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Friday, January 23, 2015

Life extension

From Wikipedia, the free encyclopedia
 
Life extension science, also known as anti-aging medicine, indefinite life extension, experimental gerontology, and biomedical gerontology, is the study of slowing down or reversing the processes of aging to extend both the maximum and average lifespan. Some researchers in this area, and "life extensionists", "immortalists" or "longevists" (those who wish to achieve longer lives themselves), believe that future breakthroughs in tissue rejuvenation, stem cells, regenerative medicine, molecular repair, pharmaceuticals, and organ replacement (such as with artificial organs or xenotransplantations) will eventually enable humans to have indefinite lifespans (agerasia[1]) through complete rejuvenation to a healthy youthful condition.

The sale of putative anti-aging products such as nutrition, physical fitness, skin care, hormone replacements, vitamins, supplements and herbs is a lucrative global industry, with the US market generating about $50 billion of revenue each year.[2] Some medical experts state that the use of such products has not been proven to affect the aging process and many claims regarding the efficacy of these marketed products have been roundly criticized by medical experts, including the American Medical Association.[2][3][4][5][6]

However, it has not been shown that the goal of indefinite human lifespans itself is necessarily unfeasible; some animals such as hydra, planarian flatworms, and certain sponges, corals, and jellyfish do not die of old age and exhibit potential immortality.[7][8][9][10] The ethical ramifications of life extension are debated by bioethicists.

Public opinion

Life extension is a controversial topic due to fear of overpopulation and possible effects on society.[11] Religious people are no more likely to oppose life extension than the unaffiliated,[12] though some variation exists between religious denominations. Blacks and Hispanics are more likely to support life extension than white people.[12] Biogerontologist Aubrey De Grey counters the overpopulation critique by pointing out that the therapy could postpone or eliminate menopause, allowing women to space out their pregnancies over more years and thus decreasing the yearly population growth rate.[13] Moreover, the philosopher and futurist Max More argues that, given the fact the worldwide population growth rate is slowing down and is projected to eventually stabilize and begin falling, superlongevity would be unlikely to contribute to overpopulation.[11]

A Spring 2013 Pew Research poll in the United States found that 38% of Americans would want life extension treatments, and 56% would reject it. However, it also found that 68% believed most people would want it and that only 4% consider an "ideal lifespan" to be more than 120 years. The median "ideal lifespan" was 91 years of age and the majority of the public (63%) viewed medical advances aimed at prolonging life as generally good. 41% of Americans believed that radical life extension would be good for society, while 51% said they believed it would be bad for society.[12] One possibility for why 56% of Americans claim they would reject life extension treatments may be due to the cultural perception that living longer would result in a longer period of decrepitude, and that the elderly in our current society are unhealthy.[14]

Average and maximum lifespans

During the process of aging, an organism accumulates damage to its macromolecules, cells, tissues and organs. Specifically, aging is characterized as and thought to be caused by "genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication."[15] Oxidation damage to cellular contents caused by free radicals is believed to contribute to aging as well.[16][16][17]
The longest a human has ever been proven to live is 122 years, the case of Jeanne Calment who was born in 1875 and died in 1997, whereas the maximum lifespan of a wildtype mouse, commonly used as a model in research on aging, is about three years.[18] Genetic differences between humans and mice that may account for these different aging rates include differences in efficiency of DNA repair, antioxidant defenses, energy metabolism, proteostasis maintenance, and recycling mechanisms such as autophagy.[19]

Average lifespan in a population is lowered by infant and child mortality, which are frequently linked to infectious diseases or nutrition problems. Later in life, vulnerability to accidents and age-related chronic disease such as cancer or cardiovascular disease play an increasing role in mortality. Extension of expected lifespan can often be achieved by access to improved medical care, vaccinations, good diet, exercise and avoidance of hazards such as smoking.

Maximum lifespan is determined by the rate of aging for a species inherent in its genes and by environmental factors. Widely recognized methods of extending maximum lifespan in model organisms such as nematodes, fruit flies, and mice include caloric restriction, gene manipulation, and administration of pharmaceuticals.[20] Another technique uses evolutionary pressures such as breeding from only older members or altering levels of extrinsic mortality.[21][22]

Theoretically, extension of maximum lifespan in humans could be achieved by reducing the rate of aging damage by periodic replacement of damaged tissues, molecular repair or rejuvenation of deteriorated cells and tissues, reversal of harmful epigenetic changes, or the enhancement of telomerase enzyme activity.[23][24] Research geared towards life extension strategies in various organisms is currently under way at a number of academic and private institutions.

Current anti-aging strategies and issues

Diets and supplements

Much life extension research focuses on nutrition—diets or supplements—as a means to extend lifespan, although few of these have been systematically tested for significant longevity effects. The many diets promoted by anti-aging advocates are often contradictory.[original research?] A dietary pattern with some support from scientific research is caloric restriction.[25][26]

Preliminary studies of caloric restriction on humans using surrogate measurements have provided evidence that caloric restriction may have powerful protective effect against secondary aging in humans. Caloric restriction in humans may reduce the risk of developing Type 2 diabetes and atherosclerosis.[27] More research is needed.

The free-radical theory of aging suggests that antioxidant supplements, such as Vitamin C, Vitamin E, Q10, lipoic acid, carnosine, and N-acetylcysteine, might extend human life. However, combined evidence from several clinical trials suggest that β-Carotene supplements and high doses of Vitamin E increase mortality rates.[28] Other substances proposed to extend lifespan include oxytocin, insulin, human chorionic gonadotropin (hCG), and erythropoietin (EPO). Resveratrol is a sirtuin stimulant that appears to extend lifespan in simple organisms such as nematodes[29] and short-lived fish.[30]

Some supplements, including the minerals selenium[31] or zinc[32][33] have been reported to extend the lifespan of rats and mice, though none have been proven to do so in humans, and significant toxic effects were observed. Metformin[34] may also extend life span in mice.

There are many traditional herbs purportedly used to extend the health-span, including a Chinese tea called Jiaogulan (Gynostemma pentaphyllum), dubbed "China's Immortality Herb."[35] Ayurveda, the traditional Indian system of medicine, describes a class of longevity herbs called rasayanas, including Bacopa monnieri, Ocimum sanctum, Curcuma longa, Centella asiatica, Phyllanthus emblica, Withania somnifera and many others. Along with their Chinese counterparts (called superior or tonic herbs), Indian rasayanas demonstrate preliminary positive results in animal models.[36]

Hormone treatments

The anti-aging industry offers several hormone therapies. Some of these have been criticized for possible dangers to the patient and a lack of proven effect. For example, the American Medical Association has been critical of some anti-aging hormone therapies.[2]

Although some recent clinical studies have shown that low-dose growth hormone (GH) treatment for adults with GH deficiency changes the body composition by increasing muscle mass, decreasing fat mass, increasing bone density and muscle strength, improves cardiovascular parameters (i.e. decrease of LDL cholesterol), and affects the quality of life without significant side effects,[37][38][39] the evidence for use of growth hormone as an anti-aging therapy is mixed and based on animal studies. An early study suggested that supplementation of mice with growth hormone increased average life expectancy.[40] Additional animal experiments have suggested that growth hormone may generally act to shorten maximum lifespan; knockout mice lacking the receptor for growth hormone live especially long.[41] Furthermore, mouse models lacking the insulin-like growth factor also live especially long and have low levels of growth hormone.[41]

Insulin like growth factor (IGF-1) restriction

People suffering from a rare condition known as Laron syndrome have a mutation in the gene that makes the receptor for growth hormone. It is theorised that this mutation may hold a key to life extension.
Longo said that some level of IGF-1 was necessary to protect against heart disease, but that lowering the level might be beneficial. A drug that does this is already on the market for treatment of acromegaly, a thickening of the bones caused by excessive growth hormone. “Our underlying hypothesis is that this drug would prolong life span,” Longo said. He said he was not taking the drug, called pegvisomant or Somavert, which is very hard to obtain.
[42]

Scientific controversy regarding anti-aging nutritional supplementation and medicine

Some critics dispute the portrayal of aging as a disease. For example, Leonard Hayflick, who determined that fibroblasts are limited to around 50 cell divisions, reasons that aging is an unavoidable consequence of entropy. Hayflick and fellow biogerontologists Jay Olshansky and Bruce Carnes have strongly criticized the anti-aging industry in response to what they see as unscrupulous profiteering from the sale of unproven anti-aging supplements.[4]

Ethics and politics of anti-aging nutritional supplementation and medicine

Politics relevant to the substances of life extension pertain mostly to communications and availability.[citation needed]

In the United States, product claims on food and drug labels are strictly regulated. The First Amendment (freedom of speech) protects third-party publishers' rights to distribute fact, opinion and speculation on life extension practices. Manufacturers and suppliers also provide informational publications, but because they market the substances, they are subject to monitoring and enforcement by the Federal Trade Commission (FTC), which polices claims by marketers. What constitutes the difference between truthful and false claims is hotly debated and is a central controversy in this arena.[citation needed]

Consumer motivations for using anti-aging products

Research by Sobh and Martin (2011) suggests that people buy anti-aging products to obtain a hoped-for self (e.g., keeping a youthful skin) or to avoid a feared-self (e.g., looking old). The research shows that when consumers pursue a hoped-for self, it is expectations of success that most strongly drive their motivation to use the product. The research also shows why doing badly when trying to avoid a feared self is more motivating than doing well. Interestingly, when product use is seen to fail it is more motivating than success when consumers seek to avoid a feared-self.[43]

Proposed strategies of life extension

Anti-aging drugs

There are a number of drugs intended to slow the aging process currently being researched. One type of research is related to the observed effects a calorie restriction diet, which has been shown to extend lifespan in some animals[44] Based on that research, there have been attempts to develop drugs that will have the same effect on the aging process as a caloric restriction diet, which are known as Caloric restriction mimetic drugs. Drugs that have been studied for possible longevity effects on laboratory animals because of a possible CR-mimic effect include Rapamycin,[45] Metformin,[46] and Resveratrol.[47] Two drugs that may have potential benefits of combating age-related maladies are Resveratrol and Rapamycin. These drugs are considered to be the forefront drugs in anti-aging research.[48] Before these drugs had been tested, the best-characterized anti-aging therapy was, and still is, calorie restriction or CR. In some studies calorie restriction has been shown to extend the life of mice, yeast, and rhesus monkeys significantly.[49][50] However, a more recent study has shown that in contrast, calorie restriction has not improved the survival rate in rhesus monkeys.[51] Long-term human trials of CR are now being done.It is the hope of the anti-aging researchers that Resveratrol and Rapamycin may act as CR mimetics to increase the life span of humans.[48]

Resveratrol was first thought to be an activator of sirtuins, a family of deacetylases, that would promote anti aging effects without having to restrict caloric intake.[52] However, recent replication studies have failed to show that Resveratrol increases the life span in yeast or mice and that Resveratrol may not activate sirtuins that are biologically beneficial to age reduction.[53][54][55][56] Another study was done showing that Resveratrol activates or inhibits fifteen or more different enzymes.[57] Of those enzymes, one stands out with potential for reducing age-related disease. AMP-activated protein kinase (AMPK) has shown to increase life span of nematodes and prevent obesity in mice.[58] Although Resveratrol has not been proven to extend the life-span of mammals at the current doses tested, Resveratrol could be used to access some of the same molecular pathways that CR does. Several examples would include diet induced obesity, some cancers, cardiovascular disease, and neurodegenerative diseases.[59]

While Resveratrol has not been proven to increase life span, Rapamycin has shown much more promise.[48] Rapamycin is shown to increase longevity by inhibiting the target of rapamycin kinase (TOR) the same way CR does.[60] Study systems including yeast, nematodes, flies, and mammals, have shown that reduction of TOR signaling will result in an increased life span.[61][45] Additionally, Rapamycin has similar effects of Resveratrol in protecting against several cancers, cardiovascular, and neurodegenerative diseases.[48][61] Rapamycin also has been shown to act as an immunosuppressant, however more testing is needed to show if the life extending dose comes at the cost of an impaired immune system.[61]

Resveratrol and Rapamycin have both shown protection against cancers, cardiovascular disease, and neurodegenerative diseases in multiple study systems.[59][61] Rapamycin looks to have more potential in life span extension than Resveratrol, but may come at a price of immune system impairment.[48][61] Clinical trials are now being performed to see if Rapamycin or Resveratrol will have anti-aging effects in humans.

Other attempts to create anti-aging drugs have taken different research paths. One notable direction of research has been research into the possibility of using the enzyme telomerase in order to counter the process of telomere shortening.[62] However, there are potential dangers in this, since some research has also linked telomerase to cancer and to tumor growth and formation.[63]

Nanotechnology

Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler, one of the founders of nanotechnology, postulated cell repair machines, including ones operating within cells and utilizing as yet hypothetical molecular computers, in his 1986 book Engines of Creation. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030.[64]

Cloning and body part replacement

Some life extensionists suggest that therapeutic cloning and stem cell research could one day provide a way to generate cells, body parts, or even entire bodies (generally referred to as reproductive cloning) that would be genetically identical to a prospective patient. Recently, the US Department of Defense initiated a program to research the possibility of growing human body parts on mice.[65]
Complex biological structures, such as mammalian joints and limbs, have not yet been replicated. Dog and primate brain transplantation experiments were conducted in the mid-20th century but failed due to rejection and the inability to restore nerve connections. As of 2006, the implantation of bio-engineered bladders grown from patients' own cells has proven to be a viable treatment for bladder disease.[66] Proponents of body part replacement and cloning contend that the required biotechnologies are likely to appear earlier than other life-extension technologies.

The use of human stem cells, particularly embryonic stem cells, is controversial. Opponents' objections generally are based on interpretations of religious teachings or ethical considerations. Proponents of stem cell research point out that cells are routinely formed and destroyed in a variety of contexts. Use of stem cells taken from the umbilical cord or parts of the adult body may not provoke controversy.[67]

The controversies over cloning are similar, except general public opinion in most countries stands in opposition to reproductive cloning. Some proponents of therapeutic cloning predict the production of whole bodies, lacking consciousness, for eventual brain transplantation.

Cyborgs

Replacement of biological (susceptible on diseases) organs with mechanical ones could extend life. This is the goal of 2045 Initiative.[68]

Cryonics

For cryonicists (advocates of cryopreservation), storing the body at low temperatures after death may provide an "ambulance" into a future in which advanced medical technologies may allow resuscitation and repair. They speculate cryogenic temperatures will minimize changes in biological tissue for many years, giving the medical community ample time to cure all disease, rejuvenate the aged and repair any damage that is caused by the cryopreservation process.
Many cryonicists do not believe that legal death is "real death" because stoppage of heartbeat and breathing—the usual medical criteria for legal death—occur before biological death of cells and tissues of the body. Even at room temperature, cells may take hours to die and days to decompose. Although neurological damage occurs within 4–6 minutes of cardiac arrest, the irreversible neurodegenerative processes do not manifest for hours.[69] Cryonicists state that rapid cooling and cardio-pulmonary support applied immediately after certification of death can preserve cells and tissues for long-term preservation at cryogenic temperatures. People, particularly children, have survived up to an hour without heartbeat after submersion in ice water. In one case, full recovery was reported after 45 minutes underwater.[70] To facilitate rapid preservation of cells and tissue, cryonics "standby teams" are available to wait by the bedside of patients who are to be cryopreserved to apply cooling and cardio-pulmonary support as soon as possible after declaration of death.[71]

No mammal has been successfully cryopreserved and brought back to life, with the exception of frozen human embryos. Resuscitation of a postembryonic human from cryonics is not possible with current science. Some scientists still support the idea based on their expectations of the capabilities of future science.[72][73]

Strategies for Engineered Negligible Senescence (SENS)

Another proposed life extension technology would combine existing and predicted future biochemical and genetic techniques. SENS proposes that rejuvenation may be obtained by removing aging damage via the use of stem cells and tissue engineering, removal of telomere-lengthening machinery, allotopic expression of mitochondrial proteins, targeted ablation of cells, immunotherapeutic clearance, and novel lysosomal hydrolases.[74]
While many biogerontologists find these ideas "worthy of discussion"[75][76] and SENS conferences feature important research in the field,[77][78] some contend that the alleged benefits are too speculative given the current state of technology, referring to it as "fantasy rather than science".[3][5]

Genetic modification

Gene therapy, in which nucleic acid polymers are delivered as a drug and are either expressed as proteins, interfere with the expression of proteins, or correct genetic mutations, has been proposed as a future strategy to prevent aging.[79][80]

A large array of genetic modifications have been found to increase lifespan in model organisms such as yeast, nematode worms, fruit flies, and mice. As of 2013, the longest extension of life caused by a single gene manipulation was roughly 150% in mice and 10-fold in nematode worms.[81]

Fooling genes

In The Selfish Gene, Richard Dawkins describes an approach to life-extension that involves "fooling genes" into thinking the body is young.[82] Dawkins attributes inspiration for this idea to Peter Medawar. The basic idea is that our bodies are composed of genes that activate throughout our lifetimes, some when we are young and others when we are older. Presumably, these genes are activated by environmental factors, and the changes caused by these genes activating can be lethal. It is a statistical certainty that we possess more lethal genes that activate in later life than in early life. Therefore, to extend life, we should be able to prevent these genes from switching on, and we should be able to do so by "identifying changes in the internal chemical environment of a body that take place during aging... and by simulating the superficial chemical properties of a young body".[83]

Reversal of informational entropy

According to some lines of thinking, the ageing process is routed into a basic reduction of biological complexity,[84] and thus loss of information. In order to reverse this loss, gerontologist Marios Kyriazis suggested that it is necessary to increase input of actionable and meaningful information both individually (into individual brains),[85] and collectively (into societal systems).[86] This technique enhances overall biological function through up-regulation of immune, hormonal, antioxidant and other parameters, resulting in improved age-repair mechanisms. Working in parallel with natural evolutionary mechanisms that can facilitate survival through increased fitness, Kyriazis claims that the technique may lead to a reduction of the rate of death as a function of age, i.e. indefinite lifespan.[87]

Mind uploading

One hypothetical future strategy that, as some suggest, "eliminates" the complications related to a physical body, involves the copying or transferring (e.g. by progressively replacing neurons with transistors) of a conscious mind from a biological brain to a non-biological computer system or computational device. The basic idea is to scan the structure of a particular brain in detail, and then construct a software model of it that is so faithful to the original that, when run on appropriate hardware, it will behave in essentially the same way as the original brain.[88] Whether or not an exact copy of one's mind constitutes actual life extension is matter of debate.

History of the life extension movement

In 1970, the American Aging Association was formed under the impetus of Denham Harman, originator of the free radical theory of aging. Harman wanted an organization of biogerontologists that was devoted to research and to the sharing of information among scientists interested in extending human lifespan.

In 1976, futurists Joel Kurtzman and Philip Gordon wrote No More Dying. The Conquest Of Aging And The Extension Of Human Life, (ISBN 0-440-36247-4) the first popular book on research to extend human lifespan. Subsequently, Kurtzman was invited to testify before the House Select Committee on Aging, chaired by Claude Pepper of Florida, to discuss the impact of life extension on the Social Security system.

Saul Kent published The Life Extension Revolution (ISBN 0-688-03580-9) in 1980 and created a nutraceutical firm called the Life Extension Foundation, a non-profit organization that promotes dietary supplements. The Life Extension Foundation publishes a periodical called Life Extension Magazine. The 1982 bestselling book Life Extension: A Practical Scientific Approach (ISBN 0-446-51229-X) by Durk Pearson and Sandy Shaw further popularized the phrase "life extension".

In 1983, Roy Walford, a life-extensionist and gerontologist, published a popular book called Maximum Lifespan. In 1988, Walford and his student Richard Weindruch summarized their research into the ability of calorie restriction to extend the lifespan of rodents in The Retardation of Aging and Disease by Dietary Restriction (ISBN 0-398-05496-7). It had been known since the work of Clive McCay in the 1930s that calorie restriction can extend the maximum lifespan of rodents. But it was the work of Walford and Weindruch that gave detailed scientific grounding to that knowledge.[citation needed] Walford's personal interest in life extension motivated his scientific work and he practiced calorie restriction himself. Walford died at the age of 80 from complications caused by amyotrophic lateral sclerosis.

Money generated by the non-profit Life Extension Foundation allowed Saul Kent to finance the Alcor Life Extension Foundation, the world's largest cryonics organization. The cryonics movement had been launched in 1962 by Robert Ettinger's book, The Prospect of Immortality. In the 1960s, Saul Kent had been a co-founder of the Cryonics Society of New York. Alcor gained national prominence when baseball star Ted Williams was cryonically preserved by Alcor in 2002 and a family dispute arose as to whether Williams had really wanted to be cryopreserved.

Regulatory and legal struggles between the Food and Drug Administration (FDA) and the Life Extension Foundation included seizure of merchandise and court action. In 1991, Saul Kent and Bill Faloon, the principals of the Foundation, were jailed. The LEF accused the FDA of perpetrating a "Holocaust" and "seeking gestapo-like power" through its regulation of drugs and marketing claims.[89]

In 2003, Doubleday published "The Immortal Cell: One Scientist's Quest to Solve the Mystery of Human Aging," by Michael D. West. West emphasised the potential role of embryonic stem cells in life extension.[90]

Scientific research

In 1991, the American Academy of Anti-Aging Medicine (A4M) was formed as a non-profit organization to create what it considered an anti-aging medical specialty distinct from geriatrics, and to hold trade shows for physicians interested in anti-aging medicine. The A4M trains doctors in anti-aging medicine and publicly promotes the field of anti-aging research. It has about 26,000 members, of whom about 97% are doctors and scientists.[91] The American Board of Medical Specialties recognizes neither anti-aging medicine nor the A4M's professional standing.[92]

In 2003, Aubrey de Grey and David Gobel formed the Methuselah Foundation, which gives financial grants to anti-aging research projects. In 2009, de Grey and several others founded the SENS Research Foundation, a California-based scientific research organization which conducts research into aging and funds other anti-aging research projects at various universities.[93] In 2013, Google announced Calico, a new company based in San Francisco that will harness new technologies to increase scientific understanding of the biology of aging.[94] It is led by Arthur D. Levinson,[95] and its research team includes scientists such as Hal V. Barron, David Botstein, and Cynthia Kenyon. In 2014, biologist Craig Venter founded Human Longevity Inc., a company dedicated to scientific research to end aging through genomics and cell therapy. It subsequently began building the a human genotype, microbiome, and phenotype database in the world to aid in its research.[96]

Aside from private initiatives, aging research is being conducted in university laboratories, and includes universities such as Harvard and UCLA. University researchers have made a number of breakthroughs in extending the lives of mice and insects by reversing certain aspects of aging.[97][98][99][100]

Ethics and politics of life extension

Though many scientists state[101] that life extension and radical life extension are possible, there are still no international or national programs focused on radical life extension. There are political forces staying for and against life extension. By 2012, in Russia, the United States, Israel, and the Netherlands, the Longevity political parties started. They aimed to provide political support to radical life extension research and technologies, and ensure the fastest possible and at the same time soft transition of society to the next step - life without aging and with radical life extension, and to provide access to such technologies to most currently living people.[102] [103]

Leon Kass (chairman of the US President's Council on Bioethics from 2001 to 2005) has questioned whether potential exacerbation of overpopulation problems would make life extension unethical.[104]

He states his opposition to life extension with the words:
"simply to covet a prolonged life span for ourselves is both a sign and a cause of our failure to open ourselves to procreation and to any higher purpose ... [The] desire to prolong youthfulness is not only a childish desire to eat one's life and keep it; it is also an expression of a childish and narcissistic wish incompatible with devotion to posterity."[105]
John Harris, former editor-in-chief of the Journal of Medical Ethics, argues that as long as life is worth living, according to the person himself, we have a powerful moral imperative to save the life and thus to develop and offer life extension therapies to those who want them.[106]

Transhumanist philosopher Nick Bostrom has argued that any technological advances in life extension must be equitably distributed and not restricted to a privileged few.[107] In an extended metaphor entitled "The Fable of the Dragon-Tyrant", Bostrom envisions death as a monstrous dragon who demands human sacrifices. In the fable, after a lengthy debate between those who believe the dragon is a fact of life and those who believe the dragon can and should be destroyed, the dragon is finally killed. Bostrom argues that political inaction allowed many preventable human deaths to occur.[108]

Aging as a disease

Most mainstream medical organizations and practitioners do not consider aging to be a disease. David Sinclair says: "I don't see aging as a disease, but as a collection of quite predictable diseases caused by the deterioration of the body".[109] The two main arguments used are that aging is both inevitable and universal while diseases are not.[110] However not everyone agrees. Harry R. Moody, Director of Academic Affairs for AARP, notes that what is normal and what is disease strongly depends on a historical context.[111] David Gems, Assistant Director of the Institute of Healthy Ageing, strongly argues that aging should be viewed as a disease.[112] In response to the universality of aging, David Gems notes that it is as misleading as arguing that Basenji are not dogs because they do not bark.[113] Because of the universality of aging he calls it a 'special sort of disease'. Robert M. Perlman, coined the terms ‘aging syndrome’ and ‘disease complex’ in 1954 to describe aging.[114]
The discussion whether aging should be viewed as a disease or not has important implications. It would stimulate pharmaceutical companies to develop life extension therapies and in the United States of America, it would also increase the regulation of the anti-aging market by the FDA.
Anti-aging now falls under the regulations for cosmetic medicine which are less tight than those for drugs.[113][115]

Asperger syndrome

From Wikipedia, the free encyclopedia
 
Asperger syndrome
Seated boy facing 3/4 away from camera, looking at a ball-and-stick model of a molecular structure. The model is made of colored magnets and steel balls.
People with Asperger syndrome often display intense interests, such as this boy's fascination with molecular structure.
Classification and external resources
ICD-10 F84.5
ICD-9 299.80
OMIM 608638
DiseasesDB 31268
MedlinePlus 001549
eMedicine ped/147
Patient UK Asperger syndrome
MeSH F03.550.325.100

Asperger syndrome (AS), also known as Asperger's syndrome, Asperger disorder (AD) or simply Asperger's, is an autism spectrum disorder (ASD) that is characterized by significant difficulties in social interaction and nonverbal communication, alongside restricted and repetitive patterns of behavior and interests. It differs from other autism spectrum disorders by its relative preservation of linguistic and cognitive development. Although not required for diagnosis, physical clumsiness and atypical (peculiar or odd) use of language are frequently reported.[1][2] The diagnosis of Asperger's was eliminated in the 2013 fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and replaced by a diagnosis of autism spectrum disorder on a severity scale.[3]

The syndrome is named after the Austrian pediatrician Hans Asperger who, in 1944, studied and described children in his practice who lacked nonverbal communication skills, demonstrated limited empathy with their peers, and were physically clumsy.[4] The modern conception of Asperger syndrome came into existence in 1981[5] and went through a period of popularization,[6][7] becoming standardized as a diagnosis in the early 1990s. Many questions and controversies remain about aspects of the disorder.[8] There is doubt about whether it is distinct from high-functioning autism (HFA);[9] partly because of this, its prevalence is not firmly established.[1]

The exact cause of Asperger's is unknown. Although research suggests the likelihood of a genetic basis,[1] there is no known genetic cause[10][11] and brain imaging techniques have not identified a clear common pathology.[1] There is no single treatment, and the effectiveness of particular interventions is supported by only limited data.[1] Intervention is aimed at improving symptoms and function. The mainstay of management is behavioral therapy, focusing on specific deficits to address poor communication skills, obsessive or repetitive routines, and physical clumsiness.[12] Most children improve as they mature to adulthood, but social and communication difficulties may persist.[8] Some researchers and people with Asperger's have advocated a shift in attitudes toward the view that it is a difference, rather than a disability that must be treated or cured.[13][14]
The extent of the overlap between AS and high-functioning autism (HFA—autism unaccompanied by intellectual disability) is unclear.[9][15][16] The ASD classification is to some extent an artifact of how autism was discovered,[17] and may not reflect the true nature of the spectrum;[18] methodological problems have beset Asperger syndrome as a valid diagnosis from the outset.[19][20] In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published in May 2013,[21] AS, as a separate diagnosis, was eliminated and folded into autism spectrum disorder.[3] Like the diagnosis of Asperger syndrome,[22] the change was controversial[22][23] and AS was not removed from the WHO's ICD-10.

The World Health Organization (WHO) defines Asperger syndrome (AS) as one of the autism spectrum disorders (ASD) or pervasive developmental disorders (PDD), which are a spectrum of psychological conditions that are characterized by abnormalities of social interaction and communication that pervade the individual's functioning, and by restricted and repetitive interests and behavior. Like other psychological development disorders, ASD begins in infancy or childhood, has a steady course without remission or relapse, and has impairments that result from maturation-related changes in various systems of the brain.[24] ASD, in turn, is a subset of the broader autism phenotype, which describes individuals who may not have ASD but do have autistic-like traits, such as social deficits.[25] Of the other four ASD forms, autism is the most similar to AS in signs and likely causes, but its diagnosis requires impaired communication and allows delay in cognitive development; Rett syndrome and childhood disintegrative disorder share several signs with autism but may have unrelated causes; and pervasive developmental disorder not otherwise specified (PDD-NOS) is diagnosed when the criteria for a more specific disorder are unmet.[26]

Characteristics

As a pervasive developmental disorder, Asperger syndrome is distinguished by a pattern of symptoms rather than a single symptom. It is characterized by qualitative impairment in social interaction, by stereotyped and restricted patterns of behavior, activities and interests, and by no clinically significant delay in cognitive development or general delay in language.[27] Intense preoccupation with a narrow subject, one-sided verbosity, restricted prosody, and physical clumsiness are typical of the condition, but are not required for diagnosis.[9]

Social interaction

A lack of demonstrated empathy has a significant impact on aspects of communal living for persons with Asperger syndrome.[2] Individuals with AS experience difficulties in basic elements of social interaction, which may include a failure to develop friendships or to seek shared enjoyments or achievements with others (for example, showing others objects of interest), a lack of social or emotional reciprocity (social "games" give-and-take mechanic), and impaired nonverbal behaviors in areas such as eye contact, facial expression, posture, and gesture.[1]
People with AS may not be as withdrawn around others compared to those with other, more debilitating forms of autism; they approach others, even if awkwardly. For example, a person with AS may engage in a one-sided, long-winded speech about a favorite topic, while misunderstanding or not recognizing the listener's feelings or reactions, such as a wish to change the topic of talk or end the interaction.[9] This social awkwardness has been called "active but odd".[1] This failure to react appropriately to social interaction may appear as disregard for other people's feelings, and may come across as insensitive.[9] However, not all individuals with AS will approach others. Some of them may even display selective mutism, speaking not at all to most people and excessively to specific people. Some may choose only to talk to people they like.[28]

The cognitive ability of children with AS often allows them to articulate social norms in a laboratory context,[1] where they may be able to show a theoretical understanding of other people's emotions; however, they typically have difficulty acting on this knowledge in fluid, real-life situations.[9] People with AS may analyze and distill their observations of social interaction into rigid behavioral guidelines, and apply these rules in awkward ways, such as forced eye contact, resulting in a demeanor that appears rigid or socially naive. Childhood desire for companionship can become numbed through a history of failed social encounters.[1]

The hypothesis that individuals with AS are predisposed to violent or criminal behavior has been investigated, but is not supported by data.[1][29] More evidence suggests children with AS are victims rather than victimizers.[30] A 2008 review found that an overwhelming number of reported violent criminals with AS had coexisting psychiatric disorders such as schizoaffective disorder.[31]

Restricted and repetitive interests and behavior

People with Asperger syndrome display behavior, interests, and activities that are restricted and repetitive and are sometimes abnormally intense or focused. They may stick to inflexible routines, move in stereotyped and repetitive ways, or preoccupy themselves with parts of objects.[27]

Pursuit of specific and narrow areas of interest is one of the most striking features of AS.[1] Individuals with AS may collect volumes of detailed information on a relatively narrow topic such as weather data or star names, without necessarily having a genuine understanding of the broader topic.[1][9] For example, a child might memorize camera model numbers while caring little about photography.[1] This behavior is usually apparent by age 5 or 6.[1] Although these special interests may change from time to time, they typically become more unusual and narrowly focused, and often dominate social interaction so much that the entire family may become immersed. Because narrow topics often capture the interest of children, this symptom may go unrecognized.[9]

Stereotyped and repetitive motor behaviors are a core part of the diagnosis of AS and other ASDs.[32] They include hand movements such as flapping or twisting, and complex whole-body movements.[27] These are typically repeated in longer bursts and look more voluntary or ritualistic than tics, which are usually faster, less rhythmical and less often symmetrical.[33]

According to the Adult Asperger Assessment (AAA) diagnostic test, a lack of interest in fiction and a positive preference towards non-fiction is common among adults with AS.[34]

Speech and language

Although individuals with Asperger syndrome acquire language skills without significant general delay and their speech typically lacks significant abnormalities, language acquisition and use is often atypical.[9] Abnormalities include verbosity, abrupt transitions, literal interpretations and miscomprehension of nuance, use of metaphor meaningful only to the speaker, auditory perception deficits, unusually pedantic, formal or idiosyncratic speech, and oddities in loudness, pitch, intonation, prosody, and rhythm.[1] Echolalia has also been observed in individuals with AS.[35]

Three aspects of communication patterns are of clinical interest: poor prosody, tangential and circumstantial speech, and marked verbosity. Although inflection and intonation may be less rigid or monotonic than in classic autism, people with AS often have a limited range of intonation: speech may be unusually fast, jerky or loud. Speech may convey a sense of incoherence; the conversational style often includes monologues about topics that bore the listener, fails to provide context for comments, or fails to suppress internal thoughts. Individuals with AS may fail to detect whether the listener is interested or engaged in the conversation. The speaker's conclusion or point may never be made, and attempts by the listener to elaborate on the speech's content or logic, or to shift to related topics, are often unsuccessful.[9]

Children with AS may have an unusually sophisticated vocabulary at a young age and have been colloquially called "little professors", but have difficulty understanding figurative language and tend to use language literally.[1] Children with AS appear to have particular weaknesses in areas of nonliteral language that include humor, irony, teasing, and sarcasm. Although individuals with AS usually understand the cognitive basis of humor, they seem to lack understanding of the intent of humor to share enjoyment with others.[15] Despite strong evidence of impaired humor appreciation, anecdotal reports of humor in individuals with AS seem to challenge some psychological theories of AS and autism.[36]

Motor and sensory perception

Individuals with Asperger syndrome may have signs or symptoms that are independent of the diagnosis, but can affect the individual or the family.[37] These include differences in perception and problems with motor skills, sleep, and emotions.

Individuals with AS often have excellent auditory and visual perception.[38] Children with ASD often demonstrate enhanced perception of small changes in patterns such as arrangements of objects or well-known images; typically this is domain-specific and involves processing of fine-grained features.[39] Conversely, compared to individuals with high-functioning autism, individuals with AS have deficits in some tasks involving visual-spatial perception, auditory perception, or visual memory.[1] Many accounts of individuals with AS and ASD report other unusual sensory and perceptual skills and experiences. They may be unusually sensitive or insensitive to sound, light, and other stimuli;[40] these sensory responses are found in other developmental disorders and are not specific to AS or to ASD. There is little support for increased fight-or-flight response or failure of habituation in autism; there is more evidence of decreased responsiveness to sensory stimuli, although several studies show no differences.[41]

Hans Asperger's initial accounts[1] and other diagnostic schemes[42] include descriptions of physical clumsiness. Children with AS may be delayed in acquiring skills requiring motor dexterity, such as riding a bicycle or opening a jar, and may seem to move awkwardly or feel "uncomfortable in their own skin". They may be poorly coordinated, or have an odd or bouncy gait or posture, poor handwriting, or problems with visual-motor integration.[1][9] They may show problems with proprioception (sensation of body position) on measures of developmental coordination disorder (motor planning disorder), balance, tandem gait, and finger-thumb apposition. There is no evidence that these motor skills problems differentiate AS from other high-functioning ASDs.[1]

Children with AS are more likely to have sleep problems, including difficulty in falling asleep, frequent nocturnal awakenings, and early morning awakenings.[43][44] AS is also associated with high levels of alexithymia, which is difficulty in identifying and describing one's emotions.[45] Although AS, lower sleep quality, and alexithymia are associated, their causal relationship is unclear.[44]

Causes

Hans Asperger described common symptoms among his patients' family members, especially fathers, and research supports this observation and suggests a genetic contribution to Asperger syndrome.
Although no specific gene has yet been identified, multiple factors are believed to play a role in the expression of autism, given the phenotypic variability seen in children with AS.[1][46] Evidence for a genetic link is the tendency for AS to run in families and an observed higher incidence of family members who have behavioral symptoms similar to AS but in a more limited form (for example, slight difficulties with social interaction, language, or reading).[12] Most research suggests that all autism spectrum disorders have shared genetic mechanisms, but AS may have a stronger genetic component than autism.[1] There is probably a common group of genes where particular alleles render an individual vulnerable to developing AS; if this is the case, the particular combination of alleles would determine the severity and symptoms for each individual with AS.[12]

A few ASD cases have been linked to exposure to teratogens (agents that cause birth defects) during the first eight weeks from conception. Although this does not exclude the possibility that ASD can be initiated or affected later, it is strong evidence that it arises very early in development.[47] Many environmental factors have been hypothesized to act after birth, but none has been confirmed by scientific investigation.[48]

Mechanism

Asperger syndrome appears to result from developmental factors that affect many or all functional brain systems, as opposed to localized effects.[49] Although the specific underpinnings of AS or factors that distinguish it from other ASDs are unknown, and no clear pathology common to individuals with AS has emerged,[1] it is still possible that AS's mechanism is separate from other ASDs.[50] Neuroanatomical studies and the associations with teratogens strongly suggest that the mechanism includes alteration of brain development soon after conception.[47] Abnormal migration of embryonic cells during fetal development may affect the final structure and connectivity of the brain, resulting in alterations in the neural circuits that control thought and behavior.[51] Several theories of mechanism are available; none are likely to provide a complete explanation.[52]
Monochrome fMRI image of a horizontal cross-section of a human brain. A few regions, mostly to the rear, are highlighted in orange and yellow.
Functional magnetic resonance imaging provides some evidence for both underconnectivity and mirror neuron theories.[53][54]

The underconnectivity theory hypothesizes underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[53] It maps well to general-processing theories such as weak central coherence theory, which hypothesizes that a limited ability to see the big picture underlies the central disturbance in ASD.[55] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[56]

The mirror neuron system (MNS) theory hypothesizes that alterations to the development of the MNS interfere with imitation and lead to Asperger's core feature of social impairment.[54][57] For example, one study found that activation is delayed in the core circuit for imitation in individuals with AS.[58] This theory maps well to social cognition theories like the theory of mind, which hypothesizes that autistic behavior arises from impairments in ascribing mental states to oneself and others,[59] or hyper-systemizing, which hypothesizes that autistic individuals can systematize internal operation to handle internal events but are less effective at empathizing by handling events generated by other agents.[60]

Diagnosis

Standard diagnostic criteria require impairment in social interaction and repetitive and stereotyped patterns of behavior, activities and interests, without significant delay in language or cognitive development. Unlike the international standard,[24] the DSM-IV-TR criteria also required significant impairment in day-to-day functioning;[27] DSM-5 eliminated AS as a separate diagnosis in 2013, and folded it into the umbrella of autism spectrum disorders.[3] Other sets of diagnostic criteria have been proposed by Szatmari et al.[61] and by Gillberg and Gillberg.[62]
Diagnosis is most commonly made between the ages of four and eleven.[1] A comprehensive assessment involves a multidisciplinary team[2][12][63] that observes across multiple settings,[1] and includes neurological and genetic assessment as well as tests for cognition, psychomotor function, verbal and nonverbal strengths and weaknesses, style of learning, and skills for independent living.[12] The "gold standard" in diagnosing ASDs combines clinical judgment with the Autism Diagnostic Interview-Revised (ADI-R)—a semistructured parent interview—and the Autism Diagnostic Observation Schedule (ADOS)—a conversation and play-based interview with the child.[8] Delayed or mistaken diagnosis can be traumatic for individuals and families; for example, misdiagnosis can lead to medications that worsen behavior.[63][64] Many children with AS are initially misdiagnosed with attention deficit hyperactivity disorder (ADHD).[1] Diagnosing adults is more challenging, as standard diagnostic criteria are designed for children and the expression of AS changes with age;[65] adult diagnosis requires painstaking clinical examination and thorough medical history gained from both the individual and other people who know the person, focusing on childhood behavior.[34] Conditions that must be considered in a differential diagnosis include other ASDs, the schizophrenia spectrum, ADHD, obsessive–compulsive disorder, major depressive disorder, semantic pragmatic disorder, nonverbal learning disorder,[63] Tourette syndrome,[33] stereotypic movement disorder, bipolar disorder, [46] and social-cognitive deficits due to brain damage from alcohol abuse.[66]

Underdiagnosis and overdiagnosis are problems in marginal cases. The cost and difficulty of screening and assessment can delay diagnosis. Conversely, the increasing popularity of drug treatment options and the expansion of benefits has motivated providers to overdiagnose ASD.[67] There are indications AS has been diagnosed more frequently in recent years, partly as a residual diagnosis for children of normal intelligence who are not autistic but have social difficulties.[68]

There are questions about the external validity of the AS diagnosis. That is, it is unclear whether there is a practical benefit in distinguishing AS from HFA and from PDD-NOS;[68] the same child can receive different diagnoses depending on the screening tool.[12] The debate about distinguishing AS from HFA is partly due to a tautological dilemma where disorders are defined based on severity of impairment, so that studies that appear to confirm differences based on severity are to be expected.[69]

Screening

Parents of children with Asperger syndrome can typically trace differences in their children's development to as early as 30 months of age.[46] Developmental screening during a routine check-up by a general practitioner or pediatrician may identify signs that warrant further investigation.[1][12]
The diagnosis of AS is complicated by the use of several different screening instruments,[12][42] including the Asperger Syndrome Diagnostic Scale (ASDS), Autism Spectrum Screening Questionnaire (ASSQ), Childhood Autism Spectrum Test (CAST) (previously called the Childhood Asperger Syndrome Test),[70] Gilliam Asperger's Disorder Scale (GADS), Krug Asperger's Disorder Index (KADI),[71] and the Autism Spectrum Quotient (AQ; with versions for children,[72] adolescents[73] and adults[74]). None have been shown to reliably differentiate between AS and other ASDs.[1]

Management

Asperger syndrome treatment attempts to manage distressing symptoms and to teach age-appropriate social, communication and vocational skills that are not naturally acquired during development,[1] with intervention tailored to the needs of the individual based on multidisciplinary assessment.[75]
Although progress has been made, data supporting the efficacy of particular interventions are limited.[1][76]

Therapies

The ideal treatment for AS coordinates therapies that address core symptoms of the disorder, including poor communication skills and obsessive or repetitive routines. While most professionals agree that the earlier the intervention, the better, there is no single best treatment package.[12] AS treatment resembles that of other high-functioning ASDs, except that it takes into account the linguistic capabilities, verbal strengths, and nonverbal vulnerabilities of individuals with AS.[1] A typical program generally includes:[12]
Of the many studies on behavior-based early intervention programs, most are case reports of up to five participants and typically examine a few problem behaviors such as self-injury, aggression, noncompliance, stereotypies, or spontaneous language; unintended side effects are largely ignored.[81] Despite the popularity of social skills training, its effectiveness is not firmly established.[82] A randomized controlled study of a model for training parents in problem behaviors in their children with AS showed that parents attending a one-day workshop or six individual lessons reported fewer behavioral problems, while parents receiving the individual lessons reported less intense behavioral problems in their AS children.[83] Vocational training is important to teach job interview etiquette and workplace behavior to older children and adults with AS, and organization software and personal data assistants can improve the work and life management of people with AS.[1]

Medications

No medications directly treat the core symptoms of AS.[79] Although research into the efficacy of pharmaceutical intervention for AS is limited,[1] it is essential to diagnose and treat comorbid conditions.[2] Deficits in self-identifying emotions or in observing effects of one's behavior on others can make it difficult for individuals with AS to see why medication may be appropriate.[79]
Medication can be effective in combination with behavioral interventions and environmental accommodations in treating comorbid symptoms such as anxiety disorder, major depressive disorder, inattention and aggression.[1] The atypical antipsychotic medications risperidone and olanzapine have been shown to reduce the associated symptoms of AS;[1] risperidone can reduce repetitive and self-injurious behaviors, aggressive outbursts and impulsivity, and improve stereotypical patterns of behavior and social relatedness. The selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine, and sertraline have been effective in treating restricted and repetitive interests and behaviors.[1][2][46]

Care must be taken with medications, as side effects may be more common and harder to evaluate in individuals with AS, and tests of drugs' effectiveness against comorbid conditions routinely exclude individuals from the autism spectrum.[79] Abnormalities in metabolism, cardiac conduction times, and an increased risk of type 2 diabetes have been raised as concerns with these medications,[84][85] along with serious long-term neurological side effects.[81] SSRIs can lead to manifestations of behavioral activation such as increased impulsivity, aggression, and sleep disturbance.[46] Weight gain and fatigue are commonly reported side effects of risperidone, which may also lead to increased risk for extrapyramidal symptoms such as restlessness and dystonia[46] and increased serum prolactin levels.[86] Sedation and weight gain are more common with olanzapine,[85] which has also been linked with diabetes.[84] Sedative side-effects in school-age children[87] have ramifications for classroom learning. Individuals with AS may be unable to identify and communicate their internal moods and emotions or to tolerate side effects that for most people would not be problematic.[88]

Prognosis

There is some evidence that children with AS may see a lessening of symptoms; up to 20% of children may no longer meet the diagnostic criteria as adults, although social and communication difficulties may persist.[8] As of 2006, no studies addressing the long-term outcome of individuals with Asperger syndrome are available and there are no systematic long-term follow-up studies of children with AS.[9] Individuals with AS appear to have normal life expectancy, but have an increased prevalence of comorbid psychiatric conditions, such as major depressive disorder and anxiety disorder that may significantly affect prognosis.[1][8] Although social impairment may be lifelong, the outcome is generally more positive than with individuals with lower functioning autism spectrum disorders;[1] for example, ASD symptoms are more likely to diminish with time in children with AS or HFA.[89] Most students with AS/HFA have average mathematical ability and test slightly worse in mathematics than in general intelligence, but some are gifted in mathematics[90] and AS has not prevented some adults from major accomplishments, such as Vernon L. Smith winning the Nobel Prize.[91]

Although many attend regular education classes, some children with AS may utilize special education services because of their social and behavioral difficulties.[9] Adolescents with AS may exhibit ongoing difficulty with self care or organization, and disturbances in social and romantic relationships. Despite high cognitive potential, most young adults with AS remain at home, yet some do marry and work independently.[1] The "different-ness" adolescents experience can be traumatic.[92] Anxiety may stem from preoccupation over possible violations of routines and rituals, from being placed in a situation without a clear schedule or expectations, or from concern with failing in social encounters;[1] the resulting stress may manifest as inattention, withdrawal, reliance on obsessions, hyperactivity, or aggressive or oppositional behavior.[78] Depression is often the result of chronic frustration from repeated failure to engage others socially, and mood disorders requiring treatment may develop.[1] Clinical experience suggests the rate of suicide may be higher among those with AS, but this has not been confirmed by systematic empirical studies.[93]

Education of families is critical in developing strategies for understanding strengths and weaknesses;[2] helping the family to cope improves outcomes in children.[30] Prognosis may be improved by diagnosis at a younger age that allows for early interventions, while interventions in adulthood are valuable but less beneficial.[2] There are legal implications for individuals with AS as they run the risk of exploitation by others and may be unable to comprehend the societal implications of their actions.[2]

Epidemiology

Prevalence estimates vary enormously. A 2003 review of epidemiological studies of children found autism prevalence rates ranging from 0.03 to 4.84 per 1,000, with the ratio of autism to Asperger syndrome ranging from 1.5:1 to 16:1;[94] combining the geometric mean ratio of 5:1 with a conservative prevalence estimate for autism of 1.3 per 1,000 suggests indirectly that the prevalence of AS might be around 0.26 per 1,000.[95] Part of the variance in estimates arises from differences in diagnostic criteria. For example, a relatively small 2007 study of 5,484 eight-year-old children in Finland found 2.9 children per 1,000 met the ICD-10 criteria for an AS diagnosis, 2.7 per 1,000 for Gillberg and Gillberg criteria, 2.5 for DSM-IV, 1.6 for Szatmari et al., and 4.3 per 1,000 for the union of the four criteria. Boys seem to be more likely to have AS than girls; estimates of the sex ratio range from 1.6:1 to 4:1, using the Gillberg and Gillberg criteria.[96]
Anxiety disorder and major depressive disorder are the most common conditions seen at the same time; comorbidity of these in persons with AS is estimated at 65%.[1] Reports have associated AS with medical conditions such as aminoaciduria and ligamentous laxity, but these have been case reports or small studies and no factors have been associated with AS across studies.[1] One study of males with AS found an increased rate of epilepsy and a high rate (51%) of nonverbal learning disorder.[97] AS is associated with tics, Tourette syndrome, and bipolar disorder, and the repetitive behaviors of AS have many similarities with the symptoms of obsessive–compulsive disorder and obsessive–compulsive personality disorder.[98] However many of these studies are based on clinical samples or lack standardized measures; nonetheless, comorbid conditions are relatively common.[8]

History

Named after the Austrian pediatrician Hans Asperger (1906–1980), Asperger syndrome is a relatively new diagnosis in the field of autism.[99] As a child, Asperger appears to have exhibited some features of the very condition named after him, such as remoteness and talent in language.[100][101] In 1944, Asperger described four children in his practice[2] who had difficulty in integrating themselves socially. The children lacked nonverbal communication skills, failed to demonstrate empathy with their peers, and were physically clumsy. Asperger called the condition "autistic psychopathy" and described it as primarily marked by social isolation.[12] Fifty years later, several standardizations of AS as a diagnosis were tentatively proposed, many of which diverge significantly from Asperger's original work.[102]
Unlike today's AS, autistic psychopathy could be found in people of all levels of intelligence, including those with intellectual disability.[103] In the context of the Nazi eugenics policy of sterilizing and killing social deviants and the mentally handicapped, Asperger passionately defended the value of autistic individuals, writing "We are convinced, then, that autistic people have their place in the organism of the social community. They fulfill their role well, perhaps better than anyone else could, and we are talking of people who as children had the greatest difficulties and caused untold worries to their care-givers."[4] Asperger also called his young patients "little professors",[4] and believed some would be capable of exceptional achievement and original thought later in life.[2] His paper was published during wartime and in German, so it was not widely read elsewhere.

Lorna Wing popularized the term Asperger syndrome in the English-speaking medical community in her 1981 publication[104] of a series of case studies of children showing similar symptoms,[99] and Uta Frith translated Asperger's paper to English in 1991.[4] Sets of diagnostic criteria were outlined by Gillberg and Gillberg in 1989 and by Szatmari et al. in the same year.[96] AS became a standard diagnosis in 1992, when it was included in the tenth edition of the World Health Organization's diagnostic manual, International Classification of Diseases (ICD-10); in 1994, it was added to the fourth edition of the American Psychiatric Association's diagnostic reference, Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).[12]

Hundreds of books, articles and websites now describe AS, and prevalence estimates have increased dramatically for ASD, with AS recognized as an important subgroup.[99] Whether it should be seen as distinct from high-functioning autism is a fundamental issue requiring further study,[2] and there are questions about the empirical validation of the DSM-IV and ICD-10 criteria.[9] In 2013, DSM-5 eliminated AS as a separate diagnosis, folding it into the autism spectrum on a severity scale.[3]

Society and culture

People identifying with Asperger syndrome may refer to themselves in casual conversation as aspies (a term first used in print by Liane Holliday Willey in 1999).[105] The word neurotypical (abbreviated NT) describes a person whose neurological development and state are typical, and is often used to refer to non-autistic people. The Internet has allowed individuals with AS to communicate and celebrate diversity with each other in a way that was not previously possible because of their rarity and geographic dispersal. A subculture of aspies has formed. Internet sites like Wrong Planet have made it easier for individuals to connect.[13]
Autistic people have advocated a shift in perception of autism spectrum disorders as complex syndromes rather than diseases that must be cured. Proponents of this view reject the notion that there is an "ideal" brain configuration and that any deviation from the norm is pathological; they promote tolerance for what they call neurodiversity.[106] These views are the basis for the autistic rights and autistic pride movements.[107] There is a contrast between the attitude of adults with self-identified AS, who typically do not want to be cured and are proud of their identity, and parents of children with AS, who typically seek assistance and a cure for their children.[108]

Some researchers have argued that AS can be viewed as a different cognitive style, not a disorder or a disability,[13] and that it should be removed from the standard Diagnostic and Statistical Manual, much as homosexuality was removed.[109] In a 2002 paper, Simon Baron-Cohen wrote of those with AS, "In the social world, there is no great benefit to a precise eye for detail, but in the worlds of maths, computing, cataloging, music, linguistics, engineering, and science, such an eye for detail can lead to success rather than failure." Baron-Cohen cited two reasons why it might still be useful to consider AS to be a disability: to ensure provision for legally required special support, and to recognize emotional difficulties from reduced empathy.[14] Baron-Cohen argues that the genes for Asperger's combination of abilities have operated throughout recent human evolution and have made remarkable contributions to human history.[110]

Memory and trauma

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