Bipolar Disorder ; blood ; immunology ; metabolism ; Depressive Disorder ; blood ; immunology ; metabolism ; Humans ; Proteomics

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

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

Pharmacotherapy of bipolar disorder is a rapidly evolving field. Mood stabilizers and anticonvulsants have varying biochemical profiles which may predispose them to different adverse effects and drug-drug interactions. Several of the new anticonvulsants appear less likely to have the problems with drug-drug interaction. To provide more effective combination pharmacotherapies, clinicians should be allowed to anticipate and avoid pharmacokinetic and pharmacodynamic drug-drug interactions. We reviewed the role of cytochrome P450 isozymes in the metabolism of the drugs and their interactions. The drug-drug interactions of several classes of drugs which used as mood stabilizers and new anticonvulsants, some of which may have psychotropic profiles, are discussed mainly in this article. Finally, potential pharmacokinetic interactions between the benzodiazepines and other coadministered drugs are discussed briefly.
Anti-Anxiety Agents* ; Anticonvulsants ; Benzodiazepines ; Bipolar Disorder ; Cytochrome P-450 Enzyme System ; Drug Therapy ; Isoenzymes ; Metabolism

There are many factors involved in the effectiveness and efficiency of psychiatric drug treatment. One of them is psychotropic drug metabolism, which takes place mostly in the liver through the P450 enzyme system. However, there are genotypic variants of this system’s enzymes that can directly affect both the efficacy and the onset of side effects of a given therapeutic regimen. These genotypic changes could partly explain the lack of efficacy of treatment in certain patients. We report the case of a patient diagnosed with bipolar type I disorder that presented multiple and frequent manic episodes in which the efficacy and tolerability of several pharmacological regimens with mood stabilizers and antipsychotics was scarce. The choice of medical treatment should be based on its efficacy and side effect profile. This decision can be made more accurately using the information provided by pharmacogenetic analysis. This case illustrates the importance of pharmacogenetic studies in clinical practice. The results of pharmacogenetic analysis helped to decide on a better treatment plan to achieve clinical improvement and reduce drug-induced adverse effects.
Antipsychotic Agents ; Bipolar Disorder ; Cytochrome P-450 Enzyme System ; Humans ; Liver ; Metabolism ; Pharmacogenetics ; Precision Medicine

Bipolar Disorder ; diagnosis ; drug therapy ; epidemiology ; metabolism ; Catatonia ; diagnosis ; drug therapy ; epidemiology ; metabolism ; Humans ; Psychotropic Drugs ; therapeutic use

Adult ; Amino Acid Metabolism, Inborn Errors ; blood ; diagnosis ; Bipolar Disorder ; blood ; diagnosis ; Gas Chromatography-Mass Spectrometry ; Humans ; Hyperhomocysteinemia ; blood ; diagnosis ; Male ; Tandem Mass Spectrometry ; Vitamin B 12 ; blood

Lithium remains the most widely used therapeutic agent for bipolar affective disorder, particularly mania. Although many investigators have studied the effects of lithium on abnormalities in monoamine neurotransmitter as a pathophysiological basis of affective disorder, the action mechanism of lithium ion remains still unknown. To explore the action mechanism of lithium in the brain, we examined the effects of lithium on the extrasynaptosomal concentrations of catecholamines and their metabolites. Synaptosomes were prepared from the rat forebrains and assays of catecholamines and metabolites were made using HPLC with an electrochemical detector. Lithium of 1mM decreased the extrasynaptosomal concentrations of NE from the control group of 3.07+/-1.19 to the treated group of 0.00+/-0.00 (ng/ml of synaptosomal suspension) but not that of DHPG. It can be suggested that lithium increases synaptosomal uptake of NE. Increased intraneuronal uptake of NE would decrease neurotransmission and extraneuronal metabolism of NE. Because increased brain NE metabolism and neurotransmission have been suggested as important components in the pathophysiology of bipolar affective disorder, especially mania, lithium-induced increase of intraneuronal NE uptake can be suspected as an action mechanism of therapeutic effect of lithium in manic patient, possibly in bipolar affective disorder.
Animals ; Bipolar Disorder ; Brain* ; Catecholamines ; Chromatography, High Pressure Liquid ; Humans ; Lithium ; Metabolism ; Mood Disorders ; Neurotransmitter Agents ; Norepinephrine* ; Prosencephalon ; Rats* ; Research Personnel ; Synaptic Transmission ; Synaptosomes

The locus coeruleus (LC) has been studied in major depressive disorder (MDD) and bipolar disorder (BD). A major problem of immunocytochemical studies in the human LC is interference with the staining of the immunocytochemical end-product by the omnipresent natural brown pigment neuromelanin. Here, we used a multispectral method to untangle the two colors: blue immunocytochemical staining and brown neuromelanin. We found significantly increased tyrosine hydroxylase (TH) in the LC of MDD patients-thus validating the method-but not in BD patients, and we did not find significant changes in the receptor tyrosine-protein kinase ErbB4 in the LC in MDD or BD patients. We observed clear co-localization of ErbB4, TH, and neuromelanin in the LC neurons. The different stress-related molecular changes in the LC may contribute to the different clinical symptoms in MDD and BD.
Aged ; Aged, 80 and over ; Bipolar Disorder ; metabolism ; pathology ; Depressive Disorder, Major ; metabolism ; pathology ; Female ; Humans ; Image Processing, Computer-Assisted ; Immunohistochemistry ; methods ; Locus Coeruleus ; metabolism ; pathology ; Male ; Melanins ; metabolism ; Microscopy ; methods ; Middle Aged ; Neurons ; metabolism ; pathology ; Receptor, ErbB-4 ; metabolism ; Sensitivity and Specificity ; Spectrum Analysis ; methods ; Tyrosine 3-Monooxygenase ; metabolism

Adult ; Antidepressive Agents ; therapeutic use ; Bipolar Disorder ; blood ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Interferon-gamma ; blood ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Perylene ; analogs & derivatives ; therapeutic use ; Phytotherapy ; Tumor Necrosis Factor-alpha ; metabolism