title: Abnormal signal transduction: a hypothetical model for bipolar affective disorder.
abstract: The molecular basis of bipolar affective disorder is poorly understood at this time. The episodic nature of the condition in which relatively euthymic periods of variable duration separate periods of mania and depression, and the specificity of lithium therapy suggests that a molecular target of the illness may be a system that bidirectionally influences neurotransmission and is affected by lithium. Signal transduction pathways, which are important mediators of neurotransmitter generated signals, may represent such a system because they: 1) generate second messenger molecules that stimulate neurotransmission and also mediate negative feedback mechanisms, and 2) appear to be a direct target of lithium's action on cells. In this paper, we present a model in which abnormal regulation of signal transduction could lead to the episodic accumulation of biologically active transducers or second messengers. These alterations may result in prolonged effector stimulation which may underlie mania, followed by excessive receptor desensitization, which may result in depression. Using our model we suggest a plausible hypothesis that can explain the clinical spectrum of the disorder and the therapeutic action of lithium.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, N.Y. 10467.
authors.forename: H M
authors.initials: HM
authors.lastname: Lachman
authors.forename: D F
authors.initials: DF
authors.lastname: Papolos
mesh_terms: D001714:Bipolar Disorder / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D010507:Periodicity; D010716:Phosphatidylinositols / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction
chemical_list: D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D008094:Lithium