Neural correlates of free T3 alteration after catecholamine depletion in subjects with remitted major depressive disorder and in controls

Abstract

RationaleThyroid hormones and their interactions with catecholamines play a potentially important role in alterations of mood and cognition. ObjectivesThis study aimed to examine the neurobiological effects of catecholamine depletion on thyroid hormones by measuring endocrine and cerebral metabolic function in unmedicated subjects with remitted MDD (RMDD) and in healthy controls. MethodsThis was a randomized, placebo-controlled, and double-blind crossover trial that included 15 unmedicated RMDD subjects and 13 healthy control subjects. The participants underwent two 3-day-long sessions at 1-week intervals; each participant was randomly administered oral α-methyl-para-tyrosine (AMPT) in one session (catecholamine depletion) and an identical capsule containing hydrous lactose (sham depletion) in the other session prior to a [18 F]-fluorodeoxyglucose positron emission tomography scan ( 18 FDG-PET). ResultsSerum concentrations of free T3 (FT3), free T4 (FT4), and TSH were obtained and assessed with respect to their relationship to regional cerebral glucose metabolism. Both serum FT3 (P = 0.002) and FT4 (P = 0.0009) levels were less suppressed after catecholamine depletion compared with placebo treatment in the entire study sample. There was a positive association between both FT3 (P = 0.0005) and FT4 (P = 0.002) and depressive symptoms measured using the MADRS. The relative elevation in FT3 level was correlated with a decrease in regional glucose metabolism in the right dorsolateral prefrontal cortex (rDLPFC; P < 0.05, corrected).Homan et al.2 ConclusionsThis study provided evidence of an association between a thyroid-catecholamine interaction and mood regulation in the rDLPFC.

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“…As we all know, thyroid hormones can regulate gene transcription through nuclear receptors, but the level of thyroid hormones in the brain cannot be measured. For example, Homan indicated that some key regions are sensitive to the low levels of hormones ( 28 ).…”

Imaging the pathophysiology of major depressive disorder - from localist models to circuit-based analysis

“…While technical limitations generally prevent the imaging of such molecules directly, their effects on structure and metabolism can nevertheless be observed using MRI. In the case of MDD, this work has focused most heavily on pro-inflammatory factors, including families of cytokines such as interleukins and interferons, hormones such as glucocorticoids (cortisol), thyroid stimulating hormone (TSH), and ghrelin [117,118]. …”

Prevalence and clinical profile of abnormal glucose in first-episode and drug-naïve patients with major depressive disorder with comorbid abnormal thyroid function: a large-scale cross-sectional study

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