The biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of aberrant neural stress... Show moreThe biological mechanisms underlying inter-individual differences in human stress reactivity remain poorly understood. We aimed to identify the molecular underpinning of aberrant neural stress sensitivity in individuals at risk for schizophrenia. Linking mRNA expression data from the Allen Human Brain Atlas to task-based fMRI revealed 201 differentially expressed genes in cortex-specific brain regions differentially activated by stress in individuals with low (healthy siblings of schizophrenia patients) or high (healthy controls) stress sensitivity. These genes are associated with stress-related psychiatric disorders (e.g. schizophrenia and anxiety) and include markers for specific neuronal populations (e.g. ADCYAP1, GABRB1, SSTR1, and TNFRSF12A), neurotransmitter receptors (e.g. GRIN3A, SSTR1, GABRB1, and HTR1E), and signaling factors that interact with the corticosteroid receptor and hypothalamic-pituitary-adrenal axis (e.g. ADCYAP1, IGSF11, and PKIA). Overall, the identified genes potentially underlie altered stress reactivity in individuals at risk for schizophrenia and other psychiatric disorders and play a role in mounting an adaptive stress response in at-risk individuals, making them potentially druggable targets for stress-related diseases. Show less
Suurland, J.; Heijden, K.B. van der; Huijbregts, S.C.J.; Goozen, S.H.M. van; Swaab, H. 2017
Nonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is... Show moreNonreciprocal action of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increases susceptibility to emotional and behavioral problems in children exposed to adversity. Little is known about the PNS and SNS in interaction with early adversity during infancy. Yet this is when the physiological systems involved in emotion regulation are emerging and presumably most responsive to environmental influences. We examined whether parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) response and recovery at six months, moderate the association between cumulative prenatal risk and physical aggression at 20 months (N = 113). Prenatal risk predicted physical aggression, but only in infants exhibiting coactivation of PNS and SNS (i.e., increase in RSA and decrease in PEP) in response to stress. These findings indicate that coactivation of the PNS and SNS in combination with prenatal risk is a biological marker for the development of aggression. Show less
Kinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale... Show moreKinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale periode is in verband gebracht met de ontwikkeling van agressief gedrag. Echter, de mate waarin deze risicofactoren de ontwikkeling van het kind beïnvloeden hangt deels af van de eigenschappen van het individuele kind, waaronder het vermogen tot zelfregulatie. In dit proefschrift is onderzocht hoe zelfregulatie, gemeten op fysiologisch, emotioneel en cognitief niveau, en prenatale risicofactoren de kwetsbaarheid voor agressief gedrag in de vroege kinderleeftijd vergroten en in hoeverre prenatale risicofactoren samenhangen met vroege zelfregulatie. Geconcludeerd kan worden dat 1) kinderen in de voorschoolse leeftijd met een verhoogde mate van agressief gedrag gekenmerkt worden door een specifieke combinatie van tekorten in zelfregulatie op emotioneel en cognitief niveau, 2) de impact van prenatale risicofactoren op de ontwikkeling van fysieke agressie in de peuterleeftijd afhankelijk is van fysiologische zelfregulatie in de babytijd, en 3) blootstelling aan prenatale risicofactoren voorspellend is voor fysiologische zelfregulatie in de babytijd. Deze bevindingen suggereren dat (preventieve) interventieprogramma’s ter voorkoming van agressief gedrag zich moeten richten op zowel beïnvloeden van prenatale omstandigheden als zelfregulatie in de vroege kindertijd. Show less
Many stress-related parameters have been associated with antisocial behavior, including low cortisol awakening responses (CAR), as well as low cortisol and alpha-amylase reactivity to stress. These... Show moreMany stress-related parameters have been associated with antisocial behavior, including low cortisol awakening responses (CAR), as well as low cortisol and alpha-amylase reactivity to stress. These parameters reflect different, yet interrelated components of the stress system, yet it remains to be determined whether they exert joint or independent effects. Therefore, this study examined them in concert, as this may offer a better explanation of the psychophysiological mechanism’s underlying antisocial behavior. Antisocial behavior was assessed through self-report by 197 general population boys and girls (Mage = 17.31, SD = 0.44). The CAR was assessed, as well as cortisol and alpha-amylase reactivity to a public speaking task. Neither stress-related parameter was independently related to antisocial behavior. The best explanation was provided by a CAR × Cortisol reactivity interaction, indicating that in youth with a low CAR, antisocial behavior was positively associated with cortisol reactivity. In youth with a high CAR, no association between antisocial behavior and cortisol reactivity was found. Between cortisol and alpha-amylase reactivity a trend toward an interaction appeared, indicating a negative association between cortisol reactivity and antisocial behavior in those with low alpha-amylase reactivity, and a positive association in those with high alpha-amylase reactivity. These findings indicate that in order to understand the mechanisms underlying antisocial behavior, the stress system should be studied comprehensively rather than focus on single parameters. Particularly cortisol parameters appear to be jointly related to antisocial behavior, the additional value of alpha-amylase reactivity to cortisol reactivity may however be limited. Show less
