Congenital anomalies in relatives of schizophrenic probands may indicate a retinoid pathology.
Retinoic acid, the morphogenic derivative of vitamin A, has been shown to alter patterns of neurulation and to regulate the expression of many genes involved in central nervous system development. Retinoid toxicity can result in craniofacial, limb, digit, heart and urogenital abnormalities. Hydrocephalus, due to increased ventricular size and/or decreased size of the hind- or forebrain, occurs frequently. Comparison of the frequency and type of congenital anomalies in extended pedigrees of 12 Ashkenazi probands with schizophrenia and seven normal Ashkenazi control probands indicates that relatives of the schizophrenic probands present a gamut of both minor and major congenital anomalies similar to, but less severe than, those caused by retinoid excess or deficiency, and at a frequency significantly greater than in control pedigrees. Within schizophrenic pedigrees, those diagnosed with schizophrenia spectrum illnesses are more likely to present such anomalies than are non-spectrum members. Retinoic acid receptors are present in all parts of the cranial region and delivery of retinoids is exquisitely controlled throughout embryonic and fetal development. Alterations in the functioning of the retinoid cascade may have profound implications for neurodevelopmental disorders like schizophrenia.
Goodman
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AB
Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000002:abnormalities*; D003241:Consanguinity; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007585:Jews / Q000235:genetics* / Q000523:psychology; D008297:Male; D019965:Neurocognitive Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014212:Tretinoin / Q000502:physiology*
D018168:Receptors, Retinoic Acid; D014212:Tretinoin