Inefficient neural system stabilization: a theory of spontaneous resolutions and recurrent relapses in psychosis

Inefficient neural system stabilization: a theory of spontaneous resolutions and recurrent relapses in psychosis

J Psychiatry Neurosci 2019;44(6):367-383 | PDF | Appendix

Lena Palaniyappan, MD, PhD

A striking feature of psychosis is its heterogeneity. Presentations of psychosis vary from transient symptoms with no functional consequence in the general population to a tenacious illness at the other extreme, with a wide range of variable trajectories in between. Even among patients with schizophrenia, who are diagnosed on the basis of persistent deterioration, marked variation is seen in response to treatment, frequency of relapses and degree of eventual recovery. Existing theoretical accounts of psychosis focus almost exclusively on how symptoms are initially formed, with much less emphasis on explaining their variable course. In this review, I present an account that links several existing notions of the biology of psychosis with the variant clinical trajectories. My aim is to incorporate perspectives of systems neuroscience in a staging framework to explain the individual variations in illness course that follow the onset of psychosis.


Submitted Mar. 13, 2018; Revised Feb. 7, 2019; Accepted Mar. 5, 2019; Published online June 27, 2017

Acknowledgement: The author gratefully acknowledges Dr. Ross Norman for initial discussions; Prof. Tim Crow (Oxford) for reviewing this hypothesis and commenting on several aspects of this manuscript; and Dr. Ridha Joober and the attendees of CCNP Annual Meeting in Kingston, Ont., in June 2017, for stimulating questions that led to revisions of this work.

Affiliations: From the Department of Psychiatry and Robarts Research Institute, University of Western Ontario and Lawson Health Research Institute, London, Ont., Canada.

Funding: L. Palaniyappan’s work is supported by the Canadian Institute of Health Research (Foundation Grant 375104), the Bucke Family Fund and the Academic Medical Organization of South Western Ontario.

Competing interests: L. Palaniyappan reports personal fees from Janssen Canada, Otsuka Canada, SPMM Course Limited, UK, and the Canadian Psychiatric Association; book royalties from Oxford University Press; investigator-initiated educational grants from Sunovion, Janssen Canada and Otsuka Canada; and travel support from Boehringer Ingelheim and Magstim Limited, outside the submitted work. In the last 3 years, L. Palaniyappan and/or his spouse have held shares in Shire Pharmaceuticals and GlaxoSmithKline in their pension funds for values less than US$10 000. L. Palaniyappan joined the JPN editorial board in October 2019, after the current work was published online.

DOI: 10.1503/cjs.180038

Correspondence to: L. Palaniyappan, Robarts Research Institute, 100 Perth Drive, London, ON N6A 5K8; lpalaniy@uwo.ca