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Frontiers in Neurology 2018Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D dopamine agonists and, to a lesser extent, levodopa. We aim to investigate...
Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D dopamine agonists and, to a lesser extent, levodopa. We aim to investigate striatal dopaminergic function in PD patients with and without ICD. PubMed, Science Direct, EBSCO, and ISI Web of Science databases were searched (from inception to March 7, 2018) to identify PET or SPECT studies reporting striatal dopaminergic function in PD patients with ICD (ICD+) compared to those without ICD (ICD-). Studies which included drug naïve patients, explored non-pharmacological procedures (e.g., deep brain stimulation), and those using brain blood perfusion or non-dopaminergic markers were excluded. Standardized mean difference (SDM) was used and random-effect models were applied. Separate meta-analyses were performed for dopamine transporter level, dopamine release, and dopamine receptors availability in the putamen, caudate, dorsal, and ventral striatum. A total of 238 studies were title and abstract screened, of which 19 full-texts were assessed. Nine studies (ICD+: = 117; ICD-: = 175 patients) were included in the analysis. ICD+ showed a significant reduction of dopamine transporter binding in the putamen (SDM = -0.46; 95% CI: -0.80, -0.11; = 2.61; = 0.009), caudate (SDM = -0.38; 95% CI: -0.73, -0.04; = 2.18; = 0.03) and dorsal striatum (SDM = -0.45; 95% CI: -0.77, -0.13; = 2.76; = 0.006), and increased dopamine release to reward-related stimuli/gambling tasks in the ventral striatum (SDM = -1.04; 95% CI: -1.73, -0.35; = 2.95; = 0.003). Dopamine receptors availability did not differ between groups. Heterogeneity was low for dopamine transporter in the dorsal striatum ( = 0%), putamen ( = 0%) and caudate ( = 0%), and pre-synaptic dopamine release in the dorsal ( = 0%) and ventral striatum ( = 0%); heterogeneity was high for dopamine transporter levels in the ventral striatum ( = 80%), and for dopamine receptors availability in the ventral ( = 89%) and dorsal ( = 86%) striatum, putamen ( = 93%), and caudate ( = 71%). ICD+ patients show lower dopaminergic transporter levels in the dorsal striatum and increased dopamine release in the ventral striatum when engaged in reward-related stimuli/gambling tasks. This dopaminergic imbalance might represent a biological substrate for ICD in PD. Adequately powered longitudinal studies with drug naïve patients are needed to understand whether these changes may represent biomarkers of premorbid vulnerability to ICD.
PubMed: 30568628
DOI: 10.3389/fneur.2018.01018 -
Journal of Gastrointestinal Surgery :... Sep 2018In previous studies, there seems to be a relationship between different genetic polymorphisms and postoperative nausea and vomiting (PONV). We perform a systematic...
BACKGROUND
In previous studies, there seems to be a relationship between different genetic polymorphisms and postoperative nausea and vomiting (PONV). We perform a systematic review of the current literature about the relationship between genetic polymorphisms and the presence of PONV.
METHODS
Two bibliographic searches were carried out in three databases (PubMed, Web of Science, and Scopus) of studies, preferably prospective, about PONV following abdominal surgery. It was completed with a backward citation searching. A total of 73 articles were found of which 6 were selected after their critical lecture using CASPe network criteria. Relative frequency and relative risk were taken in each study according to the polymorphism.
RESULTS
Studies about 5-HT3B gene receptor polymorphisms, ABCB1 transporter, and dopamine D2 receptor showed a significant association with the presence of PONV (p = 0.02, 0.01, and 0.034 respectively). In relation to cytochrome P-450 2D6 (CYP2D6) polymorphisms, two of the three analysed articles showed a significant association with postoperative vomiting (p = 0.007).
CONCLUSION
Genetic polymorphisms could play an important role in PONV. The AAG deletion in both alleles of the 5-HT3B receptor gene, the Taq IA polymorphism of the dopamine D2 receptor, and the presence of three or more functional alleles of CYP2D6 seem to be related with a higher incidence of PONV, especially in the first 24 h after surgery. The 2677TT and 3435TT genotypes of the ABCB1 transporter could reduce the PONV due to their association with a greater effectiveness of ondansetron. However, new quality studies are needed to consider this relationship.
Topics: ATP Binding Cassette Transporter, Subfamily B; Cytochrome P-450 CYP2D6; Humans; Polymorphism, Genetic; Postoperative Nausea and Vomiting; Receptors, Dopamine D2; Receptors, Serotonin, 5-HT3
PubMed: 29725907
DOI: 10.1007/s11605-018-3788-8 -
Psychopharmacology Mar 2021Although numerous studies have suggested that pharmacological alteration of the dopamine (DA) system modulates reward discounting, these studies have produced... (Meta-Analysis)
Meta-Analysis
RATIONALE
Although numerous studies have suggested that pharmacological alteration of the dopamine (DA) system modulates reward discounting, these studies have produced inconsistent findings.
OBJECTIVES
Here, we conducted a systematic review and pre-registered meta-analysis to evaluate DA drug-mediated effects on reward discounting of time, probability, and effort costs in studies of healthy rats. This produced a total of 1343 articles to screen for inclusion/exclusion. From the literature, we identified 117 effects from approximately 1549 individual rats.
METHODS
Using random effects with maximum-likelihood estimation, we meta-analyzed placebo-controlled drug effects for (1) DA D1-like receptor agonists and (2) antagonists, (3) D2-like agonists and (4) antagonists, and (5) DA transporter-modulating drugs.
RESULTS
Meta-analytic effects showed that DAT-modulating drugs decreased reward discounting. While D1-like and D2-like antagonists both increased discounting, agonist drugs for those receptors had no significant effect on discounting behavior. A number of these effects appear contingent on study design features like cost type, rat strain, and microinfusion location.
CONCLUSIONS
These findings suggest a nuanced relationship between DA and discounting behavior and urge caution when drawing generalizations about the effects of pharmacologically manipulating dopamine on reward-based decision-making.
Topics: Animals; Biological Transport; Brain; Decision Making; Delay Discounting; Dopamine Agonists; Dopamine Antagonists; Dose-Response Relationship, Drug; Male; Rats; Receptors, Dopamine D1; Receptors, Dopamine D2; Reward
PubMed: 33215269
DOI: 10.1007/s00213-020-05723-5 -
Molecular Psychiatry Jul 2023Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains... (Meta-Analysis)
Meta-Analysis
Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains still elusive. The present meta-analysis aims to assess the impact of insulin action manipulations (i.e., hyperinsulinemia, hypoinsulinemia, systemic or brain insulin resistance) on glutamatergic, dopaminergic, γ-aminobutyric acid (GABA)ergic, and serotonergic pathways in the central nervous system. More than one hundred outcomes, including transcript or protein levels, kinetic parameters, and other components of the neurotransmitter pathways, were collected from cultured cells, animals, or humans, and meta-analyzed by applying a random-effects model and adopting Hedges'g to compare means. Two hundred fifteen studies met the inclusion criteria, of which 180 entered the quantitative synthesis. Significant impairments in key regulators of synaptic plasticity processes were detected as the result of insulin handlings. Specifically, protein levels of N-methyl-D-aspartate receptor (NMDAR) subunits including type 2A (NR2A) (Hedges' g = -0.95, 95%C.I. = -1.50, -0.39; p = 0.001; I = 47.46%) and 2B (NR2B) (Hedges'g = -0.69, 95%C.I. = -1.35, -0.02; p = 0.043; I = 62.09%), and Postsynaptic density protein 95 (PSD-95) (Hedges'g = -0.91, 95%C.I. = -1.51, -0.32; p = 0.003; I = 77.81%) were found reduced in insulin-resistant animal models. Moreover, insulin-resistant animals showed significantly impaired dopamine transporter activity, whereas the dopamine D2 receptor mRNA expression (Hedges'g = 3.259; 95%C.I. = 0.497, 6.020; p = 0.021; I = 90.61%) increased under insulin deficiency conditions. Insulin action modulated glutamate and GABA release, as well as several enzymes involved in GABA and serotonin synthesis. These results suggest that brain neurotransmitter systems are susceptible to insulin signaling abnormalities, resembling the discrete psychotic disorders' neurobiology and possibly contributing to the development of neurobiological hallmarks of treatment-resistant schizophrenia.
Topics: Humans; Animals; Schizophrenia; Insulin; Neurobiology; Disks Large Homolog 4 Protein; Receptors, N-Methyl-D-Aspartate; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37085712
DOI: 10.1038/s41380-023-02065-4 -
Addiction (Abingdon, England) Jul 2009Alcohol problem use during adolescence has been linked to a variety of adverse consequences, including cigarette and illicit drug use, delinquency, adverse effects on... (Review)
Review
AIMS
Alcohol problem use during adolescence has been linked to a variety of adverse consequences, including cigarette and illicit drug use, delinquency, adverse effects on pubertal brain development and increased risk of morbidity and mortality. In addition, heavy alcohol-drinking adolescents are at increased risk of comorbid psychopathology, including internalizing symptomatology (especially depression and anxiety). A range of genetic and non-genetic factors have been implicated in both alcohol problem use as well as internalizing symptomatology. However, to what extent shared risk factors contribute to their comorbidity in adolescence is poorly understood.
DESIGN
We conducted a systematic review on Medline, PsycINFO, Embase and Web of Science to identify epidemiological and molecular genetic studies published between November 1997 and November 2007 that examined risk factors that may be shared in common between alcohol problem use and internalizing symptomatology in adolescence.
FINDINGS
Externalizing disorders, family alcohol problems and stress, as well as the serotonin transporter (5-HTT) S-allele, the monoamine oxidase A (MAOA) low-activity alleles and the dopamine D2 receptor (DDR2) Taq A1 allele have been associated most frequently with both traits. An increasing number of papers are focusing upon the role of gene-gene (epistasis) and gene-environment interactions in the development of comorbid alcohol problem use and internalizing symptomatology.
CONCLUSIONS
Further research in adolescents is warranted; the increasing availability of large longitudinal genetically informative studies will provide the evidence base from which effective prevention and intervention strategies for comorbid alcohol problems and internalizing symptomatology can be developed.
Topics: Adolescent; Alcohol-Related Disorders; Anxiety; Child; Comorbidity; Depressive Disorder; Family; Female; Genetic Predisposition to Disease; Humans; Male; Monoamine Oxidase; Personality Development; Risk Factors; Serotonin Plasma Membrane Transport Proteins; Social Environment; Socioeconomic Factors
PubMed: 19438423
DOI: 10.1111/j.1360-0443.2009.02571.x -
International Clinical... Jan 2014The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and... (Meta-Analysis)
Meta-Analysis Review
The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and personality traits, only modest progress has been made in identifying loci that robustly support these associations. The aim of this study was to provide a summary of literature data on association studies focused on the genetic modulation of personality, according to the Cloninger, Eysenck and Costa and McCrae models. PubMed was searched for papers investigating the association between any gene variant and personality traits, which were grouped into five clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d) socialization and (e) spirituality, in healthy individuals, populations and psychiatric patients. A total of 369 studies were included. No clear consensus on the role of any individual gene variant in personality modulation emerged, although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be more reliably related to anxiety and impulsivity-related traits, respectively. Because conflicting results emerged from the literature, plausibly as a result of the combined influence of many loci of small effects on personality, larger sample sizes and more narrow and specific phenotype will be the minimum requirements for future genetic studies on personality. Moreover, gene × gene and gene × environment interaction studies deserve further attention.
Topics: Anxiety; Brain-Derived Neurotrophic Factor; Catechol O-Methyltransferase; Dopamine Plasma Membrane Transport Proteins; Genome-Wide Association Study; Humans; Impulsive Behavior; Monoamine Oxidase; Personality; Personality Disorders; Psychotic Disorders; Receptors, Dopamine; Receptors, Serotonin; Serotonin Plasma Membrane Transport Proteins; Socialization; Spirituality
PubMed: 24100617
DOI: 10.1097/YIC.0b013e328364590b -
Alcoholism, Clinical and Experimental... Feb 2007Delirium tremens (DT) is one of the more severe complications of alcohol withdrawal (AW), with a 5 to 10% lifetime risk for alcohol-dependent patients. The 2 most... (Review)
Review
BACKGROUND
Delirium tremens (DT) is one of the more severe complications of alcohol withdrawal (AW), with a 5 to 10% lifetime risk for alcohol-dependent patients. The 2 most important neurosystems involved in AW are gamma-aminobutyric acid and glutamate. It is unknown whether these neurosystems are involved in the pathophysiology of DT as well. The candidate gene approach in DT could contribute to this knowledge and demonstrate a possible genetic predisposition for DT. The purpose of this study is to give an overview of all studied genetic polymorphisms in the diverse candidate genes related to DT and to summarize what these studies contribute to insights into the pathophysiology of DT.
METHODS
The inclusion criteria for this literature study were articles in English analyzing the association between a genetic polymorphism and DT without other AW syndromes. Studies were identified until February 2006 in MEDLINE and EMBASE databases.
RESULTS
We found 25 studies dealing with 30 polymorphisms, located in 19 different genes. Positive associations were found in 3 different candidate genes involved in the dopamine transmission, 1 gene involved in the glutamate pathway, 1 neuropeptide gene, and 1 cannabinoid gene. Two candidate genes involved in the dopamine transmission, dopamine receptor D3, and solute carrier family 6, were each associated with DT in 2 different study populations. The other 4 positive associations were not replicated in other studies.
CONCLUSIONS
A total of 8 positive associations out of 30 polymorphisms makes a genetic base for DT plausible. Understanding the pathophysiological process of the development of DT has, indeed, been augmented by the reviewed genetic association studies. These studies suggest that the regulation of dopaminergic neurotransmission may play an important role.
Topics: Alcohol Withdrawal Delirium; Case-Control Studies; Databases as Topic; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Polymorphism, Genetic; Receptors, Dopamine D3; Synaptic Transmission
PubMed: 17250608
DOI: 10.1111/j.1530-0277.2006.00294.x -
European Neuropsychopharmacology : the... Jun 2013Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a... (Review)
Review
Methylphenidate (MPH) is a first line option in the psychopharmacologic treatment of adults with Attention-Deficit/Hyperactivity Disorder (ADHD). However, there is a considerable proportion of adult patients who do not respond to treatment with MPH or discontinue drug therapy. Since effects of genetic variants in the response to MPH treatment might explain these negative outcomes, we conducted an electronic systematic search of MEDLINE-indexed literature looking for articles containing information about pharmacogenetics of ADHD in adults published until January, 2012. The keywords used were 'ADHD', 'Attention-Deficit/Hyperactivity Disorder' and 'gene' in combination with methylphenidate, amphetamine or atomoxetine. Only 5 pharmacogenetic studies on adult ADHD met inclusion criteria. The results evidenced that most findings obtained so far are negative, and all studies focused on MPH response. There is only one positive result, for a polymorphism at the dopamine transporter gene (DAT1) gene. The current state of the art in adult ADHD implies that pharmacogenetic tests are far from routine clinical practice. However, the integration of these studies with neuroimaging and neuropsychological tests may help to understand mechanisms of drug action and the pathophysiology of ADHD.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Drug Resistance; Humans; Methylphenidate; Nerve Tissue Proteins; Neurons; Pharmacogenetics; Polymorphism, Genetic
PubMed: 22709890
DOI: 10.1016/j.euroneuro.2012.05.006 -
American Journal of Medical Genetics.... Apr 2018Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in... (Meta-Analysis)
Meta-Analysis
Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended.
Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Biomarkers, Pharmacological; Child; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Methylphenidate; Polymorphism, Genetic; Treatment Outcome
PubMed: 29171685
DOI: 10.1002/ajmg.b.32613 -
Movement Disorders : Official Journal... Jan 2010Vascular parkinsonism (VP) remains a loose constellation of various clinical features. We systematically reviewed studies comparing clinical, neuroimaging and other... (Review)
Review
Vascular parkinsonism (VP) remains a loose constellation of various clinical features. We systematically reviewed studies comparing clinical, neuroimaging and other investigations that might distinguish VP from idiopathic Parkinson's disease (PD). Medline, Embase, Cinahl (R), and PsycINFO were searched by querying appropriate key words. Reports were included if the study population contained comparative findings between patients with VP and PD. Twenty-five articles fulfilled the selection criteria. Patients with VP were older, with a shorter duration of illness, presented with symmetrical gait difficulties, were less responsive to levodopa, and were more prone to postural instability, falls, and dementia. Pyramidal signs, pseudobulbar palsy, and incontinence were more common in VP. Tremor was not a main feature of VP. Structural neuroimaging was more likely to be abnormal in VP (90-100% of cases) than in PD (12-43% of cases), but there was no specific abnormal structural imaging pattern for VP. Two studies of presynaptic striatal dopamine transporters (using single photon emission computed tomography) showed a significant reduction in striatal uptake ratios in PD but not in VP, whereas another study found that only the mean asymmetry index was significantly lower in VP. Various other investigations, including alternative imaging techniques, electrophysiological, and neuropsychological studies, are reported, but the diverse diagnostic criteria used makes it difficult to reach any firm conclusions. The development of accepted international diagnostic criteria for VP is urgently needed to facilitate further studies.
Topics: Age Factors; Antiparkinson Agents; Brain; Cerebrovascular Disorders; Diagnosis, Differential; Dopamine Plasma Membrane Transport Proteins; Gait; Humans; Levodopa; Parkinson Disease; Parkinson Disease, Secondary; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Tremor
PubMed: 20077476
DOI: 10.1002/mds.22937