Mount Tangkuban Perahu
Tangkuban perahu is a volcano, 25 kilometers north of Bandung direction of Lembang.
Its location is in between Sagalaherang village, Sagalaherang district, Subang regency and Cikole village, Lembang district, Bandung regency. This is Bandung's most famous tourist volcano just 28 km north of the city. This volcano offers many places to see and explore.
Whether we look into the huge crater or hike down into it, stroll through the forest on its slopes, or simply enjoy the splendid panoramic scenery. Mt. Tangkuban Perahu is an interesting destination that everyone in the Bandung area is fond of visiting. When seen from Bandung, Mt. Tangkuban Perahu has a distinctive shape, like an upside down boat. Tangkuban Perahu means, in fact, "up-turned boat" This peculiar shape has stimulated the fantasy of the Sundanese people from early times as expressed in the Legend of Sangkuriang. Geologically, Mt. Tangkuban Perahu has played a significant role in the development of Parahyangan highlands. Eruptions have contributed immensely to the hills north of Bandung through lava flowing into the valleys and hardening into rock, thus forming big cliffs over which waterfalls leap. Likewise, mud flows have formed a semi-circular cone of gentle gradient (what geologists call "a fan"), which is now a mass that blocked the valley of the ancient Citarum River near present day in Padalarang (some 18 km west of Bandung), this caused a lake to form covering the whole Bandung plain.
Tangkuban Perahu is a volcano with three craters into which areas tourists can walk through. These three craters are: Kawah Ratu ("Queen Crater"), Kawah Domas ("Domas Crater"), and Kawah Upas ("Upas Crater"). Tourists can go down into the Domas Crater where exist many hot geysers in which they can boil eggs. Though the mountain appears peaceful, mild eruptions occurred in 1969, when Kawah Ratu spewed ash and barrages 500 m high. As recently as September 1992 it was closed to the public for a few days because unusually high seismic activity leads volcanologist to fear a new eruption. On the mountain's northern flank is an area called Death Valley, so named for its frequent accumulation of poisonous gases. On a reasonably clear day, from Kawah Ratu, the main crater, we can see not only the mountain range to the east, with Mt. Bukittunggul as its highest peak (2,209 m), but also two other in a northeasterly direction. The lower and nearer one is Mt. Tampomas (1,684 m) just north of Sumedang some 40 km away. To the right and about 90 km away is Mt. Ciremai close to Cirebon on the north coast. At 3,078 m, Mt. Ciremai is West Java's tallest mountain. At the foot of Mt. Tangkuban Perahu we see the Ciater tea plantation covering the rolling hills. Farther to the left are the northern coastal plains of Java, and on an extremely clear day we may even be able to see the Java Sea beyond.
Kawah Ratu, which means "Queen's Crater", is today just a big gray hole, which sometimes has a pool of water at its center. Poisonous gases sometimes accumulate in Kawah Ratu, thus making it somewhat of a risk to descend to the crater floor. Beyond the saddled shaped depression on the far side of Kawah Ratu is the still active Kawah Upas, the oldest crater on the mountain. On the very far western cliff we see a spot where all vegetation has been destroyed by constantly rising sulfurous vapors. On the crater walls, note the various layers of material consisting of rock, sand, and pebbles. Overtime, new craters have formed again and again in a rather consistent shift from west to east. The most well known of these is the Domas crater, but also there are other smaller ones in jungle on the mountain's northeastern flank. Facilities in Tangkuban Perahu Crater are comfortable parking area, souvenir kiosks, and restaurants.
The fourth generation Prado will be available in most part of the world by november this year as the 2010 model. Toyota chose to reveal this little brother of the Landcruiser at the Frankfurt show. The new Prado does appear more matured, looking more like a small Landcruiser, with the new aggressive looking front end-- new grille, new bumper and new light.
The new SUV is said to be 80mm longer, 10mm wider and 15mm lower than the previous generation. Toyota claimed that the new Prado has better aerodynamic, with drag coefficient reduced from 0.37 to 0.35. Besides that, Toyota spokesperson promised impressive Improvement in handling, stability and ride comfort.
Toyota said to have included more powerful yet more efficient newer engines on the new Prados. The UK market will only get the 171bhp 3.0 diesel engine, while other European and Asian markets can also get the 4.0 V6 Dual VVT-i, also a three-door version. The current 2.7 V6 will most likely be discontinued. Experts predicted Toyota's intention to upgrade the Prado in order to leave the lower end market for the Fortuner and RAV4 alike.
The suspension systems have been heavily revised with the top of the line Prados will get Adaptive Variable Suspension (AVS), which has excellent control over the body roll and lean, while enabling auto-levelling via switchable height control. Though It is estimated that only 10% of Prado owners will actually take the car off road, but Toyota will include the hard core CRAWL 4wd system (from big brother Landcruiser) on most of the Prado models. Let's wait till we hear the new price tags to make judgements, ok? But so far I would say that Toyota has done a pretty good job in upgrading the SUV. 
enotes.com
Definition
Acute kidney failure (AKF) occurs when there is a sudden reduction in kidney function that results in nitrogenous wastes accumulating in the blood (azotemia).
Description
The kidneys are the body's natural filtration system. They perform the critical task of processing approximately 200 quarts of fluid in the bloodstream every 24 hours. Waste products like urea and toxins, along with excess fluids, are removed from the bloodstream in the form of urine. Kidney (or renal) failure occurs when kidney functioning becomes impaired somehow. Fluids and toxins begin to accumulate in the bloodstream.
As fluids build up in the bloodstream, the patient with AKF may become puffy and swollen (edematous) in the face, hands, and feet. Their blood pressure typically begins to rise, and they may experience fatigue and nausea. Often urine output decreases drastically or is not produced at all.
Unlike chronic kidney failure, which is long term and irreversible, acute kidney failure is often a temporary condition. With proper and timely treatment, it can many times be reversed, leaving no permanent or serious damage to the kidneys.
Causes and symptoms
Acute kidney failure appears most frequently as a complication of serious illness, like heart and/or liver failure, serious infection, dehydration, severe burns, and excessive bleeding (hemorrhage). It may also be caused by an obstruction to the urinary tract or as a direct result of kidney disease, injury, or an adverse reaction to medicine. These conditions divide AKF into three main categories: prerenal, postrenal, and intrinsic (inside) conditions.
Prerenal AKF does not damage the kidney, but can cause diminished kidney function and significantly decreased renal (kidney) blood flow. It is the most common type of acute renal failure, and is often the result of:
* dehydration
* extracellular fluid (ECF) volume depletion (or other acute fluid loss from the gastrointestinal tract, kidneys, or skin)
* drugs (NSAIDS, cyclosporine, radiopaque contrast materials, or any substance toxic to the kidneys)
* hemorrhage
* septicemia, or sepsis
* congestive heart failure (CHF)
* liver failure
* burns
* decreased intravascular volume (referred to as third spacing, also found in the presence of pancreatitis, post surgical patients, and patients with a nephrotic syndrome)
Postrenal AKF is the result of an obstruction of some kind somewhere in the urinary tract, often in the bladder or ureters (the tubes leading from the kidney to the bladder). The kidneys compensate to such a degree that one kidney can be completely obstructed and the other will maintain nearly normal kidney function for the body. The conditions that often cause postrenal AKF are:
* inflammation of the prostate gland in men (prostatitis)
* enlargement of the prostate gland (benign prostatic hypertrophy)
* bladder or pelvic tumors
* kidney stones (calculi)
Intrinsic AKF involves a type of kidney disease or direct injury to the kidneys. This type of AKF accounts for 20-30% of AKF reported among hospitalized patients. Intrinsic AKF can result from:
* lack of blood supply to the kidneys (ischemia)
* use of radiocontrast agents in patients with kidney problems
* drug abuse or overdose
* long-term use of nephrotoxic medications, like certain pain medicines
* acute inflammation of the glomeruli, or filters, of the kidney (glomerulonephritis)
* kidney infections (pyelitis or pyelonephritis)
* infiltration by lymphoma, leukemia, or sarcoid carcinomas
Common symptoms of AKF include:
* Anemia. The kidneys are responsible for producing erythropoietin (EPO), a hormone that stimulates red blood cell production. If kidney disease causes shrinking of the kidney, red blood cell production is reduced, leading to anemia.
* Bad breath or bad taste in mouth. Urea in the saliva may cause an ammonia-like taste in the mouth.
* Bone and joint problems. The kidneys produce vitamin D, which helps the body absorb calcium and keeps bones strong. For patients with kidney failure, bones may become brittle. In children, normal growth may be stunted. Joint pain may also occur as a result of high phosphate levels in the blood. Retention of uric acid may cause gout.
* Edema. Puffiness or swelling in the arms, hands, feet, and around the eyes.
* Frequent urination.
* Foamy or bloody urine. Protein in the urine may cause it to foam significantly. Blood in the urine may indicate bleeding from diseased or obstructed kidneys, bladder, or ureters.
* Cola-colored urine followed by oliguria (decreased urine output) or anuria (no urine output)
* Headaches. High blood pressure may trigger headaches.
* Hypertension, or high blood pressure. The retention of fluids and wastes causes blood volume to increase. This makes blood pressure rise.
* Increased fatigue. Toxic substances in the blood and the presence of anemia may cause the patient to feel exhausted.
* Itching. Phosphorus, normally eliminated in the urine, accumulates in the blood of patients with kidney failure. An increased phosphorus level may cause the skin to itch.
* Lower back pain. Patients suffering from certain kidney problems (like kidney stones and other obstructions) may have pain where the kidneys are located, in the small of the back below the ribs.
* Nausea. Urea in the gastric juices may cause upset stomach.
Diagnosis
Kidney failure is diagnosed by a doctor, whether the patient is in the hospital or seen as an outpatient. He or she will take a complete medical history and make a thorough review of the patient's medical record, looking for exposure to nephrotoxic (medicines that can be hard on the kidneys) drugs or other clues to the patient's condition. The physician will then conduct a thorough physical examination, making a careful assessment of the patient's ECF volume and effective circulating blood volume (EBV). A nephrologist, a doctor that specializes in the kidney, may be consulted to confirm the diagnosis and recommend treatment options. He or she will look for a recent history of changes in body weight and try and determine whether the patient is taking in much more fluid than he or she is excreting. Capillary wedge pressure and cardiac output values are also effective tools in pinpointing the cause and extent of the AKF.
The patient that is suspected of having AKF will have blood and urine tests to determine the level of kidney function. A blood test will assess the levels of creatinine, blood urea nitrogen (BUN), uric acid, phosphate, sodium, and potassium. The kidney regulates these agents in the blood. Urine samples will also be collected, usually over a 24-hour period, to assess protein loss and/or creatinine clearance.
Determining the cause of kidney failure is critical to proper treatment. Prerenal or obstructive causes are often looked into first because they are the quickest types of AKF to treat. A full assessment of the kidneys is necessary to determine if the underlying disease is treatable and if the kidney failure is chronic or acute. X rays, magnetic resonance imaging (MRI), computed tomography scan (CT), ultrasound, renal biopsy, and/or arteriogram of the kidneys may be used to determine the cause of kidney failure and level of remaining kidney function. X rays and ultrasound of the bladder and/or ureters may also be needed.
Treatment
Treatment for AKF varies, since it is directed to the underlying, primary medical condition that triggered thekidney failure. Prerenal conditions may be treated with replacement fluids given through a vein, diuretics, blood transfusion, restricted salt intake, or medications. Postrenal conditions and intrarenal conditions may require surgery and/or medication.
Frequently, patients in AKF require hemodialysis, hemofiltration, or peritoneal dialysis to filter fluids and wastes from the bloodstream until the primary medical condition can be controlled.
Hemodialysis
Hemodialysis involves circulating the patient's blood outside of the body through an extracorporeal circuit (ECC), or dialysis circuit. The ECC is made up of plastic blood tubing, a filter known as a dialyzer (or artificial kidney), and a dialysis machine that monitors and maintains blood flow and administers dialysate. Dialysate is a sterile chemical solution that is used to draw waste products out of the blood. The patient's blood leaves the body through the vein and travels through the ECC and the dialyzer, where fluid removal takes place.
During dialysis, waste products in the bloodstream are carried out of the body. At the same time, electrolytes and other chemicals are added to the blood. The purified, chemically-balanced blood is then returned to the body.
A dialysis "run" typically lasts three to four hours, depending on the type of dialyzer used and the physical condition of the patient. Dialysis is used several times a week until AKF has resolved.
Blood pressure changes associated with hemodialysis may pose a risk for patients with heart problems. Peritoneal dialysis may be the preferred treatment option in these cases.
Hemofiltration
Hemofiltration, also called continuous renal replacement therapy (CRRT), is a slow, continuous blood filtration therapy used to control acute kidney failure in critically ill patients. These patients are typically very sick and may have heart problems or circulatory problems. They cannot endure the rapid filtration rates of hemodialysis. They also frequently need antibiotics, nutrition, vasopressors, and other fluids given through a vein to treat their primary condition. Because hemofiltration is continuous, prescription fluids can be given to patients in kidney failure without the risk of fluid overload.
Like hemodialysis, hemofiltration uses an ECC. A hollow fiber hemofilter is used instead of a dialyzer to remove fluids and toxins. Instead of a dialysis machine, a blood pump makes the blood flow through the ECC. The volume of blood circulating through the ECC in hemofiltration is less than that in hemodialysis. Filtration rates are slower and gentler on the circulatory system. Hemofiltration treatment will generally be used until kidney failure is reversed.
Peritoneal dialysis
Peritoneal dialysis may be used if the patient in AKF is stable and not in immediate crisis. In peritoneal dialysis (PD), the lining of the patient's abdomen, the peritoneum, acts as a blood filter. A flexible tube-like instrument (catheter) is surgically inserted into the patient's abdomen. During treatment, the catheter is used to fill the abdominal cavity with dialysate. Waste products and excess fluids move from the patient's bloodstream into the dialysate solution. After a certain time period, the waste-filled dialysate is drained from the abdomen, and replaced with clean dialysate. There are three types of peritoneal dialysis, which vary according to treatment time and administration method.
Peritoneal dialysis is often the best treatment option for infants and children. Their small size can make vein access difficult to maintain. It is not recommended for patients with abdominal adhesions or other abdominal defects (like a hernia) that might reduce the efficiency of the treatment. It is also not recommended for patients who suffer frequent bouts of an inflammation of the small pouches in the intestinal tract (diverticulitis).
Prognosis
Because many of the illnesses and underlying conditions that often trigger AKF are critical, the prognosis for these patients many times is not good. Studies have estimated overall death rates for AKF at 42-88%. Many people, however, die because of the primary disease that has caused the kidney failure. These figures may also be misleading because patients who experience kidney failure as a result of less serious illnesses (like kidney stones or dehydration) have an excellent chance of complete recovery. Early recognition and prompt, appropriate treatment are key to patient recovery.
Survival statistics also depend on the type of AKF the patient has, age at time of onset, and general health. If the patient has prerenal AKF, there is a good recovery prognosis, but the mortality rate is higher among those who fail to respond to diuretics and vasodilator therapy. Since 1980, age has become a risk factor that increased mortality in patients with acute tubular necrosis (ATN), an intrinsic form of AKF.
Up to 10% of patients who experience AKF will suffer irreversible kidney damage. They will eventually go on to develop chronic kidney failure or end-stage renal
disease. These patients will require long-term dialysis or kidney transplantation to replace their lost renal functioning.
Health care team roles
The patient who suffers from AKF will come in contact with a number of different health care professionals during both the diagnosis and treatment phase of the illness. Patients will require (according to the type and severity of their condition) laboratory work, diagnostic radiology services, pharmaceutical and nutritional interventions, dialysis (in some cases), nursing care, and disease management by a nephrologist.
The medical history, taken by a physician in the emergency room, the patient's family doctor, a fellow nurse practitioner, physician's assistant (PA), or a nephrologist is the most essential tool in determining the cause and type of AKF. The admitting physician or nephrologist will conduct a thorough physical, looking at the following areas for specific clues.
Skin. Checking the patient for areas of small, purple or red spots (petechiae), hemorrhage beneath the skin (purpura), and bluish discoloration of a fairly large area of the skin (ecchymosis) can lead to a diagnosis of an inflammatory or vascular cause for the AKF.
Eyes. Certain conditions in the eyes can point to a diagnosis of interstitial nephritis (inflammation between the cells and tissues of the kidney) or necrotizing vasculitis (inflammed blood vessels).
Cardiovascular and volume status. Evaluating the condition of the heart and the rest of the circulatory system plus volume status (fluid balance) is the most important part of diagnosing and managing AKF. Nurses and nurses' aides will measure and chart daily intake and output (measuring how much fluid the patient takes in and how much he or she excretes in a 24-hour period of time). This is one of the best ways to get a good estimate of volume status. The pulse rate and blood pressure will be taken by the physician, nurses, and nurses' aides often in both the upright (standing or sitting on the side of the bed with legs dangling down) and supine (lying down) positions. The physician will also check the pulse in the neck, examine the heart and lungs, and check for edema (fluid buildup) in the arms and legs. Different combinations of the results of these assessments point to different causes for and types of AKF.
Abdomen. The physician will feel for signs of urinary tract obstruction by palpating (pressing) on the bladder and the upper corners of the abdomen that may reveal an obstruction in the ureter (tube between the kidney and the bladder) somewhere. If the entire abdomen is unusually swollen and filled with fluid (ascites), the AKF may be the result of liver failure.
Arms and legs (extremities). The physican and nursing staff will check the patients arms and legs for edema at the time of diagnosis and throughout treatment. Edema in the arms and legs is a sign of a decrease in oxygenated blood (ischemia), muscle tenderness from rhabdomyolysis (disease of the skeletal muscle), or arthritis. The presence and degree of edema is helpful in pinpointing the cause of AKF and in measuring the patient's progress with treatment.
Nervous system. The physician will assess the patient's degree of mental clarity and nerve responses, as abnormalities in these areas of the nervous system are often common symptoms of AKF. The nursing staff also monitors the patient's mental status during the course of treatment.
Laboratory personnel will draw blood and collect urine samples to help diagnose AKF and later, to evaluate treatment. Increases in BUN (blood urea nitrogen) and creatinine (substance formed from the metabolism of creatine) are indicators of AKF.
The urinalysis is the most important test run in the early stage of AKF evaluation. Significant color changes point to an intrinsic cause for AKF. Urine dipstick tests that prove positive for proteinuria (too much protein) and blood are helpful in diagnosing many causes of AKF. The different types of sediment readings from spun urine samples can further help to distinguish the cause and type of AKF. Urine electrolytes indicate how well the tubules (part of the kidney's nephron) are working.
Nurses and nurses' aides will keep track of fluids the patient takes in (intake) and eliminates (output) to help determine the type of AKF the patient is in and to help the physician manage the patient's course of treatment. Fluid management is critical in the patient with AKF, regardless of the cause.
Patients in AKF may undergo further evaluation in the Radiology Department to determine the cause of their disease and to plan an appropriate plan of treatment. They may undergo an ultrasound examination, doppler scan, nuclear scan, MRI, renal angiography, or a renal biopsy. The ultrasound, doppler scan, and MRI are the least invasive of the procedures. Contrast material is injected for the angiogram and the renal biopsy requires taking tissue samples from the kidney itself. These procedures are performed by trained and licensed radiologic technologists and radiologists.
Nutrition is crucial to the effective management of the patient in AKF. The dietician will work closely with the patient, physician, nursing staff, and pharmacist to ensure proper electrolyte balance, whether the patient eats regular foods or is nourished by total parenteral nutrition (TPN, nutrients mixed and fed through a tube).
Some patients will require kidney dialysis that will be performed by nurses and technicians from the renal or urology department.
Since many different medications are eliminated through the kidneys, the physician works closely with the pharmacist to modify dosing and minimize the use of medications that are toxic to the kidneys.
Prevention
Since AKF can be caused by many things, prevention is difficult. Medications that may impair kidney function should be given cautiously. Patients with preexisting kidney conditions who are hospitalized for other illnesses or injuries should be carefully monitored for kidney failure complications. Treatments and procedures that may put them at risk for kidney failure (like diagnostic tests requiring radiocontrast agents or dyes) should be used with extreme caution.
KEY TERMS
Anuria—When the body ceases to make urine entirely or falls below 100 mls.
Azotemia—Too many nitrogenous compounds in the blood caused by the kidneys' failure to remove urea from the blood.
Blood urea nitrogen (BUN)—A waste product that is formed in the liver and collects in the bloodstream; patients with kidney failure have high BUN levels.
Capillary wedge pressure—The blood pressure inside of a capillary.
Cardiac output—The volume of blood pushed out by the ventricles.
Creatinine—A protein produced by muscle that healthy kidneys filter out.
Edema—The abnormal accumulation of fluid in the interstitial spaces of tissue.
Electrolytes—An element or a compound that can break into ions and conduct electrical current when melted or dissolved in water.
Erythropoietin (EPO)—A glycoprotein hormone made in the kidneys.
Extracellular fluid (ECF)—That part of body fluid made of interstitial fluid and blood plasma.
Extracorporeal—Outside of, or unrelated to, the body.
Glomeruli—The tiny structures that perform the actual mechanical filtering in the kidney.
Gout—A condition caused by error in uric acid metabolism.
Interstitial—The space between cells.
Intravascular volume—The volume of fluid inside a blood vessel.
Intrinsic—Starting from or situated inside an organ or tissue.
Ischemia—A lack of blood supply to an organ or tissue.
Lymphoma—Cancer of the lymph tissue.
Nephritis—Inflammation and abnormal functioning of the kidney.
Nephrologist—A physician who specializes in treating diseases of the kidney.
Nephrotoxic—Toxic, or damaging, to the kidney.
NSAIDS—Non-steroidal, antiinflammatory drug.
Oliguria—Abnormally low urine production.
Radiocontrast agents—Dyes administered to a patient for the purposes of a radiologic study.
Sepsis—A bacterial infection of the bloodstream.
Urea—A systemic diuretic.
Vasopressors—Medications that constrict the blood vessels.
The PSR-S710 represents a significant leap forward in the evolution of the Arranger Workstation keyboard. The addition of USB audio recording delivers tremendous benefit for all musicians -- beginner, hobbyist or pro.
A stunning 61-key Arranger Workstation, the PSR-S710 has all the features you need, including:
* 128-note polyphony
* huge sonic palette with over 850 incredible instrument Voices, including some from the PSR-S900
* realistic built-in accompaniment with enhanced guitar styles
* 16-track sequencer
* audio recorder
* large, easy-to-read screen
* Internet Direct Connect and USB connectivity
* Dozens of effects
The PSR-S710 is an impressive arranger for home, studio, or stage offering the perfect balance of functionality and affordability.
Keyboard 61 Full-size w T Response
Display Large 5.7" QVGA B/W
Lyric / Text/ Score Yes / Yes /Yes
Voices & Comp. 891 GM / XG / GS Compatible
Dual/Split Yes - L1, R1, R2
Polyphony 128 Notes
One Touch / Reg. 4 per Style / 8 pads x Unlimited
Music Database Yes
Y.E.S. / Lessons No
Styles 216 Pro + 16 Session + User
Style Sections 3 Intro/Endings + A-D + Fill x 4
MIDI In/Out + USB Slave
Storage Device USB Device
Effects 42Rev/71Chor/DSP (271X1,130X3)
Harmony 17 Types
Multi Pads 4 x 80 Banks + User
In/Out Jacks HP,FS x 2,L/R Out+Fixed,AUX in
Speakers 12cm x 2 / 5cm x 2
Amplifier 12W + 12W
Power Supply PA-301 (Included)
Included Acc. Manual, M. Rest, Data Disk
Dimensions 17 1/7" x 39 5/8" x 5 7/8"
Packaged Dim. 20.75'' x 45.5'' x 9.5''
Autism is a brain development disorder characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old.[1] Autism affects many parts of the brain; how this occurs is not understood.[2] The autism spectrum disorders (ASD) also include the related conditions Asperger syndrome and PDD-NOS, which have fewer signs and symptoms.[3]
Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by rare mutations, or by rare combinations of common genetic variants.[4] In rare cases, autism is strongly associated with agents that cause birth defects.[5] Controversies surround other proposed environmental causes, such as heavy metals, pesticides or childhood vaccines;[6] the vaccine hypotheses are biologically implausible and lack convincing scientific evidence.[7] The prevalence of ASD is about 6 per 1,000 people, with about four times as many males as females. The number of people known to have autism has increased dramatically since the 1980s, partly due to changes in diagnostic practice; the question of whether actual prevalence has increased is unresolved.[8]
Parents usually notice signs in the first two years of their child's life. Although early behavioral or cognitive intervention can help children gain self-care, social, and communication skills, there is no known cure.[9] Not many children with autism live independently after reaching adulthood, though some become successful.[10] An autistic culture has developed, with some individuals seeking a cure and others believing autism should be tolerated as a difference and not treated as a disorder.[11]
Characteristics
Autism is a highly variable brain development disorder[12] that first appears during infancy or childhood, and generally follows a steady course without remission.[13] Overt symptoms gradually begin after the age of six months, become established by age two or three years,[14] and tend to continue through adulthood, although often in more muted form.[15] It is distinguished not by a single symptom, but by a characteristic triad of symptoms: impairments in social interaction; impairments in communication; and restricted interests and repetitive behavior. Other aspects, such as atypical eating, are also common but are not essential for diagnosis.[16] Autism's individual symptoms occur in the general population and appear not to associate highly, without a sharp line separating pathologically severe from common traits.[17]
Social development
Social deficits distinguish autism and the related autism spectrum disorders (ASD; see Classification) from other developmental disorders.[15] People with autism have social impairments and often lack the intuition about others that many people take for granted. Noted autistic Temple Grandin described her inability to understand the social communication of neurotypicals, or people with normal neural development, as leaving her feeling "like an anthropologist on Mars".[18]
Unusual social development becomes apparent early in childhood. Autistic infants show less attention to social stimuli, smile and look at others less often, and respond less to their own name. Autistic toddlers differ more strikingly from social norms; for example, they have less eye contact and turn taking, and are more likely to communicate by manipulating another person's hand.[19] Three- to five-year-old autistic children are less likely to exhibit social understanding, approach others spontaneously, imitate and respond to emotions, communicate nonverbally, and take turns with others. However, they do form attachments to their primary caregivers.[20] They display moderately less attachment security than usual, although this feature disappears in children with higher mental development or less severe ASD.[21] Older children and adults with ASD perform worse on tests of face and emotion recognition.[22]
Contrary to common beliefs, autistic children do not prefer being alone. Making and maintaining friendships often proves to be difficult for those with autism. For them, the quality of friendships, not the number of friends, predicts how lonely they feel. Functional friendships, such as those resulting in invitations to parties, may affect their quality of life more deeply.[23]
There are many anecdotal reports, but few systematic studies, of aggression and violence in individuals with ASD. The limited data suggest that, in children with mental retardation, autism is associated with aggression, destruction of property, and tantrums. A 2007 study interviewed parents of 67 children with ASD and reported that about two-thirds of the children had periods of severe tantrums and about one-third had a history of aggression, with tantrums significantly more common than in children with a history of language impairment.[24] A 2008 Swedish study found that, of individuals aged 15 or older discharged from hospital with a diagnosis of ASD, those who committed violent crimes were significantly more likely to have other psychopathological conditions such as psychosis.[25]
Communication
About a third to a half of individuals with autism do not develop enough natural speech to meet their daily communication needs.[26] Differences in communication may be present from the first year of life, and may include delayed onset of babbling, unusual gestures, diminished responsiveness, and vocal patterns that are not synchronized with the caregiver. In the second and third years, autistic children have less frequent and less diverse babbling, consonants, words, and word combinations; their gestures are less often integrated with words. Autistic children are less likely to make requests or share experiences, and are more likely to simply repeat others' words (echolalia)[27][28] or reverse pronouns.[29] Joint attention seems to be necessary for functional speech, and deficits in joint attention seem to distinguish infants with ASD:[3] for example, they may look at a pointing hand instead of the pointed-at object,[19][28] and they consistently fail to point at objects in order to comment on or share an experience.[3] Autistic children may have difficulty with imaginative play and with developing symbols into language.[27][28]
In a pair of studies, high-functioning autistic children aged 8–15 performed equally well, and adults better than individually matched controls at basic language tasks involving vocabulary and spelling. Both autistic groups performed worse than controls at complex language tasks such as figurative language, comprehension and inference. As people are often sized up initially from their basic language skills, these studies suggest that people speaking to autistic individuals are more likely to overestimate what their audience comprehends.[30]
Repetitive behavior
Autistic individuals display many forms of repetitive or restricted behavior, which the Repetitive Behavior Scale-Revised (RBS-R)[31] categorizes as follows.
* Stereotypy is repetitive movement, such as hand flapping, making sounds, head rolling, or body rocking.
* Compulsive behavior is intended and appears to follow rules, such as arranging objects in a certain way.
* Sameness is resistance to change; for example, insisting that the furniture not be moved or refusing to be interrupted.
* Ritualistic behavior involves the performance of daily activities the same way each time, such as an unvarying menu or dressing ritual. This is closely associated with sameness and an independent validation has suggested combining the two factors.[32]
* Restricted behavior is limited in focus, interest, or activity, such as preoccupation with a single television program or toy.
* Self-injury includes movements that injure or can injure the person, such as eye poking, skin picking, hand biting, and head banging.[3] A 2007 study reported that self-injury at some point affected about 30% of children with ASD.[24]
No single repetitive behavior seems to be specific to autism, but only autism appears to have an elevated pattern of occurrence and severity of these behaviors.[31]
Other symptoms
Autistic individuals may have symptoms that are independent of the diagnosis, but that can affect the individual or the family.[16] An estimated 0.5% to 10% of individuals with ASD show unusual abilities, ranging from splinter skills such as the memorization of trivia to the extraordinarily rare talents of prodigious autistic savants.[33] Many individuals with ASD show superior skills in perception and attention, relative to the general population.[34] Unusual responses to sensory stimuli are more common and prominent in autistic children, although there is no good evidence that sensory symptoms differentiate autism from other developmental disorders.[35] Differences are greater for under-responsivity (for example, walking into things) than for over-responsivity (for example, distress from loud noises) or for sensation seeking (for example, rhythmic movements).[36] Several studies have reported associated motor problems that include poor muscle tone, poor motor planning, and toe walking; ASD is not associated with severe motor disturbances.[37]
Unusual eating behavior occurs in about three-quarters of children with ASD, to the extent that it was formerly a diagnostic indicator. Selectivity is the most common problem, although eating rituals and food refusal also occur;[24] this does not appear to result in malnutrition. Although some children with autism also have gastrointestinal (GI) symptoms, there is a lack of published rigorous data to support the theory that autistic children have more or different GI symptoms than usual;[38] studies report conflicting results, and the relationship between GI problems and ASD is unclear.[9]
At some point in childhood, about two-thirds of individuals with ASD are affected by sleep problems; these most commonly include symptoms of insomnia such as difficulty in falling asleep, frequent nocturnal awakenings, and early morning awakenings. Sleep problems are associated with difficult behaviors and family stress, and are often a focus of clinical attention over and above the primary ASD diagnosis.[39]
Parents of children with ASD have higher levels of stress.[40] Siblings of children with ASD report greater admiration of and less conflict with the affected sibling than siblings of unaffected children or those with Down syndrome; siblings of individuals with ASD have greater risk of negative well-being and poorer sibling relationships as adults.[41]
Classification
Autism is one of the five pervasive developmental disorders (PDD), which are characterized by widespread abnormalities of social interactions and communication, and severely restricted interests and highly repetitive behavior.[13] These symptoms do not imply sickness, fragility, or emotional disturbance.[15]
Of the five PDD forms, Asperger syndrome is closest to autism in signs and likely causes; Rett syndrome and childhood disintegrative disorder share several signs with autism, but may have unrelated causes; PDD not otherwise specified (PDD-NOS; also called atypical autism) is diagnosed when the criteria are not met for a more specific disorder.[42] Unlike autism, Asperger's has no substantial delay in language development.[1] The terminology of autism can be bewildering, with autism, Asperger's and PDD-NOS often called the autism spectrum disorders (ASD)[9] or sometimes the autistic disorders,[43] whereas autism itself is often called autistic disorder, childhood autism, or infantile autism. In this article, autism refers to the classic autistic disorder; in clinical practice, though, autism, ASD, and PDD are often used interchangeably.[44] ASD, in turn, is a subset of the broader autism phenotype (BAP), which describes individuals who may not have ASD but do have autistic-like traits, such as avoiding eye contact.[45]
The manifestations of autism cover a wide spectrum, ranging from individuals with severe impairments—who may be silent, mentally disabled, and locked into hand flapping and rocking—to high functioning individuals who may have active but distinctly odd social approaches, narrowly focused interests, and verbose, pedantic communication.[46] Sometimes the syndrome is divided into low-, medium- or high-functioning autism (LFA, MFA, and HFA), based on IQ thresholds,[47] or on how much support the individual requires in daily life; these subdivisions are not standardized and are controversial. Autism can also be divided into syndromal and non-syndromal autism; the syndromal autism is associated with severe or profound mental retardation or a congenital syndrome with physical symptoms, such as tuberous sclerosis.[48] Although individuals with Asperger's tend to perform better cognitively than those with autism, the extent of the overlap between Asperger's, HFA, and non-syndromal autism is unclear.[49]
Some studies have reported diagnoses of autism in children due to a loss of language or social skills, as opposed to a failure to make progress, typically from 15 to 30 months of age. The validity of this distinction remains controversial; it is possible that regressive autism is a specific subtype,[19][27][50][51] or that there is a continuum of behaviors between autism with and without regression.[52]
Research into causes has been hampered by the inability to identify biologically meaningful subpopulations[53] and by the traditional boundaries between the disciplines of psychiatry, psychology, neurology and pediatrics.[54] Newer technologies such as fMRI can help identify biologically-relevant phenotypes (observable traits) that can be viewed on brain scans, to help further neurogenetic studies of autism.[55] It has been proposed to classify autism using genetics as well as behavior, with the name Type 1 autism denoting rare autism cases that test positive for a mutation in the CNTNAP2 gene.[56]
Causes
It has long been presumed that there is a common cause at the genetic, cognitive, and neural levels for autism's characteristic triad of symptoms.[57] However, there is increasing suspicion that autism is instead a complex disorder whose core aspects have distinct causes that often co-occur.[57][58]
Autism has a strong genetic basis, although the genetics of autism are complex and it is unclear whether ASD is explained more by rare mutations with major effects, or by rare multigene interactions of common genetic variants.[4] Complexity arises due to interactions among multiple genes, the environment, and epigenetic factors which do not change DNA but are heritable and influence gene expression.[15] Early studies of twins estimated heritability explains more than 90% of the risk of autism, assuming a shared environment and no other genetic or medical syndromes.[43] However, most of the mutations that increase autism risk have not been identified. Typically, autism cannot be traced to a Mendelian (single-gene) mutation or to a single chromosome abnormality like Angelman syndrome or fragile X syndrome, and none of the genetic syndromes associated with ASDs has been shown to selectively cause ASD.[4] Numerous candidate genes have been located, with only small effects attributable to any particular gene.[4] The large number of autistic individuals with unaffected family members may result from copy number variations—spontaneous deletions or duplications in genetic material during meiosis.[60] Hence, a substantial fraction of autism cases may be traceable to genetic causes that are highly heritable but not inherited: that is, the mutation that causes the autism is not present in the parental genome.[59]
Autism caused by some rare mutations may disrupt some synaptic pathways, such as those involved with cell adhesion.[61] Gene replacement studies in mice suggest that autistic symptoms are closely related to later developmental steps that depend on activity in synapses and on activity-dependent changes.[62] All known teratogens (agents that cause birth defects) related to the risk of autism appear to act during the first eight weeks from conception, and though this does not exclude the possibility that autism can be initiated or affected later, it is strong evidence that autism arises very early in development.[5] Although evidence for other environmental causes is anecdotal and has not been confirmed by reliable studies,[6] extensive searches are underway.[63] Environmental factors that have been claimed to contribute to or exacerbate autism, or may be important in future research, include certain foods, infectious disease, heavy metals, solvents, diesel exhaust, PCBs, phthalates and phenols used in plastic products, pesticides, brominated flame retardants, alcohol, smoking, illicit drugs, vaccines,[8] and prenatal stress.[64] Parents may first become aware of autistic symptoms in their child around the time of a routine vaccination, and this has given rise to theories that vaccines or their preservatives cause autism. Although these theories lack convincing scientific evidence and are biologically implausible, parental concern about autism has led to lower rates of childhood immunizations and higher likelihood of measles outbreaks.[7]
Mechanism
Autism's symptoms result from maturation-related changes in various systems of the brain.[65] Despite extensive investigation, how autism occurs is not well understood. Its mechanism can be divided into two areas: the pathophysiology of brain structures and processes associated with autism, and the neuropsychological linkages between brain structures and behaviors.[65] The behaviors appear to have multiple pathophysiologies.[17]
Pathophysiology
Unlike many other brain disorders such as Parkinson's, autism does not have a clear unifying mechanism at either the molecular, cellular, or systems level; it is not known whether autism is a few disorders caused by mutations converging on a few common molecular pathways, or is (like intellectual disability) a large set of disorders with diverse mechanisms.[12] Autism appears to result from developmental factors that affect many or all functional brain systems,[66] and to disturb the timing of brain development more than the final product.[2] Neuroanatomical studies and the associations with teratogens strongly suggest that autism's mechanism includes alteration of brain development soon after conception.[5] This anomaly appears to start a cascade of pathological events in the brain that are significantly influenced by environmental factors.[67] Although many major structures of the human brain have been implicated, almost all postmortem studies have been of individuals who also had mental retardation, making it difficult to draw conclusions.[2] Brain weight and volume and head circumference tend to be greater in autistic children.[68] The cellular and molecular bases of pathological early overgrowth are not known, nor is it known whether the overgrown neural systems cause autism's characteristic signs. Current hypotheses include:
* An excess of neurons that causes local overconnectivity in key brain regions.[69]
* Disturbed neuronal migration during early gestation.[70][71]
* Unbalanced excitatory–inhibitory networks.[71]
* Abnormal formation of synapses and dendritic spines,[71] for example, by modulation of the neurexin–neuroligin cell-adhesion system,[72] or by poorly regulated synthesis of synaptic protein.[73] Disrupted synaptic development may also contribute to epilepsy, which may explain why the two conditions are associated.[74]
Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. Several symptoms consistent with a poorly regulated immune response have been reported in autistic children. It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD.[75] As autoantibodies have not been associated with pathology, are found in conditions other than ASD, and are not always present in ASD,[76] the relationship between immune disturbances and autism remains unclear and controversial.[70]
Several neurotransmitter abnormalities have been detected in autism, notably increased blood levels of serotonin. Whether these cause structural or behavioral abnormalities is unclear.[65] Some data suggest an increase in several growth hormones; other data argue for diminished growth factors.[77] Also, some inborn errors of metabolism are associated with autism but probably account for less than 5% of cases.[78]
The mirror neuron system (MNS) theory of autism hypothesizes that distortion in the development of the MNS interferes with imitation and leads to autism's core features of social impairment and communication difficulties. The MNS operates when an animal performs an action or observes another animal perform the same action. The MNS may contribute to an individual's understanding of other people by enabling the modeling of their behavior via embodied simulation of their actions, intentions, and emotions.[79] Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with Asperger's, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD.[80] However, individuals with autism also have abnormal brain activation in many circuits outside the MNS[81] and the MNS theory does not explain the normal performance of autistic children on imitation tasks that involve a goal or object.[82]
ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks.[85] In autism there is evidence for reduced functional connectivity of the default network, a large-scale brain network involved in social and emotional processing, with intact connectivity of the task-positive network, used in sustained attention and goal-directed thinking. In people with autism the two networks are not negatively correlated in time, suggesting an imbalance in toggling between the two networks, possibly reflecting a disturbance of self-referential thought.[86] A 2008 brain-imaging study found a specific pattern of signals in the cingulate cortex which differs in individuals with ASD.[87]
The underconnectivity theory of autism hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes.[88] Evidence for this theory has been found in functional neuroimaging studies on autistic individuals[30] and by a brain wave study that suggested that adults with ASD have local overconnectivity in the cortex and weak functional connections between the frontal lobe and the rest of the cortex.[89] Other evidence suggests the underconnectivity is mainly within each hemisphere of the cortex and that autism is a disorder of the association cortex.[90]
From studies based on event-related potentials, transient changes to the brain's electrical activity in response to stimuli, there is considerable evidence for differences in autistic individuals with respect to attention, orientiation to auditory and visual stimuli, novelty detection, language and face processing, and information storage; several studies have found a preference for non-social stimuli.[91] For example, magnetoencephalography studies have found evidence in autistic children of delayed responses in the brain's processing of auditory signals.[92]
Neuropsychology
Two major categories of cognitive theories have been proposed about the links between autistic brains and behavior.
The first category focuses on deficits in social cognition. The empathizing–systemizing theory postulates that autistic individuals can systemize—that is, they can develop internal rules of operation to handle events inside the brain—but are less effective at empathizing by handling events generated by other agents. An extension, the extreme male brain theory, hypothesizes that autism is an extreme case of the male brain, defined psychometrically as individuals in whom systemizing is better than empathizing;[93] this extension is controversial, as many studies contradict the idea that baby boys and girls respond differently to people and objects[94].
These theories are somewhat related to the earlier theory of mind approach, which hypothesizes that autistic behavior arises from an inability to ascribe mental states to oneself and others. The theory of mind hypothesis is supported by autistic children's atypical responses to the Sally–Anne test for reasoning about others' motivations,[93] and the mirror neuron system theory of autism described in Pathophysiology maps well to the hypothesis.[80] However, most studies have found no evidence of impairment in autistic individuals' ability to understand other people's basic emotions or goals; instead, data suggests that impairments are found in understanding more complex social emotions or in considering others' viewpoints.[95]
The second category focuses on nonsocial or general processing. Executive dysfunction hypothesizes that autistic behavior results in part from deficits in working memory, planning, inhibition, and other forms of executive function.[96] Tests of core executive processes such as eye movement tasks indicate improvement from late childhood to adolescence, but performance never reaches typical adult levels.[97] A strength of the theory is predicting stereotyped behavior and narrow interests;[98] two weaknesses are that executive function is hard to measure[96] and that executive function deficits have not been found in young autistic children.[22]
Weak central coherence theory hypothesizes that a limited ability to see the big picture underlies the central disturbance in autism. One strength of this theory is predicting special talents and peaks in performance in autistic people.[99] A related theory—enhanced perceptual functioning—focuses more on the superiority of locally oriented and perceptual operations in autistic individuals.[100] These theories map well from the underconnectivity theory of autism.
Neither category is satisfactory on its own; social cognition theories poorly address autism's rigid and repetitive behaviors, while the nonsocial theories have difficulty explaining social impairment and communication difficulties.[58] A combined theory based on multiple deficits may prove to be more useful.[101]
Screening
About half of parents of children with ASD notice their child's unusual behaviors by age 18 months, and about four-fifths notice by age 24 months.[51] As postponing treatment may affect long-term outcome, any of the following signs is reason to have a child evaluated by a specialist without delay:
* No babbling by 12 months.
* No gesturing (pointing, waving goodbye, etc.) by 12 months.
* No single words by 16 months.
* No two-word spontaneous phrases (other than instances of echolalia) by 24 months.
* Any loss of any language or social skills, at any age.[16]
The American Academy of Pediatrics recommends that all children be screened for ASD at the 18- and 24-month well-child doctor visits, using autism-specific formal screening tests.[3] In contrast, the UK National Screening Committee recommends against screening for ASD in the general population, because screening tools have not been fully validated and interventions lack sufficient evidence for effectiveness.[102] Screening tools include the Modified Checklist for Autism in Toddlers (M-CHAT), the Early Screening of Autistic Traits Questionnaire, and the First Year Inventory; initial data on M-CHAT and its predecessor CHAT on children aged 18–30 months suggests that it is best used in a clinical setting and that it has low sensitivity (many false-negatives) but good specificity (few false-positives).[51] It may be more accurate to precede these tests with a broadband screener that does not distinguish ASD from other developmental disorders.[103] Screening tools designed for one culture's norms for behaviors like eye contact may be inappropriate for a different culture.[104] Genetic screening for autism is generally still impractical.[105]
Diagnosis
Diagnosis is based on behavior, not cause or mechanism.[17][106] Autism is defined in the DSM-IV-TR as exhibiting at least six symptoms total, including at least two symptoms of qualitative impairment in social interaction, at least one symptom of qualitative impairment in communication, and at least one symptom of restricted and repetitive behavior. Sample symptoms include lack of social or emotional reciprocity, stereotyped and repetitive use of language or idiosyncratic language, and persistent preoccupation with parts of objects. Onset must be prior to age three years, with delays or abnormal functioning in either social interaction, language as used in social communication, or symbolic or imaginative play. The disturbance must not be better accounted for by Rett syndrome or childhood disintegrative disorder.[1] ICD-10 uses essentially the same definition.[13]
Several diagnostic instruments are available. Two are commonly used in autism research: the Autism Diagnostic Interview-Revised (ADI-R) is a semistructured parent interview, and the Autism Diagnostic Observation Schedule (ADOS) uses observation and interaction with the child. The Childhood Autism Rating Scale (CARS) is used widely in clinical environments to assess severity of autism based on observation of children.[19]
A pediatrician commonly performs a preliminary investigation by taking developmental history and physically examining the child. If warranted, diagnosis and evaluations are conducted with help from ASD specialists, observing and assessing cognitive, communication, family, and other factors using standardized tools, and taking into account any associated medical conditions.[107] A pediatric neuropsychologist is often asked to assess behavior and cognitive skills, both to aid diagnosis and to help recommend educational interventions.[108] A differential diagnosis for ASD at this stage might also consider mental retardation, hearing impairment, and a specific language impairment[107] such as Landau–Kleffner syndrome.[109] The presence of autism can make it harder to diagnose coexisting psychiatric disorders such as depression.[110]
Clinical genetics evaluations are often done once ASD is diagnosed, particularly when other symptoms already suggest a genetic cause.[44] Although genetic technology allows clinical geneticists to link an estimated 40% of cases to genetic causes,[111] consensus guidelines in the U.S. and UK are limited to high-resolution chromosome and fragile X testing.[44] A genotype-first model of diagnosis has been proposed, which would routinely assess the genome's copy number variations.[112] As new genetic tests are developed several ethical, legal, and social issues will emerge. Commercial availability of tests may precede adequate understanding of how to use test results, given the complexity of autism's genetics.[105] Metabolic and neuroimaging tests are sometimes helpful, but are not routine.[44]
ASD can sometimes be diagnosed by age 14 months, although diagnosis becomes increasingly stable over the first three years of life: for example, a one-year-old who meets diagnostic criteria for ASD is less likely than a three-year-old to continue to do so a few years later.[51] In the UK the National Autism Plan for Children recommends at most 30 weeks from first concern to completed diagnosis and assessment, though few cases are handled that quickly in practice.[107] A 2009 U.S. study found the average age of formal ASD diagnosis was 5.7 years, far above recommendations, and that 27% of children remained undiagnosed at age 8 years.[113] Although the symptoms of autism and ASD begin early in childhood, they are sometimes missed; years later, adults may seek diagnoses to help them or their friends and family understand themselves, to help their employers make adjustments, or in some locations to claim disability living allowances or other benefits.[114]
Underdiagnosis and overdiagnosis are problems in marginal cases, and much of the recent increase in the number of reported ASD cases is likely due to changes in diagnostic practices. The increasing popularity of drug treatment options and the expansion of benefits has given providers incentives to diagnose ASD, resulting in some overdiagnosis of children with uncertain symptoms. Conversely, the cost of screening and diagnosis and the challenge of obtaining payment can inhibit or delay diagnosis.[115] It is particularly hard to diagnose autism among the visually impaired, partly because some of its diagnostic criteria depend on vision, and partly because autistic symptoms overlap with those of common blindness syndromes.[116]
Management
The main goals of treatment are to lessen associated deficits and family distress, and to increase quality of life and functional independence. No single treatment is best and treatment is typically tailored to the child's needs.[9] Studies of interventions have methodological problems that prevent definitive conclusions about efficacy.[117] Although many psychosocial interventions have some positive evidence, suggesting that some form of treatment is preferable to no treatment, the methodological quality of systematic reviews of these studies has generally been poor, their clinical results are mostly tentative, and there is little evidence for the relative effectiveness of treatment options.[118] Intensive, sustained special education programs and behavior therapy early in life can help children acquire self-care, social, and job skills,[9] and often improve functioning and decrease symptom severity and maladaptive behaviors;[119] claims that intervention by around age three years is crucial are not substantiated.[120] Available approaches include applied behavior analysis (ABA), developmental models, structured teaching, speech and language therapy, social skills therapy, and occupational therapy.[9] Educational interventions have some effectiveness in children: intensive ABA treatment has demonstrated effectiveness in enhancing global functioning in preschool children[121] and is well-established for improving intellectual performance of young children.[119] Neuropsychological reports are often poorly communicated to educators, resulting in a gap between what a report recommends and what education is provided.[108] It is not known whether treatment programs for children lead to significant improvements after the children grow up,[119] and the limited research on the effectiveness of adult residential programs shows mixed results.[122]
Many medications are used to treat ASD symptoms that interfere with integrating a child into home or school when behavioral treatment fails.[15][123] More than half of U.S. children diagnosed with ASD are prescribed psychoactive drugs or anticonvulsants, with the most common drug classes being antidepressants, stimulants, and antipsychotics.[124] Aside from antipsychotics,[125] there is scant reliable research about the effectiveness or safety of drug treatments for adolescents and adults with ASD.[126] A person with ASD may respond atypically to medications, the medications can have adverse effects,[9] and no known medication relieves autism's core symptoms of social and communication impairments.[127] Experiments in mice have reversed or reduced some symptoms related to autism by replacing or modulating gene function after birth,[62] suggesting the possibility of targeting therapies to specific rare mutations known to cause autism.[61]
Although many alternative therapies and interventions are available, few are supported by scientific studies.[22][128][129] Treatment approaches have little empirical support in quality-of-life contexts, and many programs focus on success measures that lack predictive validity and real-world relevance.[23] Scientific evidence appears to matter less to service providers than program marketing, training availability, and parent requests.[130] Though most alternative treatments, such as melatonin, have only mild adverse effects[131] some may place the child at risk. A 2008 study found that compared to their peers, autistic boys have significantly thinner bones if on casein-free diets;[132] in 2005, botched chelation therapy killed a five-year-old child with autism.[133]
Treatment is expensive; indirect costs are more so. For someone born in 2000, a U.S. study estimated an average lifetime cost of $3.75 million (net present value in 2009 dollars, inflation-adjusted from 2003 estimate[134]), with about 10% medical care, 30% extra education and other care, and 60% lost economic productivity.[135] Publicly supported programs are often inadequate or inappropriate for a given child, and unreimbursed out-of-pocket medical or therapy expenses are associated with likelihood of family financial problems;[136] one 2008 U.S. study found a 14% average loss of annual income in families of children with ASD,[137] and a related study found that ASD is associated with higher probability that child care problems will greatly affect parental employment.[138] After childhood, key treatment issues include residential care, job training and placement, sexuality, social skills, and estate planning.[129]
Prognosis
There is no known cure.[9] Children recover occasionally, so that they lose their diagnosis of ASD;[139] this occurs sometimes after intensive treatment and sometimes not. It is not known how often recovery happens;[119] reported rates in unselected samples of children with ASD have ranged from 3% to 25%.[139] A few autistic children have acquired speech at age 5 or older.[140] Most children with autism lack social support, meaningful relationships, future employment opportunities or self-determination.[23] Although core difficulties tend to persist, symptoms often become less severe with age.[15] Few high-quality studies address long-term prognosis. Some adults show modest improvement in communication skills, but a few decline; no study has focused on autism after midlife.[141] Acquiring language before age six, having an IQ above 50, and having a marketable skill all predict better outcomes; independent living is unlikely with severe autism.[142] A 2004 British study of 68 adults who were diagnosed before 1980 as autistic children with IQ above 50 found that 12% achieved a high level of independence as adults, 10% had some friends and were generally in work but required some support, 19% had some independence but were generally living at home and needed considerable support and supervision in daily living, 46% needed specialist residential provision from facilities specializing in ASD with a high level of support and very limited autonomy, and 12% needed high-level hospital care.[10] A 2005 Swedish study of 78 adults that did not exclude low IQ found worse prognosis; for example, only 4% achieved independence.[143] A 2008 Canadian study of 48 young adults diagnosed with ASD as preschoolers found outcomes ranging through poor (46%), fair (32%), good (17%), and very good (4%); 56% of these young adults had been employed at some point during their lives, mostly in volunteer, sheltered or part-time work.[144] Changes in diagnostic practice and increased availability of effective early intervention make it unclear whether these findings can be generalized to recently diagnosed children.[8]
Epidemiology
Most recent reviews tend to estimate a prevalence of 1–2 per 1,000 for autism and close to 6 per 1,000 for ASD;[8] because of inadequate data, these numbers may underestimate ASD's true prevalence.[44] PDD-NOS's prevalence has been estimated at 3.7 per 1,000, Asperger's at roughly 0.6 per 1,000, and childhood disintegrative disorder at 0.02 per 1,000.[145] The number of reported cases of autism increased dramatically in the 1990s and early 2000s. This increase is largely attributable to changes in diagnostic practices, referral patterns, availability of services, age at diagnosis, and public awareness,[145][146] though unidentified environmental risk factors cannot be ruled out.[6] The available evidence does not rule out the possibility that autism's true prevalence has increased;[145] a real increase would suggest directing more attention and funding toward changing environmental factors instead of continuing to focus on genetics.[63]
Boys are at higher risk for ASD than girls. The sex ratio averages 4.3:1 and is greatly modified by cognitive impairment: it may be close to 2:1 with mental retardation and more than 5.5:1 without.[8] Although the evidence does not implicate any single pregnancy-related risk factor as a cause of autism, the risk of autism is associated with advanced age in either parent, and with diabetes, bleeding, and use of psychiatric drugs in the mother during pregnancy.[147] Most professionals believe that race, ethnicity, and socioeconomic background do not affect the occurrence of autism.[148]
Autism is associated with several other conditions:
* Genetic disorders. About 10–15% of autism cases have an identifiable Mendelian (single-gene) condition, chromosome abnormality, or other genetic syndrome,[149] and ASD is associated with several genetic disorders.[150]
* Mental retardation. The fraction of autistic individuals who also meet criteria for mental retardation has been reported as anywhere from 25% to 70%, a wide variation illustrating the difficulty of assessing autistic intelligence.[151] For ASD other than autism, the association with mental retardation is much weaker.[152]
* Anxiety disorders are common among children with ASD; there are no firm data, but studies have reported prevalences ranging from 11% to 84%. Many anxiety disorders have symptoms that are better explained by ASD itself, or are hard to distinguish from ASD's symptoms.[153]
* Epilepsy, with variations in risk of epilepsy due to age, cognitive level, and type of language disorder.[154]
* Several metabolic defects, such as phenylketonuria, are associated with autistic symptoms.[78]
* Minor physical anomalies are significantly increased in the autistic population.[155]
* Preempted diagnoses. Although the DSM-IV rules out concurrent diagnosis of many other conditions along with autism, the full criteria for ADHD, Tourette syndrome, and other of these conditions are often present and these comorbid diagnoses are increasingly accepted.[156]
History
A few examples of autistic symptoms and treatments were described long before autism was named. The Table Talk of Martin Luther contains the story of a 12-year-old boy who may have been severely autistic.[157] According to Luther's notetaker Mathesius, Luther thought the boy was a soulless mass of flesh possessed by the devil, and suggested that he be suffocated.[158] The earliest well-documented case of autism is that of Hugh Blair, as detailed in a 1747 court case in which his brother successfully petitioned to annul Blair's marriage to gain Blair's inheritance.[159] The Wild Boy of Aveyron, a feral child caught in 1798, showed several signs of autism; the medical student Jean Itard treated him with a behavioral program designed to help him form social attachments and to induce speech via imitation.[160]
The New Latin word autismus (English translation autism) was coined by the Swiss psychiatrist Eugen Bleuler in 1910 as he was defining symptoms of schizophrenia. He derived it from the Greek word autos (αὐτός, meaning self), and used it to mean morbid self-admiration, referring to "autistic withdrawal of the patient to his fantasies, against which any influence from outside becomes an intolerable disturbance".[161]
The word autism first took its modern sense in 1938 when Hans Asperger of the Vienna University Hospital adopted Bleuler's terminology autistic psychopaths in a lecture in German about child psychology.[162] Asperger was investigating a form of ASD now known as Asperger syndrome, though for various reasons it was not widely recognized as a separate diagnosis until 1981.[160] Leo Kanner of the Johns Hopkins Hospital first used autism in its modern sense in English when he introduced the label early infantile autism in a 1943 report of 11 children with striking behavioral similarities.[29] Almost all the characteristics described in Kanner's first paper on the subject, notably "autistic aloneness" and "insistence on sameness", are still regarded as typical of the autistic spectrum of disorders.[58] It is not known whether Kanner derived the term independently of Asperger.[163]
Kanner's reuse of autism led to decades of confused terminology like infantile schizophrenia, and child psychiatry's focus on maternal deprivation led to misconceptions of autism as an infant's response to "refrigerator mothers". Starting in the late 1960s autism was established as a separate syndrome by demonstrating that it is lifelong, distinguishing it from mental retardation and schizophrenia and from other developmental disorders, and demonstrating the benefits of involving parents in active programs of therapy.[164] As late as the mid-1970s there was little evidence of a genetic role in autism; now it is thought to be one of the most heritable of all psychiatric conditions.[165] Although the rise of parent organizations and the destigmatization of childhood ASD have deeply affected how we view ASD,[160] parents continue to feel social stigma in situations where their autistic children's behaviors are perceived negatively by others,[166] and many primary care physicians and medical specialists still express some beliefs consistent with outdated autism research.[167] The Internet has helped autistic individuals bypass nonverbal cues and emotional sharing that they find so hard to deal with, and has given them a way to form online communities and work remotely.[168] Sociological and cultural aspects of autism have developed: some in the community seek a cure, while others believe that autism is simply another way of being.[11][169]
References
# ^ a b c American Psychiatric Association (2000). "Diagnostic criteria for 299.00 Autistic Disorder". Diagnostic and Statistical Manual of Mental Disorders (4th, text revision (DSM-IV-TR) ed.). ISBN 0890420254.
# ^ a b c d Amaral DG, Schumann CM, Nordahl CW (2008). "Neuroanatomy of autism". Trends Neurosci 31 (3): 137–45. doi:10.1016/j.tins.2007.12.005. PMID 18258309.
# ^ a b c d e Johnson CP, Myers SM, Council on Children with Disabilities (2007). "Identification and evaluation of children with autism spectrum disorders". Pediatrics 120 (5): 1183–215. doi:10.1542/peds.2007-2361. PMID 17967920. http://pediatrics.aappublications.org/cgi/content/full/120/5/1183. Lay summary – AAP (2007-10-29).
# ^ a b c d Abrahams BS, Geschwind DH (2008). "Advances in autism genetics: on the threshold of a new neurobiology". Nat Rev Genet 9 (5): 341–55. doi:10.1038/nrg2346. PMID 18414403.
# ^ a b c Arndt TL, Stodgell CJ, Rodier PM (2005). "The teratology of autism". Int J Dev Neurosci 23 (2–3): 189–99. doi:10.1016/j.ijdevneu.2004.11.001. PMID 15749245.
# ^ a b c Rutter M (2005). "Incidence of autism spectrum disorders: changes over time and their meaning". Acta Paediatr 94 (1): 2–15. doi:10.1080/08035250410023124. PMID 15858952.
# ^ a b Vaccines and autism:
* Doja A, Roberts W (2006). "Immunizations and autism: a review of the literature". Can J Neurol Sci 33 (4): 341–6. PMID 17168158.
* Gerber JS, Offit PA (2009). "Vaccines and autism: a tale of shifting hypotheses". Clin Infect Dis 48 (4): 456–61. doi:10.1086/596476. PMID 19128068. http://www.journals.uchicago.edu/doi/full/10.1086/596476. Lay summary – IDSA (2009-01-30).
* Gross L (2009). "A broken trust: lessons from the vaccine–autism wars". PLoS Biol 7 (5): e1000114. doi:10.1371/journal.pbio.1000114. PMID 19478850. http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000114.
* Paul R (2009). "Parents ask: am I risking autism if I vaccinate my children?". J Autism Dev Disord 39 (6): 962–3. doi:10.1007/s10803-009-0739-y. PMID 19363650.
# ^ a b c d e Newschaffer CJ, Croen LA, Daniels J et al. (2007). "The epidemiology of autism spectrum disorders". Annu Rev Public Health 28: 235–58. doi:10.1146/annurev.publhealth.28.021406.144007. PMID 17367287.
# ^ a b c d e f g h Myers SM, Johnson CP, Council on Children with Disabilities (2007). "Management of children with autism spectrum disorders". Pediatrics 120 (5): 1162–82. doi:10.1542/peds.2007-2362. PMID 17967921. http://pediatrics.aappublications.org/cgi/content/full/120/5/1162. Lay summary – AAP (2007-10-29).
# ^ a b Howlin P, Goode S, Hutton J, Rutter M (2004). "Adult outcome for children with autism". J Child Psychol Psychiatry 45 (2): 212–29. doi:10.1111/j.1469-7610.2004.00215.x. PMID 14982237.
# ^ a b Silverman C (2008). "Fieldwork on another planet: social science perspectives on the autism spectrum". Biosocieties 3 (3): 325–41. doi:10.1017/S1745855208006236.
# ^ a b Geschwind DH (2008). "Autism: many genes, common pathways?". Cell 135 (3): 391–5. doi:10.1016/j.cell.2008.10.016. PMID 18984147.
# ^ a b c World Health Organization (2006). "F84. Pervasive developmental disorders". International Statistical Classification of Diseases and Related Health Problems (10th (ICD-10) ed.).
# ^ Rogers SJ (2009). "What are infant siblings teaching us about autism in infancy?". Autism Res. doi:10.1002/aur.81. PMID 19582867.
# ^ a b c d e f Rapin I, Tuchman RF (2008). "Autism: definition, neurobiology, screening, diagnosis". Pediatr Clin North Am 55 (5): 1129–46. doi:10.1016/j.pcl.2008.07.005. PMID 18929056.
# ^ a b c Filipek PA, Accardo PJ, Baranek GT et al. (1999). "The screening and diagnosis of autistic spectrum disorders". J Autism Dev Disord 29 (6): 439–84. doi:10.1023/A:1021943802493. This paper represents a consensus of representatives from nine professional and four parent organizations in the U.S.
# ^ a b c London E (2007). "The role of the neurobiologist in redefining the diagnosis of autism". Brain Pathol 17 (4): 408–11. doi:10.1111/j.1750-3639.2007.00103.x. PMID 17919126.
# ^ Sacks O (1995). An Anthropologist on Mars: Seven Paradoxical Tales. Knopf. ISBN 0679437851.
# ^ a b c d Volkmar F, Chawarska K, Klin A (2005). "Autism in infancy and early childhood". Annu Rev Psychol 56: 315–36. doi:10.1146/annurev.psych.56.091103.070159. PMID 15709938. A partial update is in: Volkmar FR, Chawarska K (2008). "Autism in infants: an update". World Psychiatry 7 (1): 19–21. PMID 18458791.
# ^ Sigman M, Dijamco A, Gratier M, Rozga A (2004). "Early detection of core deficits in autism". Ment Retard Dev Disabil Res Rev 10 (4): 221–33. doi:10.1002/mrdd.20046. PMID 15666338.
# ^ Rutgers AH, Bakermans-Kranenburg MJ, van IJzendoorn MH, van Berckelaer-Onnes IA (2004). "Autism and attachment: a meta-analytic review". J Child Psychol Psychiatry 45 (6): 1123–34. doi:10.1111/j.1469-7610.2004.t01-1-00305.x. PMID 15257669.
# ^ a b c Sigman M, Spence SJ, Wang AT (2006). "Autism from developmental and neuropsychological perspectives". Annu Rev Clin Psychol 2: 327–55. doi:10.1146/annurev.clinpsy.2.022305.095210. PMID 17716073.
# ^ a b c Burgess AF, Gutstein SE (2007). "Quality of life for people with autism: raising the standard for evaluating successful outcomes". Child Adolesc Ment Health 12 (2): 80–6. doi:10.1111/j.1475-3588.2006.00432.x.
# ^ a b c Dominick KC, Davis NO, Lainhart J, Tager-Flusberg H, Folstein S (2007). "Atypical behaviors in children with autism and children with a history of language impairment". Res Dev Disabil 28 (2): 145–62. doi:10.1016/j.ridd.2006.02.003. PMID 16581226.
# ^ Långström N, Grann M, Ruchkin V, Sjöstedt G, Fazel S (2008). "Risk factors for violent offending in autism spectrum disorder: a national study of hospitalized individuals". J Interpers Violence. doi:10.1177/0886260508322195. PMID 18701743.
# ^ Noens I, van Berckelaer-Onnes I, Verpoorten R, van Duijn G (2006). "The ComFor: an instrument for the indication of augmentative communication in people with autism and intellectual disability". J Intellect Disabil Res 50 (9): 621–32. doi:10.1111/j.1365-2788.2006.00807.x. PMID 16901289.
# ^ a b c Landa R (2007). "Early communication development and intervention for children with autism". Ment Retard Dev Disabil Res Rev 13 (1): 16–25. doi:10.1002/mrdd.20134. PMID 17326115.
# ^ a b c Tager-Flusberg H, Caronna E (2007). "Language disorders: autism and other pervasive developmental disorders". Pediatr Clin North Am 54 (3): 469–81. doi:10.1016/j.pcl.2007.02.011. PMID 17543905.
# ^ a b Kanner L (1943). "Autistic disturbances of affective contact". Nerv Child 2: 217–50. Reprinted in Acta Paedopsychiatr 35 (4): 100–36. 1968. PMID 4880460.
# ^ a b Williams DL, Goldstein G, Minshew NJ (2006). "Neuropsychologic functioning in children with autism: further evidence for disordered complex information-processing". Child Neuropsychol 12 (4–5): 279–98. doi:10.1080/09297040600681190. PMID 16911973.
# ^ a b Bodfish JW, Symons FJ, Parker DE, Lewis MH (2000). "Varieties of repetitive behavior in autism: comparisons to mental retardation". J Autism Dev Disord 30 (3): 237–43. doi:10.1023/A:1005596502855. PMID 11055459.
# ^ Lam KSL, Aman MG (2007). "The Repetitive Behavior Scale-Revised: independent validation in individuals with autism spectrum disorders". J Autism Dev Disord 37 (5): 855–66. doi:10.1007/s10803-006-0213-z. PMID 17048092. http://springerlink.com/content/v03747x60562638m/fulltext.html.
# ^ Treffert DA (2009). "The savant syndrome: an extraordinary condition. A synopsis: past, present, future". Philos Trans R Soc Lond B Biol Sci 364 (1522): 1351–7. doi:10.1098/rstb.2008.0326. PMID 19528017. Lay summary – Wisconsin Medical Society.
# ^ Plaisted Grant K, Davis G (2009). "Perception and apperception in autism: rejecting the inverse assumption". Philos Trans R Soc Lond B Biol Sci 364 (1522): 1393–8. doi:10.1098/rstb.2009.0001. PMID 19528022.
# ^ Rogers SJ, Ozonoff S (2005). "Annotation: what do we know about sensory dysfunction in autism? A critical review of the empirical evidence". J Child Psychol Psychiatry 46 (12): 1255–68. doi:10.1111/j.1469-7610.2005.01431.x. PMID 16313426.
# ^ Ben-Sasson A, Hen L, Fluss R, Cermak SA, Engel-Yeger B, Gal E (2009). "A meta-analysis of sensory modulation symptoms in individuals with autism spectrum disorders". J Autism Dev Disord 39 (1): 1–11. doi:10.1007/s10803-008-0593-3. PMID 18512135.
# ^ Ming X, Brimacombe M, Wagner GC (2007). "Prevalence of motor impairment in autism spectrum disorders". Brain Dev 29 (9): 565–70. doi:10.1016/j.braindev.2007.03.002. PMID 17467940.
# ^ Erickson CA, Stigler KA, Corkins MR, Posey DJ, Fitzgerald JF, McDougle CJ (2005). "Gastrointestinal factors in autistic disorder: a critical review". J Autism Dev Disord 35 (6): 713–27. doi:10.1007/s10803-005-0019-4. PMID 16267642.
# ^ Richdale AL, Schreck KA (2009). "Sleep problems in autism spectrum disorders: prevalence, nature, & possible biopsychosocial aetiologies". Sleep Med Rev. doi:10.1016/j.smrv.2009.02.003. PMID 19398354.
# ^ Montes G, Halterman JS (2007). "Psychological functioning and coping among mothers of children with autism: a population-based study". Pediatrics 119 (5): e1040–6. doi:10.1542/peds.2006-2819. PMID 17473077. http://pediatrics.aappublications.org/cgi/content/full/119/5/e1040.
# ^ Orsmond GI, Seltzer MM (2007). "Siblings of individuals with autism spectrum disorders across the life course" (PDF). Ment Retard Dev Disabil Res Rev 13 (4): 313–20. doi:10.1002/mrdd.20171. PMID 17979200. http://www.waisman.wisc.edu/family/pubs/Autism/2007%20siblings_autism_life-course.pdf. Retrieved on 2009-02-13.
# ^ Volkmar FR, State M, Klin A (2009). "Autism and autism spectrum disorders: diagnostic issues for the coming decade". J Child Psychol Psychiatry 50 (1–2): 108–15. doi:10.1111/j.1469-7610.2008.02010.x. PMID 19220594.
# ^ a b Freitag CM (2007). "The genetics of autistic disorders and its clinical relevance: a review of the literature". Mol Psychiatry 12 (1): 2–22. doi:10.1038/sj.mp.4001896. PMID 17033636.
# ^ a b c d e Caronna EB, Milunsky JM, Tager-Flusberg H (2008). "Autism spectrum disorders: clinical and research frontiers". Arch Dis Child 93 (6): 518–23. doi:10.1136/adc.2006.115337. PMID 18305076.
# ^ Piven J, Palmer P, Jacobi D, Childress D, Arndt S (1997). "Broader autism phenotype: evidence from a family history study of multiple-incidence autism families" (PDF). Am J Psychiatry 154 (2): 185–90. PMID 9016266. http://ajp.psychiatryonline.org/cgi/reprint/154/2/185.pdf.
# ^ Happé F (1999). "Understanding assets and deficits in autism: why success is more interesting than failure" (PDF). Psychologist 12 (11): 540–7. http://www.thepsychologist.org.uk/archive/archive_home.cfm/volumeID_12-editionID_46-ArticleID_133-getfile_getPDF/thepsychologist/psy_11_99_p540-547_happe.pdf.
# ^ Baron-Cohen S (2006). "The hyper-systemizing, assortative mating theory of autism" (PDF). Prog Neuropsychopharmacol Biol Psychiatry 30 (5): 865–72. doi:10.1016/j.pnpbp.2006.01.010. PMID 16519981. http://autismresearchcentre.com/docs/papers/2006_BC_Neuropsychophamacology.pdf. Retrieved on 2009-06-08.
# ^ Cohen D, Pichard N, Tordjman S et al. (2005). "Specific genetic disorders and autism: clinical contribution towards their identification". J Autism Dev Disord 35 (1): 103–16. doi:10.1007/s10803-004-1038-2. PMID 15796126.
# ^ Validity of ASD subtypes:
* Klin A (2006). "Autism and Asperger syndrome: an overview". Rev Bras Psiquiatr 28 (suppl 1): S3–S11. doi:10.1590/S1516-44462006000500002. PMID 16791390. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1516-44462006000500002&lng=en&nrm=iso&tlng=en.
* Witwer AN, Lecavalier L (2008). "Examining the validity of autism spectrum disorder subtypes". J Autism Dev Disord 38 (9): 1611–24. doi:10.1007/s10803-008-0541-2. PMID 18327636.
# ^ Stefanatos GA (2008). "Regression in autistic spectrum disorders". Neuropsychol Rev 18 (4): 305–19. doi:10.1007/s11065-008-9073-y. PMID 18956241.
# ^ a b c d Landa RJ (2008). "Diagnosis of autism spectrum disorders in the first 3 years of life". Nat Clin Pract Neurol 4 (3): 138–47. doi:10.1038/ncpneuro0731. PMID 18253102.
# ^ Ozonoff S, Heung K, Byrd R, Hansen R, Hertz-Picciotto I (2008). "The onset of autism: patterns of symptom emergence in the first years of life". Autism Res 1 (6): 320–328. doi:10.1002/aur.53. PMID 19360687.
# ^ Altevogt BM, Hanson SL, Leshner AI (2008). "Autism and the environment: challenges and opportunities for research". Pediatrics 121 (6): 1225–9. doi:10.1542/peds.2007-3000. PMID 18519493.
# ^ Reiss AL (2009). "Childhood developmental disorders: an academic and clinical convergence point for psychiatry, neurology, psychology and pediatrics". J Child Psychol Psychiatry 50 (1-2): 87–98. doi:10.1111/j.1469-7610.2008.02046.x. PMID 19220592.
# ^ Piggot J, Shirinyan D, Shemmassian S, Vazirian S, Alarcón M (2009). "Neural systems approaches to the neurogenetics of autism spectrum disorders". Neuroscience. doi:10.1016/j.neuroscience.2009.05.054. PMID 19482063.
# ^ Stephan DA (2008). "Unraveling autism". Am J Hum Genet 82 (1): 7–9. doi:10.1016/j.ajhg.2007.12.003. PMID 18179879.
# ^ a b Happé F, Ronald A (2008). "The 'fractionable autism triad': a review of evidence from behavioural, genetic, cognitive and neural research". Neuropsychol Rev 18 (4): 287–304. doi:10.1007/s11065-008-9076-8. PMID 18956240.
# ^ a b c Happé F, Ronald A, Plomin R (2006). "Time to give up on a single explanation for autism". Nat Neurosci 9 (10): 1218–20. doi:10.1038/nn1770. PMID 17001340.
# ^ a b Beaudet AL (2007). "Autism: highly heritable but not inherited". Nat Med 13 (5): 534–6. doi:10.1038/nm0507-534. PMID 17479094.
# ^ Cook EH, Scherer SW (2008). "Copy-number variations associated with neuropsychiatric conditions". Nature 455 (7215): 919–23. doi:10.1038/nature07458. PMID 18923514.
# ^ a b Betancur C, Sakurai T, Buxbaum JD (2009). "The emerging role of synaptic cell-adhesion pathways in the pathogenesis of autism spectrum disorders". Trends Neurosci. doi:10.1016/j.tins.2009.04.003. PMID 19541375.
# ^ a b Walsh CA, Morrow EM, Rubenstein JL (2008). "Autism and brain development". Cell 135 (3): 396–400. doi:10.1016/j.cell.2008.10.015. PMID 18984148.
# ^ a b Szpir M (2006). "Tracing the origins of autism: a spectrum of new studies". Environ Health Perspect 114 (7): A412–8. PMID 16835042. PMC: 1513312. http://www.ehponline.org/members/2006/114-7/focus.html.
# ^ Kinney DK, Munir KM, Crowley DJ, Miller AM (2008). "Prenatal stress and risk for autism". Neurosci Biobehav Rev 32 (8): 1519–32. doi:10.1016/j.neubiorev.2008.06.004. PMID 18598714.
# ^ a b c Penn HE (2006). "Neurobiological correlates of autism: a review of recent research". Child Neuropsychol 12 (1): 57–79. doi:10.1080/09297040500253546. PMID 16484102.
# ^ Müller RA (2007). "The study of autism as a distributed disorder". Ment Retard Dev Disabil Res Rev 13 (1): 85–95. doi:10.1002/mrdd.20141. PMID 17326118.
# ^ Casanova MF (2007). "The neuropathology of autism". Brain Pathol 17 (4): 422–33. doi:10.1111/j.1750-3639.2007.00100.x. PMID 17919128.
# ^ DiCicco-Bloom E, Lord C, Zwaigenbaum L et al. (2006). "The developmental neurobiology of autism spectrum disorder". J Neurosci 26 (26): 6897–906. doi:10.1523/JNEUROSCI.1712-06.2006. PMID 16807320. http://www.jneurosci.org/cgi/content/full/26/26/6897.
# ^ Courchesne E, Pierce K, Schumann CM et al. (2007). "Mapping early brain development in autism". Neuron 56 (2): 399–413. doi:10.1016/j.neuron.2007.10.016. PMID 17964254.
# ^ a b Schmitz C, Rezaie P (2008). "The neuropathology of autism: where do we stand?". Neuropathol Appl Neurobiol 34 (1): 4–11. doi:10.1111/j.1365-2990.2007.00872.x. PMID 17971078.
# ^ a b c Persico AM, Bourgeron T (2006). "Searching for ways out of the autism maze: genetic, epigenetic and environmental clues". Trends Neurosci 29 (7): 349–58. doi:10.1016/j.tins.2006.05.010. PMID 16808981.
# ^ Südhof TC (2008). "Neuroligins and neurexins link synaptic function to cognitive disease". Nature 455 (7215): 903–11. doi:10.1038/nature07456. PMID 18923512.
# ^ Kelleher RJ III, Bear MF (2008). "The autistic neuron: troubled translation?". Cell 135 (3): 401–6. doi:10.1016/j.cell.2008.10.017. PMID 18984149.
# ^ Tuchman R, Moshé SL, Rapin I (2009). "Convulsing toward the pathophysiology of autism". Brain Dev 31 (2): 95–103. doi:10.1016/j.braindev.2008.09.009. PMID 19006654.
# ^ Ashwood P, Wills S, Van de Water J (2006). "The immune response in autism: a new frontier for autism research". J Leukoc Biol 80 (1): 1–15. doi:10.1189/jlb.1205707. PMID 16698940. http://www.jleukbio.org/cgi/content/full/80/1/1.
# ^ Wills S, Cabanlit M, Bennett J, Ashwood P, Amaral D, Van de Water J (2007). "Autoantibodies in autism spectrum disorders (ASD)". Ann N Y Acad Sci 1107: 79–91. doi:10.1196/annals.1381.009. PMID 17804535.
# ^ Hughes JR (2008). "A review of recent reports on autism: 1000 studies published in 2007". Epilepsy Behav 13 (3): 425–37. doi:10.1016/j.yebeh.2008.06.015. PMID 18627794.
# ^ a b Manzi B, Loizzo AL, Giana G, Curatolo P (2008). "Autism and metabolic diseases". J Child Neurol 23 (3): 307–14. doi:10.1177/0883073807308698. PMID 18079313.
# ^ MNS and autism:
* Ramachandran VS, Oberman LM (2006). "Broken mirrors: a theory of autism" (PDF). Sci Am 295 (5): 62–9. PMID 17076085. http://cbc.ucsd.edu/pdf/brokenmirrors_asd.pdf. Retrieved on 2009-02-13.
* Williams JHG (2008). "Self–other relations in social development and autism: multiple roles for mirror neurons and other brain bases". Autism Res 1 (2): 73–90. doi:10.1002/aur.15.
* Dinstein I, Thomas C, Behrmann M, Heeger DJ (2008). "A mirror up to nature". Curr Biol 18 (1): R13–8. doi:10.1016/j.cub.2007.11.004. PMID 18177704.
# ^ a b Iacoboni M, Dapretto M (2006). "The mirror neuron system and the consequences of its dysfunction". Nat Rev Neurosci 7 (12): 942–51. doi:10.1038/nrn2024. PMID 17115076.
# ^ Frith U, Frith CD (2003). "Development and neurophysiology of mentalizing" (PDF). Philos Trans R Soc Lond B Biol Sci 358 (1431): 459–73. doi:10.1098/rstb.2002.1218. PMID 12689373. PMC: 1693139. http://rstb.royalsocietypublishing.org/content/358/1431/459.full.pdf.
# ^ Hamilton AFdC (2008). "Emulation and mimicry for social interaction: a theoretical approach to imitation in autism". Q J Exp Psychol 61 (1): 101–15. doi:10.1080/17470210701508798. PMID 18038342.
# ^ a b Powell K (2004). "Opening a window to the autistic brain". PLoS Biol 2 (8): E267. doi:10.1371/journal.pbio.0020267. PMID 15314667. PMC: 509312. http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020267.
# ^ Thai NJ, Longe O, Rippon G (2009). "Disconnected brains: what is the role of fMRI in connectivity research?". Int J Psychophysiol 73 (1): 27–32. doi:10.1016/j.ijpsycho.2008.12.015. PMID 19530277.
# ^ Di Martino A, Ross K, Uddin LQ, Sklar AB, Castellanos FX, Milham MP (2009). "Functional brain correlates of social and nonsocial processes in autism spectrum disorders: an activation likelihood estimation meta-analysis". Biol Psychiatry 65 (1): 63–74. doi:10.1016/j.biopsych.2008.09.022. PMID 18996505.
# ^ Broyd SJ, Demanuele C, Debener S, Helps SK, James CJ, Sonuga-Barke EJS (2009). "Default-mode brain dysfunction in mental disorders: a systematic review". Neurosci Biobehav Rev 33 (3): 279–96. doi:10.1016/j.neubiorev.2008.09.002. PMID 18824195.
# ^ Chiu PH, Kayali MA, Kishida KT et al. (2008). "Self responses along cingulate cortex reveal quantitative neural phenotype for high-functioning autism". Neuron 57 (3): 463–73. doi:10.1016/j.neuron.2007.12.020. PMID 18255038. Lay summary – Technol Rev (2007-02-07).
# ^ Just MA, Cherkassky VL, Keller TA, Kana RK, Minshew NJ (2007). "Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry". Cereb Cortex 17 (4): 951–61. doi:10.1093/cercor/bhl006. PMID 16772313. http://cercor.oxfordjournals.org/cgi/content/full/17/4/951.
# ^ Murias M, Webb SJ, Greenson J, Dawson G (2007). "Resting state cortical connectivity reflected in EEG coherence in individuals with autism". Biol Psychiatry 62 (3): 270–3. doi:10.1016/j.biopsych.2006.11.012. PMID 17336944.
# ^ Minshew NJ, Williams DL (2007). "The new neurobiology of autism: cortex, connectivity, and neuronal organization". Arch Neurol 64 (7): 945–50. doi:10.1001/archneur.64.7.945. PMID 17620483.
# ^ Jeste SS, Nelson CA 3rd (2009). "Event related potentials in the understanding of autism spectrum disorders: an analytical review". J Autism Dev Disord 39 (3): 495–510. doi:10.1007/s10803-008-0652-9. PMID 18850262.
# ^ Roberts TP, Schmidt GL, Egeth M et al. (2008). "Electrophysiological signatures: magnetoencephalographic studies of the neural correlates of language impairment in autism spectrum disorders". Int J Psychophysiol 68 (2): 149–60. doi:10.1016/j.ijpsycho.2008.01.012. PMID 18336941.
# ^ a b Baron-Cohen S (2009). "Autism: the empathizing–systemizing (E-S) theory" (PDF). Ann N Y Acad Sci 1156: 68–80. doi:10.1111/j.1749-6632.2009.04467.x. PMID 19338503. http://autismresearchcentre.com/docs/papers/2009_BC_nyas.pdf. Retrieved on 2009-06-08.
# ^ Spelke ES (2005). "Sex differences in intrinsic aptitude for mathematics and science?: a critical review" (PDF). Am Psychol 60 (9): 950–8. doi:10.1037/0003-066X.60.9.950. PMID 16366817. http://www.wjh.harvard.edu/~lds/pdfs/spelke2005.pdf. Retrieved on 2009-04-06.
# ^ Hamilton AFdC (2009). "Research review: Goals, intentions and mental states: challenges for theories of autism". J Child Psychol Psychiatry. doi:10.1111/j.1469-7610.2009.02098.x. PMID 19508497.
# ^ a b Kenworthy L, Yerys BE, Anthony LG, Wallace GL (2008). "Understanding executive control in autism spectrum disorders in the lab and in the real world". Neuropsychol Rev 18 (4): 320–38. doi:10.1007/s11065-008-9077-7. PMID 18956239.
# ^ O'Hearn K, Asato M, Ordaz S, Luna B (2008). "Neurodevelopment and executive function in autism". Dev Psychopathol 20 (4): 1103–32. doi:10.1017/S0954579408000527. PMID 18838033.
# ^ Hill EL (2004). "Executive dysfunction in autism". Trends Cogn Sci 8 (1): 26–32. doi:10.1016/j.dr.2004.01.001. PMID 14697400.
# ^ Happé F, Frith U (2006). "The weak coherence account: detail-focused cognitive style in autism spectrum disorders". J Autism Dev Disord 36 (1): 5–25. doi:10.1007/s10803-005-0039-0. PMID 16450045.
# ^ Mottron L, Dawson M, Soulières I, Hubert B, Burack J (2006). "Enhanced perceptual functioning in autism: an update, and eight principles of autistic perception". J Autism Dev Disord 36 (1): 27–43. doi:10.1007/s10803-005-0040-7. PMID 16453071.
# ^ Rajendran G, Mitchell P (2007). "Cognitive theories of autism". Dev Rev 27 (2): 224–60. doi:10.1016/j.dr.2007.02.001.
# ^ Williams J, Brayne C (2006). "Screening for autism spectrum disorders: what is the evidence?". Autism 10 (1): 11–35. doi:10.1177/1362361306057876. PMID 16522708.
# ^ Wetherby AM, Brosnan-Maddox S, Peace V, Newton L (2008). "Validation of the Infant–Toddler Checklist as a broadband screener for autism spectrum disorders from 9 to 24 months of age". Autism 12 (5): 487–511. doi:10.1177/1362361308094501. PMID 18805944.
# ^ Wallis KE, Pinto-Martin J (2008). "The challenge of screening for autism spectrum disorder in a culturally diverse society". Acta Paediatr 97 (5): 539–40. doi:10.1111/j.1651-2227.2008.00720.x. PMID 18373717.
# ^ a b McMahon WM, Baty BJ, Botkin J (2006). "Genetic counseling and ethical issues for autism". Am J Med Genet C Semin Med Genet 142C (1): 52–7. doi:10.1002/ajmg.c.30082. PMID 16419100.
# ^ Baird G, Cass H, Slonims V (2003). "Diagnosis of autism". BMJ 327 (7413): 488–93. doi:10.1136/bmj.327.7413.488. PMID 12946972. PMC: 188387. http://www.bmj.com/cgi/content/full/327/7413/488.
# ^ a b c Dover CJ, Le Couteur A (2007). "How to diagnose autism". Arch Dis Child 92 (6): 540–5. doi:10.1136/adc.2005.086280. PMID 17515625.
# ^ a b Kanne SM, Randolph JK, Farmer JE (2008). "Diagnostic and assessment findings: a bridge to academic planning for children with autism spectrum disorders". Neuropsychol Rev 18 (4): 367–84. doi:10.1007/s11065-008-9072-z. PMID 18855144.
# ^ Mantovani JF (2000). "Autistic regression and Landau–Kleffner syndrome: progress or confusion?". Dev Med Child Neurol 42 (5): 349–53. doi:10.1017/S0012162200210621. PMID 10855658.
# ^ Matson JL, Neal D (2009). "Cormorbidity: diagnosing comorbid psychiatric conditions". Psychiatr Times 26 (4). http://www.psychiatrictimes.com/display/article/10168/1403043.
# ^ Schaefer GB, Mendelsohn NJ (2008). "Genetics evaluation for the etiologic diagnosis of autism spectrum disorders". Genet Med 10 (1): 4–12. doi:10.1097/GIM.0b013e31815efdd7. PMID 18197051. Lay summary – Medical News Today (2008-02-07).
# ^ Ledbetter DH (2008). "Cytogenetic technology—genotype and phenotype". N Engl J Med 359 (16): 1728–30. doi:10.1056/NEJMe0806570. PMID 18784093.
# ^ Shattuck PT, Durkin M, Maenner M et al. (2009). "Timing of identification among children with an autism spectrum disorder: findings from a population-based surveillance study". J Am Acad Child Adolesc Psychiatry 48 (5): 474–83. doi:10.1097/CHI.0b013e31819b3848 (inactive 2009-03-27). PMID 19318992.
# ^ "Diagnosis: how can it benefit me as an adult?". National Autistic Society. 2005. http://www.nas.org.uk/nas/jsp/polopoly.jsp?a=8018. Retrieved on 2008-03-24.
# ^ Shattuck PT, Grosse SD (2007). "Issues related to the diagnosis and treatment of autism spectrum disorders". Ment Retard Dev Disabil Res Rev 13 (2): 129–35. doi:10.1002/mrdd.20143. PMID 17563895.
# ^ Cass H (1998). "Visual impairment and autism: current questions and future research". Autism 2 (2): 117–38. doi:10.1177/1362361398022002.
# ^ Ospina MB, Krebs Seida J, Clark B et al. (2008). "Behavioural and developmental interventions for autism spectrum disorder: a clinical systematic review". PLoS ONE 3 (11): e3755. doi:10.1371/journal.pone.0003755. PMID 19015734. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003755.
# ^ Krebs Seida J, Ospina MB, Karkhaneh M, Hartling L, Smith V, Clark B (2009). "Systematic reviews of psychosocial interventions for autism: an umbrella review". Dev Med Child Neurol 51 (2): 95–104. doi:10.1111/j.1469-8749.2008.03211.x (inactive 2009-03-27). PMID 19191842.
# ^ a b c d Rogers SJ, Vismara LA (2008). "Evidence-based comprehensive treatments for early autism". J Clin Child Adolesc Psychol 37 (1): 8–38. doi:10.1080/15374410701817808. PMID 18444052.
# ^ Howlin P, Magiati I, Charman T (2009). "Systematic review of early intensive behavioral interventions for children with autism". Am J Intellect Dev Disabil 114 (1): 23–41. doi:10.1352/2009.114:23;nd41. PMID 19143460.
# ^ Eikeseth S (2009). "Outcome of comprehensive psycho-educational interventions for young children with autism". Res Dev Disabil 30 (1): 158–78. doi:10.1016/j.ridd.2008.02.003. PMID 18385012.
# ^ Van Bourgondien ME, Reichle NC, Schopler E (2003). "Effects of a model treatment approach on adults with autism". J Autism Dev Disord 33 (2): 131–40. doi:10.1023/A:1022931224934. PMID 12757352.
# ^ Leskovec TJ, Rowles BM, Findling RL (2008). "Pharmacological treatment options for autism spectrum disorders in children and adolescents". Harv Rev Psychiatry 16 (2): 97–112. doi:10.1080/10673220802075852. PMID 18415882.
# ^ Oswald DP, Sonenklar NA (2007). "Medication use among children with autism spectrum disorders". J Child Adolesc Psychopharmacol 17 (3): 348–55. doi:10.1089/cap.2006.17303. PMID 17630868.
# ^ Posey DJ, Stigler KA, Erickson CA, McDougle CJ (2008). "Antipsychotics in the treatment of autism". J Clin Invest 118 (1): 6–14. doi:10.1172/JCI32483. PMID 18172517. PMC: 2171144. http://www.jci.org/articles/view/32483/version/1.
# ^ Lack of research on drug treatments:
* Angley M, Young R, Ellis D, Chan W, McKinnon R (2007). "Children and autism—part 1—recognition and pharmacological management" (PDF). Aust Fam Physician 36 (9): 741–4. PMID 17915375. http://www.racgp.org.au/afp/200709/200709angley.pdf.
* Broadstock M, Doughty C, Eggleston M (2007). "Systematic review of the effectiveness of pharmacological treatments for adolescents and adults with autism spectrum disorder". Autism 11 (4): 335–48. doi:10.1177/1362361307078132. PMID 17656398.
# ^ Buitelaar JK (2003). "Why have drug treatments been so disappointing?". Novartis Found Symp 251: 235–44; discussion 245–9, 281–97. doi:10.1002/0470869380.ch14. PMID 14521196.
# ^ Lack of support for interventions:
* Francis K (2005). "Autism interventions: a critical update" (PDF). Dev Med Child Neurol 47 (7): 493–9. doi:10.1017/S0012162205000952. PMID 15991872. http://journals.cambridge.org/production/action/cjoGetFulltext?fulltextid=313204.
* Rao PA, Beidel DC, Murray MJ (2008). "Social skills interventions for children with Asperger's syndrome or high-functioning autism: a review and recommendations". J Autism Dev Disord 38 (2): 353–61. doi:10.1007/s10803-007-0402-4. PMID 17641962.
* Schechtman MA (2007). "Scientifically unsupported therapies in the treatment of young children with autism spectrum disorders" (PDF). Pediatr Ann 36 (8): 497–8, 500–2, 504–5. PMID 17849608. http://pediatricsupersite.com/showPdf.aspx?rid=23083.
# ^ a b Aman MG (2005). "Treatment planning for patients with autism spectrum disorders". J Clin Psychiatry 66 (Suppl 10): 38–45. PMID 16401149.
# ^ Stahmer AC, Collings NM, Palinkas LA (2005). "Early intervention practices for children with autism: descriptions from community providers". Focus Autism Other Dev Disabl 20 (2): 66–79. doi:10.1177/10883576050200020301. PMID 16467905.
# ^ Angley M, Semple S, Hewton C, Paterson F, McKinnon R (2007). "Children and autism—part 2—management with complementary medicines and dietary interventions" (PDF). Aust Fam Physician 36 (10): 827–30. PMID 17925903. http://www.racgp.org.au/afp/200710/200710angley.pdf.
# ^ Hediger ML, England LJ, Molloy CA, Yu KF, Manning-Courtney P, Mills JL (2008). "Reduced bone cortical thickness in boys with autism or autism spectrum disorder". J Autism Dev Disord 38 (5): 848–56. doi:10.1007/s10803-007-0453-6. PMID 17879151. Lay summary – NIH News (2008-01-29).
# ^ Brown MJ, Willis T, Omalu B, Leiker R (2006). "Deaths resulting from hypocalcemia after administration of edetate disodium: 2003–2005". Pediatrics 118 (2): e534–6. doi:10.1542/peds.2006-0858. PMID 16882789. http://pediatrics.aappublications.org/cgi/content/full/118/2/e534.
# ^ "Consumer Price Index (estimate) 1800–2008". Federal Reserve Bank of Minneapolis. http://www.minneapolisfed.org/community_education/teacher/calc/hist1800.cfm. Retrieved on 2009-05-22.
# ^ Ganz ML (2007). "The lifetime distribution of the incremental societal costs of autism". Arch Pediatr Adolesc Med 161 (4): 343–9. doi:10.1001/archpedi.161.4.343. PMID 17404130. http://archpedi.ama-assn.org/cgi/content/full/161/4/343. Lay summary – Harvard School of Public Health (2006-04-25).
# ^ Sharpe DL, Baker DL (2007). "Financial issues associated with having a child with autism". J Fam Econ Iss 28 (2): 247–64. doi:10.1007/s10834-007-9059-6.
# ^ Montes G, Halterman JS (2008). "Association of childhood autism spectrum disorders and loss of family income". Pediatrics 121 (4): e821–6. doi:10.1542/peds.2007-1594. PMID 18381511. http://pediatrics.aappublications.org/cgi/content/full/121/4/e821.
# ^ Montes G, Halterman JS (2008). "Child care problems and employment among families with preschool-aged children with autism in the United States". Pediatrics 122 (1): e202–8. doi:10.1542/peds.2007-3037. PMID 18595965. http://pediatrics.aappublications.org/cgi/content/full/122/1/e202.
# ^ a b Helt M, Kelley E, Kinsbourne M et al. (2008). "Can children with autism recover? if so, how?". Neuropsychol Rev 18 (4): 339–66. doi:10.1007/s11065-008-9075-9. PMID 19009353.
# ^ Pickett E, Pullara O, O'Grady J, Gordon B (2009). "Speech acquisition in older nonverbal individuals with autism: a review of features, methods, and prognosis". Cogn Behav Neurol 22 (1): 1–21. doi:10.1097/WNN.0b013e318190d185 (inactive 2009-04-21). PMID 19372766.
# ^ Seltzer MM, Shattuck P, Abbeduto L, Greenberg JS (2004). "Trajectory of development in adolescents and adults with autism". Ment Retard Dev Disabil Res Rev 10 (4): 234–47. doi:10.1002/mrdd.20038. PMID 15666341.
# ^ Tidmarsh L, Volkmar FR (2003). "Diagnosis and epidemiology of autism spectrum disorders". Can J Psychiatry 48 (8): 517–25. PMID 14574827. http://ww1.cpa-apc.org:8080/Publications/Archives/CJP/2003/september/tidmarsh.asp.
# ^ Billstedt E, Gillberg C, Gillberg C (2005). "Autism after adolescence: population-based 13- to 22-year follow-up study of 120 individuals with autism diagnosed in childhood". J Autism Dev Disord 35 (3): 351–60. doi:10.1007/s10803-005-3302-5. PMID 16119476.
# ^ Eaves LC, Ho HH (2008). "Young adult outcome of autism spectrum disorders". J Autism Dev Disord 38 (4): 739–47. doi:10.1007/s10803-007-0441-x. PMID 17764027.
# ^ a b c Fombonne E (2009). "Epidemiology of pervasive developmental disorders". Pediatr Res. doi:10.1203/PDR.0b013e31819e7203 (inactive 2009-03-27). PMID 19218885.
# ^ Wing L, Potter D (2002). "The epidemiology of autistic spectrum disorders: is the prevalence rising?". Ment Retard Dev Disabil Res Rev 8 (3): 151–61. doi:10.1002/mrdd.10029. PMID 12216059.
# ^ Gardener H, Spiegelman D, Buka SL (2009). "Prenatal risk factors for autism: comprehensive meta-analysis". Br J Psychiatry 195 (1): 7–14. doi:10.1192/bjp.bp.108.051672. PMID 19567888.
# ^ Bertoglio K, Hendren RL (2009). "New developments in autism". Psychiatr Clin North Am 32 (1): 1–14. doi:10.1016/j.psc.2008.10.004. PMID 19248913.
# ^ Folstein SE, Rosen-Sheidley B (2001). "Genetics of autism: complex aetiology for a heterogeneous disorder". Nat Rev Genet 2 (12): 943–55. doi:10.1038/35103559. PMID 11733747.
# ^ Zafeiriou DI, Ververi A, Vargiami E (2007). "Childhood autism and associated comorbidities". Brain Dev 29 (5): 257–72. doi:10.1016/j.braindev.2006.09.003. PMID 17084999.
# ^ Dawson M, Mottron L, Gernsbacher MA (2008). "Learning in autism". in Byrne JH (ed.-in-chief), Roediger HL III (vol. ed.). Learning and Memory: A Comprehensive Reference. 2. Academic Press. pp. 759–72. doi:10.1016/B978-012370509-9.00152-2. ISBN 0-12-370504-5.
# ^ Chakrabarti S, Fombonne E (2001). "Pervasive developmental disorders in preschool children". JAMA 285 (24): 3093–9. doi:10.1001/jama.285.24.3093. PMID 11427137. http://jama.ama-assn.org/cgi/content/full/285/24/3093.
# ^ White SW, Oswald D, Ollendick T, Scahill L (2009). "Anxiety in children and adolescents with autism spectrum disorders". Clin Psychol Rev 29 (3): 216–29. doi:10.1016/j.cpr.2009.01.003. PMID 19223098.
# ^ Levisohn PM (2007). "The autism–epilepsy connection". Epilepsia 48 (Suppl 9): 33–5. PMID 18047599.
# ^ Ozgen HM, Hop JW, Hox JJ, Beemer FA, van Engeland H (2008). "Minor physical anomalies in autism: a meta-analysis". Mol Psychiatry. doi:10.1038/mp.2008.75. PMID 18626481.
# ^ Steyaert JG, De La Marche W (2008). "What's new in autism?". Eur J Pediatr 167 (10): 1091–101. doi:10.1007/s00431-008-0764-4. PMID 18597114.
# ^ Wing L (1997). "The history of ideas on autism: legends, myths and reality". Autism 1 (1): 13–23. doi:10.1177/1362361397011004.
# ^ Miles M (2005). "Martin Luther and childhood disability in 16th century Germany: what did he write? what did he say?". Independent Living Institute. http://www.independentliving.org/docs7/miles2005b.html. Retrieved on 2008-12-23.
# ^ Houston R, Frith U (2000). Autism in History: The Case of Hugh Blair of Borgue. Blackwell. ISBN 0-631-22089-5.
# ^ a b c Wolff S (2004). "The history of autism". Eur Child Adolesc Psychiatry 13 (4): 201–8. doi:10.1007/s00787-004-0363-5. PMID 15365889.
# ^ Kuhn R; tr. Cahn CH (2004). "Eugen Bleuler's concepts of psychopathology". Hist Psychiatry 15 (3): 361–6. doi:10.1177/0957154X04044603. PMID 15386868. The quote is a translation of Bleuler's 1910 original.
# ^ Asperger H (1938). "Das psychisch abnormale Kind" (in German). Wien Klin Wochenschr 51: 1314–7.
# ^ Lyons V, Fitzgerald M (2007). "Asperger (1906–1980) and Kanner (1894–1981), the two pioneers of autism". J Autism Dev Disord 37 (10): 2022–3. doi:10.1007/s10803-007-0383-3. PMID 17922179. http://springerlink.com/content/m55051670u35066p/fulltext.html.
# ^ Fombonne E (2003). "Modern views of autism". Can J Psychiatry 48 (8): 503–5. PMID 14574825. http://ww1.cpa-apc.org:8080/Publications/Archives/CJP/2003/september/guesteditorial.asp.
# ^ Szatmari P, Jones MB (2007). "Genetic epidemiology of autism spectrum disorders". in Volkmar FR. Autism and Pervasive Developmental Disorders (2nd ed.). Cambridge University Press. pp. 157–78. ISBN 0521549574.
# ^ Chambres P, Auxiette C, Vansingle C, Gil S (2008). "Adult attitudes toward behaviors of a six-year-old boy with autism". J Autism Dev Disord 38 (7): 1320–7. doi:10.1007/s10803-007-0519-5. PMID 18297387.
# ^ Heidgerken AD, Geffken G, Modi A, Frakey L (2005). "A survey of autism knowledge in a health care setting". J Autism Dev Disord 35 (3): 323–30. doi:10.1007/s10803-005-3298-x. PMID 16119473.
# ^ Biever C (2007-06-30). "Web removes social barriers for those with autism". New Sci (2610).
# ^ Harmon A (2004-12-20). "How about not 'curing' us, some autistics are pleading". NY Times. http://www.nytimes.com/2004/12/20/health/20autism.html?_r=1. Retrieved on 2007-11-07.
