Making Sense of: Sensitization in Schizophrenia

Weidenauer, Ana; Bauer, Martin; Sauerzopf, Ulrich; Bartova, Lucie; Praschak-Rieder, Nicole; Sitte, Harald H.; Kasper, Siegfried; Willeit, Matthäus

doi:10.1093/ijnp/pyw081

Cited by 40 publications

(42 citation statements)

References 116 publications

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“…Psychosis-inducing triggers continue to produce further episodes at this stage, although with reduced homeostatic reserve -both intrinsic and structuraleven milder doses of inciting agents may now be sufficient to induce relapses. 187,188 Furthermore, compensation through dendritic spine reduction reaches a critical point after repeated relapses with no further room for spine reduction, leading to a state of "homeostatic occlusion" (Fig. 6).…”

Section: Figmentioning

confidence: 99%

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

Palaniyappan

2019

JPN

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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. 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.

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Section: Figmentioning

confidence: 99%

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

Palaniyappan

2019

JPN

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“…When repeatedly administered, D-amphetamine (AMPH) induces behavioral sensitization and a progressive amplification in AMPH-induced DA release [14][15][16] . Since psychotic patients show elevated responses to AMPH without any prior drug exposure 1 , psychosis has been conceptualized as a state of "endogenous sensitization" 10,17,18 . The prefrontal cortex (PFC), origin of reciprocal regulatory connections to subcortical DA neurons 19 , has often been found to be structurally and functionally impaired in SCZ 20,21 .…”

Section: Introductionmentioning

confidence: 99%

On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study

et al. 2020

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Schizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of "endogenous" sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D 2/3 receptor agonist radioligand [ 11 C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the "endogenous sensitization" hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia.

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“…This approach would allow for a rapid assessment of a large number of potential biomarkers in order to determine which are relevant to either remission or no benefit and which are not, and recent literature supports the utility of biomarkers in depression research. 18 , 42 – 44 …”

Section: Discussionmentioning

confidence: 99%

Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

South

Rush

Carmody

et al. 2017

NDT

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ObjectiveThe objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables) who are very likely (75% certain) to not benefit (NB) or to remit (R), accepting that without sufficient certainty, no prediction (NP) would be made.MethodsPatients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT) + placebo (n=212) or S-CIT + bupropion-SR (n=206) were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.ResultsThe two treatment cells had comparable rates of remission (40%) and no benefit (22%). In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP). For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP). Overall, 94/418 (22%) patients were identified with a meaningful degree of certainty (69%–85% correct). Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.ConclusionIn two separate analyses with two different treatments, this analytic approach – which is also applicable to pretreatment laboratory tests – identified a meaningful proportion (over 20%) of depressed patients for whom a treatment outcome was predicted with sufficient certainty that the clinician can elect to strongly recommend for or choose to avoid a particular treatment. Different persons seem to be remitting or not benefiting with these two different treatments.

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Making Sense of: Sensitization in Schizophrenia

Cited by 40 publications

References 116 publications

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

On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study

Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

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