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Neurofunctional Differences Related to Methamphetamine and Sexual Cues in Men With Shorter and Longer Term Abstinence Methamphetamine Dependence.

ABSTRACT: BACKGROUND:Stimulant use and sexual behaviors have been linked in behavioral and epidemiological studies. Although methamphetamine-related neurofunctional differences have been investigated, few studies have examined neural responses to drug and sexual cues with respect to shorter or longer term methamphetamine abstinence in individuals with methamphetamine dependence. METHODS:Forty-nine men with shorter term methamphetamine abstinence, 50 men with longer term methamphetamine abstinence, and 47 non-drug-using healthy comparison men completed a functional magnetic resonance imaging cue-reactivity task consisting of methamphetamine, sexual, and neutral visual cues. RESULTS:Region-of-interest analyses revealed greater methamphetamine cue-related activation in shorter term methamphetamine abstinence and longer term methamphetamine abstinence individuals relative to healthy comparison men in the ventromedial prefrontal cortex. A significant interaction of group and condition in the anterior insula was found. Relative to healthy comparison participants, both shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups displayed greater sexual cue-related anterior insula activation relative to methamphetamine cues and neutral cues, but there were no differences between shorter term methamphetamine abstinence and longer term methamphetamine abstinence groups in anterior insula responses. Subsequent whole-brain analyses indicated a group-by-condition interaction with longer term methamphetamine abstinence participants showing greater sexual-related activation in the left superior frontal cortex relative to healthy comparison men. Shorter term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral cues, and longer term methamphetamine abstinence participants showed greater superior frontal cortex activation to sexual relative to neutral and methamphetamine cues. CONCLUSIONS:The findings suggest that abstinence from methamphetamine may alter how individuals respond to drug and sexual cues and thus may influence drug use and sexual behaviors. Given the use of methamphetamine for sexual purposes and responses to natural vs drug rewards for addiction recovery, the findings may have particular clinical relevance.

SUBMITTER: Chen S

PROVIDER: S-EPMC7171928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo determine the relation between height, FOXO3 genotype and age of death in humans.MethodsObservational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. A Cox regression model with age as the time scale, stratified by year of birth, was used to estimate the effect of baseline height on mortality during follow-up. An analysis of height and longevity-associated variants of the key regulatory gene in the insulin/IGF-1 signaling (IIS) pathway, FOXO3, was performed in a HHP-HAAS subpopulation. A study of fasting insulin level and height was conducted in another HHP-HAAS subpopulation.ResultsA positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003-1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002-1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10-0.42; P = 0.001).ConclusionHeight in mid-life is positively associated with mortality, with shorter stature predicting longer lifespan. Height was, moreover, associated with fasting insulin level and the longevity genotype of FOXO3, consistent with a mechanistic role for the IIS pathway.

Project description:BACKGROUND AND OBJECTIVE:Males and females who use methamphetamine (MA) differ in sociodemographics, MA diagnoses, comorbidities, and brain activity. The objective of this study was to investigate sex differences in the characteristics of MA use and dependence in patients at a Thai substance treatment center. METHODS:Demographic, MA use, and diagnostic data for 782 MA users were obtained by using the Semi-Structured Assessment for Drug Dependence and Alcoholism-Thai version. Categorical comparisons of males (n?=?413, 53%) and females (n?=?369, 47%) were made by chi-square test. Factors significantly differentiating men and women with respect to MA-dependence were identified by logistic regression analysis controlling for demographic, diagnostic, and MA use variables. RESULTS:Males admitted to residential drug treatment for MA use had an earlier age of onset for both MA use (17.7?±?4.1 vs 19.7?±?6.2 years; t?=?-5.3, P?<?0.001) and dependence (20.4?±?5.2 vs 22.2?±?6.4 years; t?=?-3.6, P?<?0.001). Females were more likely than males to be MA-dependent (79% vs 60%; ?1?=?33.7, P?<?0.001), and to experience MA withdrawal (65.3% vs 48.9%; ?1?=?21.4, P?<?0.001), withdrawal-related hypersomnia (77.2% vs 64.8%; ?1?=?14.5, P?<?0.001), fatigue (77.5% vs 70.3%; ?1?=?5.2, P?=?0.02), and psychomotor retardation (64.5% vs 57.0%; ?1?=?4.5, P?=?0.03). Similarly, females had heavier (eg, largest daily amount [?1?=?12.4, P?<?0.001), more frequent (?1?=?5.1, P?=?0.02]) and greater lifetime episodes of MA use (?1?=?24.1, P?<?0.001) than males. After controlling for such variables by logistic regression, being female remained a significant factor influencing the occurrence of MA-dependence (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.8-4.1, P?<?0.001). Shared associated factors (or comorbidities) for MA-dependence in both sexes included nicotine dependence (in males: OR 4.1, 95% CI 2.4-7.0, P?<?0.001; and in females: OR 2.4, 95% CI 1.3-4.4, P?=?0.007), greater lifetime episodes of MA use (in males: OR 3.5, 95% CI 1.9-6.4, P?<?0.001; and in females: OR 5.9, 95% CI 3.1-11.4, P?<?0.001), and more frequent use (in males: OR 5.1, 95% CI 2.8-9.1, P?<?0.001; and in females: OR 3.6, 95% CI 1.9-6.9, P?<?0.001). Comorbid antisocial personality disorder predicted MA-dependence in males only (OR 3.7, 95% CI 1.6-8.6, P?=?0.002). CONCLUSIONS:The current study highlights both common (eg, nicotine dependence and severity of MA use) and sex-specific differences (eg, MA use/dependence characteristics and comorbidities), including sex itself, with respect to MA-dependence in a Thai treatment cohort.

Project description:Background and aimsMethamphetamine use is increasingly prevalent and associated with HIV transmission. Early-phase human studies suggested naltrexone reduced amphetamine use among dependent individuals. We tested if extended-release naltrexone (XRNTX) reduces methamphetamine use and associated sexual risk behaviors among high-risk methamphetamine-dependent men who have sex with men (MSM).DesignDouble-blind, placebo-controlled, randomized trial of XRTNX versus placebo over 12 weeks from 2012 to 2015.SettingSan Francisco Department of Public Health, California, USA.ParticipantsOne hundred community-recruited, sexually-active, actively-using methamphetamine-dependent MSM. Mean age was 43.2 years; 96% were male, 3% transfemale, and 1% transmale; 55.0% were white, 19.0% African American, and 18.0% Latino.InterventionsXRNTX 380 mg (n = 50) or matched placebo (n = 50) administered by gluteal injection at 4-week intervals.MeasurementsRegression estimated average level and change in level of positive urines during the period 2-12 weeks (primary outcomes) and sexual risk behaviors (secondary outcome).FindingsNinety per cent of visits were completed. By intent-to-treat, participants assigned to XRNTX had similar differences during 2-12 weeks in methamphetamine-positive urines as participants assigned to placebo [incidence rate ratio (IRR) = 0.95, 95% confidence interval (CI) = 0.76-1.20; Bayes factor < 0.3]. Observed urine positivity declined from 78 to 70% in the XRNTX arm and 74 to 64% in the placebo arm. Adherence to injections was 96.7% in the XRNTX arm and 91.3% in the placebo arm. Sexual risk behaviors declined similarly among participants in both arms (all P > 0.05). There were no serious adverse events related to study drug and no differences in frequency of adverse events by treatment arm.ConclusionsNotwithstanding very high medication adherence for this study, extended-release naltrexone does not appear to reduce methamphetamine use or sexual risk behaviors among methamphetamine-dependent men who have sex with men compared with placebo.

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Neurofunctional Differences Related to Methamphetamine and Sexual Cues in Men With Shorter and Longer Term Abstinence Methamphetamine Dependence.

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