Lonely in the dark: trauma memory and sex-specific dysregulation of amygdala reactivity to fear signals

Abstract

Loneliness exacerbates psychological distress and increases the risk of psychopathology after trauma exposure. The prevalence of trauma-associated disorders varies substantially between sexes, and accumulating evidence indicates sex-specific effects of loneliness. However, it is still unclear whether a lack of social connectedness affects trauma-induced intrusions and the neural processing of fear signals. Moreover, it is uncertain, whether loneliness plays a different role in women and men. We used a prestratification strategy and recruited n=47 (n=20 women) healthy individuals with high loneliness and n=35 controls (n=18 women). Participants were exposed to an experimental trauma and evoked intrusive thoughts in daily life were monitored for three consecutive days. Functional magnetic resonance imaging was used to assess neural habituation to fearful faces and fear learning (conditioning and extinction) prior to trauma exposure. The total number of intrusions and amygdala reactivity in neural fear processing served as the primary study outcomes. Our results revealed a significant interaction between loneliness and sex such that loneliness was associated with more intrusions in men, but not in women. A similar pattern emerged at the neural level, with both reduced amygdala habituation to repeated fearful faces and amygdala hyperreactivity during the conditioning of fear signals in lonely men, but not in women. Our findings indicate that loneliness may confer vulnerability to intrusive memories after trauma exposure in healthy men and that this phenotype relates to altered limbic processing of fear signals. Collectively, interventions targeting social connectedness may mitigate the sequelae of traumatic experiences.

Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality

“…This adds to numerous studies revealing female gender as a risk factor for loneliness 77 , 78 . Interestingly, however, recent neuroimaging studies indicate that loneliness-associated neural effects may be more pronounced in high lonely men than women 79 , 80 .…”

Loneliness and diurnal cortisol levels during COVID-19 lockdown: the roles of living situation, relationship status and relationship quality

“…This adds to numerous studies revealing female gender as risk factor for loneliness 76,77 . Interestingly, however, recent neuroimaging studies indicate that loneliness-associated neural effects may be more pronounced in high lonely men than women 78,79 .…”

Chronic loneliness: neurocognitive mechanisms and interventions

“…Of note, a recent study found that loneliness may influence trauma memory in a sex-dependent manner. Specifically, lonely men, but not lonely women, exhibited more intrusive thoughts after experimental trauma and this phenotype was related to amygdala hyperreactivity during both fear conditioning and habituation processes, suggesting that the limbic system is a potential target for interventions that increase social connectedness [55].…”

“…Furthermore, patients with substance abuse [46][47][48], borderline personality disorder [49,50], and schizoid personality disorder [51] report more loneliness and social disconnection than healthy controls. In addition, loneliness is a potential risk factor for post-traumatic stress disorder [52,53] and enhances intrusive thoughts after trauma exposure [54,55]. Overall, loneliness and social isolation are critical risk factors for several somatic and mental disorders and thus should be considered in therapeutic protocols.…”