Genetics of Psychosis

Psychotic disorders such as schizophrenia are among the most disabling human illnesses. The causes of these illnesses have remained unknown, leading to much misunderstanding, stigmatization, and suffering. These illnesses are highly heritable, as evidenced by family association studies. Twin and adoption studies have pointed to the possibility of considerable environmental contributions to their causation. The identification of the chromosome locations and the specific genes is aided by linkage and association studies. Recent large-scale genome-wide association studies have pointed to a large number of genes that may together confer risk to this group of illnesses. These genes include those that have been previously implicated in the pathogenesis of psychotic disorders, such as glutamatergic neurotransmission, brain development and synapse plasticity, ion channels, and immune function. These genes may offer new ways to treat these serious illnesses, which are currently only treated with medications that target one system, namely dopamine. This review contains 6 figures, 9 tables, and 51 references. Key words: Brain development, complement, dopamine, familial, genome, glutamate, immune function, psychosis, schizophrenia

Enzymes that degrade phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate have different developmental profiles in chick brain

The activities and subcellular distributions of the hydrolases that degrade polyphosphoinositides were compared in the developing chick central nervous system. Specific activities increased 2- 3-fold and total activities increased 13-to 16-fold. Phosphatidylinositol 4-phosphate phosphatase is localized in membranes (78%), but is preferentially associated with nonmyelin membranes, since the increase in specific activity preceded myelination and proportions of membrane and soluble activities were constant during accumulation of myelin membranes. Phosphatidylinositol 4,5-bisphosphate phosphatase is largely soluble in embryonic (57%) and myelinated brain (50%). Although specific activity increased coincident with myelination, approximately equal increases in soluble and membrane activity indicate no preferential association with myelin membranes. Phosphatidylinositol 4,5-bisphosphate phosphodiesterase activity increased only in the early stages of myelination, but showed some preferential association with myelin membranes, since the proportion of soluble diesterase declined from 40 to 25%.Key words: brain, development, myelin, phosphodiesterase, phosphoinositide, phosphomonoesterase, phospholipids.