Relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage: a prospective observational study.

BACKGROUND: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage. METHODS: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively. RESULTS: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (rs = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization. CONCLUSIONS: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression.

Military traumatic brain injury: a challenge straddling neurology and psychiatry.

Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury (TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood-brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.

Discovery of new genetic loci for male sexual orientation in Han population.

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10-8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10-8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10-8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10-9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10-9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Psychometric properties of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype questionnaire in Chinese patients with mood disorders.

BACKGROUND: With the modification of DSM-5 mixed features specifier, a brief scale to screen mixed features in patients with mood disorders is needed in clinical practice. This study aimed to explore the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with DSM-5 Mixed subtype (CUDOS-M-C) for the Chinese patients with mood disorders. METHODS: Overall, 300 patients with major depressive episode were recruited. All participants were assessed using CUDOS-M-C, Young Mania Rating Scale, Hamilton Anxiety Scale and Montgomery-Asberg Depression Rating Scale. The receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-M-C score. The reliability and validity of CUDOS-M-C were examined using Cronbach's alpha, intraclass correlation coefficient (ICC) and principal component analysis (PCA). RESULTS: The results of PCA indicated two-factor structure as the best solution for CUDOS-M-C, which explained 54.82% of cumulative variance. The Cronbach's alpha was 0.892 and the ICC was 0.853. The area under the ROC curve of the CUDOS-M-C for participants with mixed depression was 0.927 (p<0.001) and the suitable cut-off value was 8, with a sensitivity of 91.6% and specificity of 79.9%. LIMITATIONS: Most of the patients were recruited from eastern China and further research with larger sample is warranted. And this study did not perform confirmatory factor analysis to identify the generalization of factor structure of CUDOS-M-C. Besides, the study performed the test-retest reliability of CUDOS-M-C and further analysis is needed to ascertain the patient's post-treatment changes. CONCLUSION: The CUDOS-M-C demonstrated to have satisfactory psychometric properties as a self-report scale, and could be applied to screen patients with mixed depression in clinical practice.

Interpersonal psychotherapy-based psychological intervention for patient suffering from COVID-19: A case report.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) was first found in Wuhan, China, and it has rapidly spread worldwide since the end of 2019. There is an urgent need to treat the physical and psychological aspects of COVID-19. Interpersonal psychotherapy (IPT)-based psychological intervention is an evidence-based therapy for depression and post-traumatic stress disorder. CASE SUMMARY: This report describes a case of COVID-19 in a patient who transmitted the disease to his entire family. The patient received four sessions of IPT-based psychological intervention. We used the Hamilton Rating Scale for Depression and Patient Health Questionnaire to measure depression level, and the Hamilton Anxiety Scale and Generalized Anxiety Disorder to measure anxiety among the patients. CONCLUSION: This case shows that IPT-based therapy can reduce COVID-19 patient depression and anxiety and the advantage of IPT-based therapy.

Executive function and its relation to anatomical connectome in homosexual and heterosexual men.

BACKGROUND: Sexual orientation has been suggested to affect executive function, of which the neurobiological basis is still largely unknown. In this study, we explored the interrelationship between neuropsychological characteristics in homosexual and heterosexual men and their anatomical connectome by graph theoretical analysis. METHODS: Fifty-three homosexual and 47 heterosexual males underwent diffusion tensor magnetic resonance imaging (MRI) and neuropsychological assessments. Whole-brain anatomical networks were constructed using white matter tractography, performed on the diffusion tensor imaging data. Neuropsychological tests included the Wisconsin Card Sorting Test (WCST), the Continuous Performance Test (CPT) and the Trail-Making Test (TMT). RESULTS: The cognitive performance of homosexual men was significantly poorer than their heterosexual counterparts in terms of WCST total correct responses. Anatomical connectome analysis revealed a lower (P=0.001) anatomical connectivity between left PoCG and left SMG (P=0.003) in homosexual men as compared to heterosexual men. Linear regression analyses showed that the WCST total correct responses score was significantly linked with sexual orientation (P=0.001). The anatomical connectivity strength between left PoCG and left SMG was also shown to be significantly correlated with sexual orientation (P=0.039) and education (P=0.047). CONCLUSIONS: Our study demonstrated the differences in the performance of WCST and anatomical connectome of large-scale brain networks between homosexual and heterosexual men, extending our understanding of the brain's circuitry and the characteristics of executive function in men of different sexual orientation.

Current Understanding of Gut Microbiota in Mood Disorders: An Update of Human Studies.

Gut microbiota plays an important role in the bidirectional communication between the gut and the central nervous system. Mounting evidence suggests that gut microbiota can influence the brain function via neuroimmune and neuroendocrine pathways as well as the nervous system. Advances in gene sequencing techniques further facilitate investigating the underlying relationship between gut microbiota and psychiatric disorders. In recent years, researchers have preliminarily explored the gut microbiota in patients with mood disorders. The current review aims to summarize the published human studies of gut microbiota in mood disorders. The findings showed that microbial diversity and taxonomic compositions were significantly changed compared with healthy individuals. Most of these findings revealed that short-chain fatty acids-producing bacterial genera were decreased, while pro-inflammatory genera and those involved in lipid metabolism were increased in patients with depressive episodes. Interestingly, the abundance of Actinobacteria, Enterobacteriaceae was increased and Faecalibacterium was decreased consistently in patients with either bipolar disorder or major depressive disorder. Some studies further indicated that specific bacteria were associated with clinical characteristics, inflammatory profiles, metabolic markers, and pharmacological treatment. These studies present preliminary evidence of the important role of gut microbiota in mood disorders, through the brain-gut-microbiota axis, which emerges as a promising target for disease diagnosis and therapeutic interventions in the future.

Relationship between Renalase Expression and Kidney Disease: an Observational Study in 72 Patients Undergoing Renal Biopsy.

The relationship between the levels of renalase and changes in proteinuria, hypertension, renal function, renal tubular epithelial cell apoptosis and B-cell lymphoma-2 (Bcl-2) expression was investigated in patients (chronic nephritis, primary nephrotic syndrome or other kidney disease) that underwent renal biopsy. The study group comprised 72 patients undergoing renal biopsy. Patient profiles and renal function were collected. Concentrations of renalase and Bcl-2 were measured by immunohistochemistry. Tubular injury was detected by periodic acid Schiff staining (PAS) and renal tubular epithelial cell apoptosis was assessed by TUNEL assay. The expression of renalase was significantly lower in renal biopsy specimens than in normal kidney tissues. There was a positive linear relationship between renalase and some serum and cardiac indices; a negative correlation was found between age, eGFR, Ccr and 24-h urinary protein. Renal tubule injury index and tubular epithelial cell apoptosis index showed a negative linear correlation with renalase. The results showed that renalase probably increased the expression of Bcl-2. By two independent samples t-test, renalase levels were significantly increased in the non-hypertension group than in the hypertension group. One-way ANOVA showed that renalase expression was higher in samples with Lee's grade III than in those with Lee's grade V. The expression of renalase was significantly decreased in patients who underwent renal biopsy, and was also associated with blood and renal function. The research proved that renalase may reduce renal tubular injury and apoptosis of renal tubular epithelial cells through the mitochondrial apoptosis pathway, finally achieving the purpose of delaying the progress of renal failure.

Altered microstructure of brain white matter in females with anorexia nervosa: a diffusion tensor imaging study.

OBJECTIVE: Structural studies have reported anorexia nervosa (AN) patients with abnormal gray matter in several brain regions and dysfunction in some connected neural circuits. However, the role of white matter (WM) in AN patients has rarely been investigated. The present study aimed to assess alterations in WM microstructure of the entire brain in females with AN using a voxel-based method on diffusion tensor imaging (DTI) data. MATERIALS AND METHODS: The study enrolled 8 female patients with AN and 14 age-matched females as controls (CW). The DTI data was collected from each subject to calculate the fractional anisotropy (FA) maps of the whole brain by the DTI-Studio software. Subsequently, a 2-sample t-test (P<0.05, corrected) was performed to detect the difference in FA maps of AN and CW group, and a Pearson's correlation analyzed the relationship between mean FA value of brain regions and body mass index (BMI). RESULTS: Compared with CW, AN patients revealed a significant decrease in FA maps in the left superior frontal gyrus, medial frontal gyrus, anterior cingulate cortex, middle frontal gyrus, inferior frontal gyrus, thalamus, and bilateral insula. Moreover, significantly positive correlations were established between the mean FA value of the left inferior frontal gyrus, insula as well as thalamus and BMI in AN patients. CONCLUSIONS: Our findings supported the presence of WM abnormality in patients with AN. The significant differences of FA maps, in patients with AN, were associated with their aberrant BMI. The results further improved our understanding of the pathophysiological mechanisms underlying AN.

Effective treatment of narcolepsy-like symptoms with high-frequency repetitive transcranial magnetic stimulation: A case report.

RATIONALE: Narcolepsy is a rare sleep disorder with disrupted sleep-architecture. Clinical management of narcolepsy lies dominantly on symptom-driven pharmacotherapy. The treatment role of repetitive transcranial magnetic stimulation (rTMS) for narcolepsy remains unexplored. PATIENT CONCERNS: In this paper, we present a case of a 14-year-old young girl with excessive daytime sleepiness (EDS), cataplexy and hypnagogic hallucinations. DIAGNOSES: After excluding other possible medical conditions, this patient was primarily diagnosed with narcolepsy. INTERVENTIONS: The patient received 25 sessions of high-frequency rTMS over the left dorsolateral prefrontal cortex (DLPFC). OUTCOMES: The symptoms of EDS and cataplexy significantly improved after rTMS treatment. Meanwhile, her score in the Epworth sleep scale (ESS) also remarkably decreased. LESSONS: This case indicates that rTMS may be selected as a safe and effective alternative strategy for treating narcolepsy-like symptoms. Well-designed researches are warranted in future investigations on this topic.

Circulating T lymphocyte subsets, cytokines, and immune checkpoint inhibitors in patients with bipolar II or major depression: a preliminary study.

This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected. In results, blood proportion of cytotoxic T cells significantly decreased in BD patients than in either MD patients or HCs. The plasma level of IL-6 increased in patients with BD and MD. The expression of TIM-3 on cytotoxic T cells significantly increased, whereas the expression of PD-L2 on monocytes significantly decreased in patients with BD than in HCs. These findings extended our knowledge of the immune dysfunction in patients with affective disorders.

Inhibition of c-Jun N-terminal Kinase Signaling Pathway Alleviates Lipopolysaccharide-induced Acute Respiratory Distress Syndrome in Rats.

BACKGROUND: An acute respiratory distress syndrome (ARDS) is still one of the major challenges in critically ill patients. This study aimed to investigate the effect of inhibiting c-Jun N-terminal kinase (JNK) on ARDS in a lipopolysaccharide (LPS)-induced ARDS rat model. METHODS: Thirty-six rats were randomized into three groups: control, LPS, and LPS + JNK inhibitor. Rats were sacrificed 8 h after LPS treatment. The lung edema was observed by measuring the wet-to-dry weight (W/D) ratio of the lung. The severity of pulmonary inflammation was observed by measuring myeloperoxidase (MPO) activity of lung tissue. Moreover, the neutrophils in bronchoalveolar lavage fluid (BALF) were counted to observe the airway inflammation. In addition, lung collagen accumulation was quantified by Sircol Collagen Assay. At the same time, the pulmonary histologic examination was performed, and lung injury score was achieved in all three groups. RESULTS: MPO activity in lung tissue was found increased in rats treated with LPS comparing with that in control (1.26 ± 0.15 U in LPS vs. 0.77 ± 0.27 U in control, P < 0.05). Inhibiting JNK attenuated LPS-induced MPO activity upregulation (0.52 ± 0.12 U in LPS + JNK inhibitor vs. 1.26 ± 0.15 U in LPS, P < 0.05). Neutrophils in BALF were also found to be increased with LPS treatment, and inhibiting JNK attenuated LPS-induced neutrophils increase in BALF (255.0 ± 164.4 in LPS vs. 53 (44.5-103) in control vs. 127.0 ± 44.3 in LPS + JNK inhibitor, P < 0.05). At the same time, the lung injury score showed a reduction in LPS + JNK inhibitor group comparing with that in LPS group (13.42 ± 4.82 vs. 7.00 ± 1.83, P = 0.001). However, the lung W/D ratio and the collagen in BALF did not show any differences between LPS and LPS + JNK inhibitor group. CONCLUSIONS: Inhibiting JNK alleviated LPS-induced acute lung inflammation and had no effects on pulmonary edema and fibrosis. JNK inhibitor might be a potential therapeutic medication in ARDS, in the context of reducing lung inflammatory.