Background Developing the means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to ...smoking-related cues, measured before a quit attempt, could identify smokers with heightened relapse vulnerability. Methods Before quitting smoking, 21 nicotine-dependent women underwent fMRI during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence vs. slip: smoking ≥ 1 cigarette after attaining abstinence). Prequit fMRI and ES measurements in these groups were compared. Results Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Insula and dorsal anterior cingulate cortex (dACC) reactivity induced by smoking images correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of cue-induced emotions. Conclusions These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality.
Over 200 in vivo magnetic resonance spectroscopy (MRS) studies of substance use and related disorders (SUD) were published this past decade. The large majority of this work used proton (1H)-MRS to ...characterize effects of acute and chronic exposures to drugs of abuse on human brain metabolites including N-acetylaspartate, choline-containing metabolites, creatine plus phosphocreatine, glutamate, and GABA. Some studies used phosphorus (31P)-MRS to quantify biomarkers of cerebral metabolism including phosphocreatine and adenosine triphosphate. A few studies used carbon (13C)-MRS to quantify intermediary metabolism. This Mini-review discusses select studies that illustrate how MRS can complement neurocircuitry research including by use of multimodal imaging strategies that combine MRS with functional MRI (fMRI) and/or diffusion tensor imaging (DTI). Additionally, magnetic resonance spectroscopic imaging (MRSI), which enables simultaneous multivoxel MRS acquisitions, can be used to better understand and interpret whole-brain functional or structural connectivity data. The review discusses some limitations in MRS methodology and then highlights important knowledge gaps and areas for potential future investigation, including the use of 1H- and 31P-MRS to quantify cerebral metabolism, oxidative stress, inflammation, and brain temperature, all of which are associated with SUD and all of which can influence neurocircuitry and behavior.
•Magnetic resonance spectroscopy (MRS) allows study of neurochemistry and physiology.•Brain MRS abnormalities are common in substance use disorders (SUDs).•MRS can report on brain metabolism, oxidative stress, inflammation, and temperature.•Abnormalities in these processes in SUDs can alter neurocircuitry.•Thus, harnessing these MRS capabilities could advance SUD neurocircuitry research.
Nearly 800,000 suicides occur worldwide annually and suicide rates are increasing faster than population growth. Unfortunately, the pathophysiology of suicide remains poorly understood, which has ...hindered suicide prevention efforts. However, mechanistic clues may be found by studying effects of seasonality on suicide and other mortality causes. Suicides tend to peak in spring-summer periods and nadir in fall-winter periods while circulatory system disease-related mortality tends to exhibit the opposite temporal trends. This study aimed to determine for the first time whether monthly temporal cross-correlations exist between suicide and circulatory system disease-related mortality at the population level. If so and if common biological factors moderate risks for both mortality types, such factors may be discoverable and utilized to improve suicide prevention.
We conducted time series analyses of monthly mortality data from northern (England and Wales, South Korea, United States) and southern (Australia, Brazil) hemisphere countries during the period 2009-2018 (N = 41.8 million all-cause mortality cases). We used a Poisson regression variant of the standard cosinor model to determine peak months of mortality. We also estimated cross-correlations between monthly mortality counts from suicide and from circulatory system diseases.
Suicide and circulatory disease-related mortality temporal patterns were negatively correlated in Australia (- 0.32), Brazil (- 0.57), South Korea (- 0.32), and in the United States (- 0.66), but no temporal correlation was discernable in England and Wales.
The negative temporal cross-correlations between these mortality types we found in 4 of 5 countries studied suggest that seasonal factors broadly and inversely moderate risks for circulatory disease-related mortality and suicide, but not in all regions, indicating that the effect is not uniform. Since the seasonal factors of temperature and light exert opposite effects on suicide and circulatory disease-related mortality in several countries, we propose that physiologically-adaptive circulatory system responses to heat and light may increase risk for suicide and should be studied to determine whether they affect suicide risk. For example, heat and light increase production and release of the bioactive gas nitric oxide and reduce circulatory system disease by relaxing blood vessel tone, while elevated nitric oxide levels are associated with suicidal behavior, inverse effects that parallel the inverse temporal mortality patterns we detected.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Supraphysiologic-dose anabolic-androgenic steroid use, which typically commences by the mid-20s, induces early-onset hypogonadism and excess oxidative stress. In turn, these abnormalities alter the ...function of many proteins involved in Aβ and tau-P synthesis and elimination. This could result in early-onset accumulation of these proteins in brain and increased risk for developing Alzheimer's Disease and its related dementias.
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•Supraphysiologic-dose anabolic-androgenic steroid (sAAS) use starts by the mid-20s.•sAAS use occurs primarily in men aiming to increase muscularity.•sAAS use causes health problems including hypogonadism & excess oxidative stress.•These effects may increase synthesis & decrease elimination of Aβ & tau-P proteins.•sAAS use may cause early Aβ & tau-P increases and may enhance risk for dementia.
Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain β-amyloid (Aβ) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aβ and tau-P. Aβ and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.
Xenon (Xe) is a noble gas that has been developed for use in people as an inhalational anesthestic and a diagnostic imaging agent. Xe inhibits glutamatergic N-methyl-D-aspartate (NMDA) receptors ...involved in learning and memory and can affect synaptic plasticity in the amygdala and hippocampus, two brain areas known to play a role in fear conditioning models of post-traumatic stress disorder (PTSD). Because glutamate receptors also have been shown to play a role in fear memory reconsolidation--a state in which recalled memories become susceptible to modification--we examined whether Xe administered after fear memory reactivation could affect subsequent expression of fear-like behavior (freezing) in rats. Male Sprague-Dawley rats were trained for contextual and cued fear conditioning and the effects of inhaled Xe (25%, 1 hr) on fear memory reconsolidation were tested using conditioned freezing measured days or weeks after reactivation/Xe administration. Xe administration immediately after fear memory reactivation significantly reduced conditioned freezing when tested 48 h, 96 h or 18 d after reactivation/Xe administration. Xe did not affect freezing when treatment was delayed until 2 h after reactivation or when administered in the absence of fear memory reactivation. These data suggest that Xe substantially and persistently inhibits memory reconsolidation in a reactivation and time-dependent manner, that it could be used as a new research tool to characterize reconsolidation and other memory processes, and that it could be developed to treat people with PTSD and other disorders related to emotional memory.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Opioid withdrawal symptoms (OWS) are highly aversive and prompt unprescribed opioid use, which increases morbidity, mortality, and, among individuals being treated for opioid use disorder (OUD), ...recurrence. OWS are driven by sympathetic nervous system (SNS) hyperactivity that occurs when blood opioid levels wane. We tested whether brief inhalation of xenon gas, which inhibits SNS activity and is used clinically for anesthesia and diagnostic imaging, attenuates naltrexone-precipitated withdrawal-like signs in morphine-dependent mice.
Adult CD-1 mice were implanted with morphine sulfate-loaded (60 mg/ml) minipumps and maintained for 6 days to establish morphine dependence. On day 7, mice were given subcutaneous naltrexone (0.3 mg/kg) and placed in a sealed exposure chamber containing either 21% oxygen/balance nitrogen (controls) or 21% oxygen/added xenon peaking at 30%/balance nitrogen. After 10 minutes, mice were transferred to observation chambers and videorecorded for 45 minutes. Videos were scored in a blind manner for morphine withdrawal behaviors. Data were analyzed using 2-way ANOVAs testing for treatment and sex effects.
Xenon-exposed mice exhibited fewer jumps (P = 0.010) and jumping suppression was detectible within the first 10-minute video segment, but no sex differences were detected. Brief inhalation of low concentration xenon rapidly and substantially attenuated naltrexone-precipitated jumping in morphine-dependent mice, suggesting that it can inhibit OWS. If xenon effects translate to humans with OUD, xenon inhalation may be effective for reducing OWS, unprescribed opioid use, and for easing OUD treatment initiation, which could help lower excess morbidity and mortality associated with OUD.
•Opioid withdrawal symptoms (OWS) trigger unprescribed opioid use.•Unprescribed opioid use increases risks for recurrence, morbidity, and mortality.•We tested effects of inhaled xenon gas (10 min) on OWS in morphine-dependent mice.•Xenon (20% mean concentration) reduced naltrexone-precipitated jumping counts.•Xenon is used clinically for anesthesia & imaging & may be useful for reducing OWS.
Background and Objectives
Anabolic‐androgenic steroid (AAS) use has become a major worldwide substance use disorder, affecting tens of millions of individuals. Importantly, it is now increasingly ...recognized that some individuals develop uncharacteristically violent or criminal behaviors when using AAS. We sought to summarize available information on this topic.
Methods
We reviewed the published literature on AAS‐induced behavioral effects and augmented this information with extensive observations from our clinical and forensic experience.
Results
It is now generally accepted that some AAS users develop uncharacteristically violent or criminal behaviors while taking these drugs. Although these behaviors may partially reflect premorbid psychopathology, sociocultural factors, or expectational effects, accumulating evidence suggests that they are also attributable to biological effects of AAS themselves. The mechanism of these effects remains speculative, but preliminary data suggest a possible role for brain regions involved in emotional reactivity, such as the amygdala and regions involved in cognitive control, including the frontal cortex. For unknown reasons, these effects appear idiosyncratic; most AAS users display few behavioral effects, but a minority develops severe effects.
Conclusion and Scientific Significance
Professionals encountering AAS users in clinical or forensic settings should be alert to the possibility of AAS‐induced violence or criminality and should employ strategies to assess whether AAS is indeed a contributory factor in a given case. Further research is needed to elucidate the mechanism of AAS‐induced violence and to explain why only a subset of AAS users appears vulnerable to these effects. (Am J Addict 2021;00:00–00)
Public health impact of androgens Kanayama, Gen; Kaufman, Marc J; Pope, Jr, Harrison G
Current opinion in endocrinology, diabetes and obesity./Current opinion in endocrinology, diabetes and obesity,
06/2018, Letnik:
25, Številka:
3
Journal Article
Recenzirano
Odprti dostop
To summarize recent findings regarding the public health impact of androgen abuse.
Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse ...problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease. Withdrawal from androgens after long-term use may produce prolonged and sometimes irreversible hypogonadism in men. Supraphysiologic androgen levels may sometimes cause irritability, aggressiveness, and violence, whereas androgen withdrawal may cause depression. However, these psychiatric effects are idiosyncratic, affecting only a minority of users. Emerging evidence now also suggests that long-term androgen exposure may cause neurotoxicity, raising the possibility that aging androgen abusers may be at increased risk for dementia. Several recent studies have also described androgen-induced hepatotoxicity, nephrotoxicity, and adverse musculoskeletal effects.
Recent studies have demonstrated marked adverse effects of long-term androgen abuse. As increasing numbers of androgen abusers reach middle age, these effects will likely represent an emerging public health problem.
Accumulating evidence suggests the involvement of abnormal glutamateric neurotransmission and N-methyl-D-aspartate receptor hypofunction in the pathophysiology of psychotic disorders. The purpose of ...this study was to quantify in vivo glutamate (Glu) and glycine (Gly) levels in patients with first-episode psychosis as well as age-matched healthy control subjects with magnetic resonance spectroscopy (MRS).
The subjects were 46 patients with first-episode psychosis (20 with a schizophrenia spectrum disorder, 26 with bipolar disorder) and 50 age-matched healthy control subjects. Glu and Gly levels were measured in vivo in the anterior cingulate cortex and posterior cingulate cortex of the subjects by using the echo time–averaged proton MRS technique at 4T (i.e., modified point resolved spectroscopy sequence: 24 echo time steps with 20-ms increments). Metabolite levels were quantified using LCModel with simulated basis sets.
Significantly higher Glu and Gly levels were found in both the anterior cingulate cortex and posterior cingulate cortex of patients with first-episode psychosis as compared with healthy control subjects. Glu and Gly levels were positively correlated in patients. Patients with a schizophrenia spectrum disorder and bipolar disorder showed similar abnormalities.
Our findings demonstrate abnormally elevated brain Glu and Gly levels in patients with first-episode psychosis by means of echo time–averaged proton MRS at 4T. The findings implicate dysfunction of N-methyl-D-aspartate receptor and glutamatergic neurotransmission in the pathophysiology of the acute early phase of psychotic illnesses.
Rationale
Cocaine use disorder (CUD) is associated with cognitive deficits that have been linked to poor treatment outcomes. An improved understanding of cocaine’s deleterious effects on cognition ...may help optimize pharmacotherapies. Emerging evidence implicates abnormalities in glutamate neurotransmission in CUD and drugs that normalize glutamatergic homeostasis (e.g.,
N
-acetylcysteine NAC) may attenuate CUD-related relapse behavior.
Objectives
The present studies examined the impact of chronic cocaine exposure on touchscreen-based models of learning (repeated acquisition) and cognitive flexibility (discrimination reversal) and, also, the ability of NAC to modulate cocaine self-administration and its capacity to reinstate drug-seeking behavior.
Methods
First, stable repeated acquisition and discrimination reversal performance was established. Next, high levels of cocaine-taking behavior (2.13–3.03 mg/kg/session) were maintained for 150 sessions during which repeated acquisition and discrimination reversal performance was probed periodically. Finally, the effects of NAC treatment were examined on cocaine self-administration and, subsequently, extinction and reinstatement.
Results
Cocaine self-administration significantly impaired performance under both cognitive tasks; however, discrimination reversal was disrupted considerably more than acquisition. Performance eventually approximated baseline levels during chronic exposure. NAC treatment did not perturb ongoing self-administration behavior but was associated with significantly quicker extinction of drug-lever responding. Cocaine-primed reinstatement did not significantly differ between groups.
Conclusions
The disruptive effects of cocaine on learning and cognitive flexibility are profound but performance recovered during chronic exposure. Although the effects of NAC on models of drug-taking and drug-seeking behavior in monkeys are less robust than reported in rodents, they nevertheless suggest a role for glutamatergic modulators in CUD treatment programs.
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