The Roles of Serotonin in Neuropsychiatric Disorders

Pourhamzeh, Mahsa; Moravej, Fahimeh Ghasemi; Arabi, Mehrnoosh; Shahriari, Elahe; Mehrabi, Soraya; Ward, Richard T.; Ahadi, Reza; Joghataei, Mohammad Taghi

doi:10.1007/s10571-021-01064-9

Cited by 183 publications

(107 citation statements)

References 207 publications

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“…Although serotonin has a critical role in the CNS and ENS function, the highest percentage of serotonin is in the gut enterochromaffin cells ( O’Mahony et al, 2015 ). Dysregulation of serotonergic signaling pathways has been previously implicated in many psychiatric and neurological conditions such as pain, sleep problems, appetite and mood variations ( Athar, 2010 ), and disorders like depression, anxiety, schizophrenia, attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), migraine headache, autism spectrum disorders (ASD; Pourhamzeh et al, 2021 ), bipolar disorder (BP) and addictive behavior ( Lin et al, 2014 ). Serotonin depletion has also been implicated in neurodegenerative diseases, such as Alzheimer’s disease, as serotonin levels decrease with age and neuroinflammation processes have been associated with reduction of serotonin precursors in the CNS ( Danilovich et al, 2021 ).…”

Section: Serotonin Deficiency Disordersmentioning

confidence: 99%

Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

et al. 2022

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Serotonin is a phylogenetically ancient compound found in animals, plants, and some bacteria. In eukaryotes, serotonin is synthesized from the aromatic amino acid tryptophan via the key enzymes aromatic amino acid hydroxylase (AAAH) and aromatic amino acid decarboxylase (AAAD). Serotonin is also an intermediate in the melatonin biosynthetic pathway and is involved in several vital functions. In humans, serotonin is produced in the gut and in the brain, is critical in the regulation of multiple body functions, and its depletion has been implicated in multiple neurological disorders including depression and Alzheimer’s disease, as well as other peripheral conditions namely irritable bowel syndrome and fibromyalgia. The serotonin biosynthetic pathway is well described in eukaryotes, but very little is known about this pathway in bacteria. Evidence points to similar pathways since eukaryote-like AAAH and AAAD (and their genes) have been identified in multiple bacteria, even though serotonin production has not yet been detected in most species. Although data on bacterial tryptophan decarboxylase genes are very limited and no bacterial tryptophan hydroxylase genes have been identified to date, evidence suggests that serotonin production in bacteria might occur through different AAAH and AAAD. Substrate promiscuity in these enzymes has been previously reported and seems to be the key aspect in bacterial serotonin synthesis. Considering the human gut microbiota as a potential source of serotonin, further investigation on its biosynthetic pathways in microbes might lead to important discoveries, which may ultimately foster the development of new therapeutic strategies to treat serotonin depletion-related disorders in humans.

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Section: Serotonin Deficiency Disordersmentioning

confidence: 99%

Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

et al. 2022

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“…5-Hydroxytryptamine (5-HT) is an important neurotransmitter in the cerebroenteric nervous system. Studies have shown that 5-HT plays an important role in the regulation of gastrointestinal sensation, movement, and sensitivity; the decrease of its secretion can lead to the relaxation of the esophageal smooth muscle and an increased sensitivity of the esophageal mucosa, as well as to the significant decrease in the blood level of 5-HT in patients with anxiety and depression [ 37 , 38 ]. Further, sleep disturbance and depression promote each other [ 38 ].…”

Section: Nerd and Abnormal Psychological Factorsmentioning

confidence: 99%

“…Studies have shown that 5-HT plays an important role in the regulation of gastrointestinal sensation, movement, and sensitivity; the decrease of its secretion can lead to the relaxation of the esophageal smooth muscle and an increased sensitivity of the esophageal mucosa, as well as to the significant decrease in the blood level of 5-HT in patients with anxiety and depression [ 37 , 38 ]. Further, sleep disturbance and depression promote each other [ 38 ]. A study by Lei et al [ 33 ] found that the prevalence of NERD in patients with sleep disturbance issues was higher than that in patients in the control group.…”

Section: Nerd and Abnormal Psychological Factorsmentioning

confidence: 99%

Progress on the Mechanism of Visceral Hypersensitivity in Nonerosive Reflux Disease

Niu

2022

Gastroenterology Research and Practice

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Nonerosive reflux disease (NERD) is the most common type of gastroesophageal reflux disease (GERD). Its clinical symptoms can recur, and clinical treatment is often ineffective, causing patients severe economic and psychological burden. In recent years, studies that have explored in-depth the pathogenesis of NERD have found that visceral hypersensitivity (VH) plays an important role. VH refers to the phenomenon that viscera react strongly to nociceptive stimuli or produce a negative reaction to physiological stimuli due to the decrease of one’s visceral pain threshold. Studies have found that the VH mechanism in NERD primarily includes abnormal neurotransmitters, the activation of acid-sensitive receptors, and abnormal psychological factors—all of which we review in this article.

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“…Presynaptically located autoreceptors (5-HT 1A,1B,1D ) respond to the regulation of 5-HT release through negative feedback and influence the neuronal firing rate. The 5-HTRs are located within the CNS, PNS, and other tissues, and the exact mechanisms of their action and the effects of stimulation are presented in Table 2 [132,137]. One of the new concepts of depression is that disturbances in integrated allosteric receptor-receptor interactions in highly sensitive 5-HT 1A heteroreceptor complexes may contribute to the induction of major depression (MD).…”

Section: Serotonin Receptors and Transportersmentioning

confidence: 99%

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

et al. 2021

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Statins are among the most widely used drug classes in the world. Apart from their basic mechanism of action, which is lowering cholesterol levels, many pleiotropic effects have been described so far, such as anti-inflammatory and antiatherosclerotic effects. A growing number of scientific reports have proven that these drugs have a beneficial effect on the functioning of the nervous system. The first reports proving that lipid-lowering therapy can influence the development of neurological and psychiatric diseases appeared in the 1990s. Despite numerous studies about the mechanisms by which statins may affect the functioning of the central nervous system (CNS), there are still no clear data explaining this effect. Most studies have focused on the metabolic effects of this group of drugs, however authors have also described the pleiotropic effects of statins, pointing to their probable impact on the neurotransmitter system and neuroprotective effects. The aim of this paper was to review the literature describing the impacts of statins on dopamine, serotonin, acetylcholine, and glutamate neurotransmission, as well as their neuroprotective role. This paper focuses on the mechanisms by which statins affect neurotransmission, as well as on their impacts on neurological and psychiatric diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), vascular dementia (VD), stroke, and depression. The pleiotropic effects of statin usage could potentially open floodgates for research in these treatment domains, catching the attention of researchers and clinicians across the globe.

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The Roles of Serotonin in Neuropsychiatric Disorders

Cited by 183 publications

References 207 publications

Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

Enzyme Promiscuity in Serotonin Biosynthesis, From Bacteria to Plants and Humans

Progress on the Mechanism of Visceral Hypersensitivity in Nonerosive Reflux Disease

The Effects of Statins on Neurotransmission and Their Neuroprotective Role in Neurological and Psychiatric Disorders

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