N-acetyl cysteine as therapeutic intervention in a “two-hit” model of maternal inflammation and post-natal methamphetamine exposure

Abstract

Schizophrenia is a severe neurodegenerative, pro- gressive degenerative illness, prevalent in 0.5−1% of the world population. It is causally associated with a genetic aspect as well as early-life environmental stress. Schizophrenia usually presents with a combination of negative (affective flattening, aggression, depressive-like symptoms), positive (hallucinations, delusions), cognitive (learning and memory deficits) and affective (dysphoria) symptoms or unique domains of psychopathology. Previous stud- ies indicate that environmental factors, such as prenatal inflam- mation are linked to the risk for development of schizophrenia. The “two-hit” hypothesis suggests that multiple adverse events distributed over various life periods (e.g. prenatal inflammation plus postnatal drug abuse) can result in the development of schizo- phrenia. Since oxidative stress has been observed in schizophrenia, the anti-oxidant N-acetyl cysteine (NAC), a glutathione precursor and NMDA receptor modulator, is emerging as a useful agent in the adjunctive treatment of schizophrenia, and has theoretical preventive potential