Pharmacopsychiatry 2003; 36 - 14
DOI: 10.1055/s-2003-825265

Supraphysiological doses of L-thyroxine alter regional cerebral metabolism in refractory bipolar depression: A FDG-PET study

M Bauer 1, 2, ED London 2, N Rasgon 2, SM Berman 2, MA Frye 2, JC Mazziotta 2, L Altshuler 2, PC Whybrow 2
  • 1Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Humboldt University at Berlin, Berlin, Germany
  • 2Neuropsychiatric Institute & Hospital, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

Background: To assess changes in regional brain function associated with effects of treatment with L-Thyroxine (L-T4) adjunctive to ongoing medication on mood in bipolar depressed patients.

Methods: Regional cerebral glucose metabolism, an index of local brain function, was assessed with positron emission tomography and [18F]fluorodeoxyglucose in 10 depressed, euthyroid women with bipolar disorder, before and after 7 weeks of adjunctive treatment with supraphysiological doses of L-T4 (mean dose: 320 mcg/d). Corresponding measurements were acquired in an age-matched comparison group of 10 healthy women. The primary biological measures were relative glucose metabolism in pre-selected brain regions. Treatment-associated changes in regional metabolism (relative to global activity) were tested against clinical response.

Results: Before treatment, patients differed from controls in the pattern of cerebral glucose metabolism (lower relative activity in right dorsolateral prefrontal cortex; higher activity in the right hippocampus, right ventral striatum, and cerebellum (both sides). Significant behavioral and cerebral metabolic effects accompanied changes in thyroid hormone status. L-T4 improved mood significantly; and decreased relative activity in right amygdala and ventral striatum. The decrease in relative glucose metabolism of the left amygdala was correlated with reduction in depression scores.

Conclusions: L-T4 may improve mood by affecting prefrontal, subcortical and limbic circuits that have been previously implicated in affective disorders.