Effects of Serotonin Transporter Promoter Genotype on Platelet Serotonin Transporter Functionality in Depressed Children and Adolescents

Nobile, Maria; Begni, Barbara; Giorda, Roberto; Frigerio, Alessandra; Marino, Cecilia; Molteni, Massimo; Ferrarese, Carlo; Battaglia, Marco

doi:10.1097/00004583-199911000-00014

Cited by 73 publications

(51 citation statements)

References 34 publications

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“…Previous studies showed either no effect of 5-HTTLPR genotype on Bmax of platelet We have presented preliminary female data to show that 5-HTTLPR variants do not affect significantly platelet 5-HT concentration in female healthy subjects, and in addition, our female group was substantially larger than female groups used in previous studies [9,13,23]. Peripheral 5-HT marker was used since lower baseline platelet 5-HT concentration [5,21,22] and long allele of the 5-HTTLPR [32] were proposed to be markers of good response to SSRI.…”

mentioning

confidence: 66%

The lack of genotype–phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects

Pivac

Nedić

Mustapić

et al. 2009

Neuroscience Letters

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mentioning

confidence: 66%

The lack of genotype–phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects

Pivac

Nedić

Mustapić

et al. 2009

Neuroscience Letters

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“…It may also explain differing vulnerabilities between individual subjects with identical genotypes, or between subjects reared in the same environments. At least one study 27 in human children suggests this type of complex interaction with affective disorder associated with alterations in the relationship between the genotypic variation in the serotonin transporter promoter gene and platelet serotonin transporter functionality.…”

Section: Molecular Psychiatrymentioning

confidence: 99%

Early experience and serotonin transporter gene variation interact to influence primate CNS function

et al. 2002

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Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

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“…A minority of studies (eg Franke et al, 2000Franke et al, , 2003Neuger et al, 1999;Stain-Malmgren et al, 1998) investigated maximal transport velocity (V max ) in nonseasonal depression, with some of them (Neuger et al, 1999) reporting decreased V max in female patients. Few investigated V max in direct comparison to B max (Nobile et al, 1999). A study in patients with seasonal affective disorder (SAD) showed reduced B max of [ 3 H]paroxetine in patients with SAD, but no significant differences in V max (StainMalmgren et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

Willeit

Sitte

Thierry

et al. 2007

Neuropsychopharmacol

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Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramineinduced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p ¼ 0.014) and outward (p ¼ 0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (r ¼ 0.421, p ¼ 0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

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Effects of Serotonin Transporter Promoter Genotype on Platelet Serotonin Transporter Functionality in Depressed Children and Adolescents

Cited by 73 publications

References 34 publications

The lack of genotype–phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects

The lack of genotype–phenotype relationship between platelet serotonin concentration and serotonin transporter gene promoter polymorphism in healthy subjects

Early experience and serotonin transporter gene variation interact to influence primate CNS function

Enhanced Serotonin Transporter Function during Depression in Seasonal Affective Disorder

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