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Final Paper Topic

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For my final paper, I would like to focus on the intersection between the Hypothalamic-Pituitary Thyroid Axis (HPT Axis) and the Hypothalamic-Pituitary Adrenal Axis (HPA Axis), specifically as it relates to the role of thyroid hormones in fear learning, anxiety, and depression.

I've been interested in this topic since my freshman year of college when I first learned about fear in a research setting and began to learn about behavioral endocrinology and how hormones can affect behavior. Since then, I've noticed a gap in research on connecting the dots between thyroid hormones and their mechanistic action affecting anxiety, depression, and other fear learning behaviors. This interests stems from not only the symptomatology of thyroid disorders like hyper- and hypothyroidism. Two majors symptoms of both disorders are anxiety and depression. Additionally, research shows an increased incidence of PTSD, depression, and anxiety with thyroid disorders. Additionally, thyroid disorders affect women far more than men so there could most definitely be a sex differences approach to this exploration. Clinically, it's clear that there is a link between thyroid function and fear given the psychiatric issues that are apparent in thyroid dysfunction, though research is sparse as to the mechanism underlying this connection.
Bibliography for Research Basis:
1. Wang, S., Mason, J., Southwick, S., Johnson, D., Lubin, H., & Charney, D. (1995). Relationships Between Thyroid Hormones and Symptoms in Combat-Related Posttraumatic Stress Disorder. Psychosomatic Medicine KW -, 57(4).
2. Samuels M. H. (2014). Psychiatric and cognitive manifestations of hypothyroidism. Current opinion in endocrinology, diabetes, and obesity, 21(5), 377–383. https://doi.org/10.1097/MED.0000000000000089
3. Jung, S., Kang, J., Roberts, A., Nishimi, K., Chen, Q., Sumner, J., . . . Koenen, K. (2019). Posttraumatic stress disorder and incidence of thyroid dysfunction in women. Psychological Medicine, 49(15), 2551-2560. doi:10.1017/S0033291718003495
4. Dr Selcuk Aslan, Reyhan Ersoy, Asli Cepik Kuruoglu, Ayhan Karakoc & Nuri Cakir (2005) Psychiatric symptoms and diagnoses in thyroid disorders: a cross-sectional study, International Journal of Psychiatry in Clinical Practice, 9:3, 187-192,DOI: 10.1080/13651500510029129
5. E.L. Constant, S. Adam, X. Seron, R. Bruyer, A. Seghers & C. Daumerie (2006) Hypothyroidism and Major Depression: A Common Executive Dysfunction?, Journal of Clinical and Experimental Neuropsychology, 28:5, 790-807, DOI: 10.1080/13803390591000990
I'd like to explore this link through the possible interactions of glucocorticoids and thyroid hormones. To do this, I will first need to explore the general role of thyroid hormones on cognitive function. For that, I have gathered some resources that will help paint that picture.
Bibliography for Thyroid Base Function:
1. Grigorova, M., & Sherwin, B. B. (2012). Thyroid hormones and cognitive functioning in healthy, euthyroid women: a correlational study. Hormones and behavior, 61(4), 617–622. https://doi.org/10.1016/j.yhbeh.2012.02.014
2. Di Liegro, I. (2008). Thyroid hormones and the central nervous system of mammals (Review). Molecular Medicine Reports, 1, 279-295. https://doi.org/10.3892/mmr.1.3.279
3. Barton, S. Thyroid hormone receptors and neuronal dysfunction.Nat Rev Neurosci 6, 823 (2005). https://doi.org/10.1038/nrn1795
4. Prezioso G, Giannini C, Chiarelli F: Effect of Thyroid Hormones on Neurons and Neurodevelopment. Horm Res Paediatr 2018;90:73-81. doi: 10.1159/000492129
5. Bárez-López S and Guadaño-Ferraz A (2017) Thyroid Hormone Availability and Action during Brain Development in Rodents. Front. Cell. Neurosci. 11:240. doi: 10.3389/fncel.2017.00240
6. Rivas, M. and Naranjo, J.R. (2007), Thyroid hormones, learning and memory. Genes, Brain and Behavior, 6: 40-44. doi:10.1111/j.1601-183X.2007.00321.x
I would also want to discuss the interactions of Thyroid Hormones and Glucocorticoids. Here are some resources that begin to parse out the interactions of the two systems. I additionally want to postulate receptor/ligand interactions could be playing a role, so I want to explore more resources with information on receptor information. I could also benefit from utilizing hypothalamic research and to dive deeper in two major regions of interest for interactions which would be the hypothalamus and the amygdala.
Bibliography for Glucocorticoid and Thyroid Hormone Interactions:
1. Gil-Ibáñez P, Bernal J, Morte B (2014) Thyroid Hormone Regulation of Gene Expression in Primary Cerebrocortical Cells: Role of Thyroid Hormone Receptor Subtypes and Interactions with Retinoic Acid and Glucocorticoids. PLoS ONE 9(3): e91692. https://doi.org/10.1371/journal.pone.0091692
2. Laura Bessiène, Ségolène Hescot, Alexandra Bourdin-Pintueles, Laurence Dumeige, Géraldine Vitellius, Julie Perrot, Qiong-Yao Xu, Thi-An Vu, Laurent Sachs, Eric Pussard, Marc Lombès, Say Viengchareun & Laetitia Martinerie 2019 Thyroid hormones are new key regulators of glucocorticoid metabolism. Presented at 21st European Congress of Endocrinology 2019, Lyon, France. Endocrine Abstracts 63 OC7.2
3. Robson, H., Siebler, T., Shalet, S. et al. Interactions between GH, IGF-I, Glucocorticoids, and Thyroid Hormones during Skeletal Growth. Pediatr Res 52, 137–147 (2002). https://doi.org/10.1203/00006450-200208000-00003
4. Lixin Liu, Carlton E. Dean, Tom E. Porter, Thyroid Hormones Interact with Glucocorticoids to Affect Somatotroph Abundance in Chicken Embryonic Pituitary Cells in Vitro, Endocrinology, Volume 144, Issue 9, 1 September 2003, Pages 3836–3841, https://doi.org/10.1210/en.2003-0160
5. MARK H. PERRONE, THOMAS L. GREER, PATRICIA M. HINKLE, Relationships between Thyroid Hormone and Glucocorticoid Effects in GH3 Pituitary Cells, Endocrinology, Volume 106, Issue 2, 1 February 1980, Pages 600–605, https://doi.org/10.1210/endo-106-2-600
Finally, there is some directly linked research studying the effect of thyroid hormones on fear learning. I still need to do a more thorough search to make sure I'm including any and all research on this specific topic, but so far there are a handful that explore this.
Bibliography for the role of Thyroid Hormone in Fear Learning: 
1. Montero-Pedrazuela, A., Fernández-Lamo, I., Alieva, M., Pereda-Pérez, I., Venero, C., & Guadaño-Ferraz, A. (2011). Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala. PloS one, 6(10), e26582. https://doi.org/10.1371/journal.pone.0026582
2. Yu, D., Zhou, H., Zou, L., Jiang, Y., Wu, X., Jiang, L., Zhou, Q., Yang, Y., Xu, L., & Mao, R. (2017). Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats. Frontiers in cellular neuroscience, 11, 223. https://doi.org/10.3389/fncel.2017.00223
3. Reverte, I., Pujol, A., Domingo, J. L., & Colomina, M. T. (2014). Thyroid hormones and fear learning but not anxiety are affected in adult apoE transgenic mice exposed postnatally to decabromodiphenyl ether (BDE-209).Physiology & Behavior, 133, 81–91.
4. 489. Examination of an Acute Role for Thyroid Hormone Regulation of Trauma-Related Plasticity and Memory Formation in the Amygdala. Maddox, Stephanie et al. Biological Psychiatry, Volume 81, Issue 10, S199
As of right now, I'm not sure what the exact conclusion or what will tie the paper together. I clearly have a lot of research available and a general idea of the direction I'd like to go, but I still need to do a more thorough analysis of the literature itself to determine what the exact position of my review will be. For now, I'd like to focus on the potential interactions of glucocorticoids and thyroid hormones and ways those interactions could be driving the behavioral deficits seen in thyroid disorders. I still want to even out my research and get a strong hypothalamic background and explore my regions of interest more specifically in terms of these hormones. Once I determine the overarching narrative of my paper and research, the structure and flow of my paper will be critical for its success.

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