Familial transmission of risk factors in the first-degree relatives of schizophrenic people

Schizophrenia is a complex illness with multiple pathophysiologic factors t hat contribute to its psychopathology, One strategy to identify these facto rs is to observe them in isolation from each other, by characterizing their expression in the relatives of schizophrenic probands, By Mendel's second law, each genetic factor should be independently distributed in a sibship, so that each can be observed by itself uncomplicated by the general problem s of the illness. Such independently distributed phenotypes are obviously u seful for genetic analyses; however, they can also be considered together, to model how various brain dysfunctions may combine to produce psychoses. I n addition to a sensory gating deficit linked to the alpha 7-nicotinic acet ylcholine receptor locus, schizophrenics and their families have a number o f other deficits, including decreased hippocampal volume on magnetic resona nce images and increased plasma levels of the dopamine metabolite homovanil lic acid Although such research is far from complete, a heuristic model com bining a sensory gating deficit, decreased hippocampal neuron capacity, and increased dopaminergic neurotransmission is consonant with current underst anding of the neuropsychology of schizophrenia, Biol Psychiatry 2000;47:231 -239 (C) 2000 Society of Biological Psychiatry.