Interaction of neurodevelopmental pathways and synaptic plasticity in mental retardation, autism spectrum disorder and schizophrenia: implications for psychiatry.

OBJECTIVES

Schizophrenia (SCZ), autism spectrum disorder (ASD) and mental retardation (MR) are psychiatric disorders with high heritability. They differ in their clinical presentation and in their time course of major symptoms, which predominantly occurs for MR and ASD during childhood and for SCZ during young adult age. Recent findings with focus on the developmental neurobiology of these disorders emphasize shared mechanisms of common origin. These findings propose a continuum of genetic risk factors impacting on synaptic plasticity with MR causing impairments in global cognitive abilities, ASD in social cognition and SCZ in both global and social cognition.

METHODS

We assess here the historical developments that led to the current disease concepts of the three disorders. We then analyse, based on the functions of genes mutated in two or three of the disorders, selected mechanisms shared in neurodevelopmental pathways and synaptic plasticity.

RESULTS

The analysis of the psychopathological constructs supports the existence of three distinct clinical entities but also elaborates important associations. Similarly, there are common mechanisms especially in global and social cognition.

CONCLUSIONS

We discuss implications from this integrated view on MR, ASD and SCZ for child & adolescent and adult psychiatry in pathophysiology and research perspectives.