Early cerebro-craniofacial dysmorphogenesis in schizophrenia: a lifetime trajectory model from neurodevelopmental basis to 'neuroprogressive' process

Understanding the temporal origin(s) of schizophrenia, through specifying t he earliest identifiable pathology, might indicate when to look for etiolog ical factor(s), what their nature might be, and how course of illness might evolve from these origins. From this premise, earlier formulations are ela borated to offer a rigorously data-driven model that roots schizophrenia in cerebro-craniofacial dysmorphogenesis, particularly along the mid-line but involving other structures, over weeks 9/10 through 14/15 of gestation. Ho wever, a brain that has been compromised very early in fetal life is still subject to the normal endogenous programme of developmental, maturational a nd involutional processes on which a variety of exogenous biological insult s and psychosocial stressors can impact adversely over later pregnancy, thr ough infancy and childhood, to maturation and into old age, to sculpt brain structure and function; it should be emphasised that the effects of such e ndogenous programmes and exogenous insults on such an already developmental ly-compromised brain may be different from their effects on a brain whose e arly fetal origins were unremarkable. From these early origins, a lifetime trajectory model for schizophrenia from developmental basis to 'neuroprogre ssive' process is constructed. Thereafter, consideration is given to what t he model can explain, including cerebral asymmetry and homogeneity, what it cannot explain, what empirical findings would challenge or disprove the mo del, what cellular and molecular mechanisms might underpin the model, and w hat are its implications. (C) 1999 Elsevier Science Ltd. All rights reserve d.