The Chemistry of the Brain
Gail S. Anderson in Biological Influences on Criminal Behavior, 2019
Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant drugs that are used to treat depression and other similar disorders. In general, they increase the levels of serotonin to improve mood and feelings of well-being. They have also been successfully used to reduce impulsive aggression in highly impulsive-aggressive individuals, and although it only completely prevents aggression in 30% of patients, almost half benefit from treatment. Work has shown that for SSRIs to work, the serotonin synaptic function must be working at least partially, as SSRIs attach to serotonin transporters, increasing serotonin levels within the synapse. Evidence suggests that low serotonin transporter numbers predispose to high levels of aggression, so fewer transporters would mean less to which the SSRIs could bind, resulting in blocking serotonin uptake and so reducing serotonin at the synapse. This explains why individuals carrying the S allele of 5-HTTLPR do not respond well to SSRI treatment, as they have lower levels of synthesis of the transporter protein. Neuroimaging studies have shown that SSRIs and other aggression treatments normalize the brain’s overreaction to threatening stimuli (from 122% to less than 0.1%). Selective serotonin reuptake inhibitors are one of the most commonly prescribed psychiatric medications, with a study in a large Swedish population showing that over 14% of all women and 7% of all men were prescribed SSRIs. Several studies have shown decreases in lethal and violent crime in individuals prescribed SSRIs, but controversially, others have shown an increase in violence in both adults and youth. A large Swedish study that included over 850 000 individuals prescribed SSRIs, in comparison with the entire population of the country (almost 8 million), showed a significant increase in violent crime arrests for young people (aged 15–24 years) using SSRIs, but not for other age cohorts, and found a similar association between this age cohort and non-violent criminal arrests, non-fatal accidents, and emergency treatment for alcohol misuse. Other studies have shown that youth and young adults react differently to SSRIs than other age groups, not just in propensity for violence when using such drugs but also in risk for suicide.
Biological Basis of Behavior
Mohamed Ahmed Abd El-Hay in Understanding Psychology for Medicine and Nursing, 2019
In 1948, Maurice Rapport et al. discovered a vasoconstrictor substance in blood serum; they named it serotonin, because it was a serum agent affecting vascular tone. Vittorio Erspamer in 1952 discovered that the substance which he identified in enterochromaffin cells of the gut (enteramine) in the 1930s, is the same as serotonin. About 90 percent of serotonin (5-hydroxytryptamine; 5-HT) is found in the enterochromaffin cells of the gastrointestinal tract and 8–10 percent in platelets, 1–2 percent is present in the central nervous system. Serotonin cannot cross the blood-brain barrier and therefore neural 5-HT is synthesized in situ from the amino acid L-tryptophan in the nerve terminals, that is converted to serotonin by the enzyme tryptophan hydroxylase as well as by an amino acid decarboxylase. Anatomically, most serotonergic cell bodies in the brain are located in the dorsal raphe nucleus in the upper pons and lower midbrain, and send axons to almost every brain region. In the adult brain, the axons of 5-HT neurons innervate a large number of cortical areas, including the entorhinal and cingulate cortices, which contain a moderate to high density of 5-HT receptors. However, of all cortical regions, the frontal lobe is the area richest in serotonergic terminals and 5-HT receptors. Serotonin is implicated in almost every physiological function (appetite and eating, reward, thermoregulation, cardiovascular regulation, locomotion, pain sensitivity, sexuality, sleep–wake cycle, memory, cognition, aggressiveness, responses to stressors, emotion, and mood, and impulse control) and in several human pathologies. Serotonergic dysfunction is thought to be associated with irritable bowel syndrome, restless legs syndrome, sudden infant death syndrome, autism, headache, insomnia, anxiety, depression, anorexia, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. At the present time, most of the anxiolytic and antidepressant drugs such as tricyclic and tetracyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), azapirones, and triptans used to relieve migraine, all target the serotonergic systems. In addition, atypical antipsychotics, e.g., risperidone, olanzapine, clozapine, and quetiapine interact with serotonergic receptors (5-HTA, 5-HTA-2C, 5-HT, and 5-HT). Finally, hallucinogens such as LSD, mescaline, psilocybin, and ecstasy work by attaching to serotonin receptor sites and thereby blocking transmissions in perceptual pathways (Charnay & Léger, 2010). Serotonin exerts its action via specific receptors which are identified as 5HT, 5HT, 5HT, 5HT, 5HT, 5HT, and 5HT. Various subpopulations for several of these receptors have been described. Most of these receptors are coupled to G-proteins that affect the activities of either adenylate cyclase or phospholipase Cβ. The 5HT class of receptors are ion channels (ionotropic receptors). The diversity of 5-HT receptors should eventually allow a better understanding of the different and complex processes in which serotonin is involved. Characteristics of different subtypes serotonin receptors are summarized in Table 5.2 (Charnay & Léger, 2010).
Hallucinogens
G. Hussein Rassool in Alcohol and Drug Misuse, 2017
Three neurotransmitters (the chemical messengers of brain cells): serotonin, dopamine and norepinephrine are involved and their activities are increased with the use of MDMA (Liechti, and Vollenweider 2001). The functions of serotonin are to regulate mood, sleep, pain, appetite and other behaviours. It is this particular neurotransmitter that is involved in the elevation of mood and feeling of euphoria. There is the suggestion that MDMA can cause neurons that are involved with serotonin transmission in animal studies but there are no conclusive studies in humans regarding this effect. There is evidence to suggest that compared to the nonusers, heavy MDMA users had significant impairments in visual and verbal memory (Mathias 1999). The findings of clinical studies suggest that MDMA may increase the risk of long-term, perhaps permanent, problems with memory and learning and that “heavy MDMA users experience long lasting confusion, depression, and selective impairment of working memory and attention processes” (Morgan 1999; Cohen 2001; Verkes et al. 2001; Kish 2002). However, more studies are needed on the potential effects of MDMA on the developing human nervous system and the developed brain.
Serotonin toxicity from isolated bupropion overdoses
Published in Clinical Toxicology, 2020
Alexander M. Sidlak, Karl O. Koivisto, Ryan T. Marino, Michael G. Abesamis
Background: Bupropion is a synthetic cathinone, which acts therapeutically through norepinephrine and dopamine reuptake inhibition. Recent evidence suggests that serotonin receptor activation occurs with high doses of bupropion and severe serotonin toxicity can occur after isolated bupropion overdoses. Prior observational studies may therefore underestimate the incidence of serotonin toxicity. Methods: A retrospective study of patients with bupropion toxicity at a toxicology referral center from 2015–2017 was performed. Patients who overdosed on other serotonergic medications were excluded. Serotonin toxicity was diagnosed retrospectively using Hunter Criteria. Results: Overall, 96 patients were identified with bupropion toxicity. Of these, 18 patients ingested bupropion in the absence of other serotonergic drugs. The incidence of serotonin toxicity was 33% in this population. Serotonin toxicity was more likely after a suicide attempt than those with an accidental ingestion or after recreational drug use. The median dose of bupropion ingested was 2,250 mg in the cohort diagnosed with serotonin syndrome. Conclusion: The incidence of bupropion induced serotonin toxicity is higher than reported. Clinicians should monitor for serotonergic toxicity when evaluating patients after bupropion overdose.
Evaluation of peripheral serotonin content and α
Published in International Journal of Psychiatry in Clinical Practice, 2018
Boris Aleksovski, Antoni Novotni, Viktorija Vujović, Vladimir Rendevski, Nensi Manusheva, Violeta Neceva, Ana Filipce, Aleksandar Risteski, Vasko Aleksovski, Icko Gjorgoski
Objective: We aimed to evaluate the role and the relations between peripheral platelet serotonin content, blood plasma serotonin concentration and the function of platelet α2-adrenergic receptors (α2-AR) as potential state or trait biomarkers for recurrent depressive disorder (RDD). Methods: 26 drug-free patients with life-long RDD and 31 healthy controls were included in the study. Several methodological improvements in blood collection and platelet isolation were implemented following the present standards in Haematology and Light transmission aggregometry. Results: Our results have shown lower platelet serotonin content, higher plasma serotonin concentration and desensitization of platelet α2-AR in patients with RDD. The variables were found heterogeneous and mainly influenced by the clinical characteristics of the current episode. High amplitude of the α2-AR correlated with severe anxious symptoms and high platelet serotonin content (as well as low plasma serotonin levels) were associated with psychotic symptoms. Conclusions: The evaluated peripheral markers reflect only state (but not trait) abnormalities in patients with current severe episode of RDD. The observed peripheral α2-AR and serotonin abnormalities are mutually not related and they are probably triggered by different mechanisms.
Role of the serotonin transporter in pulmonary arterial hypertension
Published in Expert Review of Clinical Pharmacology, 2008
Yvonne Dempsie, Margaret R MacLean
Pulmonary arterial hypertension is a disease in which pulmonary arterial pressure is raised, leading to right heart failure. Survival is poor despite current therapeutic strategies. The ‘serotonin hypothesis of pulmonary arterial hypertension’ arose in the 1960s following an ‘epidemic’ of pulmonary arterial hypertension in women taking the indirect serotinergic agonist aminorex as an anorexigen. In the 1980s, the hypothesis was revisited following the occurrence of pulmonary arterial hypertension associated with the use of fenfluramines as anorexigens; these are also indirect serotinergic agents. Research has identified changes in serotonin synthesis, serotonin receptor activation and serotonin uptake via the serotonin transporter in experimental and clinical pulmonary arterial hypertension. This review will discuss our current understanding of this serotonin hypothesis with particular reference to the role of the serotonin transporter.
Related Knowledge Centers
- Gastrointestinal Tract
- Tryptophan
- Platelet
- Tryptamines
- Cns
- Autacoids
- Serotonin Receptors