A multi-etiology model of systemic degeneration in schizophrenia

TL;DR

This paper proposes a multi-etiology model for schizophrenia, suggesting that diverse physiological dysfunctions can produce similar symptoms, complicating diagnosis and highlighting the potential of brain profiling for personalized diagnosis.

Contribution

It introduces a theoretical model linking various physiological parameters to schizophrenia symptoms, supporting the multiple etiologies hypothesis and advocating for brain profiling as a diagnostic tool.

Findings

Different parameter malfunctions produce similar system dysregulation

Model explains diagnostic difficulties in clinical settings

Supports brain profiling for personalized diagnosis

Abstract

We discuss the possibility of multiple underlying etiologies of the condition currently labeled as schizophrenia. We support this hypothesis with a theoretical model of the prefrontal-limbic system. We show how the dynamical behavior of this model depends on an entire set of physiological parameters, representing synaptic strengths, vulnerability to stress-induced cortisol, dopamine regulation and rates of autoantibody production. Malfunction of different such parameters produces similar outward dysregulation of the system, which may readily lead to diagnosis difficulties in a clinician's office. We further place this paradigm within the contexts of pathophysiology and of antipsychotic pharmacology. We finally propose brain profiling as the future quantitative diagnostic toolbox that agrees with a multiple etiologies hypothesis of schizophrenia.