TPH2 polymorphisms across the spectrum of psychiatric morbidity: A systematic review and meta-analysis

Neuroscience and Biobehavioral Reviews
Koen Willem OttenhofLinda Booij

Abstract

Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme in brain serotonin synthesis. The TPH2 gene has frequently been investigated in relation to psychiatric morbidity. The aim of the present review is to integrate results from association studies between TPH2 single nucleotide polymorphisms (SNPs) and various psychiatric disorders, which we furthermore quantified with meta-analysis. We reviewed 166 studies investigating 69 TPH2 SNPs in a broad range of psychiatric disorders, including over 30,000 patients. According to our meta-analysis, TPH2 polymorphisms show strongest associations with mood disorders, suicide (attempt) and schizophrenia. Despite small effect sizes, we conclude that TPH2 SNPs in the coding and non-coding areas (rs4570625, rs11178997, rs11178998, rs10748185, rs1843809, rs4290270, rs17110747) are each associated with one or more psychopathological conditions. Our findings highlight the possible common serotonergic mechanisms of the investigated psychiatric disorders. Yet, the functional relevance of most TPH2 polymorphisms is unclear. Characterizing how exactly the different TPH2 variants influence the serotonergic neurotransmission is a next necessary step in understanding the psychiatric disorders wher...Continue Reading

Citations

Jun 20, 2019·Expert Opinion on Therapeutic Targets·Elizabeth A Kulikova, Alexander V Kulikov
Jun 19, 2019·Journal of Psychopharmacology·Eva LatorreLorna W Harries
Dec 7, 2018·Frontiers in Neuroscience·Shiwan TaoZhijian Yao
Feb 1, 2020·Neuroscience and Biobehavioral Reviews·Juan A AriasAndrew H Kemp
Oct 29, 2020·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Leonardo BaldaçaraAntônio G da Silva
Mar 8, 2021·Progress in Neuro-psychopharmacology & Biological Psychiatry·Weam FageeraRidha Joober
Nov 1, 2020·Progress in Neuro-psychopharmacology & Biological Psychiatry·Tatyana StrekalovaDaniel C Anthony
Jul 28, 2020·Infant Behavior & Development·Eeva-Leena KatajaLinnea Karlsson
May 1, 2021·International Journal of Environmental Research and Public Health·Ta-Chuan YehMu-Hong Chen
Jun 22, 2021·Frontiers in Immunology·Heather M Grifka-WalkDouglas J Kominsky
Aug 24, 2021·Frontiers in Behavioral Neuroscience·Melinda A Novak, Jerrold S Meyer

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