Could maternal perinatal atypical antipsychotic treatments program later metabolic diseases in the offspring?

An association is established between schizophrenia and the development of metabolic alterations including cardiovascular diseases, type 2 diabetes and obesity. Perinatal insults, such as undernutrition, have been shown to increase the propensity to develop these pathologies, reinforcing the idea that schizophrenia may have a neurodevelopmental origin. Moreover, the use of second generation antipsychotics (SGAs) also known as "atypical" neuroleptics has also been demonstrated to exacerbate metabolic anomalies in patients with schizophrenia. SGAs are able to cross the placental barrier and have been detected in milk from women receiving atypical neuroleptics treatment during the perinatal period. To date, the consequences of such treatment have only been examined on the birth weight and the cognitive capacities of the child from women with schizophrenia, but no data is available concerning the putative long-term effects of SGAs on their body weight and metabolic parameters. We have recently reported that rat offspring from prenatally undernourished mothers exhibit a low birth weight associated with modified sensitivity to clozapine and aripiprazole in adulthood reinforcing the idea that some forms of schizophrenia may be acquired during early development. In view of these observations, the risks of perinatal exposure to SGAs must be weighed against the growing evidence that maternal psychiatric illness poses risks to the fetus/newborn as well as for long-term susceptibility to diseases. Thus, metabolic follow-up of children born from mothers treated by SGAs during the perinatal period will be clearly recommended, in particular if they exhibit alterations of their body weight during this early critical period.