A candidate molecule approach to defining developmental pathology in schizophrenia.
The evidence that schizophrenia may have its origins from early in life, possibly during prenatal brain development, is based primarily on a constellation of nonspecific anatomical findings and on the results of surveys of obstetrical complications and of childhood neurological and psychological adjustment. The developmental processes implicated by this evidence are uncertain, but speculation has centered around abnormalities of neuronal proliferation, migration, and connection formation. These developmental milestones are the results of complicated cellular processes involving molecular interactions between cells and between the extracellular and intracellular milieus. To understand how these abnormalities could relate to schizophrenia, it is necessary to characterize the molecular events that define the processes. In this article, we discuss the potential impact of a number of molecules that are important in the sequence of cellular events implicated in schizophrenia. In particular, we focus on molecular mechanisms related to cell proliferation, axonal outgrowth, cell migration, cell survival, synaptic regression, myelination, and developmental aspects of early adult life. These various candidate molecules regulate different aspects of cell growth and cell-cell interactions and are involved in the regulation of deoxyribonucleic acid (DNA) expression. Very few of these molecules have been studied in the schizophrenic brain.
Weickert
C S
CS
Clinical Brain Disorders Branch, Intramural Research Project, National Institute of Mental Health Neuroscience Center at St. Elizabeths Hospital, Washington, DC 20032, USA.
Weinberger
D R
DR
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000196:embryology / Q000254:growth & development*; D001923:Brain Chemistry / Q000502:physiology; D002648:Child; D018450:Disease Progression; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D011627:Puberty / Q000502:physiology; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*
D006133:Growth Substances