Though these analogs are not superior than D22 in discriminating among OCTs/PMAT, our findings point to development of compounds with combined ability to inhibit both low-affinity/high-capacity transporters, such as OCT3, and high-affinity/low-capacity transporters, such as SERT, as therapeutics with potentially improved efficacy for treatment of psychiatric disorders.
The most common of these variants, SERT Ala56, located in the transporter's cytosolic N-terminus, has been found to confer in transgenic mice hyperserotonemia, an ASD-associated biochemical trait, an elevated brain 5-HT clearance rate, and ASD-aligned behavioral changes.
Variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) is a particularly promising candidate in this context, which has been linked to psychiatric disorders as well as to limbic and prefrontal reactivity.
Rs25532 CC genotype showed significant association with OCD in men and were detected more in the patients reported positive family history of psychiatric disorders but the other single loci (5-HTTLPR and rs25531) did not associate with OCD.
The human monoamine transporters (hMATs) primary including hSERT, hNET and hDAT are important targets for the treatment of depression and other behavioral disorders with more than availability of 30 approved drugs.
Nevertheless, research preliminarily indicates a methylation-driven increased vulnerability of carriers of the short allele of 5-HTTLPR to psychiatric disorders when exposed to early stress or soon after exposure to stress.
In humans, the short (S) allele in the 5-HTT gene-linked polymorphic region, which decreases 5-HTT expression, has been shown to be associated with behavioral changes including an increased level of anxiety.
Alterations in 5-HT transmission have been linked to pathological symptoms in both intestinal and psychiatric disorders and selective 5-HT transporter (5-HTT) inhibitors, affecting the 5-HT system by blocking the 5-HT transporter (5-HTT) have been successfully used to treat CNS- and intestinal disorders.
Gene-by-environment studies investigating the impact of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive.
The genetic variations in norepinephrine transporter (NET) and serotonin transporter (SERT) genes have been associated with personality traits, several psychiatric disorders and the efficacy of antidepressant treatment.
Despite previous studies that associated adult psychiatric disorders with the 5-HTTLPR polymorphism and a history of childhood maltreatment, no such association was found in this sample of children at risk.
The serotonin transporter length polymorphism (5-HTTLPR) short allele (5-HTTLPR-s) has been associated with differential susceptibility for anxiety and depression in multiple psychiatric disorders.
All participants were genotyped for the presence of the 5-HTTLPR short variant and for the A/G single-nucleotide polymorphism; they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events.
A length polymorphism repeat in the 5-HTT promoter region, termed 5-HTTLPR, has been commonly investigated for an association with psychiatric disorders.
The S allele has been associated with a variety of psychiatric disorders and symptoms including alcohol dependence, but it is unknown whether 5-HTTLPR increases the risk for co-morbid sociopathy among those with alcohol dependence.
Participants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events.
The serotonin transporter promoter length polymorphism (5-hydroxytryptamine transporter length polymorphism; 5-HTTLPR) has long been implicated in autism and other psychiatric disorders.
We investigated, in a large cohort of 5,608 controls and subjects suffering from various psychiatric disorders, the frequency of haplotypes and corresponding genotypes combining the 5-HTTLPR and the other serotonin transporter promoter functional variant (rs25531).
Serotonin transporter (SERT, 5-HTT) is a key element in the serotonergic system which is probably involved in the psychiatric disorders commonly observed in people living with HIV/AIDS.
The newly derived 5-HTTLPR Phenotype Scale shows strong association with 5-HTTLPR genotype and phenotype, therefore this scale should be further investigated in relation to psychiatric disorders, as well as psychological traits and temperaments.
Comparing the genotypic and allelic frequencies of AD without and with BPSD, we did not find a difference for the 5-HTTLPR or the rs25531, even after stratification according to single SBI-BP item.