This is an invalid argument (If B, then A, therore If A, then B). 

You really need a thorough lit review. It will take a long time, but good research questions. Consider taking a logic course; would help you read other's work and write your own. A research article is nothing more than an argument.

Hi Cheryl

This is the age old 'correlation vs causation' issue. I would look out for intervention studies (maybe animal models, if they exist) that have modified levels of HGH (either increased or decreased) and measured cognitive function as an outcome. As Marcie says an exhaustive lit review is the only way, and it is likely that you will just turn up descriptive (correlational) studies if you limit to human work only.

Good luck!

John

Dear Cheryl

These scientific resources may be help you to conceptualize a few hypothesizes in the field of HGH, BDNF, depression and cognitive functions for further investigation. 

Fred Nyberg & Mathias Hallberg. (2013). Growth hormone and cognitive function

doi:10.1038/nrendo.2013.78. Nature Reviews Endocrinology 9, 357-365 (2013)

Mahajan and colleagues. (2004). Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life. European Journal of Endocrinology (2004) 151 325–332.

Lašaitė and colleagues. (2004). Psychological functioning after growth hormone therapy in adult growth hormone deficient patients. http://centromedicoathenas.com.br/Content/Uploads/Info/170.pdf

Green and colleagues. (2007). Human Growth Hormone in the treatment of Biological Depression. http://www.priory.com/psychiatry/Growth_Hormone_Depression.htm

Klose and colleagues (2012). Quality of Life in Adult Hypopituitary Patients Treated for Growth Hormone Deficiency. http://benthamopen.com/contents/pdf/TOEJ/TOEJ-6-91.pdf

Laura D. Baker, Suzanne M. Barsness, Soo Borson, George R. Merriam, Seth D. Friedman, Suzanne Craft, Michael V. Vitiello. Effects of Growth Hormone–Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults: Results of a Controlled Trial. Archives of Neurology, 2012; DOI: 10.1001/archneurol.2012.1970

Vitiello and colleagues (2006). Growth hormone releasing hormone improves the cognition of healthy older adults. http://faculty.washington.edu/vitiello/Recent%20Publications/GHRH%20and%20Cognition%20in%20Aging.pdf

As Marcie Zinn says, this is the same tautological argument that has led to the past 60 years being wasted on SSRIs - that were never going to work any better than placebo because the logic they were based on is flawed ...

https://www.academia.edu/2240421/The_failure_of_the_antidepressant_drug_discovery_process_is_systemic

Thank you so much Marcie, John and Colin, I have found a few rat studies on specific components, but not as many as I would have liked. My apologies about the way in which I wrote the question, the area was not long enough for the full question, so part of it was cut off  (did not realise it) - so I have now edited it down to the most simplest element instead for you. I was attempting to frame questions (for brevity sake) which I have been attempting to find answers for. I have also changed the questions over the past year numerous times based on the premise that my questions may be incorrect (see past posts). I have been considering the interactions between specific elements in the brain and their possible role, or combined roles in the recovery of cognitive functions in MDD and TRD. In both classes of Depression, remission of symptoms may occur but cognitive functioning does not necessarily improve. In a few studies there has been mention of HGH deficiency and when I was assessing HGH in relation to TRD I found studies with regards to HGH deficiency in brain injury. Once HGH had been administered (along with other treatments) after brain injury, cognitive functioning seemed to recover in a number of cases. This brought me to the question of whether HGH may play a contributing role in the recovery of cognitive functioning.

 There could only be correlative evidence which may guide one to possible relationships. As all of you point out, the premise and logic that is behind a question is exceptionally important and can have a negative influence on research and eventually on the outcome of the lives of others - I wholly agree with you!

I have done a great deal of research and have collected a great deal of studies on BDNF and have extensive literature in the area of Depression, but very little that I could find that I felt was valid in the area of HGH. I have discovered that most Human studies are correlational and descriptive with conflicting results occurring as well as the use of different methodologies, tests etc. 

There has not been much in the way of clinical studies of HGH that I could find in respect to Depression (I then changed my questions) so I have found that most of the studies I have located have been linked to correlational studies and case studies.

Colin, you are right, one needs to be extremely cautious....the most important indicator that I have seen of the impact of SSRI's ( and their more recent counterparts) on MDD/TRD is within the STAR trials, it was extremely interesting and an exceptional study which provided much needed data on the impact of various pharmacological treatments, as well as psychotherapy.

Thank you so much Siamak, the studies information you have provided is wonderful and it is greatly appreciated, it is the type of information that I have been looking for and your input is greatly appreciated!!

Thank you to all of you for taking the time to respond, all of your inputs have been of value.

Cheryl - Thank you for your comments

Can you provide a reference for the 'exceptional study' that you refer to  please?

The caution that must be exerted here is because it seems that about 40% of depressed patients respond no matter what you do and that response rate seems to be independent of what it is that is actually done - including just giving placebo (see Fig 2 Khan, A., Faucett, J., Lichtenberg, P., Kirsch, I., & Brown, W. A. (2012). A systematic review of comparative efficacy of treatments and controls for depression. PloS one, 7(7), e41778. - linked here  http://img.photobucket.com/albums/v462/chendrie/Khan%20fig%202.png

Hence my interest in the STAR-D approach since one explanation for these data is that they may be no more than an additive placebo effect (40% responding in Level 1, 40% of those remaining responding in Level 2 etc).

Thanks Colin, what I mean by exceptional study  is how and what was done in the study. It is the STAR D trial, because of the size of the trial (, also factors such as the involvement of patients from private and government institutions), the attempt to include as many pharmacological and other treatments, the fact that they considered the possibility of the impact of environmental variables, co-morbid disorders etc. They also included Psychotherapy and it was found that Psychotherapy is as successful as pharmacological treatments - neither of which are as successful as would be hoped for. Another point (not part of STAR-D but interesting) is that Somatic Therapies such as brain stimulation techniques do not usually have a significant population (>30) on which to base a determination that treatment is successful (significant correlation). I am aware of the placebo effect and you are perfectly correct in this. However it may be that there was increased social interaction for instance, which may have had an impact, and in the HUNT 1/2 trial with Stroke patients with depression that received more social interaction, depressive symptoms showed attrition The study did not mention it directly, however it was indicated in their method. There are aspects of the STAR D trial that I would have liked more information on, such as actual severity of disorder and the type of MDD ( they mention moderate to sever depression) in more detail and on what basis this was arrived at - in more detail (they only mentioned identified by practitioners and different practitioners use different tests and methods for arriving at a diagnosis). I admire their efforts in this trial. I have attached some of the documents from it as I am not sure which ones you have perused as they released them at stages.

 This is an interesting discussion, thank you for sharing information.

Hi Cheryl, 

I didn't study depression, but I know that GH-deficient untreated patients show it besides many other symptoms; I know too, my own experience as MD, that treating GH-deficient patients improves these symptoms. What is the reason for it? before trying to give an answer I will tell you that BDNF is one of the many neurotrophic factors induced by GH.

I don't think that correcting or improving symptoms such as depression, associated to GH-deficiency, might be due to the known GH effects on brain neurogenesis and plasticity, but related to the really complex regulation of pituitary GH secretion.

Pituitary GH release is mainly subject to a negative control from the hypothalamus. This is due to somatostatin; this peptide negatively controls the hypothalamic release of GHRH and its stimulatory effects on GH secretion. Therefore, somatostatin is the main controller of pituitary GH release.

In turn, somatostatin is mainly controlled by catecholamines, mainly noradrenaline that is formed from dopamine. High levels of noradrenaline inhibit somatostatin release, then GHRH can be released inducing GH secretion.

If you have GH-deficiency it is likely that somatostatin levels are decreased, consequently there is no need for increased catecholamines levels. Perhaps there is the answer to your question. 

If you administer GH, it produces a positive feed-back on somatostatin, leading to the release of this peptide. This, in turn would lead to increased catecholamines turnover....

While all of these mechanisms are real and we described it years ago in Trends on Endocrinology and Metabolism, my description about what could happen in GH-deficiency associated depression is only a hypothesis.

Best regards

Jesús Devesa

I am absolutely delighted - thank you Jesus this definitely provides some ideas to look at with regards to my question on depressive symptomology!! This would explain numerous elements of depression and the impact of some pharmacological drugs which act more on serotonin, rather than dopamine. I do not have expertise in the field of endocrinology, but this is exactly what I was looking for and am extremely grateful for this input. This also assists in finding another way to induce BDNF, if a patient is unable to exercise which has been found in correlational studies to increase BDNF. This also gives me a perspective on how BDNF and GH could possibly relate to neurotransmitter levels in relation to cognitive functioning, which has been an important component of what I have been considering. I now need to change the question based on this information and I can now also compare it to the work of Robert Cloninger and continue to build new questions and hypotheses. Your input is greatly appreciated!

I would sincerely like to read "Trends on Endocrinology and Metabolism" if it is still available for reading - it will be fascinating for me and of great interest as it will be a valuable resource for what I am working on. Thanks once again Jesus!

Dear: Cheryl Johnston

I send you greetings from Cuba, I am cardiovascular surgeon and dedicate myself to heart transplants, I see on your profile that you have experience in the world of psychology.

I wanted to ask if you think that the recipients of organs are affected psychologically by knowing they have transplanted a heart the opposite sex.

Le thank you for your response

Brotherly

Dr.Nizahel Estevez Alvarez. MD

Dear Nizahel, I will send you a message on Research Gate - thank you for your post!

As a patient diagnosed with AO-GHD due to brain trauma, I can attest the lack of GH causes (not correlates) many other somatic symptoms, depression included.  My thoughts are GHD not only manifests physiological symptoms such as joint pain, undue fatigue and exhaustion, muscle atrophy, increased adipose tissue, glucose intolerance, etc., but also in neurochemical imbalances commonly treated by psychopharmacology in affectance and anxiety disorders.  Not only is the physical health and well-being affected, but also mental and emotional resiliency.  I'll forward some research materials for you later, but you are on the right track!

GH deficiency leads to an altered metabolic turnover of a number of neurotransmitters; among them mainly are brain catecholamines. 

Hi Dr. Devesa, I have been looking for literature that shows GH as a causal and direct factor for BDNF increase in neural tissue. I have found so far  correlations about this GH effect on BDNF.  As an example  Zhang et al., 2014 showed that BDNF is increased by rhGH administration but GH treatment also increases IGF-1, so this clearly could be an indirect GH-effect.

Do you know any paper that shows a direct effect of GH in BDNF expression? 

Also I would like to know your opinion on GH crossing the BBB to have actions in neural tissue.

Thanks!

Hi Carlos, I read years ago about a direct effect of GH on BDNF expression but I don't remember the authors. In the study of Zhang et al. 2014, they correlate GH effects on cognition with an increased expression of hppocampal and prefrontal BDNF and TrkB. They attribute it to GH and not to IGF-I. In fact, though GH induces IGF-I expression in human fetal neural stem cells (Pathipathi et al. 2011), many of the GH effects on brain function are independent of IGF-I: In fact, studies in rats submitted to moderate and severe hypoxia showed that the spatial distribution of the neuroprotection conveyed by GH correlates with the spatial distribution of the constitutive neural GHR, but not with the neuroprotection offered by IGF-I treatment in this model. Therefore, these effects of GH are mediated through GHR and do not involve IGF-I induction (Scheepens et al, 2001). 

With regard to the possibility of GH crossing the BBB to have neural actions it has been demonstrated by Pan et al. 2005) that GH easily cross this barrier. This has been observed too in a number of different studies in rats, including some from our group. In turn, it is hard to IGF-I to cross the BBB (Riikonen et al. 2006) since it has to bind to its carrier proteins for doing it, while GH can enter into the CSF by simple diffusion.

Best regards