Yanbin Jia

A Meta-Analysis of Oxidative Stress Markers in Depression.

Object Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis aims to analyse the clinical data quantitatively by comparing the oxidative stress markers between depressed patients and healthy controls. Methods A search was conducted to collect the studies that measured the oxidative stress markers in depressed patients. Studies were searched in Embase, Medline, PsychINFO, Science direct, CBMDisc, CNKI and VIP from 1990 to May 2015. Data were subjected to meta-analysis by using a random effects model for examining the effect sizes of the results. Bias assessments, heterogeneity assessments and sensitivity analyses were also conducted. Results 115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin, high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy (p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were no differences between the depressed patients and controls for other oxidative stress markers. Conclusion This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication. The pathophysiological relationships between oxidative stress and depression, and the potential benefits of antioxidant supplementation deserve further research.

Interhemispheric resting state functional connectivity abnormalities in unipolar depression and bipolar depression.

Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in interhemispheric functional connectivity between BD and UD.

Similarities of biochemical abnormalities between major depressive disorder and bipolar depression: a proton magnetic resonance spectroscopy study.

BACKGROUND Depression in the context of bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD), leading to mistreatments and poor clinical outcomes for many bipolar patients. Previous neuroimaging studies found mixed results on brain structure, and biochemical metabolism of the two disorders. To eliminate the compounding effects of medication, and aging, this study sought to investigate the brain biochemical changes of treatment-naïve, non-late-life patients with MDD and BD in white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC) and hippocampus by using proton magnetic resonance spectroscopy ((1)H-MRS). METHODS Three groups of participants were recruited: 26 MDD patients, 20 depressed BD patients, and 13 healthy controls. The multi-voxel (1)H-MRS [repetition time (TR)=1000ms; echo-time (TE)=144ms] was used for the measurement of N-acetylaspartate(NAA), choline containg compounds (Cho), and creatine (Cr) in three brain locations: white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC), and hippocampus. Two ratios of NAA/Cr and Cho/Cr as a measure of brain biochemical changes were compared among three experimental groups. RESULTS On the comparison of brain biochemical changes, both MDD patients and BD patients showed many similarities compared to the controls. They both had a significantly lower NAA/Cr ratio in the left WMP lobe. There were no significant differences among three experimental groups for Cho/Cr ratio in the WMP lobe, and for the ratios of NAA/Cr and Cho/Cr in the bilateral ACC and hippocampus. The only difference between MDD and BD patients existed for the NAA/Cr ratio in the right WMP lobe. While MDD patients had a significantly lower NAA/Cr ratio than controls, BD patients showed no such differences. On the comparison of correlation of medical variables and brain biochemical changes, all participants demonstrated no significant correlations. CONCLUSION Reduced NAA/Cr ratio at the left WMP lobe indicated the dysfunction of neuronal viability in deep white matter, in both MDD and BD patients who shared similarities of brain biochemical abnormalities, which might imply an overlap in neuropathology of depression.

Frontal white matter biochemical abnormalities in first-episode, treatment-naive patients with major depressive disorder: A proton magnetic resonance spectroscopy study

BACKGROUND Previous neuroimaging studies found evidence of brain functional and structural abnormalities in patients with major depressive disorder (MDD), but they rarely excluded compounding effects of some important factors, such as medication and brain degeneration. This study sought to explore the brain biochemical changes of first-episode, treatment-naive, non-late-life adult patients with MDD in the frontal white matter and gray matter by using proton magnetic resonance spectroscopy (1H MRS). METHODS Twenty-four first-episode, treatment-naive, non-late-life adult depressed patients and 13 healthy controls were enrolled in this study. Subjects underwent two-dimensional multivoxel 1H MRS at 1.5 T to obtain bilateral metabolite levels from the dorsolateral prefrontal white matter and anterior cingulate gray matter. RESULTS Patients with MDD showed significantly lower N-acetylaspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios in the left dorsolateral prefrontal white matter, and lower NAA/Cr ratios in the right dorsolateral prefrontal white matter when compared with the control subjects. There were no significant differences in the metabolite ratios in the bilateral anterior cingulate gray matter. CONCLUSIONS These findings suggest that biochemical abnormalities in prefrontal white matter may occur early in the course of MDD and may be related to the neuropathology of depression.

Cerebellar microstructural abnormalities in bipolar depression and unipolar depression: A diffusion kurtosis and perfusion imaging study

BACKGROUND Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in cerebellum between BD and UD. METHODS Patients with BD (n=35) and UD (n=30) during a depressive episode as well as 40 healthy controls underwent diffusional kurtosis imaging (DKI) and three dimensional arterial spin labeling (3D ASL). The DKI parameters including mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr),fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) and 3D ASL parameters (i.e. cerebral blood flow) was measured by using regions-of-interest (ROIs) analysis in the superior cerebellar peduncles (SCP), middle cerebellar peduncles (MCP) and dentate nuclei (DN) of cerebellum. RESULTS Patients with UD exhibited significant differences from controls for DKI measures in bilateral SCP and MCP and cerebral blood flow (CBF) in bilateral SCP and left DN. Patients with BD exhibited significant differences from controls for DKI measures in the right MCP and left DN and CBF in the left DN. Patients with UD showed significantly lower MD values compared with patients with BD in the right SCP. Correlation analysis showed there were negative correlations between illness duration and MD and Dr values in the right SCP in UD. LIMITATIONS This study was cross-sectional and the sample size was not large. Parts of the patients included were under medication prior to MRI scanning. CONCLUSIONS Our findings provide new evidence of microstructural changes in cerebellum in BD and UD. The two disorders may have overlaps in microstructural abnormality in MCP and DN during the depressive period. Microstructural abnormality in SCP may be a key neurobiological feature of UD.

Hippocampal N-acetylaspartate and morning cortisol levels in drug-naive, first-episode patients with major depressive disorder: effects of treatment

An excess of glucocorticoids has been associated with hippocampal pathology in major depressive disorder (MDD). However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear, and the effects of antidepressant treatment on the measures are not well studied. For this study, 26 first-episode, treatment-naive, non-late-life adult depressed patients and 13 healthy controls were enrolled. Subjects underwent proton magnetic resonance spectroscopy (1H MRS) to obtain metabolite levels from the bilateral hippocampus. Patients with MDD were treated with serotonergic–noradrenergic reuptake inhibitor duloxetine for 12 weeks. After the 12-week period, all subjects with MDD underwent 1H MRS again. Morning serum cortisol levels also were measured both before and after antidepressant treatment. Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine (NAA/Cr) and choline (Cho)/Cr) in the bilateral hippocampus. After treatment, NAA/Cr ratios increased significantly in the right hippocampus compared with pre-treatment values. There was no correlation between morning serum cortisol levels and bilateral hippocampal NAA/Cr or Cho/Cr in patients with MDD. These findings suggest that there are unaltered hippocampal metabolites in the early stage of MDD. Antidepressant treatment may affect hippocampal NAA levels in patients with MDD. In addition, the results do not support cortisol-mediated hippocampal neurotoxicity as the major etiological mechanism.

Disrupted Resting-State Functional Connectivity in Nonmedicated Bipolar Disorder.

Purpose To investigate the whole-brain intrinsic functional connectivity patterns of patients with bipolar disorder (BD). Materials and Methods This prospective study was approved by the research ethics committee, and all participants provided informed consent. Thirty-seven patients with nonmedicated BD II depression and 37 healthy control participants underwent resting-state functional magnetic resonance (MR) imaging. Whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). Clinical state was assessed by using the 24-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. Two-sample t test and nonparametric correlation analysis were used. Results Compared with healthy control participants, patients with BD II showed decreased FCS in the default mode network (ie, the bilateral medial prefrontal cortex, bilateral middle temporal gyrus, left precuneus, and right posterior cingulate cortex), right supramarginal gyrus and angular gyrus, right superior frontal gyrus, and right superior parietal gyrus and increased FCS in the bilateral temporal pole (including the parahippocampal gyrus and amygdale), left anterior cingulate cortex, left superior temporal gyrus, right lingual gyrus, and left anterior lobe of the cerebellum (P < .05; AlphaSim corrected). Conclusion These results suggest that patients with BD have disrupted intrinsic functional connectivity mainly in the default mode network and limbic system, which might be associated with the pathophysiologic structure of BD. (©) RSNA, 2016.

The correlation between biochemical abnormalities in frontal white matter, hippocampus and serum thyroid hormone levels in first-episode patients with major depressive disorder

BACKGROUND Previous neuroimaging studies found evidence of potential brain biochemical abnormalities in patients with major depressive disorder (MDD). Abnormal serum thyroid hormone levels were also found in MDD patients, which may correlated with the abnormal biochemical metabolism of brain. However, they rarely excluded the compounding effects of medication, and brain degeneration. This study sought to investigate the relationship between the biochemical metabolism and the serum thyroid hormone levels in first-episode, treatment-naive, non-late-life patients with MDD. METHODS 26 first-episode, treatment-naive, non-late-life patients with MDD and 13 healthy controls were enrolled in this study. Participants underwent two-dimensinal multivoxel proton magnetic resonance spectroscopy ((1)H MRS) [repetition time (TR)=1000ms; echo-time (TE)=144ms] at 1.5T to obtain bilateral metabolite levels from the white matter in prefrontal (WMP) lobe, anterior cingulate cortex (ACC), and hippocampus. The ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline containg compounds (Cho)/creatine (Cr) were calculated. Morning serum free triiodothyronine (FT3), free thyroxin (FT4), total triiodothyronine (T3), total thyroxin (T4), and thyroid-stimulating hormone (TSH) were measured before antidepressant treatment. RESULTS On the comparison of brain biochemical changes, MDD patients had a significantly lower NAA/Cr ratio in the left WMP, and lower NAA/Cr and Cho/Cr ratios in the right WMP when compared to the controls. There were no significant differences in the metabolite ratios in the bilateral ACC, and hippocampus. On the comparison of serum thyroid hormone levels, MDD patients had a significantly decreased T3 and TSH levels. On the comparison of correlation of brain biochemical changes and serum thyroid hormone levels in patients with MDD, the NAA/Cr ratio in the right WMP was positively correlated with the level of TSH. CONCLUSION These findings suggest that biochemical abnormalities and thyroid dysfunction may emerge early in the course of MDD. Dysfunction of neuronal function in the WMP may correlate with the abnormal TSH in patients with MDD, which may be related to the neuropathology of depression.

Common and Specific Abnormalities in Cortical Thickness in Patients with Major Depressive and Bipolar Disorders

Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders. We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface. Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients. Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.

Reduced interhemispheric resting‐state functional connectivity in unmedicated bipolar II disorder

Abnormalities in structural and functional brain connectivity have been increasingly reported in patients with bipolar disorder (BD) by recent neuroimaging studies. However, relatively little is known about the changes in functional interaction between the cerebral hemispheres in BD. The present study aimed to examine the interhemispheric functional connectivity of the whole brain in patients with BD II during resting state.