TY - JOUR
T1 - Neurocognitive and functional heterogeneity in depressed youth
AU - Baller, Erica B.
AU - Kaczkurkin, Antonia N.
AU - Sotiras, Aristeidis
AU - Adebimpe, Azeez
AU - Bassett, Danielle S.
AU - Calkins, Monica E.
AU - Chand, Ganesh B.
AU - Cui, Zaixu
AU - Gur, Raquel E.
AU - Gur, Ruben C.
AU - Linn, Kristin A.
AU - Moore, Tyler M.
AU - Roalf, David R.
AU - Varol, Erdem
AU - Wolf, Daniel H.
AU - Xia, Cedric H.
AU - Davatzikos, Christos
AU - Satterthwaite, Theodore D.
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
PY - 2021/3
Y1 - 2021/3
N2 - Depression is a common psychiatric illness that often begins in youth, and is sometimes associated with cognitive deficits. However, there is significant variability in cognitive dysfunction, likely reflecting biological heterogeneity. We sought to identify neurocognitive subtypes and their neurofunctional signatures in a large cross-sectional sample of depressed youth. Participants were drawn from the Philadelphia Neurodevelopmental Cohort, including 712 youth with a lifetime history of a major depressive episode and 712 typically developing (TD) youth matched on age and sex. A subset (MDD n = 368, TD n = 200) also completed neuroimaging. Cognition was assessed with the Penn Computerized Neurocognitive Battery. A recently developed semi-supervised machine learning algorithm was used to delineate neurocognitive subtypes. Subtypes were evaluated for differences in both clinical psychopathology and brain activation during an n-back working memory fMRI task. We identified three neurocognitive subtypes in the depressed group. Subtype 1 was high-performing (high accuracy, moderate speed), Subtype 2 was cognitively impaired (low accuracy, slow speed), and Subtype 3 was impulsive (low accuracy, fast speed). While subtypes did not differ in clinical psychopathology, they diverged in their activation profiles in regions critical for executive function, which mirrored differences in cognition. Taken together, these data suggest disparate mechanisms of cognitive vulnerability and resilience in depressed youth, which may inform the identification of biomarkers for prognosis and treatment response.
AB - Depression is a common psychiatric illness that often begins in youth, and is sometimes associated with cognitive deficits. However, there is significant variability in cognitive dysfunction, likely reflecting biological heterogeneity. We sought to identify neurocognitive subtypes and their neurofunctional signatures in a large cross-sectional sample of depressed youth. Participants were drawn from the Philadelphia Neurodevelopmental Cohort, including 712 youth with a lifetime history of a major depressive episode and 712 typically developing (TD) youth matched on age and sex. A subset (MDD n = 368, TD n = 200) also completed neuroimaging. Cognition was assessed with the Penn Computerized Neurocognitive Battery. A recently developed semi-supervised machine learning algorithm was used to delineate neurocognitive subtypes. Subtypes were evaluated for differences in both clinical psychopathology and brain activation during an n-back working memory fMRI task. We identified three neurocognitive subtypes in the depressed group. Subtype 1 was high-performing (high accuracy, moderate speed), Subtype 2 was cognitively impaired (low accuracy, slow speed), and Subtype 3 was impulsive (low accuracy, fast speed). While subtypes did not differ in clinical psychopathology, they diverged in their activation profiles in regions critical for executive function, which mirrored differences in cognition. Taken together, these data suggest disparate mechanisms of cognitive vulnerability and resilience in depressed youth, which may inform the identification of biomarkers for prognosis and treatment response.
UR - http://www.scopus.com/inward/record.url?scp=85091772446&partnerID=8YFLogxK
U2 - 10.1038/s41386-020-00871-w
DO - 10.1038/s41386-020-00871-w
M3 - Article
C2 - 33007777
AN - SCOPUS:85091772446
SN - 0893-133X
VL - 46
SP - 783
EP - 790
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 4
ER -