| 1. |
- Bershad, Anya K., et al.
(author)
-
Effects of MDMA on attention to positive social cues and pleasantness of affective touch
- 2019
-
In: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 44:10, s. 1698-1705
-
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.
|
|
| 2. |
- Cavallo, Joel S., et al.
(author)
-
Acquisition of Conditioning between Methamphetamine and Cues in Healthy Humans
- 2016
-
In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:8, s. e0161541-
-
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.
|
|
| 3. |
- Johansson Capusan, Andrea, et al.
(author)
-
Re-examining the link between childhood maltreatment and substance use disorder: a prospective, genetically informative study
- 2021
-
In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:7, s. 3201-3209
-
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.
|
|
| 4. |
- Kroll, Sara, et al.
(author)
-
Negative self-evaluation induced by acute stress indexed using facial EMG
- 2021
-
In: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 133
-
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.
|
|
| 5. |
|
|
| 6. |
- Mayo, Leah, et al.
(author)
-
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
-
In: Biological Psychiatry. - : ELSEVIER SCIENCE INC. - 0006-3223 .- 1873-2402. ; 87:6, s. 538-547
-
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.
|
|
| 7. |
- Mayo, Leah, et al.
(author)
-
In the face of stress: Interpreting individual differences in stress-induced facial expressions
- 2019
-
In: NEUROBIOLOGY OF STRESS. - : ELSEVIER SCIENCE INC. - 2352-2895. ; 10
-
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.
|
|
| 8. |
- Mayo, Leah M., et al.
(author)
-
Acquisition of Conditioned Responses to a Novel Alcohol-Paired Cue in Social Drinkers
- 2016
-
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
-
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.
|
|
| 9. |
- Mayo, Leah M, et al.
(author)
-
Conditioned Preference to a Methamphetamine-Associated Contextual Cue in Humans
- 2013
-
In: Neuropsychopharmacology. - : Nature Publishing Group: Open Access Hybrid Model Option A. - 0893-133X .- 1740-634X. ; 38:6, s. 921-929
-
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.
|
|
| 10. |
- Mayo, Leah M., 1987-, et al.
(author)
-
Gender differences in the behavioral and subjective effects of methamphetamine in healthy humans
- 2019
-
In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 236:8, s. 2413-2423
-
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.
|
|
| 11. |
- Mayo, Leah M., 1987-, et al.
(author)
-
Protective effects of elevated anandamide on stress and fear-related behaviors : translational evidence from humans and mice
- 2020
-
In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:5, s. 993-1005
-
Journal article (peer-reviewed)abstract
- Post-traumatic stress disorder (PTSD) is a common, debilitating condition with limited treatment options. Extinction of fear memories through prolonged exposure therapy, the primary evidence-based behavioral treatment for PTSD, has only partial efficacy. In mice, pharmacological inhibition of fatty acid amide hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear extinction, suggesting that FAAH inhibitors may aid fear extinction-based treatments. A human FAAH 385C-greater thanA substitution encodes an FAAH enzyme with reduced catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore offer a genetic model to evaluate the impact of elevations in AEA signaling in humans, helping to inform whether FAAH inhibitors have the potential to facilitate fear extinction therapy for PTSD. To overcome the challenge posed by low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423 individuals to examine the balanced groups of CC, AC, and AA individuals (n = 25/group). Consistent with its loss-of-function nature, the A allele was dose dependently associated with elevated basal AEA levels, facilitated fear extinction, and enhanced the extinction recall. Moreover, the A-allele homozygotes were protected against stress-induced decreases in AEA and negative emotional consequences of stress. In a humanized mouse model, AA homozygous mice were similarly protected against stress-induced decreases in AEA, both in the periphery, and also in the amygdala and prefrontal cortex, brain structures critically involved in fear extinction and regulation of stress responses. Collectively, these data suggest that AEA signaling can temper aspects of the stress response and that FAAH inhibition may aid the treatment for stress-related psychiatric disorders, such as PTSD.
|
|
| 12. |
- Mayo, Leah, et al.
(author)
-
Psychophysiological and Neural Support for Enhanced Emotional Reactivity in Female Adolescents With Nonsuicidal Self-injury
- 2021
-
In: Biological Psychiatry. - : Elsevier. - 2451-9022. ; 6:7, s. 682-691
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Nonsuicidal self-injury (NSSI) is prevalent in adolescent populations worldwide. Emotion dysregulation is believed to contribute to NSSI, but underlying mechanisms are less known. We combined psychophysiological and neural data with subjective self-report in close temporal proximity to examine the mechanisms underlying emotion processing in adolescents with NSSI relative to control adolescents without a psychiatric diagnosis. METHODS: Thirty female adolescents with NSSI and 30 age-matched female control subjects were included in this case-control study. Participants were presented with negative affective pictures during a functional magnetic resonance imaging scan. In a separate facial electromyography session, the same participants were shown positive and negative affective images and also provided ratings of valence and arousal. RESULTS: Participants with NSSI responded to affective images with greater positive (e.g., zygomatic) and greater negative (e.g., corrugator) reactivity. We found no differences in self-reported affect in response to the images. Analyses of the negative picture-viewing functional magnetic resonance imaging data showed a significant positive correlation between anterior insula response and the averaged electromyography magnitude in NSSI, but not in control subjects. CONCLUSIONS: Adolescents with NSSI show enhanced emotional reactivity that is associated with anterior insula responding, but no abnormalities in self-reported affect. This discrepancy between self-report and objective measures of emotional reactivity potentially indicates a suppression of the emotional reaction in adolescents with NSSI. Moreover, the current data suggest potential targets for novel therapeutic approaches that can be combined with existing clinical treatment, such as real-time electromyography-based biofeedback focusing on emotional awareness, labeling, and expressing emotional experiences.
|
|
| 13. |
- Mayo, Leah, et al.
(author)
-
Putting a good face on touch: Facial expression reflects the affective valence of caress-like touch across modalities
- 2018
-
In: Biological Psychology. - : ELSEVIER SCIENCE BV. - 0301-0511 .- 1873-6246. ; 137, s. 83-90
-
Journal article (peer-reviewed)abstract
- Touch plays a central role in interpersonal behavior, especially in its capacity to convey-and induce- changes in affect. Previous research has established that slow, caress-like stroking over the skin elicits positive subjective affective responses, with higher ratings of "pleasantness" compared to a faster-moving touch stimulus. Ratings of pleasantness are associated with increased activity of a distinct class of nerve fibers: C-tactile (CT) afferents. Here, we used facial electromyography (EMG) to determine if touch that optimally activates CT afferents also influences facial muscle activity believed to reflect changes in affect. We found that less pleasant, fast-moving stroking (30 cm/s) elicited robustly negative facial EMG responses, as indexed by stronger contraction of the corrugator muscle. In contrast, pleasant, slow-moving stroking (3 cm/s) that optimally activates CT afferents resulted in decreased negative facial affective responses, manifested as significant corrugator relaxation compared to fast stroking. Moreover, the facial tracking of affective valence during touch was supra-modal, with similar effects during both directly-experienced touch and viewing of touch videos. The results of this EMG study imply that touch that fails to optimally activate CT afferent produces a negative affective response, whereas pleasant, caress-like touch has not only subjective but expressive correlates, reflected in net positive affective changes in facial expression.
|
|
| 14. |
- Mayo, Leah, et al.
(author)
-
Targeting the Endocannabinoid System in the Treatment of Posttraumatic Stress Disorder : A Promising Case of Preclinical-Clinical Translation?
- 2022
-
In: Biological Psychiatry. - : Elsevier Science Inc. - 0006-3223 .- 1873-2402. ; 91:3, s. 262-272
-
Research review (peer-reviewed)abstract
- The endocannabinoid (eCB) system is one the most ubiquitous signaling systems of the brain and offers a rich pharmacology including multiple druggable targets. Preclinical research shows that eCB activity influences functional connectivity between the prefrontal cortex and amygdala and thereby influences an organisms ability to cope with threats and stressful experiences. Animal studies show that CB1 receptor activation within the amygdala is essential for extinction of fear memories. Failure to extinguish traumatic memories is a core symptom of posttraumatic stress disorder, suggesting that potentiating eCB signaling may have a therapeutic potential in this condition. However, it has been unknown whether animal findings in this domain translate to humans. Data to inform this critical question are now emerging and are the focus of this review. We first briefly summarize the biology of the eCB system and the animal studies that support its role in fear extinction and stress responding. We then discuss the pharmacological eCB-targeting strategies that may be exploited for therapeutic purposes: direct CB1 receptor activation, using Delta(9)-tetrahydrocannabinol or its synthetic analogs; or indirect potentiation, through inhibition of eCB-degrading enzymes, the anandamide-degrading enzyme fatty acid amide hydrolase; or the 2-AG (2-arachidonoyl glycerol)-degrading enzyme monoacylglycerol lipase. We then review recent human data on direct CB1 receptor activation via Delta(9)-tetrahydrocannabinol and anandamide potentiation through fatty acid amide hydrolase blockade. The available human data consistently support a translation of animal findings on fear memories and stress reactivity and suggest a potential therapeutic utility in humans.
|
|
| 15. |
- Middleton, Steven J, et al.
(author)
-
Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice.
- 2022
-
In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156 .- 0006-8950. ; 145:10, s. 3637-3653
-
Journal article (peer-reviewed)abstract
- Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch.
|
|
| 16. |
- Ney, Luke J., et al.
(author)
-
Translation of animal endocannabinoid models of PTSD mechanisms to humans: Where to next?
- 2022
-
In: Neuroscience and Biobehavioral Reviews. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0149-7634 .- 1873-7528. ; 132, s. 76-91
-
Journal article (peer-reviewed)abstract
- The endocannabinoid system is known to be involved in mechanisms relevant to PTSD aetiology and maintenance, though this understanding is mostly based on animal models of the disorder. Here we review how human paradigms can successfully translate animal findings to human subjects, with the view that substantially increased insight into the effect of endocannabinoid signalling on stress responding, emotional and intrusive memories, and fear extinction can be gained using modern paradigms and methods for assessing the state of the endocannabinoid system in PTSD.
|
|
| 17. |
- Perini, Irene, et al.
(author)
-
Altered relationship between subjective perception and central representation of touch hedonics in adolescents with autism-spectrum disorder
- 2021
-
In: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 11:1
-
Journal article (peer-reviewed)abstract
- An impairment of social communication is a core symptom of autism-spectrum disorder (ASD). Affective touch is an important means of social interaction, and C-Tactile (CT) afferents are thought to play a key role in the peripheral detection and encoding of these stimuli. Exploring the neural and behavioral mechanisms for processing CT-optimal touch (similar to 3 cm/s) may therefore provide useful insights into the pathophysiology of ASD. We examined the relationship between touch hedonics (i.e. the subjective pleasantness with which affective touch stimuli are perceived) and neural processing in the posterior superior temporal sulcus (pSTS). This region is less activated to affective touch in individuals with ASD, and, in typically developing individuals (TD), is correlated positively with touch pleasantness. TD and ASD participants received brushing stimuli at CT-optimal, and CT-non-optimal speeds during fMRI. Touch pleasantness and intensity ratings were collected, and affective touch awareness, a measure of general touch hedonics was calculated. As expected, slow touch was perceived as more pleasant and less intense than fast touch in both groups, whereas affective touch awareness was moderately higher in TD compared to ASD. There was a strong, positive correlation between right pSTS activation and affective touch awareness in TD, but not in ASD. Our findings suggest that altered neural coupling between right pSTS and touch hedonics in ASD may be associated with social touch avoidance in ASD.
|
|
| 18. |
- Perini, Irene, et al.
(author)
-
Beyond distress : a role for positive affect in nonsuicidal self-injury
- 2021
-
In: Current Opinion in Behavioral Sciences. - : Elsevier. - 2352-1546. ; 39, s. 209-215
-
Journal article (peer-reviewed)abstract
- The ability to generate and regulate emotional experiences is critical to psychological well-being. Impairments in emotion regulatory processes have transdiagnostic associations with psychopathology. Nonsuicidal self-injury (NSSI) is prevalent in adolescent populations, especially clinical adolescent populations, and often linked to emotion regulatory deficits. Clinical observations propose a role for NSSI behaviors in regulating affect, suggesting that these behaviors may arise when other emotion regulatory strategies are insufficient or inaccessible. Experimental evidence has begun to explore the psychophysiological and neural underpinnings of emotion processing in NSSI populations. Thus far, a primary focus has been the role of NSSI in regulation of affect in response to stressful or negative states or stimuli, often suggesting enhanced reactivity in such situations. However, recent evidence suggests that NSSI populations may also display heightened reactivity to positive or rewarding stimuli. Here, we highlight this emerging data and how it may be integrated into existing NSSI framework.
|
|
| 19. |
- Perini, Irene, et al.
(author)
-
Brain-based Classification of Negative Social Bias in Adolescents With Nonsuicidal Self-injury : Findings From Simulated Online Social Interaction.
- 2019
-
In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 13, s. 81-90
-
Journal article (peer-reviewed)abstract
- Background: Interpersonal stress and perceived rejection have been clinically observed as common triggers of nonsuicidal self-injury (NSSI), with self-injury behavior regulating both affective and social experiences. We investigated whether the subjective interpretation of social interaction in a simulated online environment might be biased in the NSSI group, and the brain mechanisms underlying the experience.Methods: Thirty female adolescent patients with NSSI and thirty female age-matched controls were investigated in this case-control study. In our novel task that simulates interaction on current social media platforms, participants indicated whether they liked or disliked pictures of other players during a functional magnetic resonance imaging (fMRI) scan. Participants also viewed positive and negative feedback directed toward them by others. The task also assessed the subjective effects of the social interaction. Finally, subjects underwent a separate facial electromyography session, which measured facial expressions processing.Outcomes: Behaviorally, the NSSI group showed a negative bias in processing social feedback from others. A multi-voxel pattern analysis (MVPA) identified brain regions that robustly classified NSSI subjects and controls. Regions in which mutual activity contributed to the classification included dorsomedial prefrontal cortex and subgenual anterior cingulate cortex, a region implicated in mood control. In the NSSI group, multi-voxel classification scores correlated with behavioral sensitivity to negative feedback from others. Results remained significant after controlling for medication, symptoms of depression, and symptoms of borderline personality disorder.Interpretation: This study identified behavioral and neural signatures of adolescents with NSSI during social interaction in a simulated social media environment. These findings highlight the importance of understanding social information processing in this clinical population and can potentially advance treatment approaches.
|
|
| 20. |
- Perini, Irene, 1983-, et al.
(author)
-
Resilience to substance use disorder following childhood maltreatment: association with peripheral biomarkers of endocannabinoid function and neural indices of emotion regulation
- 2023
-
In: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; :6, s. 2563-2571
-
Journal article (peer-reviewed)abstract
- Childhood maltreatment (CM) is a risk factor for substance use disorders (SUD) in adulthood. Understanding the mechanisms by which people are susceptible or resilient to developing SUD after exposure to CM is important for improving intervention. This case-control study investigated the impact of prospectively assessed CM on biomarkers of endocannabinoid function and emotion regulation in relation to the susceptibility or resilience to developing SUD. Four groups were defined across the dimensions of CM and lifetime SUD (N = 101 in total). After screening, participants completed two experimental sessions on separate days, aimed at assessing the behavioral, physiological, and neural mechanisms involved in emotion regulation. In the first session, participants engaged in tasks assessing biochemical (i.e., cortisol, endocannabinoids), behavioral, and psychophysiological indices of stress and affective reactivity. During the second session, the behavioral and brain mechanisms associated with emotion regulation and negative affect were investigated using magnetic resonance imaging. CM-exposed adults who did not develop SUD, operationally defined as resilient to developing SUD, had higher peripheral levels of the endocannabinoid anandamide at baseline and during stress exposure, compared to controls. Similarly, this group had increased activity in salience and emotion regulation regions in task-based measures of emotion regulation compared to controls, and CM-exposed adults with lifetime SUD. At rest, the resilient group also showed significantly greater negative connectivity between ventromedial prefrontal cortex and anterior insula compared to controls and CM-exposed adults with lifetime SUD. Collectively, these peripheral and central findings point to mechanisms of potential resilience to developing SUD after documented CM exposure.
|
|
| 21. |
- Perini, Irene, 1983-, et al.
(author)
-
Social Acts and Anticipation of Social Feedback
- 2022
-
In: Neuroscience of Social Stress. - Cham : Springer. - 9783031042560 - 9783031042553 ; , s. 393-416
-
Book chapter (other academic/artistic)abstract
- Socialization happens so regularly in humans that it can be perceived as an effortless activity. However, it reflects a sophisticated behavior, pervaded by anticipation and emotion. The fast-paced social interplay, strongly mediated by facial expressions, can be considered one of the most frequent high-order motor acts within the human behavioral repertoire. The ability to adequately process social feedback is critical for appropriate socialization and affects well-being. The social difficulties often observed in psychiatric patients highlight the link between mental health and successful socialization and the importance of characterizing the behavioral and neural mechanisms of social interaction. This chapter will present some cross-species evidence on the cortical regions engaged during social interactions including facial expressions, and the impact of induced or perceived social stress on the experience of social interactions.
|
|
| 22. |
- Ree, Anbjorn, et al.
(author)
-
Touch targeting C-tactile afferent fibers has a unique physiological pattern: A combined electrodermal and facial electromyography study
- 2019
-
In: Biological Psychology. - : ELSEVIER SCIENCE BV. - 0301-0511 .- 1873-6246. ; 140, s. 55-63
-
Journal article (peer-reviewed)abstract
- Caress-like touch is thought to rely on C-tactile (CT) fiber signaling. Here, the arousing and emotional effects of CT-optimal touch were assessed via participants skin conductance level (SCL), facial electromyography (EMG) responses and subjective ratings of pleasantness and intensity. Temporal facial EMG analysis was based on the conduction velocity of CT-fibers. 45 healthy participants received CT-optimal touch, control touch and visual control input during 2-minute trials. CT optimal touch was significantly more pleasant and intense than control touch. In the initial 700 ms of stimulation there was no difference in facial EMG responses to touch. Between 700 and 6300 ms there was a significant reduction of corrugator activity in response to CT optimal touch only, possibly reflecting the affective value of CT optimal touch. Based on the temporal dynamics of the reduced corrugator activity, we suggest that CT fibers are involved in mediating a reduction in corrugator activity.
|
|
| 23. |
|
|
| 24. |
- Spagnolo, Primavera A., et al.
(author)
-
FAAH Gene Variation Moderates Stress Response and Symptom Severity in Patients with Posttraumatic Stress Disorder and Comorbid Alcohol Dependence
- 2016
-
In: Alcoholism. - : WILEY-BLACKWELL. - 0145-6008 .- 1530-0277. ; 40:11, s. 2426-2434
-
Journal article (peer-reviewed)abstract
- BackgroundA common single nucleotide polymorphism (C385A) in the human fatty acid amide hydrolase (FAAH) gene has been associated with decreased distress responses in healthy volunteers, but its role in psychiatric disorders remains unknown. Here, we obtained genotypes and carried out a secondary analysis of subjects from a trial of comorbid posttraumatic stress disorder (PTSD) and alcohol dependence (AD). We evaluated the effects of C385A variation on behavioral and biochemical biomarkers of distress responses. MethodsForty-nine patients with PTSD and AD were admitted for 4weeks to an experimental medicine unit at the National Institutes of Health Clinical Center. Following detoxification, stress reactivity and peripheral endocannabinoid (eCB) levels were assessed in response to a challenge session using personalized auditory guided imagery. Over the course of the study, subjects were also evaluated for changes in PTSD symptom severity. ResultsFAAH C385A allele carriers showed a marked increase in serum anandamide levels at baseline and throughout the stress challenge procedure compared with C allele homozygotes, while levels of eCBs primarily metabolized through other enzymatic activity, such as 2-arachidonoylglycerol, did not differ between genotype groups. FAAH C385A carriers also had decreased subjective anxiety responses to the stress challenge. Similar effects of FAAH C385A genotype were found at the level of clinical PTSD symptom severity, in particular in the arousal domain. ConclusionsThis is to our knowledge the first study showing that FAAH C385A variation modulates stress responses in subjects with disorders characterized by increased stress reactivity. These findings point to the eCB pathway as a promising target for future antistress therapeutics.
|
|
| 25. |
- Van Hedger, Kathryne, et al.
(author)
-
Effects of Acute Drug Administration on Emotion : a Review of Pharmacological MRI Studies
- 2021
-
In: Current Addiction Reports. - : SPRINGERNATURE. - 2196-2952. ; 8:2, s. 181-193
-
Research review (peer-reviewed)abstract
- Purpose of Review Many drug users claim to use drugs to cope with negative emotions, which may, in turn, result in persistent emotional blunting or anhedonia even when they are not using drugs. The purpose of this review is to describe the ways acute administration of psychoactive drugs impacts brain regions during emotion-related tasks, as a first step in understanding how drugs influence emotion processing in the brain. Recent Findings Drugs have varying effects on neural responses to emotional stimuli. In general, alcohol, analgesics, and psychedelics reduce neural reactivity to negative emotional stimuli in the amygdala and other brain regions. Other drugs produce mixed effects: Stimulants such as caffeine and modafinil increase brain activation while viewing emotional stimuli, whereas MDMA decreases activation during presentation of negative images. The effects of cannabinoids (cannabidiol and THC) are mixed. There are also inconsistent findings on the associations between neural responses to emotional stimuli and subjective drug effects. Consistent with the notion that individuals might use drugs non-medically to diminish the experience of negative emotions, several drugs of abuse decrease neural responses to negative stimuli in limbic brain regions. These neural actions may underlie the reported "emotional blunting" of drugs, which may contribute to drug-seeking behavior. Future work is needed to examine these limbic responses in relation to self-reports of changes in affect, both during acute administration and after extended drug use.
|
|
