TY - JOUR
T1 - The putative role of the relaxin-3/RXFP3 system in clinical depression and anxiety
T2 - A systematic literature review
AU - Wong, Win Lee Edwin
AU - Dawe, Gavin Stewart
AU - Young, Allan H.
N1 - Funding Information:
Allan H. Young declares the following competing interests. Employed by King’s College London; Honorary Consultant SLaM (NHS UK). Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: AstraZeneca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS. Consultant to Johnson & Johnson. Consultant to Livanova. Received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova. Principal Investigator in the Restore-Life VNS registry study funded by LivaNova. Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression”. Principal Investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants”. Principal Investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”. UK Chief Investigator for Novartis MDD study MIJ821A12201. Grant funding (past and present): NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK). Janssen (UK). No shareholdings in pharmaceutical companies.
Funding Information:
Wong, Win Lee Edwin is supported by the National University of Singapore President's Graduate Fellowship. Gavin S. Dawe's research is supported by the Ministry of Education, Singapore, under its Academic Research Fund Tier 3 Award (MOE2017-T3-1-002), and by the National Medical Research Council, Singapore, under its NMRC NUHS Centre Grant (NMRC/CG/M009/2017_NUH/NUHS). Allan H. Young's independent research is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Funding Information:
Wong, Win Lee Edwin is supported by the National University of Singapore President’s Graduate Fellowship . Gavin S. Dawe’s research is supported by the Ministry of Education, Singapore , under its Academic Research Fund Tier 3 Award (MOE2017-T3-1-002), and by the National Medical Research Council, Singapore , under its NMRC NUHS Centre Grant ( NMRC/CG/M009/2017_NUH/NUHS ). Allan H. Young's independent research is funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.
Publisher Copyright:
© 2021 Elsevier Ltd
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - The relaxin-3/RXFP3 system is one of several neuropeptidergic systems putatively implicated in regulating the behavioural alterations that characterise clinical depression and anxiety, making it a potential target for clinical translation. Accordingly, this systematic review identified published reports on the role of relaxin-3/RXFP3 signalling in these neuropsychiatric disorders and their behavioural endophenotypes, evaluating evidence from animal and human studies to ascertain any relationship. We searched PubMed, EMBASE, PsycINFO and Google Scholar databases up to February 2021, finding 609 relevant records. After stringent screening, 51 of these studies were included in the final synthesis. There was considerable heterogeneity in study designs and some inconsistency across study outcomes. However, experimental evidence is consistent with an ability of relaxin-3/RXFP3 signalling to promote arousal and suppress depressive- and anxiety-like behaviour. Moreover, meta-analyses of six to eight articles investigating food intake revealed that acute RXFP3 activation had strong orexigenic effects in rats. This appraisal also identified the lack of high-quality clinical studies pertinent to the relaxin-3/RXFP3 system, a gap that future research should attempt to bridge.
AB - The relaxin-3/RXFP3 system is one of several neuropeptidergic systems putatively implicated in regulating the behavioural alterations that characterise clinical depression and anxiety, making it a potential target for clinical translation. Accordingly, this systematic review identified published reports on the role of relaxin-3/RXFP3 signalling in these neuropsychiatric disorders and their behavioural endophenotypes, evaluating evidence from animal and human studies to ascertain any relationship. We searched PubMed, EMBASE, PsycINFO and Google Scholar databases up to February 2021, finding 609 relevant records. After stringent screening, 51 of these studies were included in the final synthesis. There was considerable heterogeneity in study designs and some inconsistency across study outcomes. However, experimental evidence is consistent with an ability of relaxin-3/RXFP3 signalling to promote arousal and suppress depressive- and anxiety-like behaviour. Moreover, meta-analyses of six to eight articles investigating food intake revealed that acute RXFP3 activation had strong orexigenic effects in rats. This appraisal also identified the lack of high-quality clinical studies pertinent to the relaxin-3/RXFP3 system, a gap that future research should attempt to bridge.
KW - Anxiety
KW - Depression
KW - Neuropeptide
KW - Neuropsychiatric disorder
KW - Relaxin-3
KW - RXFP3
UR - http://www.scopus.com/inward/record.url?scp=85116036558&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2021.09.028
DO - 10.1016/j.neubiorev.2021.09.028
M3 - Review article
AN - SCOPUS:85116036558
SN - 0149-7634
VL - 131
SP - 429
EP - 450
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
ER -