Bipolar disorder

Depression, a prevalent psychiatric disorder that significantly impacts quality of life. Cholinergic transmission dysregulation potentially contributes to emotional and behavioral disturbances. While acetylcholinesterase is commonly studied in depression, the role of butyrylcholinesterase (BChE) remains unclear. We recently developed the butyrylcholinesterase (BChE)-activatable molecular sensor (BCC) for real-time visualization of BChE activity, demonstrating its efficiency in vitro and in tumor-bearing mice. In this translational study, we employed BCC to investigate BChE changes in depressio

Bipolar disorder (BD) is a severe psychiatric disorder characterized by alternating manic/hypomanic and depressive episodes. However, the molecular mechanism of transition between both states is unknown yet. Our study reveals that knockdown of the circadian clock gene Per2 in the hippocampal CA1 induces mania-like behaviors in rats. In contrast, overexpression of Per2 in the same region results in depression-like behaviors, indicating that Per2 expression levels may mediate the manic/depressive phenotype switch. In addition, we found that phosphorylation of the transcriptional factor CREB regu

To develop new therapeutic options for the treatment of bipolar disorder, animal models are a valuable tool to understand underlying changes in neurobiology. By manipulating the prefrontal dopamine D1 receptor our group was able to induce mania- as well as depressive-like behavior in rats. As social behavior is largely affected in bipolar disorder, we aim to phenotype our model in this respect. Therefore, a test battery including social hierarchy in three different tests (social dominance tube test, food competition test, urine scent mark test), sexual motivation and sexual behavior in adult r

Bipolar disorder (BD) is a chronic mood disorder characterized by recurrent episodes of depression and (hypo-) mania. The gut microbiome is a potential avenue through which metabolic signaling, inflammatory pathways and environmental factors influence mood disorders via the gut-brain axis. Fecal microbiota transplantation (FMT) is a translational tool for investigating the connections between the gut microbiome and the brain, and there is evidence that FMT from humans to mice can induce changes in affective behavior. In this study, we compared the behavior, gut-brain metabolomic profiles, and

…diseases such as major depression, bipolar disorder and schizophrenia. These deficits have been linked to the dysfunction of the mesocorticolimbic dopamine transmission suggesting the existence of common underlying pathophysiological mechanisms. Numerous clinical studies have described a decrease in n-3 polyunsaturated fatty acids (PUFAs) in subpopulations of patients suffering from psychiatric disorders (Conklin et al., 2010; Messamore and McNamara, 2016). Moreover, preclinical results from our laboratory

Magnetic Resonance Imaging has advanced our understanding of the neuroanatomical basis of psychosis. However, persistent challenges, including underpowered datasets, recruitment difficulties, high costs, and an overrepresentation of Western populations, hinder progress. Here, we introduce the Psychosis MRI Shared Data Resource (Psy-ShareD), a new open-access repository that aims to address these challenges by harmonising MRI datasets from labs around the world, to build a large globally representative resource. Psy-ShareD provides easily accessible and curated data, allowing a wide variety of

Lithium is a primary treatment for patients with bipolar disorder, effectively managing the extreme mood swings. However, side effects of lithium treatment including increased thirst often lead to significant discomfort and potentially impact patient compliance with the medication regimen. In an effort to understand the underlying mechanisms of lithium-induced thirst, we have conducted studies using mice as a model organism. These studies involve administering lithium chloride (LiCl) either through intraperitoneal injections or by supplementing lithium salts into the animals' diet. Observation

Basal ganglia is proposed to mediate symptoms underlying bipolar disorder (BD). To understand the cell type-specific gene expression and network changes of BD basal ganglia, we performed single-nucleus RNA sequencing of 30,752 nuclei from caudate, putamen, globus pallidus, and substantia nigra of control human postmortem brain and 24,672 nuclei from BD brain. Differential expression analysis revealed major difference lying in caudate, with BD medium spiny neurons (MSNs) expressing significantly higher PDE5A, a cGMP-specific phosphodiesterase. Gene co-expression analysis (WGCNA) showed a strong

Bipolar disorder (BD) patients have shown increased circulating levels of pro-inflammatory cytokines and cortisol and decreased levels of Brain-Derived-Neurotrophic Factor (BDNF) suggesting that these mediators might be involved in the occurrence of affective episodes disrupting brain plasticity. Aim of the study was to assess variations in peripheral neuroendocrine and inflammatory markers during acute phases of the disease and euthymia as possible predictors of affective episodes and as a reliable signature of the disease. BD patients were enrolled during depressive or manic/hypomanic phases

…research, EDA could be associated with Bipolar Disorder (BD) mood episodes, but results remain inconclusive due to heterogeneous study design and the presence of cofounders. During sleep main confounders such as physical activity and marked temperature changes decrease. Therefore, we measured EDA with wearable devices during the day and night to explore whether EDA is a better biomarker of mood episodes during sleep. We analysed 140 participants from the TIMEBASE study, 102

…psychiatric conditions such as bipolar disorder (BD) (McReynolds, 1962). Open-field animal behaviors have been well-studied for this purpose; however, a corresponding human subject paradigm is still lacking, and quantifying complex spontaneous human behaviors is challenging. Here, we demonstrate a semi-supervised model to quantify undirected human behavior, differentiate subtle hallmark behavioral features of BD, and create a natural language generative model to provide nuanced interpretations of behaviors wi

Weighted Gene Co-expression Network Analysis (WGCNA) is a widely used bioinformatics method that defines gene clusters (modules) based on correlated expression levels, allowing users to study relationships between modules, define groups of genes subserving common biological functions, and compare network topologies across distinct sets of expression data. WGCNA overcomes many challenges of gene-based studies, but it remains difficult to compare WGCNA results across studies, since gene modules are highly dependent on user parameters, experimental conditions, and other variables. As such, no con

…across different psychiatric disorders raising the question of how these genetic variants relate to the corresponding pharmacological treatments. In this talk, I will outline our work investigating whether functional information from a range of open bioinformatics datasets such as protein interaction network (PPI), brain eQTL, and gene expression pattern across the brain can uncover the relationship between GWAS-identified genetic variation and the genes targeted by current drugs for psychiatr