Sex-differential markers of psychiatric risk and treatment response based on premature aging of functional brain network dynamics and peripheral physiology.
cardiometabolic aging
functional brain network flexibility
major depressive disorder
psychosis
sex differences
Journal
Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264
Informations de publication
Date de publication:
15 Oct 2024
15 Oct 2024
Historique:
received:
21
06
2024
revised:
16
09
2024
accepted:
06
10
2024
medline:
18
10
2024
pubmed:
18
10
2024
entrez:
17
10
2024
Statut:
aheadofprint
Résumé
Aging is a multilevel process of gradual decline that predicts morbidity and mortality. Independent investigations have implicated senescence of brain and peripheral physiology in psychiatric risk, but it is unclear whether these effects stem from unique or shared mechanisms. To address this question, we analyzed clinical, blood chemistry and resting state functional neuroimaging data in a healthy aging cohort (N= 427; age 36-100 years) and two disorder-specific samples encompassing patients with early psychosis (100 patients, 16-35 years) and major depressive disorder (MDD) (104 patients, 20-76 years). We identified sex-dependent coupling between blood chemistry markers of metabolic senescence (i.e., homeostatic dysregulation), functional brain network aging, and psychiatric risk. In females, premature aging of frontoparietal and somatomotor networks was linked to greater homeostatic dysregulation. It also predicted the severity and treatment resistance of mood symptoms (depression/anxiety [all three samples], anhedonia [MDD]) and social withdrawal/behavioral inhibition (avoidant personality disorder [healthy aging]; negative symptoms [early psychosis]). In males, premature aging of the default mode, cingulo-opercular, and visual networks was linked to reduced homeostatic dysregulation and predicted severity and treatment resistance of symptoms relevant to hostility/aggression (antisocial personality disorder [healthy aging]; mania/positive symptoms [early psychosis]), impaired thought processes (early psychosis, MDD) and somatic problems (healthy aging, MDD). Our findings identify sexually dimorphic relationships between brain dynamics, peripheral physiology, and risk for psychiatric illness, suggesting that the specificity of putative risk biomarkers and precision therapeutics may be improved by considering sex and other relevant personal characteristics.
Sections du résumé
BACKGROUND
BACKGROUND
Aging is a multilevel process of gradual decline that predicts morbidity and mortality. Independent investigations have implicated senescence of brain and peripheral physiology in psychiatric risk, but it is unclear whether these effects stem from unique or shared mechanisms.
METHODS
METHODS
To address this question, we analyzed clinical, blood chemistry and resting state functional neuroimaging data in a healthy aging cohort (N= 427; age 36-100 years) and two disorder-specific samples encompassing patients with early psychosis (100 patients, 16-35 years) and major depressive disorder (MDD) (104 patients, 20-76 years).
RESULTS
RESULTS
We identified sex-dependent coupling between blood chemistry markers of metabolic senescence (i.e., homeostatic dysregulation), functional brain network aging, and psychiatric risk. In females, premature aging of frontoparietal and somatomotor networks was linked to greater homeostatic dysregulation. It also predicted the severity and treatment resistance of mood symptoms (depression/anxiety [all three samples], anhedonia [MDD]) and social withdrawal/behavioral inhibition (avoidant personality disorder [healthy aging]; negative symptoms [early psychosis]). In males, premature aging of the default mode, cingulo-opercular, and visual networks was linked to reduced homeostatic dysregulation and predicted severity and treatment resistance of symptoms relevant to hostility/aggression (antisocial personality disorder [healthy aging]; mania/positive symptoms [early psychosis]), impaired thought processes (early psychosis, MDD) and somatic problems (healthy aging, MDD).
CONCLUSIONS
CONCLUSIONS
Our findings identify sexually dimorphic relationships between brain dynamics, peripheral physiology, and risk for psychiatric illness, suggesting that the specificity of putative risk biomarkers and precision therapeutics may be improved by considering sex and other relevant personal characteristics.
Identifiants
pubmed: 39419460
pii: S0006-3223(24)01667-6
doi: 10.1016/j.biopsych.2024.10.008
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024. Published by Elsevier Inc.