Neuroimmune mechanisms connecting violence with internalizing symptoms: A high-dimensional multimodal mediation analysis.
Hum Brain Mapp
; 45(2): e26615, 2024 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-38339956
ABSTRACT
Violence exposure is associated with worsening anxiety and depression symptoms among adolescents. Mechanistically, social defeat stress models in mice indicate that violence increases peripherally derived macrophages in threat appraisal regions of the brain, which have been causally linked to anxious behavior. In the present study, we investigate if there is a path connecting violence exposure with internalizing symptom severity through peripheral inflammation and amygdala connectivity. Two hundred and thirty-three adolescents, ages 12-15, from the Chicago area completed clinical assessments, immune assays and neuroimaging. A high-dimensional multimodal mediation model was fit, using violence exposure as the predictor, 12 immune variables as the first set of mediators and 288 amygdala connectivity variables as the second set, and internalizing symptoms as the primary outcome measure. 56.2% of the sample had been exposed to violence in their lifetime. Amygdala-hippocampus connectivity mediated the association between violence exposure and internalizing symptoms ( ζ Ì Hipp π Ì Hipp = 0.059 $$ {\hat{\zeta}}_{\mathrm{Hipp}}{\hat{\pi}}_{\mathrm{Hipp}}=0.059 $$ , 95 % CI boot = 0.009,0.134 $$ 95\%{\mathrm{CI}}_{\mathrm{boot}}=\left[\mathrm{0.009,0.134}\right] $$ ). There was no evidence that inflammation or inflammation and amygdala connectivity in tandem mediated the association. Considering the amygdala and the hippocampus work together to encode, consolidate, and retrieve contextual fear memories, violence exposure may be associated with greater connectivity between the amygdala and the hippocampus because it could be adaptive for the amygdala and the hippocampus to be in greater communication following violence exposure to facilitate evaluation of contextual threat cues. Therefore, chronic elevations of amygdala-hippocampal connectivity may indicate persistent vigilance that leads to internalizing symptoms.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neuroinmunomodulación
/
Exposición a la Violencia
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hum Brain Mapp
/
Hum. brain mapp
/
Human brain mapping
Asunto de la revista:
CEREBRO
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos