Abstract
In the recent decades, a paradigmatic change in psychosis research and treatment shifted attention toward the early and particularly the prodromal stages of illness. Despite substantial progress with regard to the neuronal underpinnings of psychosis development, the crucial biological mechanisms leading to manifest illness are yet insufficiently understood. Until today, one significant approach to elucidate the neurobiology of psychosis has been the modeling of psychotic symptoms by psychedelic substances in healthy individuals. These models bear the opportunity to evoke particular neuronal aberrations and the respective psychotic symptoms in a controlled experimental setting. In the present paper, we hypothesize that experimental psychiatry bears unique opportunities in elucidating the biological mechanisms of the prodromal stages of psychosis. Psychosis risk symptoms are attenuated, transient, and often only retrospectively reported. The respective neuronal aberrations are thought being dynamic. The correlation of unstable psychopathology with observed neurofunctional disturbances is thus yet largely unclear. In modeling psychosis, the experimental setting allows not only for evoking particular symptoms, but for the concomitant assessment of psychopathology, neurophysiology, and neuropsychology. Herein, the glutamatergic model will be highlighted exemplarily, with special emphasis on its potential contribution to the elucidation of psychosis development. This model of psychosis appears as candidate for modeling the prodrome by inducing psychotic-like symptoms in healthy individuals. Furthermore, it alters pre-attentive processing like the Mismatch Negativity, an electrophysiological component which has recently been identified as a potential predictive marker of psychosis development. In summary, experimental psychiatry bears the potential to further elucidate the biological mechanisms of the psychosis prodrome. A better understanding of the respective pathophysiology might assist in the identification of predictive markers, and the development of preventive treatments.
Highlights
Since more than 10 decades, researchers aim at understanding the neurobiological mechanisms of psychosis
We aim to investigate if and how experimental psychiatry may further elucidate the biological mechanisms of the psychosis prodrome
A synopsis of the literature shows that the prodrome of psychosis has been almost neglected by experimental psychiatry and the focus has yet been on manifest psychotic disorders
Summary
Since more than 10 decades, researchers aim at understanding the neurobiological mechanisms of psychosis. Concomitant with the debut of modern nosology in the late nineteenth century, almost all pioneer thinkers of psychiatry provided theoretical models regarding the underlying biological mechanisms of psychosis even though the experimental techniques at the time did not allow for any empirical evidence. Bleuler, who gave birth to the name “schizophrenia,” provided a sophisticated theoretical model of disrupted neural association networks contributing to the schizophrenic Grundsymptome [3]. In this tradition, one of the last hypotheses can be found in the seminal works of the German psychiatrist Gerd Huber, who proposed an elaborated model to trace back subtle psychopathological changes to neurofunctional disturbances of the limbic system [4, 5]. Not all hypotheses of that kind led to fruitful insights, the increasingly elaborated methods of biological psychiatry partially provided empirical evidence for some models in demonstrating, e.g., reductions in brain volume [6], functional aberrations of association cortices [7], and limbic neuropathology [8], thereby justifying the modeling approach as one primary route to guide empirical and experimental work
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