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Frontiers in Neuroendocrinology Oct 2023Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females,... (Review)
Review
Substance use disorder (SUD) is a chronic condition characterized by pathological drug-taking and seeking behaviors. Remarkably different between males and females, suggesting that drug addiction is a sexually differentiated disorder. The neurobiological bases of sex differences in SUD include sex-specific reward system activation, influenced by interactions between gonadal hormone level changes, dopaminergic reward circuits, and epigenetic modifications of key reward system genes. This systematic review, adhering to PICOS and PRISMA-P 2015 guidelines, highlights the sex-dependent roles of estrogens, progesterone, and testosterone in SUD. In particular, estradiol elevates and progesterone reduces dopaminergic activity in SUD females, whilst testosterone and progesterone augment SUD behavior in males. Finally, SUD is associated with a sex-specific increase in the rate of opioid and monoaminergic gene methylation. The study reveals the need for detailed research on gonadal hormone levels, dopaminergic or reward system activity, and epigenetic landscapes in both sexes for efficient SUD therapy development.
Topics: Female; Humans; Male; Dopamine; Epigenesis, Genetic; Gonadal Steroid Hormones; Meta-Analysis as Topic; Progesterone; Sex Characteristics; Substance-Related Disorders; Systematic Reviews as Topic; Testosterone
PubMed: 37543184
DOI: 10.1016/j.yfrne.2023.101085 -
Brain and Behavior Jun 2023Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically... (Review)
Review
BACKGROUND
Primary generalized dystonia due to the DYT1 gene is an autosomal dominant disorder caused by a GAG deletion on chromosome 9q34. It is a well-defined, genetically proven, isolated dystonia syndrome. However, its pathophysiology remains unclear.
OBJECTIVES
This study was aimed at profiling the functional neuroimaging findings in DYT1 dystonia and harmonizing the pathophysiological implications for DYT1 dystonia from the standpoint of different neuroimaging techniques.
METHODS
A systematic review was conducted using identified studies published in English from Medline, PsycINFO, Embase, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR), between 1985 and December 2019 (PROSPERO protocol CRD42018111211).
RESULTS
All DYT1 gene carriers irrespective of clinical penetrance have reduced striatal GABA, dopamine receptors and increased metabolic activity in the lentiform nucleus, supplementary motor area, and cerebellum in addition to an abnormal cerebellothalamocortical pathway. Nonmanifesting carriers on the other hand have a disruption of the distal (thalamocortical) segment and have larger putaminal volumes than manifesting carriers and healthy controls. Activation of the midbrain, thalamus, and sensorimotor cortex was only found in the manifesting carriers.
CONCLUSIONS
Therefore, we propose that DYT1 dystonia is a cerebellostriatothalamocortical network disorder affecting either the structure or function of the different structures or nodes in the network.
Topics: Humans; Dystonia; Dystonic Disorders; Molecular Chaperones; Neuroimaging
PubMed: 37165749
DOI: 10.1002/brb3.3023 -
Behavioral and Brain Functions : BBF Nov 2016The association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The association between the dopamine D2 receptor (DRD2) gene and schizophrenia has been studied though no conclusive outcomes have been attained. The aim of this study was to perform a systematic review and meta-analysis to explore the relation between three polymorphisms of the DRD2 gene (C957T, TaqI and Ser311Cys) and schizophrenia.
METHODS
The search was made in PubMed and EBSCO databases (up to February 2016). The systematic review included 34 case-control association studies (34 for C957T, 16 for TaqI and 36 for Ser311Cys). The association analysis comprised the allelic, additive, dominant, and recessive genetic models. The meta-analysis was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement.
RESULTS
The meta-analysis showed that TaqI (additive model: OR 0.57, 95% CI 0.30-1.14) and C957T (additive model: OR 0.75, 95% OR 0.58-0.97, recessive model: OR 0.79, 95% CI 0.64-0.98) exert a protective effect against developing schizophrenia. However, the sub-analysis for the C957T variant showed that this polymorphism exhibits a risk factor effect on Chinese individuals (allelic model: OR 1.33, 95% CI 1.04-1.70).
CONCLUSION
Our meta-analysis suggests an association of the DRD2 gene and the risk for schizophrenia, given that TaqI and C957T polymorphisms presented a protective effect against schizophrenia, and in the sub-analyses the C957T variant increased the risk for this disorder in the Chinese population.
Topics: Alleles; Case-Control Studies; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Receptors, Dopamine D2; Risk Factors; Schizophrenia
PubMed: 27829443
DOI: 10.1186/s12993-016-0114-z -
Translational Psychiatry Jan 2017Disrupted-in-Schizophrenia 1 (DISC1) is a gene known as a risk factor for mental illnesses possibly associated with dopamine impairments. DISC1 is a scaffold protein... (Review)
Review
Disrupted-in-Schizophrenia 1 (DISC1) is a gene known as a risk factor for mental illnesses possibly associated with dopamine impairments. DISC1 is a scaffold protein interacting with proteins involved in the dopamine system. Here we summarise the impact of DISC1 disruption on the dopamine system in animal models, considering its effects on presynaptic dopaminergic function (tyrosine hydroxylase levels, dopamine transporter levels, dopamine levels at baseline and after amphetamine administration) and postsynaptic dopaminergic function (dopamine D1 and D2 receptor levels, dopamine receptor-binding potential and locomotor activity after amphetamine administration). Our findings show that many but not all DISC1 models display (1) increased locomotion after amphetamine administration, (2) increased dopamine levels after amphetamine administration in the nucleus accumbens, and (3) inconsistent basal dopamine levels, dopamine receptor levels and binding potentials. There is also limited evidence for decreased tyrosine hydroxylase levels in the frontal cortex and increased dopamine transporter levels in the striatum but not nucleus accumbens, but these conclusions warrant further replication. The main dopaminergic findings are seen across different DISC1 models, providing convergent evidence that DISC1 has a role in regulating dopaminergic function. These results implicate dopaminergic dysregulation as a mechanism underlying the increased rate of schizophrenia seen in DISC1 variant carriers, and provide insights into how DISC1, and potentially DISC1-interacting proteins such as AKT and GSK-3, could be used as novel therapeutic targets for schizophrenia.
Topics: Amphetamine; Animals; Dopamine; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Locomotion; Mice; Nerve Tissue Proteins; Nucleus Accumbens; Rats; Receptors, Dopamine D1; Receptors, Dopamine D2; Tyrosine 3-Monooxygenase
PubMed: 28140405
DOI: 10.1038/tp.2016.282 -
Frontiers in Pharmacology 2020Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for...
BACKGROUND
Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. C. A. Mey (PG) is an important herbal drug which has been used for benefiting Qi for thousand years. C. A. Mey and its compounds (PGC) possess various pharmacological activities, including anti-fatigue. Here, we conducted a systematic review of both randomized clinical trials (RCTs) and preclinical animal studies to investigate the efficacy and safety of PGC for fatigue.
METHODS
Electronic searches were performed in 7 databases from the time of each database's inception to August 2019. The methodological quality of RCTs was assessed using 7-item checklist recommended by Cochrane Collaboration or by the CAMARADES 10-item quality checklist. All the data were analyzed using Rev-Man 5.3 and Stata SE software.
RESULTS
Eight eligible RCTs and 30 animal studies were identified. The risk of bias scores in RCTs ranged from 4/7 to 7/7, and of animal studies varied from 4/10 to 7/10. Meta-analyses showed that PGC was superior to placebo according to their respective fatigue scales, heart rate recovery, and clinical effect (P < 0.05). There were a similar number of adverse effects between PGC and placebo group (P > 0.05). Meta-analyses showed that PGC can significantly decrease level of blood lactate, blood urea nitrogen, creatine kinase, malondialdehyde, and lactic dehydrogenase in serum, level of malondialdehyde in liver and level of gamma-aminobutyric acid, 5-hydroxytryptamine in brain tissue, and increase swimming time, level of glutathione peroxidase, glucose, superoxide dismutase in serum, level of glycogen and activity of superoxide dismutase, glutathione peroxidase, and catalase in skeletal muscle, level of hepatic glycogen in liver and level of dopamine, acetylcholine in brain tissue, compared with control (P < 0.05). Meta-analyses showed no significant difference in animal body weight between PGC and control (P > 0.05).
CONCLUSION
The present findings supported, to a certain degree, that PGC can be recommended for routine use in fatigue. The possible mechanism of PGC resists fatigue, mainly through antioxidant stress, regulating carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulating neurotransmitter disorder in central nervous system.
PubMed: 32765262
DOI: 10.3389/fphar.2020.01031 -
Prilozi (Makedonska Akademija Na... Nov 2016The incidence of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) is high as CKD and CHF share underlying risk factors such as arterial... (Review)
Review
The incidence of chronic kidney disease (CKD) in patients with chronic heart failure (CHF) is high as CKD and CHF share underlying risk factors such as arterial hypertension, diabetes mellitus and atherosclerosis. Cardiac failure leads to renal hypoperfusion and dysfunction and then fluid overload and need for aggressive diuretic therapy. However, development of diuretic resistance represents a significant problem in the management of these patients. The role of Renal Replacement Therapy (RRT) is important for patients who do not response to conservative management of fluid overload facilitating the failing heart to restore function. According to the guidelines, venovenous isolated Ultrafiltration (UF) is indicated for patients with refractory congestion not responding to medical therapy with loop diuretics and infusion of dopamine. A systematic review of randomized controlled trials on the effect of UF vs. IV furosemide for decompensated heart failure showed a benefit of UF on total body weight loss and on readmissions due to heart failure in patients with decompensated heart failure and CKD. Peritoneal dialysis (PD) can provide efficient ultrafiltration and sodium extraction in volume overloaded patients followed by decline of hospitalization days, decrease of body weight and improvement of LVEF in patients with refractory heart failure. The continuous draw of ultrafiltrate is followed by a lesser risk of abrupt hypotension and better preservation of the residual kidney function. This represents a significant advantage of PD over intermittent UF by dialysis. In conclusion, application of UF by dialysis and PD is followed by significant total body weight loss, reduced need for hospital readmissions and better quality of life. PD has a higher probability of preservation of residual kidney function and can be used by patients at home.
Topics: Heart Failure; Humans; Renal Insufficiency; Renal Replacement Therapy
PubMed: 27883326
DOI: 10.1515/prilozi-2016-0015 -
Movement Disorders Clinical Practice Sep 2023Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD). (Review)
Review
BACKGROUND
Continuous subcutaneous apomorphine infusion (CSAI) is one of the advanced therapies for Parkinson's disease (PD).
METHODS
A systematic review of all published articles in English on CSAI for PD till January 30, 2022 was conducted.
RESULTS
A total of 82 articles met the search criteria. Publications included retrospective or prospective open-label observational studies, with a limited number of randomized control trials (RCT). Publications were highly heterogeneous and focused on different aspects of CSAI and included clinical audits, effects on cognition/behavior, axial symptoms, nocturnal issues, adverse events/reasons for discontinuation and comparison with other continuous dopaminergic therapies. CSAI was used in patients who presented severe motor fluctuations not resolved by oral therapy, poor candidates for deep brain stimulation (DBS) due to cognitive/behavioral issues or in those with DBS weaning effect. Recent studies have also shown that CSAI was useful for nocturnal usage in advanced PD, in addition to daytime utilization. Adverse effects were common and include skin lesions, sedation and nausea. Pump management difficulties and patient decisions were common reasons for therapy dropout, predominantly during the initial stages of the CSAI.
CONCLUSION
There is consistent agreement on the benefits of CSAI in reducing OFF periods and improving ON periods without troublesome dyskinesia and specific motor and non-motor symptoms. Although there is a paucity of RCTs, current data from almost 30 years of use suggests CSAI to be beneficial in advanced cases of PD.
Topics: Apomorphine; Parkinson Disease; Humans; Infusions, Subcutaneous; Antiparkinson Agents; Dopamine Agonists; Deep Brain Stimulation
PubMed: 37772305
DOI: 10.1002/mdc3.13810 -
The Cochrane Database of Systematic... Sep 2017Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatorenal syndrome is defined as severe renal failure occurring in people with cirrhosis and ascites. Systematic reviews of randomised clinical trials found that, compared with placebo, terlipressin may reduce mortality and improve renal function in people with hepatorenal syndrome, but we need current evidence from systematic reviews on the benefits and harms of terlipressin versus other vasoactive drugs.
OBJECTIVES
To evaluate the beneficial and harmful effects of terlipressin versus other vasoactive drugs for people with hepatorenal syndrome.
SEARCH METHODS
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and Science Citation Index Expanded; conducted manual searches of references in relevant literature; and wrote to experts and pharmaceutical companies (date of last search November 2016).
SELECTION CRITERIA
Randomised clinical trials comparing terlipressin versus any other type of vasoactive drugs for hepatorenal syndrome. We allowed albumin and other cointerventions if provided equally in the comparison groups.
DATA COLLECTION AND ANALYSIS
Three authors independently extracted data. The primary outcomes were mortality, hepatorenal syndrome (persistent hepatorenal syndrome despite treatment), and serious adverse events. We conducted meta-analyses and present the results as risk ratios (RR) with 95% confidence intervals (CI). We performed sensitivity, subgroup, and Trial Sequential Analyses and evaluated bias control based on the Cochrane Hepato-Biliary Group domains.
MAIN RESULTS
We included 10 randomised clinical trials with 474 participants. The trials compared terlipressin versus noradrenaline (seven trials), octreotide (one trial), midodrine and octreotide (one trial), or dopamine (one trial). All participants in both groups received albumin as cointervention. We classified two trials at low risk of bias and eight trials at high risk of bias in the assessment of mortality and all trials at high risk of bias for remaining outcomes. In five trials, investigators specifically stated that they did not receive funding from for-profit organisations. We had no information about the funding source from the remaining five trials.Terlipressin was not superior or inferior compared with other vasoactive drugs in regard to mortality when including the two trials with a low risk of bias (RR 0.92, 95% CI 0.63 to 1.36; 94 participants, very low quality evidence) or when including all 10 trials (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). One meta-analysis including nine trials suggested a beneficial effect of terlipressin on hepatorenal syndrome (RR 0.79, 95% CI 0.63 to 0.99; 394 participants; I² = 26%; very low quality evidence). Due to the high mortality of hepatorenal syndrome, the registration of other serious adverse events is uncertain, but comparing terlipressin and other vasoactive drugs we found no significant difference (RR 0.96, 95% CI 0.88 to 1.06; 474 participants; I² = 0%; very low quality evidence). Several trials did not report systematically of adverse events, but terlipressin seemed to increase the risks of diarrhoea or abdominal pain, or both (RR 3.50, 95% CI 1.19 to 10.27; 221 participants; 5 trials, I² = 0%). However, Trial Sequential Analyses found insufficient evidence to support or refute any differences between interventions for all outcomes. Considering reversal of hepatorenal syndrome, subgroup analyses on the type of other vasoactive drugs found that terlipressin was superior compared with midodrine and octreotide (RR 0.47, 95% CI 0.30 to 0.72) or octreotide alone (RR 0.56, 95% CI 0.33 to 0.96), but each subgroup only included one small trial. None of the remaining subgroup or sensitivity analyses found differences between terlipressin and other vasoactive drugs. We downgraded the evidence to very low quality because of the high risk of bias, imprecision, and the results of the Trial Sequential Analyses.
AUTHORS' CONCLUSIONS
This review found insufficient evidence to support or refute beneficial or harmful effects of terlipressin and albumin versus other vasoactive drugs and albumin. Additional research is needed to evaluate if clinically meaningful differences exist between interventions.
Topics: Antihypertensive Agents; Dopamine; Hepatorenal Syndrome; Humans; Lypressin; Midodrine; Norepinephrine; Octreotide; Randomized Controlled Trials as Topic; Terlipressin; Vasoconstrictor Agents
PubMed: 28953318
DOI: 10.1002/14651858.CD011532.pub2 -
Healthcare (Basel, Switzerland) Apr 2023Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This... (Review)
Review
Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.
PubMed: 37046974
DOI: 10.3390/healthcare11071046 -
Clinical Drug Investigation Apr 2021BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The... (Meta-Analysis)
Meta-Analysis
UNLABELLED
BACKGROUND AND OBJECTIVE: Safinamide is a novel anti-parkinsonian drug with possible anti-dyskinetic properties. Parkinson's disease (PD) is a complex disease. The objective of this systematic review and meta-analysis is to evaluate the efficacy and safety of safinamide administration compared to placebo in PD patients on multiple outcomes.
METHODS
PubMed, EMBASE, Cochrane CENTRAL, LILACS, and trial databases were searched up to 23 December 2020 for randomized controlled studies (RCTs) comparing safinamide to placebo, alone or as add-on therapy in PD. Data were extracted from literature and regulatory agencies. Primary outcomes were ON-time without troublesome dyskinesia, OFF-time, and Unified Parkinson's Disease Rating Scale (UPDRS) section III (UPDRS-III). Secondary outcomes included any dyskinesia rating scale (DRS), ON-time with troublesome dyskinesia, UPDRS-II, and Parkinson's Disease Questionnaire 39 (PDQ-39). In order to estimate mean difference (MD) and odds ratios with 95% confidence intervals (CI), generic inverse variance and Mantel-Haenszel methods were used for continuous and dichotomous variables, respectively. Analyses were performed grouping by PD with (PDwMF) or without (PDwoMF) motor fluctuations, safinamide dose, and concomitant dopaminergic treatment. Summary of findings with GRADE were performed.
RESULTS
Six studies with a total of 2792 participants were identified. In PDwMF patients, safinamide 100 mg as add-on to levodopa (L-dopa) significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49), reduced OFF-time (MD = - 1.06 h; 95% CI from - 1.60 to - 0.51), and improved UPDRS-III (MD = - 2.77; 95% CI from - 4.27 to - 1.28) with moderate quality of evidence. Similar results were observed for the 50 mg dose. However, the quality of evidence was moderate only for ON-time without troublesome dyskinesia, whereas for OFF-time and UPDRS-III was low. In PDwoMF patients taking a single dopamine agonist, safinamide 100 mg resulted in little to no clinically significant improvement in UPDRS-III (MD = - 1.84; 95% CI from - 3.19 to - 0.49), with moderate quality of evidence. Conversely, in PDwoMF patients, the 200 mg and 50 mg doses showed nonsignificant improvement in UPDRS-III, with very low and moderate quality of evidence, respectively. In PDwMF patients taking safinamide 100 mg or 50 mg, nonsignificant differences were observed for ON-time with troublesome dyskinesia and DRS, with high and low quality of evidence, respectively. In the same patients, UPDRS-II was significantly improved at the 100 mg and 50 mg dose, with high and moderate quality of evidence. In PDwoMF, UPDRS-II showed a little yet significant difference only at 100 mg, with low quality of evidence. PDQ-39 resulted significantly improved only with the 100 mg dose in PDwMF, with low quality of evidence.
CONCLUSION
Overall, safinamide is effective in PDwMF patients taking L-dopa both at 100 and 50 mg daily. Evidence for efficacy in early PD is limited. Further trials are needed to better evaluate the anti-dyskinetic properties of safinamide.
Topics: Alanine; Antiparkinson Agents; Benzylamines; Dopamine Agonists; Humans; Levodopa; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 33674954
DOI: 10.1007/s40261-021-01011-y