Impact of Endocannabinoid System Manipulation on Neurodevelopmental Processes Relevant to Schizophrenia

The neurodevelopmental hypothesis of schizophrenia has received much support from epidemiological and neuropathological studies and provides a framework to explain how early developmental abnormalities might manifest as psychosis in early adulthood. According to this theory, the onset of schizophrenia is likely the result of a complex interplay between a genetic predisposition and environmental factors whose respective influence might contribute to the etiology and progression of the disorder. The two most sensitive windows for neurodevelopment are the prenatal/ perinatal and the adolescent windows, both of which are characterized by specific processes impinging upon brain structure and functionality, whose alterations may contribute to the onset of schizophrenia. An increasing number of articles suggest the involvement of the endocannabinoid system in the modulation of at least some of these processes, especially in the prenatal/perinatal window. Thus, it is not surprising that disturbing the physiological role of endocannabinoid signaling in these sensitive windows might alter the correct formation of neuronal networks, eventually predisposing to neuropsychiatric diseases later in life. We review the most recent preclinical studies that evaluated the impact of endocannabinoid system modulation in the two sensitive developmental windows on neurodevelopmental processes that possess a specific relevance to schizophrenia.