COMMENTARY
Trends and dynamics of youth suicides in developing countries See page 1117 Suicide rates vary widely according to time, region, age group, sex, and race. Despite mixed trends of increases or decreases in suicide rates around the world, suicide remains an important public-health problem worldwide. In this issue of The Lancet, Rita Aaron and colleagues describe youth-suicide rates in a rural development block with a population of 108 000 in southern India. Their findings of high suicide rates are remarkable. The total number of suicides for 10–14-year-olds was low, although a small population base may have contributed to skewed high rates in some years. However, consistent findings for 15–19-year-olds resulted in average suicide rates of 148 per 100 000 for girls and 58 per 100 000 for boys. These suicide rates are about 50–70 times higher for girls and about four times higher for boys than the rates in the USA and UK.1,2 Suicide is the leading cause of death at these ages in this region of India; it is the third leading cause in the USA. These investigators had previously reported3 high rates of suicide in the general population of the same region, almost seven times the rates in the USA and European Union.4 The higher suicide rates in southern India might indeed reflect true rates. Aaron and colleagues, in today’s report and previously,3 suggest that reliable methods of identifying suicide victims could be a reason for finding high rates. The discrepancies in suicide rates between southern India and other parts of India could be attributed to different reporting and classification systems. The legal consequences of criminal charges for a suicidal act, societal stigma, and collection of suicide data by the police rather than an independent coroner probably contributed to under-reporting of suicide in other parts of India, as might occur in other countries.5 However, caution is needed about possible overidentification of suicides because of the research interest in ascertainment and classification of death by suicide. The small population base of Aaron and colleagues’ study might also have contributed to high rates by uncovering even a small number of suicides. Nonetheless, their report begs for further investigation of why there were such high suicide rates, especially in adolescents and females. Global suicide rates have been fluctuating over recent decades, decreasing in developed countries such as the USA, countries in the European Union, and Japan, and increasing in eastern Europe, especially in Russia and countries of the former Soviet Union, Sri Lanka, and China.4,6 What appears to be common in the countries that had increasing suicide rates is the sociocultural upheaval brought about by changes in the political and economic system leading to free markets and open society. One striking aspect of the suicide rates in southern India is a higher suicide rate in girls than boys, which has also been observed in China and Singapore.1,6 The question of whether the politico-economical and sociocultural upheaval affects the younger population, especially girls, more than other groups is an important area for further study. However, one can surmise that intergenerational and gender conflicts are more intense in a traditional agricultural society transforming into an egalitarian industrial society than in stable developed countries. March 1 issues of both Time and Newsweek magazines covered outsourcing of jobs from the USA to India and the accompanying socioeconomic and cultural changes. A report7 from Sri Lanka, which has the highest 1090
national suicide rate in the world, described possible reasons for high suicide rates: conflicts between collectivism and individualism, rigid hierarchical structure, repressive education, and influence of foreign culture through cinema and television. Additionally, the influence of the deeply rooted religious belief of Hindus and Buddhists in rebirth and karma (ie, not regarding death as the final step) and self-sacrifice cannot be overlooked as a potential contributing factor to the high suicide rates in India. Self-immolation, exclusively used by adolescent girls, might be indicative of such cultural and religious factors. Suicide-attempt rates are higher in young people than other age groups in the USA and western countries, although suicide-completion rates are low, especially by overdose with drugs in girls.1,8 In Aaron and colleagues’ study, 40% of all suicide victims died from pesticide indigestion, a highly lethal method. This finding raises concerns about easy access to lethal agents by impulsive adolescents and timely access to rescue facilities. Additionally, the suggestibility and contagiousness of suicidal behaviour have been well documented in adolescents,1,8 especially in smaller communities, leading to endemic spread of suicidal behaviour. In terms of preventive intervention, there are comprehensive guidelines developed by the American Academy of Child and Adolescent Psychiatry.8 Depression and substance abuse are well-established risk factors for suicide in both adults and adolescents. The same risk factors were also recognised in India,9 and China.10 However, practice guidelines designed for specialists, such as child and adolescent psychiatrists, to assess and treat risk factors (eg, depression) would not be practicable in developing countries. Ganju11 reported that there are about 1500 psychiatrists and 500 clinical psychologists in India, where the population is over a billion. Access problems of children and adolescents with a psychiatric illness to a specially trained child and adolescent psychiatrist have been well documented, even in the USA.12 Promotion of training and education of qualified mental-health professionals, including child and adolescent psychiatrists, is justified considering the size of the public-health problems that can lead to suicide. The effectiveness of specific suicide-prevention programmes, such as teen hotlines, crisis centres, and school education, has not been proven yet, in part due to the small numbers of suicides in a large population base. The small region of Aaron and colleagues’ study, with a pocket of high suicide rates, is probably well suited for studies of risk factors and innovative and effective youthsuicide prevention programmes. We have no conflict of interest to declare.
*Wun Jung Kim, Tanvir Singh Medical College of Ohio, Toledo, OH 43614, USA (e-mail:
[email protected]) 1
2 3
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Gould MS, Greenberg T, Velting DM, Shaffer D. Youth suicide risk and preventive interventions: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry 2003; 42: 386–405. McClure GM. Suicides in children and adolescents in England and Wales 1970–1998. Br J Psychiatry 2001; 178: 469–74. Joseph A, Abraham S, Muliyil JP, et al. Evaluation of suicide rates in rural India using verbal autopsies, 1994-9. BMJ 2003; 326: 1121–22. Levi F, La Vecchia C, Lucchini D, et al. Trends in mortality from suicide, 1965–99. Acta Psychiatr Scand 2003; 108: 341–49. Murthy RS. Approaches to suicide prevention in Asia and the Far East. In: Hawton K, Van Heeringen K, eds. The international handbook of suicide and attempted suicide. Chichester: Wiley, 2000: 631–41. Phillips MR, Li X, Zhang Y. Suicide rates in China, 1995–99. Lancet 2002; 359: 835–40.
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Bolz W. Psychological analysis of the Sri Lankan conflict culture with special reference to the high suicide rate. Crisis 2002; 23: 167–70. 8 Shaffer D, Pfeffer CR, the AACAP Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with suicidal behavior. J Am Acad Child Adolesc Psychiatry 2001; 40: 24S–51S. 9 Vijaykumar L, Rajkumar S. Are risk factors for suicide universal? A case control study in India. Acta Psychiatr Scand 1999; 99: 407–11. 10 Phillips MR, Yang G, Zhang Y, Wang L, Ji H, Zhou M. Risk factors for suicide in China: a national case-control psychological autopsy study. Lancet 2002; 360: 1728–36. 11 Ganju V. The mental health system in India: history, current system, and prospects. Int J Psychiatric Law 2000; 23: 393–402. 12 Kim WJ. Child and Adolescent Psychiatry Workforce: a critical shortage and national challenge. Acad Psychiatry 2003; 27: 277–82.
Proteomic pointers in HIV neurocognitive disorder
colleagues’ findings1 must be interpreted cautiously for several reasons. First, the number of individuals studied was small, with only nine classified as cognitively impaired. The sample was also restricted to Puerto Rican women aged 21–45 years. Future studies will need to examine larger and more representative groups. Second, and related to the above, is the fact that statistical approaches with tree modelling are typically designed to maximise the likelihood of finding interesting splits, which raises the possibility that such solutions capitalise on chance. Whilst Luo and colleagues provide some reassurance through an internal cross-validation, clearly the stability of these solutions will need to be assessed in larger independent samples. Third, unlike in some other dementias, HIV-associated cognitive impairments do not usually deteriorate steadily towards dementia and may even remain unchanged. For example, a 1-year follow-up6 of 37 individuals with minor cognitive motor disorder found that only 51% were still classified with this disorder; 16% improved to the point of being neuropsychologically normal, and 3% declined (figure, A). It would be interesting to know whether the proteomics profiles of monocyte-derived microglia from cognitively impaired people change with changes in clinical presentation. In a more general sense, since many of the cognitive impairments associated with HIV are mild (figure, B) and yet are predictive of neuropathological events,3 5 it will be important in future studies to determine whether these phenomic profiles actually represent early markers of injury in the central nervous system or largely reflect the more advanced phases of the immunopathological process. At a basic science level, Luo and colleagues’ observations1 indicate that there is a peripheral monocytic-cell proteinsignature that is associated with HIV cognitive impairments. If the finding is replicated, further questions arise. For example, what is the identity of this protein peak? The answer would provide a good lead as to the role of this protein in mediating neurodegeneration. Also, does this peripheral marker indicate that brain dysfunction in HIV patients is mediated by processes outside the brain? One possibility is that these altered mononuclear cells arise from alterations in the bone marrow. The potential interaction between these two tissue compartments is demonstrated by the observation that viral sequences in the brain are more closely related to virus resident in the bone marrow than to virus isolated from circulating monocytes obtained months
Recently, Xiaoguang Luo and colleagues1 identified a macrophage protein fingerprint by proteomic profiling that distinguishes individuals with HIV-1-related cognitive impairments from those who are unimpaired. This observation, on a general level, shows the potential power of proteomics (the analysis of the protein complement of the genome) for the analysis of cellular proteins and how they may vary in disease. The study also raises intriguing possibilities about the causation and identification of HIVrelated cognitive impairments. The advent of proteomics has expanded the focus on cellular function from examination of gene structure and function to analysis of their encoded proteins. Analysing encoded proteins is an important advance because protein activity, such as that regulated by glycosylation or phosphorylation, cannot be ascertained from analysis of gene transcription or translation. Proteomic analysis is usually done by a combination of two-dimensional gelelectrophoresis to separate and visualise proteins, and mass spectrometry to identify proteins. The mass spectrometry is usually done with a method called matrix-assisted laser desorption and ionisation and time of flight (MALDITOF). However, gel-electrophoresis/mass-spectrometry may not be able to characterise all proteome elements, with proteins at low concentration, which could have roles as regulatory or signalling molecules.2 Luo and colleagues1 used the more recently developed surface-enhanced laser desorption and ionisation and time of flight (SELDI-TOF) technology, which allows more accurate A B 60 Demented quantification than traditional methods MCMD WNL 87% from smaller samples with multiple test WNL NP impaired 3·8% NP impaired 11% 50 runs, to specifically assess low1·9% n=311 MCMD 2% molecular-weight proteins. Monocytes from the peripheral blood of 31 control 40 or HIV-infected individuals with or 38% 0·5% NP WNL 18·3% without cognitive impairments were 26·3% impaired NP impaired 55% 30 4·8% lysed and analysed by proteomics. 7% n=121 MCMD Several protein peaks at various 20 molecular weights were identified. Of a total of 177 peaks from the lysates, two WNL 16% 26·5% 25·4% peaks at 5028 and 4320 Da could be NP impaired 30% MCMD 10 17·7% 15·1% MCMD 51% used to separate HIV-1 seronegative n=37 HAD 3% controls from the HIV-1 infected 0 individuals, with a sensitivity of 100% CDC A HIV– CDC B CDC C and a specificity of 80%. Within the (n=212) (n=437) (n=213) (n=113) HIV-infected groups one protein of Neurocognitive complications of HIV infection6 4348 Da was the most sensitive in A: 1-year progression. B: percentage of individuals with neurocognitive disorders in various HIV successfully discriminating between disease groups according to 1993 Center for Disease Control and Prevention (CDC) classification. those HIV-infected individuals with or CDC A=individuals with documented HIV infection who are symptom free; CDC B=individuals with clinical conditions that are not indicative of AIDS; CDC C=individuals who had at least without cognitive impairments non-specific one episode of illness that is indicative of AIDS. WNL=within normal limits on neuropsychological (sensitivity 100%, specificity 75%). testing, NP impaired=asymptomatic cognitive impairment, MCMD=minor cognitive motor disorder, Although provocative, Luo and HAD=HIV-associated dementia. Not normal (%)
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