Early life stress and the anxious brain: evidence for a neural mechanism linking childhood emotional maltreatment to anxiety in adulthood

Abstract

Background Childhood emotional maltreatment (CEM) increases likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms. Methods One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood. Results During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray matter volumes also partially mediated the CEM-anxiety relationship. Conclusions Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.

Impact of juvenile chronic stress on adult cortico-accumbal function: Implications for cognition and addiction

“…Given the requirement of NMDA receptor-mediated activity within PFC circuits during cognitive tasks (Arnsten & Rubia, 2012), this would presumably result in less recruitment of the PFC as required for effective top-down control. In support of this, reduced neural activity within the PFC when performing a variety of executive function tasks is commonly observed in human adults reporting experience of chronic juvenile stressors (Table 2; e.g., Casement et al, 2015; Fonzo et al, 2016; Philip et al, 2013b; 2016). However, chronic juvenile stress is also associated with increased brain-derived neurotrophic factor (BDNF) in the PFC of adult rats (Table 1; Han et al, 2011b; Meng et al, 2011; Shao et al, 2013), which is surprising given that reduced gray matter, reduced dendritic length or elaboration, and reduced plasticity are often observed in the adult PFC following juvenile stress in both humans and animal models (Tables 1 & 2).…”

Family-Related Stress versus External Stressors: Differential Impacts on Alcohol and Illicit Drug Use in Young Men

“…This view on their childhood would be more confronting than to simply acknowledge that their parents did not show interest in setting rules or monitoring their social contacts. However, even though the omission of parental care, control and monitoring does not provoke – in general – dramatic symptoms or recollections, studies showed that an emotionally abusive or neglectful parenting style deeply affected the self-representations [56] or the cerebral activation patterns of the individual later in life [57]. For example, students who had experienced and evaluated experiences of emotional abuse or neglect were shown to have developed profoundly anchored cognitive schemas of vulnerability and the impact of these internalizations on observed outcomes such as anxiety and depression might be even stronger, than the direct effects of the underlying events themselves [58].…”

A relationship between early life stress and depression: the role of the serotonin transporter gene polymorphism (5-HTTLPR)

“…Early life stress has been linked to long term functional and structural changes to the amygdala, hippocampus, and the Hypothalamic-Pituitary-Adrenal axis [14,56,57]. The amygdala processes emotional stimuli and dysfunction in this brain region is associated with deficits in emotion regulation, anxiety and depression.…”