Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.
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.
Further, 2 genetic polymorphisms: the 5-HTTLPR and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms were not directly associated with familial risk for affective disorder and did not predict illness onset.
Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD.
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.
Human norepinephrine and serotonin transporters (hNET and hSERT) are closely related monoamine transporters (MATs) that regulate neurotransmitter signaling in neurons and are primary targets for a wide range of therapeutic drugs used in the treatment of mood disorders.
If this finding is replicated, further work on genetic variants with low 5-HTT activity may facilitate the differential diagnosis of affective disorders, the assessment of suicidal behaviour, and the prediction of good clinical response to antidepressants.
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.
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.
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).
In this study, we investigated the possibility that the 5-HTTLPR might be associated with depressive symptomatology in a sample of mood disorder subjects.
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.
Interactions with antidepressants, as well as other biochemical evidence, implicate the serotonin transporter 5-HTT in the etiology of affective disorders.
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.
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.
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.
Negative affect such as depression and anxiety has been reported to be associated with morbidity and mortality, and polymorphisms of the serotonin transporter (5HTT) gene may be associated with such affect disorders.
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.
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.
Positive associations of the 5-HTTLPR polymorphism with mood disorders, anxiety-related personality traits, autism and late-onset Alzheimer's disease have been published, although some non replications were also reported.