Study on the correlation between suicidal ideation and ABI3BP gene、DPYSL2 gene methylation in pediatric bipolar disorder with depressive episode.

Patients with bipolar disorder have a higher risk of suicide than the general population. This study aimed to explore the correlation between suicide and gene methylation, as screened by genome-wide scanning, in children and adolescents with bipolar disorder. A total of 45 children and adolescents with bipolar disorder were divided into a suicidal ideation group (n = 41), a non-suicidal ideation group (n = 4), a low-risk group (n = 12), and a middle-to-high-risk group (n = 33). A pre-experiment was conducted on the suicidal ideation (n = 6) and non-suicidal ideation groups (n = 4). Blood samples were scanned using an Illumina HD 850K microarray, and methylation levels were analysed. Differential methylation sites among the sample groups were screened from the original data, and genes related to suicide were identified. Methylation of the ABI3BP and DPYSL2 genes was detected by pyrophosphate sequencing and statistically analysed. There was a significant difference in age between the low- and middle-risk groups. The results of GO analysis for the suicidal ideation and non-suicidal ideation groups showed that the differential methylation sites were mainly involved in the interferon-γ-mediated signalling pathway, with the main signalling pathways being the inflammatory bowel disease (IBD) pathway and type 1 diabetes mellitus (T1DM) pathway. There were significant differences in the methylation of ABI3BP, HLA-DQB1, HLA-DRB1, AUTS2, SP3, NINJ2, DPYSL2, and other genes between the suicidal and non-suicidal ideation groups. There was also a statistically significant difference in the gene methylation levels between the two groups. However, there was no significant difference in the degree of methylation of the ABI3BP and DPYSL2 genes between the low- and middle-to-high-risk groups. These results suggest that suicidal ideation is correlated with the methylation levels of differentially methylated genes in children with bipolar disorder. However, the severity of suicide risk in paediatric patients with bipolar disorder may not be correlated with the degree of methylation of the ABI3BP and DPYSL2 genes. Therefore, further validation was required.

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.

BACKGROUND: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD). METHODS: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated. RESULTS: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%). LIMITATIONS: A short-term non-inferiority study without a placebo arm. CONCLUSIONS: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

Exploring neurometabolic alterations in bipolar disorder with suicidal ideation based on proton magnetic resonance spectroscopy and machine learning technology.

Bipolar disorder (BD) is associated with a high risk of suicide. We used proton magnetic resonance spectroscopy (1H-MRS) to detect biochemical metabolite ratios in the bilateral prefrontal white matter (PWM) and hippocampus in 32 BD patients with suicidal ideation (SI) and 18 BD patients without SI, identified potential brain biochemical differences and used abnormal metabolite ratios to predict the severity of suicide risk based on the support vector machine (SVM) algorithm. Furthermore, we analyzed the correlations between biochemical metabolites and clinical variables in BD patients with SI. There were three main findings: (1) the highest classification accuracy of 88% and an area under the curve of 0.9 were achieved in distinguishing BD patients with and without SI, with N-acetyl aspartate (NAA)/creatine (Cr), myo-inositol (mI)/Cr values in the bilateral PWM, NAA/Cr and choline (Cho)/Cr values in the left hippocampus, and Cho/Cr values in the right hippocampus being the features contributing the most; (2) the above seven features could be used to predict Self-rating Idea of Suicide Scale scores (r = 0.4261, p = 0.0302); and (3) the level of neuronal function in the left hippocampus may be related to the duration of illness, the level of membrane phospholipid catabolism in the left hippocampus may be related to the severity of depression, and the level of inositol metabolism in the left PWM may be related to the age of onset in BD patients with SI. Our results showed that the combination of multiple brain biochemical metabolites could better predict the risk and severity of suicide in patients with BD and that there was a significant correlation between biochemical metabolic values and clinical variables in BD patients with SI.

The Chinese Brief Cognitive Test: Normative Data Stratified by Gender, Age and Education.

The aim of this study was to develop a brief version of cognitive assessment test for evaluating the efficacy of treatments targeting cognitive impairments in Chinese schizophrenia patients, to examine its reliability, and establish normative data. Stratified according to age, gender, and educational level, healthy adult subjects were recruited from fifteen institutions in seven administrative regions of China and 723 valid samples were obtained, of which 50 were retested. Generalized Linear Models were conducted to analyze the effects of age, sex, and education. There was no significant difference between genders, while significant effects were demonstrated respectively among age and education on the normative data of C-BCT. The Cronbach α of C-BCT is 0.75, and the test-retest reliability (ICC) ranged from 0.62 to 0.76. Normative data of C-BCT were generated by gender, age and education, and the effects of these demographic factors were analyzed. It revealed good internal consistency and test-retest reliability of C-BCT.

High-frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Accelerates onset Time of Beneficial Treating Effects and Improves Clinical Symptoms of Depression.

BACKGROUND: In recent years, more and more patients with depression demonstrate suicidal intention and suicidal behavior. OBJECTIVE: To evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in treating depression with suicidal ideation. METHODS: Eighty-nine depression patients with suicide intention were administrated drugs combined with four weeks of Active rTMS (n=40) or sham (n=49) rTMS treatment. The 24-item Hamilton Depression Rating Scale for Depression (HAMD-24) and Self-rating Idea of Suicide Scale (SIOSS) were used to evaluate suicide risk and depression severity at baseline, weeks 2 and 4. A 25% reduction in HAMD-24 score from baseline was defined as treatment response. More than a 20% reduction in HAMD-24 score from baseline within the first 2 weeks of treatment was defined as an early improvement. RESULTS: No statistical significance was found for baseline sociodemographic and illness characteristics between the two groups (P >0.05). There was a significant difference for HAMD-24 and SIOSS scores between the two groups at weeks 2 and 4. Active rTMS group demonstrated a more significant score reduction compared to the Sham rTMS group at weeks 2 and 4. There was a significantly greater number of patients with early improvement observed in the Active rTMS group compared to those in the Sham rTMS group at weeks 2 (P <0.05). There was a significant difference in responder rates between the two groups at weeks 4 for HAMD-24 scores (P <0.05). CONCLUSION: rTMS could accelerate the onset time of beneficial treating effects and improve clinical symptoms of depression. During the treatment course, cognitive disorder, sleep disorder, anxiety/ somatization, retardation, and hopelessness symptoms were improved dramatically, and suicidal ideation was reduced.

BHLHE40 modulates post-traumatic stress disorder behaviors with the involvement of the PI3K/AKT signaling pathway.

Post-traumatic stress disorder (PTSD) is closely related to the exposure to traumatic events and results in the structural and functional changes of hippocampus. Human basic helix-loop-helix family member e40 (BHLHE40) was reported to be implicated with neuron maturity and neuronal differentiation. The present study aimed to reveal the role of BHLHE40 on single-prolonged stress (SPS) model of PTSD in mice. The morris water maze test, open field test and contextual fear test were conducted to assess memory deficits, anxiety-like behaviors, and freezing of mice. Western blot was performed to identify proteins and reveal their levels in hippocampal tissues. We found that mice receiving SPS exhibited increased anxiety-like behaviors, memory deficits, and prolonged freezing time. The protein levels of BHLHE40 were downregulated in the hippocampal tissues of SPS mice. SPS reduced the protein levels of glutamate receptors, while overexpression of BHLHE40 promoted glutamate receptor protein levels in SPS mice. Moreover, BHLHE40 overexpression activated the PI3K/AKT pathway. BHLHE40 overexpression ameliorated the SPS-induced PTSD-like behavioral deficits. Overall, BHLHE40 promotes glutamate receptor protein levels to ameliorate PTSD-like behaviors with the involvement of the PI3K/AKT pathway. This novel discovery may provide a potential target for the improvement of PTSD.

Neurometabolic alterations in bipolar disorder with anxiety symptoms: A proton magnetic resonance spectroscopy study of the prefrontal whiter matter.

To identify the pathophysiological mechanism of bipolar disorder (BD) patients with anxiety symptoms, we analyzed the differences of brain biochemical metabolism in BD patients with and without anxiety symptoms. We collected 39 BD patients who had been untreated with drugs in one month and were divided into the anxiety symptoms group (20 cases) and non-anxiety symptoms group (19 cases) according to whether they had anxiety symptoms. We used proton magnetic resonance spectroscopy (1H-MRS) to detect the biochemical metabolite ratios of the prefrontal whiter matter (PWM) in all patients. The right PWM mI/Cr ratios in BD patients with anxiety symptoms were higher than those in BD patients without anxiety symptoms and the Cho/Cr ratios in the left PWM were negatively correlated with age and age of onset in BD patients with anxiety symptoms. These findings indicated that BD patients with anxiety symptoms have increased levels of inositol metabolism in the right PWM. Furthermore, the level of membrane phospholipid catabolism in the left PWM of BD patients with anxiety symptoms decreased with increasing age and onset age. Our results provide some references for the pathophysiological mechanism in BD patients with anxiety symptoms.

The Association Between Child Abuse and Emotional and Behavioral Problems in Chinese School-Aged Boys With Attention Deficit Hyperactivity Disorder.

The aim of our study was to investigate the relationship between child abuse and emotional and behavioral problems in Chinese school-aged boys with attention deficit hyperactivity disorder (ADHD). Forty-eight school-aged boys with ADHD and 77 male healthy controls completed the final assessments that included the Child Behavior Checklist, the Barratt Impulsiveness Scale Version 11, the Screen for Child Anxiety Related Disorders, the Depression Self-Rating Scale for Children, and the Childhood Trauma Questionnaire, Short Form. Our findings showed that child abuse could associate with the behavioral problems in ADHD. Regression analysis further showed that child abuse (especially emotional abuse and physical abuse), adverse living conditions, and school anxiety significantly could be contributors to behavioral problems in boys with ADHD. Our study indicated that child abuse may be associated with the behavioral problems in Chinese school-aged boys with ADHD.

Correlation of maternal abuse during pregnancy with infant temperament and development.

OBJECTIVE: To investigate the effects of domestic violence (DV) against pregnant women on their infant's development in China. DESIGN: 247 mothers were interviewed using the Chinese version of the Abuse Assessment Screen, and all participants underwent postnatal assessment with the Edinburgh Postpartum Depression Scale (EDPS). Plasma glutamate (Glu), γ-aminobutyric acid (GABA) and cortisol levels of the neonates were measured. After a 10-month follow-up, the infants were assessed using the Revised Infant Temperament Questionnaire (RITQ) and Bayley Scales of Infant Development (BSID). RESULTS: 86 infants of abused mothers (DV group) and 137 infants of non-abused mothers (non-DV group) completed the 10-month follow-up. Neonate levels of plasma Glu, GABA and cortisol were significantly higher in the DV group than in the non-DV group. Scores for the temperament factors, rhythmicity, approach/withdrawal, mood, distractibility and persistence, of the RITQ were rated significantly higher, and results for the Psychomotor Development Index (PDI) of the BSID were significantly lower in the DV group than in the non-DV group at 10 months. After adjustment for the EPDS as a covariate, only distractibility of the RITQ showed a statistically significant difference between the two groups. In correlation analysis, infant mood correlated significantly with levels of plasma Glu (ß=0.2345) and GABA (ß=0.2554), whether or not the EPDS scores were adjusted. Infant persistence and threshold of stimuli scores did not correlate significantly with DV during pregnancy after adjustment for the EPDS. CONCLUSIONS: DV against pregnant women may be associated with impaired temperament and development in their infants.

Correlation of domestic violence during pregnancy with plasma amino-acid neurotransmitter, cortisol levels and catechol-o-methyltransferase Val(158)Met polymorphism in neonates.

INTRODUCTION: To explore the correlation between domestic violence during pregnancy and glutamate (Glu), r-aminobutyric acid (GABA), plasma cortisol levels and catechol-o-methyltransferase (COMT) gene polymorphism (rs4818) in neonates. METHODS: Using the Abuse Assessment Survey, 64 abused pregnant women (DV) and 117 non-abused pregnant women (non-DV) were screened for two study groups. Blood in neonatal umbilical vein was collected immediately after delivery. Plasma Glu, GABA, cortisol levels and rs4818 polymorphism in the genotypes and alleles of the two neonatal groups were compared. RESULTS: In the DV group, 49 women (76.6%) experienced emotional abuse, 29 women (45.3%) experienced sexual abuse, 28 (43.8%) women experienced emotional abuse plus sexual abuse, and two women (3.1%) experienced emotional abuse plus physical abuse. We found that plasma Glu, GABA and cortisol levels were higher in DV neonates than in non-DV neonates. Furthermore, we observed a significantly positive correlation between maternal emotional abuse, sexual abuse and plasma levels of Glu, GABA and cortisol in neonates. By genetic analysis we found a significant difference in rs4818SNP genotype and allele between the two neonatal groups. The ratios of CC genotype and C allele were higher in DV neonates than in non-DV neonates, and the ratios of GG genotype and G allele were lower in DV neonates than in non-DV neonates. One-way ANOVA test showed that GABA level was lower in CC carriers than CG carriers. DISCUSSION: Domestic violence during pregnancy might be associated with increased plasma levels of glutamate, GABA, cortisol and COMT gene polymorphism in neonates.

Relationship between domestic violence and postnatal depression among pregnant Chinese women.

OBJECTIVE: To investigate the prevalence of domestic violence during pregnancy and postnatal depression, and to explore the relationship between domestic violence and postnatal depression among Chinese women. METHODS: In a cross-sectional survey, 846 pregnant women were screened with the Abuse Assessment Screen; 215 women completed the postnatal follow-up. All participants underwent psychosocial assessment, with the Edinburgh Postpartum Depression Scale being used for the evaluation of postnatal depression. RESULTS: The overall prevalence of domestic violence during pregnancy was 11.3%, and the most common form of domestic violence was psychologic abuse. The follow-up interviews showed a higher prevalence of postnatal depression among women who had been abused during pregnancy (25.1%) than among those who had not (6.0%). Psychologic abuse during pregnancy, an unexpected pregnancy, an attitude of acceptance toward violence, and concern over the newborn's health were related with postnatal depression. CONCLUSION: Domestic violence during pregnancy and related factors contributed to postnatal depression in a population of Chinese women. The findings emphasize the importance of intervention among vulnerable populations in low-income countries.

Association between Cognitive Distortion, Type D Personality, Family Environment, and Depression in Chinese Adolescents.

Purpose. Depression prevalence and risk increase among adolescents are related to biological, psychosocial, and cultural factors. Little is known about the association between cognitive distortion, type D personality, family environment, and depression. The aim of this paper was to examine the relationships of cognitive distortion, type D personality, family environment, and depression in a sample of Chinese adolescents. Methods. A sample of Chinese adolescents with depression and the controls were investigated cross-sectionally with life orientation test-revised (LOT-R), type D personality Scale-14 (DS14), family environment scale (FES), and Zung self-depression scale (SDS); respectively, all scales were administered in Chinese. Results. Chinese-depressed adolescents showed more cognitive distortion, type D personality, and adverse family environment than control groups. Furthermore, lower level of Optimism, negative affectivity, and poor family cohesion may increase the risk of depression in Chinese adolescents. Conclusions. Our study indicates that lower level of Optimism, Negative Affectivity, and poor Family Cohesion factors were implicated to contribute to depression in Chinese adolescents. Lower level of optimism and negative affectivity may be crucial associated factors of depression among these samples. our findings pointed to the importance of broad screening and intervention of vulnerable population.

[Correlation between domestic violence in pregnancy and the levels of plasma amino acids and cortisol in the neonates].

OBJECTIVE: To explore the correlation between domestic violence in pregnancy and plasma glutamate (Glu), gamma-aminobutyric acid (GABA) and cortisol levels in neonates. METHODS: By cross-sectional survey and domestic violence (DV) interview with Abuse Assessment Survey (AAS), 56 abused pregnant women were screened and 107 non-abused pregnant women served as controls. Blood from umbilical vein of neonatal were collected immediately after delivery. Levels of Glu, GABA in plasma were assayed by using high performance liquid chromatography with electrochemical detection on samples. Levels of plasma cortisol were detected by with immunoradiometric assay. All variables of the two groups were compared. Chi-square, t/z-test, Spearman correlation, liner regression analysis were adopted. RESULTS: In the DV group, there were 49 women (87.5%) experiencing psychological abuse and 2 (3.6%) physical abuse during pregnancy. Moreover, 29 women (51.8%) experienced sexual abuse in the period of pregnancy. By comparison, our study showed higher levels of plasma Glu, GABA and cortisol in neonates of the DV group than those of the controls [(1509 +/- 339) pmol/L vs (811 +/- 270) pmol/L, (1460 +/- 369) pmol/L vs (707 +/- 296) pmol/L, (491 +/- 87) microg/L vs (392 +/- 108) microg/L, t = 14.326, t = 14.138, t = 5.916, P < 0.001]. Spearman correlation analysis showed significantly positive correlation between severity of psychological abuse and levels of Glu, GABA and cortisol (r = 0.705, 0.696, 0.425, P < 0.01) and positive correlation between the severity of sexual abuse and levels of Glu, GABA and cortisol (r = 0.471, 0.424, 0.274, P < 0.01). CONCLUSION: Domestic violence in pregnancy may alter the levels of some excitatory and inhibitory amino acids and change the endocrinic function in neonates.