title: Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study.
abstract: Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 (n=15) or placebo (n=10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P<0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores (P<0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.|Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Berman
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Stamm
authors.affiliation: Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Plotkin
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Adli
authors.affiliation: Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Pilhatsch
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: London
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, Semel Institute Biostatistics Core, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: G S
authors.initials: GS
authors.lastname: Hellemann
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Whybrow
authors.affiliation: Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schlagenhauf
mesh_terms: D000328:Adult; D000679:Amygdala / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D001931:Brain Mapping; D003863:Depression / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010919:Placebos; D049268:Positron-Emission Tomography / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D013974:Thyroxine / Q000187:drug effects* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D005947:Glucose; D013974:Thyroxine