The different 5-HT (serotonin) receptors including the serotonin transporter (5-HTT) are candidate genes for affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD).
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.
A functional polymorphism within the promoter region of the 5-HTT gene, leading to different transcriptional efficiency, was repeatedly reported to influence the response to SSRIs in mood disorders while the response of patients with OCD seems unrelated.
It is not known how 5-HTTLPR genotype x childhood adversity (CA) interactions that are associated with an increased risk for affective disorders in population studies operate at the neural systems level.
Serotonin transporter gene (SLC6A4) has been shown to play an important role in the pathophysiology of mood disorders including poststroke depression (PSD).
We investigated the serotonin transporter gene (5-HTTLPR) in the functioning of euthymic patients with mood disorders (n=285) and healthy controls (n=94).
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.
In our sample of 814 patients comprising 114 with schizophrenia, 416 with bipolar affective disorder and 284 with unipolar affective disorder, we studied interactions between the tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR), and the dopamine receptor (DRD4) genes in relation to five major psychiatric symptomatology scores.
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.
Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.
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.
Polymorphic regions consisting of a variable number of tandem repeats within intron 2 of the gene coding for the serotonin transporter protein 5-HTT have been associated with susceptibility to affective disorders.
The serotonin transporter (SERT) gene is a particularly interesting candidate for genetic involvement in affective disorders owing to its role in both the regulation of serotonergic neurotransmission and the mechanism of action of many antidepressant drugs.
Although the serotonin transporter length polymorphic region (5-HTTLPR) polymorphism is an extensively-investigated genetic marker of anxiety related personality traits (neuroticism and harm avoidance) and affective disorders, effect sizes in meta-analyses are small, if present at all, and all available primary studies to date lack mandatory statistical power.
These findings provide novel evidence for both independent and interactive effects of 5-HTTLPR genotype and neuroticism on amygdala communication, which may mediate effects on risk for mood and affective disorders.
Serotonin transporter promoter length polymorphism (5-HTTLPR) has been implicated in the pathogenesis of mood disorders and in the therapeutic response to serotonergic drugs.
A functional polymorphism of the 5-HTT gene (a 44-base pair insertion/deletion in the 5-HTT-linked polymorphic region [5-HTTLPR]) was studied in a population of 237 consecutive patients with affective disorder (unipolar or bipolar) and 187 control subjects.