Influence of Levothyroxine in Augmentation Therapy for Bipolar Depression on Central Serotonergic Function

Uhl, Idun; Bez, Jennifer; Stamm, Thomas; Pilhatsch, Maximilian; Assion, H.-J.; Norra, Christine; Lewitzka, Ute; Schlagenhauf, Florian; Bauer, Moisés Evandro; Juckel, Georg

doi:10.1055/s-0034-1383654

Cited by 6 publications

(7 citation statements)

References 13 publications

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Section: Clinical Aspects Of Thyroid-related Cns Changesmentioning

confidence: 99%

“…Another potential mechanism of the TH augmentation of antidepressant efficacy is through an increase in serotonergic neurotransmission [ 44 , 45 ]. Uhl et al investigated the loudness dependence of auditory evoked potentials (LDAEP) as a measure of central serotonergic activity and response to levothyroxine [ 45 ]. In this 6-week, double-blind, randomized, placebo-controlled study, the efficacy of levothyroxine adjunctive treatment compared to placebo was monitored in 20 patients with bipolar depression.…”

Section: Clinical Aspects Of Thyroid-related Cns Changesmentioning

confidence: 99%

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Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Jurado-Flores

Warda

Mooradian

2022

Journal of the Endocrine Society

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Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis and apathy especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

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Section: Clinical Aspects Of Thyroid-related Cns Changesmentioning

confidence: 99%

Section: Clinical Aspects Of Thyroid-related Cns Changesmentioning

confidence: 99%

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Jurado-Flores

Warda

Mooradian

2022

Journal of the Endocrine Society

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“…Returning to the rodent models, Fu et al showed that the administration of L-T 4 to aged mice can significantly improve their learning and memory capacities, through increases of both serum and 16 brain concentrations of free T 3 and T 4 (Fu et al, 2014). Similar treatments also can counteract depression in rats and humans (Bauer et al, 2005;Ge et al, 2016;Uhl et al, 2014). Depression is known to be linked with an impaired neurogenesis (Jacobs, 2002;Schoenfeld and Cameron, 2015).…”

Section: Roles Of Th In the Ageing Brainmentioning

confidence: 99%

Comparative approaches to understanding thyroid hormone regulation of neurogenesis

Gothié

Demeneix

Remaud

2017

Molecular and Cellular Endocrinology

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Thyroid hormone (TH) signalling, an evolutionary conserved pathway, is crucial for brain function and cognition throughout life, from early development to ageing. In humans, TH deficiency during pregnancy alters offspring brain development, increasing the risk of cognitive disorders. How TH regulates neurogenesis and subsequent behaviour and cognitive functions remains a major research challenge. Cellular and molecular mechanisms underlying TH signalling on proliferation, survival, determination, migration, differentiation and maturation have been studied in mammalian animal models for over a century. However, recent data show that THs also influence embryonic and adult neurogenesis throughout vertebrates (from mammals to teleosts). These latest observations raise the question of how TH availability is controlled during neurogenesis and particularly in specific neural stem cell populations. This review deals with the role of TH in regulating neurogenesis in the developing and the adult brain across different vertebrate species. Such evo-devo approaches can shed new light on (i) the evolution of the nervous system and (ii) the evolutionary control of neurogenesis by TH across animal phyla. We also discuss the role of thyroid disruptors on brain development in an evolutionary context.

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“…In our previous study, SCH induced depression-like behavior in rats accompanied by subtle hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis ( 6 ). Clinical studies have demonstrated that treatment with levothyroxine (LT4) improves mood and normalizes the elevated relative cerebral glucose metabolism in several brain areas of depression patients ( 7 , 8 ). However, the correct dosage of LT4 remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/β-Catenin Pathway

Qin

et al. 2016

Front. Endocrinol.

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Metabolic disease subclinical hypothyroidism (SCH) is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES) in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days. The rats’ plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic–pituitary–adrenal (HPA) activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment downregulated the elevated plasma thyroid-stimulating hormone concentration and the hypothalamic mRNA expression of thyrotropin-releasing hormone in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the open-field test, increased sucrose preference in the sucrose preference test, and decreased immobility in the forced swimming test compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels, and the hypothalamic corticotrophin-releasing hormone mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment upregulated the relative ratio of phosphorylated-GSK3β (p-GSK3β)/GSK3β and protein levels of p-GSK3β, cyclin D1, and c-myc, while downregulating the relative ratio of phosphorylated-β-catenin (p-β-catenin)/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by downregulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/β-catenin pathway.

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Influence of Levothyroxine in Augmentation Therapy for Bipolar Depression on Central Serotonergic Function

Abstract: The hypothesis of a relationship between response of augmentation therapy with levothyroxine in bipolar depression and serotonergic activity could not be confirmed.

Cited by 6 publications

References 13 publications

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Comparative approaches to understanding thyroid hormone regulation of neurogenesis

Resveratrol Ameliorates the Anxiety- and Depression-Like Behavior of Subclinical Hypothyroidism Rat: Possible Involvement of the HPT Axis, HPA Axis, and Wnt/β-Catenin Pathway

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