| 1. |
- Bershad, Anya K., et al.
(author)
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Effects of MDMA on attention to positive social cues and pleasantness of affective touch
- 2019
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In: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 44:10, s. 1698-1705
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Journal article (peer-reviewed)abstract
- The psychostimulant drug +/- 3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, "affective" touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.
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| 2. |
- Cavallo, Joel S., et al.
(author)
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Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans
- 2016
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:8, s. e0161541-
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Journal article (peer-reviewed)abstract
- Environmental stimuli repeatedly paired with drugs of abuse can elicit conditioned responses that are thought to promote future drug seeking. We recently showed that healthy volunteers acquired conditioned responses to auditory and visual stimuli after just two pairings with methamphetamine (MA, 20 mg, oral). This study extended these findings by systematically varying the number of drug-stimuli pairings. We expected that more pairings would result in stronger conditioning. Three groups of healthy adults were randomly assigned to receive 1, 2 or 4 pairings (Groups P1, P2 and P4, Ns = 13, 16, 16, respectively) of an auditory-visual stimulus with MA, and another stimulus with placebo (PBO). Drug-cue pairings were administered in an alternating, counterbalanced order, under double-blind conditions, during 4 hr sessions. MA produced prototypic subjective effects (mood, ratings of drug effects) and alterations in physiology (heart rate, blood pressure). Although subjects did not exhibit increased behavioral preference for, or emotional reactivity to, the MA-paired cue after conditioning, they did exhibit an increase in attentional bias (initial gaze) toward the drug-paired stimulus. Further, subjects who had four pairings reported " liking" the MApaired cue more than the PBO cue after conditioning. Thus, the number of drug-stimulus pairings, varying from one to four, had only modest effects on the strength of conditioned responses. Further studies investigating the parameters under which drug conditioning occurs will help to identify risk factors for developing drug abuse, and provide new treatment strategies.
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| 3. |
- Johansson Capusan, Andrea, et al.
(author)
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Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study
- 2021
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In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:7, s. 3201-3209
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Journal article (peer-reviewed)abstract
- Childhood maltreatment is considered a risk factor for substance use disorders (SUD), but this is largely based on retrospective self-reports that are subject to recall bias, designs that do not control for familial confounding, or both. The specific contribution of childhood maltreatment to SUD risk thus remains unclear. Here, we evaluated this contribution in a prospective cohort with objectively recorded childhood maltreatment, using a design that allows controlling for familial confounding. We used medical records and registers to study 525 young adults (20-37 years) with prospectively and objectively documented severe maltreatment exposure, 1979 clinical controls (unexposed former child and adolescent psychiatry patients), 1388 matched healthy controls; and their siblings and cousins. We examined the association between maltreatment and SUD using Cox regression models in the population, as well as stratified within siblings in the same family. SUD risk was significantly increased with childhood maltreatment exposure (crude HR: 6.61, 95% CI: 5.81-7.53; HR adjusted for sex, birthyear, externalizing problems, parents SUD and socioeconomic factors: 3.50, 95% CI 2.95, 4.16). An approximately threefold elevated SUD risk remained when comparing exposed individuals with their unexposed siblings (adjusted HR: 3.12, 95% CI 2.21, 4.42). We provide estimates of the association between childhood maltreatment and SUD accounting for possible confounds of both recall bias and familial factors. When familial confounding is controlled for, SUD risk attributable to severe childhood maltreatment is decreased, but nevertheless considerable. These findings establish a specific contribution of childhood maltreatment to SUD, underscoring the need for SUD prevention in young people exposed to maltreatment.
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| 4. |
- Kroll, Sara, et al.
(author)
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Negative self-evaluation induced by acute stress indexed using facial EMG
- 2021
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In: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 133
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Journal article (peer-reviewed)abstract
- Maladaptive stress responses are a key feature of several psychiatric disorders, but findings of stress effects on social behavior are inconsistent. Using a within-subject design, we investigated, in 35 healthy participants, the effects of acute stress on psychophysiological and behavioral responses during a simulated online social interaction task. Participants were exposed to established stress and non-stress exposure procedures in two separate sessions. During the task, participants liked or disliked pictures of other putative players and, similarly, saw their own picture being judged by others. After stress exposure, corrugator muscle activity (frowning) was significantly increased when participants saw their own picture while anticipating feedback from others. Consistently, zygomatic muscle activity (smiling) for self-evaluation was lower after stress than in the non-stress session. We found self-report of stress to be a significant predictor of corrugator activity in both sessions, indicating that higher levels of subjective stress overall were accompanied by increased negative self-evaluation. Surprisingly, no stress effects were found on behavioral measures of other-evaluation (i.e., percentage of dislikes to others), but corrugator response significantly predicted the percentage of dislikes during the stress session only. Overall, our findings suggest that stress increases negative self-evaluation as indexed by elevated corrugator activity. Furthermore, stress might sharpen the consistency between corrugator activity and negative evaluation of others. Our results indicate that negative self-evaluation might be a useful therapeutic target in patients with stressrelated psychiatric disorders. In this context, facial muscle activity may be an adequate biomarker for identifying stress-related differences in self-evaluation.
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| 5. |
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| 6. |
- Mayo, Leah, et al.
(author)
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Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial
- 2020
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In: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 87:6, s. 538-547
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Journal article (peer-reviewed)abstract
- BACKGROUND: Posttraumatic stress disorder, an area of large unmet medical needs, is characterized by persistence of fear memories and maladaptive stress responses. In rodents, elevation of the endocannabinoid anandamide due to inhibition of fatty acid amide hydrolase (FAAH) facilitates fear extinction and protects against the anxiogenic effects of stress. We recently reported that elevated anandamide levels in people homozygous for a loss-of-function FAAH mutation are associated with a similar phenotype, suggesting a translational validity of the preclinical findings. METHODS: In this double-blind, placebo-controlled experimental medicine study, healthy adults were randomized to an FAAH inhibitor (PF-04457845, 4 mg orally, once daily; n = 16) or placebo (n = 29) for 10 days. On days 9 and 10, participants completed a task battery assessing psychophysiological indices of fear learning, stress reactivity, and stress-induced affective responses. RESULTS: FAAH inhibition produced a 10-fold increase in baseline anandamide. This was associated with potentiated recall of fear extinction memory when tested 24 hours after extinction training. FAAH inhibition also attenuated autonomic stress reactivity, assessed via electrodermal activity, and protected against stress-induced negative affect, measured via facial electromyography. CONCLUSIONS: Our data provide preliminary human evidence that FAAH inhibition can improve the recall of fear extinction memories and attenuate the anxiogenic effects of stress, in a direct translation of rodent findings. The beneficial effects of FAAH inhibition on fear extinction, as well as stress- and affect-related behaviors, provide a strong rationale for developing this drug class as a treatment for posttraumatic stress disorder.
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| 7. |
- Mayo, Leah, et al.
(author)
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In the face of stress: Interpreting individual differences in stress-induced facial expressions
- 2019
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In: NEUROBIOLOGY OF STRESS. - : ELSEVIER SCIENCE INC. - 2352-2895. ; 10
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Research review (peer-reviewed)abstract
- Stress is an inevitable part of life that can profoundly impact social and emotional functioning, contributing to the development of psychiatric disease. One key component of emotion and social processing is facial expressions, which humans can readily detect and react to even without conscious awareness. Facial expressions have been the focus of philosophic and scientific interest for centuries. Historically, facial expressions have been relegated to peripheral indices of fixed emotion states. More recently, affective neuroscience has undergone a conceptual revolution, resulting in novel interpretations of these muscle movements. Here, we review the role of facial expressions according to the leading affective neuroscience theories, including constructed emotion and social-motivation accounts. We specifically highlight recent data (Mayo et al, 2018) demonstrating the way in which stress shapes facial expressions and how this is influenced by individual factors. In particular, we focus on the consequence of genetic variation within the endocannabinoid system, a neuromodulatory system implicated in stress and emotion, and its impact on stress-induced facial muscle activity. In a re-analysis of this dataset, we highlight how gender may also influence these processes, conceptualized as variation in the "fight-or-flight" or "tend-and-befriend" behavioral responses to stress. We speculate on how these interpretations may contribute to a broader understanding of facial expressions, discuss the potential use of facial expressions as a trans-diagnostic marker of psychiatric disease, and suggest future work necessary to resolve outstanding questions.
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| 8. |
- Mayo, Leah M., et al.
(author)
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Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers
- 2016
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In: Journal of Studies on Alcohol and Drugs. - Piscataway, NJ, United States : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 77:2, s. 317-326
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Journal article (peer-reviewed)abstract
- Objective: This study examined the acquisition of conditioning between novel stimuli and single doses of alcohol in social drinkers. Environmental stimuli present during the consumption of alcohol or other drugs come to elicit conditioned responses that subsequently increase drug seeking. However, relatively few studies have examined the process of acquisition of these conditioned drug responses in human subjects. Method: We used a procedure previously developed to study acquisition of conditioned responses to a methamphetamine-associated cue. In the present study we applied the paradigm to alcohol, pairing de novo neutral cues with alcohol in social drinkers (N=36). We obtained measures of self-report, behavioral preference, emotional reactivity (assessed using facial electromyography), and attention to specific cues paired with administration of 0.6 g/kg 95% absolute alcohol or placebo. Results: After conditioning, participants showed an increase in attention toward the alcohol-paired cue, and this increase was associated with ratings of liking the alcohol-containing beverage during the conditioning sessions. In contrast to our previous findings with methamphetamine, the alcohol-paired cue did not elicit changes in emotional reactivity (measured by facial electromyography) or behavioral preference. Conclusions: This study extends our previous findings with a stimulant drug to. alcohol and highlights possible similarities and differences in conditioning with different classes of drugs. Conditioning with alcohol was less robust than with methamphetamine, but in both cases the conditioning that did occur was related to positive subjective drug response.
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| 9. |
- Mayo, Leah M, et al.
(author)
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Conditioned Preference to a Methamphetamine-Associated Contextual Cue in Humans
- 2013
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In: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:6, s. 921-929
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Journal article (peer-reviewed)abstract
- Classical conditioning is widely used to study motivational properties of addictive drugs in animals, but has rarely been used in humans. We established a procedure suitable for studying the neurobiology and individual determinants of classical conditioning in humans. Healthy volunteers were randomly assigned to four groups that received methamphetamine or placebo in the presence of distinctive environmental cues under paired or unpaired conditions. During each session, subjects performed tasks known to activate the ventral striatum. Tasks were performed in the presence of a distinctive context, consisting of a screen background image of a beach or mountains, accompanied by corresponding sounds. Separate groups of subjects carried out the tasks under high ($35-50) or low ($5-20) reward conditions. Within each of the two reward conditions, one group (paired) received methamphetamine (20 mg, oral) or placebo consistently associated with one of the contexts, while the other (unpaired) received drug or placebo unrelated to context. A fifth group (paired) performed the tasks with contextual cues but in the absence of monetary incentives. Before and after conditioning, participants carried out a series of forced choice tasks for the contextual cues, and change of preference over time was analyzed. All paired groups showed a significant increase in preference for the drug-associated context, with a linear trend for increase across the levels of reward. Preference was unrelated to subjective drug effects, and did not change in the unpaired group. These data support the translational utility of our conditioning procedure for studies of reward mechanisms in humans.
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| 10. |
- Mayo, Leah M., 1987-, et al.
(author)
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Gender differences in the behavioral and subjective effects of methamphetamine in healthy humans
- 2019
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 236:8, s. 2413-2423
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Journal article (peer-reviewed)abstract
- RationaleMethamphetamine (MA) use is steadily increasing and thus constitutes a major public health concern. Women seem to be particularly vulnerable to developing MA use disorder, as they initiate use at a younger age and transition more quickly to problematic use. Initial drug responses may predict subsequent use, but little information exists on potential gender differences in the acute effects of MA prior to dependence.ObjectiveWe examined gender differences in the acute effects of MA on subjective mood and reward-related behavior in healthy, non-dependent humans.MethodsMen (n = 44) and women (n = 29) completed 4 sessions in which they received placebo or MA under double-blind conditions twice each. During peak drug effect, participants completed the monetary incentive delay task to assess reaction times to cues signaling potential monetary losses or gains, in an effort to determine if MA would potentiate reward-motivated behavior. Cardiovascular and subjective drug effects were assessed throughout sessions.ResultsOverall, participants responded more quickly to cues predicting incentivized trials, particularly large-magnitude incentives, than to cues predicting no incentive. MA produced faster reaction times in women, but not in men. MA produced typical stimulant-like subjective and cardiovascular effects in all participants, but subjective ratings of vigor and (reduced) sedation were greater in women than in men.ConclusionsWomen appear to be more sensitive to the psychomotor-related behavioral and subjective effects of MA. These findings provide initial insight into gender differences in acute effects of MA that may contribute to gender differences in problematic MA use.
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