The discovery of serotonin was made in 1948 by Irvine Page, Maurice M. Rapport, and Arda Green, who never imagined the important biological roles that this fundamental molecule has in all living beings, from plants to animals and humans. The importance of serotonin in humans lies in the fact that alterations in its neurotransmission can produce various chronic or acute mental illnesses at the central nervous system level. This includes disruptions in its synthesis to its quantum release, the presence and type of receptors, the transporters' functionality, the presence of isoforms, and interactions with other neurotransmitters. Serotonin's participation has been demonstrated in conditions such as autism, schizophrenia, hyperactivity, depression, anxiety, obsessive-compulsive disorder, aggression, insomnia, and stress. This amazing discovery has significantly influenced the fields science, medicine, and researchers within the field of serotonin. Pathological conditions and experimental models in which 5-HT or closely related molecules have been pharmacologically modulated suggest that 5-HT concentration must remain within normal ranges for proper brain function. The versatility of 5-HT is evident in its capacity to produce a range of physiological effect, sometimes even opposing ones, are determined by the receptor subtypes it interacts with and the intracellular signalling pathways coupled to them. Among these, the 5-HT2A receptor is a component of the serotonin system deeply implicated in effects related to psychosis and memory deficits. This intricate involvement poses a significant challenge to unravel its role in patients suffering from these conditions. In a recent bibliometric analysis of schizophrenia and serotonin, we promoted the practical concept of serotoninomics, whose purpose is to find precise answers to basic, clinical, translational, medical, and clinical pharmacological research questions on serotonin.Schizophrenia is a chronic and complicated psychiatric and psychological illness. It is characterised by a set of symptoms that include hallucinations, delusions, speech or behavioural disorders, emotional blunting, anhedonia, alogia, apathy, and other defective cognitive abilities. Schizophrenia is a devastating developmental disorder that arises from the interaction between genetic and environmental factors (1). Several lines of evidence suggest that the serotonergic system plays a critical role in the pathogenesis of schizophrenia in at least a subpopulation of patients. According to the neuropathological changes, this heterogeneous condition has been divided into three main domains: positive symptoms, negative symptoms, and cognitive dysfunction. Additionally, some researchers have conceptualised schizophrenia as a disease of functional "dysconnectivity" (2)(3)(4) or "synapse disorder" (5,6), affecting the serotonin quantum release machinery within the synapse during its synthesis, its interaction with its receptors, or its correlation with other neurotransmitters (i.e. dopamine, glutamate, GABA) (7,8). Acute relapses of this disease are characterised by the exacerbation of positive psychotic symptoms, while chronic disabilities occur due to cognitive causes and negative symptoms (apathy and social withdrawal) (9). The disease profoundly affects not only the individuals who suffer from it but also their families and caregivers, typically manifesting during late adolescence or early adulthood. (1,9).Because the condition is so heterogeneous, the presence of symptoms from these domains in the disease makes its diagnosis and treatment difficult. The development of some mental diseases, including schizophrenia, are marked by subtle molecular, heritable, and epigenetic changes, which initiate a cascade of events within individual cells before overt signs and symptoms manifest themselves. These events include effective quantum release; appropriate signalling by receptors and activation by second messengers; the functionality of transporters; the ability to take up, store, and release serotonin; the presence of isoforms; the activity of tryptophan hydroxylase-2 (TPH2; lack of activity); the availability of the amino acid L-tryptophan (L-Trp); deviation towards other pathways of its metabolism how to as the kynurenine-like pathway; mutations; and other dysfunctions. Therefore, individuals with schizophrenic parents or siblings will have a higher risk of developing the disease due to this hereditary component (between 8% and 12%; (10). The most common theory regarding the neurobiology of schizophrenia is a chemical imbalance in the brain, marked by deregulation of the mesolimbic pathway as a result of dopaminergic hyperactivity and, in some cases, alterations in the serotonergic system in specific nuclei of the brain (prefrontal cortex, temporal cortex, thalamus, hypothalamus, and basal ganglia) or in the interaction between dopamine and serotonin (9).Serotonin is a molecule with numerous functions within the central nervous system (CNS), which is why it plays an essential role in the delicate balance of neuronal function. Alterations in serotonin concentration can contribute to the onset of schizophrenia, and conversely, schizophrenia can gradually affect the serotonergic systems of the brain (11). As the initial molecular and genetic changes progress, often silently and insidiously, these molecular perturbations extend to higher organisational levels: tissues, organs, and systems. In this way, all of these changes will culminate in dysregulations that will contribute to the characteristic symptoms of schizophrenia (i.e. altered perception) (12). A key limitation in the study of schizophrenia is that it is difficult to conclusively determine causation, given the interactive influences exerted by the different molecular and physiological mechanisms involved (9,11,12). Therefore, the understanding of these early molecular events is essential for unravelling schizophrenia's...

Surely, Vittorio Erspamer, discoverer of Enteramine in 1935, and Irvine Page, Maurice M. Rapport and Arda Green, discoverers of Serotonin in 1948, never imagined the biological importance that this fundamental molecule has in the living beings of our planet; from its physiological, passing through endocrine, neural, developmental and reproductive functions and even its role in evolution. For this reason, our workgroup is commemorating these researchers and celebrating their great discovery, which deeply influenced science and medicine, in the present perspective article. As a consequence of their seminal work, and the work of many other researchers in the field of serotonin over the following years, now we stand in front of the practical concept of “Serotoninomics,” which we think will contribute to find out precise answers regarding basic, clinical, and translational research related to serotonin, just as the emerging medical and “omics” sciences have done before.

Background: Schizophrenia is a chronic mental illness that affects millions of individuals worldwide. The etiological origin of schizophrenia is heterogeneous, but it has been shown to be associated with dysfunction in serotonin activity, serotonin receptors, and serotonin metabolism in the brain. Bibliometric analysis is a tool used to scrutinise and analyse research activities and evidence in a specific research area. No existing bibliometric analyses have considered both serotonin and schizophrenia.Methods: We conducted a bibliometric analysis including 12,027 studies related to the schizophrenia–serotonin link published from the inception of the study to 2023 and available in the Scopus database. We used VOSviewer software to identify global trends, analyse the author and editors keywords, the most cited articles and author, as well as the most productive institutes and journals publishing research on schizophrenia–serotonin link.Results: Most publications related to the link between schizophrenia and serotonin are focused on adult humans and examine topics such as antipsychotic agents, depression, and serotonin uptake inhibitors. The Journal of Clinical Psychiatry has published the most papers on the schizophrenia–serotonin relationship. Among nations, the United States is the leader in publications. King’s College London is the institution with the highest number of publications, and H. Y. Meltzer is the most influential author. Growing trends in schizophrenia–serotonin research are personalised medicine, alternative medicine, transcranial magnetic stimulation, artificial intelligence, nervous system inflammation, brain-gut axis, and the gut microbiome.Conclusion: Since 1950, there have been several fluctuations in the number of published studies related to schizophrenia and serotonin. We believe that the development of novel medications and treatments for schizophrenia will be increased in the future, as well as research into genetic risks, psychological factors, and cranial neuroimaging components. Future schizophrenia and serotonin research is likely to focus on personalised medicine, alternative therapies, novel pathogenesis of schizophrenia, and the use of emerging technologies such as artificial intelligence.

Serotoninomics is an expanding field that focuses on the comprehensive study of the serotoninergic system, including serotonin’s biosynthesis, metabolism, and regulation, as well as related scientific methodologies 5-hydroxytryptamine (5-HT). This field explores serotonin’s complex roles in various physiological and pathological contexts. The essential amino acid tryptophan (Trp) is a precursor for several metabolic and catabolic pathways, with the kynurenine (KYN) pathway being particularly significant, representing about 95% of Trp metabolism. In contrast, only a small portion (1–2%) of dietary Trp enters the serotonin pathway. Anthranilic acid (AA), a metabolite in the KYN pathway, has emerged as a potential biomarker and therapeutic target for schizophrenia. Elevated serum AA levels in patients with schizophrenia have been associated with neurotoxic effects and disruptions in neurotransmission, suggesting AA’s critical role in the disorder’s pathophysiology. Furthermore, the 5-HT_2A receptor’s involvement is particularly noteworthy, especially in relation to schizophrenia’s positive symptoms. Recent findings indicate that 5-HT_2A receptor hyperactivity is linked to positive symptoms of schizophrenia, such as hallucinations and delusions. This study investigates serotoninomics’ implications for neuropsychiatric disorders, focusing on AA in schizophrenia and analysing recent research on serotonin signalling pathways and AA’s neurochemical effects. Understanding the roles of the 5-HT_2A receptor and AA in neuropsychiatric disorders could lead to the development of more precise and less invasive diagnostic tools, specific therapeutic strategies, and improved clinical outcomes. Ongoing research is essential to uncover these pathways’ exact mechanisms and therapeutic potential, thereby advancing personalised medicine and innovative treatments in neuropsychiatry.

In mammals, the pineal hormone melatonin is the most powerful pacemaker of the master circadian clock and is responsible for reproduction in seasonal breeders. It is also well known that melatonin and its metabolites play antioxidant roles in many tissues, including reproductive cells. Melatonin synthesis and secretion from the pineal gland occurs during scotophase (the dark phase during a day–night cycle), while its inhibition is observed during photophase (period of light during a day–night cycle). Short-day breeders, such as goats, are stimulated to breed in a manner dependent on high endogenous levels of melatonin. This hormone can be synthesized in various extra-pineal tissues, such as retina, gastrointestinal tract, ovaries, and testis, with its main function being as a local antioxidant, given that melatonin and its metabolites are potent scavengers of reactive oxygen and nitrogen species. Moreover, it has been reported that some functions of melatonin can be exerted through plasma membrane and intracellular receptors expressed in the male reproductive system, including germ cells, immature and mature spermatozoa. It has been shown that melatonin may enhance gamete cryosurvival mainly by its addition into the media and/or in exogenous melatonin treatments in several species. In the present review, the physiological effects of endogenous melatonin in mammals are described, with a deeper focus on caprine reproduction. Additionally, results from recent investigations on the roles of exogenous melatonin aimed at improving the reproductive efficiency of goat bucks are discussed. There are contradictory findings and a limited amount of research available in the field of goat sperm cryopreservation associated with the use of melatonin. Understanding and improving goat reproduction and production is essential for many marginalized human populations around the world who directly depend on goats to maintain and improve their lifestyle.