Serotonin

Serotonin is a monoamine that could be found in plans, animals and human body. The homeostasis of serotonin is maintained by the series of interdependent processes that include synthesis, storage, transport and removal/degradation. In the human body serotonin is synthesized in two independent compartments that are separated by brain-blood barrier. The majority of serotonin is synthesized in enterochromaffin cells of the gastrointestinal tract, released in the blood stream and stored in blood platelets. About 5% of serotonin is synthesized in the brain within serotonergic neurons. As a neurotransmitter serotonin plays an important role in the regulation of physiological functions like body temperature, sleep, vomiting, sexuality, appetite, behaviour and cognitive functions such as learning and memory. The dysfunction of the serotonergic system has been implicated in the aetiology of a variety of psychiatric (depression, schizophrenia, alcoholism) and neurological (migraine, Alzheimer’s disease, epilepsy) disorders. Recent genetic association studies of the neuropsychiatric disorders have focused on functional polymorphisms i.e. DNA sequence variations that alter the expression and/or functioning of the gene product in the loci encoding different genes. Some of them are genes for tryptophan hydroxylase, serotonin transporter and serotonergic receptors

Serotonin

Serotonin is a monoamine that could be found in plans, animals and human body. The homeostasis of serotonin is maintained by the series of interdependent processes that include synthesis, storage, transport and removal/degradation. In the human body serotonin is synthesized in two independent compartments that are separated by brain-blood barrier. The majority of serotonin is synthesized in enterochromaffin cells of the gastrointestinal tract, released in the blood stream and stored in blood platelets. About 5% of serotonin is synthesized in the brain within serotonergic neurons. As a neurotransmitter serotonin plays an important role in the regulation of physiological functions like body temperature, sleep, vomiting, sexuality, appetite, behaviour and cognitive functions such as learning and memory. The dysfunction of the serotonergic system has been implicated in the aetiology of a variety of psychiatric (depression, schizophrenia, alcoholism) and neurological (migraine, Alzheimer’s disease, epilepsy) disorders. Recent genetic association studies of the neuropsychiatric disorders have focused on functional polymorphisms i.e. DNA sequence variations that alter the expression and/or functioning of the gene product in the loci encoding different genes. Some of them are genes for tryptophan hydroxylase, serotonin transporter and serotonergic receptors

Binding of Dihydroergosine to 5-HT1A Receptors of Human and Rat Brain

Interaction of the ergot alkaloid dihydroergosine with the binding of (3H)8-hydroxy-2-(di-n-propylamino)tetralin (3H8-OH-DPAT), a selective agonist for 5-HT1A binding sites, to hippocampal membra-nes isolated from human and rat brain was studied. Competition binding experiments showed that dihydroergosine is a potent dis-placer of (3H)8-OH-DPAT binding at brain 5-HT1A receptors of both species. Scatchard analysis of (3H)8-OH-DPAT binding to rat hippocampal membranes in the presence of dihydroergosine revealed that this ergot compound markedly decreases the number and the affinity of hippocampal (3H)8-OH-DPAT labelled binding sites. Pre-incubation of rat hippocampal membranes for 180 min with dihy-droergosine (2 nmol dm-3) completely prevented the binding of (3H)8-OH-DPAT (2 nmol dm-3). The data suggest that dihydroergo-sine is approximately as potent a ligand as 8-OH-DPAT for the hippocampal 5-HT1A receptors from human and rat brains, although their kinetics of association and dissociation are apparently different

Thyroid Activity in Patients with Major Depression

Hypothalamus-pituitary-thyroid (HPT) axis dysfunction has been associated with pathophysiology of major depression. The aim of the study was to determine serum levels of total 3,5,3’-triiodothyronine (T3), total thyroxine (T4) and thyroid-stimulating-hormone (TSH) in patients with major depression and healthy controls. The study included 53 medication-free patients with depression and 49 healthy controls. Exclusion criteria for patients was: other axis-I and axis-II diagnoses, intensive psychotherapy or electroconvulsive therapy, prior clinical and/or laboratory evidence of hypoor hyperthyroidism, alcohol or nicotine dependence, pregnancy, hormone supplement therapy, somatic illnesses (diabetes, renal or hepatic disorders), infections or autoimmune diseases, recent surgical treatment or significantly changed body weight. For controls: the presence of psychiatric disorders and/or thyroid dysfunctions. The diagnosis of major depression was made using structured clinical interview based on DSM-IV criteria. The results showed significantly lower T3 and TSH levels in patients compared to controls. There was no significant difference in T4 values between patients with depression and control subjects. The results showing altered levels of thyroid hormones in depression indicate that further research on thyroid hormone activity can contribute to the better understanding of the biological basis of depression. Based on the high frequency of the subtle neuroendocrine disorders coexisting with depression, the association of thyroid abnormalities and depression should not be underestimated. Future research should identify different behavioral endophenotypes characteristic for depression, which would greatly facilitate delineating the biological phenomena associated with this psychiatric illness

SMOKING AND SCHIZOPHRENIA

Smoking prevalence for schizophrenic patients is higher than this for general population. More than 60% of schizophrenic patients are current smokers, which contributes to excessive mortality in these patients. The reasons for high frequency of both smoking prevalence and heavy smoking in schizophrenic patients is thought to be at least partially related to enhancement of brain dopaminergic activity, which, in turn, results in behavioral reinforcement due to stimulant effects. Smoking stimulates dopaminergic activity in the brain by inducing its release and inhibiting its degradation. There is also evidence that cigarette smoking can reduce deficits relative to dopamine hypofunction in prefrontal cortex. Recent neuroimaging studies have further contributed the evidence of complex influences of cigarette smoking on brain dopaminergic function. It has been suggested that smoking may be an attempt by schizophrenic patients to alleviate cognitive deficits and to reduce extrapyramidal side-effects induced by antipsychotic medication. Cigarette smoke also increases the activity of CYP 1A2 enzymes, thus decreasing the concentration of many drugs, including clozapine and olanzapine. There is also evidence that smoking is associated with increased clearance of tiotixene, fluphenazine and haloperidol. Given the high frequency of smoking in schizophrenic patients, clinicians need to check smoking status in each patient. Schizophrenic patients who smoke may require higher dosages of antipsychotics than nonsmokers. Conversely, upon smoking cessation, smokers may require a reduction in the dosage of antipsychotics

Serum Lipid Levels in Patients with Alzheimer’s Disease

The role of lipids in the aetiology and progress of Alzheimer’s disease (AD) is still unclear. High lipid levels could be one of the risk factors for AD, but no association or even protective effects of high cholesterol levels in the development of the AD were also found. The aim of the study was to determine serum levels of total cholesterol, high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C) and triglycerides (TG) in female patients with AD and in healthy elderly controls. The 50 patients met the diagnostic criteria of probable AD according to the NINDS-ADRDA and DSM-IV criteria. Cognitive impairment was evaluated using the Mini Mental State Examination (MMSE). Patients were subdivided into two groups of 19 patients in the middle (MMSE 10-19) and 31 patients in the late (MMSE 0-9) phase of AD. Psychotic and non-psychotic features, evaluated by means of Neuropsychiatric Inventory, were presented in 13 and 37 patients with AD, respectively. Control group consisted of 58 subjects without cognitive impairment (MMSE >27) and with lipid levels within normal range. Serum lipid levels were determined by the enzymatic colour tests and by the enzymatic clearance assay. Significantly lower lipid levels were found in patients with AD, than in controls. Patients in the late phase of AD had significantly lower entire lipid profile than controls and significantly lower cholesterol and LDL-C levels than patients in the middle stage of AD. There was no difference in lipid levels between patients with and without psychotic features. The significant positive correlations were found between MMSE scores and cholesterol, LDL-C levels and age in all AD patients. The results support the presumption that lipid profile might be connected with the aetiology and progress of AD and showed the association between low serum cholesterol and LDL-C levels and cognitive decline in patients with AD. Further studies are needed to confirm the relationship between lipid levels and cognition, and to validate the lipid profile as a biological marker for the progress of AD

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed

Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

The serotonergic system and cognitive function

Symptoms of cognitive dysfunction like memory loss, poor concentration, impaired learning and executive functions are characteristic features of both schizophrenia and Alzheimer’s disease (AD). The neurobiological mechanisms underlying cognition in healthy subjects and neuropsychiatric patients are not completely understood. Studies have focused on serotonin (5-hydroxytryptamine, 5-HT) as one of the possible cognitionrelated biomarkers. The aim of this review is to provide a summary of the current literature on the role of the serotonergic (5-HTergic) system in cognitive function, particularly in AD and schizophrenia

Platelet serotonin concentration and monoamine oxidase activity in hypothyroid patients

BACKGROUND/AIM: The relationship between the hypothalamic-pituitary-thyroid (HPT) axis and the serotonergic (5-hydroxytryptamine, 5-HT) system is not clear. The aim of the study was to determine platelet biochemical markers (5-HT concentration and monoamine oxidase B, MAO-B, activity) in hypothyroid patients. ----- METHODS: The study included 25 medication-free female hypothyroid patients in postoperative follow-up after total thyroidectomy due to papillary thyroid carcinoma, who had not been treated with synthetic thyroxine (T(4)) for 4 weeks, and 44 age-matched euthyroid healthy women. The platelet 5-HT concentration, platelet MAO-B activity, total T(4) and thyroid-stimulating hormone (TSH) levels were determined using spectrofluorimetric methods, radioimmunoassay and fluoroimmunoassay, respectively. ----- RESULTS: Hypothyroid patients had significantly higher TSH, significantly lower T(4) levels and platelet 5-HT concentrations, and unchanged platelet MAO-B activity than healthy subjects. A positive correlation was found between the 5-HT concentration and platelet MAO-B activity, and between the platelet MAO-B activity and T(4) in control subjects. ----- CONCLUSIONS: Reduced platelet 5-HT concentrations in hypothyroid patients suggests a complex interaction between the 5-HT system and HPT axis activity, which could be related to the frequent occurrence of depressive symptoms in hypothyroid patients. The determination of platelet 5-HT concentrations should be considered a diagnostic tool for the evaluation of depressive symptoms in hypothyroid patients during the hormone withdrawal procedure