Good Example Of Review Of The Subsections Critical Thinking

Critical Review of Article 5

Critical Review of Article 5

Introduction

The article under review is “The anxiolytic and anti-depressant-like effects of testosterone and estrogenic in gonadectomised male rats.” The authors include Nicole Carrier, Samantha Saland, Florian Duclot Huan He,Roger Mercer and Mohammed Kabbaj. The introduction is well designed starting with mentioning of the importance of androgen as a protective hormone in the development of affective disorders and how it can improve symptoms in both women and men. The articles review the difficulty in relating testosterone levels and its effects on depression as both high and low levels produce effects on depression that are conflicting. However, low concentrations of testosterone coincide with an increase in depressive’s symptoms as seen in aging men or males with hypogonadism (Farinetti et al., 2015, p.166). The introduction also points out that the mechanisms underlying testosterone modulatory effects are a mystery though it mainly acts on the brain. The primary sites in the brain at which it acts include the hippocampus, (a part of the limbic areas of the brain) and the dentate gyrus. The physiologic actions are mediated by its metabolites. These are the dihydrotestosterone (that results from 5a-reduction of testosterone) and estradiol (that results from aromatase reduction of testosterone).Their primary actions are due to their effects on neuronal plasticity (i.e. the ability of the damaged part of the brain to re-format) in the limbic system. The authors’ central purpose is to establish the effects of testosterone on depression and to decipher the mechanisms by which it does so (Carrier et al., 2015, p. 1).

The objective of writing the article is to provide an understanding of the influence of hormones on neurobiological systems that regulate anxiety and depressive behaviour. The authors suggest that this would increase the capacity of scientists to develop new drug targets to treat various mental illness in both men and women. The title of the article itself is relevant as it precisely states the objective of the study. This is because the title tells the writer that the article would be about the role of testosterone in protecting male rodents from anxiety and depressive mood disorders. True to its word, the article talks about testosterone, its molecular mechanisms and its role in alleviating anxiety and depression. The article abstract correctly states its content that is re-iterated in the introduction. It points out that there is evidence of pervasive sex differences in anxiety and depressive disorders and that women suffer more than men. It then says that the source of this is gonadal hormones. The introduction builds upon the abstract by providing further information on the same. The structure of the introduction reveals a high degree of organisation with a coherent flow of information. It starts with an opening statement about anxiety and depressive disorders and how mystery still bogs the role of testosterone .It goes on to provide the epidemiological details of the disease (population parameters and sex disparity) after which, it gives possible reasons for the epidemiological differences. It ends by re-affirming the importance of understanding the influence of hormones in the regulation of anxiety and depressive disorders. It also points out its significance in the development of new drug targets for treatment of various illnesses in both men and women. All the information leads to the purpose of the study, i.e. the big picture.
Most of the information is a compilation of findings from pre-clinical and clinical studies done on animal models. These involved behavioural tests done on rodents. Some of the information also came from previous reports. Gonadectomized male rats were implanted with a placebo, testosterone or estradiol pellet (Carrier et al., 2015, p. 2). The subsequent protective anxiolytic and antidepressant-like effects of testosterone wand its aromatized metabolite, estradiol were examined using the open field and sucrose preference test. The researchers also analysed their effect on gene expression in the hippocampus using genome-wide complementary analysis. Eventually, they assessed the contribution of testosterone’s aromatization within the dentate gyrus by locally infusing the aromatase inhibitor. Its efficacy was confirmed by liquid chromatography-tandem mass spectrometry. The methods were valid and relevant. Since the topic of research was scientific, it follows that the methods of research had to be scientific. The animal models used were adult sprang-Dawley rats. The rats were fed and given water and kept in pairs. They conducted the tests during the first four hours of the light phase of the light/dark cycle.
The methods were appropriate in relation to the objective of the study. This is because being live beings; it is essential that the rats live in a healthy environment that looks similar to that of their natural environment. Hence, the importance of the keeping them on a 12 –hour/12-hour light/dark cycle. The scientists then performed the gonadectomy (i.e. removal of the gonads) after administration of anaesthesia after which they administered slow-release testosterone and estradiol or placebo pellets subcutaneously into the rats. To ensure the research was not erroneous, the researchers considered factors that could affect the results. For example, age, degree of hypogonadism, the environment, the timing, dose, duration and route of androgen replacement. They also implanted osmotic minimums into the dentate gyrus using cannula for delivering fadrozole. To ensure accuracy, they excluded rats where they did incorrect cannula placements. They realized that the route of administration was also important with transdermal applications more efficient than injection. The sample chosen for the study was adequate for the clinical studies though there is a need for the authors to do more studies on other animal models apart from only rodents. Also, there is a necessity of the authors to cite more reports on previous studies to compare and contrast between the effectiveness of the methods they used and those used in earlier studies.
The design of the experiment is sound and flows logically. They first start by administering the testosterone on the gonadectomised male rats and after that analysed the genetic influence in hippocampus using the sucrose preference test. They then examined the effects of testosterone and estrogenic supplementation on gene expression in the hippocampus of gonadectomised male rats using microarray analysis and quantification using polymerase chain reaction tests. This ties in well with the objective of the study as its aim are to qualify the effects of testosterone on the brain. Ten days after this, they analysed the anxiety and depressive-like behaviours following aromatase inhibition in the dentate gyrus. This was conducted using the behavioural tests i.e. the open field test and the sucrose preference test. The open field test tested for locomotors activity and general anxiety-like behaviour while the sucrose preference test tested for anhedonia (ability to experience pleasure from activities usually found enjoyable by regular people).The data was then statistically analysed. All the methods augur well with the objectives of the study. The design was, therefore, systematic and well-flowing. The methods are clearly outlined and pertinent and completely relate to the question or purpose of the research. The samples chosen for the clinical studies is good as rats are considered the most useful research specimen next to monkeys. Rats are easily tameable and easier handle as well as to observe for results. However, the sample should have also incorporated other animals, for example, monkey. Monkeys are more closely related to human beings and therefore making the research and its results easier to apply on people. The sequence of methods is flawless. The researchers first ensure that all the rats are healthy then present them to their ideal environmental living conditions before embarking on the experiments. Any erroneous conduction of the test is done away it prominently, and the same experiment repeated using a different sample.
The results for the second sub-experiment (effect on gene regulation is in the form of tables with rows and columns). The tables are well drawn and labelled. All the columns and rows are in correct alignment (Carrier et al., 2015, p. 5). The results are in three groups: those showing the effects of testosterone, those showing the effects of estradiol and those indicating the impact of both testosterone and estradiol. Each table has a relevant that corresponds to the general objective of the research. The presentation of the table is in a way that makes it easy to contrast and compare effects of testosterone and estradiol and common effects on the brain. The tables complement the results in the text in a much more detailed context. While the text presents the results in a summarised general way about the effects of the testosterone and estradiol in gene regulation, the tables go further and name the specific genes affected, and the signalling pathways affected. There are no discrepancies between the data in the text and the data in the diagrammatical presentation. All the calculations are well outlined making it easy to compare. The diagrammatic presentation of the results is in such a way that makes it possible for a layman to describe the role of testosterone in the body easily. They fulfil the objectives of the authors as laid out in the introduction and the title.
“The contributing role of gonadal hormones in pronounced sex differences in depressive disorders is both organizational and activational in origin. Sexual differentiation of the brain is a hormone-dependent process, whereby testes-derived testosterone irreversibly masculinises the brain, relying principally on its local conversion to estradiol via p450 aromatase. In adulthood, gonadal testosterone produces activational, or reversible, effects that contribute to sex differences at molecular, cellular, and functional levels (28–30). As such, investigation of sex differences relevant to depressive disorders is inherently complex. In this study, a focus on activational effects of testosterone and estradiol on affective behaviors was permitted by depletion of the peripheral source of testosterone via gonadectomy of adult male rats” (Carrier et al., 2015).
Physiological actions of testosterone are mediated by the active metabolites mentioned above. The metabolites act on significant receptors in the brain and affect gene transcription in the nuclei of the cells in the brain to bring about the ant-anxiety and anti-depressant effects of the hormone. The authors of the article under review arrived at the conclusion that the mechanism of action is mainly through the MAPK/extracellular signal-regulated kinase (ERK) pathway. Both testosterone and estradiol offer protection against anhedonia acting in the hippocampus and dentate gyrus. Testosterone supplementation upregulated some genes and growth factors that stimulate intracellular signalling cascade while it down regulated some genes. All in all the authors interpret the results to mean that the anti-anxiety and anti-depressant activity of testosterone is via the synergistic action of both of its metabolites (Dihydrotestosterone and estradiol).Both of these act in the hippocampus and the dentate gyrus. The authors go on to suggest the need for an investigation to differentiate effects of the hormone on the different sexes, i.e. male and females. The interpretation considers key areas in the field such as depression, affective disorders and hormonal replacement therapy emphasizing the importance of conducting more studies in this area. The interpretation is also well flowing with the authors starting from the implications of the data. They then advance on to show various ways of using the data for further research and medical use.

Strengths and Weaknesses

The research was well done, and the article well written except for only a few shortcomings. The authors designed the experiment in a well flowing manner citing the methods precisely as well as the types of experiments they conducted. Each activity in the research served a definite aim and combined they gave the overall picture of the study. The authors took the time to ensure the eradication of all loop-holes for error, and they mentioned this in the text. The representation of the data was correctly done making it easy for someone to know the results without having to go through the whole article. The results also re-affirmed the goal of the study. The entire process of the experiment as well as the data that resulted from it also flowed logically and tied in well with the objectives of the research. The authors built their interpretation from the outcome of the experiment citing all the possible effects of testosterone in relation to depression and anxiety as well as the mechanisms of action of the hormone. However, there were several shortcomings of the research. For instance, as mentioned above, the samples taken for the study was inadequate. Since the research is to enable better human beings health care, the researchers should have considered using animal models (male rats) that relate more closely to people biologically (Farinetti, A., et al., 2015). They should have used a primate for instance. In addition despite the great presentation of the data, there is a need for the researchers to use a simpler way of depicting the genetic effects of testosterone in the brain. The use of minus signs in the values represented in the table can be confusing at first unless one decides to take a keener look.

Conclusion

The research adds to valuable knowledge on the effects of testosterone on the human mind in alleviating depression and anxiety. It reiterates the views of other researchers that worked on the same subject previously.
“A large body of evidence exists debating underlying mechanisms contributing to the different efficacy profiles of antidepressants in men and women. Among these, signalling pathways related to synaptic plasticity emerged as critical mediators of current antidepressant efficacy. Specifically, the MAPK/extracellular signal-regulated kinase (ERK) pathway has been identified as an integral component of the antidepressant response profile (31–34). For example, stress-mediated alterations in ERK signalling convey depressive-like behavioural responses in rodents that are reversible by chronic fluoxetine treatment’’ (Carrier et al., 2015).
Testosterone indeed plays a significant role in the brain. The information is useful in the management of psychotic disorders relating to mood disorders, depression and anxiety. However this makes one ask the question: Is it a cheaper or a more expensive alternative to existing medical interventions? Examples of such disorders include, bipolar disorders (both bipolar type 1 and bipolar type II), depression, cyclothymic and dysthymia and even schizophrenia. Testosterone can be used to manage these conditions. This would have significant effects on the society economically, socially and politically. For instance, it would result in a much healthier population and improvement in the economy as people will spend less money on the management of people suffering from depression and anxiety disorders. As a result, the money that would have been used to buy other more expensive drugs will go into development of other economic projects. Consequently, there be less opportunities for people to stigmatise those suffering from anxiety and depressive disorders thus promoting social cohesion and unity. Furthermore, since these health conditions cut across various ethnic and indigenous groups, their management with the same drug will serve as a unifying factor for most countries in the world. However, scientists should focus more on developing a drug that acts with similar efficacy to both women and men. Therefore, there is still a need for further research.

References

Carrier, N. et al. (2015). The Anxiolytic and Antidepressant-like Effects of Testosterone and Oestrogen in Gonadectomised Male Rats. Biological Psychiatry.
Farinetti, A., et al. (2015). Testosterone and estradiol differentially affect cell proliferation in the subventricular zone of young adult gonadectomized male and female rats. Neuroscience 286: 162-170.
Khakpai, F. (2014). The effect of opiodergic system and testosterone on anxiety behavior in gonadectomized rats. Behavioural brain research 263: 9-15.
Messaoudi, M., Nejdi, A., Bisson, J., Rozan, P., Javelot, H., & Lalonde, R. (2008). Anxiolytic And Antidepressant-Like Effects Of Garum Armoricum (Ga), A Blue Ling Fish Protein Autolysate In Male Wistar Rats. Current Topics in Nutraceutical Research, 6(3), 115-123.