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. CAS The role of 5-HT receptors in depression. Molecular Psychiatry chad a bousman. Xu Z, Jiang H, Zhong P, Yan Z, Chen S, Feng J. The .gov means its official. Zipursky RB, Meyer JH, Verhoeff NP. 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. Malison RT, Price LH, Berman R, van Dyck CH, Pelton GH, Carpenter L, et al. Sci Rep. 2017;7:110. However,effects of prior antidepressant use were not reliably excluded. Interestingly, lower levels of SERT would produce higher levels of synaptic serotonin. However, the theory that serotonin levels are. Monoamine depletion studies: implications for antidepressant discontinuation syndrome. DOI: 10.1038/s41380-022-01661- Journal . In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Mol Psychiatry. Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n=561), and three meta-analyses of overlapping studies examining SERT binding (largest n=1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. Therapeutic Adv Psychopharmacol. We demonstrate the utility of such methods for 5-HT detection, raising the possibility of fast quantification of neurotransmitters secreted from patient-derived live neuronal cells. Serotonin and dopamine transporter binding in children with autism determined by SPECT. Availability of dopamine and serotonin transporters in opioid-dependent users--a two-isotope SPECT study. Generation of functional human serotonergic neurons from fibroblasts. Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling. FOIA : 14-05207-EF-1. 2011;68:444. Altered serotonergic activity is associated with various other mood disorders. Neuropsychopharmacology. 2016;233:11120. Lack of brain serotonin affects postnatal development and serotonergic neuronal . Serotonin 1A receptor availability in patients with schizophrenia and schizo-affective disorder: a positron emission tomography imaging study with [, Frankle WG, Narendran R, Huang Y, Hwang DR, Lombardo I, Cangiano C, et al. 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. Wan J, Wanling P, Li X, Qian T, Song K, Zeng J, et al. We also searched citations and consulted with experts. GlaxoSmithKline. Turn-on near-infrared fluorescent sensor for selectively imaging serotonin. Anal Bioanal Chem. 2008;13:279313. Karg K, Burmeister M, Shedden K, Sen S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited. 2017;6:123. http://creativecommons.org/licenses/by-nc/3.0/. Clin Psychopharmacol Neurosci. Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [. BMJ. Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression. Soliman MA, Aboharb F, Zeltner N, Studer L. Pluripotent stem cells in neuropsychiatric disorders. Kiyohara C, Yoshimasu K. Association between major depressive disorder and a functional polymorphism of the 5-hydroxytryptamine (serotonin) transporter gene: A meta-analysis. Pilkington PD, Reavley NJ, Jorm AF. PET brain imaging with [. 2010;647:906. Report No. The identification of depression and assessment of confounders and interaction effects were limited by the data available in the original studies on which the included reviews and meta-analyses were based. A large body of evidence supports the association between the serotonergic system with MDD and other mood disorders. 2015;234:16471. 2021. https://www.psychiatry.org/patients-families/what-is-psychiatry-menu. Molecular Psychiatry 26 , 2753-2763 ( 2021) Cite this article 1800 Accesses 4 Citations 4 Altmetric Metrics Abstract The serotonergic system in the human brain modulates several physiological. The association between availability of serotonin transporters and time to relapse in heroin users: a two-isotope SPECT small sample pilot study. The serotonin transporter is a key brain protein that modulates the reuptake of the neurotransmitter serotonin from synaptic spaces back into the presynaptic neuron. Thank you for visiting nature.com. Monoamine depletion studies investigate the direct effects of monoamines on mood. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in 2017 Sep; 105:33-41. . PET, positron-emission tomography; SPECT, single photon emission computed tomography; 5-HT, 5-hydroxytryptamine; SERT, serotonin transporter. The serotonin transporter protein (SERT) transports serotonin out of the synapse, thereby lowering the availability of serotonin in the synapse [39, 40]. Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons. Many general practitioners also subscribe to this view [17] and popular websites commonly cite the theory [18]. Am J Psychiatry. Vadodaria KC, Mertens J, Paquola A, Bardy C, Li X, Jappelli R, et al. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in J Clin Psychiatry. STrengthening the REporting of Genetic Association Studies (STREGA) An Extension of the STROBE Statement. Associate Editor. Cell. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. 2014;92:10009. Two meta-analyses of overlapping studies examining the 5-HT1A receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. 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]. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n=1002). Murphy DG, Daly E, Schmitz N, Toal F, Murphy K, Curran S, et al. Nichkova MI, Huisman H, Wynveen PM, Marc DT, Olson KL, Kellermann GH. Zhou Z, Zhen J, Karpowich NK, Law CJ, Reith MEA, Wang D-N. Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures. Border R, Johnson EC, Evans LM, Smolen A, Berley N, Sullivan PF, et al. 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Molecular Psychiatry christoph anacker. Therapeutic Advances in. Google Scholar. The serotonin transporter (SERT) availability for heroin users and controls. 2018;21:95100. Studies of experimental procedures (tryptophan depletion) involving a sham or control condition. Increased serotonin and dopamine transporter binding in psychotropic medication-naive patients with generalized social anxiety disorder shown by. 2014;56:4752. Similarly, early studies based on tens of thousands of participants suggested a statistically significant interaction between the SERT gene, forms of stress or maltreatment and depression [60,61,62], with a small odds ratio in the only study that reported this (1.18, 95% CI 1.09 to 1.28) [62]. Serotonin-1A receptor alterations in depression: A meta-analysis of molecular imaging studies. 2020 Dec;213 Suppl 11:S3-S32.e1. A large systematic umbrella review published in Molecular Psychiatry suggests a lack of consistent evidence linking serotonin and depression, concluding that there is no support for the hypothesis that depression is caused by lowered serotonin activity or concentration. 1Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. A SPECT study found elevated SERT availability in acutely abstinent patients with cocaine dependency.51) The association between serotonin and addiction remains to be elucidated. The biochemistry of affective disorders. 2009;81:9462. 2018;105:13746. Google Scholar. Cowen PJ, Browning M. What has serotonin to do with depression? Delgado PL. Recognition and sensing of low-epitope targets via ternary complexes with oligonucleotides and synthetic receptors. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. Mean differences were converted to effect sizes where appropriate data were available. 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. 2020;25:32138. Kapur S, Remington G. Serotonin-dopamine interaction and its relevance to schizophrenia. This project received funding from the European Unions Horizon 2020 research and innovation program under grant agreement number GrapheneCore3 881603. Serotonin transporter availability in patients with schizophrenia: a positron emission tomography imaging study with [. Google Scholar. In vitro selection of structure-switching, self-reporting aptamers. These two studies consist of by far the largest and most comprehensive study to date [32] and a high-quality meta-analysis that involved a consistent re-analysis of primary data across all conducted studies, including previously unpublished data, and other comprehensive quality checks [27, 59] (see Table1). Many of these headlines have been spurred on by a well-publicized article in Molecular Psychiatry, a detailed review that casts doubt on the antidepressant properties of medications being the. J Anal Toxicol. 2020;20:555361. Altered receptor and/or serotonin transporter (SERT) function may be associated with mental disorders. Schafer JL, Kang J. Berger M, Gray JA, Roth BL. 1990;18:291317. The present umbrella review was reported in accordance with the 2009 PRISMA statement [22]. Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Article Yao F, Peng X, Su Z, Tian L, Guo Y, Kang XF. Accessed March 2, 2021. Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K, et al. Authors of papers were contacted for clarification when data was missing or unclear. Brain serotonin1A receptor binding measured by positron emission tomography with [. How do antidepressants work? 2020;10:2045125320970325. Reduced midbrain serotonin transporter availability in drug-nave patients with depression measured by SERT-specific [(123)I] nor-beta-CIT SPECT imaging. The 5-HT aptamers undergo conformational rearrangement upon target capture and serve as gatekeepers of ionic flux through the nanopipette opening. 2016;7:215. Vadodaria KC, Marchetto MC, Mertens J, Gage FH. Introduction. Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. 2010;1:17785. Although umbrella reviews typically restrict themselves to systematic reviews and meta-analyses, we aimed to provide the most comprehensive possible overview. 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]. Unable to load your collection due to an error, Unable to load your delegates due to an error. ISSN 1359-4184 (print). Only 31% adequately assessed risk of bias in individual studies (a further 44% partially assessed this), and only 50% adequately accounted for risk of bias when interpreting the results of the review. 2020;93:53754. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. We generated human serotonergic neurons in vitro and detected secreted 5-HT using aptamer-coated nanopipettes in a low nanomolar range, with the possibility of detecting significantly lower (picomolar) concentrations. Br J Gen Pract. Studies conducted on trauma-exposed human subjects suggest that differences in trauma type and extent of exposure combine to affect development, maintenance, and treatment of a variety of psychiatric syndromes. This funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Reduced brain serotonin transporter availability in major depression as measured by [. Demasi M, Gtzsche PC. BioRxiv 2020. https://doi.org/10.1101/2020.02.24.962282. On the other hand, another study from our lab indicated that a higher level of SERT availability was associated with a greater likelihood of relapse among former heroin users.49) We speculate, therefore, that serotonin may play a number of roles in heroin addiction. We report ratings of individual items on the relevant measure, and the percentage of items that were adequately addressed by each study (Table1, with further detail in TablesS3 and S4). Serotonin is one of the most important neurotransmitters influencing mental health and, thus, is a potential target for pharmaco-logical treatments. Serotonin transporter binding in bipolar disorder assessed using [. Association between the dexamethasone suppression test and serotonin transporter availability in healthy volunteer: a SPECT with [(123)I] ADAM study. Nucleic Acids Res. We are experimenting with display styles that make it easier to read articles in PMC. Nakatsuka N, Failletaz A, Eggemann D, Forro C, Voros J, Momotenko D. Aptamer conformational change enables serotonin biosensing with nanopipettes. 2022 Sep 28;23(19):11450. doi: 10.3390/ijms231911450. 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. 2022 Oct 7;23(19):11898. doi: 10.3390/ijms231911898. Further research is required to clarify the effects of different drugs on neurochemical systems, including the serotonin system, especially during and after long-term use, as well as the physical and psychological consequences of such effects. Their results are comorbidities, including genes widely explored in psychiatry interesting and reinforce the need for further investigation, and epileptology (Hu and Russek, 2008; Esmail et al., 2015), especially when compared to studies showing the efficacy and could shed light on specific differences between types of of tDCS in depressive . already built in. Reproduced based on Yeh et al. Studies published in full in peer reviewed literature. Bioanal Rev. An official website of the United States government. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. More information: Joanna Moncrieff et al, The serotonin theory of depression: a systematic umbrella review of the evidence, Molecular Psychiatry (2022). Gryglewski G, Lanzenberger R, Kranz GS, Cumming P. Meta-analysis of molecular imaging of serotonin transporters in major depression. We searched for systematic reviews, meta-analyses, and large database studies in these six areas in PubMed, EMBASE and PsycINFO using the Healthcare Databases Advanced Search tool provided by Health Education England and NICE (National Institute for Health and Care Excellence). Perceptions of the biology of depression. SERT binding potential is an index of the concentration of the serotonin transporter protein and SERT concentrations can also be measured post-mortem. Subsequent research has not confirmed an effect with numerous negative studies in volunteers. Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression. University of Michigan . Nat Struct Mol Biol. Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schnemann HJ. Treatment reduces SERT [ 46,47,48 ] to investigate the structure and dynamics of aptamer-ligand complexes, sullivan,. Sj, Lin SH, Yeh TL, Lee IH, Chen PS, et al to systematic and!, actis P. 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