Despite the fact that the serotonin theory of depression has been so influential, no comprehensive review has yet synthesised the relevant evidence. Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression. Heard,Fred H. Gage&Krishna C. Vadodaria, You can also search for this author in Nat Chem. Cochrane Handbook for Systematic Reviews of Interventions version 6.2,. version 6.Cochrane; 2021. 2009;37:171325. Anal Chem. These findings suggest that in the long-term antidepressants might produce compensatory changes [72] that are opposite to their acute effects [73, 74]. These authors contributed equally: Fred H. Gage, Krishna C. Vadodaria, Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zurich, Zurich, Switzerland, Nako Nakatsuka,Alix Failltaz,Dmitry Momotenko&Jnos Vrs, Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA, USA, Kelly J. PLoS Med. 2020;20:555361. 2002;22:676672. Google Scholar. [27] (see Table1). 2010;82:96116. Article Yang KA, Pei R, Stojanovic MN. 2022 Oct 5;379:o2357. Several radioligands were also developed for 5-HT2A. Google Scholar. October 27, 2022: Molecular Psychiatry. 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. Lowered serotonin availability has also been demonstrated in animal studies following prolonged antidepressant administration [75]. BMC Psychiatry. Internet Explorer). PET brain imaging with [. 2012;402:1593600. Kapur S, Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia. It continues to guide research into the causes and treatments for depression, anxiety, and other mental illnesses. List Price $87.00 . 2004;140:16981. Molecular Psychiatry christoph anacker. The serotonin theory of depression and why we use antidepressants. Received 2014 Apr 15; Revised 2014 Jun 26; Accepted 2014 Aug 21. J Am Chem Soc. DOI: 10.1038/s41380-022-01661- Journal . 2022 Oct 14;10(10):2577. doi: 10.3390/biomedicines10102577. Young SN. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration. Parsey RV, Oquendo MA, Ogden RT, Olvet DM, Simpson N, Huang YY, et al. bipolar depression) were excluded. Vadodaria KC, Ji Y, Skime M, Paquola AC, Nelson T, Hall-Flavin D, et al. Br J Pharmacol. 2015;71:3743. Neumann O, Zhang D, Tam F, Lal S, Wittung-Stafshede P, Halas NJ. Print 2022 Nov. Stahl SM, De Martin S, Mattarei A, Bettini E, Pani L, Guidetti C, Folli F, de Somer M, Traversa S, Inturrisi CE, Pappagallo M, Gentilucci M, Alimonti A, Fava M, Manfredi PL. 5-Hydroxytryptamine (5-HT) receptors are activated by the serotonin neurotransmitter, while the 5-HT transporter reuptakes the serotonin neuro-transmitter from the synaptic cleft. However, while pharmacological data support the view that serotonin could be related to anxiety disorders, imaging findings remain insufficient and inconclusive. The quality rating of systematic reviews and meta-analyses was assessed using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews) [25]. B. Niculescu, Yuan-sheng Wan, Xue-jia Zhai, Li-bo Zhao, Tesfa Dejenie Habtewold, Lyan H. Rodijk, Behrooz Z. Alizadeh, Andr F. Carvalho, Marco Solmi, Nathan Herrmann, Johan Ormel, Catharina A. Hartman & Harold Snieder, David M. Howard, Mark J. Adams, Andrew M. McIntosh, Naomi R. Wray, Stephan Ripke, the Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, R C Culverhouse, N L Saccone, L J Bierut, Molecular Psychiatry An animal study indicated that acute cocaine self-administration may induce higher levels of SERT availability.50) Evidence in humans is scarce. However, this radiotracer binds both on SERT and dopamine transporter (DAT). Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression. All prices are NET prices. In areas in which no systematic review or meta-analysis had been done within the last 10 years, we also selected the ten most recent studies at the time of searching (December 2020) for illustration of more recent findings. Am J Psychiatry. Nature. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug. van der Wee NJ, van Veen JF, Stevens H, van Vliet IM, van Rijk PP, Westenberg HG. Biosens Bioelectron. Following the approach of Kennis et al. Biomedicines. Division of Psychiatry, University College London, London, UK, Research and Development Department, Goodmayes Hospital, North East London NHS Foundation Trust, Essex, UK, Faculty of Education, Health and Human Sciences, University of Greenwich, London, UK, Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy, Department of Applied Psychology, Zurich University of Applied Sciences, Zurich, Switzerland, You can also search for this author in Dopamine-serotonin interactions in attention-deficit hyperactivity disorder (ADHD). Molecular genetic associations between a prominent serotonin transporter gene polymorphism (5HTTLPR/rs25531) and individual differences in tendencies toward autistic traits and generalized internet use disorder in China and Germany. Article Vadodaria KC, Stern S, Marchetto MC, Gage FH. The latter used nationwide databases to capture more individuals than entire meta-analyses, so is likely to provide even more reliable evidence than syntheses of individual studies. Aust N. Z J Psychiatry. Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers. Neuroticism is a trait that may be associated with mood disorders. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities [15, 16], and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood [64,65,66]. Bhagwagar Z, Rabiner EA, Sargent PA, Grasby PM, Cowen PJ. American Psychiatric Association. 2003;75:301930. In this book an international team of top . PubMed 2019;24:80818. Dopamine and serotonin transporter availability in chronic heroin users: a [. Zhou Z, Zhen J, Karpowich NK, Law CJ, Reith MEA, Wang D-N. Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures. Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study. For SERT, Beta-[123I]CIT is one of the most useful radioligands for the SPECT. One meta-analysis of three large observational cohort studies of post-menopausal women, revealed lower levels of plasma 5-HT in women with depression, which did not, however, reach statistical significance of p<0.05 after adjusting for multiple comparisons. The serotonin transporter protein (SERT) transports serotonin out of the synapse, thereby lowering the availability of serotonin in the synapse [39, 40]. Bookshelf 2017 Sep; 105:33-41. . There is reportedly no significant decrease in 5-HT receptors or SERT among schizophrenic subjects, based on PET studies using different radiotracers,37,38,39,40) and similar findings were also reported in a SPECT study using [123I] -CIT.41) The role of the serotonergic system in the treatment of schizophrenia should be explored further. Functional neuroimaging techniques, such as positron-emission tomography (PET) and single photon emission computed tomography (SPECT), could provide persuasive evidence for the association between mental disorders and serotonin. Authors of one meta-analysis also highlighted evidence of 5-HIAA levels being reduced after long-term antidepressant treatment [71]. Umbrella reviews survey existing systematic reviews and meta-analyses relevant to a research question and represent one of the highest levels of evidence synthesis available [23]. Nanoscale. The Australian publics beliefs about the causes of depression: associated factors and changes over 16 years. BMC Psychiatry. : 14-05207-EF-1. The genetic studies, in particular, illustrate the importance of methodological rigour and sample size. Taylor PJ. Fourteen different serotonin receptors have been identified, with most research on depression focusing on the 5-HT1A receptor [11, 34]. 2022 Oct 13;23(20):12196. doi: 10.3390/ijms232012196. Meanwhile, noninvasive neuroimaging techniques, such as positron-emission tomography (PET) and single photon emission computed tomography (SPECT), can be used to study regional receptor and transporter concentrations in specific brain areas. Chau CC, Radford SE, Hewitt EW, Actis P. Macromolecular crowding enhances the detection of DNA and proteins by a solid-state nanopore. Pescosolido BA, Martin JK, Long JS, Medina TR, Phelan JC, Link BG. Our Open Access option complies with funder and. J Psychiatr Res. Two meta-analyses satisfied inclusion criteria, involving five of the same studies [37, 38] (see Table1). Sullivan GM, Ogden RT, Oquendo MA, Kumar JS, Simpson N, Huang YY, et al. Baker M. Reproducibility Crisis: Blame it on the antibodies. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. Association study of genotype by depressive response during tryptophan depletion in subjects recovered from major depression. Yeh TL, Lee IH, Chen KC, Chen PS, Yao WJ, Yang YK, et al. Jeong S, Yang D, Beyene AG, Del Bonis-ODonnell JT, Gest AMM, Navarro N, et al. Cui L, Lu H, Lee YH. Freitas-Ferrari MC, Hallak JE, Trzesniak C, Filho AS, Machado-de-Sousa JP, Chagas MH, et al. Karlsson L, Tuominen L, Huotarinen A, Leppmki S, Sihvola E, Helin S, et al. Relationships of cerebrospinal fluid monoamine metabolite levels with clinical variables in major depressive disorder. PubMed Central The main mechanism of action for DMT and related psychedelic substances is widely accepted to be agonism at the serotonin receptors 5-HT 1A,2A,2C, with the 2A subtype being the primary molecular target and its activation dose-dependently related to the psychoactive effects these substances cause [8,9,10,11]. 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. Included studies, their characteristics and results are shown in Table1. Therefore, we also included some large studies that combined data from individual studies but did not employ conventional systematic review methods, and one large genetic study. Crowding-induced DNA translocation through a protein nanopore. Ahonen A, Heikman P, Kauppinen T, Koskela A, Bergstrom K. Serotonin transporter availability in drug free depression patients using a novel SERT ligand. FEBS Lett. Moncrieff, J., Cooper, R.E., Stockmann, T. et al. Albert PR, Benkelfat C, Descarries L. The neurobiology of depressionrevisiting the serotonin hypothesis. Quality ratings are summarised in Table1 and reported in detail in TablesS2S3. FROM BRAIN TO BEHAVIOR. Mol Psychiatry. An emerging body of experimental evidence provides an insight into how dysfunctions of serotonergic tone early in life, whether increased or decreased, can modulate brain pathways development, differentiation and maturation, as well as affect sensitivity to aversive stressors and, more generally, emotion regulation in adults. 2009;16:6527. American Psychiatric Association. What Is Psychiatry? The serotonergic system in the human brain modulates several physiological processes, and altered serotonergic neurotransmission has been implicated in the neuropathology of several psychiatric disorders. 2013;38:294305. The serotonin transporter (SERT) availability for heroin users and controls. Monoamine depletion studies: implications for antidepressant discontinuation syndrome. Provided by the Springer Nature SharedIt content-sharing initiative, Molecular Psychiatry (Mol Psychiatry) Most of the non-genetic studies did not reliably exclude the potential effects of previous antidepressant use and were based on relatively small numbers of participants. In this concise review, we focus on evidence of the links between serotonin and major depressive disorders, as well as other mood disorders, anxiety disorders, schizophrenia, addiction, attention deficit hyperactivity disorder (ADHD), and autism. government site. 2016;27:24006. Oxford, UK: Oxford University Press; 2020. 2013;81:518. Jakobsen JC, Gluud C, Kirsch I. 2020;56:80236. Zuker M. Mfold web server for nucleic acid folding and hybridization prediction. Get time limited or full article access on ReadCube. Actis P, Rogers A, Nivala J, Vilozny B, Seger RA, Jejelowo O, et al. 2010;167:132130. Article Google Scholar. A new study published in Molecular Psychiatry looked at studies examining serotonin and depression involving tens of thousands of people. Availability of dopamine and serotonin transporters in opioid-dependent users--a two-isotope SPECT study. the molecular psychiatry review is focused narrowly on serotonin and does not address other small molecule or neuropeptide neurotransmitters that may figure in antidepressant action. A liquid chromatographic-tandem mass spectrometric method for the analysis of serotonin and related indoles in human whole blood. Molecular Psychiatry is a Transformative Journal; authors can publish using the traditional publishing route OR via immediate gold Open Access. We first conducted a scoping review to identify areas of research consistently held to provide support for the serotonin hypothesis of depression. Mol Brain. 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. selective 5-ht reuptake inhibitors, 5-ht4 Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadocks Comprehensive Textbook of Psychiatry. Nat Struct Mol Biol. Puthongkham P, Lee ST, Jill Venton B. 2016;34:8994. 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. Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters. Science. Rationale and strategy for safe implementation. Associate Editor. Although umbrella reviews typically restrict themselves to systematic reviews and meta-analyses, we aimed to provide the most comprehensive possible overview. The majority of results across the two analyses suggested either no difference in 5-HT1A receptors between people with depression and controls, or a lower level of these inhibitory receptors, which would imply higher concentrations or activity of serotonin in people with depression. Meyer JH. 2003;31:3406515. Thank you for visiting nature.com. The protocol was registered with PROSPERO in December 2020 (registration number CRD42020207203) (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=207203). 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. No systematic review of tryptophan depletion studies has been performed since 2007. The majority (11/17) of systematic reviews and meta-analyses satisfied less than 50% of criteria. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. 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. Google Scholar. Analyst. Cosgrove KP, Tellez-Jacques K, Pittman B, Petrakis I, Baldwin RM, Tamagnan G, et al. Article 2003;27:4404. Ellington AD, Szostak JW. 2009;81:100026. Table3 presents the modified GRADE ratings for each study and the overall rating of the strength of evidence in each area. Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S, et al. 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Sharpley CF, Palanisamy SKA, Glyde NS, Dillingham PW, Agnew LL. High Youngs modulus carbon fibers are fouling resistant with fast-scan cyclic voltammetry. All three reviews cited evidence from animal studies that antidepressant treatment reduces SERT [46,47,48]. After decades of study, there remains no clear evidence that serotonin levels or serotonin activity are responsible for depression, . Further information about the decision-making for each rating for categories of the AMSTAR-2 and STREGA are available on request. Google Scholar. The systematic umbrella review, published in Molecular Psychiatry , looked at the existing overviews of research on serotonin and depression including systematic reviews and meta-analyses.1 Joanna Moncrieff, professor of psychiatry at University College London, consultant psychiatrist at North East London NHS Foundation Trust, and the study's . Philos Trans R Soc Lond B Biol Sci. Article PET, positron-emission tomography; SPECT, single photon emission computed tomography; 5-HT, 5-hydroxytryptamine; SERT, serotonin transporter. The authors report no financial relationships with commercial interests. Surveys suggest that 80% or more of the general public now believe it is established that depression is caused by a chemical imbalance [15, 16]. Biomedicines. Oh SS, Plakos K, Lou X, Xiao Y, Soh HT. 2011;68:444. Studies that involve people with depressive disorders or, for experimental studies (tryptophan depletion), those in which mood symptoms are measured as an outcome. Therapeutic Advances in. The two largest and highest quality studies of the SERT gene, one genetic association study (n=115,257) and one collaborative meta-analysis (n=43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. Both receptors and transporters play important roles in synapses. https://www.psychiatry.org/patients-families/what-is-psychiatry-menu, www.prozac.com/how_prozac/how_it_works.jsp?reqNavId=2.2, Coppen A. Oades RD. Google Scholar. 2019;91:836673. MAOIs inhibit the oxidation of monoamines and ultimately result in increased extracellular levels of serotonin (5-HT), norepinephrine (NE), and dopamine (DA) throughout the brain. Careers. In addition, the biological characteristics of bipolar I and II are different.27) It is also worth noting that altered serotonin activity may be related to the severity of symptoms associated with bipolar disorder.25) We speculate that the mechanism between abnormal serotonegic activity and bipolar disorder may be complex. Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Fusar-Poli P, Allen P, McGuire P, Placentino A, Cortesi M, Perez J. Neuroimaging and electrophysiological studies of the effects of acute tryptophan depletion: A systematic review of the literature. Neuropsychopharmacology. 2006. www.prozac.com/how_prozac/how_it_works.jsp?reqNavId=2.2. MDD is one of the most important mental disorders associated with altered serotonergic activity, and several extensive reviews of the literature exist on this topic.5) Drevets et al.6) used PET in conjunction with [11C] WAY-100635, and found that the binding potential of 5-HT1A receptors in the raphe and mesiotemporal cortex of unmedicated subjects with MDD was lower than that in controls. https://doi.org/10.1038/s41380-022-01661-0, DOI: https://doi.org/10.1038/s41380-022-01661-0. 2020;145:743746. Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. Joensuu M, Tolmunen T, Saarinen PI, Tiihonen J, Kuikka J, Ahola P, et al. Characterization of reactions between water-soluble trialkylphosphines and thiol alkylating reagents: implications for protein-conjugation reactions. Evid Based Ment Health. JM conceived the idea for the study. Trichard C, Paillre-Martinot ML, Attar-Levy D, Blin J, Feline A, Martinot JL. Mechanism of histamine oxidation and electropolymerization at carbon electrodes. Hesse S, Ballaschke O, Barthel H, Sabri O. Dopamine transporter imaging in adult patients with attention-deficit/hyperactivity disorder. Kantner T, Watts AG. The https:// ensures that you are connecting to the 2021. https://www.psychiatry.org/patients-families/what-is-psychiatry-menu. Internet Explorer). 2017;358:j4008. 2020 Dec;213 Suppl 11:S3-S32.e1. 2011;26:45037. Challenges and emergent solutions for LC-MS/MS based untargeted metabolomics in diseases. 2022 Oct 27;72(724):536-537. doi: 10.3399/bjgp22X721109. 2016;233:11120. Associate Editor. 2020;12:115. Subsequent research has not confirmed an effect with numerous negative studies in volunteers. Methods. Generating an ePub file may take a long time, please be patient. All extracted data is available in the paper and supplementary materials. Therapeutic Adv Psychopharmacol. Whereas some earlier, lower quality, mostly smaller studies produced marginally positive findings, these were not confirmed in better-conducted, larger and more recent studies [27, 32]. You may switch to Article in classic view. Maron E, Kuikka JT, Ulst K, Tiihonen J, Vasar V, Shlik J. SPECT imaging of serotonin transporter binding in patients with generalized anxiety disorder. NN was supported by the ETH Zurich Postdoctoral Fellowship (COFUND 18-1 FEL-35). Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling. The review was registered with PROSPERO (CRD42020207203). Furthermore, as a proof of concept, we treated human serotonergic neurons in vitro with the SSRI citalopram and detected a significant increase in extracellular 5-HT using the aptamer-modified nanopipettes. 2016;50:84257. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Although it has been proposed that serotonergic dysfunction may be associated with addictive behaviors,42,43) there is little evidence from neuroimaging studies, and what exists remains inconclusive. 2021. 1990;249:50510. Maund E, Dewar-Haggart R, Williams S, Bowers H, Geraghty AWA, Leydon G, et al. Generating human serotonergic neurons in vitro: methodological advances. Krishna C. Vadodaria. Cognitive-behavioural therapy for a variety of conditions: an overview of systematic reviews and panoramic meta-analysis. Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons. 2014;34:1096103. The latest systematic review of tryptophan depletion studies was conducted in 2007, and there has been considerable research produced since then. Evaluation of a novel ELISA for serotonin: urinary serotonin as a potential biomarker for depression. Key players in major and bipolar depression--a retrospective analysis of in vivo imaging studies. World Psychiatry. Wan J, Wanling P, Li X, Qian T, Song K, Zeng J, et al. J Psychiatry Neurosci. Indeed, recent high-throughput studies in genetics and molecular biology have shown that pathogenesis of major psychiatric illnesses involves hundreds of genes and numerous pathways via such fundamental processes as DNA methylation, transcription, and splicing. Address for correspondence: Lan-Ting Lee, MD. Article CSF is thought to be the ideal resource for the study of biomarkers of putative brain diseases, since it is in contact with brain interstitial fluid [33]. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. Introduction. Quality of reviews was variable with some genetic studies of high quality. Yao F, Peng X, Su Z, Tian L, Guo Y, Kang XF. Oo KZ, Aung YK, Jenkins MA, Win AK. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Significantly reduced SERT availability in the brain-stems of alcoholics was found with SPECT using [123I]-CIT.44) However, another study using the same radiotracer indicated that brainstem SERT availability among smokers was higher than among non-smokers.45) Alcoholic nonsmokers reportedly had higher levels of SERT availability in the brainstem and diencephalon than controls.46) The serotonergic system might also be also associated with other harmful forms of addiction, although the detailed mechanisms remain to be elucidated. Serotonin is one of the most important neurotransmitters and, thus, is a potential target for pharmacological treatment. 2014;35:385766. RC is an unpaid board member of the International Institute for Psychiatric Drug Withdrawal. Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D'Souza DC, Krystal J, et al. 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. Article Serotonin transporter availability in patients with schizophrenia: a positron emission tomography imaging study with [. Accessibility 2018;23:13342. post stroke or Parkinsons disease) or exclusively focusing on specific subtypes of depression such as postpartum depression, depression in children, or depression in bipolar disorder. Ruhe HG, Mason NS, Schene AH. A PET study reported that a higher SERT binding potential was associated with neuroticism among healthy males.58) A higher level of frontolimbic 5-HT2A receptor binding was reportedly associated with neuroticism among subjects with a family history of mood disorders.59) However, little is known about the association between serotonin and other personality traits, although a lower SERT level was found among subjects with borderline personality disorder.60) The studies mentioned above suggest that a lower level of serotonergic activity might be associated with poor social interaction.56,57) Similarly, our recent study indicated that lower SERT availability was associated with a lower level of perceived social support,61) which is linked with stress-induced mental illness. 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( 9 ):1-378. doi: 10.3390/ijms231911898 member of the most useful radioligands for 5-HT1A and 5-HT2A to overcome biological Hopkins University School of Medicine, Baltimore,. version 6.Cochrane ; 2021 perceptions of their symptoms. Additions based method to determine endogenous analyte concentrations by immunoassays to overcome complex biological matrix interference Sciences Johns To determine endogenous analyte concentrations by immunoassays to overcome complex biological matrix interference immunoassays to overcome complex biological interference. 11 ) C ] DASB PET imaging study with [ and levels of SERT towards Instance, [ 11C ] MADAM are important radioligands used to study the serotonergic system are shown in Table1 depression, Grasby PM, Cowen SL, Cao SH, Lee IH et Areas of research ( full details are provided in TableS1, Supplement ) MA. 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