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. However, it is still unclear whether a lack of social connectedness affects trauma-related intrusions and the neural processing of fear signals. Moreover, it is uncertain, whether loneliness plays a different role in women and men. A prestratification strategy is used and n = 47 (n = 20 women) healthy lonely individuals and n = 35 controls (n = 18 women) are recruited. Participants are exposed to an experimental trauma and evoked intrusive thoughts in daily life are monitored for three consecutive days. Functional magnetic resonance imaging is used to assess neural habituation to fearful faces and fear learning (conditioning and extinction) prior to trauma exposure. The results reveal a significant interaction between loneliness and sex such that loneliness is associated with more intrusions in men, but not in women. A similar pattern emerges 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. The 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.

Homeostatic Regulation of Energetic Arousal During Acute Social Isolation: Evidence From the Lab and the Field

“…In the field study, however, our exploratory analysis showed that gender was not related to any of the outcomes, and it did not interact with type of day. Given recent evidence suggesting gender-related neurophysiological effects of chronic loneliness (Morr et al, 2022; Spreng et al, 2020), future studies will need to test the effects of acute social isolation on energy and fatigue in men as well as women to confirm the generalizability of these findings. It is worth highlighting the correlational nature of the field study so we could not establish the causality of the found effects.…”

Cross-ancestry and sex-stratified genome-wide association analyses of amygdala and subnucleus volumes

“…We used ancestry-specific LD references for ancestry-specific GWASs, cross-ancestry LD reference for crossancestry GWASs, as well as ancestry-and sex-specific LD references for sex-stratified GWASs. These LD references were constructed based on imputed genotype data from 35,474 (16,899 males and 18,575 females) UKB and 6,923 (2,397 males and 4,526 females) CHIMGEN participants. Since the sample sizes of EUR-GWASs were at least four times greater than those of EAS-GWASs, for the sake of simplicity, we used the EUR-LD reference to pool GWAS results and to identify new associations and loci.…”

Chronic Loneliness: Neurocognitive Mechanisms and Interventions

“…Furthermore, patients with substance abuse [64][65][66], borderline personality disorder [67,68], and schizoid personality disorder [69] report more loneliness and social disconnection than healthy controls. In addition, loneliness is a potential risk factor for post-traumatic stress disorder [70,71] and enhances intrusive thoughts after trauma exposure [72,73]. Overall, loneliness and social isolation are critical risk factors for several somatic and mental disorders and thus should be considered in therapeutic protocols.…”

“…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 [73]. Furthermore, the above-mentioned alterations in hippocampus-DMN covariation may reflect the neurobiological basis for an increased negative memory retrieval [92].…”

“…Furthermore, amygdala hyperreactivity might be another mechanism underlying the elevated prevalence of psychiatric disorders in high-lonely individuals. Recently, we found amygdala hyperreactivity and increased intrusive thought formation after trauma exposure in high-lonely men [73]. Heightened amygdala reactivity predicts depressive [116] and post-traumatic stress disorder symptoms [117].…”