Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric condition characterized by severe impulsiveness, inattention and overactivity. Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, is one of the most frequently prescribed treatments for ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise neurochemical mechanisms of action are under debate. For the most part, MPH’s influence on subcortical dopamine neurotransmission is thought to play a crucial role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate tonic dopamine while inhibiting phasic transmitter release in subcortical structures, leading to reduced postsynaptic receptor stimulation and psychomotor activation in response to salient stimuli. Volkow and colleagues [56] suggest that by amplifying a weak striatal dopamine signal, MPH increases the perception of a stimulus or task as salient. The enhanced interest for the task is thought to increase attention and improve performance. Recent animal studies have however shown that when administered at doses producing clinically relevant drug plasma levels and enhancing cognitive function, MPH preferentially activates dopamine and noradrenaline efflux within the prefrontal cortex relative to the subcortical structures [5]. Overall, we suggest that the delineated theories of MPH therapeutic action should not be discussed as exclusive. Studies are outlined that allow integrating the different findings and models

Spreading positive change: Societal benefits of meditation

Research over the past decades has revealed a variety of beneficial effects of meditation training. These beneficial effects span the levels of health and well-being, cognition, emotion, and social behavior. Around the same time, sociologists have shown that traits and outcomes on the individual level have the potential to spread in communities over three or more degrees. This means, for example, that changes can spread from one person to the next, and on to yet another person. Here, we propose that meditation-induced changes may likewise spread through the social networks of meditation practitioners. Such spreading may happen by positively influencing others through prosocial actions, improved cognitive functioning, and increased positive affect. Positive affective states and their underlying physiological correlates may also be shared in the literal sense. We argue that the spreading of positive meditation effects could provide the basis for collective responses to some of the urgent challenges we face in our current time and society and call for future meditation research to examine the phenomenon

Spreading positive change: Societal benefits of meditation

Research over the past decades has revealed a variety of beneficial effects of meditation training. These beneficial effects span the levels of health and well-being, cognition, emotion, and social behavior. Around the same time, sociologists have shown that traits and outcomes on the individual level have the potential to spread in communities over three or more degrees. This means, for example, that changes can spread from one person to the next, and on to yet another person. Here, we propose that meditation-induced changes may likewise spread through the social networks of meditation practitioners. Such spreading may happen by positively influencing others through prosocial actions, improved cognitive functioning, and increased positive affect. Positive affective states and their underlying physiological correlates may also be shared in the literal sense. We argue that the spreading of positive meditation effects could provide the basis for collective responses to some of the urgent challenges we face in our current time and society and call for future meditation research to examine the phenomenon

Plasma oxytocin is modulated by mental training, but does not mediate its stress-buffering effect

Based on its role in social processing and stress, oxytocin has been suggested to mediate stress reduction of socio-affective, compassion-based mental training. We tested this hypothesis in the ReSource Project, a 9-month longitudinal mental training study. Participants practiced three different types of mental training, targeting either attentional abilities (Presence Module), socio-affective or socio-cognitive abilities (Affect and Perspective Modules). We investigated plasma oxytocin levels, and their link to cortisol and subjective reactivity to acute psychosocial stress as a function of previous mental training (n = 313). In a subsample (n = 113), to better understand oxytocin’s involvement in the effects of socio-affective training, we explored oxytocin, cortisol and subjective experiential responses to a single Loving-kindness Meditation (LKM) conducted after three months of Affect training (versus rest without prior training). We found that, independent of mental training, stress triggered acute oxytocin release. Following a single LKM, however, acute oxytocin release was unaffected. Training effects were only found in overall oxytocin release during both, stress and LKM. Compared to no training, 3-month compassion-based Affect training decreased overall oxytocin levels in the context of psychosocial stress, but increased overall oxytocin levels during LKM. Training-induced changes in overall oxytocin were unrelated to cortisol and subjective stress reactivity. Based on Quintana and Guastella's (2020) theory of oxytocin as an allostatic hormone with anticipatory properties, we interpret training-induced changes in overall oxytocin levels as alterations in the anticipated emotional relevance of specific events. After training socio-affective skills for three months, the stressful situation may have lost its emotional saliency, whereas the meditation technique itself gained emotional relevance. We conclude that changes in peripheral oxytocin release do not mediate stress reduction after mental training, and encourage the investigation of an allostatic concept of oxytocin in future research

Association of Short-term Change in Leukocyte Telomere Length With Cortical Thickness and Outcomes of Mental Training Among Healthy Adults

Importance:Telomere length is associated with the development of age-related diseases and structural differences in multiple brain regions. It remains unclear, however, whether change in telomere length is linked to brain structure change, and to what extent telomere length can be influenced through mental training. Objectives:To assess the dynamic associations between leukocyte telomere length (LTL) and cortical thickness (CT), and to determine whether LTL is affected by a longitudinal contemplative mental training intervention. Design, Setting, and Participants:An open-label efficacy trial of three 3-month mental training modules with healthy, meditation-naive adults was conducted. Data on LTL and CT were collected 4 times over 9 months between April 22, 2013, and March 31, 2015, as part of the ReSource Project. Data analysis was performed between September 23, 2016, and June 21, 2019. Of 1582 eligible individuals, 943 declined to participate; 362 were randomly selected for participation and assigned to training or retest control cohorts, with demographic characteristics matched. The retest control cohorts underwent all testing but no training. Intention-to-treat analysis was performed. Interventions:Training cohort participants completed 3 modules cultivating interoception and attention (Presence), compassion (Affect), or perspective taking (Perspective). Main Outcomes and Measures:Change in LTL and CT. Results:Of the 362 individuals randomized, 30 participants dropped out before study initiation (initial sample, 332). Data were available for analysis of the training intervention in 298 participants (n = 222 training; n = 76 retest control) (175 women [58.7%]; mean [SD] age, 40.5 [9.3] years). The training modules had no effect on LTL. In 699 observations from all 298 participants, mean estimated changes in the relative ratios of telomere repeat copy number to single-copy gene (T/S) were for no training, 0.004 (95% CI, -0.010 to 0.018); Presence, -0.007 (95% CI, -0.025 to 0.011); Affect, -0.005 (95% CI, -0.019 to 0.010); and Perspective, -0.001 (95% CI, -0.017 to 0.016). Cortical thickness change data were analyzed in 167 observations from 67 retest control participants (37 women [55.2%], mean [SD] age, 39.6 [9.0] years). In this retest control cohort subsample, naturally occurring LTL change was related to CT change in the left precuneus extending to the posterior cingulate cortex (mean t161 = 3.22; P < .001; r = 0.246). At the individual participant level, leukocyte telomere shortening as well as lengthening were observed. Leukocyte telomere shortening was related to cortical thinning (t77 = 2.38; P = .01; r = 0.262), and leukocyte telomere lengthening was related to cortical thickening (t77 = 2.42; P = .009; r = 0.266). All analyses controlled for age, sex, and body mass index. Conclusions and Relevance:The findings of this trial indicate an association between short-term change in LTL and concomitant change in plasticity of the left precuneus extending to the posterior cingulate cortex. This result contributes to the evidence that LTL changes more dynamically on the individual level than previously thought. Further studies are needed to determine potential long-term implications of such change in relation to cellular aging and the development of neurodegenerative disorders. No effect of contemplative mental training was noted in what may be, to date, the longest intervention with healthy adults. Trial Registration:ClinicalTrials.gov identifier: NCT01833104

Contemplative mental training reduces hair glucocorticoid levels in a randomized clinical trial

Objective To investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. Methods An open-label efficacy trial that comprised three distinct 3-month modules targeting attention and interoception, socio-affective or socio-cognitive abilities through dyadic exercises and secularised meditation practices was conducted with healthy adults. Participants underwent the training for three months, nine months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four timepoints: pre-training and after three, six and nine months. The main outcome measures were cortisol (HC) and cortisone (HE) concentrations in hair and self-reported long-term stress. Results Of 362 initially randomized individuals, 30 dropped out before study initiation (N = 332; mean age-40. 7 ± SD = 9.2 years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TCs) revealed consistent decreases in HC and HE levels over the first three (TC3) to six months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end-of-training, HC: TC1, t(355) = 2.59, p = .010; est.:0.35[0.14]; TC2, t(363) = 4.06, p < .001; est.:0.48[0.12]; TC3: t(368) = 3.18, p = .002; est.:0.41[0.13]; HE: TC1, t(435) = 3.23, p = .001; est.:0.45[0.14]; TC2: t(442) = 2.60, p = .010; est.:0.33[0.13]; TC3: t(446) = 4.18, p < .001; est.:0.57[0.14]). Training effects on HC increased with practice frequency, and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol to dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. Conclusions Our results point to the reduction of long-term cortisol exposure as a mechanism through which contemplative mental training may exert positive effects on practitioners' health. Trial registration: ClinicalTrials.gov identifier: NCT0183310

Post-hypnotic safety suggestion improves stress coping with long-lasting effects

Abstract Effective coping with acute stress is important to promote mental health and to build stress resilience. Interventions improving stress coping usually require long training periods. In this study, we present a hypnosis-based intervention that produces long-term effects after a single hypnosis session. In that session, we established a post-hypnotic safety suggestion that participants can activate afterwards with a cue, the Jena Safety Anchor. We tested 60 participants in our study who all received the hypnosis session and a stress task. The safety group used the Jena Safety Anchor during acute stress (Trier Social Stress Test, TSST). The control group used a neutral anchor. We measured subjective stress responses via self-reports and physiological stress responses via saliva and blood samples as well as heart rate. One week later, all participants filled in an online survey to measure long-term effects of the post-hypnotic safety suggestion. We found that participants using the Jena Safety Anchor during the TSST reported significantly lower stress compared to the control group. The safety group also reported significantly fewer negative thoughts concerning their TSST performance than the control group during the stress recovery phase and 1 week later. All participants indicated that the Jena Safety Anchor still worked 1 week after its establishment. Suggestibility did not affect the efficacy of the Jena Safety Anchor. Our findings demonstrate that post-hypnotic safety suggestions improve stress coping with long-lasting effects, which makes it a promising intervention to promote mental health and establish stress resilience in just one hypnosis session

The role of sex and gender socialization in stress reactivity

Individual health is determined by a myriad of factors. Interestingly, simply being male or female is one such factor that carries profound implications for one’s well-being. Intriguing differences between men and women have been observed with respect to vulnerability to and prevalence of particular illnesses. The activity of the major stress hormone axis in humans, the hypothalamus-pituitary-adrenal axis, is directly and indirectly associated with the onset and propagation of these conditions. Previous studies have shown differences between men and women at the level of stress hormone regulation, suggesting that the metabolic effects of stress may be related to susceptibility for stress-related disease. While the majority of studies have suggested that biological differences are responsible, few have also considered the role of gender socialization. In this selective review, the authors summarize evidence on sex differences and highlight some recent results from endocrinological, developmental, and neuroimaging studies that suggest an important role of gender socialization on the metabolic effects of stress. Finally, a model is proposed that integrates these specific findings, highlighting gender socialization and stress responsivity

Empathic Stress in Stranger Dyads: Examining the Role of Oxytocin and Testosterone Release after the Manipulation of the Observer’s Empathic Involvement

Psychosocial stress does not only affect individuals directly. The mere observation of a stressed target can also elicit a full-blown stress response in the observing individual. This so-called empathic stress includes two types: resonant and vicarious stress. In stress resonance, the observer shows a stress response, which is proportional to the target’s stress response. Conversely, vicarious stress evolves independently of the target’s actual stress response and is rather a projection of the observer’s own perspective onto the stressful situation. Given the immense importance of chronic stress in the development of stress-associated diseases (Chrousos, 2009; Herman, 2022), empathic stress may represent a health risk, especially in individuals who are frequently confronted with other’s stress. To date, not much is known about the biophysiological mechanisms of empathic stress between strangers (Engert et al., 2019). Therefore, in the current study, we assessed oxytocin and testosterone in observers, while they were watching an unknown target undergoing the Trier Social Stress Test (TSST; Kirschbaum et al., 1993). Further, we experimentally manipulated environmental factors for observers or, more precisely, their empathic involvement with the target. To facilitate relating to the target’s state, and thus induce a more empathic stance, observers were themselves exposed to the TSST approximately one week before observing the target in the TSST (empathy group). To create distance to the target’s stressful state, and induce a perspective of power, observers were asked to determine the target’s financial compensation based on their performance in the TSST (power group). Additionally, a control group without any manipulation was tested