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  By Denis Katz, MD, MHA Founder, Salience Clinical For decades, psychiatry has framed major depressive disorder (MDD) as a disorder of chemistry, an imbalance of serotonin, norepinephrine, or dopamine. That model produced meaningful therapeutic advances, yet it has not consistently delivered durable remission for a substantial proportion of patients. Roughly one-third remain treatment resistant, and among responders, relapse is common. Incremental modulation of synaptic signaling alone appears to have reached a ceiling in its ability to transform long-term outcomes at scale. The next shift in neuropsychiatry will not be chemical. It will be architectural. By “architectural,” we mean the topology, coupling, and switching behavior of large-scale brain networks that shape how information is processed. From neurotransmitters to networks Advances in high-resolution functional MRI, multimodal imaging, and computational modeling over the past decade have transformed our unde...

The Architectural Turn in Depression Why Network Topology Will Redefine CNS Strategy By Denis Katz, MD, MHA Founder, Salience Clinical, LLC For decades, psychiatry has framed major depressive disorder (MDD) as a  disorder of chemistry , an imbalance of serotonin, norepinephrine, or dopamine. That model produced meaningful therapeutic advances, yet it has not consistently delivered durable remission for a substantial proportion of patients. Roughly one-third remain treatment resistant, and among responders, relapse is common. Incremental modulation of synaptic signaling alone appears to have reached a ceiling in its ability to transform long-term outcomes at scale. The next shift in neuropsychiatry will not be chemical. It will be architectural. By “architectural,” we mean the topology, coupling, and switching behavior of large-scale brain networks that shape how information is processed. From neurotransmitters to networks Advances in high-resolution functional MRI, multimodal imagi...