After doing much research I found that the most notable impairment in Treatment Resistant Depresssion is verbal working memory. After considering research across many mental disorders and neurodegenerative diseases the role of both BDNF and IGF-I in combination and the impact of neurotransmitters on these two factors has led me to the possible hypothesis that in general cognitive impairments may be linked to vulnerability within the hippocampus to the levels of BOTH BDNF and IGF-I...therefore to neuroplasticity issues. This led me to further consider the role of both BDNF and IGF-I in verbal working memory, with the possibility that if BOTH influenced verbal working memory, verbal working memory impairments could possibly indicate a deficit in both. Your input would be welcomed.
Here are some papers that may interest you or give you inspiration for further elaboration of your question:
Estrada JA, Contreras I, Pliego-Rivero FB, Otero GA.: Molecular mechanisms of cognitive impairment in iron deficiency: Alterations in brain-derived neurotrophic factor and Insulin-like growth factor expression and function in the central nervous system. Nutr Neurosci. 2014 Sep;17(5):193-206. doi: 10.1179/1476830513Y.0000000084. Epub 2013 Nov 26.
Yau SY, Lau BW, Zhang ED, Lee JC, Li A, Lee TM, Ching YP, Xu AM, So KF. Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats.Neuroscience. 2012 Oct 11;222:289-301. doi: 10.1016/j.neuroscience.2012.07.019.
David Bellar, John Gunstad, Ellen L. Glickman (2010) :The Relationship Of Age, Igf-1 And Bdnf To Working Memory In Healthy Older Adults: 817 . Journal: Medicine and Science in Sports and Exercise - MED SCI SPORT EXERCISE , vol. 42, 2010, DOI: 10.1249/01.MSS.0000385543.36993.f1
Karin Schon et al.: Ph.D., Department of Anatomy and Neurobiology, Boston University School of Medicine, 650 Albany Street, X-141, Boston, Massachusetts 02118, U.S.A., [email protected] who assessed a. recognition memory, peripheral neurotrophin levels and aerobic fitness. .
Mitschelen, Matthew | Yan, Han | Farley, Julie A. | Warrington, Junie P. | Han, Song | Hereñú, Claudia B. | Csiszar, Anna | Ungvari, Zoltan | Bailey-Downs, Lora C. | Bass, Caroline E. | Sonntag, William E.: Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: A potential model of geriatric depression Neuroscience 2011;185:50-60.
Stern SA, Alberini CM.:Mechanisms of memory enhancement. Wiley Interdiscip Rev Syst Biol Med. 2013 Jan-Feb;5(1):37-53. doi: 10.1002/wsbm.1196. Epub 2012 Nov 13. Review.
This is fantastic, thank you so much Beatrice!! I am going to enjoy reading these articles as information is few and far between, your help is greatly appreciated!!
An alternative hypothesis is that reduced hippocampal density due to inflammatory processes or oxidative stress may underly the WM problems and low BDNF levels in depression. There is some evidence that reductions in BDNF do not cause depression directly but because of its effects on neuroplasticity, new learning/problem solving becomes more difficult, which is likley to explain negative attributions, low self-efficacy, rumination and negative beliefs. You may also want to read Castren & Rantamaki (2010) Role of BDNF in the etiology of depression. CNS Drugs; 24(1): 1-7.
Thank you Ari, I was hoping to gain some insight into this, and what you have said, I have seen in the literature available. Naturally it is known that exercise increases BDNF, but the further question I have is that naturally some pharmacological drugs for Depression will increase BDNF expression through the increase or decrease of neurotransmitters, however even though BDNF expression increases cognitive impairments, such as working memory new learning etc do not seem to necessarily improve. In Brain injuries, the use of exogenuous GH (which increases IGF-I in the hippocampus) seems to have a positive impact on cognitive impairments, whichbhas brought me to the question of whether both have to be increased to gain the desired results, as with volume loss in the hippocampus etc both apper to be suppressed. Treatments do not seem to include IGF-I and I have wondered if IGF-I blood tests have been done on Depressed patients and if results have been recorded. If you know anything more on this I would be delighted to hear about it.
The only paper I could find was:
Krogh J1, Rostrup E2, Thomsen C3, Elfving B4, Videbech P5, Nordentoft M6. The effect of exercise on hippocampal volume and neurotrophines in patients with major depression--a randomized clinical trial. J Affect Disord. 2014 Aug;165:24-30.
Hi, I am researching the impact of BDNF on hippocampal processing and trauma, also looking at verbal memory. Here is our hypothesis paper and my original poster if that helps. Results so far indicate some relationship between BDNF and associative processing but we still need to collect more data. Expected to complete Spring 2015. Feel free to get in touch. Jess M.
Conference Paper PTSD, Navigation and Genetics (British Neuroscience Associat...
Article PTSD recovery, Spatial Processing, and the val66met Polymorphism
Thank you so much Jessica, this is extremely useful and the kind of information I am looking for. Your input is greatly appreciated!
Glad to be of help and good to know there's someone else out there interested in something similar.
Thanks Jessica, I have come to a hypothesis after seeing the effects of increased BDNF and IGF-I in brain injury patients case studies, that cognitive impairments can be resolved. Though I have not established the mechanism it is often seen that though people recover from symptoms of a disorder (psychological/physiological), cognitive impairments often remain, which means that a different mechanism at work, and I have not seen any data that sheds light on the IGF-I levels in these types of patients, which has led me to the thought that IGF-I (Liver produced) could be a possible mechanism, but that it works in combination with BDNF to differentiate and proliferate stem cells in the hippocampus, reducing oxidative stress etc, and allowing coupling with the amygdala...where emotions can be linked to external events/ I am so pleased that there is someone else who is looking into this!
Interesting, there is a lot about hyper active immunity and overactive amygdala too- which, lack of hippocampal integrity (due to BDNF gene status) can only exacerbate I guess?
Yes I think it makes it worse, but needs to be proven. I have a theory which may be of use to you. It is a bit longwinded so when I have some spare time tomorrow I will place it here for you, as I think you may find it quite interesting and parts of it may be relevant re BDNF and IGF-I. Your input is super, thanks Jessica!
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