Evidence map›Paper›PMID 25514753›Full record

Trial reportTranslational psychiatry2014

The functional -1019C/G HTR1A polymorphism and mechanisms of fear.

B Straube, A Reif, J Richter, U Lueken, H Weber, V Arolt, A Jansen, P Zwanzger, K Domschke, P Pauli and 12 more

Open access · goldAbstract readClinical TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Translational psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Review
  6. A neuroeconomic investigation ofAnxiety, stress, and coping · 2020
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. "DNA Methylation signatures in panic disorder".Translational psychiatry · 2017
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Genetic influences on the neural and physiological bases of acute threat: A research domain criteria (RDoC) perspective.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2016
    Review
  20. Neuroimaging of Fear-Associated Learning.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016
    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

22 authors at 9 institutions in 1 country.

B StraubeDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
A ReifDepartment of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
J RichterDepartment of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
U LuekenInstitute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
H WeberDepartment of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
V AroltDepartment of Psychiatry, University of Münster, Münster, Germany.
A JansenDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
P ZwanzgerDepartment of Psychiatry, University of Münster, Münster, Germany.
K DomschkeDepartment of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
P PauliDepartment of Psychology, University of Würzburg, Würzburg, Germany.
C Konrad1] Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany [2] Department of Psychiatry, University of Münster, Münster, Germany.
A L GerlachDepartment of Psychology, University of Cologne, Cologne, Germany.
T Lang1] Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany [2] University of Bremen and Christoph-Dornier Foundation for Clinical Psychology, Bremen, Germany.
T FydrichDepartment of Psychology, Humboldt University, Berlin, Germany.
G W AlpersDepartment of Psychology, Clinical and Biological Psychology, School of Social Sciences, Mannheim, Germany.
A StröhleDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
A WittmannDepartment of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
B PfleidererDepartment of Clinical Radiology, University of Münster, Münster, Germany.
H-U WittchenInstitute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany.
A HammDepartment of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
J DeckertDepartment of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany.
T KircherDepartment of Psychiatry and Psychotherapy, Philipps-University Marburg, Marburg, Germany.
University of Münster · DEUniversity of Würzburg · DEPhilipps University of Marburg · DEUniversität Greifswald · DECharité - Universitätsmedizin Berlin · DETU Dresden · DEDornier Flugzeugwerke (Germany) · DEHumboldt-Universität zu Berlin · DEUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n=185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n=245; after CBT: n=171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n=39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.

Indexed as

AgoraphobiaPanic DisorderAdultAmygdalaCerebral CortexCognitive Behavioral TherapyFearFemaleGenotypeHumansMagnetic Resonance ImagingMaleMiddle AgedReceptor, Serotonin, 5-HT1ATreatment OutcomeHTR1A protein, humanReceptor, Serotonin, 5-HT1A

Identifiers

PMID25514753
PMCPMC4270311
OpenAlexW2018236912

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LicenceCC BY-NC-SA
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Registered trials

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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.