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Vulnerability of the Brain to Neuropsychiatric Disorders Resulting from Abnormal Thyroid Hormone or Vitamin D Homeostasis

  • Sarah J. Bailey
  • Peter J. McCafferyEmail author
Chapter

Abstract

Nutritional modification is an approach to augment protection of the brain from psychiatric disease that is both inexpensive and with fewer side-effects than most psychoactive drugs. Two factors derived from nutritional sources that regulate gene transcription via nuclear receptors are thyroid hormone and vitamin D. Both of these factors thus lie at a nexus of environmental and genetic regulation of gene expression. Changes in both pathways have been associated with schizophrenia and depression but unlike dietary supplements such as omega-3 fatty acids, their mode of signalling is well understood. This chapter details the association of thyroid hormone and vitamin D with these psychiatric disorders. Likely targets for these two nuclear receptor regulators include the dopamine receptors, serotonergic pathways, hippocampal neurogenesis as well as components of the developing brain. The association of the nuclear receptor signalling pathways with several diseases suggests that they are less likely to be responsible for the unique features of each disease but are involved in aspects common to the disorders, as has been proposed for genes such as DISC1. An imbalance in the thyroid hormone and vitamin D pathways may contribute to depression and schizophrenia and restoration of homeostasis may provide a route by which the brain may be protected.

Keywords

Depression Schizophrenia RXR Nuclear receptor Thyroid hormone Vitamin D Serotonin Dopamine receptor 

Abbreviations

ATP

Adenosine triphosphate

BDNF

Brain derived neurotrophic factor

CNS

Central nervous system

Cnr

Cannabinoid receptor

CSF

Cerebrospinal fluid

GABA

Gamma-aminobutyric acid

GDNF

Glial cell line derived neurotrophic factor

5-HT

5-hydroxytryptamine

5HTT

5-hydroxytryptamine transporter

5-HT1A

5-hydroxytryptamine receptor 1A

N-CoR

Nuclear receptor co-repressor

NGF

Nerve growth factor

PI3K–PKB

Phosphatidylinositide 3-kinase-protein kinase B

RA

All-trans retinoic acid

SAD

Seasonal affective disorder

Scn4b

Sodium channel subunit

SMRT

Silencing mediator for retinoid and thyroid hormone receptors

T4

Thyroxine

T3

Triiodothyronine

TH

Thyroid hormone

TR

Thyroid hormone receptor

TRH

Thyrotropin-releasing hormone

TSH

Thyroid stimulating hormone

TTR

Transthyretin

VD

Vitamin D

VDR

Vitamin D receptor

Notes

Acknowledgements

We would like to thank Dr. Michelle Lane for her reading of the text and excellent suggestions as well as thanking Jemma Ransom for her reading of the section on schizophrenia.

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  1. 1.Department of Pharmacy & PharmacologyUniversity of BathBath, AvonUK
  2. 2.Institute of Medical SciencesUniversity of AberdeenAberdeenUK

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