Association among abnormal glycolipids, reproductive hormones, and cognitive dysfunction in female patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition. METHODS: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test). RESULTS: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients. CONCLUSIONS: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients.

Effects of Plasmapheresis on Serum Lithium Levels in an ICU Patient with Bipolar Disorder: A Case Study.

ABSTRACT: This is a case description of a patient with bipolar disorder undergoing lithium therapy who received plasmapheresis for neuromyelitis optica spectrum disorder. Plasmapheresis resulted in lower and subtherapeutic serum lithium levels. Using therapeutic drug monitoring, a dose escalation of 80% was necessary to maintain therapeutic serum lithium levels. This underscores the importance of individualized therapy through therapeutic drug monitoring.

The association of blood biomarkers with cerebral white matter and myelin content in bipolar disorder: a systematic review.

OBJECTIVES: Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD. METHODS: PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included. RESULTS: Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region). CONCLUSION: This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.

Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder.

Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive-compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.

The influence of chronic inflammation on the illnesscourse of bipolar disorder: A longitudinal study.

INTRODUCTION: C-reactive protein (CRP) is a systemic inflammatory marker, which indicates systemic inflammatory processes It is involved in different inflammatory processes of the body and is a reliable marker for the general inflammatory state of the body. High sensitive CRP seems to play a key role as a state and trait marker of bipolar disorder (BD). In the current study, we tried to determine the long-term effect of CRP levels on clinical symptoms and illness course of bipolar disorder. METHODS: For the current study, we examined 106 patients with BD for a period of four years. Participants underwent a clinical screening for depressive and manic episodes with the Hamilton Depression Scale (HAMD) and the Young Mania Rating Score (YMRS) and a serological diagnostic for inflammatory parameters every six months, thus leading to 8 measurement times in total. Patients with the presence of severe medical or neurological comorbidities such as active cancer, chronic obstructive lung disease, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis and acute infections were not included in the study. RESULTS: In our sample, 26% showed a mean hsCRP above 5 mg/dl. Those patients showed a significantly higher mean YMRS score than those with a mean hsCRP under 5 mg/dl during our observation period. Regarding HAMD there was no significant difference in hsCRP values. The existence of lithium treatment showed no significant influence on mean hsCRP levels between the start and endpoint. CONCLUSION: Individuals who were exposed to a higher level of inflammation over time suffered from more manic symptoms in this period. These findings underline the hypothesis that inflammatory processes have an accumulative influence on the illness course of BD, especially concerning manic symptoms and episodes.

AI algorithm combined with RNA editing-based blood biomarkers to discriminate bipolar from major depressive disorders in an external validation multicentric cohort.

Bipolar disorder (BD) is a leading cause of disability worldwide, as it can lead to cognitive and functional impairment and premature mortality. The first episode of BD is usually a depressive episode and is often misdiagnosed as major depressive disorder (MDD). Growing evidence indicates that peripheral immune activation and inflammation are involved in the pathophysiology of BD and MDD. Recently, by developing a panel of RNA editing-based blood biomarkers able to discriminate MDD from depressive BD, we have provided clinicians a new tool to reduce the misdiagnosis delay observed in patients suffering from BD. The present study aimed at validating the diagnostic value of this panel in an external independent multicentric Switzerland-based cohort of 143 patients suffering from moderate to major depression. The RNA-editing based blood biomarker (BMK) algorithm developped allowed to accurately discriminate MDD from depressive BD in an external cohort, with high accuracy, sensitivity and specificity values (82.5 %, 86.4 % and 80.8 %, respectively). These findings further confirm the important role of RNA editing in the physiopathology of mental disorders and emphasize the possible clinical usefulness of the biomarker panel for optimization treatment delay in patients suffering from BD.

Serum Galectin-1, Galectin-9, and YKL-40 levels in bipolar disorder and their relationship with cognitive functions.

PURPOSE: The number of studies conducted on the role of neuroinflammation in the etiopathogenesis of bipolar disorder has been increasing in recent years. The role of Galectin-1, Galectin-9, and YKL-40, which are considered to play roles in neuroinflammation and the etiopathogenesis of bipolar disorder, and the relationship of these parameters with cognitive functions were investigated in the present study. METHOD: Serum Galectin-1, Galectin-9, and YKL-40 levels were measured with the ELISA Method in 64 bipolar euthymic patients and 64 healthy controls. The Stroop and trail-making tests were administered to assess cognitive functions in all participants. RESULTS: Serum Galectin-1, Galectin-9, and YKL-40 levels were statistically and significantly lower in the patient group when compared to the healthy control group. The scores of the Stroop test and trail-making tests were statistically higher in the patient group than in the healthy control group. There was a weak and positive correlation between serum Galectin-1, Galectin-9, and YKL-40 levels and cognitive performance in all participants. DISCUSSION AND CONCLUSION: Statistically significant low levels of serum Galectin-1, Galectin-9, and YKL-40 detected in the patient group suggest that these parameters have important roles in neuroinflammation. The statistically higher Stroop and trail-making test scores of the patient group compared to the control group indicates that the cognitive performance of the patient group was weaker. Also, the positive correlation between Galectin-1, Galectin-9, and YKL-40 levels and cognitive performance suggests that these molecules may have a neuroprotective role. We think that the present study will contribute to this field where there is very limited data in the literature.

Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) Levels in Adolescent with Bipolar Disorder and Their Relationship with Metabolic Parameters.

Peroxisome proliferator-activated receptor gamma (PPARγ) is one of the immune and metabolic regulatory agents. This study examined the serum PPARγ levels and metabolic syndrome (MetS) parameters in pediatric bipolar disorder (PBD) adolescents and compared them with healthy subjects. Serum PPARγ levels, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and fasting insulin levels of 39 PBD-type I (age range: 14-18) and 36 age- and sex-matched healthy control subjects were compared. The anthropometric measurements were also analyzed, including body weight, height, body mass index (BMI), waist circumference (WC), and blood pressure measurements. The PPARγ levels were significantly lower, and the MetS prevalence was significantly higher in the PBD group than in the control group. The mean BMI, WC, serum TG, and FBG values of the PBD group were statistically higher than the healthy control group. There was no significant relationship between the PPARγ levels and metabolic parameters except fasting glucose. Lower PPARγ activity and higher MetS prevalence in PBD indicate dysregulation of immune and metabolic regulatory parameters. These results may shed light on developing new PBD medications.

Circulating hsa-let-7e-5p and hsa-miR-125a-5p as Possible Biomarkers in the Diagnosis of Major Depression and Bipolar Disorders.

BACKGROUND: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders. METHODS: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires. RESULTS: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%. CONCLUSIONS: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD.

A High-Methionine Diet for One-Week Induces a High Accumulation of Methionine in the Cerebrospinal Fluid and Confers Bipolar Disorder-like Behavior in Mice.

Methionine (Met) is considered the most toxic amino acid in mammals. Here, we investigated biochemical and behavioral impacts of ad libitum one-week feeding of high-Met diets on mice. Adult male mice were fed the standard rodent diet that contained 0.44% Met (1×) or a diet containing 16 graded Met doses (1.2×-13×). High-Met diets for one-week induced a dose-dependent decrease in body weight and an increase in serum Met levels with a 2.55 mM peak (versus basal 53 µM) on the 12×Met diet. Total homocysteine (Hcy) levels were also upregulated while concentrations of other amino acids were almost maintained in serum. Similarly, levels of Met and Hcy (but not the other amino acids) were highly elevated in the cerebrospinal fluids of mice on the 10×Met diet; the Met levels were much higher than Hcy and the others. In a series of behavioral tests, mice on the 10×Met diet displayed increased anxiety and decreased traveled distances in an open-field test, increased activity to escape from water soaking and tail hanging, and normal learning/memory activity in a Y-maze test, which were reflections of negative/positive symptoms and normal cognitive function, respectively. These results indicate that high-Met ad libitum feeding even for a week can induce bipolar disorder-like disease models in mice.

Malondialdehyde as a candidate biomarker for bipolar disorder: A meta-analysis.

Malondialdehyde (MDA) represents one of the final products of lipid peroxidation that is thought to be enhanced and accelerated in patients affected by bipolar disorder (BD). Purpose of the present article is to critically summarize the available data about MDA as a candidate biomarker for BD. First, we carried out a systematic review of the literature selecting those papers that evaluated MDA levels in BD. Then, we performed two separate meta-analyses: one of the studies that compared healthy controls (HC) with unmedicated BD and one with the studies that assessed MDA levels before and after treatment in BD, showing that bipolar patients experience more oxidative stress than healthy subjects and that treatment is effective in reducing MDA levels. In the first set of studies, we also explored through a meta-regression whether age, gender and experiencing an episode specifically influenced the difference between BD and HC in MDA levels. Bipolar patients compared to healthy subjects had higher MDA levels (SMD: 0.94, 95% CI: 0.23-1.64). Age (p < 0.01), gender (p < 0.01) and the presence of a current mood episode (p < 0.01) significantly influenced MDA plasma/serum levels. Specifically, studies that included more female, older subjects and more BD in euthymia were more likely to have higher MDA levels. Finally, patients after treatment had lower levels of MDA compared to baseline (SMD: -0.52, 95% CI: -0.85 -0.19). More studies are needed to draw definitive conclusions.

Plasma Levels of the Cytokines B Cell-Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL) in Schizophrenia, Bipolar, and Major Depressive Disorder: A Cross Sectional, Multisite Study.

BACKGROUND: Immune dysfunction has been implicated in the pathogenesis of schizophrenia and other nonaffective psychosis (SCZ), bipolar spectrum disorder (BIP) and major depressive disorder (MDD). The cytokines B cell-activating factor (BAFF) and A proliferation-inducing ligand (APRIL) belong to the tumor necrosis factor (TNF) super family and are essential in orchestrating immune responses. Abnormal levels of BAFF and APRIL have been found in autoimmune diseases with CNS affection. METHODS: We investigated if plasma levels of BAFF and APRIL differed between patients with SCZ, BIP, and MDD with psychotic symptoms (n = 2009) and healthy control subjects (HC, n = 1212), and tested for associations with psychotic symptom load, controlling for sociodemographic status, antipsychotic and other psychotropic medication, smoking, body-mass-index, and high sensitivity CRP. RESULTS: Plasma APRIL level was significantly lower across all patient groups compared to HC (P < .001; Cohen's d = 0.33), and in SCZ compared to HC (P < .001; d = 0.28) and in BIP compared to HC (P < .001; d = 0.37). Lower plasma APRIL was associated with higher psychotic symptom load with nominal significance (P = .017), but not with any other clinical characteristics. Plasma BAFF was not significantly different across patient groups vs HC, but significantly higher in BIP compared to HC (P = .040; d = 0.12) and SCZ (P = .027; d = 0.10). CONCLUSIONS: These results show aberrant levels of BAFF and APRIL and association with psychotic symptoms in patients with SCZ and BIP. This suggest that dysregulation of the TNF system, mediated by BAFF and APRIL, is involved in the pathophysiology of psychotic disorders.

Comparison of thyroid-stimulating hormone levels in adolescents with schizophrenia, bipolar disorder, unipolar depression, conduct disorders, and hyperkinetic disorders.

ABSTRACT: The aim of this study was to retrospectively compare values of thyroid-stimulating hormone (TSH) in adolescent patients diagnosed with schizophrenia, bipolar disorder, unipolar depression (UNI-DEP), conduct disorders (CD), and hyperkinetic disorders.The research involved 1122 patients (718 women, 64%); aged 12 to 18 hospitalized in the Department of Adolescent Psychiatry, Medical University of Lodz. We analyzed TSH levels in the whole study population and compared it between the above-mentioned subgroups of diagnoses.Mean serum TSH concentration in the studied population (n = 1122) was 2.06 µIU/mL. The values of percentiles were as follows: 2.5th - 0.53 µIU/mL, 10th - 0.89 µIU/mL, 25th - 1.31 µIU/mL, 50th - 1.9 µIU/mL, 75th - 2.6 µIU/mL, 90th - 3.43 µIU/mL, 97.5th - 4.72 µIU/mL. TSH values were negatively correlated with patients' age (P = .00001). Patients with bipolar depression had higher TSH levels than patients with CD (P = .002). Also, when male and female groups were examined separately we found that female patients with UNI-DEP and bipolar disorder had higher TSH levels than female patients with CD (P = .001; P = .001).Our results confirm that there may be a higher prevalence of thyroid dysfunctions in bipolar and UNI-DEP subgroups among adolescents and that it is worthy to consider some kind of interventions regarding thyroid function in depressed individuals.

Comparison of thyroid function in different emotional states of drug-naïve patients with bipolar disorder.

BACKGROUND: Previous studies have shown that bipolar disorder is closely related to thyroid dysfunction. Psychiatric drugs have a large or small effect on thyroid function, and thyroid hormone levels can also affect the effect of drug treatment. Therefore, the purpose of this study is assessment the thyroid function of drug-naive bipolar disorder across different mood states, with the expectation of providing support for treatment options. METHODS: The present study is a cross-sectional study. Patients diagnosed with bipolar disorder according to the International Classification of Diseases diagnostic Criteria, Edition 10 (ICD 10) and who had never received medication were included in the study. The Montgomery Depression Scale (MADRS) was used to assess depressive symptoms and the Young Mania Rating Scale (YMRS) for manic symptoms. Thyroid function indicators include thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), and total thyroxine (TT4). Levels of TSH, TT4, FT4, TT3, and FT3 were measured within 48 h of hospitalization, between 06:00 and 08:00. RESULTS: The data analysis finally covered the data of 291 subjects (136 in a bipolar manic group, 128 in a bipolar depressive group, and 27 in a bipolar mixed group), including 140 males and 151 females, with an average age of 27.38 ± 8.01. There was no significant difference in age, sex, marital status, work status, family history, and course of illness among the manic group, depressive group, and mixed group. The level of FT3, the rate of thyroid hormone increased secretion, and the total abnormality rate of thyroid hormone secretion in the manic group were significantly higher than those in the depressive group. CONCLUSION: These findings indicate that thyroid functions were significantly different between depressive and manic episodes in BD patients. In clinical practice, it is necessary to take into account the differences in thyroid hormone levels in patients with BD across different emotional states in choosing drug.

Individuals with bipolar disorder have a higher level of uric acid than major depressive disorder: a case-control study.

At present, no well-established biomarkers were ever found to distinguish unipolar depression and bipolar disorder (BD). This study aimed to provide a clearer comparison of UA levels between BD and major depressive disorder. Peripheral UA of 119 patients with BD in acute stage (AS) and 77 in remission stage (RS), and 95 patients with UD in AS and 61 in RS were measured, so were 180 healthy controls. UA levels in BD group were higher than UD and HC groups regardless of the AS or RS, while differences in UA levels between UD group and HC group were not significant. Differences in UA levels of BD-M (bipolar mania/hypomania) were higher than BD-D (bipolar depression) subgroups, and UA levels of BD-M and BD-D subgroups were higher than UD and HC groups. The comparison of number of participants with hyperuricemia among groups confirmed the above results. There were no significant differences in UA levels of between drug-use and drug-free/naïve subgroups. UA could distinguish BD and UD significantly both in acute and remission stage. The study suggests patients with BD had a higher level of UA than UD, especially in mania episode. UA may be a potential biomarker to distinguish BD from UD.

Serum hepcidin / ferroportin levels in bipolar disorder and schizophrenia.

BACKGROUND: Despite several alternatives for cellular iron influx, the only mechanism for cellular iron efflux is ferroportin mediated active transport. In cases of ferroportin dysfunction, iron accumulates in the cell and causes ferroptosis. Hepcidin suppresses ferroportin levels and inflammatory activation increases hepcidin production. Mild inflammation in schizophrenia and bipolar disorder may alter hepcidin and ferroportin. METHODS: The study included a total of 137 patients aged 18-65 years, 57 diagnosed with schizophrenia and 80 with bipolar disorder, according to the DSM-IV diagnostic criteria, and a control group (HC) of 42 healthy individuals. Biochemical analyses, thyroid function tests, hemogram, serum iron level, iron-binding capacity, and ferritin levels were examined. Serum levels of hepcidin and ferroportin were measured with enzyme-linked immunosorbent assay (ELISA) method. RESULTS: A statistically significant difference was determined between the groups in terms of the serum ferroportin levels (F = 15.69, p < 0.001). Post-hoc analyses showed that the schizophrenia group had higher ferroportin levels than in the bipolar group (p < 0.001) and HCs (p < 0.001). Hepcidin levels did not differ between the groups. Chlorpromazine equivalent doses of antipsychotics correlated with ferroportin levels (p = 0.024). CONCLUSION: Ferroportin levels were increased in the schizophrenia group, although iron and hepcidin levels were within normal ranges. Antipsychotics may alter the mechanisms which control ferroportin levels. Further studies are needed to examine the relationships between antipsychotics and iron metabolism for determination of causal relationship.

Increased Global-Brain Functional Connectivity Is Associated with Dyslipidemia and Cognitive Impairment in First-Episode, Drug-Naive Patients with Bipolar Disorder.

Objectives: Previous researches have demonstrated that abnormal functional connectivity (FC) is associated with the pathophysiology of bipolar disorder (BD). However, inconsistent results were obtained due to different selections of regions of interest in previous researches. This study is aimed at examining voxel-wise brain-wide functional connectivity (FC) alterations in the first-episode, drug-naive patient with BD in an unbiased way. Methods: A total of 35 patients with BD and 37 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI). Global-brain FC (GFC) was applied to analyze the image data. Support vector machine (SVM) was adopted to probe whether GFC abnormalities could be used to identify the patients from the controls. Results: Patients with BD exhibited increased GFC in the left inferior frontal gyrus (LIFG), pars triangularis and left precuneus (PCu)/superior occipital gyrus (SOG). The left PCu belongs to the default mode network (DMN). Furthermore, increased GFC in the LIFG, pars triangularis was positively correlated with the triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) and negatively correlated with the scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) coding test and Stroop color. Increased GFC values in the left PCu/SOG can be applied to discriminate patients from controls with preferable sensitivity (80.00%), specificity (75.68%), and accuracy (77.78%). Conclusions: This study found increased GFC in the brain regions of DMN; LIFG, pars triangularis; and LSOG, which was associated with dyslipidemia and cognitive impairment in patients with BD. Moreover, increased GFC values in the left PCu/SOG may be utilized as a potential biomarker to differentiate patients with BD from controls.

Identification of potential plasma protein biomarkers for bipolar II disorder: a preliminary/exploratory study.

The diagnostic peripheral biomarkers are still lacking for the bipolar II disorder (BD-II). We used isobaric tags for relative and absolute quantification technology to identify five upregulated candidate proteins [matrix metallopeptidase 9 (MMP9), phenylalanyl-tRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin type 9 (PCSK9)] for the diagnosis of BD-II. We analysed the differences in the plasma levels of these candidate proteins between BD-II patients and controls (BD-II, n = 185; Controls, n = 186) using ELISA. To establish a diagnostic model for the prediction of BD-II, the participants were divided randomly into a training group (BD-II, n = 149; Controls, n = 150) and a testing group (BD-II, n = 36; Controls, n = 36). Significant increases were found in all five protein levels between BD-II and controls in the training group. Logistic regression was analysed to form the composite probability score of the five proteins in the training group. Receiver-operating characteristic curve analysis revealed the diagnostic validity of the probability score [area under curve (AUC) = 0.89, P < 0.001]. The composite probability score of the testing group also showed good diagnostic validity (AUC = 0.86, P < 0.001). We propose that plasma levels of PRDX2, CA-1, FARSB, MMP9, and PCSK9 may be associated with BD-II as potential biomarkers.

Plasma oxysterols: Altered level of plasma 24-hydroxycholesterol in patients with bipolar disorder.

Cholesterol and its oxygenated metabolites, including oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorders. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders. Recent studies have shown that Bipolar disorder (BD) is associated with the disruption of cholesterol metabolism. The present study was aimed at investigating the profile of oxysterols in plasma, their ratio to total cholesterol and their association with clinical parameters in patients with BD. Thirty three men diagnosed with BD and forty healthy controls matched for age and sex were included in the study. Oxysterol levels were measured by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry. Significantly higher levels were observed for cholestane-3ß,5α,6ß-triol, 27-hydroxycholesterol (27-OHC) and Cholestanol in patients with BD. The concentration of 24-hydroxycholesterol (24-OHC) was significantly lower in patients compared to controls. 24-OHC was also negatively correlated to MAS subscale score (r =-0.343; p = 0.049). In patients, 24-OHC was inversely correlated with age (r = -0.240; p = 0.045). Multivariate analysis found that BD acute decompensation was independently related to the rise in plasma 24-OHC (p = 0.002; OR = 0.966, 95 % CI [0.945 - 0.987]). However, the 24-OHC assay relevance as a biomarker of this disease deserves further investigation in other studies.

A pilot study indicating the dysregulation of the complement and coagulation cascades in treated schizophrenia and bipolar disorder patients.

A better understanding of the proteome profile after bipolar disorder (BD) and schizophrenia (SCZ) treatment, besides monitoring disease progression, may assist on the development of novel therapeutic strategies with the ability to reduce or control possible side effects. In this pilot study, proteomics analysis employing nano liquid chromatography coupled to mass spectrometry (nLC-MS) and bioinformatic tools were applied to identify differentially abundant proteins in serum of treated BD and SCZ patients. In total, 10 BD patients, 10 SCZ patients, and 14 healthy controls (HC) were included in this study. 24 serum proteins were significantly altered (p < 0.05) in BD and SCZ treated patients and, considering log2FC > 0.58, 8 proteins presented lower abundance in the BD group, while 7 proteins presented higher abundance and 2 lower abundance in SCZ group when compared against HC. Bioinformatics analysis based on these 24 proteins indicated two main altered pathways previously described in the literature; furthermore, it revealed that opposite abundances of the complement and coagulation cascades were the most significant biological processes involved in these pathologies. Moreover, we describe disease-related proteins and pathways associations suggesting the necessity of clinical follow-up improvement besides treatment, as a precaution or safety measure, along with the disease progression. Further biological validation and investigations are required to define whether there is a correlation between complement and coagulation cascade expression for BD and SCZ and cardiovascular diseases.