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Variations in Patients With Bipolar Affective Disorders

Ewen MacDonald, PhD; David Rubinow, MD; Markku Linnoila, MD, PhD

Arch Gen Psychiatry. 1984;41(5):487-493.

Abstract
• The sensitivity of RBC membrane (RBCM)Ca²⁺—adenosine triphosphatase (Ca²⁺-ATPase) to calmodulin stimulation was repeatedly studied in healthy volunteers and in 12 patients with affective disorders. Whereas control response was relatively stable, the patients showed great variability. This phenomenon was not due to formation of resealed vesicles in the RBCM nor to the quantity of calmodulin remaining in the RBCM preparations present in the cells before hemolysis. Changes in calmodulin sensitivity did not correlate with changes of mood or of drug treatment. When Ca²⁺-ATPase was relatively unresponsive to calmodulin, considerable enzyme activity was maintained at low calcium concentrations without calmodulin. In samples showing a large response to calmodulin, virtually no enzyme activity was detected at low calcium concentrations without exogenous calmodulin. Thus, calcium dependence and calmodulin sensitivity of the Ca²⁺-ATPase appeared to correlate positively with each other. As a similar phenomenon has been linked to changes in the composition of membrane phospholipids responsible for the regulation of Ca²⁺-ATPase activity, variations in baseline activity and calmodulin-induced stimulation of this enzyme may represent a fundamental defect in systems regulating membrane phospholipid composition.

Author Affiliations
From the National Institutes of Neurological and Communicative Disorders and Stroke (Dr MacDonald) and Mental Health (Drs Rubinow and Linnoila), National Institutes of Health, Bethesda, Md.

Footnotes
Accepted for publication June 21, 1983.

Reprint requests to Room 3B-23, Bldg 10, Bethesda, MD 20205 (Dr Linnoila).

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ABSTRACT