Serotonin gene polymorphisms and bipolar I disorder

Focus on the serotonin transporter

Hader A. Mansour, Michael E. Talkowski, Joel Wood, Lora Pless, Mikhil Bamne, Kodavali V. Chowdari, Michael Allen, Charles L. Bowden, Joseph Calabrese, Rif S. El-Mallakh, Andrea Fagiolini, Stephen V. Faraone, Mark D. Fossey, Edward S. Friedman, Laszlo Gyulai, Peter Hauser, Terence A. Ketter, Jennifer Loftis, Lauren B. Marangell, David J. Miklowitz & 9 others Andrew A. Nierenberg, Jayendra Patel, Gary S. Sachs, Pamela Sklar, Jordan W. Smoller, Michael E. Thase, Ellen Frank, David J. Kupfer, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The pathogenesis of bipolar disorder may involve, at least in part, aberrations in serotonergic neurotransmission. Hence, serotonergic genes are attractive targets for association studies of bipolar disorder. We have reviewed the literature in this field. It is difficult to synthesize results as only one polymorphism per gene was typically investigated in relatively small samples. Nevertheless, suggestive associations are available for the 5HT2A receptor and the serotonin transporter genes. With the availability of extensive polymorphism data and high throughput genotyping techniques, comprehensive evaluation of these genes using adequately powered samples is warranted. We also report on our investigations of the serotonin transporter, SLC6A4 (17q11.1-q12). An insertion/deletion polymorphism (5HTTLPR) in the promoter region of this gene has been investigated intensively. However, the results have been inconsistent. We reasoned that other polymorphism/s may contribute to the associations and the inconsistencies may be due to variations in linkage disequilibrium (LD) patterns between samples. Therefore, we conducted LD analyses, as well as association and linkage using 12 polymorphisms, including 5HTTLPR. We evaluated two samples. The first sample consisted of 135 US Caucasian nuclear families having a proband with bipolar I disorder (BDI, DSM IV criteria) and available parents. For case-control analyses, the patients from these families were compared with cord blood samples from local Caucasian live births (n=182). Our second, independent sample was recruited through the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD, 545 cases, 548 controls). No significant associations were detected at the individual polymorphism or haplotype level using the case-control or family-based analyses. Our analyses do not support association between SLC6A4 and BDI families. Further studies using sub-groups of BDI are worthwhile.

Original languageEnglish (US)
Pages (from-to)590-602
Number of pages13
JournalAnnals of Medicine
Volume37
Issue number8
DOIs
StatePublished - Dec 2005

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Bipolar Disorder
Serotonin
Genes
Linkage Disequilibrium
Genotyping Techniques
Live Birth
Nuclear Family
Fetal Blood
Genetic Promoter Regions
Synaptic Transmission
Diagnostic and Statistical Manual of Mental Disorders
Haplotypes
Parents

Keywords

  • Association
  • Bipolar disorder
  • Genetic
  • Polymorphism
  • Serotonin
  • Serotonin transporter

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mansour, H. A., Talkowski, M. E., Wood, J., Pless, L., Bamne, M., Chowdari, K. V., ... Nimgaonkar, V. L. (2005). Serotonin gene polymorphisms and bipolar I disorder: Focus on the serotonin transporter. Annals of Medicine, 37(8), 590-602. https://doi.org/10.1080/07853890500357428

Serotonin gene polymorphisms and bipolar I disorder : Focus on the serotonin transporter. / Mansour, Hader A.; Talkowski, Michael E.; Wood, Joel; Pless, Lora; Bamne, Mikhil; Chowdari, Kodavali V.; Allen, Michael; Bowden, Charles L.; Calabrese, Joseph; El-Mallakh, Rif S.; Fagiolini, Andrea; Faraone, Stephen V.; Fossey, Mark D.; Friedman, Edward S.; Gyulai, Laszlo; Hauser, Peter; Ketter, Terence A.; Loftis, Jennifer; Marangell, Lauren B.; Miklowitz, David J.; Nierenberg, Andrew A.; Patel, Jayendra; Sachs, Gary S.; Sklar, Pamela; Smoller, Jordan W.; Thase, Michael E.; Frank, Ellen; Kupfer, David J.; Nimgaonkar, Vishwajit L.

In: Annals of Medicine, Vol. 37, No. 8, 12.2005, p. 590-602.

Research output: Contribution to journalArticle

Mansour, HA, Talkowski, ME, Wood, J, Pless, L, Bamne, M, Chowdari, KV, Allen, M, Bowden, CL, Calabrese, J, El-Mallakh, RS, Fagiolini, A, Faraone, SV, Fossey, MD, Friedman, ES, Gyulai, L, Hauser, P, Ketter, TA, Loftis, J, Marangell, LB, Miklowitz, DJ, Nierenberg, AA, Patel, J, Sachs, GS, Sklar, P, Smoller, JW, Thase, ME, Frank, E, Kupfer, DJ & Nimgaonkar, VL 2005, 'Serotonin gene polymorphisms and bipolar I disorder: Focus on the serotonin transporter', Annals of Medicine, vol. 37, no. 8, pp. 590-602. https://doi.org/10.1080/07853890500357428
Mansour HA, Talkowski ME, Wood J, Pless L, Bamne M, Chowdari KV et al. Serotonin gene polymorphisms and bipolar I disorder: Focus on the serotonin transporter. Annals of Medicine. 2005 Dec;37(8):590-602. https://doi.org/10.1080/07853890500357428
Mansour, Hader A. ; Talkowski, Michael E. ; Wood, Joel ; Pless, Lora ; Bamne, Mikhil ; Chowdari, Kodavali V. ; Allen, Michael ; Bowden, Charles L. ; Calabrese, Joseph ; El-Mallakh, Rif S. ; Fagiolini, Andrea ; Faraone, Stephen V. ; Fossey, Mark D. ; Friedman, Edward S. ; Gyulai, Laszlo ; Hauser, Peter ; Ketter, Terence A. ; Loftis, Jennifer ; Marangell, Lauren B. ; Miklowitz, David J. ; Nierenberg, Andrew A. ; Patel, Jayendra ; Sachs, Gary S. ; Sklar, Pamela ; Smoller, Jordan W. ; Thase, Michael E. ; Frank, Ellen ; Kupfer, David J. ; Nimgaonkar, Vishwajit L. / Serotonin gene polymorphisms and bipolar I disorder : Focus on the serotonin transporter. In: Annals of Medicine. 2005 ; Vol. 37, No. 8. pp. 590-602.
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