A load on the mind. Neural mechanisms of stress sensitivity

Contains fulltext : 178904.pdf (publisher's version ) (Open Access)Radboud University, 4 december 2017Promotores : Fernandez, G.S.E., Tendolkar, I. Co-promotor : Klumper, F

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

Contains fulltext : 167313.pdf (publisher's version ) (Open Access)Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress.11 p

Association between neuroticism and amygdala responsivity emerges under stressful conditions

Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas individual differences in neuroticism are thought to modulate the effect of stress on mental health, the mechanistic link between stress, neuroticism and amygdala responsivity is unknown. Thus, we studied the relationship between experimentally induced stress, individual differences in neuroticism, and amygdala responsivity. To this end, fearful and happy faces were presented to a large cohort of young, healthy males (n=120) in two separate functional MRI sessions (stress versus control) in a randomized, controlled cross-over design. We revealed that amygdala reactivity was modulated by an interaction between the factors of stress, neuroticism, and the emotional valence of the facial stimuli. Follow-up analysis showed that neuroticism selectively enhanced amygdala responses to fearful faces in the stress condition. Thus, we show that stress unmasks an association between neuroticism and amygdala responsivity to potentially threatening stimuli. This effect constitutes a possible mechanistic link within the complex pathophysiology of affective disorders, and our novel approach appears suitable for further studies targeting the underlying mechanisms

Acute stress enhances emotional face processing in the aging brain

Background: Healthy aging has been associated with stable emotional wellbeing and attenuated brain responses to negative stimuli. At the same time, depressive symptoms are common in older adults. The neural mechanisms behind this paradox remain to be clarified. We hypothesized that acute stress could alter emotion processing in the healthy aging brain, and therefore constitute a pathway to vulnerability. Methods: Using a randomized, controlled cross-over design we explored the influence of acute stress on brain responses to happy and fearful facial expressions in 25 older adults (aged 60-75) and 25 young (aged 18-30) controls. Groups were matched on trait anxiety and education. Subjects each underwent two separate fMRI sessions involving acute stress or a control procedure. Results: Affective and physiological responses to the stressor were similar between the two age groups. On whole-brain level, we revealed a significant age by stress interaction in the fusiform gyrus, indicating a selective enhancement of neural activity with stress in the elderly only. When specifically aiming our analysis at the amygdala, we found the same stress-related increase in activity in the elderly only. The modulation of amygdala reactivity due to stress correlated with trait conscientiousness in the elderly exclusively. Conclusions: Healthy, older adults showed increased responsivity of brain regions involved in face and emotion processing while stressed, compared with younger adults. These findings suggest that increased reactivity of this neural circuitry after acute stress may constitute one mechanism by which emotional wellbeing during healthy aging could rapidly change into heightened vulnerability for affective disorders

Association between neuroticism and amygdala responsivity emerges under stressful conditions

Contains fulltext : 149357.pdf (Publisher’s version ) (Closed access)Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas individual differences in neuroticism are thought to modulate the effect of stress on mental health, the mechanistic link between stress, neuroticism and amygdala responsivity is unknown. Thus, we studied the relationship between experimentally induced stress, individual differences in neuroticism, and amygdala responsivity. To this end, fearful and happy faces were presented to a large cohort of young, healthy males (n=120) in two separate functional MRI sessions (stress versus control) in a randomized, controlled cross-over design. We revealed that amygdala reactivity was modulated by an interaction between the factors of stress, neuroticism, and the emotional valence of the facial stimuli. Follow-up analysis showed that neuroticism selectively enhanced amygdala responses to fearful faces in the stress condition. Thus, we show that stress unmasks an association between neuroticism and amygdala responsivity to potentially threatening stimuli. This effect constitutes a possible mechanistic link within the complex pathophysiology of affective disorders, and our novel approach appears suitable for further studies targeting the underlying mechanisms.7 p

Sex modulates the interactive effect of the serotonin transporter gene polymorphism and childhood adversity on hippocampal volume.

Item does not contain fulltextThe common genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR) has been related to depressive symptoms, in particular after stressful life events. Although it has been investigated in the past, results suggesting that the 5-HTTLPR genotype also affects hippocampal volume are often inconsistent and it remains unclear to what extent reduced hippocampal volume is influenced by the effect of stressful life events and 5-HTTLPR genotype. Moreover, sex, which is known to affect the prevalence of depression substantially, has not been taken into account when trying to disentangle the interactive effect of common genetic variation and environmental stressors on the hippocampus. We investigated this potentially relevant three-way interaction using an automatic magnetic resonance imaging (MRI)-based segmentation of the hippocampus in 357 healthy individuals. We determined the 5-HTTLPR genotype as a biallelic locus and childhood adversity (CA) using a standard questionnaire. An interaction for hippocampal volume was found between the factors sex, genotype, and severe CA (p=0.010) as well as an interaction between genotype and severe CA (p=0.007) in men only. Post hoc tests revealed that only male S'-allele carriers with severe CA had smaller hippocampi (p=0.002). Interestingly, there was no main effect of genotype in men, while female S'-allele carriers had smaller hippocampi than L'L' carriers (p=0.023). Our results indicate that sex modulates the interactive effect of the 5-HTTLPR genotype and CA on hippocampal volume. While the S'-allele is associated with hippocampal volume independent of CA in women, men only have smaller hippocampi if they carry the risk allele and experienced severe CA.1 juli 201

Childhood abuse and deprivation have a distinct gender-dependent neural morphology in a healthy sample

Item does not contain fulltext1 p

Beloop van COVID-19-infecties en impact op mentale gezondheid; opzet van een landelijk casusregister [Course of COVID-19 infections and impact on mental health; setting up a national case register]

Achtergrond: De Nederlandse Vereniging voor Psychiatrie (NVvP) heeft een casusregister opgezet om de (neuro-)psychiatrische gevolgen van covid-19-besmetting in kaart te brengen. Doel: Inzicht krijgen in zowel kwetsbaarheden als beschermende factoren voor het krijgen van een covid-19-besmetting en het beloop hiervan in een (neuro)psychiatrische populatie. Methode: We verzamelen informatie van zo veel mogelijk patiënten met psychiatrische problematiek (zowel pre-existente psychiatrische problematiek als tijdens de infectie ontstane (neuro)psychiatrische klachten) en een covid-19-besmetting. De dataverzameling bestaat uit o.a. demografische gegevens, gegevens over de covid-19-besmetting en gegevens over de psychiatrische problematiek en de behandeling daarvan. Om een zo representatief mogelijk cohort te krijgen roepen wij alle ziekenhuizen, ggz-instellingen, verslavingszorg en andere zorginstellingen voor mensen met een psychiatrische aandoening in Nederland op om deel te nemen aan het CoviP-casusregister

The etiology of rhabdomyolysis: an interaction between genetic susceptibility and external triggers

Contains fulltext : 231548.pdf (Publisher’s version ) (Open Access)BACKGROUND AND PURPOSE: Rhabdomyolysis is a medical emergency characterized by acute skeletal muscle breakdown with a sudden rise and subsequent fall of serum creatine kinase (CK) levels. Rhabdomyolysis events are provoked by exposure to external triggers, possibly in combination with an increased genetic susceptibility. We aimed to describe comprehensively the external triggers and potentially pathogenic genetic variants possibly implicated in increased rhabdomyolysis susceptibility. METHODS: We performed a retrospective single-center study, including a total of 1302 patients with an acute CK level exceeding 2000 IU/l. RESULTS: Anoxia was the most frequently reported trigger (40%). A subset of 193 patients were clinically suspected of an underlying genetic disorder (recurrent episodes, a positive family history, very high or persistently increased CK levels). In 72 of these patients, an unequivocal genetic defect was identified. A total of 22 genes with pathogenic variants were identified, including 52 different variants. Of those, 11 genes have been previously associated with rhabdomyolysis (ACADVL, ANO5, CPT2, DMD, DYSF, FKRP, HADHA, PGM1, LPIN1, PYGM, RYR1). Eleven genes are probably implicated in increased susceptibility (including AGL, CAPN3, CNBP, DMPK, MAGT1, ACADM, SCN4A, SGCA, SGCG, SMPD1, TANGO2). CONCLUSION: These findings suggest that the spectrum of genetic susceptibility for rhabdomyolysis has not yet been completely clarified. With the increasing availability of next-generation sequencing in a diagnostic setting, we expect that in more cases a genetic defect will be identified

Good vibrations: An observational study of real-life stress induced by a stage performance

Stressors induce physiological changes in the brain and periphery that support adaptive defensive responses. The consequences of psychological stress on cognitive functioning are often measured in laboratory settings using experimentally induced stress that leads to mainly negative subjective feelings. There is a need for verification of these studies using real-life stressors that may potentially induce both positive and negative subjective feelings. In an observational study, we investigated real-life stress induced by voluntary stage performance at a large-scale music festival, including 126 participants (60 female, age range = 16-57 years). Our primary measurements involved salivary cortisol, heart rate, blood pressure, and positive and negative affect. In addition, participants completed a 2-back working memory task and a speeded decision-making task. We found that stage performance significantly increased salivary cortisol - with a particularly low number of cortisol non-responders - and heart rate, even when controlling for potential confounding factors, such as sleep, movement, and alcohol use. Interestingly, stage performance significantly decreased negative affect while increasing positive affect. This positively experienced stressor ("eustressor") was related to impaired working memory performance: the stronger the increases in cortisol, the slower participants responded to targets. Decision-making, however, was not affected. In conclusion, we show how stressful experiences in real-life can lead to positive affect, but still have a similar negative impact on cognitive functioning. We suggest that future research should focus more on the consequences of real-life stressors, and the consequences of eustress, in order to extend our understanding of the concept of psychological stress