ArticleThe international journal of neuropsychopharmacology2014
Familial risk for major depression is associated with lower striatal 5-HT₄ receptor binding.
Erratum issuedOpen access · bronzeAbstract read
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Article in The international journal of neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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30citing papers in PubMed
2.6field-weighted citation impact, top 11% of its field
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
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- Chronic, combinatorial targeting of NMDARs and 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Sex hormones and serotonin 4 receptor brain binding in men with and without major depressive disorder.Neuroscience applied · 2025Article
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- No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.Clinical epigenetics · 2024Article
- The Serotonin 4 Receptor Subtype: A Target of Particular Interest, Especially for Brain Disorders.International journal of molecular sciences · 2024Review
- Striatal Serotonin 4 Receptor is Increased in Experimental Parkinsonism and Dyskinesia.Journal of Parkinson's disease · 2024Article
- Low-grade inflammation and serotonin 4 receptor binding in the healthy and the depressed brain.Neuroscience applied · 2024Article
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
- Stress Hormone Dynamics Are Coupled to Brain Serotonin 4 Receptor Availability in Unmedicated Patients With Major Depressive Disorder: A NeuroPharm Study.The international journal of neuropsychopharmacology · 2023Article
- Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression-a NeuroPharm study.Translational psychiatry · 2023Article
- Serotonin 4 Receptor Brain Binding in Major Depressive Disorder and Association With Memory Dysfunction.JAMA psychiatry · 2023Article
- Latest updates on the serotonergic system in depression and anxiety.Frontiers in synaptic neuroscience · 2023Review
- The Roles of Serotonin in Neuropsychiatric Disorders.Cellular and molecular neurobiology · 2022Review
- Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study.Translational psychiatry · 2022Article
- Cold-Blooded and on Purpose: A Review of the Biology of Proactive Aggression.Brain sciences · 2021Review
- 5-HTACS chemical neuroscience · 2021Article
- Translating the promise of 5HTPsychological medicine · 2021Review
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
Corrections and comments
- Erratum issuedErratum.2016
Authors and funding
10 authors at 3 institutions in 1 country.
Karine MadsenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Eva TorstensenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Klaus K HolstNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Mette E HaahrNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Ulla KnorrNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Vibe G FrokjaerNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Malene Brandt-LarsenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Pernille IversenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Patrick M FisherNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen).
Gitte M KnudsenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Torstensen, Holst, Haahr, Frokjaer, Fisher, and Knudsen); Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Drs Madsen, Holst, Haahr, Frokjaer, Iversen, Fisher, and Knudsen); Department of Biostatistics, University of Copenhagen, Denmark (Dr Holst); Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Knorr); PET and Cyclotron Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Dr Brandt-Larsen); Center for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark (Dr Iversen). gmk@nru.dk.
Copenhagen University Hospital · DKRigshospitalet · DKUniversity of Copenhagen · DK
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe 5-HT4 receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT4 receptor's in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [(11)C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD.
methodsWe studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first-degree relatives treated for MDD.
resultsWe found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012).
conclusionsOur data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression, and that lower striatal 5-HT4 receptor binding is associated with increased risk for developing MDD. The finding is intriguing considering that the 5-HT4 receptor has been suggested to be an effective target for antidepressant treatment.
Indexed as
Genetic Predisposition to DiseaseAdultAgedAged, 80 and overBrainCarbon RadioisotopesFamilyFemaleHumansMajor Depressive DisorderMaleMiddle AgedPiperidinesPositron-Emission TomographyProtein BindingRadiopharmaceuticalsCarbon RadioisotopesPiperidinesRadiopharmaceuticalsReceptors, Serotonin, 5-HT4SB 207145Serotonin Plasma Membrane Transport ProteinsSLC6A4 protein, human5-HT4 receptordepressionMDDPETserotonin
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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 Socratic graph.