1.Early Diagnosis of Bipolar Disorder Coming Soon: Application of an Oxidative Stress Injury Biomarker (BIOS) Model.
Zhiang NIU ; Xiaohui WU ; Yuncheng ZHU ; Lu YANG ; Yifan SHI ; Yun WANG ; Hong QIU ; Wenjie GU ; Yina WU ; Xiangyun LONG ; Zheng LU ; Shaohua HU ; Zhijian YAO ; Haichen YANG ; Tiebang LIU ; Yong XIA ; Zhiyu CHEN ; Jun CHEN ; Yiru FANG
Neuroscience Bulletin 2022;38(9):979-991
Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism*
;
Bipolar Disorder/metabolism*
;
Depressive Disorder, Major/diagnosis*
;
Early Diagnosis
;
Humans
;
Oxidative Stress
2.Roles of m6A modification in neurological diseases.
Yuan ZHANG ; Si ZHANG ; Mengmeng SHI ; Menglin LI ; Jiayu ZENG ; Jie HE
Journal of Central South University(Medical Sciences) 2022;47(1):109-115
N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications for eukaryotic mRNA. Under the catalytic regulation of relevant enzymes, m6A participates in the body's pathophysiological processes via mediating RNA transcription, splicing, translation, and decay. In the past, we mainly focused on the regulation of m6A in tumors such as hematological tumors, cervical cancer, breast cancer. In recent years, it has been found that m6A is enriched in mRNAs of neurogenesis, cell cycle, and neuron differentiation. Its regulation in the nervous system is gradually being recognized. When the level of m6A modification and the expression levels of relevant enzyme proteins are changed, it will cause neurological dysfunction and participate in the occurrence and conversion of neurological diseases. Recent studies have found that the m6A modification and its associated enzymes were involved in major depressive disorder, Parkinson's disease, Alzheimer's disease, Fragile X syndrome, amyotrophic lateral sclerosis, and traumatic brain injury, and they also play a key role in the development of neurological diseases and many other neurological diseases. This paper mainly reviewed the recent progress of m6A modification-related enzymes, focusing on the impact of m6A modification and related enzyme-mediated regulation of gene expression on the central nervous system diseases, so as to provide potential targets for the prevention of neurological diseases.
Adenosine/metabolism*
;
Depressive Disorder, Major
;
Epigenesis, Genetic
;
Humans
;
Methylation
;
RNA, Messenger/metabolism*
3.Disturbance of the Glutamatergic System in Mood Disorders.
Chansoo JUN ; Yera CHOI ; Soo Mee LIM ; Sujin BAE ; Young Sun HONG ; Jieun E. KIM ; In Kyoon LYOO
Experimental Neurobiology 2014;23(1):28-35
The role of glutamatergic system in the neurobiology of mood disorders draws increasing attention, as disturbance of this system is consistently implicated in mood disorders including major depressive disorder and bipolar disorder. Thus, the glutamate hypothesis of mood disorders is expected to complement and improve the prevailing monoamine hypothesis, and may indicate novel therapeutic targets. Since the contribution of astrocytes is found to be crucial not only in the modulation of the glutamatergic system but also in the maintenance of brain energy metabolism, alterations in the astrocytic function and neuroenergetic environment are suggested as the potential neurobiological underpinnings of mood disorders. In the present review, the evidence of glutamatergic abnormalities in mood disorders based on postmortem and magnetic resonance spectroscopy (MRS) studies is presented, and disrupted energy metabolism involving astrocytic dysfunction is proposed as the underlying mechanism linking altered energy metabolism, perturbations in the glutamatergic system, and pathogenesis of mood disorders.
Astrocytes
;
Bipolar Disorder
;
Brain
;
Complement System Proteins
;
Depressive Disorder, Major
;
Energy Metabolism
;
Glutamic Acid
;
Magnetic Resonance Spectroscopy
;
Mood Disorders*
;
Neurobiology
4.Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation.
Nana YU ; Huina SONG ; Guangpin CHU ; Xu ZHAN ; Bo LIU ; Yangling MU ; Jian-Zhi WANG ; Yisheng LU
Neuroscience Bulletin 2023;39(4):617-630
Malfunction of the ventral subiculum (vSub), the main subregion controlling the output connections from the hippocampus, is associated with major depressive disorder (MDD). Although the vSub receives cholinergic innervation from the medial septum and diagonal band of Broca (MSDB), whether and how the MSDB-to-vSub cholinergic circuit is involved in MDD is elusive. Here, we found that chronic unpredictable mild stress (CUMS) induced depression-like behaviors with hyperactivation of vSub neurons, measured by c-fos staining and whole-cell patch-clamp recording. By retrograde and anterograde tracing, we confirmed the dense MSDB cholinergic innervation of the vSub. In addition, transient restraint stress in CUMS increased the level of ACh in the vSub. Furthermore, chemogenetic stimulation of this MSDB-vSub innervation in ChAT-Cre mice induced hyperactivation of vSub pyramidal neurons along with depression-like behaviors; and local infusion of atropine, a muscarinic receptor antagonist, into the vSub attenuated the depression-like behaviors induced by chemogenetic stimulation of this pathway and CUMS. Together, these findings suggest that activating the MSDB-vSub cholinergic pathway induces hyperactivation of vSub pyramidal neurons and depression-like behaviors, revealing a novel circuit underlying vSub pyramidal neuronal hyperactivation and its associated depression.
Rats
;
Mice
;
Animals
;
Rats, Sprague-Dawley
;
Depressive Disorder, Major/metabolism*
;
Basal Forebrain
;
Depression
;
Hippocampus/metabolism*
;
Cholinergic Agents
5.Lower Serum Cholesterol Level is Associated with More Serious Injury in psychiatric Patients with Suicide Attempt.
Yong Ku KIM ; Heon Jeong LEE ; Ji Yeon KIM ; Min Soo LEE ; So Hyun CHOI
Journal of the Korean Society of Biological Psychiatry 1999;6(2):227-234
An association of low total cholesterol in blood with psychiatric diseases and suicidal behavior has been suggested. As part of an attempt to further explore this relationship, we examine first, whether serum cholesterol levels in psychiatric patients with suicidal attempt would be lower than in non-suicidal psychiatric inpatients or normal controls, second, whether such significant difference of cholesterol levels would be present when the diagnostic groups are analyzed separately, third whether low cholesterol level would be associated with a history of serious suicidal attempts, and finally, whether low cholesterol level in suicide attempters is as state or a trait marker. We determined the serum cholesterol levels in 231 patients admitted to an emergency room following an suicidal attempt, in the same numbers of age-, sex- and diagnosis-matched non-suicidal psychiatric controls, and in the same numbers of age-, sex matched normal controls. The seriousness of an attempt was divided into 5 grades according to the degree of the resulting medical injury. Total cholesterol levels in suicide attempters were significantly lower compared with both psychiatric and normal controls, when sex, age, and nutritional status(i.e., body mass index) were controlled for. This significant relationship was observed in major depressive disorders and personality disorders, but not in schizophrenia and bipolar type I disorders. The severity of suicide by a lowering of blood cholesterol was related to the magnitude of the cholesterol reduction. After treatment of their psychiatric ailments, the cholesterol levels in suicide attempters were significantly increased. This result suggests that low cholesterol level in psychiatric patients might be a potential biological marker of suicide risk. It is hypothesized that low cholesterol levels is associated with the suicide by modifying the serotonin metabolism, the production of interleukin-2 and melatonin metabolism in psychiatric patients.
Biomarkers
;
Cholesterol*
;
Depression
;
Depressive Disorder, Major
;
Emergency Service, Hospital
;
Humans
;
Inpatients
;
Interleukin-2
;
Melatonin
;
Metabolism
;
Personality Disorders
;
Schizophrenia
;
Serotonin
;
Suicide*
6.Decreased occipital GABA concentrations in patients with first-episode major depressive disorder: a magnetic resonance spectroscopy study.
Zhe SONG ; Peiyu HUANG ; Lihua QIU ; Qizhu WU ; Qiyong GONG ; Bida ZHANG ; Keith HEBERLEIN ; Peng XIE
Journal of Biomedical Engineering 2012;29(2):233-236
Gamma amino butyric acid (GABA) is the major inhibitory neurotransmitter in the human brain. Alterations in GABAergic function are associated with a variety of neurological and psychiatric disorders. However, noninvasive in vivo measurement of GABA is difficult because of its low concentration and the presence of overlapping resonances. To study GABA concentration in the occipital cortex in major depressive disorder (MDD), a group of medication-naive, first episode depressed patients (n = 18, HAMD > 17), and a group of healthy controls (n = 23) were investigated using a Point Resolved Spectroscopy (MEGA-PRESS) on a 3.0 T MR scanner. The results showed that occipital GABA levels were significantly lower (P < 0.001) in the patient group than those in the healthy controls, yet the correlations between the severity of MDD (HAMD, BDI) and the GABA concentration is insignificant. Therefore, our data suggest that patients with first episode, unmedicated MDD have changes in cortical concentrations of GABA. This biochemical abnormality may be a marker of a trait vulnerability to mood disorder, and may explain the visual problem of severe MDD patients.
Adolescent
;
Adult
;
Depressive Disorder, Major
;
metabolism
;
Female
;
Humans
;
Magnetic Resonance Spectroscopy
;
Male
;
Occipital Lobe
;
metabolism
;
Young Adult
;
gamma-Aminobutyric Acid
;
analysis
;
metabolism
7.Effects of Mirtazapine on Hippocampal Metabolites of Female Patients with Major Depression.
Yoon Young NAM ; Chan Hyung KIM ; Seung Koo LEE ; Dong Pyo JANG ; Jae Jin KIM ; Ji Woong KIM ; Sun Il KIM ; Hong Shick LEE
Korean Journal of Psychopharmacology 2005;16(2):146-155
OBJECTIVE: Recent studies suggested that the neurotrophic effects might be a major therapeutic mechanism of antidepressants. However, these effects have not been confirmed yet in depressed patients. We investigated whether mirtazapine treatment has the neurotrophic effects in depressed patient by using (1)H-MRS and explored the relationship between these effects and clinical improvements and neuropsychological functions. METHODS: Fourteen female, right-handed patients with major depressive disorder and 12 healthy controls participated in the study. Before the treatment with mirtazapine, we measured severity of illness, neuropsychological functions, and the levels of NAA, Cho and Cr in both hippocampi using (1)H-MRS in the depressed subjects. After the treatment with mirtazapine for 6 weeks, we repeated the measures of the pretreatment condition in the depressed subjects. We also measured variables of severity of illness and hippocampal metabolites with (1)H-MRS in the control group. RESULTS: There were no significant differences in NAA/Cr, Cho/Cr, and Cho/NAA between the depressed subjects and the control group. However, after the treatment with mirtazapine, there were significant improvements in severity of illness, immediate memory, and delayed memory. The posttreatment ratio of the total hippocampal Cho/Cr was significantly lowered than the ratio of the pretreatment Cho/Cr. However, the percent changes of the hippocampal Cho/Cr from the pretreatment Cho/Cr ratio were not correlated with the changes of severity of illness or neuropsychological functions from the pretreatment condition. CONCLUSIONS: These findings indicate that mirtazapine may reduce the level of choline metabolites by stabilizing the effect on the cholinergic neurons, reducing turnover or metabolism of neuronal membranes, or modulating the neuroendocrine systems in the depressed patients. However, this effect is not necessarily related to clinical improvements. Further studies on the therapeutic action of mirtazapine are needed.
Antidepressive Agents
;
Choline
;
Cholinergic Neurons
;
Depression*
;
Depressive Disorder, Major
;
Female*
;
Hippocampus
;
Humans
;
Magnetic Resonance Spectroscopy
;
Membranes
;
Memory, Short-Term
;
Metabolism
;
Neurons
;
Neurosecretory Systems
;
Repression, Psychology
8.Microarray Analysis of the Major Depressive Disorder mRNA Profile Data.
Lishu GAO ; Yue GAO ; Enping XU ; Jian XIE
Psychiatry Investigation 2015;12(3):388-396
OBJECTIVE: Major depressive disorder (MDD) is a common mood disorder associated with several psychophysiological changes like disturbances of sleep, appetite, or sexual desire, and it affects the patients' life seriously. We aimed to explore a genetic method to investigate the mechanism of MDD. METHODS: The mRNA expression profile (GSE53987) of MDD was downloaded from Gene Expression Omnibus database, including 105 samples of three brain regions in post-mortem tissue suffered from MDD and unaffected controls. Differentially expressed genes (DEGs) in MDD were identified using the Limma package in R. Gene Ontology functions and Kyoto Enrichment of Genes and Genomes pathways of the selected DEGs were enriched using Database for Annotation, Visualization and Integrated Discovery. Protein-protein interactive network of DEGs was constructed using the Cytoscape software. RESULTS: Totally, 241 DEGs in MDD-hip group, 218 DEGs in MDD-pfc group, and 327 DEGs in MDD-str group were identified. Also, different kinds of biological processes of DEGs in each group were enriched. Besides, glycan biosynthesis of DEGs in MDD-str group, RIG-I-like receptor signaling and pyrimidine metabolism of DEGs in the MDD-hip group were enriched, respectively. Moreover, several DEGs like PTK2, TDG and CETN2 in MDD-str group, DCT, AR and GNRHR in MDD-pfc group, and AKT1 and IRAK1 in MDD-hip group were selected from PPI network. CONCLUSION: Our data suggests that the brain striatum tissue may be greatly affected by MDD, and DEGs like PTK2, GALNT2 and GALNT2 in striatum, AR in prefrontal cortex and IRAK1 and IL12A in hippocampus may provide novel therapeutic basis for MDD treatment.
Appetite
;
Biological Processes
;
Brain
;
Depressive Disorder, Major*
;
Gene Expression
;
Gene Ontology
;
Genome
;
Hippocampus
;
Metabolism
;
Microarray Analysis*
;
Mood Disorders
;
Prefrontal Cortex
;
RNA, Messenger*
9.Glucocorticoid receptor and treatment of psychotic major depression.
Xin HUI ; Cai-hong ZHOU ; Ming-wei WANG
Acta Pharmaceutica Sinica 2005;40(11):961-966
Animals
;
Brain
;
metabolism
;
Dehydroepiandrosterone
;
therapeutic use
;
Depressive Disorder, Major
;
drug therapy
;
metabolism
;
physiopathology
;
Humans
;
Metyrapone
;
therapeutic use
;
Mifepristone
;
therapeutic use
;
Psychotic Disorders
;
drug therapy
;
metabolism
;
physiopathology
;
Pyrimidines
;
therapeutic use
;
Receptors, Corticotropin-Releasing Hormone
;
antagonists & inhibitors
;
Receptors, Glucocorticoid
;
antagonists & inhibitors
;
metabolism
10.TREK1 potassium channels and depression.
Dong-Qing YE ; Zhi-Jun ZHANG ; Yang LI
Acta Pharmaceutica Sinica 2012;47(11):1403-1408
Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
Animals
;
Antidepressive Agents
;
pharmacology
;
Depressive Disorder, Major
;
genetics
;
metabolism
;
physiopathology
;
Drug Delivery Systems
;
Gene Knockout Techniques
;
Humans
;
Neuronal Plasticity
;
Polymorphism, Genetic
;
Potassium Channels, Tandem Pore Domain
;
genetics
;
metabolism
;
physiology
;
Receptors, Serotonin
;
metabolism
;
Receptors, Serotonin, 5-HT4
;
Serotonin
;
pharmacology