The microtubule-associated molecular pathways may be genetically disrupted in patients with Bipolar Disorder. Insights from the molecular cascades

J Affect Disord. 2016 Jan 15;190:429-438. doi: 10.1016/j.jad.2015.10.016. Epub 2015 Oct 23.


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 ( 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.

Keywords: Aurora; Integrin; Microtubule-related process; Pathway analysis; Reelin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Databases, Genetic
  • Databases, Pharmaceutical
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Variation / genetics
  • Humans
  • Integrins / genetics*
  • Lithium / pharmacology*
  • Male
  • Microtubules / drug effects
  • Microtubules / genetics*
  • Nerve Tissue Proteins / genetics*
  • Serine Endopeptidases / genetics*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*
  • Transcription Factors / genetics*
  • mRNA Cleavage and Polyadenylation Factors / genetics*


  • CPEB1 protein, human
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Integrins
  • Nerve Tissue Proteins
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Lithium
  • Serine Endopeptidases
  • reelin protein