Role Of Serotonin In Depression Research Articles

Re-analysis of a meta-analysis about tryptophan and depression

This is a reanalysis of a meta-analysis about L-tryptophan blood levels and depression, which became part of the controversy around a recent umbrella review about the role of serotonin in depression. The reanalysis revealed major methodological limitations, raising doubts on the conclusions in the original publication that levels of tryptophan are lowered among depressed compared to non-depressed individuals. The data is also compatible with a null effect and no firm conclusion should be made.

Commentary: Recent disputes on the role of serotonin in depression.

Commentary: Recent disputes on the role of serotonin in depression.

Serotonin and Depression: Scrutiny of New Targets for Future Anti-Depressant Drug Development.

The "serotonin hypothesis of depression" is approximately fifty years old, and in spite of vast literature, the exact role of serotonin in depression pathophysiology is still unclear, as whether a lower serotonin level causes depression or depression causes a reduction in serotonin level has become a tough challenge for researchers to understand the actual involvement of serotonin in depression. Several pre-clinical and clinical studies have illustrated the multi-faceted signalling action of serotonin in depression and vouch for the significant or unavoidable role of serotonin in depression. In this review, the journey of the serotonin hypothesis of depression from the 1950s to the present time has been analysed to understand the serotonin hypothesis of depression and investigate the new molecular targets for the development of new future anti- depressants. The old and new theories of possible cellular mechanisms found to be involved in the pathophysiology of major depression or stress, such as polymorphism of serotonin transporters, enzyme modulating serotonergic activity, reduction in the level of serotonin and involvement of different sub-types of receptors, have been discussed in the respective review. Thus, in this review, the new signature targets to increase serotonin levels have been identified, which would help the researcher in the drug development of new faster-acting antidepressants.

Detecting Pharmacologically Induced Serotonin Release in Depression With Positron Emission Tomography Imaging: A New Approach

In the current issue of Biological Psychiatry, Erritzoe et al. ( 1 Erritzoe D. Godlewska B.R. Rizzo G. Searle G.E. Agnorelli C. Lewis Y. et al. Brain serotonin release is reduced in patients with depression: A [11C]Cimbi-36 positron emission tomography study with a d-amphetamine challenge. Biol Psychiatry. 2023; 93: 1089-1098 Abstract Full Text Full Text PDF Scopus (5) Google Scholar ) used positron emission tomography (PET) imaging of the 5-HT2A receptor agonist [11C]Cimbi-36 in combination with a d-amphetamine challenge to demonstrate for the first time lower, on average, capacity for serotonin release in the frontal cortex of participants with major depressive disorder or comorbid depression with Parkinson’s disease compared with demographically similar healthy control subjects. There has been some recent controversy regarding the role of serotonin in depression, with an umbrella analysis, a meta-analysis of meta-analyses, disputing the serotonin hypothesis of depression ( 2 Moncrieff J. Cooper R.E. Stockmann T. Amendola S. Hengartner M.P. Horowitz M.A. The serotonin theory of depression: A systematic umbrella review of the evidence [published online Jul 20]. Mol Psychiatry. 2022; Crossref Scopus (105) Google Scholar ), generating discussion, pro and con, in both the scientific community and the general media. The umbrella analysis cites data from many studies using many modalities, but no studies that include in vivo PET imaging of the brain to infer capacity for serotonin release. This is not because such data were ignored, but rather because they didn’t exist, as a method for reliably and robustly quantifying serotonin release with PET had not yet been developed at the time the literature search was performed in that study. In 2020, Erritzoe et al. ( 3 Erritzoe D. Ashok A.H. Searle G.E. Colasanti A. Turton S. Lewis Y. et al. Serotonin release measured in the human brain: A PET study with [11C]Cimbi-36 and d-amphetamine challenge. Neuropsychopharmacology. 2020; 45: 804-810 Crossref PubMed Scopus (20) Google Scholar ) published a demonstration, for the first time, of an approach to reliably detect pharmacologically induced cortical serotonin release in humans. In their new article ( 1 Erritzoe D. Godlewska B.R. Rizzo G. Searle G.E. Agnorelli C. Lewis Y. et al. Brain serotonin release is reduced in patients with depression: A [11C]Cimbi-36 positron emission tomography study with a d-amphetamine challenge. Biol Psychiatry. 2023; 93: 1089-1098 Abstract Full Text Full Text PDF Scopus (5) Google Scholar ), they’ve applied this approach in a sample of participants with depression. This methodological breakthrough did not come about by implementation of new technology but rather from combining existing methods and ideas in a novel way. SEE CORRESPONDING ARTICLE ON PAGE 1089 SEE CORRESPONDING ARTICLE ON PAGE 1089 Brain Serotonin Release Is Reduced in Patients With Depression: A [11C]Cimbi-36 Positron Emission Tomography Study With a d-Amphetamine ChallengeBiological PsychiatryVol. 93Issue 12PreviewThe serotonin hypothesis of depression proposes that diminished serotonergic (5-HT) neurotransmission is causal in the pathophysiology of the disorder. Although the hypothesis is over 50 years old, there is no firm in vivo evidence for diminished 5-HT neurotransmission. We recently demonstrated that the 5-HT2A receptor agonist positron emission tomography (PET) radioligand [11C]Cimbi-36 is sensitive to increases in extracellular 5-HT induced by an acute d-amphetamine challenge. Here we applied [11C]Cimbi-36 PET to compare brain 5-HT release capacity in patients experiencing a major depressive episode (MDE) to that of healthy control subjects (HCs) without depression. Full-Text PDF

Creation of the viral vectors for the inhibition of the serotonergic neurons using light sensitive proton pump

Depression is the most frequently diagnosed psychiatric disease in Western countries. Although a variety of pharmacological treatments for this disorder are available, a significant proportion of patients is treatment-resistant and/or suffer from side effects. There is a growing need for a complex understanding of the underlying pathogenic mechanisms in the neural circuits and effort for developing novel therapies for the depression. The role of serotonin in depression and antidepressant treatment remains unclear despite decades of research. New optogenetic tools for manipulation of neuronal activity have enabled the investigation of the contribution of distinct neural circuit elements to the pathogenesis of depression. In this study, we used the specific lentiviral vectors for the inhibition of serotonergic neurons. The proton pump archaerhodopsin-3 (eArchT3.0) has been expressed in the serotonergic neurons under the control of tryptophan hydroxylase 2 promotor. Green light stimulation of eArchT3.0 expressing neurons led to a reduced percentage of c-Fos expressing cells among thоse neurons, which indicates a decrease in their activity.

Dose dependent effects of serotonergic agents on anxiety.

The role of serotonin in depression and anxiety is still highly controversial. In this experiment the effect of two substances upon anxiety was studied in rats. Forty adult (45-55 weeks old) male Wistar rats were used to study the following behavioral parameters on elevated plus maze test: open arm and closed arm entries; open arm, closed arm and central square activity duration, open arm preference and total distance traveled. A single injected dose of the antidepressant fluoxetine had no significant effect on animals' activity in the open-arm test, neither in a small dosage (5 mg/kgbw) nor in a higher one (10 mg/kgbw), whereas a single high dose of buspirone significantly impeded the open-arm activity of the rats. None of the substances influenced the general locomotor activity significantly, but the higher doses of buspirone mainly blocked the closed-arm entries and they even decreased the total distance traveled. Acute fluoxetine and buspirone administration influenced the rats' behavior in the elevated plus-maze test in a dose dependent manner. Anxiolytic effects occur after small doses but anxiogenic-like effects were noticed in rodents when higher doses were used.

The Role of Serotonin in Depression and Clotting in the Coronary Artery Disease Population

Despite the strong evidence that depression is an independent risk factor for coronary artery disease (CAD), the underlying physiological mechanisms linking depression and CAD remain poorly understood. This review of the literature focuses on the current understanding of the physiological effects of serotonin on depression and clotting as well as its role in CAD. Articles for this review were identified using CINAHL, PsychINFO, and MEDLINE searches. Results revealed that depression is an independent risk factor for CAD. Although the physiological mechanisms underlying depression and related increases in acute coronary events remain unclear, serotonin plays an important role in depression and CAD. Elevated platelet serotonin levels promote clotting, which may be a potential underlying mechanism linking depression with CAD. This review of the literature suggests that elevated platelet serotonin levels may be associated with depression and the occurrence of major adverse coronary events. Future research should investigate if platelet serotonin levels contribute at least in part to the acute coronary events seen in patients with CAD who have elevated levels of platelet serotonin when depressed.

No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.

Physiology to functionality: the brain and neurotransmitter activity.

The monoamine hypothesis of depression proposes that the biological basis for depression is a deficiency in the neurotransmitters serotonin or noradrenaline, or both. Over the past 30 years this hypothesis has been refined as more experimental and clinical evidence has emerged. The selective serotonin reuptake inhibitors in particular have made a significant contribution to our understanding of the role of serotonin in depression. Our knowledge of the noradrenergic system is less complete, mainly because, until recently, no equivalent agents were available for this system. With the advent of reboxetine, the first selective noradrenaline reuptake inhibitor, attention is again focusing on the role of noradrenaline in depression. To an extent, the action of the selective inhibitors can be predicted through knowledge of the neuroanatomy of the central and peripheral nervous systems. With regard to depression, the most important pathways are those of the serotonergic and noradrenergic neurones projecting to the prefrontal cortex, from the raphe nucleus and locus coeruleus, respectively. However, increasing the levels of the monoamines in the central nervous system affects many other pathways and a wide range of serotonin and adrenergic receptors, leading to a multiplicity of potential beneficial and adverse events. In addition, the complex intracellular responses are beginning to be examined, again with the aid of the selective antidepressants.

The role of serotonin in depression and anxiety

The different coping responses to three types of aversive events - future threats, acute events and chronic stress - may be modulated by 5HT projections. Dysfunction in these coping mechanisms could cause, respectively: generalised anxiety disorder, panic, and depression. This theory proposes that dorsal raphe nucleus projections to 5HT(2) and 5HT(1D) receptors mediate anticipatory anxiety and normally motivate avoidance of threats. The brain aversion system may be held in check by dorsal raphe nucleus 5HT projections to mediate behavioural inhibition during anticipatory anxiety. Proximal aversive stimuli such as pain and asphyxia elicit the fight-flight reflex mediated by the amygdala-hypothalamic-periaqueductal grey brain aversion system. Panic attacks may thus be due to spontaneous activation of this system. Median raphe projections to 5HT(1A) receptors have been implicated in adaptation to chronic stress-resilence. There is good evidence that 5HT(1A) function breaks down in depression and causes the depressed state. Experimental tests of this theory suggest that viewing anxiety, panic, and depression as dysfunctions in neurochemically and anatomically specific coping systems is heuristically useful.

The role of serotonin in depression and anxiety.

Although many serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified, our knowledge of many of the subtypes is limited. However, we do know that 5-HT1A agonists are involved in the treatment of certain anxiety disorders, that 5-HT1C and 5-HT2 receptor antagonists may be indicated for the treatment of generalized anxiety disorder, and that 5-HT1D receptor agonists are used in the treatment of migraine. Recent research has identified that various abnormalities in serotonergic function are involved in the pathogenesis of depression and anxiety, and has facilitated the development of new pharmacological agents with great therapeutic potential, for example the selective serotonin reuptake inhibitors (SSRIs). These agents appear to be effective in the treatment of many anxiety states and may have greater efficacy than other agents in the treatment of certain affective disorders. As the central serotonergic system continues to be "mapped", newer and more selective drugs are likely to be introduced, thereby possibly improving the overall successful management of depression and anxiety disorders.

Animal study on the role of serotonin in depression

1. In our series of experiments the role of serotonin in human depression was studied by using animal models of depression. 2. The results of these studies support the hypothesis that some types of human depression may be primarily due to an excessive transmission of serotonin at the synapse.

Role of Serotonin in Depressiona

Annals of the New York Academy of SciencesVolume 600, Issue 1 p. 486-499 Role of Serotonin in Depressiona HERBERT Y. MELTZER, HERBERT Y. MELTZER Department of Psychiatry Case Western Reserve University School of Medicine Cleveland, Ohio 44106Search for more papers by this author HERBERT Y. MELTZER, HERBERT Y. MELTZER Department of Psychiatry Case Western Reserve University School of Medicine Cleveland, Ohio 44106Search for more papers by this author First published: October 1990 https://doi.org/10.1111/j.1749-6632.1990.tb16904.xCitations: 148 a Supported in part by NIMH grant number MH-41684, MH-41683, MH-41594, grants from the Cleveland Foundation, The Prentiss Foundation, and the Sawyer Foundation. Dr. Meltzer is the recipient of a Research Scientist Award grant number MH-47808. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume600, Issue1The Neuropharmacology of SerotoninOctober 1990Pages 486-499 RelatedInformation

The Role of Serotonin in Depression

The Role of Serotonin in Depression