Given that the 5-HTTLPR polymorphism has been associated with mood disorders, it is plausible that the abnormal pattern of regional brain activity detected here, in children carrying the S allele, increases susceptibility to emotional dysregulation and depressive symptoms.
In particular, the presence of one or two copies of the short (s) allele of the 5-HTTLPR polymorphism has been associated with reduced serotonin transporter expression and function, and vulnerability to affective disorders.
To investigate whether the distribution of the alleles of the 5-HTTLPR is associated with a genetic predisposition to affective disorder and whether these variations interact with life events in relation to depressive symptoms, neuroticism and salivary cortisol.
The main conclusions of the review are: i) there is an association between TPH2 and genetically defined behavioral variations, ii) the haplotypes, including some human TPH2 gene SNPs, can predict the risk of affective disorders and the sensitivity to antidepressant therapeutics, iii) mutations decreasing TPH2 activity produce negative effects on behavior and, possibly, on survival, iv) the effect of dietary tryptophan manipulations on human mood and behavior is modest compared with that of inhibitors of 5-HT transporter and monoamine oxidase.
Moreover, BDNF gene expression is also significantly reduced in leukocytes from healthy subjects carrying the S allele of the 5-HTTLPR, suggesting that the changes observed in SERT mutant rats may also be present in humans and may confer enhanced vulnerability to mood disorders.
5-HTT CpG methylation may be an important regulator of 5-HTT expression early in development and may contribute to the risk for mood disorders observed in 'high-risk'5-HTTLPR carriers.
Three genes contributed exclusively to mood disorders, one through a main effect (HTR5A (rs1657268)) and two through gene-environment interactions with CPA (HTR1A (rs878567) and SLC6A4 (rs3794808)).
A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear.
Moreover, the 5-HTTLPR polymorphism has been associated with anxiety-related traits such as neuroticism and harm avoidance (HA), which are known to influence the risk to develop mood disorders and response to treatments.
Further investigations in larger samples are needed to clarify the usefulness of 5-HTTLPR and BDNF Val66Met genotyping in the optimization of non-pharmacological treatments in mood disorders.
Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.
We investigated the influence of 5-HTT-linked polymorphic region (5-HTTLPR) and 5-HTT 17 bp variable number of tandem repeat polymorphism (5-HTTVNTR) polymorphisms on concentrations of monoamine metabolites in cerebrospinal fluid (CSF) among treatment-resistant patients with mood disorders.
Several studies have implicated an insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (SLC6A4; 5-HTT) in the development of mood disorders.
The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies.
In the present study, we evaluated the impact of the BDNF Val66Met polymorphism on individual differences in personality traits in a sample of healthy volunteers in relation to other common gene variants thought to be involved in the pathophysiology of affective disorders, such as the serotonin transporter promoter polymorphism (5-HTTLPR) and a variable number of tandem repeat polymorphism of the dopamine transporter gene (DAT VNTR).
Polymorphism at the serotonin transporter linked polymorphic region (5-HTTLPR) has been associated with neuroticism, increased risk for affective disorders and greater vulnerability to mood change following serotonin (5-HT) depletion.
In turn, corticolimbic circuit function predicts individual differences in an experimental index of temperamental anxiety and, thus, might reflect a predictive biological marker of increased risk for mood disorders associated with the 5-HTTLPR.
These results suggest that neuroticism mediates the association between 5HTT-LPR genotype and lifetime major depression, consistent with models of the aetiology of depression which suggest that anxiety-related personality traits represent a substantial risk factor for affective disorder.
Therefore, SERT knockout mice can be used as a tool to study 5-HTTLPR-related variations in personality and may be the etiology of affective disorders.
A functional polymorphism (a 44-base pair insertion (L)/deletion (S)) in the promoter of the gene encoding the serotonin transporter (5-HTTLPR), associated with mood disorders, has been inconsistently associated with suicidality.