The 5HTTLPR s allele: a possible mediating variable between environmental factors and affective disorders

Gonda, Xenia; Lazary, Judid
January 2008
Annals of General Psychiatry;2008 Supplement 1, Vol. 7, Special section p1
Academic Journal
Possibilities for research concerning the genetic background of psychiatric disorders and psychological traits has been vastly expanding in the last decade. Amongst several approaches, the 5HTTLPR, a functional polymorphism located in the promoter sequence of the serotonin transporter gene is a likely candidate in delineating genetic factors in the background of affective disorders. The 5HTTLPR polymorphism of the serotonin transporter gene has been found to be associated with both clinical and subclinical forms of depression and anxiety, as well as traits related to neuroticism and affective temperaments carrying a depressive component. Other studies have described its association with biological markers of depression in healthy samples. The s allele has also been described to be associated with resilience and response to stress. Results thus so far indicate that this polymorphism plays a crucial role in the background of affective disorders, while within the boundary of health it is manifested in the form of increased neuroticism or more marked emergence of neuroticism-related traits and in the more pronounced presence of dominant affective temperaments. Although the frequency of the s allele of this polymorphism, which is associated with increased vulnerability towards affective disorders, has been found to be 43% within the Caucasian population, the lifetime prevalence of unipolar and bipolar depression is around 18-20%. Thus it seems likely that although the presence of this allele predisposes to the development of affective disorders, other factors, such as environmental stress and life events are also necessary for the development of clinical depression. The nature of the manifested affective disorder is also determined by the interaction of environmental and genetic factors (gene x environment interaction) as well as the interaction of several genes (gene x gene interaction). Although complex interactions play a governing role in the manifestation of affective symptomatology, the presence of the 5HTTLPR s allele seems to increase vulnerability to environmental influences and stress and thus plays a crucial and permissive role in the development of clinical depression.


Related Articles

  • Serotonin transporter gene associated with lithium prophylaxis in mood disorders. Serretti, A.; Lili, R.; Mandelli, L.; Lorenzi, C.; Smeraldi, E. // Pharmacogenomics Journal;2001, Vol. 1 Issue 1, p71 

    Presents a study that investigated the possible association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene and the prophylactic efficacy of lithium in mood disorders. Method of the study; Results and discussion; Conclusion.

  • The DAOA/G30 locus and affective disorders: haplotype based association study in a polydiagnostic approach. Gawlik, Micha; Wehner, Ingeborg; Mende, Meinhard; Jung, Sven; Pfuhlmann, Bruno; Knapp, Michael; Stöber, Gerald // BMC Psychiatry;2010, Vol. 10, p59 

    Background: The DAOA/G30 (D-amino acid oxidase activator) gene complex at chromosomal region 13q32-33 is one of the most intriguing susceptibility loci for the major psychiatric disorders, although there is no consensus about the specific risk alleles or haplotypes across studies. Methods: In a...

  • Association studies of bipolar disorder at the human serotonin transporter gene (hSERT; 5HTT). Rees, M.; Norton, N.; Jones, I.; McCandless, F.; Scourfield, J.; Holmans, P.; Moorhead, S.; Feldman, E.; Sadler, S.; Cole, T.; Redman, K.; Farmer, A.; McGuffin, P.; Owen, M.J.; Craddock, N. // Molecular Psychiatry;1997, Vol. 2 Issue 5, p398 

    The human serotonin transporter gene (hSERT) is a strong candidate for involvement in the pathogenesis of mood disorder and, using a UK Caucasian case-control sample, Collier et al found a significant association between bipolar disorder and the 12 allele of the VNTR polymorphism in intron 2 of...

  • Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism. Flory, J.D.; Manuck, S.B.; Ferrell, R.E.; Dent, K.M.; Peters, D.G.; Muldoon, M.F. // Molecular Psychiatry;1999, Vol. 4 Issue 1, p93 

    A deletion/insertion polymorphism in the transcriptional control region of the serotonin transporter gene (5HTTLPR) was reported to be associated with dimensional measures of neuroticism, although subsequent replication attempts have failed. These replication attempts, however, have been...

  • Serotonin Transporters. Inoue, Takeshi; Kusumi, Ichiro; Yoshioka, Mitsuhiro // Current Drug Targets - CNS & Neurological Disorders;Oct2002, Vol. 1 Issue 5, p519 

    The serotonin transporter is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuropsychiatric and related disorders. The discovery that the...

  • Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Kunugi, H.; Hattori, M.; Kato, T.; Tatsumi, M.; Sakai, T.; Sasaki, T.; Hirose, T.; Nanko, S. // Molecular Psychiatry;1997, Vol. 2 Issue 6, p457 

    There is some evidence suggesting that a polymorphism of variable number of tandem repeats (VNTR) in the second intron of the serotonin transporter (5-HTT) gene and another variation which lies 1.2 kb upstream of the promoter of the gene (5-HTTLPR) are associated with affective disorders....

  • Monoamine Metabolites Level in CSF is Related to the 5-HTT Gene Polymorphism in Treatment-Resistant Depression. Kishida, Ikuko; Aklillu, Eleni; Kawanishi, Chiaki; Bertilsson, Leif; Ågren, Hans // Neuropsychopharmacology;Oct2007, Vol. 32 Issue 10, p2143 

    The serotonin (5-hydroxytryptamine) transporter (5-HTT) is considered to affect the pathogenesis of mood disorders. Large number of genetic association studies between 5-HTT functional polymorphisms and vulnerability of mood disorders and therapeutic response to antidepressants has been carried...

  • CYP2C9 gene and susceptibility to major depressive disorder. LLerena, A; Berecz, R; Dorado, P; González, A P; Peñas-LLedó, E M; De la Rubia, A // Pharmacogenomics Journal;2003, Vol. 3 Issue 5, p300 

    Alteration of monoaminergic neurotransmission has been implicated in the pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to be modulated by serotonin in vitro. The present study was aimed at analysing the frequency of CYP2C9 alleles (*1, *2, *3) among patients...

  • Promoter Polymorphism in the Serotonin Transporter (5-HTT) Gene Is Significantly Associated with Leukocyte Telomere Length in Han Chinese. Li, Ping; Liu, Tiantian; Liu, Jiajia; Zhang, Qing; Lou, Fenglan; Kong, Feng; Cheng, Guanghui; Björkholm, Magnus; Zheng, Chengyun; Xu, Dawei // PLoS ONE;Apr2014, Vol. 9 Issue 4, p1 

    The serotonin transporter gene (5-HTT)-linked polymorphic region (5-HTTLPR) plays an important role in modulating mood and behavior by regulating 5-HTT expression and thereby controlling the concentration of serotonin (5-HT) in brain synapses: The homozygous shorter allele (S/S) in 5-HTTLPR...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics