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

The Combined Dexamethasone/TSST Paradigm – A New Method for Psychoneuroendocrinology

The two main physiological systems involved in the regulation of the stress response are the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). However, the interaction of these systems on the stress response remains poorly understood. To better understand the cross-regulatory effects of the different systems involved in stress regulation, we developed a new stress paradigm that keeps the activity of the HPA constant when exposing subjects to psychosocial stress. Thirty healthy male participants were recruited and randomly assigned to either a dexamethasone (DEX; n = 15) or placebo (PLC; n = 15) group. All subjects were instructed to take the Dexamethasone (2 mg) or Placebo pill the night before coming to the laboratory to undergo the Trier Social Stress Task (TSST). Salivary cortisol, salivary alpha amylase (sAA), heart rate, blood pressure and subjective stress were assessed throughout the protocol. As expected, the DEX group presented with suppressed cortisol levels. In comparison, their heart rate was elevated by approximately ten base points compared to the PLC group, with increases throughout the protocol and during the TSST. Neither sAA, nor systolic or diastolic blood pressures showed significant group differences. Subjective stress levels significantly increased from baseline, and were found to be higher before and after the TSST after DEX compared to placebo. These results demonstrate a significant interaction between the HPA and the SNS during acute stress. The SNS activity was found to be elevated in the presence of a suppressed HPA axis, with some further effects on subjective levels of stress. The method to suppress the HPA prior to inducing stress was found to completely reliable, without any adverse side effects. Therefore, we propose this paradigm as a new method to investigate the interaction of the two major stress systems in the regulation of the stress response

Assessment of the cortisol awakening response: expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research

Detailed assessment of the hemodynamic response to psychosocial stress using real-time MRI

Purpose: To demonstrate that combining the Montreal Imaging Stress Task (MIST) with real-time cardiac magnetic resonance imaging (MRI) allows detailed assessment of the cardiovascular mental stress response.Materials and Methods: 22 healthy volunteers (1:1 M:F, 26-64 years) underwent MRI during rest and the MIST. Real-time spiral phase contrast MR, accelerated with sensitivity encoding (SENSE) was used to assess stroke volume (SV), and radial k-t SENSE was used to assess ventricular volumes. Simultaneous heart rate (HR) and blood pressure (BP) measures allowed calculation of cardiac output (CO), systemic vascular resistance (SVR), and arterial compliance (TAC). Endocrine responses were assessed using salivary cortisol.Results: In response to stress. BP increased due to increased CO and reduced TAC but not increased SVR, which fell. HR, not SV, determined CO increases. Greater BP responses occurred in men due to greater CO increases and relatively higher SVR. Older participants had greater BP responses due to greater falls in TAC. Greater cortisol response was correlated with greater falls In TAC but resting cortisol and TAC were not related.Conclusion: This new approach allows detailed, accurate assessment of stress physiology. Preliminary findings suggest stress exposes relationships, not seen at rest, of cardiovascular function with age, sex, and endocrine function

Acute Stress-Induced Blood Lipid Reactivity in Hypertensive and Normotensive Men and Prospective Associations with Future Cardiovascular Risk.

Hyperreactivity to stress may be one explanation for the increased risk of cardiovascular disease (CVD) in individuals with essential hypertension. We investigated blood lipid reactivity to the Montreal Imaging Stress Task (MIST), a psychosocial stressor, in hypertensive and normotensive men and tested for prospective associations with biological risk factors. Fifty-six otherwise healthy and medication-free hypertensive and normotensive men underwent the MIST. We repeatedly measured cortisol and blood lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)) immediately before and up to 1 h after stress. Lipid levels were corrected for stress hemoconcentration. Thirty-five participants completed follow-up assessment 2.9 ± 0.12 (SEM) years later. CVD risk was assessed by prospective changes in TC/HDL-C ratio, IL-6, D-dimer, and HbA1c from baseline to follow-up. The MIST induced significant changes in all parameters except TC (p-values ≤ 0.043). Compared with normotensives, hypertensives had higher TC/HDL-C-ratio and TG (p-values ≤ 0.049) stress responses. Blood lipid stress reactivity predicted future cardiovascular risk (p = 0.036) with increases in HbA1c (ß = 0.34, p = 0.046), IL-6 (ß = 0.31, p = 0.075), and D-dimer (ß = 0.33, p = 0.050). Our results suggest that the greater blood lipid reactivity to psychosocial stress in hypertensives, the greater their future biological CVD risk. This points to lipid stress reactivity as a potential mechanism through which stress might increase CVD risk in essential hypertension

Self-esteem change and diurnal cortisol secretion in older adulthood

Objective: Research suggests that self-esteem can decline in older adulthood. This process could remove a buffer that normally protects individuals against distress-related changes in cortisol secretion. We examined this possibility by testing whether change in self-esteem would predict alterations in cortisol secretion, particularly among older adults who reported high levels of depressive symptoms or perceived stress. Methods: 147 older adults (Aged 60+) completed three days of diurnal cortisol measurements at three different time points, namely every two years over a total period of four years. Measures of self-esteem, depressive symptoms, and perceived stress were assessed at T1 and T2. Potential demographic and health-related confounds were measured at baseline (partnership status, SES, mortality risk index, and medication). Results: Linear regression models indicated that a decline in self-esteem from T1 to T2 predicted elevated cortisol output (AUCG) from T2 to T3, F (1, 137) = 8.09, β = -.25, R2 = .05, p = .005. Interaction analyses revealed that this association was particularly strong among participants who experienced higher T1 or T2 levels of depressive symptoms or perceived stress, +1 SD: βs = -.34 to -.51, ps .43. Conclusions: Declines in self-esteem represent a mechanism that contributes to higher levels of diurnal cortisol secretion if older adults experience psychological distress. Increases in self-esteem, by contrast, can ameliorate older adults’ cortisol regulation in stressful circumstances

Manual-protocol inspired technique for improving automated MR image segmentation during label fusion

Recent advances in multi-atlas based algorithms address many of the previous limitations in model-based and probabilistic segmentation methods. However, at the label fusion stage, a majority of algorithms focus primarily on optimizing weight-maps associated with the atlas library based on a theoretical objective function that approximates the segmentation error. In contrast, we propose a novel method-Autocorrecting Walks over Localized Markov Random Fields (AWoL-MRF)-that aims at mimicking the sequential process of manual segmentation, which is the gold-standard for virtually all the segmentation methods. AWoL-MRF begins with a set of candidate labels generated by a multi-atlas segmentation pipeline as an initial label distribution and refines low confidence regions based on a localized Markov random field (L-MRF) model using a novel sequential inference process (walks). We show that AWoL-MRF produces state-of-the-art results with superior accuracy and robustness with a small atlas library compared to existing methods. We validate the proposed approach by performing hippocampal segmentations on three independent datasets: (1) Alzheimer\u27s Disease Neuroimaging Database (ADNI); (2) First Episode Psychosis patient cohort; and (3) A cohort of preterm neonates scanned early in life and at term-equivalent age. We assess the improvement in the performance qualitatively as well as quantitatively by comparing AWoL-MRF with majority vote, STAPLE, and Joint Label Fusion methods. AWoL-MRF reaches a maximum accuracy of 0.881 (dataset 1), 0.897 (dataset 2), and 0.807 (dataset 3) based on Dice similarity coefficient metric, offering significant performance improvements with a smaller atlas library (\u3c 10) over compared methods. We also evaluate the diagnostic utility of AWoL-MRF by analyzing the volume differences per disease category in the ADNI1: Complete Screening dataset. We have made the source code for AWoL-MRF public at: https://github.com/CobraLab/AWoL-MRF

Correlation between self-esteem and stress response in Chinese college students: The mediating role of the need for social approval

The need for social approval Internal locus of control Mediation analysis a b s t r a c t Interpersonal theories of self-esteem assume that the importance that others place on oneself contributes to individual levels of self-esteem. Recent studies further suggest a possible link between self-esteem and the endocrine stress response, mediated through individual levels of locus of control, without taking levels of social approval into account. The present set of studies aimed to explore the correlation between self-esteem and stress response in Chinese students, and simultaneously take into account the possible mediating role of internal locus of control and need for social approval. In study one, twenty-eight college students' heart rates and saliva samples were collected while they underwent the Trier Social Stress Test (TSST). Their self-esteem scores were assessed using the Rosenberg self-esteem scale. Results showed a positive correlation between self-esteem and their endocrine stress responses to the TSST. In study two, forty-one college students' heart rates were collected while they underwent the TSST. Their locus of control scores were assessed by the Internality, Powerful Others, and Chance Scale, and their social approval scores were assessed by the Marlowe-Crowne Social Desirability Scale. Results indicated a significant positive correlation between self-esteem and heart rate changes during the TSST, with a mediating role of the need for social approval in the association between self-esteem and heart rate stress responses. We speculate that cultural differences may moderate the association between self-esteem and stress response