What does this research mean for the field?

Major depressive disorder comprises two distinct cognitive subtypes—widespread impairment and relative preservation—that are biologically underpinned by specific structural-functional brain network deviations, synaptic gene expression, and neurotransmitter receptor distributions. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To characterize cognitive heterogeneity in major depressive disorder and determine its underlying brain network, transcriptomic, and neurotransmitter profiles.

September 8, 2026Psychiatry and Clinical Neurosciences

Cognitive heterogeneity in major depressive disorder: Neuroimaging, transcriptomic, and neurotransmitter profiles

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Authors

YYYushun Yan JYJia'ao Yu LZLiang Zuo

Discussion

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Overview

Multimodal neuroimaging analysis reveals distinct cognitive subtypes linked to brain network disruptions in major depressive disorder, highlighting underlying molecular and synaptic pathways.

Key Points

To characterize cognitive heterogeneity in major depressive disorder and determine its underlying brain network, transcriptomic, and neurotransmitter profiles.
Assessed 198 participants with major depressive disorder and 275 healthy controls using multi-domain cognitive testing and multimodal MRI acquisition.
Identified cognitive dimensions using a semi-supervised approach and mapped individual-level structural-enriched functional networks (SFNs) using network-based statistics.
Correlated spatial patterns of network deviations with meta-analytic neurocognitive maps, cortical transcriptomic data, and neurotransmitter receptor density distributions.
Identified two distinct depression subgroups: Cluster 1 with widespread cognitive impairments (n = 103) and Cluster 2 with preserved cognitive function (n = 95).
Observed an abnormally enhanced structural-functional subnetwork in depression (P_perm = 0.042) that spatially correlated with meta-analytic neurocognitive maps (r = 0.181, P < 0.001).
Demonstrated that network deviation patterns correlated with 2,458 genes enriched in synaptic and neurodegenerative pathways (P_FDR < 0.05) and three neurotransmitter systems, including NMDA, CB1, and norepinephrine transporters (P_FDR = 0.028).

Cite This Study

Yan et al. (2026) studied this question.

synapsesocial.com/papers/6a9fd82f58e84d0ff5b47739 https://doi.org/10.1111/pcn.70126

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September 8, 2026Psychiatry and Clinical Neurosciences

Cognitive heterogeneity in major depressive disorder: Neuroimaging, transcriptomic, and neurotransmitter profiles

View Full Paper

Ask AI

Bookmark

Authors

YYYushun Yan JYJia'ao Yu LZLiang Zuo

Discussion

Member takes

Overview

Multimodal neuroimaging analysis reveals distinct cognitive subtypes linked to brain network disruptions in major depressive disorder, highlighting underlying molecular and synaptic pathways.

Key Points

To characterize cognitive heterogeneity in major depressive disorder and determine its underlying brain network, transcriptomic, and neurotransmitter profiles.
Assessed 198 participants with major depressive disorder and 275 healthy controls using multi-domain cognitive testing and multimodal MRI acquisition.
Identified cognitive dimensions using a semi-supervised approach and mapped individual-level structural-enriched functional networks (SFNs) using network-based statistics.
Correlated spatial patterns of network deviations with meta-analytic neurocognitive maps, cortical transcriptomic data, and neurotransmitter receptor density distributions.
Identified two distinct depression subgroups: Cluster 1 with widespread cognitive impairments (n = 103) and Cluster 2 with preserved cognitive function (n = 95).
Observed an abnormally enhanced structural-functional subnetwork in depression (P_perm = 0.042) that spatially correlated with meta-analytic neurocognitive maps (r = 0.181, P < 0.001).
Demonstrated that network deviation patterns correlated with 2,458 genes enriched in synaptic and neurodegenerative pathways (P_FDR < 0.05) and three neurotransmitter systems, including NMDA, CB1, and norepinephrine transporters (P_FDR = 0.028).

Cite This Study

Yan et al. (2026) studied this question.

synapsesocial.com/papers/6a9fd82f58e84d0ff5b47739 https://doi.org/10.1111/pcn.70126

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