Laterality in Animals: Relevance to Schizophrenia

Abstract

Anomalies in the laterality of numerous newocognitive dimensions associated with schizophrenia have been documented, but their role in the etiology and early development of the disorder remain unclear. In the study of normative neurobehavioral organization, animal models have shed much light on the mechanisms underlying and the factors affecting adult patterns of both functional and structural asymmetry. Nonhuman species have more recently been used to investigate the environmental, genetic, and neuroendocrine factors associated with developmental language disorders in humans. We propose that the animal models used to study the basis of lateralization in normative development and language disorders such as dyslexia could be modified to investigate lateralized phenomena in schizophrenia.Key words: Animal models, laterality in animals, functional and structural asymmetry, language, hand preference.Schizophrenia Bulletin, 25(l):41-62,1999.Throughout the history of the brain and behavioral sciences, it has been largely accepted that cerebral lateralization was a unique feature of the human brain, particularly for functions underlying language and hand preference (Glick et al. 1979;MacNeilage et al. 1987; Denenberg 1988). However, accumulated evidence now supports the existence of lateralization at the structural and functional levels in a range of species. A portion of the literature on animal laterality will be discussed in this article, but the reader is referred to a number of recent, comprehensive reviews for more detailed coverage of functional, anatomical, and neurochemical asymmetries in nonhuman species (Denenberg 1984; Diamond 1984;Gerendai 1984;Goldman-Rakic and Rakic 1984; Bianki 1988;Springer and Deutsch 1989;Ward 1991;Hellige 1993;Hiscock and Kinsbourne 1995).Despite the large and growing literature describing behavioral, neuroanatomical, and neurophysiological asymmetries in nonhuman species, research on animal laterality has not been well integrated into the mainstream of human brain research. Nevertheless, a few investigators have demonstrated success in applying animal models of laterality to the study of human brain development and behavioral disorders. For example, Denenberg, Fitch, Rosen, and colleagues have used rodents to model the anomalous laterality patterns associated with developmental dyslexia and language impairment (Rosen et al.

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

“…[134][135][136] Neuroanatomical studies have found differences between schizophrenia patients and controls in the number, density or distribution of neurons between the left and right hemispheres. 8,137,138 Abnormalities of laterality have also been revealed by brain imaging studies measuring subregional tissue volume, blood flow, and metabolism.…”

“…There is an unclear relationship between these structural abnormalities, and the behavioral asymmetries in schizophrenia which are purportedly manifested in motor, sensory, language and cognitive function. 134,135 The idea that these lateralization abnormalities arise during development is gaining support, but little attention has been given to the possible involvement of a viral infection.…”

“…Studies of mouse models indicate that autoimmunity and the maternal or fetal immune status are potentially important determinants of lateralization differences during neurodevelopment. 134 Conversely, cerebral asymmetries influence immune responses. 143 Therefore it is conceivable that abnormalities in lateralization during neurodevelopment, whatever their cause, could lead to aberrant immune responses to a viral infection (eg occurring during adolescence), which could be the proximate trigger of schizophrenia symptoms.…”

Laterality in Functional Brain Imaging Studies of Schizophrenia

“…Links between clinical features of schizophrenia and brain function have been guided by hypotheses relating behavior to brain regions and systems that have been implicated in schizophrenia. These links are based on preclinical research (Cowell et al 1999, this issue) and the emergence of symptoms commonly seen in schizophrenia that also occur following brain lesions. Persistent negative symptoms were initially related to frontal lobe dysfunction, because similar behaviors are evident as sequelae of frontal lobe damage.…”

Is Schizophrenia a Lateralized Brain Disorder? Editor's Introduction

“…Lateralization of brain structure and function, initially considered unique to humans, is evident in other species. Cowell et al (1999, this issue) examine the evidence for cerebral lateralization in animals. They point out the lack of integration between animal and human work.…”