The use of antioxidant compounds in the treatment of first psychotic episode: Highlights from preclinical studies

Abstract

Recent evidence highlighted a pathogenetic link between redox dysregulation and the early stages of psychosis. Indeed, an increasing number of studies have pointed toward an association between oxidative stress, both at central and peripheral levels, and first psychotic episode. Moreover, basal low antioxidant capacity has been shown to directly correlate with cognitive impairment in the early onset of psychosis. In this context, the possibility to use antioxidant compounds in first psychotic episode, especially as supplementation to antipsychotic therapy, has become the focus of numerous investigations on rodents with the aim to translate data on the possible effects of antioxidant therapies to large populations of patients, with a diagnosis of the first psychotic episode. In this review, we will discuss studies, published from January 1st, 2007 to July 31st, 2017, investigating the effects of antioxidant compounds on neuropathological alterations observed in different rodent models characterized by a cluster of psychotic-like symptoms reminiscent of what observed in human first psychotic episode. A final focus on the effective possibility to directly translate data obtained on rodents to humans will be also provided.

Schizophrenia Increases Variability of the Central Antioxidant System: A Meta-Analysis of Variance From MRS Studies of Glutathione

“…A representative model of schizophrenia that is true to its heterogenous clinical phenotype likely includes both redox-deficient and redox-sufficient individuals. We, like many other observers in the field ( 49 ), consider antioxidant system to be an important non-dopaminergic target for early intervention in schizophrenia; addressing the questions raised here will be of critical importance to realize the potential promise of this pathway in treating psychotic disorders.…”

Antioxidant Properties of Second-Generation Antipsychotics: Focus on Microglia

“…As mentioned above, an increasing number of studies have pointed toward an association between the occurrence of oxidative stress and the risk to develop psychosis. There are numerous preclinical studies highlighting the therapeutic potential of antioxidants for the treatment of FEP [ 155 ], a critical intervention period in schizophrenia. One of the most used antioxidants is represented by N -acetylcysteine (NAC) that has been shown to counteract schizophrenia-like bio-behavioral changes in rats exposed to maternal immune [ 156 ], prevent the loss of cortical inhibitory parvalbumin-positive interneurons [ 71 ], and reverse dysregulated mitochondrial activity and the related production of ROS/RNS [ 157 ] in different animal models of schizophrenia.…”

“…One of the most used antioxidants is represented by N -acetylcysteine (NAC) that has been shown to counteract schizophrenia-like bio-behavioral changes in rats exposed to maternal immune [ 156 ], prevent the loss of cortical inhibitory parvalbumin-positive interneurons [ 71 ], and reverse dysregulated mitochondrial activity and the related production of ROS/RNS [ 157 ] in different animal models of schizophrenia. Other antioxidants that have been considered in preclinical studies, in particular to manage psychotic symptoms, are represented by apocynin, omega-3 fatty acids, vitamin C, and ebselen [ 155 ].…”

Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

“…A similar beneficial behavior was also observed for apocynin, a natural compound also known as acetovanillone. A more limited number of contributions also investigated the role of vitamin C, omega-3 fatty acids, and ebselen [ 86 ]. In particular, Cabungcal et al studied the effects of the adolescent treatment with the latter compound, a well-known GPX-mimic, in rats with a neonatal ventral hippocampal lesion, a developmental rodent model of schizophrenia.…”

“…Phenelzine (21, Scheme 4) (β-phenylethylhydrazine) is a non-selective irreversible MAO inhibitor endowed with antidepressant activity and that has also been reported to be effective in Schiavone and Trabace recently reviewed the scientific contributions from the 2007-2017 timeframe, investigating the effects of antioxidant compounds on neuropathological alterations in psychotic rodent models [86]. N-acetylcysteine is among the most studied supplements and showed positive effects in preventing or ameliorating neuropathological and behavioral alterations in the ketamine perinatal model of psychosis and in several other preclinical studies.…”