A unified pathogenic hypothesis for mental disorders based on schismogenesis

Area of Science:

• Neuroscience
• Psychiatry
• Systems Biology

Background:

• Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Schizophrenia (SCZ) exhibit significant genetic, epigenetic, and phenotypic overlap.
• Existing models (e.g., triple network, social disconnection) explore shared pathophysiological mechanisms but lack a unifying framework.

Purpose of the Study:

• To propose schismogenesis, a transdisciplinary construct, as a unifying framework for understanding MDD, BD, and SCZ.
• To elucidate the role of schismogenesis in functional dissociation and network rigidity within neural, cognitive, and social systems.

Main Methods:

• Conceptual framework development based on transdisciplinary constructs.
• Analysis of existing literature on MDD, BD, SCZ, and network dynamics.
• Hypothesizing the role of positive feedback loops and inhibitory control deficits.

Main Results:

• Schismogenesis, characterized by positive feedback loops and insufficient inhibition, leads to functional dissociation and rigid network states (hyper/hypoactivation).
• This process underlies core psychopathology in MDD, BD, and SCZ, varying with network localization.
• The hypothesis posits schismogenesis as an evolutionary adaptation to overwhelming stress, involving system breakdown for damage prevention.

Conclusions:

• Schismogenesis offers a unifying perspective on the shared pathophysiology of MDD, BD, and SCZ.
• The reversibility of schismogenesis, particularly via reintegration interventions, presents novel therapeutic targets.