-
Experimental Brain Research Dec 2022This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible... (Review)
Review
This systematic review (SR) was aimed at answering two questions: (1) how sex and ovarian hormones alter behavior associated with cocaine use; (2) which possible neurobiological mechanisms explain behavioral differences. Three different researchers conducted a search in PUBMED for all kinds of articles published between the years of 1991 to 2021 on the theme "reproductive cycle and cocaine", "estrous cycle and cocaine", "menstrual cycle and cocaine", "fluctuation of ovarian hormones and cocaine", "estrogen and cocaine" and "progesterone and cocaine". Sixty original studies were identified and subdivided into experimental rodent studies and clinical trials. Experimental studies were characterized by author/year, species/strain, sex/number, age/weight, dose/route/time of administration, hormonal assessment, or administration. Clinical trials were characterized by author/year, sex/number, age, exclusion criterion, dose/route of administration/time of cocaine, and hormonal assessment. Results gathered showed that rodent females develop increased consumption, seeking behavior, craving, relapse, locomotion, increases in stress and anxiety, among other behavioral alterations during peaks of estrogen. These observations are related to the direct effects played by ovarian hormones (in particularly estradiol), in dopamine, but also in serotonin neurons, and in brain regions such as the tegmental area, the nucleus accumbens, the hypothalamus, the amygdala and the prefrontal cortex. Increased sensitization to cocaine presented by high estradiol females was linked to the activation of a CBR1-mediated mechanism and GABA-A-dependent suppression of inhibitory synaptic activity of the prelimbic prefrontal cortex. Estradiol facilitation of cocaine-increased locomotion and self-administration was shown to require the release of glutamate and the activation of metabotropic glutamate receptors subtype 5. Clinical studies also tend to point to a stimulatory effect of estradiol on cocaine sensitization and a neuroprotective effect of progesterone. In conclusion, the results of the present review indicate a need for further preclinical and clinical trials and neurobiological studies to better understand the relationship between sex and ovarian hormones on cocaine sensitization.
Topics: Humans; Female; Cocaine; Progesterone; Ovariectomy; Estradiol; Estrogens
PubMed: 36264315
DOI: 10.1007/s00221-022-06479-4 -
International Journal of Developmental... Dec 2022The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic...
PURPOSE
The aim of this systematic review was to explore and discuss the literature concerning the effects of hypoxia or anoxia during the perinatal period on the serotoninergic network in rodents, through mechanisms that lead to changes in serotonergic neurons, levels, segments of central nervous system affected, 5-HT transporter, and 5-HT receptor.
METHODS
Literature searches were performed in Embase, Medline (PubMed), Web of Science, and SCOPUS, from April to July 2021, with a total of 1045 published studies found. Using a predefined protocol, as registered on the CAMARADES website, 10 articles were included in this review. The PRISMA statement was used for reporting this systematic review. The internal validity was assessed using the SYRCLE's risk of bias tool.
RESULTS
Our main findings show that hypoxia in the first days of postnatal life led to a disturbance in the serotonergic system with reduced in 5-HT fibers, reduced brain levels of 5-HT and 5-HIAA, reduced SERT protein expression, and reduced receptor 5-HT . Putative mechanisms involving damage in the serotoninergic system include retrograde cell death resulting from primary damage mainly in forebrain areas, which impairs remote areas including serotonergic raphe nuclei. Other probable mechanisms associated with the serotoninergic network damage may be triggered by excitotoxic lesion and neuroinflammation.
CONCLUSION
Hypoxia at the beginning of an animal's life leads to modification of the serotonergic components associated with putative mechanisms that include cell damage and neuroinflammation.
Topics: Animals; Hypoxia; Models, Theoretical; Raphe Nuclei; Serotonergic Neurons; Serotonin
PubMed: 35996828
DOI: 10.1002/jdn.10226 -
The International Journal of... Dec 2022Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.
METHODS
We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.
RESULTS
Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.
CONCLUSIONS
Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Piperazines; Sulfides; Randomized Controlled Trials as Topic; Cognitive Dysfunction; Treatment Outcome; Double-Blind Method
PubMed: 35981958
DOI: 10.1093/ijnp/pyac054 -
Life Sciences Oct 2022Maternal exposure to a high-fat diet (HFD) during pregnancy and lactation has been related to changes in the hypothalamic circuits involved in the regulation of food... (Review)
Review
Maternal exposure to a high-fat diet (HFD) during pregnancy and lactation has been related to changes in the hypothalamic circuits involved in the regulation of food intake. Furthermore, maternal HFD during the critical period of development can alter the offspring's metabolic programming with long-term repercussions. This study systematically reviewed the effects of HFD consumption during pre-pregnancy, pregnancy and/or lactation. The main outcomes evaluated were food intake, body weight and cellular or molecular aspects of peptides and hypothalamic receptors involved in the regulation of energy balance in mice. Two independent authors performed a search in the electronic databases Medline/PubMed, LILACS, Web of Science, EMBASE, SCOPUS and Sigle via Open Gray. The experimental studies of mice exposed to HFD during pregnancy and/or lactation that evaluated body composition, food intake, energy expenditure and hypothalamic components related to energy balance were included. Internal validity was assessed using the SYRCLE risk of bias. The Kappa index was measured to analyze the agreement between reviewers. The PRISMA statement was used to report this systematic review. Most studies demonstrated that there was a higher body weight, body fat deposits and food intake, as well as alterations in the expression of hypothalamic neuropeptides in offspring that consumed HFD. Therefore, the maternal diet can affect the phenotype and metabolism of the offspring, in addition to harming the hypothalamic circuits and favoring the orexigenic pathways.
Topics: Animals; Body Weight; Diet, High-Fat; Eating; Energy Metabolism; Female; Humans; Maternal Nutritional Physiological Phenomena; Mice; Neuropeptides; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 35963301
DOI: 10.1016/j.lfs.2022.120880 -
Supportive Care in Cancer : Official... Nov 2022To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To identify effective and safe interventions to prevent acute phase chemotherapy-induced nausea and vomiting (CINV) in adult and pediatric patients.
METHODS
We conducted a systematic review of randomized trials evaluating interventions to prevent acute CINV. Outcomes assessed were complete chemotherapy-induced vomiting (CIV) control, complete chemotherapy-induced nausea (CIN) control, complete CINV control, and discontinuation of antiemetics due to adverse effects.
RESULTS
The search identified 65,172 citations; 744 were evaluated at full-text, and 295 (25 pediatric) met eligibility criteria. In patients receiving highly emetogenic chemotherapy (HEC), complete CIV (risk ratio (RR) 1.23, 95% confidence interval (CI) 1.05-1.44) and CIN (RR 1.34, 95% CI 1.10-1.62) control improved when olanzapine was added. The addition of a neurokinin-1 receptor antagonist (NK1RA) to a corticosteroid plus a serotonin-3 receptor antagonist (5HT3RA) also improved complete CIV (RR 1.11, 95% CI 1.08-1.14) and CIN (RR 1.05, 95% CI 1.01-1.08) control. Compared to granisetron/ondansetron, palonosetron provided improved complete CIV control when the 5HT3RA was given alone or when combined with dexamethasone. In patients receiving moderately emetogenic chemotherapy (MEC), dexamethasone plus a 5HT3RA improved complete CIV control compared to a 5HT3RA alone (RR 1.29, 95% CI 1.21-1.39). Only a single meta-analysis evaluating the safety outcome was possible.
CONCLUSIONS
For patients receiving HEC, various antiemetic regimens improved CIV and CIN control. For patients receiving MEC, administration of a 5HT3RA plus dexamethasone improved CIV control. Analysis of antiemetic safety was constrained by lack of data.
Topics: Adult; Humans; Child; Antiemetics; Neoplasms; Nausea; Vomiting; Dexamethasone; Antineoplastic Agents
PubMed: 35953731
DOI: 10.1007/s00520-022-07287-w -
Journal of Affective Disorders Nov 2022Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also... (Meta-Analysis)
Meta-Analysis Review
AIMS
Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results. In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD.
METHODS AND RESULTS
We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment. In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97 %, 95 % CI 0.17, 3.77, P = 0.032, I = 87.4 %). These results did not substantially change when analysis was restricted to patients with history of atherosclerotic cardiovascular disease (ASCVD). Similarly, FMD changes were higher in individuals receiving SSRIs compared to not-treated subjects (pooled mean difference 2.5 %. 95 % CI 0.7, 4.2, P < 0.001, I = 82.7 %).
LIMITATIONS
Substantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents.
CONCLUSION
SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD.
PROSPERO REGISTRATION
CRD42021252241.
Topics: Cardiovascular Diseases; Endothelium, Vascular; Humans; Selective Serotonin Reuptake Inhibitors
PubMed: 35944740
DOI: 10.1016/j.jad.2022.08.007 -
Molecular Psychiatry Aug 2023The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin... (Meta-Analysis)
Meta-Analysis
The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use (n = 1869). Two meta-analyses of overlapping studies examining the 5-HT receptor (largest n = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers (n = 566), but weak evidence of an effect in those with a family history of depression (n = 75). Another systematic review (n = 342) and a sample of ten subsequent studies (n = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study (n = 115,257) and one collaborative meta-analysis (n = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
Topics: Humans; Depression; Serotonin; Receptor, Serotonin, 5-HT1A; Tryptophan; Hydroxyindoleacetic Acid; Antidepressive Agents; Serotonin Plasma Membrane Transport Proteins
PubMed: 35854107
DOI: 10.1038/s41380-022-01661-0 -
The Journal of Headache and Pain Jul 2022In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the absence of head-to-head trials, comprehensive evidence comparing onset of efficacy of novel agents for acute treatment of migraine is lacking. This study aimed to explore the relative efficacy of lasmiditan (serotonin [5-hydroxytryptamine] 1F receptor agonist) versus rimegepant and ubrogepant (calcitonin gene-related peptide antagonists) for the acute oral treatment of migraine through network meta-analysis (NMA).
METHODS
Data included in the NMA were identified through a systematic literature search (conducted April 2018, updated May/December 2020) of phase II-IV, randomised controlled trials (RCTs) in adults with chronic/episodic migraine with/without aura. Treatments included: lasmiditan 50, 100, 200 mg; rimegepant 75 mg; ubrogepant 25, 50, 100 mg. Pairwise treatment comparisons from Bayesian fixed-effect/random-effects NMA, adjusted by baseline risk where appropriate, were conducted. Comparisons were reported as odds ratios with 95% credible intervals. Early-onset efficacy endpoints included: pain freedom at 2 hours and pain relief at 1 and 2 hours. Adverse drug reaction (ADR) profiles were summarised. Heterogeneity and inconsistency in the network were explored; sensitivity analyses investigated robustness of findings.
RESULTS
Across 12 RCTs included in the base case, females represented >80% of included patients (mean age 37.9-45.7 years). Odds of achieving both pain freedom and pain relief at 2 hours were higher with lasmiditan 100 and 200 mg versus rimegepant 75 mg and ubrogepant 25 and 50 mg. Results for pain relief at 1 hour were consistent with those at 2 hours, but fewer comparisons were available. There were no statistically significant differences between lasmiditan 50 mg and ubrogepant or rimegepant for any outcome. Sensitivity analyses were in the same direction as base case analyses. Most commonly reported ADRs (incidence ≥2%) were: dizziness, fatigue, paraesthesia, sedation, nausea/vomiting and muscle weakness with lasmiditan; nausea with rimegepant; and nausea, somnolence and dry mouth with ubrogepant.
CONCLUSIONS
The efficacy findings of this indirect comparison indicate that lasmiditan 100 mg or 200 mg might be an appropriate acute treatment option for patients with migraine seeking a fast onset of action. Differently from rimegepant and ubrogepant, lasmiditan use is associated with mainly neurological events, which are mostly mild or moderate in severity and self-limiting. 350/350 words.
Topics: Adult; Benzamides; Double-Blind Method; Female; Humans; Middle Aged; Migraine Disorders; Network Meta-Analysis; Piperidines; Pyridines; Pyrroles; Randomized Controlled Trials as Topic
PubMed: 35790906
DOI: 10.1186/s10194-022-01440-w -
Mini Reviews in Medicinal Chemistry 2023Severe dengue is characterized by thrombocytopenia, hemorrhaging, and/or capillary extravasation and may be linked to a reduced plasma concentration of serotonin...
BACKGROUND
Severe dengue is characterized by thrombocytopenia, hemorrhaging, and/or capillary extravasation and may be linked to a reduced plasma concentration of serotonin (5-hydroxytriptamine, or 5-HT).
OBJECTIVE
The aim of the current contribution was to conduct a systematic bibliographic review of reports on the role of the peripheral serotonergic system in the pathophysiology of severe dengue.
METHODS
A bibliographic review was carried out of in vivo/in vitro models, clinical trials, and case series studies from 2010-2019. The selective criteria were the use of treatments with serotonin reuptake inhibitors and/or agonists/antagonists of 5-HT receptors and their impact on inflammation, coagulation, and endothelium. Moreover, cross-sectional and cohort studies on the relationship between intraplatelet and plasma 5-HT levels in patients with dengue were also included. The risk of bias in the selected reports was examined with domain-based assessment utilizing Cochrane-type criteria. The main results are summarized in Tables and Figures.
RESULTS
Based on descriptions of the effect of serotonergic drugs on 5-HT levels and the findings of clinical trials of dengue treatment, most receptors of the peripheral serotonergic system, and especially 5-HT2A, seem to participate in regulating serum 5-HT during severe dengue. Therefore, the peripheral serotonergic system probably contributes to thrombocytopenia and capillary extravasation.
CONCLUSION
Regarding dengue, 5-HT may be a key parameter for predicting severity, and an understanding of 5-HT-related mechanisms could possibly facilitate the development of new therapies. These proposals require further research due to the limited number of publications on the role of serotonergic receptors at the peripheral level.
Topics: Humans; Cross-Sectional Studies; Selective Serotonin Reuptake Inhibitors; Serotonin; Severe Dengue; Thrombocytopenia
PubMed: 35726421
DOI: 10.2174/1389557522666220619231643 -
Neuroscience and Biobehavioral Reviews Aug 2022The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain... (Review)
Review
The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain information about personal experiences, general facts, and events. Several psychiatric or neurological diseases, such as depression, attention-deficit-hyperactivity disorder (ADHD), and dementia, show alterations in serotonergic signalling and attendant memory disorders. Nevertheless, understanding serotonergic neurotransmission and its influence on memory remained a challenge until today. In this systematic review, we summarize recent psychopharmacological studies in animals and humans from a psychological memory perspective, in consideration of task-specific requirements. This approach has the advantage that comparisons between serotonin (5-HT)-related neurochemical mechanisms and manipulations are each addressing specific mnemonic circuits. We conclude that applications of the same 5-HT-related treatments can differentially affect unrelated tasks of declarative memories. Moreover, the analysis of specific mnemonic phases (e.g., encoding vs. consolidation) reveals opposing impacts of increased or decreased 5-HT tones, with low 5-HT supporting spatial encoding but impairing the consolidation of objects and verbal memories. Promising targets for protein synthesis-dependent consolidation enhancements include 5-HT receptor agonists and 5-HT receptor antagonists, with the latter being of special interest for the treatment of age-related decline. Further implications are pointed out as base for the development of novel therapeutic targets for memory impairment of neuropsychiatric disorders.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Humans; Memory; Memory Disorders; Serotonin
PubMed: 35691469
DOI: 10.1016/j.neubiorev.2022.104729