Following the approach of Kennis et al. 2022 Sep 28;23(19):11450. doi: 10.3390/ijms231911450. Johannes Thome 2019;13:113. The serotonin theory of depression: a systematic umbrella review of the evidence. Ten simple rules for conducting umbrella reviews. PubMed Science. The genetic studies, in particular, illustrate the importance of methodological rigour and sample size. : 14-05207-EF-1. RN, raphe nuclei; AC, anterior cingulated cortex; AMY, amygdala; ANG, angular gyrus; DLP, dorsolateral prefrontal cortex; ITG, inferior temporal gyrus; MTG, middle temporal gyrus; STG, superior temporal gyrus; HIP, hippocampus; INS, insular cortex; MFC, medial prefrontal cortex; ORB, orbitofrontal cortex; PC, posterior cingulated cortex; SG, supramarginal gyrus; VLP, ventrolateral prefrontal cortex; VPFC, ventral prefrontal cortex; MPFC, medial PFC; DLPFC, dorsolateral PFC; CIN, cingulate cortex; PHG, parahippocampal gyrus; TEM, temporal cortex; PAR, parietal cortex; OCC, occipital cortex. Fava GA. May antidepressant drugs worsen the conditions they are supposed to treat? Although some earlier meta-analyses of case-control studies showed a statistically significant association between the 5-HTTLPR and depression in some ethnic groups [57, 58], two recent large, high quality studies did not find an association between the SERT gene polymorphism and depression [27, 32]. In vitro selection of structure-switching, self-reporting aptamers. What is quality of evidence and why is it important to clinicians? Areas of research that provided moderate or high certainty of evidence such as the studies of plasma serotonin and metabolites and the genetic and gene-stress interaction studies all showed no association between markers of serotonin activity and depression. Makkonen I, Riikonen R, Kokki H, Airaksinen MM, Kuikka JT. Molecular Psychiatry, 11 (3), 224-226. None of the analyses corrected for multiple testing, and one review was of very low quality [37]. Venkatesan BM, Bashir R. Nanopore sensors for nucleic acid analysis. Vadodaria KC, Ji Y, Skime M, Paquola AC, Nelson T, Hall-Flavin D, et al. Last accessed 27th Jan 2009. Healy D. Serotonin and depression. Could psychedelic drugs have a role in the treatment of schizophrenia? FEBS Lett. Article If the results do represent a positive finding that is independent of medication, they would suggest that depression is associated with higher concentrations or activity of serotonin. The association between availability of serotonin transporters and time to relapse in heroin users: a two-isotope SPECT small sample pilot study. The association between addiction and the serotonergic system could be complex, as the direction of its effects remains unclear. In addition, one analysis was of very low quality [37], including not reporting on the numbers involved in each analysis and using one-sided p-values, and one was strongly influenced by three studies and publication bias was present [38]. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. Nichkova MI, Huisman H, Wynveen PM, Marc DT, Olson KL, Kellermann GH. Serotonin, Mental disorders, Positron-emission tomography, Single photon emission computed tomography, Important PET and SPECT radioligands for serotonergic targets (5-HT. Columbia University Irving Medical Center. Ogawa S, Tsuchimine S, Kunugi H. Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: A meta-analysis of historic evidence. 2018;6:115. Recognition and sensing of low-epitope targets via ternary complexes with oligonucleotides and synthetic receptors. 1 and TableS1 for details of the selection process). Lebowitz MS, Ahn W-K, Nolen-Hoeksema S. Fixable or fate? Moreover, the association between serotonin and schizophrenia, which is the most severe psychiatric disorder, has also not been demonstrated by neuroimaging studies. 2012;29:9157. Anal Chem. In vivo hippocampal serotonin dynamics in male and female mice: Determining effects of acute escitalopram using fast scan cyclic voltammetry. Read J, Renton J, Harrop C, Geekie J, Dowrick C. A survey of UK general practitioners about depression, antidepressants and withdrawal: implementing the 2019 Public Health England report. The authors acknowledge Prof. Unwin for sharing the WEC-SPM software package that was used to control the nanopipette instrument and Dr. Alex Colburn for supplying a low-noise current amplifier (University of Warwick). Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers. For example, in another PET study that used the same radioligand, MDD patients using antidepressants had greater 5-HT1A receptor binding potential in the raphe and mesiotemporal cortex than controls and antidepressant-nave patients with MDD; however, receptor binding potential was not significantly different between drug-nave MDD patients and controls.10) All of these earlier studies indicate that serotonin receptors are associated with MDD. Nat Nanotechnol. Authors of papers were contacted for clarification when data was missing or unclear. 2020;12:115. Psychol Methods. Mol Psychiatry. Psychopharmacology. selective 5-ht reuptake inhibitors, 5-ht4 PubMed Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Careers. Anal Chem. In order to cover the different areas and to manage the large volume of research that has been conducted on the serotonin system, we conducted an umbrella review. American Psychiatric Association. Mass Spectrom Rev. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). 1). 2009;81:100026. Reseptor serotonin atau juga dikenal sebagai reseptor 5-hidroksitriptamin atau reseptor 5-HT adalah kelompok dari reseptor terhubung-protein G dan reseptor kanal ion ( ligand-gated ion channels, LGIC) yang ditemukan pada sistem saraf pusat dan sistem saraf tepi. Yao F, Peng X, Su Z, Tian L, Guo Y, Kang XF. 2015;589:172834. 2021. Nano Lett. Pharm Ther. Thank you for visiting nature.com. Proc Natl Acad Sci USA. 2011;9:915. Kemp JJ, Lickel JJ, Deacon BJ. Mol Psychiatry (2022). 2009;6:e1000022. Front Chem. Sharma S, Singh N, Tomar V, Chandra R. A review on electrochemical detection of serotonin based on surface modified electrodes. 1995;115:106470. BioRxiv 2020. https://doi.org/10.1101/2020.02.24.962282. Thank you for visiting nature.com. Psychopharmacology. Behav Res Ther. Molecular Psychiatry margit burmeister. These are important tools that can be used to acquire in vivo brain images and quantitative measurements with regard to the activities of the serotonergic system.3,4). Biosens Bioelectron. Article The serotonin 2A receptor (5-HT 2A R) is extensively expressed in the cerebral cortex where it is believed to play a critical role in perception, cognition, and psychosis. Cochrane Handbook for Systematic Reviews of Interventions version 6.2,. version 6.Cochrane; 2021. In addition to their physiologic actions, amines have been implicated in both acute and chronic anxiety. Moreno FA, Erickson RP, Garriock HA, Gelernter J, Mintz J, Oas-Terpstra J, et al. # 6. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. As with all research synthesis, the findings of this umbrella review are dependent on the quality of the included studies, and susceptible to their limitations. The authors also acknowledge technical assistance from Stephen Wheeler (ETH Zurich). 2016;38:11239. Am J Psychiatry. 5-HT radioligands for human brain imaging with PET and SPECT. Cui L, Lu H, Lee YH. 2015;234:16471. 2014;34:1096103. A liquid chromatographic-tandem mass spectrometric method for the analysis of serotonin and related indoles in human whole blood. Nucleic Acids Res. Voltammetric detection of 5-hydroxytryptamine release in the rat brain. The majority (11/17) of systematic reviews and meta-analyses satisfied less than 50% of criteria. This "progress" of molecular psychiatry,. This is consistent with research on many other biological markers [21]. Article A possible link between depression and the repeat length polymorphism in the promoter region of the SERT gene (5-HTTLPR), specifically the presence of the short repeats version, which causes lower SERT mRNA expression, has been proposed [55]. J Anal Toxicol. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Dankoski EC, Mark Wightman R. Monitoring serotonin signaling on a subsecond time scale. Mol Psychiatry 26, 27532763 (2021). Other explanations for the effects of antidepressants have been put forward, however, including the idea that they work via an amplified placebo effect or through their ability to restrict or blunt emotions in general [19, 20]. MAH is supported by a Clinical Research Fellowship from North East London NHS Foundation Trust (NELFT). Heard,Fred H. Gage&Krishna C. Vadodaria, You can also search for this author in Nikolaus S, Hautzel H, Heinzel A, Mller HW. What Is Psychiatry? Decreased brain serotonin 5-HT1A receptor availability in medication-naive patients with major depressive disorder: an in-vivo imaging study using PET and [carbonyl-11C]WAY-100635. Ann Clin Lab Sci. Molecular Psychiatry chad a bousman. Berger M, Gray JA, Roth BL. Familial risk for mood disorder and the personality risk factor, neuroticism, interact in their association with frontolimbic serotonin 2A receptor binding. A link between lowered serotonin and depression was first suggested in the 1960s [1], and widely publicised from the 1990s with the advent of the Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants [2,3,4]. Several radioligands were also developed for 5-HT2A. The review, published in the journal Molecular Psychiatry, looked at studies examining serotonin and depression involving tens of thousands of people. Matrix effects: the Achilles heel of quantitative high-performance liquid chromatography-electrospray-tandem mass spectrometry. PLoS ONE. We used the following terms in all searches: (depress* OR affective OR mood) AND (systematic OR meta-analysis), and limited searches to title and abstract, since not doing so produced numerous irrelevant hits. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration. Chou YH, Wang SJ, Lin CL, Mao WC, Lee SM, Liao MH. An animal study indicated that acute cocaine self-administration may induce higher levels of SERT availability.50) Evidence in humans is scarce. Fourteen different serotonin receptors have been identified, with most research on depression focusing on the 5-HT1A receptor [11, 34]. The certainty of each study was based on an algorithm that prioritised sample size and uniform analysis using original data (explained more fully in the supplementary material), following suggestions that these are the key aspects of reliability [27, 32]. Ramon-Marquez T, Medina-Castillo AL, Fernandez-Gutierrez A, Fernandez-Sanchez JF. Average causal effects from nonrandomized studies: a practical guide and simulated example. Stem Cell Rep. 2017;6:175769. Therefore, we chose to include meta-analyses that did not involve a systematic review and a large genetic association study on the premise that these studies contribute important data on the question of whether the serotonin hypothesis of depression is supported. the display of certain parts of an article in other eReaders. 2016;21:6270. Clipboard, Search History, and several other advanced features are temporarily unavailable. ISSN 1359-4184 (print), The serotonin theory of depression: a systematic umbrella review of the evidence, https://doi.org/10.1038/s41380-022-01661-0, Global population attributable fraction of potentially modifiable risk factors for mental disorders: a meta-umbrella systematic review, Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs, Associations between the 1438A/G, 102T/C, and rs7997012G/A polymorphisms of HTR2A and the safety and efficacy of antidepressants in depression: a meta-analysis, A systematic review and narrative synthesis of data-driven studies in schizophrenia symptoms and cognitive deficits, Evidence-based umbrella review of 162 peripheral biomarkers for major mental disorders, The genetics of depression: successful genome-wide association studies introduce new challenges, Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions, Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression, Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=207203, https://www.psychiatry.org/patients-families/what-is-psychiatry-menu, www.prozac.com/how_prozac/how_it_works.jsp?reqNavId=2.2, https://www.psychiatrictimes.com/view/psychiatrys-new-brain-mind-and-legend-chemical-imbalance, https://doi.org/10.1038/s41380-020-00870-9, http://creativecommons.org/licenses/by/4.0/, The emergence of psychoanalytical electrochemistry: the translation of MDD biomarker discovery to diagnosis with electrochemical sensing, The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes, Selective Serotonin Reuptake Inhibitor Use in Pregnancy and Protective Mechanisms in Preeclampsia, Effects of chronic fluoxetine treatment on anxiety- and depressive-like behaviors in adolescent rodents systematic review and meta-analysis.
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