Correspondence Kasturba Medical College POB 53, KMC, Lighthouse Hill Road Mangalore 575001

doi:10.1016/j.mehy.2005.03.008

417 Karnataka, India Tel.: +91 94484 37749 (C.J. Kumar) E-mail address: jairaj81in@yahoo.co.in (C.J. Kumar)

Asthma, major depression and brain-derived neurotrophic factor

I have read with great interest the recent article, Therapeutic value of antidepressants in asthma by Karamitsos et al. [1]. The authors suggested that antidepressants may have a therapeutic role in asthma by suppressing production of proimfammatory cytokines and inducing production of antiinammatory ones [1]. However, one should be cautious that antidepressant treatment may increase brain-derived neurotrophic factor (BDNF) which may deteriorate, rather then improve, asthma. BDNF, a member of the neurotrophic factor family, plays an important role in the growth, development, maintenance, and function of several neuronal systems. It has been proposed that BDNF plays an important role in the pathogenesis of major depressive disorder (MDD) and, therefore, in the mechanisms underlying antidepressant action [2]. This proposal was further supported by the nding of increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication [3], and the ndings that serum BDNF was signicantly lower in the antidepressant-naive MDD group than in the treated or in the control group [4]. While BDNF is highly concentrated in the brain, it is also abundantly present in the lung [5]. Utilising a mouse model of asthma, Braun et al. [6] have identied BDNF as a candidate molecule for mediating functional neuronal changes in allergic bronchial asthma. In a later report, the same study group further reported that enhanced platelet BDNF is associated with airow limitation and airway hyper-responsiveness in asthma patients [7]. From the above ndings, it is probable that antidepressant treatment in asthma patients may further worsen asthma condition due to the increase of peripheral BDNF levels. From Medline search, there is still no study of the antidepressant effects on the pulmonary BDNF levels. It should be noted that, in animal studies, the alteration of the central BDNF levels by antidepressants depended on the type of antidepressants, the treatment duration, the drug dosage and the brain regions studied [8,9]. Considering the higher rate of depression in asthma, and the potential value of antidepressants in asthma by modulating immune reacting [1], it is suggested that the dose, the duration and the type of antidepressants for such intervention need to be tested in animal model asthma. Furthermore, whether BDNF may play a role in the biological linkage between asthma and major depression may be of interest for further exploration.

References
[1] Krommydas G, Gourgoulianis KI, Karamitsos K, Krapis K, Kotrotsiou E, Molyvdas PA. Therapeutic value of antidepressants in asthma. Med Hypotheses 2005;64:93840. [2] Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597606. [3] Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001;50:2605. [4] Shimizu E, Hashimoto K, Okamura N, Koike K, Komatsu N, Kumakiri C, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003;54:705. [5] Lommatzsch M, Braun A, Mannsfeldt A, Botchkarev VA, Botchkareva NV, Paus R, et al. Abundant production of brain-derived neurotrophic factor by adult visceral epithelia. Implications for paracrine and target-derived Neurotrophic functions. Am J Pathol 1999;155:118393. [6] Braun A, Lommatzsch M, Mannsfeldt A, Neuhaus-Steinmetz U, Fischer A, Schnoy N, et al. Cellular sources of enhanced brain-derived neurotrophic factor production in a mouse model of allergic inammation. Am J Respir Cell Mol Biol 1999;21:53746. [7] Lommatzsch M, Schloetcke K, Klotz J, Schuhbaeck K, Zingler D, Zingler C, et al. Brain-derived neurotrophic factor in platelets and airow limitation in asthma. Am J Respir Crit Care Med 2005;171:11520. [8] Xu H, Steven Richardson J, Li XM. Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus. Neuropsychopharmacology 2003;28:5362.

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[9] Jacobsen JP, Mork A. The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brainderived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res 2004;1024: 18392.

Correspondence No. 201 Shih-Pai Road, Sec. 2 Taipei 11217 Taiwan Division of Psychiatry School of Medicine National Yang-Ming University, Taiwan Tel.: +886 2 28757027x276; fax: +886 2 28725643 E-mail address: sjtsai@vghtpe.gov.tw

Shih-Jen Tsai Department of Psychiatry Taipei Veterans General Hospital

doi:10.1016/j.mehy.2005.03.003