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Psychiatry Research Oct 2021Robust evidence suggests that depression, and risk for depression, are associated with the generation of stressful life events. This tendency to generate stress may be... (Review)
Review
AIM
Robust evidence suggests that depression, and risk for depression, are associated with the generation of stressful life events. This tendency to generate stress may be genetically determined. This systematic review aimed to identify specific molecular genetic markers associated with the generation of interpersonal stressful life events, at least in part dependent on individuals' behavior.
METHOD
We followed the PRISMA guidelines in searching six electronic databases (PubMed, MEDLINE, PsycINFO, CINAHL, Cochrane, and EMBASE) from inception to January 2021, and we reviewed the reference lists of eligible articles for additional records. We restricted eligibility to empirical studies involving at least one genetic marker and including proximal life events. We evaluated the risk of bias using the Newcastle Ottawa Scale for observational studies. The outcome permitted a distinction between life events dependent on the individual's agency versus independent events.
RESULTS
Seven studies, including 3585 participants, met eligibility criteria. Three were longitudinal, and four were cross-sectional; six included adolescents and young adults, and one focused on middle adulthood. Four examined the serotonin-transporter-linked promoter region (5-HTTLPR), two examined the rs53576 single nucleotide polymorphism of the oxytocin receptor gene (OXTR), and one examined a multilocus genetic profile score including four hypothalamic-pituitary-adrenal (HPA) axis genes. There were no significant direct correlations between genotype and life events in any study. Instead, their relation was significantly moderated by symptoms, exposure to early adversity, or attachment. Consistent with the stress generation hypothesis, this moderation relation was significant in predicting exposure to dependent life events but was not significant in predicting independent life event exposure.
CONCLUSIONS
There is evidence that genetic variation in the serotonin, HPA axis, and oxytocin systems moderates the effects of psychosocial vulnerability markers on the generation of proximal, dependent life events. Future research should examine additional genetic markers in systems known to confer risk for stress generation.
PROSPERO
CRD42019136886.
Topics: Adolescent; Adult; Cross-Sectional Studies; Genetic Markers; Genotype; Humans; Hypothalamo-Hypophyseal System; Life Change Events; Pituitary-Adrenal System; Serotonin Plasma Membrane Transport Proteins; Stress, Psychological; Young Adult
PubMed: 34371296
DOI: 10.1016/j.psychres.2021.114139 -
Neurological Sciences : Official... Jan 2018We performed this systematic review and meta-analysis to evaluate the tolerability and efficacy of intranasal sumatriptan, a selective serotonin agonist, compared to... (Meta-Analysis)
Meta-Analysis Review
We performed this systematic review and meta-analysis to evaluate the tolerability and efficacy of intranasal sumatriptan, a selective serotonin agonist, compared to placebo or other migraine therapeutics for the treatment of acute migraine attacks. We searched PubMed, SCOPUS, Embase, and Cochrane CENTRAL for relevant randomized controlled trials (RCTs). Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. We performed subgroup and meta-regression analyses for different doses and treatment endpoints. Sixteen RCTs (n = 5925 patients) matched our inclusion criteria. The overall effect-estimate showed that intranasal sumatriptan was superior to placebo in terms of pain relief (RR = 1.70, 95% CI [1.31, 2.21], p < 0.0001) and headache relief (RR = 1.58, 95% CI [1.35, 1.84], p < 0.00001) at 2 h. Although sumatriptan was superior to placebo in terms of headache relief at 30 min (RR = 1.31, 95% CI [1.08, 1.59], p = 0.005), no significant difference was found between both groups in terms of the frequency of pain-free participants at 30 min (RR = 1.18, 95% CI [0.49, 2.88], p = 0.71). Subgroup analysis and meta-regression models showed that increasing the dose of sumatriptan reduced the time needed for headache relief; however, this clinical improvement with higher doses was associated with more frequent adverse events in comparison to smaller doses. In conclusion, intranasal sumatriptan is effective for the treatment of acute migraine attacks. However, it was associated with a six-fold increase in the risk of taste disturbance, compared to the placebo. Future RCTs are recommended to provide head-to-head comparison of different administration routes and drug formulations of sumatriptan.
Topics: Acute Disease; Administration, Intranasal; Humans; Migraine Disorders; Pain Management; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Sumatriptan; Treatment Outcome
PubMed: 28942578
DOI: 10.1007/s10072-017-3119-y -
Journal of Alzheimer's Disease : JAD 2016There is uncertainty about the efficacy and tolerability of serotonin 2A (5-HT2A) receptor negative modulators for Parkinson's disease psychosis (PDP). (Meta-Analysis)
Meta-Analysis Review
Serotonin 2A Receptor Inverse Agonist as a Treatment for Parkinson's Disease Psychosis: A Systematic Review and Meta-analysis of Serotonin 2A Receptor Negative Modulators.
BACKGROUND
There is uncertainty about the efficacy and tolerability of serotonin 2A (5-HT2A) receptor negative modulators for Parkinson's disease psychosis (PDP).
OBJECTIVE
This is the first meta-analysis of randomized placebo-controlled trials (RCTs) testing negative modulators of the 5-HT2A receptor as a treatment for PDP.
METHODS
The primary outcome was the Scale for Assessment of Positive Symptoms (SAPS)-hallucinations (H) and -delusions (D) scores (SAPS-H+D). Other outcome measures were SAPS-H, SAPS-D, the Unified Parkinson's Disease Rating Scale Part II and III (UPDRS-II+III), discontinuation rates, and individual adverse events.
RESULTS
Four RCTs were identified that met inclusion criteria, all assessing the 5-HT2A inverse agonist pimavanserin (including 417 drug-treated and 263 placebo-treated PDP patients). Pimavanserin significantly decreased SAPS-H+D scores compared to placebo [weighted mean differences (WMD) = -2.26, 95% confidence interval (95% CI) = -3.86 to -0.67, p = 0.005, I2 = 30% , N = 4 studies, n = 502 patients]. Moreover, pimavanserin was superior to placebo for reducing SAPS-H (WMD = -2.15, 95% CI = -3.45 to -0.86, p = 0.001, I2 = 0% , N = 2, n = 237) and SAPS-D scores (WMD = -1.32, 95% CI = -2.32 to -0.32, p = 0.010, I2 = 0% , N = 2, n = 237). Pimavanserin was associated with less orthostatic hypotension than placebo (risk ratio = 0.33, 95% CI = 0.15-0.75, p = 0.008, I2 = 0% , number needed to harm = 17, p = 0.01, N = 3, n = 476). There were no significant differences in rates of all-cause discontinuation, adverse events, and death, UPDRS-II+III scores, and incidences of individual adverse events (other than orthostatic hypotension) between pimavanserin and placebo groups.
CONCLUSIONS
Pooled RCT results suggest that pimavanserin is beneficial for the treatment of PDP and is well tolerated. We did not identify other negative modulators of the 5-HT2A receptor for the treatment of PDP.
Topics: Antiparkinson Agents; Humans; Parkinson Disease; Randomized Controlled Trials as Topic; Receptor, Serotonin, 5-HT2A; Serotonin 5-HT2 Receptor Agonists
PubMed: 26757194
DOI: 10.3233/JAD-150818 -
European Journal of Pain (London,... Apr 2022Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Evidence for perioperative methods to prevent persistent postsurgical pain (PPP) is uncertain, in part because few treatments have been directly compared. Here we have used component network meta-analysis (cNMA) to incorporate both direct and indirect evidence in the evaluation of the efficacy and tolerability of pharmacological and neural block treatments.
DATABASES AND DATA TREATMENT
We searched the Cochrane Central Registry of Controlled Trials, Embase, MEDLINE, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry up to January 2021 for randomized, double-masked, controlled trials that reported the prevalence of PPP. We assessed trial quality with the Cochrane risk of bias tool (RoB 2.0). We analysed the results with frequentist cNMA models. The primary outcome was the relative risk (RR) of PPP. We assessed efficacy in relation to a clinically important effect size of RR = 0.9, which is a 10% improvement with treatment.
RESULTS
The analysis included 107 trials (13,553 participants) of 13 treatments. The effects of complex interventions were the multiplicative effects of their components. Compared with placebo, serotonin-norepinephrine reuptake inhibitors (SNRIs), neural block alone, or in combination with NMDA receptor blockers or gabapentanoids were effective. Treatments with benefit in the immediate post-operative period predicted a reduced risk of PPP.
CONCLUSIONS
Several treatments and treatment combinations effectively reduce PPP prevalence. Pain outcomes in the immediate postoperative period are an important mediator of PPP. Multimodal interventions can be analysed using cNMA.
SIGNIFICANCE
Systematic reviews of PPP prevention usually focus on the efficacy of specific treatments in comparison with control interventions. In this study we used component network meta-analysis to compare interventions to each other, including both pharmacological and neural block techniques, and multimodal interventions. Interventions that are not effective alone may improve the efficacy of multimodal interventions that include neural block techniques. Immediate postoperative benefit was an important mediator for reduction of PPP.
STUDY REGISTRATION
PROSPERO: CRD42018085570 https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Nerve Block; Network Meta-Analysis; Pain, Postoperative; Selective Serotonin Reuptake Inhibitors
PubMed: 35090077
DOI: 10.1002/ejp.1915 -
Acta Gastro-enterologica Belgica 2021Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity... (Review)
Review
BACKGROUND
Intestinal pseudo obstruction both acute and chronic is an uncommon severe motility disorder that affect both children and adults, can lead to significant morbidity burden and have no standard management strategy. Prucalopride a highly selective serotonin receptor agonist is an effective laxative with reported extra colon action. We aim to report our experience in children with acute and chronic intestinal pseudo obstruction who responded to prucalopride and systemically review the use of prucalopride in intestinal pseudo obstruction.
METHODS
A report of clinical experience and systemic review of the relevant medical databases to identify the outcome of usage of prucalopride in patients with acute and chronic intestinal pseudo obstruction. Studies meeting the selection criteria were reviewed including abstract only and case reports.
RESULTS
All reported cases showed clinical response to prucalopride. There were three full text, two abstracts only and three case reports all reporting clinical improvement with prucalopride.
CONCLUSION
Prucalopride appears to show promising results in children and adults with acute and chronic intestinal pseudo obstruction.
Topics: Adult; Benzofurans; Child; Colon; Humans; Intestinal Pseudo-Obstruction; Laxatives
PubMed: 34599567
DOI: 10.51821/84.3.002 -
Cureus Apr 2023Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective... (Review)
Review
Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that affects approximately 2% of the human population. Traditional treatment of OCD includes selective serotonin reuptake inhibitor (SSRI) or serotonin reuptake inhibitor (SRI) treatment along with cognitive behavioral therapy (CBT). Nearly 25%-30% of OCD patients do not respond to SSRIs. Glutamatergic agents are currently being studied for the treatment of OCD due to the glutamatergic pathway in the brain, related to OCD, and the role of the cortico-striato-thalamic circuit (CSTC). This review assesses the clinical effectiveness of N-methyl-D-aspartate (NMDA) antagonists, ketamine/esketamine, memantine, and amantadine, for adult patients with OCD. Inclusion criteria include human studies published within the last 15 years, with patients diagnosed with OCD, aged over 18 years, with only psychiatric comorbidities, and full-text articles. Papers that included interventions other than CBT, exposure with response prevention (ERP), and SSRI/SRI were excluded. Articles were searched for using PubMed, PubMed Central, Medical Literature Analysis and Retrieval System Online, GeorgiA LIbrary LEarning Online, EBSCO Information Services, OpenAthens, Multidisciplinary Digital Publishing Institute, and Google Scholar databases, last searched on December 2, 2022. The risk of bias was assessed using Cochrane Risk of Bias tools, the Scale for the Assessment of Narrative Review Articles (SANRA) checklist for literature reviews, and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for quasi-experimental studies. Results were presented and synthesized by Excel spreadsheet analysis. The database search yielded 4,221 articles, which was cut down to 18 articles by inclusion/exclusion criteria, including duplications. 80% of the ketamine studies resulted in a significant reduction of obsessions and compulsions based on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), and each of the memantine and amantadine studies displayed clinical effectiveness, also. Limitations include the small number of amantadine studies and the limited availability of other NMDA receptor (NMDAR) antagonist-focused studies. This systematic review shows that ketamine is an effective drug for the treatment of non-refractory, mild to moderate OCD, and memantine and amantadine are effective augmentation agents for the treatment of mild to severe OCD.
PubMed: 37213965
DOI: 10.7759/cureus.37833 -
Schizophrenia Research. Cognition Dec 2023In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on...
BACKGROUND
In a previous meta-analysis, the use of serotonin(5-HT) receptor partial agonists of the azapirone class as an add-on therapy was associated with beneficial effects on positive symptoms and attention/processing speed in schizophrenia patients. This meta-analysis builds on that study by examining the effects of adjunctive treatment with 5-HT partial agonists in improving other domains of neurocognitive function in schizophrenia patients.
METHODS
A literature search was performed from 1987 to May 2023 to identify randomized controlled trials. The standardized mean difference (SMD) with 95 % confidence intervals (CI) was calculated when there were two or more studies. Four studies, involving 313 patients, met the inclusion criteria and were used in the analysis.
RESULTS
5-HT partial agonists (buspirone or tandospirone) did not have a significant effect on verbal learning (SMD = 0.08, 95 % CI = -0.31 to 0.47) or working memory (SMD = 0.15, 95 % CI = -0.09 to 0.39). Regarding executive functions (Wisconsin Card Sorting Test), positive but non-significant results were seen with the category number (SMD = 0.26, 95 % CI = -0.81 to 1.32), while non-significant effects were noted for percent preservation errors (SMD = -0.10, 95 % CI = -0.53 to 0.33).
CONCLUSIONS
The absence of any significant benefits in the cognitive domains studied here may have been due to the variance in the concomitant medication (typical vs atypical antipsychotic drugs), the level of cognition at baseline, or other factors. Further studies with various types of 5-HT agonists are warranted to examine the potential cognitive efficacy of stimulating these receptors.
PubMed: 37732133
DOI: 10.1016/j.scog.2023.100290 -
Biological Research For Nursing Jan 2015Coping refers to the way that an individual manages stress. Coping strategies vary; for example, problem-focused coping is directed at reducing or removing a stressor,... (Review)
Review
Coping refers to the way that an individual manages stress. Coping strategies vary; for example, problem-focused coping is directed at reducing or removing a stressor, while emotion-focused coping is directed more at managing reactions that accompany the stressor. How individuals cope with stress can impact their health, but the physiological effects of coping are not well understood. The field of genetics provides tools that could help illuminate the physiology of coping. This review of the literature was conducted to determine what is currently known about the phenotype of coping from a genetic perspective. PubMed, HubMed, PsychInfo, Medline, Scopus, and Google Scholar databases were used to conduct the search, and reference lists were reviewed to identify additional publications. Only studies that measured coping style or a coping domain specifically, were written in English language, and were human-subject focused were included in the review. We identified 19 studies that met these criteria, and 2 types of genetic studies emerged for the review: heritability (n = 9) and candidate gene association (n = 10) studies. Heritability estimates of .68-.76 support a nonadditive genetic component to coping. Replication of association was found for the serotonin transporter and adrenergic receptor beta 2 genes. In addition to finding evidence supporting a role for genetic variability with coping phenotype, it is worth noting that the review revealed a lack of consistency in instruments used to phenotype coping across studies.
Topics: Adaptation, Psychological; Humans; Stress, Psychological
PubMed: 25504954
DOI: 10.1177/1099800414527340 -
Neuroscience and Biobehavioral Reviews Sep 2014Serotonergic dysfunction is thought to contribute to the pathophysiology of schizophrenia but the evidence has not been systematically synthesised before. We therefore... (Meta-Analysis)
Meta-Analysis Review
Serotonergic dysfunction is thought to contribute to the pathophysiology of schizophrenia but the evidence has not been systematically synthesised before. We therefore systematically reviewed postmortem and in vivo molecular imaging studies of serotonin function in schizophrenia. We identified fifty relevant studies investigating eight different serotonin receptor systems in a total of 684 patients and 675 controls. Meta-analysis of postmortem studies found an elevation in prefrontal 5-HT1A receptors with a moderate to large effect size (N=8, 85 patients and 94 controls, SMD=0.60; CI: 0.17-1.03; p=0.007) and a reduction with a large effect size in prefrontal 5-HT2A receptors (N=8, 168 patients and 163 controls, SMD=-0.73; CI: -1.33, -0.12; p=0.019) in schizophrenia vs healthy controls. The evidence for alterations in serotonin transporter availability or other serotonin receptors (5-HT1B; 5-HT1D; 5-HT3; 5-HT4; 5-HT7) is limited. There are fewer studies investigating 5-HT receptors in schizophrenia with neuroimaging. Findings indicated possible 5-HT alterations at psychosis onset, although due to the limited number it was not possible to combine studies in a meta-analysis. Further in vivo studies, particularly in drug naive patients using radiotracers that can index high affinity states, will help determine if the postmortem findings are primary or secondary to other factors.
Topics: Brain; Humans; Molecular Imaging; Receptors, Serotonin; Schizophrenia
PubMed: 24971825
DOI: 10.1016/j.neubiorev.2014.06.005 -
Progress in Neuro-psychopharmacology &... Dec 2020Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD...
BACKGROUND
Global reports estimate the number of betel quid (BQ) chewers up to 600 million. The proportion of betel quid dependence (BQD) is 20%-90% among current users. BQD mechanisms are not fully understood, and no pharmacological solution exists for its cessation therapy.
METHODS
We present a systematic review on BQD mechanisms and examine potential cessation therapeutic drugs. We conducted a systematic literature search in PubMed and Web of Science databases and identified the latest 10 years' relevant articles for reviews.
RESULTS
Functional magnetic resonance imaging results demonstrate that neurological mechanisms link the brain reward, cognitive, and impulsive systems in BQ or BQD users. The use of the areca nut increases both brain serotonin and noradrenaline levels, whereas arecoline, a potentially addictive areca nut component, has monoamine oxidase-A (MAO-A) inhibitor-like properties. MAO-A inhibitors prevent neurotransmitter breakdown and increase dopamine and serotonin concentrations in the brain. A reduction of daily BQ use was observed among patients with depression after antidepressant therapy, including MAO-A inhibitor and selective serotonin reuptake inhibitor (SSRI). Arecoline is a nicotinic acetylcholine receptor agonist expressed in Xenopus oocytes. However, relatively negligible amounts of nicotine are detected in the areca nut.
CONCLUSION
In conclusion, the current evidence provides a better understanding of the neurological and pharmacological mechanisms behind BQD. Arecoline, an MAO-A inhibitor, may account for BQD. Future translational studies are needed to verify the efficacy of potential BQD cessation drugs. MAO-A inhibitor and SSRI would thus be potentially promising targets for clinical trials.
Topics: Animals; Areca; Arecoline; Behavior, Addictive; Brain Chemistry; Humans; Magnetic Resonance Imaging; Monoamine Oxidase Inhibitors; Substance-Related Disorders
PubMed: 32454163
DOI: 10.1016/j.pnpbp.2020.109982