Exercise Regulates the Metabolic Homeostasis of Methamphetamine Dependence
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC9323070 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundEffective pharmacotherapies to treat methamphetamine (MA) dependence have not been identified, and behavioral therapies are marginally effective. Based on behavioral studies demonstrating the potential efficacy of aerobic exercise for improving depressive symptoms, anxiety, cognitive deficits, and substance use outcomes, the study described here is examining exercise as a potential treatment for MA-dependent individuals.MethodsThis study is randomizing 150 participants with MA dependence at a residential treatment facility for addictive disorders to receive either a thrice-weekly structured aerobic and resistance exercise intervention or a health education condition. Recruitment commenced in March, 2010. Enrollment and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates.ConclusionsSeeking evidence for a possibly effective adjunct to traditional behavioral approaches for treatment of MA dependence, this study is assessing the ability of an 8-week aerobic and resistance exercise protocol to reduce relapse to MA use during a 12-week follow-up period after discharge from residential-based treatment. The study also is evaluating improvements in health and functional outcomes during and after the protocol. This paper describes the design and methods of the study.
| S-EPMC4431553 | biostudies-literature
Project description:Understanding methamphetamine associated psychotic (MAP) symptom typologies could aid in identifying individuals at risk of progressing to schizophrenia and guide early intervention.Latent class analysis (LCA) of psychotic symptoms collected from 40 (n?=?40) methamphetamine dependent individuals with a history of psychotic symptoms but no history of a primary psychotic disorder.Three typologies were identified. In one, persecutory delusions dominated (Type 1), in another persecutory delusions were accompanied by hallucinations (Type 2), and in the third a high frequency of all the assessed hallucinatory and delusional symptoms was observed (Type 3).MAP is a heterogeneous syndrome with positive symptom typologies.This study represents the first attempt at identifying typologies of MAP and highlights the potential utility of LCA in future large-scale studies.
| S-EPMC4369467 | biostudies-literature
Project description:To examine whether overlapping cognitive deficits exist in currently drug-abstinent chronic methamphetamine (MA) abusers and schizophrenia (SZ) patients.Both SZ and chronic MA abuse are associated with frontostriatal disruption as well as deficits in cognitive control, such as selective attention. To identify overlapping cognitive profiles, we compared performance of the 2 groups on the Stroop attention task.Data were analyzed from 69 MA abusers who had been MA-abstinent for differing periods of time and from 23 SZ patients and 38 non-substance-abusing controls.The MA abusers in early abstinence displayed more Stroop interference than the SZ patients (P=0.004), long-term abstinent MA abusers (P=0.009), and controls (P=0.002). In the MA abusers, the magnitude of Stroop interference correlated positively with longer drug use (P=0.01) and negatively with longer drug abstinence (P=0.04). No correlations were found between psychotic symptoms and task performance.On this task of attentional selection, only the MA abusers in early stages of abstinence showed performance deficits compared with controls. More research is needed to further elucidate overlapping patterns between MA abuse and SZ.
| S-EPMC3269832 | biostudies-literature
Project description:Several lines of evidence implicate serotonergic dysfunction in diverse psychiatric disorders including anxiety, depression, and drug abuse. Mice with a knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor response to cocaine and elevated motivation to self-administer cocaine and alcohol. Previous genetic studies showed significant associations of HTR1B with alcohol dependence and substance abuse, but were followed by inconsistent results. We examined a case-control genetic association study of HTR1B with methamphetamine-dependence patients in a Japanese population. The subjects were 231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A-700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant difference in allelic and genotypic distributions of the SNPs between methamphetamine dependence and the control. Genetic associations of HTR1B were tested with several clinical phenotypes of methamphetamine dependence and/or psychosis, such as age at first abuse, duration of latency from the first abuse to onset of psychosis, prognosis of psychosis after therapy, and complication of spontaneous relapse of psychotic state. There was, however, no asscocation between any SNP and the clinical phenotypes. Haplotype analyses showed the three SNPs examined were within linkage disequilibrium, which implied that the three SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency was not different between the groups. The present findings may indicate that HTR1B does not play a major role in individual susceptibility to methamphetamine dependence or development of methamphetamine-induced psychosis.
| S-EPMC3137174 | biostudies-literature
Project description:Methamphetamine dependence is a serious worldwide public health problem with major medical, psychiatric, socioeconomic and legal consequences. Various neuronal mechanisms implicated in methamphetamine dependence have suggested several pharmacological approaches. A literature search from a range of electronic databases (PubMed, EMBASE, PsycInfo, the NIDA research monograph index and the reference list of clinicaltrials.gov) was conducted for the period from January 1985 to October 2009. There were no restrictions on the identification or inclusion of studies in terms of publication status, language and design type. A variety of medications have failed to show efficacy in clinical trials, including a dopamine partial agonist (aripiprazole), GABAergic agents (gabapentin) and serotonergic agents (SSRI, ondansetron, mirtazapine). Three double-blind placebo-controlled trials using modafinil, bupropion and naltrexone have shown positive results in reducing amphetamine or methamphetamine use. Two studies employing agonist replacement medications, one with d-amphetamine and the other with methylphenidate, have also shown promise. Despite the lack of success in most studies to date, increasing efforts are being made to develop medications for the treatment of methamphetamine dependence and several promising agents are targets of further research.
| S-EPMC2883750 | biostudies-literature
Project description:Methamphetamine use disorder is associated with a high likelihood of relapse. Identifying robust predictors of relapse that have explanatory power is critical to develop secondary prevention based on a mechanistic understanding of relapse. Computational approaches have the potential to identify such predictive markers of psychiatric illness, with the advantage of providing a finer mechanistic explanation of the cognitive processes underlying psychiatric vulnerability. In this study, sixty-two recently sober methamphetamine-dependent individuals were recruited from a 28-day inpatient treatment program, and completed a Stop Signal Task (SST) while undergoing functional magnetic resonance imaging (fMRI). These individuals were prospectively followed for 1 year and assessed for relapse to methamphetamine use. Thirty-three percent of followed participants reported relapse. We found that neural activity associated with two types of Bayesian prediction error, i.e. the difference between actual and expected need to stop on a given trial, significantly differentiated those individuals who remained abstinent and those who relapsed. Specifically, relapsed individuals exhibited smaller neural activations to such Bayesian prediction errors relative to those individuals who remained abstinent in the left temporoparietal junction (Cohen's d = 0.91), the left inferior frontal gyrus (Cohen's d = 0.57), and left anterior insula (Cohen's d = 0.63). In contrast, abstinent and relapsed participants did not differ in neural activation to non-model based task contrasts or on various self-report clinical measures. In conclusion, Bayesian cognitive models may help identify predictive biomarkers of relapse, while providing a computational explanation of belief processing and updating deficits in individuals with methamphetamine use disorder.
| S-EPMC6444286 | biostudies-literature
Project description:Integration of metabolic, stress and immune responses plays a fundamental role during animal development to maintain energy homeostasis while ensuring growth and proper developmental timing. Perturbation of metabolic and immune signaling circuits has detrimental consequences to animal development including growth retardation, organ malfunction and emergence of the metabolic syndrome. Here, we demonstrate that the Drosophila basic region-leucine zipper (bZIP) protein, Activating transcription factor 3 (Atf3), safeguards a balance of metabolic and immune system responses during fly development. Loss of Atf3 function results in lethality during late-larval and pupal stages. Atf3-deficient larvae exhibit phenotypes resembling the metabolic syndrome in mammals. Excessive accumulation of lipids in the larval fat body and gut is accompanied by altered expression of genes involved in lipid metabolism. Moreover, the fat body of atf3 mutants becomes infiltrated by hemocytes. The major pro-inflammatory pathways signaling through JNK and Imd are hyperactivated in atf3 mutants, causing ectopic expression of antimicrobial peptide genes. Suppression of the immune response, achieved by reducing the gene dose of the transcription factors FOXO or NF-kappaB/Relish, significantly improves lipid metabolism and normalizes gene expression profile of atf3 mutants. In addition, heterozygosity of relish partially rescues lethality of the atf3 mutants. Our data thus identify Atf3 as an essential player that links metabolic and immune system homeostasis during animal development. Examination of mRNA levels from four genotypes of male, 3rd instar Drosophila melanogaster larvae. mRNA levels from four genotypes relative to y w control were determined using two biological replicates per genotype. Genome build: BDGP R5/dm3, April 2006
2012-11-05 | E-GEOD-36377 | biostudies-arrayexpress
Project description:Phosphatidylserine (PS), synthesized in the endoplasmic reticulum (ER) by phosphatidylserine synthase (PSS), is transported to the plasma membrane (PM) and mitochondria through distinct routes. The in vivo functions of PS at different subcellular locations and the coordination between different PS transport routes are not fully understood. Here, we report that Drosophila PSS regulates cell growth, lipid storage and mitochondrial function. In pss RNAi, reduced PS depletes plasma membrane Akt, contributing to cell growth defects; the metabolic shift from phospholipid synthesis to neutral lipid synthesis results in ectopic lipid accumulation; and the reduction of mitochondrial PS impairs mitochondrial protein import and mitochondrial integrity. Importantly, reducing PS transport from the ER to PM by loss of PI4KIII? partially rescues the mitochondrial defects of pss RNAi. Together, our results uncover a balance between different PS transport routes and reveal that PSS regulates cellular homeostasis through distinct metabolic mechanisms.
| S-EPMC6946173 | biostudies-literature
Project description:Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins.
| S-EPMC3457521 | biostudies-literature
Project description:BackgroundStimulant drugs are second only to cannabis as the most widely used class of illicit drug globally, accounting for 68 million past-year consumers. Dependence on amphetamines (AMPH) or methamphetamine (MA) is a growing global concern. Yet, there is no established pharmacotherapy for AMPH/MA dependence. A comprehensive assessment of the research literature on pharmacotherapy for AMPH/MA dependence may inform treatment guidelines and future research directions.MethodsWe systematically reviewed the peer-reviewed literature via the electronic databases PubMed, EMBASE, CINAHL and SCOPUS for randomised controlled trials reported in the English language examining a pharmacological treatment for AMPH/MA dependence or use disorder. We included all studies published to 19 June 2019. The selected studies were evaluated for design; methodology; inclusion and exclusion criteria; sample size; pharmacological and (if included) psychosocial interventions; length of follow-up and follow-up schedules; outcome variables and measures; results; overall conclusions and risk of bias. Outcome measures were any reported impact of treatment related to AMPH/MA use.ResultsOur search returned 43 studies that met our criteria, collectively enrolling 4065 participants and reporting on 23 individual pharmacotherapies, alone or in combination. Disparate outcomes and measures (n = 55 for the primary outcomes) across studies did not allow for meta-analyses. Some studies demonstrated mixed or weak positive signals (often in defined populations, e.g. men who have sex with men), with some variation in efficacy signals dependent on baseline frequency of AMPH/MA use. The most consistent positive findings have been demonstrated with stimulant agonist treatment (dexamphetamine and methylphenidate), naltrexone and topiramate. Less consistent benefits have been shown with the antidepressants bupropion and mirtazapine, the glutamatergic agent riluzole and the corticotropin releasing factor (CRF-1) antagonist pexacerfont; whilst in general, antidepressant medications (e.g. selective serotonin reuptake inhibitors [SSRIs], tricyclic antidepressants [TCAs]) have not been effective in reducing AMPH/MA use.ConclusionsNo pharmacotherapy yielded convincing results for the treatment of AMPH/MA dependence; mostly studies were underpowered and had low treatment completion rates. However, there were positive signals from several agents that warrant further investigation in larger scale studies; agonist therapies show promise. Common outcome measures should include change in use days. Future research must address the heterogeneity of AMPH/MA dependence (e.g. coexisting conditions, severity of disorder, differences between MA and AMPH dependence) and the role of psychosocial intervention.
| S-EPMC7125061 | biostudies-literature