Childhood Maltreatment in Females Is Associated with Enhanced Fear Acquisition and an Overgeneralization of Fear

Abstract

Childhood maltreatment may alter fear neurocircuitry, which results in pathological anxiety and depression. One alteration of fear-related behaviors that has been observed in several psychiatric populations is an overgeneralization of fear. Thus, we examined the association between childhood maltreatment and fear generalization in a non-clinical sample of young adults. Two hundred and ninety-one participants underwent differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS−), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS−, and several generalization stimuli (GS) without the presence of the US. Participants also completed questionnaires that assessed symptoms of childhood maltreatment, anxiety, depression, and post-traumatic stress disorder (PTSD). Participants reporting high childhood maltreatment (n = 71; 23 males, 48 females) exhibited significantly greater anxiety, depression, and symptoms of PTSD than participants reporting low childhood maltreatment (n = 220; 133 males, 87 females). Females reporting high childhood maltreatment demonstrated significantly enhanced fear learning and greater fear generalization, based on their fear-potentiated startle responses. Our findings suggest that childhood maltreatment may sex-dependently influence the development of fear neurocircuitry and result in greater fear generalization in maltreated females.

Resilience to Early Life Adversity Effects on Stress Reactivity by Postnatal Knockdown of 5-HT1AAutoreceptors

“…The extent to which ELA determines vulnerability to future stressors, HPA axis reactivity, and psychopathology can be influenced profoundly by genetic predisposition and biological sex. 48–53 The serotonin 1A receptor (5HT 1A ) has been implicated in the regulation of neuroendocrine responses to stress in juvenile and adult animals, 548–12 and the C(-1019)G polymorphism in the promoter region of the human 5HT1AR gene is associated with depression and antidepressant treatment resistance. 13,14 5HT 1A autoreceptors in the raphé nuclei of the brainstem inhibit the activity of 5HT neurons and thereby reduce 5HT release at terminal projection sites in limbic and cortical projection areas, including the hippocampus.…”

Adverse Childhood Experiences, Brain Function, and Psychiatric Diagnoses in a Large Adult Clinical Cohort

“…Additional studies have demonstrated the increased risk of mental health disorders with early life adversity such as personality disorders, substance disorders, and behavioral disorders, and sleep disorders, among others (5)(6)(7). Further, studies have found that childhood maltreatment leads to increased and overgeneralized fear responses in females, which may predispose them to psychopathology in adulthood (8).…”

Central amygdala CRF+ neurons promote heightened threat reactivity following early life adversity in mice

“…Clinical evidence has identified a critical influence of heightened amygdala activity towards fearful stimuli contributing to disrupted emotional regulation in children, adolescents, and adults following ELA 5 – 10 . Heightened behavioral and neural responding to fearful stimuli may represent a failure to appropriately regulate and titrate reactivity to real or perceived threat 7 , 11 – 13 . However, the mechanisms that gate excessive reactivity to threat and that increase susceptibility in ELA-exposed individuals remain poorly understood.…”