- Email: [email protected]
May genetic factors play a role in the risk of antidepressant-induced suicide?
1380
Correspondence
Human embryonic stem cell research and self evolution Dear Editor, Human embryonic stem cell research (HESCR) has remarkable medical potential for the betterment of the human race. In his recent correspondence letter Dr. Subbanna [1] from the Department of Pharmacology in Christian Medical College, Vellore, mentioned that promoters of HESCR are those who promote humans to change the genotype and thereby encourage self evolution, and detractors of HESCR are those who try to protect their natural tendency to evolve through mutations and natural selection. It is apparent that the battle between promoters and detractors of HESCH is based on moral views. Why should we wait for years together for mutations to occur for the betterment of the human race when the desired result is achievable by HESCR in the near future? The self evolution of humans for the betterment is in the hands of humans themselves and, therefore, there is a dire need for international uniform medicolegal guidelines in relation to HESCR. An International Penal Code legalizing the practice of HESCR for the betterment of the human race, and to consider that destroying an embryo for research does not amount to murder or homicide, should be the prompt initiative needed to be taken by an internationally reputed organization like the United Nations. Obtaining stem cells from embryos necessarily kills them, thus raising thorny questions and arguments about the use of embryonic human material
for research [2]. The debate on moral views of HESCR would not hinder its progress if legalized worldwide with necessary safeguards to prevent its abuse.
References [1] Subbanna PKT. Ehical conflicts in human embryonic stem cell research – a war between the ‘‘selfish genes’’? Med Hypotheses 2007;68:1181–2. [2] Robertson JA. Ethics and policy in embryonic stem cell research. Kennedy Inst Ethics J 1999;9:109–36.
Ritesh G. Menezes Department of Forensic Medicine and Toxicology, Manipal College of Medical Sciences, Pokhara, Nepal Tel.: +977 9804106112 E-mail address: [email protected] Tanuj Kanchan Department of Forensic Medicine and Toxicology, Kasturba Medical College, Mangalore, India Nishanth B. Bhat Department of Microbiology, Manipal College of Medical Sciences, Pokhara, Nepal Sadip Pant Manipal College of Medical Sciences, Pokhara, Nepal
doi:10.1016/j.mehy.2007.03.028
May genetic factors play a role in the risk of antidepressant-induced suicide? As for 2004, the US and European regulatory agencies began implementing verification programs to assess the influence on suicidal behaviour from the use of antidepressants such as SSRIs [1–3]. With the increasing number of cases reported, several newly developed antidepressants were withdrawn from the market, although the mechanisms whereby
these drugs can cause suicide remained unclear. It has been posited, in any case, that some antidepressants may induce anxiety or mania, and thus their use should be avoided [1,2]. On the other hand, it is possible that the side effects associated with use of these drugs may not be present in all individuals taking these medications [3]. To explain this interin-
Correspondence dividual variability, we hypothesize that genetic factors may account for a large part in the liability to anti-depressant induced suicidal behaviour. In particular, it is feasible that specific genetic polymorphisms affecting the function of the serotonin system (SERT) may predict the antidepressant-induced suicidality. Similarly, genetic mutations may exert an influence on the expression of a number of drug-metabolizing enzymes, such as the cytochrome P-450 enzymes that are responsible for the biotransformation of most antidepressants. Polymorphisms of genes controlling these enzymes could also be associated with the propensity for various kinds of side effects, including violence and selfharm [4]. Future pharmacogenomics and whole-genome genetic association studies [5,6] in patients with DSM-IV major depression, especially in suicide victims, are needed to confirm our hypothesis.
References [1] Check E. Drug suicide risks prompt call for FDA action. Nature 2004;427(6974):474. [2] Holden C. FDA weighs suicide risk in children on antidepressants. Science (Washington, DC) 2004;303(5659):745.
1381 [3] Rubino A, Roskell N, Tennis P, et al. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study. BMJ 2007;334(7587): 242. [4] Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005;5:6–13. [5] Goldstein DB, Tate SK, Sisodiya SM. Pharmacogenetics goes genomic. Nat Rev Genet 2003;4:937–47. [6] Evans WE, Relling MV. Moving towards individualized medicine with pharmacogenomics. Nature 2004;429(6900):464–8.
Da Yong Lu School of Life Sciences, Shanghai University, Shanghai 200444, PR China Tel.: +86 021 66163545; fax: +86 021 66132177 E-mail address: [email protected] Ting Ren Lu College of Sciences, Shanghai University, Shanghai 200444, PR China Jian Ding Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
doi:10.1016/j.mehy.2007.03.027
A new prognostic marker for obstructive sleep apnea: Hepcidin To the Editor, Obstructive sleep apnea syndrome (OSAS) is characterized by an intermittent, complete or partial upper airway obstruction during sleep causing hypoxia, sleep disruption, daytime sleepiness, mental and physical effects, is the second most common respiratory condition; affecting 0.3–4% of the middle-aged population [1]. OSAS is strongly associated with cardiovascular morbidity, including an increased risk of endothelial dysfunction and atherosclerosis [2]. The increased prevalence of hypertension and atherogenesis among OSAS patients has been attributed to sympathetic activation and endothelial dysfunction, likely resulting from initiation and propagation of inflammatory responses within the microvasculature [3]. There is increasing evidence that OSAS associated with inflammatory cytokines and markers such
as C-reactive protein, interleukin (IL)-6, fibrinogen and tumor necrosis factor-a. [4]. Hepcidin, an iron-regulatory hormone produced by the liver, regulates extracellular iron concentration by inhibiting intestinal iron absorption and iron release from macrophage [5,6]. Hepcidin production increases during inflammation, bringing about a decrease in dietary iron absorption and sequestration of iron in reticuloendothelial macrophages. Hepcidin can be considered as an acute phase plasma protein. Several studies have demonstrated that IL-6 is an important activator of hepcidin expression during inflammation [5,6]. OSAS, a potent activator of inflammation, increases IL-6 secretion; therefore, OSAS may also increase hepcidin secretion indirectly. It is well known that ferritin, which reflects body iron stores, is closely associated with insulin resistance and can be considered as a marker for
Correspondence
Human embryonic stem cell research and self evolution Dear Editor, Human embryonic stem cell research (HESCR) has remarkable medical potential for the betterment of the human race. In his recent correspondence letter Dr. Subbanna [1] from the Department of Pharmacology in Christian Medical College, Vellore, mentioned that promoters of HESCR are those who promote humans to change the genotype and thereby encourage self evolution, and detractors of HESCR are those who try to protect their natural tendency to evolve through mutations and natural selection. It is apparent that the battle between promoters and detractors of HESCH is based on moral views. Why should we wait for years together for mutations to occur for the betterment of the human race when the desired result is achievable by HESCR in the near future? The self evolution of humans for the betterment is in the hands of humans themselves and, therefore, there is a dire need for international uniform medicolegal guidelines in relation to HESCR. An International Penal Code legalizing the practice of HESCR for the betterment of the human race, and to consider that destroying an embryo for research does not amount to murder or homicide, should be the prompt initiative needed to be taken by an internationally reputed organization like the United Nations. Obtaining stem cells from embryos necessarily kills them, thus raising thorny questions and arguments about the use of embryonic human material
for research [2]. The debate on moral views of HESCR would not hinder its progress if legalized worldwide with necessary safeguards to prevent its abuse.
References [1] Subbanna PKT. Ehical conflicts in human embryonic stem cell research – a war between the ‘‘selfish genes’’? Med Hypotheses 2007;68:1181–2. [2] Robertson JA. Ethics and policy in embryonic stem cell research. Kennedy Inst Ethics J 1999;9:109–36.
Ritesh G. Menezes Department of Forensic Medicine and Toxicology, Manipal College of Medical Sciences, Pokhara, Nepal Tel.: +977 9804106112 E-mail address: [email protected] Tanuj Kanchan Department of Forensic Medicine and Toxicology, Kasturba Medical College, Mangalore, India Nishanth B. Bhat Department of Microbiology, Manipal College of Medical Sciences, Pokhara, Nepal Sadip Pant Manipal College of Medical Sciences, Pokhara, Nepal
doi:10.1016/j.mehy.2007.03.028
May genetic factors play a role in the risk of antidepressant-induced suicide? As for 2004, the US and European regulatory agencies began implementing verification programs to assess the influence on suicidal behaviour from the use of antidepressants such as SSRIs [1–3]. With the increasing number of cases reported, several newly developed antidepressants were withdrawn from the market, although the mechanisms whereby
these drugs can cause suicide remained unclear. It has been posited, in any case, that some antidepressants may induce anxiety or mania, and thus their use should be avoided [1,2]. On the other hand, it is possible that the side effects associated with use of these drugs may not be present in all individuals taking these medications [3]. To explain this interin-
Correspondence dividual variability, we hypothesize that genetic factors may account for a large part in the liability to anti-depressant induced suicidal behaviour. In particular, it is feasible that specific genetic polymorphisms affecting the function of the serotonin system (SERT) may predict the antidepressant-induced suicidality. Similarly, genetic mutations may exert an influence on the expression of a number of drug-metabolizing enzymes, such as the cytochrome P-450 enzymes that are responsible for the biotransformation of most antidepressants. Polymorphisms of genes controlling these enzymes could also be associated with the propensity for various kinds of side effects, including violence and selfharm [4]. Future pharmacogenomics and whole-genome genetic association studies [5,6] in patients with DSM-IV major depression, especially in suicide victims, are needed to confirm our hypothesis.
References [1] Check E. Drug suicide risks prompt call for FDA action. Nature 2004;427(6974):474. [2] Holden C. FDA weighs suicide risk in children on antidepressants. Science (Washington, DC) 2004;303(5659):745.
1381 [3] Rubino A, Roskell N, Tennis P, et al. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: retrospective cohort study. BMJ 2007;334(7587): 242. [4] Ingelman-Sundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects and functional diversity. Pharmacogenomics J 2005;5:6–13. [5] Goldstein DB, Tate SK, Sisodiya SM. Pharmacogenetics goes genomic. Nat Rev Genet 2003;4:937–47. [6] Evans WE, Relling MV. Moving towards individualized medicine with pharmacogenomics. Nature 2004;429(6900):464–8.
Da Yong Lu School of Life Sciences, Shanghai University, Shanghai 200444, PR China Tel.: +86 021 66163545; fax: +86 021 66132177 E-mail address: [email protected] Ting Ren Lu College of Sciences, Shanghai University, Shanghai 200444, PR China Jian Ding Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
doi:10.1016/j.mehy.2007.03.027
A new prognostic marker for obstructive sleep apnea: Hepcidin To the Editor, Obstructive sleep apnea syndrome (OSAS) is characterized by an intermittent, complete or partial upper airway obstruction during sleep causing hypoxia, sleep disruption, daytime sleepiness, mental and physical effects, is the second most common respiratory condition; affecting 0.3–4% of the middle-aged population [1]. OSAS is strongly associated with cardiovascular morbidity, including an increased risk of endothelial dysfunction and atherosclerosis [2]. The increased prevalence of hypertension and atherogenesis among OSAS patients has been attributed to sympathetic activation and endothelial dysfunction, likely resulting from initiation and propagation of inflammatory responses within the microvasculature [3]. There is increasing evidence that OSAS associated with inflammatory cytokines and markers such
as C-reactive protein, interleukin (IL)-6, fibrinogen and tumor necrosis factor-a. [4]. Hepcidin, an iron-regulatory hormone produced by the liver, regulates extracellular iron concentration by inhibiting intestinal iron absorption and iron release from macrophage [5,6]. Hepcidin production increases during inflammation, bringing about a decrease in dietary iron absorption and sequestration of iron in reticuloendothelial macrophages. Hepcidin can be considered as an acute phase plasma protein. Several studies have demonstrated that IL-6 is an important activator of hepcidin expression during inflammation [5,6]. OSAS, a potent activator of inflammation, increases IL-6 secretion; therefore, OSAS may also increase hepcidin secretion indirectly. It is well known that ferritin, which reflects body iron stores, is closely associated with insulin resistance and can be considered as a marker for