Oxazepam and cognitive reappraisal: A randomised experiment.

BACKGROUND: Cognitive reappraisal is a strategy for emotional regulation, important in the context of anxiety disorders. It is not known whether anxiolytic effects of benzodiazepines affect cognitive reappraisal. AIMS: We aimed to investigate the effect of 25 mg oxazepam on cognitive reappraisal. METHODS: In a preliminary investigation, 33 healthy male volunteers were randomised to oxazepam or placebo, and then underwent an experiment where they were asked to use cognitive reappraisal to upregulate or downregulate their emotional response to images with negative or neutral emotional valence. We recorded unpleasantness ratings, skin conductance, superciliary corrugator muscle activity, and heart rate. Participants completed rating scales measuring empathy (Interpersonal Reactivity Index, IRI), anxiety (State-Trait Anxiety Inventory, STAI), alexithymia (Toronto Alexithymia Scale-20, TAS-20), and psychopathy (Psychopathy Personality Inventory-Revised, PPI-R). RESULTS: Upregulation to negative-valence images in the cognitive reappraisal task caused increased unpleasantness ratings, corrugator activity, and heart rate compared to downregulation. Upregulation to both negative- and neutral-valence images caused increased skin conductance responses. Oxazepam caused lower unpleasantness ratings to negative-valence stimuli, but did not interact with reappraisal instruction on any outcome. Self-rated trait empathy was associated with stronger responses to negative-valence stimuli, whereas self-rated psychopathic traits were associated with weaker responses to negative-valence stimuli. CONCLUSIONS: While 25 mg oxazepam caused lower unpleasantness ratings in response to negative-valence images, we did not observe an effect of 25 mg oxazepam on cognitive reappraisal.

Does Alcohol Hangover Affect Emotion Regulation Capacity? Evidence From a Naturalistic Cross-Over Study Design.

AIMS: The aim of this study was to investigate the effects of alcohol hangover on emotion regulation. METHODS: Forty-five non-smoking, healthy participants aged between 18 and 30 years completed a lab-based emotion regulation task assessing cognitive reappraisal and an emotion regulation questionnaire (State-Difficulties in Emotion Regulation Scale [S-DERS]) when hungover (morning following a night of heavy drinking) and under a no-hangover condition in a naturalistic, within-subjects design study. RESULTS: Participants reported poorer emotion regulation overall (P < 0.001, d = 0.75), and for the subscales 'Non-Acceptance', 'Modulation' and 'Clarity' (Ps ≤ 0.001, ds ≥ 0.62), but not 'Awareness' on the S-DERS, in the hangover versus the no-hangover condition. Hangover did not impair emotion regulation ability as assessed using the lab-based task (Ps ≥ 0.21, ds ≤ 0.40), but there was a general negative shift in valence ratings (i.e. all images were rated more negatively) in the hangover relative to the no-hangover condition (P < 0.001, d = 1.16). CONCLUSION: These results suggest that emotion regulation in everyday life and emotional reactivity may be adversely affected by alcohol hangover, but some emotion regulation strategies (e.g. deliberate cognitive reappraisal) may be unaffected.

Effects of exogenous testosterone application on network connectivity within emotion regulation systems.

Studies with steroid hormones underlined the vital role of testosterone on social-emotional processing. However, there is still a lack of studies investigating whether testosterone modulates network connectivity during resting-state. Here, we tested how the exogenous application of testosterone would affect functional connectivity between regions implicated in emotion regulation. In total, 96 male participants underwent resting-state fMRI scanning. Before the measurement, half of the subjects received 5 g TestimTM gel (containing 50 mg testosterone) and the other half a corresponding amount of placebo gel. Seeds for the connectivity analysis were meta-analytically defined. First, all regions associated with emotion regulation were chosen via Neurosynth (data driven). Among those, specific seeds were selected and categorized based on the neural model of emotion regulation by Etkin and colleagues (Etkin et al., 2015) (theory-guided). Resting-state connectivity analysis revealed decreased connectivity between the right DLPFC and the right amygdala as well as between the VMPFC and the left IPL for the testosterone group compared to the placebo group. A complementary dynamic causal modeling (DCM) analysis on findings from the resting-state connectivity analysis underlined a bidirectional coupling which was decreased close to zero by testosterone administration. Our results demonstrate that testosterone administration disrupts resting-state connectivity within fronto-subcortical and fronto-parietal circuits. The findings suggest that even without a specific task (e.g. challenge, reward processing) testosterone modulates brain networks important for social-emotional processing.

Hormone-epigenome interactions in behavioural regulation.

Interactions between hormones and epigenetic factors are key regulators of behaviour, but the mechanisms that underlie their effects are complex. Epigenetic factors can modify sensitivity to hormones by altering hormone receptor expression, and hormones can regulate epigenetic factors by recruiting epigenetic regulators to DNA. The bidirectional nature of this relationship is becoming increasingly evident and suggests that the ability of hormones to regulate certain forms of behaviour may depend on their ability to induce changes in the epigenome. Moreover, sex differences have been reported for several epigenetic modifications, and epigenetic factors are thought to regulate sexual differentiation of behaviour, although specific mechanisms remain to be understood. Indeed, hormone-epigenome interactions are highly complex and involve both canonical and non-canonical regulatory pathways that may permit for highly specific gene regulation to promote variable forms of behavioural adaptation.

The Effect of Chronic Treatment with Lacosamide and Topiramate on Cognitive Functions and Impaired Emotional Responses in a Pilocarpine-induced Post-status Epilepticus Rat Model.

INTRODUCTION: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients. AIM: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus. MATERIALS AND METHODS: Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test. RESULTS: The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats. CONCLUSIONS: Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment.

Suggestion of cognitive enhancement improves emotion regulation.

Cognitive training seems a promising approach to enhance emotion regulation. To establish a causal connection, researchers must compare the training intervention with a control group that accounts for improvements induced by some factors other than the training. Despite this familiar methodology, the influence of expectations on the transfer effects of training remains poorly understood. We tested this possibility in 2 experiments, where a procedure was designed to intentionally induce a placebo effect via the suggestion of cognitive enhancement to evaluate the role of expectation in emotion regulation gains from cognitive training. Both the Placebo and Control groups completed the identical short-term working memory training (20 min) in Experiment 1. New participants were recruited to complete a long-term pseudotraining program (7 days) in Experiment 2. The results from the 2 experiments consistently showed that the Placebo group, who expected benefits from the training, unlike the Control group, showed less negative emotion and better regulatory effects after pseudotraining, irrespective of the duration of the training. Thus, inadequate control of expectation is a fundamental design flaw that potentially undermines any causal inferences. These findings also suggest a novel perspective for optimizing the experimental designs in psychological interventions and advancing the understanding of emotion regulation enhancement. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Greater delay discounting and cannabis coping motives are associated with more frequent cannabis use in a large sample of adult cannabis users.

BACKGROUND: Self-regulation deficits expressed through a decreased ability to value future rewards (delay discounting (DD)) and impaired emotion regulation (negative urgency (NU), cannabis coping motives (CCM), and anxiety sensitivity (AS)) relate to more frequent or problematic cannabis use. However, there is a need to better understand how self-regulation and emotion regulation constructs reflect competition between deliberative and reactive systems that drive individual differences in cannabis use patterns. Further, few studies assess frequency of cannabis use within and across days of use, which may obscure differentiation of individual differences. METHODS: In a large national sample of 2545 cannabis users, Latent Class Analysis was used to derive participant sub-classes based on two frequency indices, self-reported cannabis use days and times cannabis was used per day. Three classes emerged: Low (1-9 days/month, 1 time/day; 23 %), moderate (10-29 days/month, 2-3 times/day; 41 %), and high (30 days/month, ≥4 times/day; 36 %). Relationships among frequency classes and emotional regulation and impulsivity were assessed with a multinomial logistic regression. RESULTS: Higher frequency use was associated with greater DD (χ2 = 6.0, p = .05), greater CCM (χ2 = 73.3, p < .001), and lower cognitive AS (χ2 = 12.1, p = .002), when controlling for demographics, tobacco use, and number of cannabis administration methods. Frequency class and NU were not significantly associated. CONCLUSIONS: Identifying meaningful patterns of cannabis use may improve our understanding of individual differences that increase risk of frequent or problematic cannabis use. Excessive delay discounting and using cannabis to cope with negative affect may be relevant targets for treatments designed to reduce cannabis use.

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

PURPOSE OF REVIEW: This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use. RECENT FINDINGS: There is some recent evidence suggesting cannabinoids, cannabidiol or cannabidiol-enriched cannabis preparations have anxiolytic properties. In addition, depression may be worsened by cannabis use, however, randomized controlled trials (RCT) are lacking. New evidence also suggests that cannabidiol or cannabidiol-enriched cannabis use for PTSD and emotion regulation can induce hyporesponse to fear and stress. Further, several lines of evidence point to the endocannabinoid system as a key player in some of the reviewed disorders, in particular anxiety and PTSD. SUMMARY: The most recent evidence for a therapeutic use of cannabinoids in the reviewed conditions is weak and lacking well designed RCTs. However, there is some indication of the role of the endocannabinoid system in these conditions that warrant further studies.

A preliminary study of association between adolescent estradiol level and dorsolateral prefrontal cortex activity during emotion regulation.

Non-human primate models have been useful in clarifying estradiol's role in cognitive processing. These animal studies indicate estradiol impacts cognitive processes supported by regions within dorsolateral prefrontal cortex (DLPFC). Although human functional neuroimaging studies have begun to find similar relationships between estradiol in women for some forms of 'cold' cognitive control, to date no studies have examined the relationship between estradiol and DLPFC function in the context of active attempts to regulate one's emotions. Here, we asked whether peripheral 17-beta estradiol levels in adolescent girls in different pubertal developmental stages (age = 14.9 years ± 1.74) were related to engagement of DLPFC regions during the use of a cognitive strategy for regulating emotion known as reappraisal using functional Magnetic Resonance Imaging. Findings indicated that higher estradiol levels predicted greater DLPFC activity during the down-regulation of negative emotion using reappraisal. This is the first report of an association between estradiol level and DLPFC activity during cognitive reappraisal of negative emotion. The study suggests a possibility that estradiol might positively contribute to regulatory function of a cortical system important for emotional experiences.

Cannabis-associated impairments in the fading affect bias and autobiographical memory specificity.

We investigated potential relationships between cannabis use and 2 phenomena associated with autobiographical remembering: the fading affect bias (FAB) and memory specificity. The FAB is an emotional affect regulation mechanism that is observed when the intensity of affect associated with experiencing negative memories fades faster than the intensity of affect associated with experiencing positive memories. Memory specificity refers to the level of detail with which events are recalled. No studies have examined the relationships between cannabis use, the FAB, and memory specificity simultaneously. Chronic cannabis users (N = 47) and non-users (N = 52) recalled and described positive and negative autobiographical events and rated the affective intensity for the events at the time of occurrence and at time of test. Participants retrieved additional memories using a sentence-completion recall task, which were coded for specificity. Cannabis users showed reduced fading affect for unpleasant events and reduced memory specificity compared to non-users.

Associations of depression severity with heart rate and heart rate variability in young adults across normative and clinical populations.

Limitations of current depression treatments may arise from a lack of knowledge about unique psychophysiological processes that contribute to depression across the full range of presentations. This study examined how individual variations in heart rate (HR) and heart rate variability (HRV) are related to depressive symptoms across normative and clinical populations in 152 young adults (aged 18-35 years). Moderating effects of sex and antidepressant medication status were considered. Electrocardiogram data were collected during "vanilla" baseline and in response to positive and negative emotional cues. Linear regressions and repeated-measures mixed models were used to assess the relationships between Beck Depression Inventory-II (BDI-II) scores, sex, antidepressant use, and cardiovascular outcomes. Baseline models yielded significant main effects of BDI-II and sex on HR and significant interactions between antidepressant medication status and BDI-II on HRV outcomes. The main effects of BDI-II and sex on HR were no longer significant after controlling for cardiorespiratory fitness. Participants who denied current antidepressant use (n = 137) exhibited a negative association and participants who endorsed current antidepressant (n = 15) use exhibited a positive association between BDI-II scores and HRV. Emotional reactivity models were largely non-significant with the exception of a significant main effect of antidepressant medication status on high-frequency HRV reactivity. Results indicated antidepressant medication use may moderate the relationship between depression severity and cardiovascular functioning, but this requires replication given the modest proportion of medicated individuals in this study. Overall, findings suggest cardiovascular processes and cardiorespiratory fitness are linked to depression symptomatology and may be important to consider in depression treatment.

Restoring emotional stability: Cortisol effects on the neural network of cognitive emotion regulation.

Effective emotion regulation in stressful contexts is a key feature of mental health. Acute stress, however, impairs prefrontal top-down control, probably leading to a decline of emotion regulatory capacities. By contrast, the delayed cortisol increase in response to a stressor or after a pharmacological manipulation has been linked to mood-protecting effects and emotion regulation success. In this functional magnetic resonance imaging study, healthy men and women received either 30 mg cortisol or placebo 90 min before they were exposed to an emotion regulation paradigm involving neutral and negative pictures. As expected, behavioural and brain imaging data indicated successful induction and downregulation of negative emotions via cognitive reappraisal and distraction. Cortisol enhanced regulatory activity in the ventrolateral prefrontal cortex when participants used distraction and reduced emotion-related activation in the amygdala when regulating emotions via cognitive reappraisal. Together, these findings provide first evidence for a delayed glucocorticoid-induced facilitation of cognitive emotion regulation processes that might be beneficial for restoring emotional stability in the aftermath of stressful events.

Atypical but not typical antipsychotic drugs ameliorate phencyclidine-induced emotional memory impairments in mice.

Schizophrenia is associated with cognitive impairments related to hypofunction in glutamatergic N-methyl-D-aspartate receptor (NMDAR) transmission. Phencyclidine (PCP), a non-competitive NMDAR antagonist, models schizophrenia-like behavioral symptoms including cognitive deficits in rodents. This study examined the effects of PCP on emotional memory function examined in the passive avoidance (PA) task in mice and the ability of typical and atypical antipsychotic drugs (APDs) to rectify the PCP-mediated impairment. Pre-training administration of PCP (0.5, 1, 2 or 3 mg/kg) dose-dependently interfered with memory consolidation in the PA task. In contrast, PCP was ineffective when administered after training, and immediately before the retention test indicating that NMDAR blockade interferes with memory encoding mechanisms. The typical APD haloperidol and the dopamine D2/3 receptor antagonist raclopride failed to block the PCP-induced PA impairment suggesting a negligible role of D2 receptors in the PCP impairment. In contrast, the memory impairment was blocked by the atypical APDs clozapine and olanzapine in a dose-dependent manner while risperidone was effective only at the highest dose tested (1 mg/kg). The PCP-induced impairment involves 5-HT1A receptor mechanisms since the antagonist NAD-299 blocked the memory impairment caused by PCP and the ability of clozapine to attenuate the impairment by PCP. These results indicate that atypical but not typical APDs can ameliorate NMDAR-mediated memory impairments and support the view that atypical APDs such as clozapine can modulate glutamatergic memory dysfunctions through 5-HT1A receptor mechanisms. These findings suggest that atypical APDs may improve cognitive impairments related to glutamatergic dysfunction relevant for emotional memories in schizophrenia.