Article

Clinical and pathogenic aspects of candidate genes for lithium prophylactic efficacy.

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.
Journal of Psychopharmacology (Impact Factor: 2.81). 09/2011; 26(3):368-73. DOI: 10.1177/0269881111415736
Source: PubMed

ABSTRACT A number of candidate genes for lithium prophylactic efficacy have been proposed, some of them being also associated with a predisposition to bipolar illness. The aim of the present study was to investigate a possible association between polymorphisms of 14 common genes with the quality of prophylactic lithium response in patients with bipolar mood disorder, in relation to the putative role of these genes in the pathogenesis of this disorder. Some association with lithium prophylactic efficacy was found for the polymorphisms of 5HTT, DRD1, COMT, BDNF and FYN genes, but not for 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GSK-3, NTRK2, GRIN2B and MMP-9. Possible aspects of these genes with regard to the mechanism of lithium activity and pathogenesis of bipolar mood disorder are discussed.

0 Bookmarks
 · 
144 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Published data on the association between GSK3B -50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B -50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92-1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84-1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97-1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96-1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B -50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: -0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: -0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: -0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism -50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.
    Molecular Biology Reports 06/2014; 41(9). DOI:10.1007/s11033-014-3441-x · 1.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aberrant synaptic plasticity, originating from abnormalities in dopamine and/or glutamate transduction pathways, may contribute to the complex clinical manifestations of bipolar disorder (BD). Dopamine and glutamate systems cross-talk at multiple levels, such as at the postsynaptic density (PSD). The PSD is a structural and functional protein mesh implicated in dopamine and glutamate-mediated synaptic plasticity. Proteins at PSD have been demonstrated to be involved in mood disorders pathophysiology and to be modulated by antipsychotics and mood stabilizers. On the other side, post-receptor effectors such as protein kinase B (Akt), glycogen synthase kinase-3 (GSK-3) and the extracellular signal-regulated kinase (Erk), which are implicated in both molecular abnormalities and treatment of BD, may interact with PSD proteins, and participate in the interplay of the dopamine-glutamate signalling pathway. In this review, we describe emerging evidence on the molecular cross-talk between dopamine and glutamate signalling in BD pathophysiology and pharmacological treatment, mainly focusing on dysfunctions in PSD molecules. We also aim to discuss future therapeutic strategies that could selectively target the PSD-mediated signalling cascade at the crossroads of dopamine-glutamate neurotransmission.
    Journal of Psychopharmacology 02/2014; 28(6). DOI:10.1177/0269881114523864 · 2.81 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. The aim of the study was to assess neurobiological and temperamental correlates in offspring of lithium-treated patients, related to parental lithium response. Methods. The study comprised 27 female and 23 male subjects, aged 17-54 years, the offspring of 36 bipolar patients receiving lithium for 5-38 years. Thirteen subjects were offspring of excellent lithium responders (ELR), 25 of partial lithium responders and 12 of lithium non-responders. In all subjects, serum brain-derived neurotrophic factor (BDNF), matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured, and the subjects were assessed by the Temperament Scale of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) and the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) scale. Results. In offspring of the ELR, the percentage of persons treated for mood disorder was higher (46 vs. 16%), and higher mean BDNF and MMP-9 levels and lower IL-6 levels were found, compared with the remaining subjects. There were also differences between the ELR and the remaining patients on the TEMPS-A and O-LIFE scale, and within the ELR, between subjects treated for mood disorders and the healthy ones. Conclusions. The offspring of ELR show distinct neurobiological and temperamental profiles compared to other lithium-treated patients.
    The World Journal of Biological Psychiatry 05/2014; DOI:10.3109/15622975.2014.913810 · 3.57 Impact Factor