Neurochemical models of psychosis risk and onset

TY - CHAP

T1 - Neurochemical models of psychosis risk and onset

AU - Oliver, Dominic

AU - Modinos, Gemma

AU - McGuire, Philip

N1 - Publisher Copyright: © 2020 Elsevier Inc. All rights reserved.

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Although clinical intervention at the clinical high risk stage has the potential to prevent the onset of psychosis, there are still no licensed pharmacological treatments for this purpose. The development of preventative treatments is informed by models of psychosis onset, especially those that reflect the time course and symptomatology of the disorder. This chapter describes four different preclinical models of psychosis onset, involving a neonatal hippocampal lesion, prenatal immune activation, and administration of PCP (phencyclidine) or methylazoxymethanol acetate (MAM), respectively. While all these models are useful, the neonatal hippocampal model lacks construct validity, the evidence linking prenatal immune activation with psychosis is limited, and the chronic PCP model does not have a neurodevelopmental component. The MAM model reproduces a neurodevelopmental trajectory of neural and behavioral changes that resemble those evident in human studies of psychosis onset. Collectively, these models have advanced knowledge of the mechanisms underlying the onset of psychotic disorders and have provided a rationale for novel preventative interventions.

AB - Although clinical intervention at the clinical high risk stage has the potential to prevent the onset of psychosis, there are still no licensed pharmacological treatments for this purpose. The development of preventative treatments is informed by models of psychosis onset, especially those that reflect the time course and symptomatology of the disorder. This chapter describes four different preclinical models of psychosis onset, involving a neonatal hippocampal lesion, prenatal immune activation, and administration of PCP (phencyclidine) or methylazoxymethanol acetate (MAM), respectively. While all these models are useful, the neonatal hippocampal model lacks construct validity, the evidence linking prenatal immune activation with psychosis is limited, and the chronic PCP model does not have a neurodevelopmental component. The MAM model reproduces a neurodevelopmental trajectory of neural and behavioral changes that resemble those evident in human studies of psychosis onset. Collectively, these models have advanced knowledge of the mechanisms underlying the onset of psychotic disorders and have provided a rationale for novel preventative interventions.

KW - Animal models

KW - Chronic PCP

KW - Clinical high risk for psychosis

KW - MAM

KW - Neonatal hippocampal lesion

KW - Prenatal immune activation

KW - Psychosis risk

UR - https://www.scopus.com/pages/publications/85142032046

U2 - 10.1016/B978-0-12-813201-2.00012-0

DO - 10.1016/B978-0-12-813201-2.00012-0

M3 - Chapter

AN - SCOPUS:85142032046

SN - 9780128132029

SP - 229

EP - 247

BT - Risk Factors for Psychosis

PB - Elsevier

ER -