS total score (F = 26.55, p < 0.001), subscales of immediate memory (F = 3.95, p = 0.02), language (F = 54.11, p < 0.001) and delayed memory (F = 11.19, p = 0.001) among the three groups after controlling for gender, education, smoking and body mass index (BMI). These differences in the RBANS total score, subscales of language and delayed memory passed the Bonferroni corrections (all, p < 0.05). Compared to healthy controls, FDDP and MDP had poorer cognitive performance including the RBANS total score, and subscales of language and delayed memory (all, p < 0.05) after controlling for the variables. FDDP experienced greater language deficits than MDP (p < 0.05) after controlling for the variables. Education was correlated with the language score in FDDP (r = 0.61, p < 0.001). Multivariate regression analysis indicated that education was an independent contributor to the language score in FDDP (ß = 3.11, t = 5.48, p < 0.001). Our findings indicated that FDDP had poorer language performance than MDP. Moreover, education could influence the language performance in FDDP.

Brain-derived neurotrophic factor, sex hormones and cognitive decline in male patients with schizophrenia receiving continuous antipsychotic therapy.

BACKGROUND: There are systematic differences in clinical features between women and men with schizophrenia (SCZ). The regulation of sex hormones may play a potential role in abnormal neurodevelopment in SCZ. Brain-derived neurotrophic factor (BDNF) and sex hormones have complex interacting actions that contribute to the etiology of SCZ. AIM: To investigate the influence of BDNF and sex hormones on cognition and clinical symptomatology in chronic antipsychotic-treated male SCZ patients. METHODS: The serum levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E2), progesterone, testosterone (T), prolactin (PRL) and BDNF were compared between chronic antipsychotic-treated male (CATM) patients with SCZ (n = 120) and healthy controls (n = 120). The Positive and Negative Syndrome Scale was used to quantify SCZ symptoms, while neuropsychological tests were used to assess cognition. Neuropsychological tests, such as the Digit Cancellation Test (DCT), Semantic Verbal Fluency (SVF), Spatial Span Test (SS), Paced Auditory Serial Addition Test (PASAT), Trail Making Task (TMT-A), and Block Design Test (BDT), were used to assess executive functions (BDT), attention (DCT, TMT-A), memory (SS, PASAT), and verbal proficiency (SVF). RESULTS: Although E2 levels were significantly lower in the patient group compared to the healthy controls, T, PRL, and LH levels were all significantly higher. Additionally, the analysis revealed that across the entire sample, there were positive correlations between E2 Levels and BDNF levels as well as BDNF levels and the digital cancellation time. In CATM patients with SCZ, a significant correlation between the negative symptoms score and PRL levels was observed. CONCLUSION: Sex hormones and BDNF levels may also be linked to cognitive function in patients with chronic SCZ.

Associations of decreased serum total protein, albumin, and globulin with depressive severity of schizophrenia.

Objective: Depression and schizophrenia (SCH) were accompanied by an acute phase response (APR) that was implicated in the alterations in total protein (TP), albumin, and globulin levels. The aims of this study are to examine serum TP, albumin, globulin levels, depressive symptoms, and their associations in patients with SCH. Methods: We recruited 34 patients with SCH and 136 healthy controls (HCs) according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Psychiatric symptoms and biomarkers were assessed using the Chinese version of the Positive and Negative Syndrome Scale (PANSS) as well as the bromocresol green and biuret methods. Results: Serum TP (F = 46.11, p < 0.001, η2 = 0.19), albumin (F = 31.69, p < 0.001, η2 = 0.14), and globulin (F = 12.48, p < 0.001, η2 = 0.06) levels were lower in patients than those in HCs after adjusting for covariates. Serum TP (r = -0.37, p = 0.03) and albumin (r = -0.37, p = 0.03) levels were negatively correlated with depressive score in patients. Stepwise multivariate regression analysis showed the negative associations of depressive score with serum TP (ß = -0.13, t = -2.92, p = 0.007), albumin (ß = -0.23, t = -2.36, p = 0.03), and globulin (ß = -0.16, t = -2.40, p = 0.02) levels in patients. Serum TP, albumin, and globulin levels exhibited the accuracies of 87.1, 70.0, and 69.4% in discriminating between patients and HCs (area under the curve [AUC]: 0.78, 0.68, and 0.77; sensitivity/specificity: 52.9%/95.6%, 55.9%/73.5%, and 76.5%/67.6%). Conclusion: Our data suggested that decreased serum TP, albumin, and globulin should be regarded as the SCH risk factors and were implicated in the depressive severity of SCH, which further provided the support for the hypothesis that SCH and depression were accompanied by the abnormal inflammatory cytokines with the APR.

Morinda officinalis oligosaccharides mitigate chronic mild stress-induced inflammation and depression-like behaviour by deactivating the MyD88/PI3K pathway via E2F2.

Morinda officinalis oligosaccharides (MOs) are natural herbal extracts that have been shown to exert antidepressant effects. However, the mechanism of this effect remains unclear. Here, we explored the mechanism by which MOs improved experimental depression. Using a chronic mild stress (CMS) murine model, we examined whether MOs could protect against depressive-like behaviour. Lipopolysaccharide (LPS)- and ATP-treated BV2 cells were used to examine the potential mechanism by which MOs mediate the inflammatory response. We found that MOs prevented the CMS-induced reduction in the sucrose preference ratio in the sucrose preference test (SPT) and shortened the immobility durations in both the tail suspension test (TST) and forced swim test (FST). We also noticed that MOs suppressed inflammatory effects by deactivating the MyD88/PI3K pathway via E2F2 in CMS mice or LPS- and ATP-stimulated BV2 cells. Furthermore, overexpression of E2F2 blunted the beneficial effects of MOs in vitro. Collectively, these data showed that MOs exerted antidepressant effects in CMS mice by targeting E2F2-mediated MyD88/PI3K signalling pathway.

Comparisons of Serum Interleukin-8 Levels in Major Depressive Patients With Drug-Free Versus SSRIs Versus Healthy Controls.

Objective: The interleukin-8 (IL-8) has been reported to play an important role in depression, which might be modulated by the selective serotonin reuptake inhibitors (SSRIs). Thus, the aim of this study was to investigate serum IL-8 levels, depressive symptom, and their associations in drug-free MDD patients, MDD patients with SSRIs, and healthy controls (HCs). Methods: Fifty-seven drug-free MDD patients (male/female = 35/22, mean age: 39.24 years), 30 MDD patients with SSRIs (male/female = 11/19, mean age: 39.73 years), and 101 HCs (male/female = 52/49, mean age: 37.38 years) were recruited in this cross-sectional study. Serum IL-8 levels and depressive symptom were assessed using the Flow Cytometer and Hamilton Depression Scale (HAMD). The analysis of variance was used for the comparison between groups. The relationship between serum log10 IL-8 levels and HAMD score was analyzed by Pearson correlation. Results: Serum log10IL-8 levels were lower in all patients than HCs after controlling for covariates (F = 4.86, p = 0.03). There was significant difference in serum Log10IL-8 levels among three groups after controlling for covariates (F = 14.63, p < 0.001). Serum Log10IL-8 levels in drug-free patients were lower compared to HCs (F = 19.38, p < 0.001) or patients with SSRIs (F = 21.89, p < 0.001) after controlling for covariates. However, there was not difference in serum log10IL-8 levels between patients with SSRIs and HCs after controlling for covariates. Moreover, serum Log10IL-8 levels were negatively correlated with HAMD score in all patients (r = -0.37, p = 0.02). Also, serum Log10IL-8 levels were negatively correlated with HAMD score in drug-free patients (r = -0.74, p = 0.01), but not in patients with SSRIs. Conclusion: Our data supported that the decline in serum IL-8 levels was association with depression. Moreover, the SSRIs might modulate increased serum IL-8 levels of depression.

Sleep disorder as a clinical risk factor of major depression: associated with cognitive impairment.

BACKGROUND: This research aims explored the sleep disorder (SD) role in major depressive disorder (MDD), and the SD influencing their cognition. METHODS: 372 MDD patients and 457 healthy controls (HCs) were enrolled. RESULTS: Patients increased a 38.88 times SD risk compared with HCs. In patients, visuospatial/constructional score was lower in SD than non-SD, and PSQI score was negatively associated with visuospatial/constructional score of SD. In SD and non-SD, RBANS scores were lower in MDD than HCs, excepted for visuospatial/constructional in non-SD. CONCLUSION: The SD as a MDD risk factor, has more serious visuospatial/constructional impairment alleviated via improving sleep/depression in patients.

Associations among gonadal hormone, triglycerides and cognitive decline in female patients with major depressive disorders.

BACKGROUND: Cognitive impairment has been identified as a core feature of depression. Serum triglycerides (TG), gonadal hormone and sex difference were shown to influence cognitive performance. The purpose of this study was to investigate the associations among serum TG, gonadal hormone, sex difference and cognitive performance in patients with major depressive disorders (MDD). METHODS: The enrolled 183 patients (male/female = 80/103) meeting DSM-IV criteria for MDD were divided into high TG group (patients-HTG) and normal TG group (patients-NTG) according to TG level. Serum TG, estradiol (E2) and testosterone (T) levels were measured by the glycerokinase peroxidase-peroxidase and chemiluminescence methods. Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The study was conducted between August 2016 and January 2020. RESULTS: In female, patients-HTG had lower immediate memory, language, attention, delayed memory and RBANS total scores than patients-NTG after adjusting for covariates. There were significant differences in serum E2 and T levels between patients-HTG and patients-NTG in female after controlling for covariates. In female patients-HTG, serum E2 level was positively associated with immediate memory, delayed memory and RBANS total scores, and serum T level was positively related to immediate memory, language and RBANS total scores. These findings were not seen in male patients. CONCLUSIONS: Our data suggested that patients-HTG exhibited poorer cognitive function compared with patients-NTG in female. Moreover, the decline in serum gonadal hormone level might contribute to the high TG development of female MDD, and was further implicated in their cognitive decline.

Association between stereopsis deficits and attention decline in patients with major depressive disorder.

Cognitive and sensory deficits were considered a core feature of major depressive disorder (MDD). However, few studies investigated stereopsis integrity in patients with MDD. Thus, the objectives of this study investigated stereopsis integrity and its correlations with cognitive function and depressive symptom in patients with MDD. 90 patients with MDD and 116 healthy controls (HCs) were enrolled in this study. Their stereoacuity was evaluated using the Titmus Stereopsis Test as well as assessing their cognitive function and depressive symptom by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Hamilton Depression Scale (HAMD). Log seconds of arc was significantly higher in patients than HCs (1.92 ± 0.41 versus 1.67 ± 0.16, t = 5.35, p < 0.0001). The percentage of patients with correct stereopsis detection was markedly declined in 400 (z = 3.06, p = 0.002), 200 (z = 3.84, p < 0.001), 140 (z = 4.73, p < 0.001), 100 (z = 4.58, p < 0.001), 80 (z = 5.06, p < 0.001), 60 (z = 4.72, p < 0.001), 50 (z = 4.24, p < 0.001), and 40 (z = 4.85, p < 0.001) seconds of arc compared with HCs. Log seconds of arc was significantly correlated with the RBANS total score (r = -0.38, p < 0.0001), subscores of attention (r = -0.49, p < 0.0001) and language (r = -0.33, p = 0.001) rather than HAMD score (r = 0.03, p = 0.78) in MDD patients. In addition, log seconds of arc was significantly related to the RBANS total score (r = -0.58, p < 0.0001) and language score (r = -0.45, p = 0.006) rather than attention score (r = -0.30, p = 0.07) in HCs. Further stepwise multivariate regression analyses showed the negative correlation of log seconds of arc with attention score (ß = -0.80, t = -3.95, p < 0.0001) rather than HAMD score (ß = -0.008, t = -0.09, p = 0.93) in MDD patients. However, there was no relationship between log seconds of arc and attention score in HCs (ß = 1.52, t = 1.19, p = 0.24). Our results identified the marked deficits of stereopsis in MDD patients that were tightly correlated with their attention functioning rather than depressive symptom.

Independent replications and integrative analyses confirm TRANK1 as a susceptibility gene for bipolar disorder.

Genetic analyses for bipolar disorder (BD) have achieved prominent success in Europeans in recent years, whereas its genetic basis in other populations remains relatively less understood. We herein report that the leading risk locus for BD in European genome-wide association studies (GWAS), the single-nucleotide polymorphism (SNP) rs9834970 near TRANK1 at 3p22 region, is also genome-wide significantly associated with BD in a meta-analysis of four independent East Asian samples including 5748 cases and 65,361 controls (p = 2.27 × 10-8, odds ratio = 1.136). Expression quantitative trait loci (eQTL) analyses and summary data-based Mendelian randomization (SMR) analyses in multiple human brain samples suggest that lower TRANK1 mRNA expression is a principal BD risk factor explaining its genetic risk signals at 3p22. We also identified another SNP rs4789 in the 3' untranslated region (3'UTR) of TRANK1 showing stronger eQTL associations as well as genome-wide significant association with BD. Despite the relatively unclear neuronal function of TRANK1, our mRNA expression analyses in the human brains and in rat primary cortical neurons reveal that genes highly correlated with TRANK1 are significantly enriched in the biological processes related to dendritic spine, synaptic plasticity, axon guidance and circadian entrainment, and are also more likely to exhibit strong associations in psychiatric GWAS (e.g., the CACNA1C gene). Overall, our results support that TRANK1 is a potential BD risk gene. Further studies elucidating its roles in this illness are needed.

Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Elevated activity of plasma superoxide dismutase in never-treated first-episode schizophrenia patients: Associated with depressive symptoms.

Oxidative stress in excess may be engaged in the pathophysiological development of schizophrenia (SCZ). Previous research showed altered activity of superoxide dismutase (SOD) in patients suffering from SCZ, with inconsistent results. However, few studies have analyzed the relationship between SOD activity and psychopathological symptoms in never-treated first-episode (NTFE) patients with SCZ. The activities of manganese SOD (MnSOD) and total SOD were measured in a large sample of 166 NTFE patients with SCZ, and 133 healthy controls. The patients' symptoms were evaluated by the Positive and Negative Syndrome Scale (PANSS), as well as the depressive and cognitive factors originated from the PANSS five-factor model. NTFE patients had significantly higher activities of MnSOD and total SOD than healthy controls (both p < 0.01). Correlation analysis displayed a notably positive correlation between both MnSOD or total SOD activities and the PANSS depressive factor, as well as between MnSOD activity and the PANSS general psychopathology subscale score (all p < 0.05). Stepwise multiple regression analysis revealed that both MnSOD and total SOD were independent factors affecting PANSS depressive factor and PANSS general psychopathology subscale score. Our findings suggest that increased SOD activity may be associated with comorbid depressive symptoms in NTFE patients with SCZ.

The role of lipoprotein profile in depression and cognitive performance: a network analysis.

Lipid profile (total cholesterol and lipoprotein fractions) has been found to correlate with depression and cognitive impairment across the lifespan. However, the role of lipid levels in self-rated depressive state and cognitive impairment remains unclear. In this study, we examined the relationship between lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) and cognition in adults with and without self-rated depression. Four hundred and thirty-eight healthy participants completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Self-Rating Depression Scale (SDS), and a serum lipoprotein test. Using multivariate ANOVA, partial correlation and network analysis, a network linking lipoprotein profile, depressive state and cognition was constructed. A significant difference in serum lipid profile between the high and low depressive groups was detected. Depressive state had a strong negative correlation with cognitive performance. Of the lipid profile, only high-density lipoprotein was positively correlated with depressive symptom severity, whereas the other three indices showed negative correlation with both depressive state and cognitive performance. Our results suggest that serum lipid profile may be directly linked to self-rated depression and cognitive performance. Further studies recruiting larger clinical samples are needed to elucidate the specific effect of lipoprotein on cognitive impairment in mood disorder.

Further confirmation of netrin 1 receptor (DCC) as a depression risk gene via integrations of multi-omics data.

Genome-wide association studies (GWAS) of major depression and its relevant biological phenotypes have been extensively conducted in large samples, and transcriptome-wide analyses in the tissues of brain regions relevant to pathogenesis of depression, e.g., dorsolateral prefrontal cortex (DLPFC), have also been widely performed recently. Integrating these multi-omics data will enable unveiling of depression risk genes and even underlying pathological mechanisms. Here, we employ summary data-based Mendelian randomization (SMR) and integrative risk gene selector (iRIGS) approaches to integrate multi-omics data from GWAS, DLPFC expression quantitative trait loci (eQTL) analyses and enhancer-promoter physical link studies to prioritize high-confidence risk genes for depression, followed by independent replications across distinct populations. These integrative analyses identify multiple high-confidence depression risk genes, and numerous lines of evidence supporting pivotal roles of the netrin 1 receptor (DCC) gene in this illness across different populations. Our subsequent explorative analyses further suggest that DCC significantly predicts neuroticism, well-being spectrum, cognitive function and putamen structure in general populations. Gene expression correlation and pathway analyses in DLPFC further show that DCC potentially participates in the biological processes and pathways underlying synaptic plasticity, axon guidance, circadian entrainment, as well as learning and long-term potentiation. These results are in agreement with the recent findings of this gene in neurodevelopment and psychiatric disorders, and we thus further confirm that DCC is an important susceptibility gene for depression, and might be a potential target for new antidepressants.

Prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff.

BACKGROUND: The high prevalence of depression in general population was related to its social-demographics and cognitive performance. However, no studies investigated the prevalence of depression, its social-demographic and cognitive correlates in psychiatric medical staff. Thus, the aims of this study investigated the prevalence, social-demographic and cognitive correlates of depression in Chinese psychiatric medical staff. METHODS: 186 Chinese psychiatric medical staff were enrolled in Wenzhou Kangning Hospital. Depressive symptom score was assessed by the Self-rating Depression Scale (SDS). Cognition was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: The prevalence of depression was 17.74% in these medical staff. The RBANS total score in participants with depressive symptom was significantly lower than that in participants with not depressive symptom after controlling for the confounding variables. The Person correlation analysis found that the normal SDS score in these medical staff was significantly related to age, education, occupations, RBANS total score and subscale scores. Stepwise multivariate regression analysis further identified that age and RBANS total score were significantly associated with the normal SDS score in these medical staff. LIMITATIONS: The limitations included cross-sectional study design, the small sample size, and the self-rating scale of depression. CONCLUSIONS: The prevalence of depression in Chinese psychiatric medical staff was higher in comparison with Chinese general population, but lower in comparison with Chinese medical staff. Cognitive deficits might be considered a core feather of depression that should be a valuable target for future interventions. Age influenced depressive symptom in these medical staff .

Association between decreased serum TBIL concentration and immediate memory impairment in schizophrenia patients.

Cognitive impairment is a core feature of schizophrenia (SCH). In addition to the toxic effect of Bilirubin (BIL), it has antioxidant properties that were associated with the psychopathology and cognitive impairment of psychiatric disorders. The aim of this study was to examine the correlation of serum total BIL (TBIL) concentration with cognitive impairment in SCH patients. We recruited 34 SCH patients and 119 healthy controls (HCs) in this case-control design. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Serum TBIL concentration was measured using the immunoturbidimetric method. Serum TBIL concentration was significantly decreased in SCH patients compared to HCs after adjusting for age, gender, and education. Serum TBIL concentration in SCH patients was also positively correlated with the RBANS immediate memory score. Further stepwise multiple regression analysis confirmed the positive association between serum TBIL concentration and immediate memory score in SCH patients. Our findings supported that the decline in serum TBIL concentration was associated with the immediate memory impairment and psychopathology of SCH.

Sex Differences in the Prevalence and Clinical Features of Comorbid Depressive Symptoms in Never-Treated Chinese Patients With First-Episode Schizophrenia.

BACKGROUND: Many studies have indicated a sex-specific effect in many aspects of schizophrenia. The presence of depressive symptomatology exists in all phases of schizophrenia. The aim of this study is to investigate the sex differences in the proportion of comorbid depressive symptoms and sex-specific relationships between depressive symptoms and clinical correlates in never-treated Chinese patients with first-episode schizophrenia (NTFE patients), which have not been reported yet. METHODS: Via a cross-sectional design, 240 NTFE inpatients (male/female = 111/129) between ages 16 and 45 years and meeting DSM-IV-TR criteria of schizophrenia were recruited. The Positive and Negative Syndrome Scale (PANSS) was used for the psychopathology, and the 17-item Hamilton Depression Rating Scale (HDRS-17) for the comorbid depressive symptoms. This study was conducted from June 2013 to December 2015. RESULTS: The proportion of patients with depressive symptoms (total score on HDRS-17 ≥ 8) in men was significantly higher than in women (male: 62.2%, female: 48.1%; χ²1 = 4.28, P = .039). Male patients had significantly greater depressive symptoms as shown on the HDRS-17 than female patients (t1, 238 = 2.75, P = .006). Further, we found that age, the age at onset, smoking rate, and PANSS total and general psychopathology, negative symptoms, and cognitive factor subscores favored significant sex differences in female patients (all P < .05). Interestingly, we found sex differences in the correlation between the HDRS-17 score and clinical phenotype, showing that in male patients, the PANSS general psychopathology subscore (ß = 0.75, t = 7.72, P < .001) and total score (ß = 0.44, t = 4.81, P < .001) significantly predicted the HDRS-17 total score, while in female patients, the PANSS general psychopathology subscore (ß = 0.74, t = 8.45, P < .001), total score (ß = 0.47, t = 5.71, P < .001), and cognitive factor subscore (ß = 0.24, t = 2.60, P < .001) significantly predicted the HDRS-17 total score. CONCLUSIONS: Our results indicate sex differences in the frequency and severity of comorbid depressive symptoms and in associations between depressive symptoms and clinical correlates in NTFE patients.

Association between decreased HDL levels and cognitive deficits in patients with bipolar disorder: a pilot study.

BACKGROUND: Cognitive deficits are common in patients with bipolar disorder (BD). Abnormal high density lipoprotein (HDL) levels have been implicated in cognitive deficits associated with ageing and neurodegenerative disorders. The present study aimed to investigate serum HDL levels, cognitive deficits and their association in patients with BD. METHODS: Thirty-seven patients with BD and 37 gender- and age-matched healthy controls (HCs) were recruited in a case-control study. Cognition was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and serum HDL levels were measured using enzymatic colourimetry. RESULTS: There was no difference in serum HDL levels between patients with BD and HCs after adjusting for gender, age, education and body mass index (BMI). Cognitive test scores in patients with BD were significantly lower than those in HCs except for the visuospatial/constructional index after adjusting for confounding variables. Serum HDL levels were positively correlated with RBANS total score and language score in patients with BD. Stepwise multiple regression analysis showed that serum HDL levels were significantly correlated with RBANS total score and subscale scores on immediate memory and language in patients with BD after adjusting for confounding factors. CONCLUSIONS: Our findings suggest that patients with BD had poorer cognitive performance than HCs except for the visuospatial/constructional domain, and decreased serum HDL levels were correlated with cognitive deficits, especially in immediate memory and language domains in patients with BD.