title: The microtubule-associated molecular pathways may be genetically disrupted in patients with Bipolar Disorder. Insights from the molecular cascades.
abstract: Bipolar Disorder is a severe disease characterized by pathological mood swings from major depressive episodes to manic ones and vice versa. The biological underpinnings of Bipolar Disorder have yet to be defined. As a consequence, pharmacological treatments are suboptimal. In the present paper we test the hypothesis that the molecular pathways involved with the direct targets of lithium, hold significantly more genetic variations associated with BD. A molecular pathway approach finds its rationale in the polygenic nature of the disease. The pathways were tested in a sample of ∼ 7,000 patients and controls. Data are available from the public NIMH database. The definition of the pathways was conducted according to the National Cancer Institute (http://pid.nci.nih.gov/). As a result, 3 out of the 18 tested pathways related to lithium action resisted the permutation analysis and were found to be associated with BD. These pathways were related to Reelin, Integrins and Aurora. A pool of genes selected from the ones linked with the above pathways was further investigated in order to identify the fine molecular mechanics shared by our significant pathways and also their link with lithium mechanism of action. The data obtained point out to a possible involvement of microtubule-related mechanics.
authors.affiliation: Department of Biomedical and Neuromotor Sciences - DIBINEM - University of Bologna, Bologna, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Drago
authors.affiliation: Department of Biomedical Science and Morphological and Functional Images, University of Messina, Via Consolare Valeria, 98125 Messina, Italy. Electronic address: ccrisafulli@unime.it.
authors.forename: Concetta
authors.initials: C
authors.lastname: Crisafulli
authors.affiliation: Department of Biomedical Science and Morphological and Functional Images, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Sidoti
authors.affiliation: Department of Biomedical Science and Morphological and Functional Images, University of Messina, Via Consolare Valeria, 98125 Messina, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Calabrò
authors.affiliation: Department of Biomedical and Neuromotor Sciences - DIBINEM - University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D030541:Databases, Genetic; D062313:Databases, Pharmaceutical; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D016023:Integrins / Q000235:genetics*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: C490386:CPEB1 protein, human; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D016023:Integrins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D008094:Lithium; C000717127:RELN protein, human; D012697:Serine Endopeptidases
keywords: Aurora; Integrin; Microtubule-related process; Pathway analysis; Reelin