-
International Journal of Molecular... Oct 2021Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies...
Noradrenaline (NE) is a catecholamine acting as both a neurotransmitter and a hormone, with relevant effects in modulating feeding behavior and satiety. Several studies have assessed the relationship between the noradrenergic system and Eating Disorders (EDs). This systematic review aims to report the existing literature on the role of the noradrenergic system in the development and treatment of EDs. A total of 35 studies were included. Preclinical studies demonstrated an involvement of the noradrenergic pathways in binge-like behaviors. Genetic studies on polymorphisms in genes coding for NE transporters and regulating enzymes have shown conflicting evidence. Clinical studies have reported non-unanimous evidence for the existence of absolute alterations in plasma NE values in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN). Pharmacological studies have documented the efficacy of noradrenaline-modulating therapies in the treatment of BN and Binge Eating Disorder (BED). Insufficient evidence was found concerning the noradrenergic-mediated genetics of BED and BN, and psychopharmacological treatments targeting the noradrenergic system in AN. According to these data, further studies are required to expand the existing knowledge on the noradrenergic system as a potential target for treatments of EDs.
Topics: Adrenergic Neurons; Animals; Brain; Feeding Behavior; Feeding and Eating Disorders; Humans; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins
PubMed: 34681746
DOI: 10.3390/ijms222011086 -
EJNMMI Research 2015In specialized movement disorder centers, Parkinson's disease (PD) is wrongly diagnosed in 6 to 25% of cases. To improve the accuracy of the clinical diagnosis, it is...
The diagnostic accuracy of dopamine transporter SPECT imaging to detect nigrostriatal cell loss in patients with Parkinson's disease or clinically uncertain parkinsonism: a systematic review.
In specialized movement disorder centers, Parkinson's disease (PD) is wrongly diagnosed in 6 to 25% of cases. To improve the accuracy of the clinical diagnosis, it is necessary to have a reliable and practical reference standard. Dopamine transporter single-photon emission computed tomography (DAT SPECT) imaging might have the potential (high diagnostic accuracy and practical to use) to act as reference standard in detecting nigrostriatal cell loss in patients with (early stage) parkinsonism. We performed a systematic review to evaluate if DAT SPECT imaging can be used as such. Relevant studies were searched in the MEDLINE and EMBASE databases. Studies were selected when they met the following criteria: (1) all patients were adults with a clinical diagnosis of PD or clinically uncertain parkinsonism and (2) the study reported original data. In addition, studies needed to fulfill one of the two following criteria: (1) patients underwent at least one DAT SPECT and had a neuropathological confirmed diagnosis and (2) patients underwent at least two DAT SPECT scans, performed at least 2 years apart. The search identified 1,649 articles. Eight studies fulfilled our selection criteria and were included in this review. There was only one study including patients with diagnostic uncertainty. Sensitivity and specificity of DAT SPECT imaging to detect nigrostriatal cell loss were 98%. The other studies included patients with a diagnosis of PD in whom there was no uncertainty. In these studies, sensitivity was 100%. Our systematic review indicates that DAT SPECT imaging seems to be accurate to detect nigrostriatal cell loss in patients with parkinsonism.
PubMed: 25853018
DOI: 10.1186/s13550-015-0087-1 -
Neuroscience and Biobehavioral Reviews Jan 2018Response inhibition has been shown to be associated with monoamine-related gene polymorphisms, although evidence is inconclusive. To comprehensively examine these... (Meta-Analysis)
Meta-Analysis Review
Response inhibition has been shown to be associated with monoamine-related gene polymorphisms, although evidence is inconclusive. To comprehensively examine these genotype effects on behavioural correlates of response inhibition in non-clinical adult populations, we performed a two-step approach. A systematic review of studies using Go/No-Go and/or Stop-Signal paradigms was first carried out. Thirty-eight eligible research articles were identified, which examined over 15 candidate genes. Remarkably, no firm conclusions could be drawn from these studies. Thus, in a second step, we conducted meta-analyses using random effects models on those polymorphisms that had previously been investigated in at least three studies. Specifically, data from 11 studies was analysed in three meta-analyses for the following polymorphisms: SLC6A3 3'UTR VNTR (k=6 samples; n=1463 participants), COMT Val158Met SNP (k=7 samples; n=784) and SLC6A4 5-HTTLPR (k=4 samples, n=204). None of these polymorphisms showed a reliable association with response inhibition performance. The methodological and theoretical implications of these findings are discussed, along with recommendations for future research.
Topics: Catechol O-Methyltransferase; Dopamine Plasma Membrane Transport Proteins; Humans; Inhibition, Psychological; Polymorphism, Genetic; Psychomotor Performance; Serotonin Plasma Membrane Transport Proteins
PubMed: 29155230
DOI: 10.1016/j.neubiorev.2017.11.009 -
Journal of Neurology, Neurosurgery, and... Apr 2022A number of promising biomarkers for predicting imminent α-synucleinopathies have been suggested in isolated rapid eye movement sleep behaviour disorder (iRBD).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
A number of promising biomarkers for predicting imminent α-synucleinopathies have been suggested in isolated rapid eye movement sleep behaviour disorder (iRBD). However, existing evidence is conflicting without quantitative evaluation.
METHODS
PubMed, Web of Science and ClinicalTrials.gov were searched through June 2021 to identify possible predictors of phenoconversion from iRBD to Parkinson's disease (PD). The pooled HRs and standardised mean differences (SMDs) with 95% CIs were calculated using fixed-effects or random-effects model.
RESULTS
A total of 123 studies were included in the meta-analysis. Significant motor dysfunction (HR 1.83, 95% CI 1.33 to 2.51, I=86.8%, p<0.001), constipation (HR 1.52, 95% CI 1.26 to 1.84, I=8.3%, p=0.365), orthostatic hypotension (HR 1.93, 95% CI 1.05 to 3.53, I=54.9%, p=0.084), hyposmia (HR 2.78, 95% CI 1.83 to 4.23, I=23.9%, p=0.255), mild cognitive impairment (HR 2.27, 95% CI 1.58 to 3.27, I=0%, p=0.681) and abnormal colour vision (SMD -0.34, 95% CI -0.63 to -0.05, I=45.6%, p=0.087) correlated with susceptibility to PD. The process can also be traced by putaminal dopamine transporter imaging (HR 2.60, 95% CI 1.94 to 3.48, I=0%, p=0.781) and tonic electromyographic activity (HR 1.50, 95% CI 1.04 to 2.15, I=70%, p=0.018).
CONCLUSIONS
The predictive value of each biomarker was initially highlighted with comprehensive evaluation. Combining specific predictors with high sensitivity is promising for detecting phenoconversion in the prodromal stage. Large-scale and multicentre studies are pivotal to extend our findings.
Topics: Biomarkers; Cognitive Dysfunction; Humans; Parkinson Disease; Prodromal Symptoms; REM Sleep Behavior Disorder; Synucleinopathies
PubMed: 34937751
DOI: 10.1136/jnnp-2021-328062 -
Therapeutic Drug Monitoring Apr 2024Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
BACKGROUND
Compared with antipsychotics, the relationship between antidepressant blood (plasma or serum) concentrations and target engagement is less well-established.
METHODS
We have discussed the literature on the relationship between plasma concentrations of antidepressant drugs and their target occupancy. Antidepressants reviewed in this work are citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine, duloxetine, milnacipran, tricyclic antidepressants (amitriptyline, nortriptyline, and clomipramine), bupropion, tranylcypromine, moclobemide, and vortioxetine. Four electronic databases were systematically searched.
RESULTS
We included 32 articles published 1996-2022. A strong relationship between serotonin transporter (SERT) occupancy and drug concentration is well established for selective serotonin reuptake inhibitors. Lower limits of recommended therapeutic reference ranges largely corroborate with the findings from positron emission tomography studies (80% SERT occupancy). Only a few novel studies have investigated alternative targets, that is, norepinephrine transporters (NETs), dopamine transporters (DATs), or monoamine oxidase A (MAO-A). For certain classes of drugs, positron emission tomography study data are inconclusive. Low DAT occupancy after bupropion treatment speculates its discussed mechanism of action. For MAO inhibitors, a correlation between drug concentration and MAO-A occupancy could not be established.
CONCLUSIONS
Neuroimaging studies are critical in TDM-guided therapy for certain antidepressants, whereas for bupropion and MAO inhibitors, the available evidence offers no further insight. Evidence for selective serotonin reuptake inhibitors is strong and justifies a titration toward suggested ranges. For SNRIs, duloxetine, and venlafaxine, NETs are sufficiently occupied, well above the SERT efficacy threshold. For these drugs, a titration toward higher concentrations (within the recommended range) should be considered in case of no response at lower concentrations.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride; Bupropion; Duloxetine Hydrochloride; Monoamine Oxidase Inhibitors; Antidepressive Agents; Positron-Emission Tomography; Monoamine Oxidase
PubMed: 38287888
DOI: 10.1097/FTD.0000000000001142 -
Psychiatry Research. Neuroimaging Jun 2020A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of...
A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.
Topics: Anorexia Nervosa; Binge-Eating Disorder; Bulimia Nervosa; Cerebrovascular Circulation; Humans; Parietal Lobe; Positron-Emission Tomography; Prefrontal Cortex; Tomography, Emission-Computed, Single-Photon
PubMed: 32234640
DOI: 10.1016/j.pscychresns.2020.111065 -
European Psychiatry : the Journal of... Jun 2019Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stimulant drugs can cause persistent changes in the brain. Imaging studies show that these changes are most apparent in dopamine transporter (DAT) or receptor availability within the striatum.
METHODS
This work focuses on influences of stimulant use on dopaminergic function assessed using nuclear-medicine imaging (PET/SPECT). Included are 39 studies on 655 cocaine, amphetamine, methamphetamine or nicotine users, as well as 690 healthy controls. Metaanalyses were conducted separately for D2/D3 receptors and dopamine transporters of the entire striatum, its subregions caudate and putamen respectively.
RESULTS
Meta-analyses results regarding nicotine did not show significant effects between smokers and nonsmokers. In cocaine users there was a significant decrease in dopamine receptor availability in all regions. The striatal DAT availability was significantly increased in cocaine users. Methamphetamine users showed a significantly decreased dopamine receptor and transporter density in all regions. Significant results also indicate a lower transporter availability in all regions. Amphetamine users showed reduced DAT availability in the striatum, as well as in the sub regions.
CONCLUSION
This meta-analysis provides evidence that there are ongoing changes in the dopaminergic system associated with the use of stimulants. Especially the results of cocaine, methamphetamine and amphetamine use mainly showed a downregulation. In addition, this meta-analysis is the first to include nicotine. This subset of studies showed evidence for a decreased receptor and DAT availability but no significant results were found in the metaanalyses.
Topics: Amphetamine-Related Disorders; Brain; Central Nervous System Stimulants; Dopamine; Dopamine Plasma Membrane Transport Proteins; Heroin Dependence; Humans; Methamphetamine; Neostriatum; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon
PubMed: 30981746
DOI: 10.1016/j.eurpsy.2019.03.003 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2020A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in...
A systematic review of association studies on the role of single nucleotide variants (SNVs) of the dopaminergic system genes on the effectiveness of clozapine in schizophrenia has been perfromed. A search of literature was conducted in PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web of Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, e-Library from 1995-2019. Association studies of 53 SNPs of genes encoding dopamine receptor isoforms (), dopamine transporter () and catechol-O- methyltransferase (), and the nature of their association with the therapeutic response to clozapine were analyzed. The results of SNPs studies of and genes are the most controversial. This can be explained by the heterogeneity of the samples and the lack of standardization of methods for evaluating the effectiveness of treatment in the context of association studies. The clear population specificity of the association of some SNPs of , and genes with the response to clozapine therapy has been shown. Most of the identified associations are haplotype specific. The obtained regularities of the effect of SNPs of dopaminergic system genes on the effectiveness of clozapine therapy should be considered in an individual approach to treatment of schizophrenia.
Topics: Catechol O-Methyltransferase; Clozapine; Dopamine; Genotype; Humans; Pharmacogenetics; Polymorphism, Single Nucleotide; Russia; Schizophrenia
PubMed: 32790988
DOI: 10.17116/jnevro202012007195 -
Translational Psychiatry Aug 2018Despite intense research, the underlying mechanisms and the etiology of Tourette's syndrome (TS) remain unknown. Data from molecular imaging studies targeting the... (Meta-Analysis)
Meta-Analysis
Despite intense research, the underlying mechanisms and the etiology of Tourette's syndrome (TS) remain unknown. Data from molecular imaging studies targeting the dopamine system in Tourette patients are inconclusive. For a better understanding of the striatal dopamine function in adult dopamine-antagonist-free patients we performed a systematic review in August 2017 identifying 49 PET and SPECT studies on the topic of TS. A total of 8 studies appraised the dopamine transporter (DAT) with 111 Tourette patients and 93 healthy controls, and could be included in a meta-analytic approach. We found a significantly increased striatal DAT binding in Tourette patients (Hedges' g = 0.49; 95% CI: (0.01-0.98)), although this effect did not remain significant after correcting for age differences between cohorts. A second meta-analysis was performed for the striatal dopamine receptor including 8 studies with a total of 72 Tourette patients and 71 controls. This analysis revealed a nonsignificant trend toward lower dopamine 2/3 receptor binding in striatum of Tourette patients. Other analyses regarding study population characteristics in both the DAT and receptor meta-analysis did not show any meaningful results. Our results indicate that dopaminergic alterations in TS are likely and thereby this data would be in line with the current pathophysiological hypotheses of a dysfunction in the dopamine system, e.g., the hypothesis of tonic-phasic dysfunction. However, these analyses suffer from low effect sizes probably due to the heterogeneity of TS and highlight the need for further large-scaled neuroimaging studies.
Topics: Case-Control Studies; Dopamine; Dopamine Antagonists; Dopamine Plasma Membrane Transport Proteins; Humans; Neostriatum; Neuroimaging; Positron-Emission Tomography; Receptors, Dopamine D2; Tomography, Emission-Computed, Single-Photon; Tourette Syndrome
PubMed: 30072700
DOI: 10.1038/s41398-018-0202-y