TY - JOUR
T1 - Normative modelling of molecular-based functional circuits captures clinical heterogeneity transdiagnostically in psychiatric patients
AU - Lawn, Timothy
AU - Giacomel, Alessio
AU - Martins, Daniel
AU - Veronese, Mattia
AU - Howard, Matthew
AU - Turkheimer, Federico E
AU - Dipasquale, Ottavia
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6/5
Y1 - 2024/6/5
N2 - Advanced methods such as REACT have allowed the integration of fMRI with the brain’s receptor landscape, providing novel insights transcending the multiscale organisation of the brain. Similarly, normative modelling has allowed translational neuroscience to move beyond group-average differences and characterise deviations from health at an individual level. Here, we bring these methods together for the first time. We used REACT to create functional networks enriched with the main modulatory, inhibitory, and excitatory neurotransmitter systems and generated normative models of these networks to capture functional connectivity deviations in patients with schizophrenia, bipolar disorder (BPD), and ADHD. Substantial overlap was seen in symptomatology and deviations from normality across groups, but these could be mapped into a common space linking constellations of symptoms through to underlying neurobiology transdiagnostically. This work provides impetus for developing novel biomarkers that characterise molecular- and systems-level dysfunction at the individual level, facilitating the transition towards mechanistically targeted treatments.
AB - Advanced methods such as REACT have allowed the integration of fMRI with the brain’s receptor landscape, providing novel insights transcending the multiscale organisation of the brain. Similarly, normative modelling has allowed translational neuroscience to move beyond group-average differences and characterise deviations from health at an individual level. Here, we bring these methods together for the first time. We used REACT to create functional networks enriched with the main modulatory, inhibitory, and excitatory neurotransmitter systems and generated normative models of these networks to capture functional connectivity deviations in patients with schizophrenia, bipolar disorder (BPD), and ADHD. Substantial overlap was seen in symptomatology and deviations from normality across groups, but these could be mapped into a common space linking constellations of symptoms through to underlying neurobiology transdiagnostically. This work provides impetus for developing novel biomarkers that characterise molecular- and systems-level dysfunction at the individual level, facilitating the transition towards mechanistically targeted treatments.
KW - Humans
KW - Schizophrenia/physiopathology
KW - Magnetic Resonance Imaging
KW - Adult
KW - Male
KW - Brain/physiopathology
KW - Female
KW - Bipolar Disorder/physiopathology
KW - Attention Deficit Disorder with Hyperactivity/physiopathology
KW - Mental Disorders/physiopathology
KW - Young Adult
KW - Models, Neurological
KW - Middle Aged
KW - Nerve Net/physiopathology
UR - http://www.scopus.com/inward/record.url?scp=85195351262&partnerID=8YFLogxK
U2 - 10.1038/s42003-024-06391-3
DO - 10.1038/s42003-024-06391-3
M3 - Article
C2 - 38839931
SN - 2399-3642
VL - 7
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 689
ER -