Functional Cortical Effects of Novel Allelic Variants of the Serotonin Transporter Gene-linked Polymorphic Region (5-HTTLPR) in Humans

Gallinat, Jürgen; Muller, Danièle; Bierbrauer, Jürgen; Rommelspacher, H.; Juckel, G.; Wernicke, Catrin

doi:10.1055/s-2007-984464

Cited by 7 publications

(2 citation statements)

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“…The other observed genotypes (l A /l G , s/l A , s/l G , s/s) had an LD which was in a similar range but higher than the one observed in the l A /l A genotype. These data provide first evidence for a functional role of these new variants of the 5-HTTLPR in humans and indicate that its functional impact is mainly driven by the presence of the l A /l A genotype compared to all other genotypes [71] . The data offer a rationale to subdivide the l allele of the 5-HTTLPR into l A and l G alleles with respect to their 5-HT activity as indicated by the LD.…”

Section: New Genetic Variation Modifying the 5-httlpr Effects On Protmentioning

confidence: 65%

Genes and Neuroimaging: Advances in Psychiatric Research

Gallinat¹,

Bauer²,

Heinz³

2008

Neurodegener Dis

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Major psychiatric disorders, including schizophrenia, bipolar disorder and substance addiction, are partly heritable and show a multifactorial pattern of heredity. Although the introduction of explicit diagnostic criteria has improved clinical research on psychiatric disorders, the concept is only of limited use for exploring their genetic underpinnings. On the behavioral level, psychopathological symptoms can hardly separate the many pathophysiological subgroups. Contrary to nosological categories, biologically based phenotypes – referred to as intermediate phenotypes – consisting of neuropsychological, electrophysiological, functional and structural brain imaging parameters, could represent the genetic basis more directly. Thus intermediate phenotypes are being targeted in current molecular genetic investigations. In this article, we review existing data on the effects of genetic variation in the dopamine and serotonin systems (catechol-O-methyltransferase, the serotonin-transporter-linked polymorphic region) on the morphometric, metabolic and functional characteristics of the cerebral cortex and limbic structures. The gene-driven modulation of these brain circuits is discussed with regard to their behavioral correlates and their role for psychiatric diseases. Furthermore, recently identified putative susceptibility genes for schizophrenia (neuregulin 1, dysbindin, G72) are briefly discussed.

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Section: New Genetic Variation Modifying the 5-httlpr Effects On Protmentioning

confidence: 65%

Genes and Neuroimaging: Advances in Psychiatric Research

Gallinat¹,

Bauer²,

Heinz³

2008

Neurodegener Dis

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“…The long allele was later stratified into two alleles: La and Lg, based on an A > G substitution in the 5-HTTLPR. However, a functional similarity was noted between Lg and S (Gallinat et al, 2007). The exact relationship between the genotype, expression of 5-HTT and psychiatric/depressive symptomatology however has not been elucidated, with contradictory results seen in the psychiatric literature.…”

Section: Discussionmentioning

confidence: 94%

Imaging serotonergic transmission with [11C]DASB-PET in depressed and non-depressed patients infected with HIV

et al. 2010

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Introduction Site-selective imaging can provide significant insight into the mechanism of HIV-associated neurological disease. The goal of this study was to evaluate the involvement of serotonergic transmission in HIV-associated depression using [11C]DASB, a serotonin transporter (5-HTT)-specific radiopharmaceutical for positron emission tomography (PET). Methods 9 depressed HIV+ subjects (HIV-D), 9 nondepressed HIV+ subjects (HIV-ND) and 7 healthy controls (HC) underwent an MRI scan and a [11C]DASB-PET scan. The outcome measure was 5-HTT binding potential normalized to nondisplaceable tissue radioligand (BPND). Results HIV-ND subjects had lower mean regional 5-HTT BPND estimates across regions, compared to HC, while HIV-D subjects demonstrated higher mean regional binding values than HIV-ND subjects in most regions. Prior to correction for the false discovery rate, HIV-ND had significantly lower BPND values compared to HC subjects in two regions (insula and anterior cingulate) and all HIV+ patients had significantly lower binding than HC in all regions except for the midbrain, thalamus and pons. After correction for the false discovery rate, only the insula showed significantly lower binding in HIV+ subjects compared to HC (P < 0.0045). Despite a significant difference in the duration of illness between the HIV-D and HIV-ND groups, there was no definite correlation between the duration of illness and BPND. Conclusion Lower [11C]DASB binding in HIV+ patients compared to HC may reflect serotonergic neuronal loss as a component of generalized HIV-associated neurodegeneration. Higher mean regional BPND values in HIV-D compared to HIV-ND subjects could reflect increased density of 5-HTT, leading to increased clearance of serotonin from the synapse, which could account, in part, for symptoms of depression. The lack of correlation between duration of illness and binding argues against these findings being the result of differential neurodegeneration only. Our findings suggest a possible role for dysregulated serotonergic transmission in HIV-associated depression.

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Distinct regulation of brain-derived neurotrophic factor and noradrenaline in S100B knockout mice

Schulte‐Herbrüggen

Hörtnagl

Ponath

et al. 2008

Neuroscience Letters

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Functional Cortical Effects of Novel Allelic Variants of the Serotonin Transporter Gene-linked Polymorphic Region (5-HTTLPR) in Humans

Abstract: The data provide a rationale to subdivide the L allele of the 5-HTTLPR into L (A) and L (G) alleles in terms of their serotonin activity as indicated by the LD. The present IN VIVO measurements provide a basis for grouping the L (G) and S alleles for further investigations.

Cited by 7 publications

References 48 publications

Genes and Neuroimaging: Advances in Psychiatric Research

Genes and Neuroimaging: Advances in Psychiatric Research

Imaging serotonergic transmission with [11C]DASB-PET in depressed and non-depressed patients infected with HIV

Distinct regulation of brain-derived neurotrophic factor and noradrenaline in S100B knockout mice

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