Depression as Episodic Dimensionality Collapse: The Hippocampal Substrate of Temporal Richness

Depression as Episodic Dimensionality Collapse: The Hippocampal Substrate of Temporal RichnessAbstractDepression is not a chemical imbalance. It is dimensional collapse. For seventy years, psychiatry has described depressive symptoms with exquisite detail yet cannot predict relapse better than chance (AUC 0.55–0.65). We propose the stress/hippocampal subtype of major depressive disorder—comprising 50–70% of cases—represents the progressive loss of episodic richness across all three temporal dimensions: past (specific memory retrieval), present (vivid sensory engagement), and future (detailed scenario construction). This is not metaphor. It is physics. The hippocampus generates navigable experiential space-time through pattern separation mechanisms. When chronic stress damages this substrate (cortisol → neurogenesis suppression → volume loss), the brain loses the computational resolution to distinguish distinct episodes. The three-dimensional space collapses to “flatland.” The framework solves anomalies unexplained by neurochemical models, including the 6–8 week latency of SSRIs (neurogenesis timeline) and the 4-hour efficacy of ketamine (dendritic spine restoration). We present a roadmap for two validation studies: (1) Prospective monitoring (N = 150) testing whether Pattern Separation Fidelity declines 2–4 weeks prior to relapse, and (2) A Ketamine pilot (N = 20) testing whether structural resolution restores before mood improves.Extended DescriptionThis preprint introduces a novel mechanistic framework that reframes a substantial proportion (estimated 50–70%) of major depressive disorder (MDD) cases as the progressive collapse of experiential dimensionality driven by hippocampal substrate failure under chronic stress.The core thesis is that the hippocampus functions as the brain’s generator of navigable experiential space-time, relying on dentate gyrus pattern separation to orthogonalize similar experiences into distinct episodic representations. Chronic stress and inflammation disrupt this process via cortisol-mediated suppression of adult neurogenesis, reduced dendritic spine density, and eventual hippocampal volume loss. The result is a computationally constrained brain that can no longer sustain high-resolution distinctions across past, present, and future, leading to the characteristic flattening of subjective experience: overgeneral autobiographical memory, reduced vividness of sensory engagement, impaired episodic future thinking, and a pervasive sense of temporal sameness (“flatland”).The model resolves several longstanding anomalies in depression research and treatment: The 6–8 week latency of SSRIs is explained by their role in stimulating hippocampal neurogenesis, requiring 4–6 weeks for new neurons to integrate and restore pattern separation capacity (Santarelli et al., 2003). Ketamine’s rapid (4-hour) antidepressant effects are attributed to acute restoration of dendritic spines in CA1 via BDNF-mTOR signaling, providing temporary structural scaffolding that re-enables episodic processing before sustained mood improvement (Rawat et al., 2022; Caffino et al., 2023). Preservation of semantic memory despite profound episodic deficits reflects the lower metabolic cost of cortical semantic networks compared to metabolically expensive hippocampal episodic systems (Williams et al., 2007). Proposed objective biomarkers shift assessment from subjective symptom scales to direct computational probes of hippocampal integrity: Mnemonic Similarity Task (MST) to quantify pattern separation fidelity. Allocentric spatial navigation tasks (e.g., Four Mountains Test) leveraging the evolutionary linkage between physical navigation and mental time travel. Heart rate variability (HRV) as an early indicator of constrained autonomic-metabolic budget. A staged cascade is outlined: (0) vulnerability (declining HRV), (1) structural erosion (suppressed neurogenesis), (2) resolution loss (pattern separation failure, “brain fog”), (3) full dimensional collapse (episodic shutdown and mood crash).Two falsifiable validation studies are detailed: An 18-month prospective longitudinal study (N = 150 remitted MDD patients) using weekly digital assessments (mobile MST, NLP-based Episodic Richness Index, HRV) to test whether pattern separation decline predicts relapse 14–28 days in advance. A ketamine mechanism pilot (N = 20) with measurements at baseline, +4 h, and +24 h to demonstrate structural restoration (MST and allocentric navigation improvement) precedes valence/mood improvement (MADRS). By moving from neurochemical to structural-computational accounts, this framework offers a unified explanation of phenomenology, treatment timelines, cognitive specificity, and relapse risk, paving the way for precision biomarkers and early intervention. Keywords : major depressive disorder, hippocampus, pattern separation, episodic memory, dimensional collapse, neurogenesis, ketamine, SSRI latency, biomarkers, prospective relapse prediction, stress subtype, mental time travel,