Possible relevance of phospholipid abnormalities and genetic interactions in psychiatric disorders: the relationship between dyslexia and schizophrenia.
The fatty acids of cell membrane phospholipids are essential for normal membrane structures, for the functioning of membrane-bound and membrane-associated proteins and for normal cell-signalling responses. In dyslexia, there is evidence for reduced incorporation of docosahexaenoic acid and arachidonic acid into cell membranes, while in schizophrenia, there is evidence for an increased rate of docosahexaenoic acid and arachidonic acid loss from membranes because of enhanced phospholipase A2 activity. The presence of both defects will cause a much greater degree of abnormality than either one alone. It is hypothesized that unequivocal clinical schizophrenia may occur when both genes are present in the same individual. The dyslexia gene along will produce dyslexia while the schizophrenia gene alone may produce bipolar or schizoaffective disorders. These proposals could explain: 1. The reduced asymmetry of the brain, especially of the planum temporale in both schizophrenia and dyslexia; 2. The schizotypal personality characteristics of dyslexics; 3. The increased risks of dyslexia in families with a schizophrenic proband; 4. The increased risks of bipolar and schizoaffective disorders in families with a schizophrenic proband; 5. The earlier onset and possibly increased severity of both disorders in males since females have a lower requirement for arachidonic acid and docosahexaenoic acid; 6. The absence of selective pressure against schizophrenia since reproduction would be impaired only when the schizophrenic gene coexisted with a dyslexic gene. The schizophrenic gene alone might even lead to improved reproductive performance.
Horrobin
D F
DF
Scotia Research Institute, Kentville, Nova Scotia, Canada.
Glen
A I
AI
Hudson
C J
CJ
D016718:Arachidonic Acid / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D004410:Dyslexia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D004777:Environment; D005228:Fatty Acids, Essential / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*
D005228:Fatty Acids, Essential; D008563:Membrane Lipids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2