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European Archives of Psychiatry and... Aug 2021The objective is to understand genetic predisposition to delirium. Following PRISMA guidelines, we undertook a systematic review of studies involving delirium and... (Meta-Analysis)
Meta-Analysis
The objective is to understand genetic predisposition to delirium. Following PRISMA guidelines, we undertook a systematic review of studies involving delirium and genetics in the databases of Pubmed, Scopus, Cochrane Library and PsycINFO, and performed a meta-analysis when appropriate. We evaluated 111 articles, of which 25 were finally included in the analysis. The studies were assessed by two independent researchers for methodological quality using the Downs and Black Tool and for genetic analysis quality. We performed a meta-analysis of 10 studies of the Apolipoprotein E (APOE) gene, obtaining no association with the presence of delirium (LOR 0.18, 95% CI - 0.10-0.47, p = 0.21). Notably, only 5 out of 25 articles met established criteria for genetic studies (good quality) and 6 were of moderate quality. Seven studies found an association with APOE4, the dopamine transporter gene SCL6A3, dopamine receptor 2 gene, glucocorticoid receptor, melatonin receptor and mitochondrial DNA haplotypes. One genome-wide association study found two suggestive long intergenic non-coding RNA genes. Five studies found no association with catechol-o-methyltransferase, melatonin receptor or several interleukins genes. The studies were heterogenous in establishing the presence of delirium. Future studies with large samples should further specify the delirium phenotype and deepen our understanding of interactions between genes and other biological factors.
Topics: Delirium; Genetic Predisposition to Disease; Humans
PubMed: 33779822
DOI: 10.1007/s00406-021-01255-x -
BMC Endocrine Disorders Nov 2021Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the recurrent rate of hyperprolactinemia after DAs withdrawal. However, few of them have concerned the recurrence risk of prolactinoma following the withdrawal of DAs.
METHODS
Three medical databases, PubMed, EMBASE and Cochrane library, were retrieved up to February, 14, 2021 to identify studies related to recurrence of prolactinoma and withdrawal of DAs. Statistical analyses including meta-analysis, sensitivity analysis, meta-regression, funnel plot and Egger test were performed through software R.
RESULTS
A total of 3225 studies were retrieved from the three data bases, and 13 studies consisted of 616 patients and 19 arms were finally included in this systematic analysis. There was no significant heterogeneity among the included studies, and fixed effect model was thus used. The pooled recurrence proportion of prolactinoma after withdrawal of DA was 2% with a 95% confidence interval (CI) of 1-3%.
CONCLUSION
Our study showed a very low recurrent rate of prolactinomas after DAs withdrawal. Much more prospective studies with larger cases and longer follow-up period are encouraged to confirm our finding.
TRIAL REGISTRATION
Registration number CRD42021245888 (PROSPERO).
Topics: Bromocriptine; Cabergoline; Deprescriptions; Dopamine Agonists; Humans; Neoplasm Recurrence, Local; Pituitary Neoplasms; Prolactinoma
PubMed: 34774043
DOI: 10.1186/s12902-021-00889-1 -
Intensive Care Medicine Jul 2002To determine the magnitude of the treatment effect of low-dose dopamine on renal function in patients at risk of and in patients with early renal injury. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine the magnitude of the treatment effect of low-dose dopamine on renal function in patients at risk of and in patients with early renal injury.
DATA SOURCES
MEDLINE, citation review of relevant primary and review articles, personal files, and contact with expert informants.
STUDY SELECTION
Randomized controlled studies that compared low-dose dopamine with placebo for the prevention or treatment of acute renal dysfunction. From 122 articles screened, 21 met the inclusion criteria for this meta-analysis. Of these six, were excluded.
DATA EXTRACTION
Fifteen studies containing 970 subjects were analyzed. Descriptive and outcome data were extracted. The main outcome measure was the absolute change in serum creatinine. In addition the number of patients who developed an acute decline in renal function was recorded. The meta-analysis was performed using the random effects model.
DATA SYNTHESIS
The meta-analysis demonstrated no significant difference between the absolute change in serum creatinine (5.1 micromol/l, 95% CI of -6.5 to +16.7) and the incidence of acute renal dysfunction (31% vs 33%, relative risk 1.01, 95% CI of 0.79-1.28) between those patients receiving low-dose dopamine and the control group. In addition, no sub-group of patients showed improved renal function with low-dose dopamine.
CONCLUSIONS
The results of this meta-analysis confirms that low-dose dopamine has no reno-protective effect. Considering the potential side-effects of dopamine this agent should not be used for this indication.
Topics: Creatine; Dopamine; Dose-Response Relationship, Drug; Female; Humans; Kidney; Kidney Function Tests; Male; Placebos; Randomized Controlled Trials as Topic; United States
PubMed: 12122525
DOI: 10.1007/s00134-002-1346-y -
Neuroscience and Biobehavioral Reviews Jan 2022Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve... (Meta-Analysis)
Meta-Analysis Review
Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.
Topics: Humans; Magnetic Resonance Imaging; Melanins; Schizophrenia; Substantia Nigra
PubMed: 34718049
DOI: 10.1016/j.neubiorev.2021.10.028 -
Frontiers in Cellular Neuroscience 2021The dopamine D1 receptor (D1R) is a Gα-coupled GPCR that is expressed in the midbrain and forebrain, regulating motor behavior, reward, motivational states, and...
The dopamine D1 receptor (D1R) is a Gα-coupled GPCR that is expressed in the midbrain and forebrain, regulating motor behavior, reward, motivational states, and cognitive processes. Although the D1R was initially identified as a promising drug target almost 40 years ago, the development of clinically useful ligands has until recently been hampered by a lack of suitable candidate molecules. The emergence of new non-catechol D1R agonists, biased agonists, and allosteric modulators has renewed clinical interest in drugs targeting this receptor, specifically for the treatment of motor impairment in Parkinson's Disease, and cognitive impairment in neuropsychiatric disorders. To develop better therapeutics, advances in ligand chemistry must be matched by an expanded understanding of D1R signaling across cell populations in the brain, and in disease states. Depending on the brain region, the D1R couples primarily to either Gα or Gα through which it activates a cAMP/PKA-dependent signaling cascade that can regulate neuronal excitability, stimulate gene expression, and facilitate synaptic plasticity. However, like many GPCRs, the D1R can signal through multiple downstream pathways, and specific signaling signatures may differ between cell types or be altered in disease. To guide development of improved D1R ligands, it is important to understand how signaling unfolds in specific target cells, and how this signaling affects circuit function and behavior. In this review, we provide a summary of D1R-directed signaling in various neuronal populations and describe how specific pathways have been linked to physiological and behavioral outcomes. In addition, we address the current state of D1R drug development, including the pharmacology of newly developed non-catecholamine ligands, and discuss the potential utility of D1R-agonists in Parkinson's Disease and cognitive impairment.
PubMed: 35110997
DOI: 10.3389/fncel.2021.806618 -
Pediatric Research Dec 2022This systematic review aims to examine the associations between features of gut microbiome and Attention Deficit/Hyperactivity Disorder (ADHD) risk or severity in...
BACKROUND
This systematic review aims to examine the associations between features of gut microbiome and Attention Deficit/Hyperactivity Disorder (ADHD) risk or severity in children, adolescents and young adults.
METHODS
Eligible studies were identified in PubMed and Google Scholar databases until December 31, 2020.
RESULTS
The search identified a total of 1197 items, of which 11 were included in this systematic review. The findings regarding alpha, beta diversity, bacterial phyla, orders and families were inconclusive. At the genus level an increased abundance of Odoribacter (two studies) and Eggerthella (two studies) was found in ADHD; on the contrary, decreased abundance of Faecalibacterium (three studies) was noted, whereas one study suggested its inverse association with ADHD severity and hyperactivity. One study indicated that Bacteroides species also correlated with levels of hyperactivity and impulsivity. At the species level, a lower abundance of Faecalibacterium prausnitzii, but higher of Odoribacter splanchnicus and Bacteroides uniformis was reported.
CONCLUSIONS
This systematic review highlights associations between gut microbiome features and ADHD. Potential mechanisms differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines.
IMPACT
The existence of correlations between features of gut microbiome and ADHD manifestation or its severity in children, adolescents and young adults. Associations between gut microbiome features and ADHD are highlighted. Potential mechanisms seem to differ by microorganism and include effects on neurotransmitter production, dopamine metabolism, modulation of inflammation and neurodevelopment through the release of cytokines. As correlations between gut microbiome features and ADHD seem to exist, additional studies are needed for further investigation.
Topics: Child; Adolescent; Young Adult; Humans; Attention Deficit Disorder with Hyperactivity; Gastrointestinal Microbiome; Dopamine
PubMed: 35354932
DOI: 10.1038/s41390-022-02027-6 -
Academic Emergency Medicine : Official... May 2024Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct... (Review)
Review
BACKGROUND
Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct evidence on the effectiveness of capsaicin and dopamine antagonists in its clinical management.
METHODS
A bibliographic search was conducted to address the following population-intervention-control-outcome (PICO) question: (P) adults >18 years old with a diagnosis of acute CHS presenting to the ED; (I) dopamine antagonists (e.g., haloperidol, droperidol) and topical capsaicin; (C) usual care or no active comparator; and (O) symptoms improvement/resolution in ED, ED length of stay, admission rate, ED recidivism, need for rescue medication, and adverse events. This systematic review was conducted in accordance with PRISMA reporting recommendations.
RESULTS
From 53 potentially relevant articles, seven articles were included: five observational studies and two randomized controlled trials, including a total of 492 patients. Five of these studies evaluated the efficacy of capsaicin cream (n = 386), and two examined dopamine antagonists (haloperidol, droperidol; n = 106). There was mixed evidence for the efficacy of capsaicin for reducing nausea and emesis. Both studies evaluating dopamine antagonists detected clinical benefit to usual care or no active comparator.
CONCLUSIONS
There is limited direct evidence on the efficacy of dopamine antagonists or capsaicin for treating CHS in the ED. Current evidence is mixed for capsaicin and potentially beneficial for dopamine antagonists. Because of the small number of studies, small number of participants, lack of standardization of treatment administration, and risk of bias of the included studies, methodologically rigorous trials on both types of intervention are needed to directly inform ED management of CHS.
Topics: Humans; Vomiting; Emergency Service, Hospital; Capsaicin; Dopamine Antagonists; Administration, Topical; Adult; Antiemetics; Syndrome; Female; Male; Cannabinoid Hyperemesis Syndrome
PubMed: 37391387
DOI: 10.1111/acem.14770 -
International Journal of Molecular... Mar 2023Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain... (Review)
Review
Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
Topics: Humans; Antipsychotic Agents; Dopamine; Schizophrenia; Schizophrenia, Treatment-Resistant; beta-Arrestins
PubMed: 36983018
DOI: 10.3390/ijms24065945 -
The British Journal of Psychiatry : the... Jun 2014The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The hypothesis that cortical dopaminergic alterations underlie aspects of schizophrenia has been highly influential.
AIMS
To bring together and evaluate the imaging evidence for dopaminergic alterations in cortical and other extrastriatal regions in schizophrenia.
METHOD
Electronic databases were searched for in vivo molecular studies of extrastriatal dopaminergic function in schizophrenia. Twenty-three studies (278 patients and 265 controls) were identified. Clinicodemographic and imaging variables were extracted and effect sizes determined for the dopaminergic measures. There were sufficient data to permit meta-analyses for the temporal cortex, thalamus and substantia nigra but not for other regions.
RESULTS
The meta-analysis of dopamine D2/D3 receptor availability found summary effect sizes of d = -0.32 (95% CI -0.68 to 0.03) for the thalamus, d = -0.23 (95% CI -0.54 to 0.07) for the temporal cortex and d = 0.04 (95% CI -0.92 to 0.99) for the substantia nigra. Confidence intervals were wide and all included no difference between groups. Evidence for other measures/regions is limited because of the small number of studies and in some instances inconsistent findings, although significant differences were reported for D2/D3 receptors in the cingulate and uncus, for D1 receptors in the prefrontal cortex and for dopamine transporter availability in the thalamus.
CONCLUSIONS
There is a relative paucity of direct evidence for cortical dopaminergic alterations in schizophrenia, and findings are inconclusive. This is surprising given the wide influence of the hypothesis. Large, well-controlled studies in drug-naive patients are warranted to definitively test this hypothesis.
Topics: Brain; Corpus Striatum; Dopamine; Humans; Positron-Emission Tomography; Schizophrenia; Temporal Lobe; Thalamus; Tomography, Emission-Computed, Single-Photon
PubMed: 25029687
DOI: 10.1192/bjp.bp.113.132308 -
Translational Psychiatry Mar 2016The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence... (Meta-Analysis)
Meta-Analysis Review
The D2 dopamine receptor mediates neuropsychiatric symptoms and is a target of pharmacotherapy. Inter-individual variation of D2 receptor density is thought to influence disease risk and pharmacological response. Numerous molecular imaging studies have tested whether common genetic variants influence D2 receptor binding potential (BP) in humans, but demonstration of robust effects has been limited by small sample sizes. We performed a systematic search of published human in vivo molecular imaging studies to estimate effect sizes of common genetic variants on striatal D2 receptor BP. We identified 21 studies examining 19 variants in 11 genes. The most commonly studied variant was a single-nucleotide polymorphism in ANKK1 (rs1800497, Glu713Lys, also called 'Taq1A'). Fixed- and random-effects meta-analyses of this variant (5 studies, 194 subjects total) revealed that striatal BP was significantly and robustly lower among carriers of the minor allele (Lys713) relative to major allele homozygotes. The weighted standardized mean difference was -0.57 under the fixed-effect model (95% confidence interval=(-0.87, -0.27), P=0.0002). The normal relationship between rs1800497 and BP was not apparent among subjects with neuropsychiatric diseases. Significant associations with baseline striatal D2 receptor BP have been reported for four DRD2 variants (rs1079597, rs1076560, rs6277 and rs1799732) and a PER2 repeat polymorphism, but none have yet been tested in more than two independent samples. Our findings resolve apparent discrepancies in the literature and establish that rs1800497 robustly influences striatal D2 receptor availability. This genetic variant is likely to contribute to important individual differences in human striatal function, neuropsychiatric disease risk and pharmacological response.
Topics: Brain; Genetic Variation; Humans; Molecular Imaging; Positron-Emission Tomography; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 26926883
DOI: 10.1038/tp.2016.22