Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men

Henningsson, Susanne; Borg, Jacqueline; Lundberg, J.; Bah, Jessica; Lindström, Mats; Ryding, Erik; Jovanovic, Hristina; Saijo, Tomoyuki; Inoue, Makoto; Rosén, Ingmar; Träskman‐Bendz, Lil; Farde, Lars; Eriksson, Elias

doi:10.1016/j.biopsych.2009.04.009

Cited by 52 publications

(45 citation statements)

References 64 publications

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“…Indeed, our results are coherent with those showing that SSRI failed to increase both hippocampal BDNF protein levels in BDNF homozygote Met/Met mice (Bath et al, 2012). Since the BDNF Met polymorphism influences brain 5-HT transporter expression or the density of serotonergic neurons, the altered 5-HT transporter expression and function associated with the BDNF Met polymorphism might be involved in the blunted response to SSRI treatments in Met patients (Henningsson et al, 2009;Hensler et al, 2007;Yu et al, 2012).…”

Section: Discussionsupporting

confidence: 93%

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Colle

Gressier

Verstuyft

et al. 2015

Journal of Affective Disorders

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Section: Discussionsupporting

confidence: 93%

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Colle

Gressier

Verstuyft

et al. 2015

Journal of Affective Disorders

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“…These results suggest that the adolescent P21–42 period is crucial for the development of the serotonergic system in mice and the BDNF Val66Met SNP is associated with impaired serotonergic development and innervation of the infralimbic prefrontal cortex. These observations are in accordance with previous human and rodent studies showing that BDNF deficiency leads to deficits in serotonergic neuron development (44–49). …”

Section: Resultssupporting

confidence: 93%

“…Previously, the variant BDNF Met allele has been associated with decreased 5-HT 1A receptor binding, as well as SERT density in the cortex and hippocampus in human carriers (44, 45). In accordance, BDNF Met/Met mice exhibit perturbations in the serotonergic system due to reduced trophic support (Figure 3A and B).…”

Section: Discussionmentioning

confidence: 99%

Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice

Dincheva

Yang

et al. 2017

AJP

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Objective Adolescence is a developmental stage in which the incidence of psychiatric disorders, such as anxiety disorders, peaks. Selective serotonin reuptake inhibitors (SSRIs) are the main class of agents used to treat anxiety disorders. However, the impact of SSRIs on the developing brain during adolescence remains unknown. The present study sought to determine the impact of developmentally-timed SSRI administration in a genetic mouse model displaying elevated anxiety-like behaviors. Method Knock-in mice containing a common human SNP (Val66Met; rs6265) in BDNF, a growth factor implicated in the mechanism of action of SSRIs, were studied based on their established phenotype of increased anxiety-like behavior. Timed administration of fluoxetine was delivered during one of three developmental periods (postnatal days (P)21–42, P40–61, or P60–81), spanning the transition from childhood to adulthood. Neurochemical and anxiety-like behavioral analyses were performed. Results We identified a “sensitive period” in peri-adolescence (P21–P42), in which developmentally-timed fluoxetine administration rescued anxiety-like phenotypes in BDNF Val66Met mice in adulthood. Compared to littermate controls, BDNFMet/Met mice exhibited diminished maturation of serotonergic fibers projecting particularly to the prefrontal cortex, as well as decreased expression of the serotonergic trophic factor S100B in the dorsal raphe. Interestingly, deficient serotonergic innervation, as well as S100B levels, were rescued with timed peri-adolescent fluoxetine administration. Conclusions Our findings suggest that SSRI administration during a peri-adolescent “sensitive period” leads to long-lasting anxiolytic effects in a genetic mouse model of elevated anxiety-like behaviors. These persistent effects highlight the role of BDNF in the maturation of the serotonin system, and the capacity to enhance its development through a pharmacological intervention.

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“…Functional studies of SERT function in heterozygous BDNF knockout mice showed a decreased rate of serotonin uptake in the ventral hippocampus (Daws et al, 2007;Guiard et al, 2008). In line with this, a positron emission tomography (PET) study of 25 healthy individuals showed that the val/val genotype was associated with increased SERT binding in men (Henningsson et al, 2009). In addition, a val66met interaction with the 5-HTTLPR (5-HT-transporter-linked promoter region) polymorphism in relation to neuroticism (a risk factor for developing major depression) has been reported (Terracciano et al, 2010).…”

Section: Introductionmentioning

confidence: 81%

Cerebral 5-HT_2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels

Klein

Trajkovska

Erritzoe

et al. 2010

J Cereb Blood Flow Metab

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Recent studies have proposed an interrelation between the brain-derived neurotrophic factor (BDNF) val66met polymorphism and the serotonin system. In this study, we investigated whether the BDNF val66met polymorphism or blood BDNF levels are associated with cerebral 5-hydroxytryptamine 2A (5-HT 2A ) receptor or serotonin transporter (SERT) binding in healthy subjects. No statistically significant differences in 5-HT 2A receptor or SERT binding were found between the val/val and met carriers, nor were blood BDNF values associated with SERT binding or 5-HT 2A receptor binding. In conclusion, val66met BDNF polymorphism status is not associated with changes in the serotonergic system. Moreover, BDNF levels in blood do not correlate with either 5-HT 2A or SERT binding.

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Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men

Cited by 52 publications

References 64 publications

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice

Cerebral 5-HT_2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels

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Genetic Variation in Brain-Derived Neurotrophic Factor Is Associated with Serotonin Transporter but Not Serotonin-1A Receptor Availability in Men

Cited by 52 publications

References 64 publications

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice

Cerebral 5-HT2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels

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Cerebral 5-HT_2A Receptor and Serotonin Transporter Binding in Humans Are Not Affected by the val66met BDNF Polymorphism Status or Blood BDNF Levels