Molecular Psychiatry: Is the neurogenesis hypothesis of depression and antidepressant action only applicable to the young?

Saturday, March 14, 2009

Is the neurogenesis hypothesis of depression and antidepressant action only applicable to the young?

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Molecular Psychiatry advance online publication 13 January 2009; doi: 10.1038/mp.2008.147

Ageing abolishes the effects of fluoxetine on neurogenesis

S Couillard-Despres¹, C Wuertinger¹, M Kandasamy¹, M Caioni¹, K Stadler¹, R Aigner¹, U Bogdahn¹ and L Aigner^1,2

Department of Neurology, University of Regensburg, Regensburg, Germany
Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, Austria

Correspondence: Dr S Couillard-Despres, Department of Neurology, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg D-93053, Germany. E-mail: sebastien.couillard-despres@klinik.uni-regensburg.de

Received 9 July 2008; Revised 26 November 2008; Accepted 15 December 2008; Published online 13 January 2009.

Abstract

Depression constitutes a widespread condition observed in elderly patients. Recently, it was found that several drugs employed in therapies against depression stimulate hippocampal neurogenesis in young rodents and nonhuman primates. As the rate of neurogenesis is dramatically reduced during ageing, we examined the influences of ageing on neurogenic actions of antidepressants. We tested the impact of fluoxetine, a broadly used antidepressant, on hippocampal neurogenesis in mice of three different age groups (100, 200 and over 400 days of age). Proliferation and survival rate of newly generated cells, as well as the percentage of cells that acquired a neuronal phenotype were analyzed in the hippocampus of mice that received fluoxetine daily in a chronic manner. Surprisingly, the action of fluoxetine on neurogenesis was decreasing as a function of age and was only significant in young animals. Hence, fluoxetine increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age). The data indicate that the action of fluoxetine on neurogenesis is highly dependent on the age of the treated individual. Although the function of neurogenesis in the clinical manifestation of depression is currently a matter of speculation, this study clearly shows that the therapeutic effects of antidepressants in elderly patients are not mediated by neurogenesis modulation.

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My latest editorial - May 2009

Update on Molecular Psychiatry:
New publication guidelines and new ways to stay current

The field of molecular psychiatry has evolved considerably from when Molecular Psychiatry was launched in 1996. We present here brief and updated guidelines for publication as well as details on two innovative electronic resources – our blog and twitter.

We now receive over 700 manuscripts annually and can only publish a very small fraction of what we receive. In the light of the resulting high rejection rate, I am often asked what type of paper has the highest likelihood of acceptance. Here are some guidelines on the content and format that can lead to the highest likelihood of success.

On the important point of content, we seek work that is either conceptually novel or persuasively conclusive and that advances the field. Given the growth of approaches in psychiatric research, we are very open to the most diverse range of papers: from the epidemiological all the way to the most fundamental basic science, including in that broad range all aspects of translational and clinical research, pharmacology, genetics, genomics, proteomics, metabolomics, imaging, behavior, and animal-model research. I cannot think of an innovative, ground breaking or conclusive paper relevant to psychiatry that we would not be interested in. What is important is not so much the area, but either innovation and conceptual novelty or a definitive study that provides conclusive evidence.

Regarding format: because of the tremendous pressure on our space, brevity is encouraged. Most scientific work can benefit from a careful format and style revision aimed at achieving maximum clarity and brevity. Frankly, while your own story may be captivating to you, neither reviewers nor readers have the time or the disposition to go through pages and pages of details or speculation. Please build your paper around data and provide a succinct description of what led you to collect those data, including the guiding hypotheses and methods used, and then provide a brief discussion of your results in the context of where that particular area of research is now and where it is going. We will not publish your article if your results cannot speak for themselves and you need thousands of words of introduction and discussion to highlight them.

One of our goals has been to foster dialogue in the field. Originally, that occurred in our Letters to the Editor and News & Commentary sections. However, the competition for our space makes the fostering of such dialogue increasingly difficult, as it is hard to justify rejecting a highly meritorious paper for lack of space as we dedicate space to interesting, but not critical, correspondence. Furthermore, there is now an increasing discrepancy between the immediacy of electronic publishing and the time constraints of print. In order to facilitate a dialogue in the field and to rapidly alert authors to emerging articles, I am personally creating two new resources for the field that will be mostly related to Molecular Psychiatry, but will occasionally include updates, news, and comments on other material that is of relevance to our field. Those resources are a new Molecular Psychiatry blog and a twitter.

The Molecular Psychiatry blog can be found at http://molecularpsychiatry.blogspot.com. In this blog we will give authors the option to provide summaries of their papers with links to the journal site containing the full article. Those summaries would appear in the blog in conjunction with Advance Online Publication. A dialogue around the paper and its subject matter can then rapidly develop in real-time with comments, questions and answers from the scientific community at large. Authors are not required to respond to comments, but may do so if they feel appropriate. As a safety measure, I will moderate this blog; therefore, material will only be posted with my approval. This will protect authors from inappropriate comments or nuisance. Having grown up in a military dictatorship that enforced official censorship of the press, I have a heartfelt commitment to freedom of speech and will only screen out truly inappropriate blog submissions. Authors and the public can e-mail me if they think that my screening is inappropriate. It is hoped that the blog will foster a lively real-time dialogue that will energize authors and readers.

Our second outreach innovation will be through twitter. For those interested in twittering on Molecular Psychiatry, just go into your twitter account and search for “Julio Licinio.” Subscribe to my open twitter and as any exciting development emerges in Molecular Psychiatry or in other publications, I will twitter about those. For my older colleagues who do not know what twitter is, please get a tutorial from your children, grandchildren, or young relatives, students, or anyone under 30. You can also go to http://www.twitter.com. Briefly, by subscribing to twitter you can tell others or hear from others what is happening now. I am using my twitter to rapidly disseminate exciting emerging data with relevant weblinks. The beauty of twitter is that each message can have a maximum of 140 characters. Those brief notifications are sufficient to keep you in touch with the latest findings, without the unnecessary distraction that would be caused by lengthy texts. I will mostly twitter take-home summaries of interesting papers as soon as they come out in Molecular Psychiatry online (ahead of print). Occasional twitters of groundbreaking work in the field, published elsewhere, will also be sent out – in moderation – as alerts of critical new data, without overwhelming your mailboxes.

Julio Licinio
Editor

Molecular Psychiatry

WELCOME

Saturday, March 14, 2009

Is the neurogenesis hypothesis of depression and antidepressant action only applicable to the young?