The Balance in the Head: How Developmental Factors Explain Relationships Between Brain Asymmetries and Mental Diseases.

Cerebral lateralisation is a core organising principle of the brain that is characterised by a complex pattern of hemispheric specialisations and interhemispheric interactions. In various mental disorders, functional and/or structural hemispheric asymmetries are changed compared to healthy controls, and these alterations may contribute to the primary symptoms and cognitive impairments of a specific disorder. Since multiple genetic and epigenetic factors influence both the pathogenesis of mental illness and the development of brain asymmetries, it is likely that the neural developmental pathways overlap or are even causally intertwined, although the timing, magnitude, and direction of interactions may vary depending on the specific disorder. However, the underlying developmental steps and neuronal mechanisms are still unclear. In this review article, we briefly summarise what we know about structural, functional, and developmental relationships and outline hypothetical connections, which could be investigated in appropriate animal models. Altered cerebral asymmetries may causally contribute to the development of the structural and/or functional features of a disorder, as neural mechanisms that trigger neuropathogenesis are embedded in the asymmetrical organisation of the developing brain. Therefore, the occurrence and severity of impairments in neural processing and cognition probably cannot be understood independently of the development of the lateralised organisation of intra- and interhemispheric neuronal networks. Conversely, impaired cellular processes can also hinder favourable asymmetry development and lead to cognitive deficits in particular.