Shaojia Lu

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.

Altered fractional amplitude of low frequency fluctuation associated with cognitive dysfunction in first-episode drug-naïve major depressive disorder patients

BackgroundPrevious studies have demonstrated that abnormities of both resting-state brain activity and cognitive dysfunction are frequently observed in patients with major depressive disorder (MDD). However, the underlying relationship between these two aspects is less investigated. In this context, the aim of the present study was to investigate the association between cognitive dysfunction and altered resting-state brain function in first-episode drug-naïve MDD patients.MethodsTwenty-five drug-naïve MDD patients and twenty-six age-, sex-, and education-matched normal controls were recruited in this study. Cognitive function was evaluated by using a series of validated test procedures. The resting-state functional magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner and analysed using the fractional amplitude of low frequency fluctuation (fALFF) method. Correlations of fALFF values with cognitive dysfunction were further analysed.ResultsCompared with healthy controls, MDD patients showed significantly fewer completed categories in the Wisconsin Card Sorting Test (WCST) and decreased scores in the first and second subtests of the Continuous Performance Test (CPT). However, the two groups did not differ in their performance on the Stroop Colour Word Test and Trail-making Test. MDD patients exhibited significantly decreased fALFF values in the left superior frontal gyrus (SFG), left middle frontal gyrus, and left inferior frontal gyrus, as well as increased fALFF values in the left inferior temporal gyrus (ITG), bilateral parahippocampal gyrus, and the right caudate. Finally, the correlation analyses revealed that fALFF values in the left SFG and left ITG were associated with the number of WSCT completed categories and scores on the second subtest of the CPT in MDD, respectively.ConclusionsThe present findings suggest that there is little evidence of an association between regional abnormalities in resting-state brain function and cognitive deficits in MDD.

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity

Objective: Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. Methods: In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. Results: Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. Conclusion: The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

A randomized, 13-week study assessing the efficacy and metabolic effects of paliperidone palmitate injection and olanzapine in first-episode schizophrenia patients

Background: This study was conducted to evaluate the efficacy and metabolic effects of paliperidone palmitate (PP) injections against oral olanzapine in first‐episode schizophrenia (FES) patients. Methods: Eligible patients were randomized to receive PP or olanzapine. Efficacy assessments and weight‐related parameters were assessed at baseline, weeks 1, 5, 9, and endpoint or at early withdrawal. Lipid, glucose, insulin and prolactin were evaluated at baseline and endpoint or at early withdrawal. Results: The Positive And Negative Syndrome Scale (PANSS) scores declined significantly after treatment in both groups. Significant increases in weight‐related parameters from baseline to endpoint were shown in both groups. Although there was no significant difference in PANSS scores and weight‐related parameters between the two groups through the whole 13‐week study. The increased level of triglyceride and HOMA‐IR at endpoint from baseline in the olanzapine group was higher than the PP group. There was a stronger elevation of prolactin level in the PP group. Conclusions: In summary, PP and olanzapine showed similar improvement in the treatment of FES patients. This study also reinforced the necessity for regular monitoring of metabolic parameters in schizophrenia patients prescribed atypical antipsychotics. Clinical trial registration numbers: ChiCTR‐IOR‐14005304. Date of registration: 2014‐10‐11. HighlightsPaliperidone palmitate injection and olanzapine showed similar improvement in the treatment of first‐episode schizophrenia patients.This study reinforced the necessity for regular monitoring of metabolic parameters in schizophrenia patients prescribed atypical antipsychotics.A stronger elevation of prolactin level was found in the paliperidone palmitate group.

Neural correlates of childhood trauma with executive function in young healthy adults

The aim of this study was to investigate the relationship among childhood trauma, executive impairments, and altered resting-state brain function in young healthy adults. Twenty four subjects with childhood trauma and 24 age- and gender-matched subjects without childhood trauma were recruited. Executive function was assessed by a series of validated test procedures. Localized brain activity was evaluated by fractional amplitude of low frequency fluctuation (fALFF) method and compared between two groups. Areas with altered fALFF were further selected as seeds in subsequent functional connectivity analysis. Correlations of fALFF and connectivity values with severity of childhood trauma and executive dysfunction were analyzed as well. Subjects with childhood trauma exhibited impaired executive function as assessed by Wisconsin Card Sorting Test and Stroop Color Word Test. Traumatic individuals also showed increased fALFF in the right precuneus and decreased fALFF in the right superior temporal gyrus. Significant correlations of specific childhood trauma severity with executive dysfunction and fALFF value in the right precuneus were found in the whole sample. In addition, individuals with childhood trauma also exhibited diminished precuneus-based connectivity in default mode network with left ventromedial prefrontal cortex, left orbitofrontal cortex, and right cerebellum. Decreased default mode network connectivity was also associated with childhood trauma severity and executive dysfunction. The present findings suggest that childhood trauma is associated with executive deficits and aberrant default mode network functions even in healthy adults. Moreover, this study demonstrates that executive dysfunction is related to disrupted default mode network connectivity.

Relationships between dorsolateral prefrontal cortex metabolic change and cognitive impairment in first-episode neuroleptic-naive schizophrenia patients.

Abstract The present study aimed to explore the possible associations between the dorsolateral prefrontal cortex (DLPFC) metabolites and the cognitive function in first-episode schizophrenia (FES). This study included 58 patients with FES (29 males and 29 females; mean age, 22.66 ± 7.64 years) recruited from the First Affiliated Hospital, College of Medicine, Zhejiang University, and 43 locally recruited healthy controls (16 males and 27 females; mean age, 23.07 ± 7.49 years). The single-voxel proton magnetic resonance spectroscopy was used to measure the levels of N-acetylaspartate (NAA); complex of glutamate, glutamine, and &ggr;-aminobutyric acid (Glx); choline-containing compounds; and myo-inositol in the DLPFC. The ratios of metabolites to creatine (Cr) were calculated. The cognitive function was assessed by Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Correlation analysis was used to assess the relationships between the DLPFC metabolites and the cognitive function.Compared with the healthy controls, the patients with FES showed significantly reduced scores in each part of the MCCB, significantly reduced NAA/Cr, and significantly increased Glx/Cr in the left DLPFC. Poor performance in verbal learning and visual learning was correlated to the reduced NAA/Cr ratio in the left DLPFC. These findings suggest that a lower NAA/Cr ratio in the left DLPFC is associated with the cognitive deficits in patients with FES, and may be an early biochemical marker for the cognitive impairment in schizophrenia.

Association of Genetic Polymorphisms with Age at Onset in Han Chinese Patients with Bipolar Disorder

Bipolar disorder (BD) is a chronic and disabling disorder characterized by manic, hypomanic, or depressive episodes, with an estimated lifetime prevalence ranging from 1% to 5%. Globally, it is a leading cause of disability and a socioeconomic burden. Gene-environment interactions are thought to be involved in the neurobiology of BD, with genetic factors contributing to 60%–85% of BD patients. Twin studies have shown a heritability of 59%, and an increased risk of BD has been found in first-degree relatives of probands [1]. Currently, many genes have been reported as possible risk factors for BD, including PBRM1, CACNA1C, ANK3, ODZ4, SYNE1, ITIH1, GABRB1, DAOA, NCAN, and TRANK1. Environmental factors such as maternal stress, prenatal malnutrition, preterm birth, childhood abuse, stressful life events, and cannabis use can also contribute to the development of BD. Early recognition and treatment of BD can improve treatment responses and the prognosis [2]. However, there is always a long delay from the onset of disease to a definite diagnosis. Nearly half of BD patients develop their first mood episode at puberty. Kataoka et al. have found a significant association of early disease onset in BD probands with de novo protein-altering mutations when compared with non-carriers [3]. Therefore, age at onset (AAO) may be a potential clinical marker for genetic susceptibility to BD. The relationship between risk genes for BD and AAO, however, has not been fully investigated. In this study, we aimed to explore the correlation between high-risk single-nucleotide polymorphism (SNP) loci and AAO in Chinese patients with BD. A total of 224 Han Chinese participants with BD were consecutively recruited from the First Affiliated Hospital of Zhejiang University School of Medicine from August 2011 to March 2016. The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and further confirmed by the Structural Clinical Interview for DSM-IV. All patients were diagnosed with either type I or II BD. The exclusion criteria included prior or current comorbidity of other psychiatric diseases, alcohol or other psychoactive substance abuse, poisoning, or other physical conditions that could cause emotional lability. After a search of gene linkage analysis or genomewide association studies in databases (PubMed, EMBASE, and the Cochrane Library) up to February 2016, 35 SNP loci were screened as candidates. The genotypes were determined by the MassArray system (Agena iPLEX assay, San Diego, CA), with a 384-element SpectroCHIP gene array. Given our small sample size, the minor allele frequency of each SNP locus was required to be [ 0.05, and 26 SNP loci were finally included in the analysis. To determine the relationship between SNP loci and AAO of BD, Plink and Haploview statistical software was used and logistic regression analysis was performed. All study & Yi Xu xuyizju@zju.edu.cn

Neuronavigation-guided high-dose repetitive transcranial magnetic stimulation for the treatment of depressive adolescents with suicidal ideation: a case series

Background A high proportion of adolescents with major depressive disorder currently do not respond to conventional treatment. Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for major depressive disorder. Case We report on 3 cases of adolescents with suicidal ideation receiving 7 daily 10 Hz left prefrontal rTMS combined with pharmacotherapy treatment over 1 week for major depressive episode. The left dorsolateral prefrontal cortex was identified using magnetic resonance imaging-guided neuronavigation prior to stimulation. The suicidal ideation of these patients lessened significantly following rTMS treatment. Regarding adverse effects, symptoms of hypomania occurred in two patients since day 4, but no other side effects were found. Conclusion Neuronavigation-guided high-dose rTMS may be an effective and feasible treatment option for depressive adolescents with suicidal ideation. Caution over treatment-emergent mania/hypomania associated with rTMS is required.

The relationship between the alterations in metabolite levels in the dorsolateral prefrontal cortex and clinical symptoms of patients with first-episode schizophrenia: a one year follow-up study

Background Reduced brain metabolites such as N-acetyl-aspartate (NAA), glutamate (Glx), Choline (Cho) and myo-inositol (MI) have been repeatedly found in first-episode schizophrenia (FES) and suggest neuronal loss or dysfunction. However, the potential relationship between the metabolite level and the clinical symptoms or the recovery of FES remained unclear. Objectives This study aimed to investigate the correlation between the alterations in dorsolateral prefrontal cortex (DLPFC) metabolite levels of patients with first-episode schizophrenia (FES) and the changes in clinical symptoms after one year treatment. Materials and Methods FES patients underwent 1H-MRS scan twice: one time at the baseline and the other one year later, while the healthy group patients underwent only once at the baseline time. The symptom severity of patients was measured by PANSS. Principal Observations An increase in the NAA/Cr level was detected in the left DLPFC of patients with FES. The change in the NAA/Cr level was significantly correlated with the alteration in their PANSS-P score. The Cho/Cr levels on both sides of DLPFC in patients with FES were lower compared with the healthy controls both at the baseline and after the treatment. The NAA/Cr and MI/Cr levels in the right DLPFC were decreased after the treatment. Conclusions (1) the depletion of NAA in left DLPFC might be a state characteristic; (2) the Cho/Cr level might be the potential endophenotype of schizophrenia; (3) the decrease of NAA/Cr and MI/Cr level in right DLPFC might be due to the development of schizophrenia.