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Objective: The optimism trait is considered one of the most important psychological factors in protecting and promoting health. This study aims to investigate whether trait optimism may help to cope better with the common cold by reducing the subjective perception of cold symptoms and affecting the immune response., Methods: To do so, 212 volunteers from the Pittsburg Cold Study 3 within the Common Cold Project were exposed to Rhinovirus (RV39). On the 5 days following the inoculation, a daily symptoms scale, nasal wash, and blood samples were collected to assess Jackson Symptoms (nasal congestion, sneezing, runny nose, sore throat, cough, headache, chills, and malaise) and control the Immune System response to infection (concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and interferon (IFN)-α)., Results: Results showed that approximately 30% of the inoculated participants were finally diagnosed with a common cold, showing higher Jackson Symptom severity and Immune System Response (IL-1β, IL-6, IL-8, IL-10, TNFα and IFNα). Importantly, moderation regression analyses showed that higher optimism scores were related to lower Jackson Symptom severity and TNFα response to infection in cold-diagnosed participants., Conclusions: Our results provide important evidence for the protective role of optimism, a trait factor that promotes a better perception of wellbeing and less need for immune system resources to successfully cope with the common cold., Competing Interests: The authors report no conflicts of interest. Authors has full control of all primary data and agree to allow the journal to review their data if requested. Moreover, there were no potential conflicts of interest with the organization that sponsored the research., (© 2024 The Authors.)

Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex has emerged as a valuable tool in psychiatric research. Understanding the impact of affective states, such as stress at the time of stimulation, on the efficacy of prefrontal tDCS is crucial for advancing tDCS interventions. Stress-primed tDCS, wherein stress is used as a priming agent, has the potential to modulate neural plasticity and enhance cognitive functions, particularly in emotional working memory. However, prior research using stress-primed tDCS focused solely on non-emotional working memory performance, yielding mixed results. In this sham-controlled study, we addressed this gap by investigating the effects of stress-primed bifrontal tDCS (active versus sham) on both non-emotional and emotional working memory performance. The study was conducted in 146 healthy individuals who were randomly assigned to four experimental groups. The Trier Social Stress Test (TSST) or a control variant of the test was used to induce a stress versus control state. The results showed that stress priming significantly enhanced the effects of tDCS on the updating of emotional content in working memory, as evidenced by improved accuracy. Notably, no significant effects of stress priming were found for non-emotional working memory performance. These findings highlight the importance of an individual's prior affective state in shaping their response to tDCS, especially in the context of emotional working memory., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Acute psychosocial stress effects on inhibition have been investigated in young adults, but little is known about these effects in older adults. The present study investigated effects of the Trier Social Stress Test on cognitive inhibition (i.e., ability to ignore distracting information) using a cross-over (stress vs. control) design in healthy young (N = 50; 18-30 years; M age  = 23.06) versus older adults (N = 50; 65-84 years; M age  = 71.12). Cognitive inhibition was measured by a letter flanker task and psychophysiological measures (cortisol, heart rate, subjective stress) validated the stress induction. The results showed that while stress impaired overall accuracy across age groups and sessions, stress (vs. control) made older adults' faster in session 1 and slower in session 2. Given that session 2 effects were likely confounded by practice effects, these results suggest that acute psychosocial stress improved older adults' RTs on a novel flanker task but impaired RTs on a practiced flanker task. That is, the interaction between stress and learning effects might negatively affect response execution when testing older adults on flanker tasks. If confirmed by future research, these results might have important implications especially in settings where repeated cognitive testing is performed under acute stress., (© 2023. Springer Nature Limited.)

Introduction: The phonological and semantic verbal fluency tasks are frequently used in neuropsychological assessment due to their easy application and good sensitivity to dementia. In Argentina, the psychometric evidence for these tasks is limited, with a special lack of knowledge of the temporal stability of its measurements. The psychometric production is even lower for the action fluency variant (emission of verbs in the infinitive in one minute). In effect, this research analyzes the test-retest reliability of three verbal fluency tasks in Argentine adults., Subjects and Methods: The sample was made up of 85 Argentine (average age, 63.7 years), 75,3% women and with a medium-high educational level. A prospective longitudinal design was carried out, administering phonological, semantic and action fluency tasks at two different times with an interval of up to four months. The intraclass correlation coefficient (ICC), a statistical method suggested for test-retest reliability studies, was analyzed. For the interpretation of the ICC, the Fleiss criteria were adopted., Results: The phonological and semantic fluency tasks showed good reliability, with ICCs of 0.77 and 0.79. The fluidity of action variant yielded ICC of 0.90, indicating excellent reliability., Conclusions: All fluency tasks have appropriate temporal stability, and their use is recommended when prospective neuropsychological research is planned (with language evaluation at different times) or as a method of monitoring the evolution of aphasic patients undergoing neurorehabilitation. Based on its excellent reliability, it is recommended to use the action variant more frequently.

Background: Patients with depression and mild cognitive impairment (MCI) are at greater risk of developing dementia. Depression involves a higher risk of suicidal ideation (SI) and suicide attempts (SA). Biomarkers of Alzheimer's Disease (AD) could help to clarify the role of depression and SI in AD., Method: Fifty-nine participants aged > 50 with criteria of MCI positive (MCI-AD) (n=22) and negative (MCI-Non AD) (n=24) AD and healthy controls (HC) (n=13) were evaluated. We used the Geriatric Depression Scale (GDS-30) and the GDS-SI factor to measure depression and indirect risk for suicide, respectively. Additionally, AD biomarkers such as amyloid-ß (Aß), hyperphosphorilated tau (P-tau), and total tau (T-tau) in cerebrospinal fluid (CSF) were analyzed., Results: No significant differences between the groups were found in depression. However, in the MCI-AD group, lower P-tau and T-tau levels were related to higher GDS-SI scores, suggesting that MCI-AD patients with lower AD pathology are at a higher risk of suicide., Conclusions: The result highlights the importance of considering SI in the initial phases of AD, and the potential role of AD biomarkers in early detection of symptoms.

The coronavirus disease 2019 (COVID-19) pandemic led to various government-imposed limitations on social interaction and strict home confinement. Such involuntary social-distancing policies can exacerbate feelings of loneliness and alter emotional well-being. Dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis is a potential mechanism for loneliness' deleterious health effects. In this study, we explored whether pre-pandemic diurnal cortisol output (AUC G ), a measure of HPA axis function, may predict the propensity to changes in loneliness during long-term COVID-19 home confinement and if extraversion would moderate this relationship. This association has been explored by analysing the impact of COVID-19 pandemic and strict home confinement on social and emotional loneliness in 45 Spanish young adults. Diurnal cortisol levels were measured from five saliva samples obtained across a day just before the pandemic, and data about participants' perceived loneliness, empathic state, extraversion, and prospective volunteering were obtained both before and during the confinement. Participants' social and family loneliness increased during long-term strict home confinement, while prospective volunteering tendencies and extraversion decreased. Importantly, after adjusting for relevant confounders, moderation analyses revealed that in young adults with high pre-pandemic extraversion, a higher AUC G predicted a larger increase in social loneliness during confinement, while in individuals with low extraversion, AUC G was negatively related to change in loneliness. Our findings highlight the utility of pre-pandemic diurnal cortisol output in predicting the social impact of COVID-19 home confinement, presenting this hormone as a potential biomarker for a priori identification of at-risk groups during public health crises., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Baliyan, Cimadevilla, Pulopulos, Castillejo, Sandi and Venero.)

There is a growing interest in applying double-dose repetitive transcranial Magnetic Stimulation (rTMS) as a therapeutic tool for stress-related psychiatric disorders. Such stimulation protocols may shorten the treatment duration and may result in faster symptom improvement. Currently, theta-burst stimulation (TBS) protocols have gained attention because of their significantly reduced treatment duration, compared to conventional rTMS. However, the effect of one or twice daily rTMS sessions remains unclear in relation to stress. Using a two-period cross-over design, we examined the impact of double-dosed intermittent (TBS) over the left dorsolateral prefrontal cortex on stress responses (salivary cortisol) in thirty-eight healthy participants after being stressed by a validated psychosocial stress task: the Trier Social Stress Test. After the first active iTBS session, as contrasted to sham, no differential effects on salivary output were observed. However, after the second active session, there was a significantly smaller decrease of salivary cortisol concentrations in the active iTBS condition compared to sham. Our results suggest that double-dosed iTBS after being stressed might differently affect stress recovery compared to a single session of iTBS., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Previous research supports the distinction between proactive and reactive control. Although the dorsolateral prefrontal cortex (DLPFC) has been consistently related to these processes, lateralization of proactive and reactive control is still under debate. We manipulated brain activity to investigate the role of the left and right DLPFC in proactive and reactive cognitive control. Using a single-blind, sham-controlled crossover within-subjects design, 25 young healthy females performed the 'AX' Continuous Performance Task after receiving sham vs active high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) to increase left and right DLPFC activity. Reaction times (RTs) and pupillometry were used to assess patterns of proactive and reactive cognitive control and task-related resource allocation, respectively. We observed that, compared to sham, HF-rTMS over the left DLPFC increased proactive control. After right DLPFC HF-rTMS, participants showed slower RTs on AX trials, suggesting more reactive control. However, this latter result was not supported by RTs on BX trials (i.e. the trial that specifically assess reactive control). Pupil measures showed a sustained increase in resource allocation after both active left and right HF-rTMS. Our results with RT data provide evidence on the role of the left DLPFC in proactive control and suggest that the right DLPFC is implicated in reactive control., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Subjective memory complaints (SMCs) may affect decision-making processes. This study aimed to investigate the neuronal correlates of feedback processing during a decision-making task in young and older adults with and without SMCs. Event-related potentials and behavioral performance during the Iowa gambling task were recorded in a total of 136 participants (65 young adults, 71 older adults). The participants were divided into two groups according to their SMCs (with SMCs: n = 60, without SMCs: n = 76). Feedback-related negativity (FRN) and P3 were analyzed in the feedback stage of the decision-making process. Older adults with SMCs scored worse in the ambiguity phase than older adults without SMCs. The FRN latency was longer for losses in older people with SMCs than in older people without SMCs in the first block. No significant differences between young and older adults with and without SMCs were observed in the other ERP measures. Compared to young adults, older adults showed delayed latency in the FRN component and reduced amplitudes and delayed latency in the P3 component. In conclusion, older people with SMCs present deficits in the decision-making process. These deficits are observed at the behavioral level, but also in neural mechanisms of early feedback processing of negative outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Garrido-Chaves, Perez, Perez-Alarcón, Crespo-Sanmiguel, Paiva, Hidalgo, Pulopulos and Salvador.)

Many authors have proposed that early life stress (ELS) provokes a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and contributes negatively to the management of stress in adulthood. However, these associations have not always been observed, making it necessary to include new factors that could explain the different results found. In this regard, people with ELS experiences report less social support during adulthood, suggesting that loneliness could be a mediating factor. Thus, our aims were to investigate whether ELS was related to both perceived stress and diurnal HPA axis activity, and whether loneliness mediates these relationships, in a community sample ( N =187, 18-55years old). Fourteen cortisol samples were collected on two non-consecutive days to obtain the overall diurnal cortisol, diurnal cortisol slope, and bedtime levels. Additionally, ELS was assessed with the Risky Families Questionnaire (RFQ) and the Recalled Childhood and Adolescence Perceived Stress (ReCAPS) measure. Results revealed that ELS was associated with perceived stress, but not HPA axis functioning, and loneliness mediated the relationship between ELS and perceived stress, but not between ELS and HPA axis functioning. Similar results were found for both ELS questionnaires, suggesting that the ReCAPS is an adequate tool. These results highlight the importance of loneliness in understanding the long-term effects of ELS, and they indicate different effects of ELS on subjective and physiological stress indicators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Crespo-Sanmiguel, Zapater-Fajarí, Pulopulos, Hidalgo and Salvador.)

Subjective memory complaints (SMCs) are commonly related to aging, but they are also presented by young adults. Their neurophysiological mechanisms are not thoroughly understood, although some aspects related to affective state have been mentioned. Here, we investigated whether facial emotion processing is different in young people with (n = 41) and without (n = 39) SMCs who were exposed to positive, negative, and neutral faces, by recording the event-related potential (ERP) activity. From the ERP activity, the N170 (an index of face processing) and the LPP (an index of motivated attention) components were extracted. Regarding the N170, results showed less amplitude for positive and neutral faces in the participants with SMCs than in those without SMCs. Moreover, women with SMCs displayed longer latencies for neutral faces than women without SMCs. No significant differences were found between the groups in the LPP component. Together, our findings suggest deficits in an early stage of facial emotion processing in young people with SMCs, and they emphasize the importance of further examining affective dimensions.

There are important individual differences in adaptation and reactivity to stressful challenges. Being subjected to strict social confinement is a distressful psychological experience leading to reduced emotional well-being, but it is not known how it can affect the cognitive and empathic tendencies of different individuals. Cortisol, a key glucocorticoid in humans, is a strong modulator of brain function, behavior, and cognition, and the diurnal cortisol rhythm has been postulated to interact with environmental stressors to predict stress adaptation. The present study investigates in 45 young adults (21.09 years old, SD = 6.42) whether pre-pandemic diurnal cortisol indices, overall diurnal cortisol secretion (AUCg) and cortisol awakening response (CAR) can predict individuals' differential susceptibility to the impact of strict social confinement during the Coronavirus Disease 2019 (COVID-19) pandemic on working memory, empathy, and perceived stress. We observed that, following long-term home confinement, there was an increase in subjects' perceived stress and cognitive empathy scores, as well as an improvement in visuospatial working memory. Moreover, during confinement, resilient coping moderated the relationship between perceived stress scores and pre-pandemic AUCg and CAR. In addition, in mediation models, we observed a direct effect of AUCg and an indirect effect of both CAR and AUCg, on change in perceived self-efficacy. These effects were parallelly mediated by the increase in working memory span and cognitive empathy. In summary, our findings reveal the role of the diurnal pattern of cortisol in predicting the emotional impact of the COVID-19 pandemic, highlighting a potential biomarker for the identification of at-risk groups following public health crises.

Resilience, the ability to overcome adversity and face stressful demands and experiences, has been strongly associated with successful aging, a low risk of diseases and high mental and physical functioning. This relationship could be based on adaptive coping behaviors, but more research is needed to gain knowledge about the strategies employed to confront social stress. Thus, we aimed to investigate the role of the use of active or passive coping strategies by resilient people in dealing with stressful situations. For this purpose, we measured resilience, coping strategies, and perceived stress in 66 healthy older adults (31 men and 35 women) between 56 and 75 years old who were exposed to stress (Trier Social Stress Test, TSST) or a control situation. The stress response was analyzed at endocrine (cortisol) and psychological (anxiety) levels. In the stress condition, moderated mediation analysis showed a conditional indirect effect of resilience on cortisol reactivity through active coping. However, passive coping strategies did not mediate the resilience-cortisol relationship. In addition, neither active nor passive coping mediated the relationship between resilience and the anxiety response. These results suggest that resilience is associated with active coping strategies, which in turn could explain, at least in part, individual differences in the cortisol response to a psychosocial laboratory stressor. These factors may prevent the development of stress-related pathologies associated with aging and facilitate healthy and satisfactory aging., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zapater-Fajarí, Crespo-Sanmiguel, Pulopulos, Hidalgo and Salvador.)

Intermittent theta burst stimulation (iTBS) delivered to the dorsolateral prefrontal cortex (DLPFC) has been investigated as a promising treatment for stress and stress-related mental disorders such as major depression, yet large individual differences in responsiveness demand further exploration and optimization of its effectiveness. Clinical research suggests that resting-state functional connectivity (rsFC) between the DLPFC and the anterior cingulate cortex (ACC) can predict iTBS treatment response in depression. The present study aimed to investigate whether rsFC between the left DLPFC and ACC subregions could predict the degree to which the stress system is affected by iTBS. After assessment of baseline resting-state fMRI data, 34 healthy female participants performed the Trier Social Stress Test on two separate days, each followed by active or sham iTBS over the left DLPFC. To evaluate iTBS effects on the stress-system, salivary cortisol was measured throughout the procedure. Our results showed that a stronger negative correlation between the left DLPFC and the caudal ACC was linked to a larger attenuation of stress-system sensitivity during active, but not during sham iTBS. In conclusion, based on individual rsFC between left DLPFC and caudal ACC, iTBS could be optimized to more effectively attenuate deregulation of the stress system., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The aim of this study was to investigate whether the nighttime cortisol release was associated with subjective and objective sleep quality and the discrepancy between them. Forty-five healthy older adults (age range from 56 to 75 years) collected salivary samples immediately before sleep and immediately after awakening on two consecutive nights. Actigraphy was used to assess objective sleep quality and quantity. A sleep diary was used to assess subjective sleep quality. Linear mixed models were performed using subjective and objective sleep quality data from 76 nights to investigate between-subject associations. We observed that larger changes in cortisol levels between sleep onset and awakening, reflecting a healthier circadian rhythm of the Hypothalamic-Pituitary-Adrenal (HPA) axis, were associated with better subjective sleep quality, but not with objective sleep quality. Moreover, smaller changes in nighttime cortisol were associated with lower subjective sleep quality relative to objective sleep quality. All these results were observed even after controlling for important confounders such as sleep quantity, age, sex, subjective socioeconomic status, stress perception, depression, physical activity, and adherence to the salivary sampling protocol. This study demonstrates that subjective sleep quality in older people may be explained, to some extent, by the activity of the HPA axis.

Over the last years, individualization of repetitive Transcranial Magnetic Stimulation (rTMS) parameters has been a focus of attention in the field of non-invasive stimulation. It has been proposed that in stress-related disorders personality characteristics may influence the clinical outcome of rTMS. However, the underlying physiological mechanisms as to how personality may affect the rTMS response to stress remains to be clarified. In this sham-controlled crossover study, after being stressed by the Trier Social Stress Test, 38 healthy females received two sessions of intermittent theta burst stimulation (iTBS) applied to the left dorsolateral prefrontal cortex. To take possible personality influences into account, they also completed the Temperament and Character Inventory. Mood and salivary cortisol were assessed throughout the experimental protocol. Overall, two iTBS sessions did not significantly alter mood or influenced cortisol secretion. When taking into account personality features, higher scores on the character dimension Cooperativeness was related to decreased cortisol output, only when active iTBS was administered after the social stressor. In line with other studies, personality features such as the character dimension Cooperativeness may be of particular interest to explain individual neurobiological responses to neurostimulation., Competing Interests: The authors have declared that no competing interests exist.

Background: Understanding the factors involved in the psychophysiological response of people in acute stressful situations is crucial to the prevention and treatment of stress-related health problems. We aim to integrate the results of studies investigating the role of sex and age in the inter-individual variability in several biomarkers of the stress response., Methods: We summarize the main findings of our research group and other laboratories regarding sex and age-related differences in the psychophysiological response to psychosocial stress., Results: Sex-related differences in the stress response are observed in blood pressure and cortisol, but not in heart rate, heart rate variability, or salivary alpha-amylase. Additionally, age may explain differences in cortisol levels and basal sympathetic nervous system activity., Conclusions: The results highlight the importance of taking sex and age into account in order to understand the stress response and its possible negative effects on health.

In older people, less diurnal variability in cortisol levels has been consistently related to worse physical performance, especially to slower walking speed (WS). The cortisol awakening response (CAR) is a discrete component of the hypothalamic-pituitary-adrenal axis that has been related to several health problems, such as cardiovascular disease and/or worse performance on executive function and memory. The relationship between the CAR and physical performance in older people is poorly understood. In this study, in 86 older people (mean age = 64.42, SD = 3.93), we investigated the relationship between the CAR and WS, a commonly used measure of physical performance in the older population that has also been related to health problems, such as cardiovascular disease and executive function performance in older people. Additionally, we studied whether the relationship between the CAR and WS was independent from cortisol levels on awakening and several possible confounders. Results showed that a CAR of reduced magnitude (measured with 3 samples each day, for two consecutive days, and calculated as the area under the curve with respect to the increase), but not cortisol levels on awakening, was related to slower WS. In addition, this relationship was independent from cortisol levels on awakening. It is possible that a CAR of reduced magnitude would contribute to less diurnal cortisol variability, affecting physical performance. Additionally, it is possible that a CAR of reduced magnitude affects WS through a possible negative effect on executive function, or that the association between the CAR and WS is due to the fact that both are related to similar health problems and to changes in cognitive performance in older people.

Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis). The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in non-stressful conditions. To do so, declarative and working memory performance were measured in 31 men and 35 women between 55 and 77 years of age. On a different day, the magnitude of their cortisol response to acute psychosocial stress was measured. The relationship between the cortisol response and memory performance was U shaped: a low cortisol response to stress was related to poorer declarative and working memory performance, whereas those who did not increase their cortisol levels and those who had the largest cortisol increase had better declarative and working memory capabilities. Sex did not moderate these relationships. These results suggest that a low cortisol response to stress could reflect a defective HPA-axis response to stressors that is accompanied by poorer memory performance. Conversely, a high cortisol response seems to reflect a correct functioning of the HPA-axis and may protect against memory deficits in the later stages of human life.

Rubinstein-Taybi syndrome (RSTS) is an inheritable disease associated with mutations in the gene encoding the CREB (cAMP response element-binding protein)-binding protein (CBP) and characterized by growth impairment, learning disabilities, and distinctive facial and skeletal features. Studies in mouse models for RSTS first suggested a direct role for CBP and histone acetylation in cognition and memory. Here, we took advantage of the genetic tools for generating mice in which the CBP gene is specifically deleted in postmitotic principal neurons of the forebrain to investigate the consequences of the loss of CBP in the adult brain. In contrast to the conventional CBP knock-out mice, which exhibit very early embryonic lethality, postnatal forebrain-restricted CBP mutants were viable and displayed no overt abnormalities. We identified the dimer of histones H2A and H2B as the preferred substrate of the histone acetyltransferase domain of CBP. Surprisingly, the loss of CBP and subsequent histone hypoacetylation had a very modest impact in the expression of a number of immediate early genes and did not affect neuronal viability. In addition, the behavioral characterization of these mice dissociated embryonic and postnatal deficits caused by impaired CBP function, narrowed down the anatomical substrate of specific behavioral defects, and confirmed the special sensitivity of object recognition memory to CBP deficiency. Overall, our study provides novel insights into RSTS etiology and clarifies some of the standing questions concerning the role of CBP and histone acetylation in activity-driven gene expression, memory formation, and neurodegeneration.