Evidence map›Paper›PMID 26509115›Full record

ArticleNeuroImage. Clinical2015

The 5-HTTLPR variant in the serotonin transporter gene modifies degeneration of brain regions important for emotion in behavioral variant frontotemporal dementia.

Jennifer S Yokoyama, Luke W Bonham, Virginia E Sturm, Babu Adhimoolam, Anna Karydas, Giovanni Coppola, Bruce L Miller, Katherine P Rankin

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NeuroImage. Clinical, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
0.4field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
  5. Review
  6. Article
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jennifer S YokoyamaDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Luke W BonhamDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Virginia E SturmDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Babu AdhimoolamDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Anna KarydasDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Giovanni CoppolaDepartments of Neurology and Psychiatry, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
Bruce L MillerDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
Katherine P RankinDepartment of Neurology, Memory and Aging Center, University of California, San Francisco, San Francisco, CA 94158, USA.
University of California, San Francisco · USUniversity of California, Los Angeles · US

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Transgenic Mouse Models of Tau PathologiesP01AG017586 · NIA · UNIVERSITY OF PENNSYLVANIA · PI LEE, VIRGINIA M · 2000 to 2021
$37.3M
PrPSc SPECIFIC INTERACTION WITH NOVEL PrP-Fc FUSION PROTEINSP50AG023501 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, YADONG · 2004 to 2018
$27.1M
Attention and Semantic Evaluation as Predictors of Empathy in Healthy Aging and Frontotemporal DementiaRF1AG029577 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RANKIN, KATHERINE P · 2019 to 2019
$4.0M
Measuring Altered Social Behavior in Neurodegenerative DiseaseR01AG029577 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RANKIN, KATHERINE P · 2008 to 2018
$3.6M
Identifying the Neural Basis and Functional Role of Emotional Empathy in DementiaK23AG040127 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STURM, VIRGINIA EMILY · 2012 to 2016
$713k
RNA signatures of frontotemporal dementia and ALS due to C9ORF72 expansionK01AG049152 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YOKOYAMA, JENNIFER S · 2015 to 2019
$648k
NIA NIH HHS K01 AG049152NIA NIH HHS K01-AG049152NIA NIH HHS K23 AG040127NIA NIH HHS P01 AG017586NIA NIH HHS P01 AG019724NIA NIH HHS P50 AG023501NIA NIH HHS P50-AG03006NIA NIH HHS RF1 AG029577
6 · The paper itself

Abstract

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. 5-HTTLPR-s modifies the serotonergic systems that support emotion and behavioral regulation by reducing gene expression, which slows the reuptake of serotonin, and is associated with distinct morphological and functional effects. Serotonergic systems are also shown to be dysfunctional in behavioral variant frontotemporal dementia (bvFTD), a disease characterized by marked socioemotional dysfunction. However, studies of 5-HTTLPR-s effects in bvFTD have been inconsistent. Our objective was to investigate the patterns of gray matter volume by 5-HTTLPR-s genotype in both healthy older controls and bvFTD patients. We performed voxel-based morphometry of 179 cognitively normal older adults and 24 bvFTD cases to determine brain changes associated with dose (0/1/2) of 5-HTTLPR-s allele. 5-HTTLPR-s frequency did not differ between controls and bvFTD. We found a significant interaction effect whereby carrying more 5-HTTLPR-s alleles in bvFTD was associated with smaller volume in left inferior frontal gyrus (T = 4.86, PFWE = 0.03) and larger volume in right temporal lobe (T = 5.01, PFWE = 0.01). These results suggest that the 5-HTTLPR-s allele differentially influences brain morphology in bvFTD. We propose that patients with bvFTD and 5-HTTLPR-s have altered volumes in regions that support socioemotional behavior, which may be a developmental or disease-related compensation for altered serotonergic activity.

Indexed as

AgedAged, 80 and overFemaleFrontotemporal DementiaGene FrequencyGenetic VariationGenotypeGray MatterHumansImage Processing, Computer-AssistedMagnetic Resonance ImagingMaleMiddle AgedMood DisordersPsychiatric Status Rating ScalesSerotonin Plasma Membrane Transport ProteinsSerotonin Plasma Membrane Transport ProteinsSLC6A4 protein, humanAmygdalaEmotionFrontotemporal dementiaNeurodegenerationSerotonin transporter geneStructural MRI

Identifiers

PMID26509115
PMCPMC4576414
OpenAlexW2130435769

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.