Cross-diagnostic evaluation of minor physical anomalies in psychiatric disorders.
Bipolar disorder
Minor physical anomalies
Neurodevelopment
Schizophrenia
Journal
Journal of psychiatric research
ISSN: 1879-1379
Titre abrégé: J Psychiatr Res
Pays: England
ID NLM: 0376331
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
19
05
2021
revised:
11
07
2021
accepted:
16
07
2021
pubmed:
30
7
2021
medline:
29
10
2021
entrez:
29
7
2021
Statut:
ppublish
Résumé
Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia). Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO). MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders. MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.
Sections du résumé
BACKGROUND
Minor physical anomalies (MPA) are markers of impaired neurodevelopment during the prenatal stage. Assessing MPA across psychiatric disorders may help understand their shared nature. In addition, MPA in family members would indicate a shared liability and endophenotype potential. We examined familial aggregation of MPA and their role as transdiagnostic and disorder-specific markers of 5 major psychiatric/neuropsychiatric conditions (schizophrenia, bipolar disorder, substance dependence, obsessive-compulsive disorder, and Alzheimer's dementia).
METHODS
Modified Waldrop's MPA scale was applied on 1321 individuals from 439 transdiagnostic multiplex families and 125 healthy population controls (HC). Stage of fetal development (morphogenetic/phenogenetic)- and anatomical location (craniofacial/peripheral)-based sub-scores were calculated. Familiality and endophenotypic potential of MPA were analyzed with serial negative binomial mixed-effect regression. Cross-diagnostic differences and the effect of family history density (FHD) of each diagnosis on MPA were assessed. Mixed-effects Cox models estimated the influence of MPA on age-at-onset of illness (AAO).
RESULTS
MPA were found to be heritable in families with psychiatric disorders, with a familiality of 0.52. MPA were higher in psychotic disorders after controlling for effects of sex and intrafamilial correlation. Morphogenetic variant MPA was noted to be lower in dementia in comparison to HC. FHD of schizophrenia and bipolar disorder predicted higher, and that of dementia and substance dependence predicted lower MPA. MPA brought forward the AAO [HR:1.07 (1.03-1.11)], and this was more apparent in psychotic disorders.
CONCLUSION
MPA are transmissible in families, are specifically related to the risk of developing psychoses, and predict an earlier age at onset. Neurodevelopmentally informed classification of MPA has the potential to enhance the etiopathogenic and translational understanding of psychiatric disorders.
Identifiants
pubmed: 34325233
pii: S0022-3956(21)00460-X
doi: 10.1016/j.jpsychires.2021.07.028
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
54-62Investigateurs
Naren P Rao
(NP)
Palanimuthu T Sivakumar
(PT)
Arun Kandasamy
(A)
Jayant Mahadevan
(J)
Urvakhsh Meherwan Mehta
(UM)
Odity Mukherjee
(O)
Meera Purushottam
(M)
Bhupesh Mehta
(B)
Thennarasu Kandavel
(T)
B Binukumar
(B)
Jitender Saini
(J)
Deepak Jayarajan
(D)
A Shyamsundar
(A)
Sydney Moirangthem
(S)
K G Vijay Kumar
(KGV)
Jagadisha Thirthalli
(J)
Bangalore N Gangadhar
(BN)
Mitradas M Panicker
(MM)
Upinder S Bhalla
(US)
Sumantra Chattarji
(S)
Padinjat Raghu
(P)
Mahendra Rao
(M)
Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.