Systemic lupus erythematosus of the central nervous system: 2. Molecular theories and models for mental disease.
A molecular theory attempting to account for the complexity and diversity of the manifestations of systemic lupus erythematosus (SLE) central nervous system (CNS) disease is presented. The clinical manifestations of seizures, pareses, and movement and cranial nerve disorders can be accounted for primarily by immune-complex-mediated small and medium-sized cerebral vasculopathy. The disorders of thought and affect can be explained predominantly by systemic and intrathecal synthesis of antineuronal autoantibodies and brain-enzyme-inhibiting factors leading to alterations in the quantity of mesolimbic neurotransmitter release. It is possible that a multitude of different molecular pathologic derangements can lead to the same or different CNS dysfunctions. The final clinical expression of CNS disease in patients with SLE is dictated by the permutations and combinations of the individuals' underlying genetic predisposition, environmental triggers, specific systemic and intrathecal antineuronal autoantibodies, and the diversity and extent of immune-complex-mediated cerebral vasculopathy. Ways in which SLE-CNS disease may be viewed as a theoretical model for the nature and etiology of mental disease are discussed.
Moskowitz
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D001323:Autoantibodies; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology; D001523:Mental Disorders / Q000209:etiology* / Q000276:immunology; D009474:Neurons / Q000276:immunology
D001323:Autoantibodies