Objective: The present study combined transcriptomic data and computational techniques based on gene expression signatures to identify new bioactive compounds or Food and Drug Administration-approved drugs for the treatment of bipolar disorder (BD). Methods: Five transcriptomic datasets containing 165 blood samples from individuals with BD were selected from the Gene Expression Omnibus (GEO). The number of participants varied from six to 60, with a mean age between 35 and 48 years and a gender difference between them. Most of these patients were receiving pharmacological treatment. Master regulator analysis (MRA) and gene set enrichment analysis (GSEA) were performed to identify genes that were significantly different between patients with BD and healthy controls and their associations with mood states in patients with BD. In addition, molecules that could reverse the transcriptomic profiles of BD-altered regulons were identified from the Library of Network-Based Cellular Signatures Consortium (LINCS) and the Broad Institute Connectivity Map Drug Repurposing Database (cMap) databases. Results: MRA identified 59 candidate master regulators (MRs) that modulate regulatory units enriched with BD-altered genes. In contrast, GSEA identified 134 enriched genes and 982 regulons whose activation state was determined. Both analyses revealed genes exclusively associated with mania, depression, or euthymia, and some genes were shared among these three mood states. We identified bioactive compounds and licensed drug candidates, including antihypertensives and antineoplastic agents, as promising candidates for the treatment of BD. However, experimental validation is essential to confirm these findings in further studies. Conclusion: Although our data are still preliminary, they provide some insights into the biological patterns of different mood states in patients with BD and their potential therapeutic targets. The strategy of transcriptomics plus bioinformatics offers a way to advance drug discovery and personalized medicine by using gene expression information. Objective Administrationapproved Administration approved . (BD) Methods 16 GEO. GEO (GEO) 60 3 4 them (MRA (GSEA addition BDaltered altered NetworkBased Network Based LINCS (LINCS cMap (cMap databases Results 5 MRs (MRs contrast 13 98 determined mania depression euthymia agents However studies Conclusion preliminary targets information (BD 1 (GEO 6 9

Abstract Background Emerging evidence indicates that inflammation plays an important role as a mechanism underlying mental disorders. However, most of the research on inflammatory mechanisms focuses on serum levels of interleukins and very few studies have investigated molecules that initiate and expand innate immune pathways such as damage-associated molecular patterns (DAMPs). Objectives This study investigated the levels of DAMPs among patients diagnosed with major depressive disorder (MDD), bipolar disorder (BD) I and II, schizophrenia (SCZ), and generalized anxiety disorder (GAD). We quantified serum levels of heat shock proteins (HSPs) 70 and 60 and of S100 calcium-binding protein B (S100B). Methods Serum levels of HSP70, HSP60, and S100B were assessed in a sample of participants with psychiatric disorders (n = 191) and a control group (CT) (n = 59) using enzyme-linked immunosorbent assay (ELISA). Results Serum HSP70 concentrations were significantly higher in the MDD group compared to the CT, SCZ, and BD groups. The GAD group had higher concentrations of HSP70 than the SCZ group. Exploring associations with medications, lithium (p = 0.003) and clozapine (p = 0.028) were associated with lower HSP70 levels. Approximately 64% of the sample had DAMPs levels below the limits of detection indicated by the respective ELISA kit. Conclusion This was the first study to assess DAMPs levels in a transdiagnostic sample. Our preliminary findings suggest that HSP70 may be associated with MDD pathophysiology. Medications such as lithium and clozapine were associated with lower HSP70 levels in BD and SCZ groups, respectively. Therefore, it is worth mentioning that all participants were medicated and many psychotropic drugs exert an anti-inflammatory effect, possibly reducing the signs of inflammation. However damageassociated damage DAMPs. . (DAMPs) MDD, , (MDD) (BD II (SCZ) GAD. (GAD) HSPs (HSPs 7 6 S S10 calciumbinding calcium binding S100B. SB (S100B) HSP HSP60 n 191 CT (CT 59 enzymelinked enzyme linked ELISA. (ELISA) HSP7 groups medications p 0.003 0003 0 003 0.028 0028 028 64 kit pathophysiology respectively Therefore antiinflammatory anti effect (DAMPs (MDD (SCZ (GAD S1 (S100B HSP6 19 5 (ELISA 0.00 000 00 0.02 002 02 1 0.0 0.

Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals’ blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Objective: Cardiovascular disease is the leading cause of death in patients with bipolar disorder. The aim of this study was to evaluate the factors associated with positive coronary calcium score (CCS) in individuals with bipolar disorder type 1. Methods: Patients from the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre, Brazil, underwent computed tomography scanning for calcium score measurement. Clinical and sociodemographic variables were compared between patients according to their CCS status: negative (CCS = 0) or positive (CCS > 0). Poisson regression analysis was used to examine the association of CCS with number of psychiatric hospitalizations. Results: Out of 41 patients evaluated, only 10 had a positive CCS. Individuals in the CCS-positive group were older (55.2±4.2 vs. 43.1±10.0 years; p = 0.001) and had more psychiatric hospitalizations (4.7±3.0 vs. 2.6±2.5; p = 0.04) when compared with CCS- negative subjects. The number of previous psychiatric hospitalizations correlated positively with CCS (p < 0.001). Conclusion: Age and number of psychiatric hospitalizations were significantly associated with higher CCS, which might be a potential method for diagnosis and stratification of cardiovascular disease in bipolar patients. There is a need for increased awareness of risk assessment in this population.