Morphologic Markers of Neurodevelopmental Paths: Revisited

Abstract

Recent decades have seen a transformation in attitudes, both lay and scientific, about the causes of schizophrenia. There is no longer much debate that schizophrenia reflects brain dysfunction, but there remain many questions about the nature of this dysfunction and its basic causes. Gerald Edelman (1988) presented compelling arguments that all function (or dysfunction) is ultimately rooted in structure (or dysmorphology). Functioning of the brain may be altered by structural abnormalities at the level of individual molecules (i.e., those comprising receptors and membrane elements), at the level of molecular aggregates comprising cells and their interactions, or at the level of interconnected networks of cells, comprising functional anatomic systems. To understand the causes of schizophrenia it is important to determine what structural anomalies exist at the molecular, cellular, and gross anatomic levels, and how these structural abnormalities are related to physiologic abnormalities. Although ultimately even gross anatomic features are explicable in terms of more microscopic processes, it is striking that in schizophrenia, we have clues to pathophysiology that are so obvious -- on a scale that they may be observed by the unaided eye. Characterizing the gross anatomic abnormalities in schizophrenia therefore offers a useful starting point in our attempts to appreciate the fundamental causes of schizophrenia. Once abnormalities on the macroscopic level are more clearly understood, in terms of their population distributions, antecedents, and associated features, organized searches for the more molecular changes underlying these abnormalities may be conducted.

“Morphology... is the largest single basis of behavior.”

(G. Edelman, 1992, Bright Air, Brilliant Fire, Basic Books, NY, p. 49).