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Autistic Disorder: Diagnosis and Treatment • Diagnosis • Epidemiology • Etiology • Treatment Diagnosis of Autism • Triad of symptom clusters repeatedly found: – Impaired social interactions – Abnormal language development – Restricted and repetitive patterns of behaviour Social Impairments • marked impairments in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body posture, and gestures to regulate social interaction • failure to develop peer relationships appropriate to developmental level • a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people • lack of social or emotional reciprocity Language Impairments • delay in, or total lack of, the development of spoken language • in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others • stereotyped and repetitive use of language or idiosyncratic language • lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level Behavioural Impairments • encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus • apparently inflexible adherence to specific, nonfunctional routines or rituals • stereotyped and repetitive motor mannerisms • persistent preoccupation with parts of objects Diagnosis of Pervasive Developmental Disorders a) Autism -at least 6 symptoms, including 2 from social domain, 1 from communication area, and 1 from behavioural domain b) Asperger’s Disorder -at least 3 symptoms, including 2 from social realm and 1 from behavioural realm with “no clinically significant delays in language or cognitive development” c) Pervasive Developmental Disorder Not Otherwise Specified - ?? Other Pervasive Developmental Disorders • Rett’s Syndrome • Childhood Disintegrative Disorder • Diagnosis • Epidemiology • Etiology • Treatment Epidemiology of Autism • Autism : ~1/1,000 • All pervasive developmental disorders: ~1/300 • Male:female ratio: 4:1 (but approaches 1:1 as IQ drops) Increasing Prevalence of Autism Epidemiology of Autism • 2/3 to 3/4 have intellectual disabilities • 1/3 develop seizures, usually in adolescence • ~5% of patients have a known chromosomal abnormality • Diagnosis • Epidemiology • Etiology – Neurobiology – Genetics – Psychological Factors – Environmental factors • Treatment Neurobiology of Autism • Considered a “neurodevelopmental disorder” (i.e., caused by abnormal development of the brain) • Although many (perhaps most) brain regions have been implicated in autism, two findings stand out • Brain imaging – Brain size – Corpus callosum – Functional brain imaging “Physically, the 11 children were essentially normal. Five had relatively large heads.” -Kanner, 1943 Increased Brain Size In Autism • Several studies suggest patients have increased head circumference, and up to 20% of patients may have head circumferences above the 97th percentile • Autopsy studies also suggest that some patients have increased brain weight • Most MRI studies of the brain in autism in the past 10 years have reported increased brain volume in patients Increased Brain Size In Autism • While it appears that patients with autism have enlarged brain size, at least at some point in their life, the timing and persistence of this increase is uncertain • While some suggest that it persists into adulthood, others hypothesize that an initial period of rapid brain growth is followed by a period of slowed cerebral growth, so that by adolescence, brain size is no different from unaffected people Brain Size in Preschoolers with Autism Total Cerebral Volume (mL) 1500 1400 Patients Controls p<0.001 p<0.001 Courchesne, 2001 Sparks, 2001 1300 1200 1100 1000 Brain Size In Older Children, Adolescents, And Adults with Autism Total Cerebral Volume (mL) 1600 Controls 1500 1400 p=0.03 Patients p=0.03 p=0.1 p=0.4 1300 1200 1100 1000 Courchesne, 2001 Aylward, 2002 Hardan, 2001 Piven, 1996 • Brain imaging – Brain size – Corpus callosum – Functional brain imaging Corpus Callosum in Autism Author Result Filipek et al., 1992 no difference Egaas et al., 1995 (posterior third) Piven et al., 1997 (middle and posterior) Manes et al., 1999 (total and body) Hardan et al., 2000 (anterior; trend to total cc) Boger-Megiddo et al., 2003 Vidal et al., 2003 (total) (total, anterior, and posterior) Corpus Callosum in Autism: Shape Differences Vidal et al., 2003 Corpus Callosum and Cerebral Lateralization in Autism • Given its role in cerebral lateralization, the relative reduction of the size of the corpus callosum suggests aberrant lateralization of cerebral function in autism • Consistent with this, several studies have found increased rates of left- and mixed-handedness in autism as well as increased rates of right-hemisphere dominance for language • Two MRI studies (Herbert et al., 2002; Rojas et al., 2002) have reported reduced or reversed patters of asymmetry in language-related brain regions in patients with autism • Brain imaging – Brain size – Corpus callosum – Functional brain imaging fMRI of Facial Processing in Autism • Abnormalities of facial processing in autism have been consistently reported in clinical studies • In three studies of facial processing using fMRI, patients have not used brain regions typically involved in this task but rather have used regions more typically used for object recognition • Diagnosis • Epidemiology • Etiology – Neurobiology – Genetics – Psychological Factors – Environmental factors • Treatment Genetics of Autism • 5% of patients have gross cytogenetic abnormalities • Sibling recurrence rate is 2% to 5% • Heritability of autism is about 90% • “Unaffected” relatives have increased rates of social, language, and behavioural problems • Diagnosis • Epidemiology • Etiology – Neurobiology – Genetics – Psychological Factors – Environmental factors • Treatment Psychological Factors in Autism • Main deficit in autism is controversial • Predominant theory is that patients with autism lack a “theory of mind” – the ability to understand other people’s thought processes and to make inferences about the thoughts of others Comparison of Theory of Mind and Comparison Test Theory of Mind in Autism • In addition to performing more poorly on tests of Theory of Mind, subjects with autism also appear to activate brain regions thought to be involved in “mentalizing” less than controls (amygdala and prefrontal cortex) • Diagnosis • Epidemiology • Etiology – Neurobiology – Genetics – Psychological Factors – Environmental factors • Treatment Environmental Factors in Autism • No proven link between environmental factors and autism, although many suggested • Much recent attention on MMR vaccine, but large scale epidemiological studies suggest no relationship • Diagnosis • Epidemiology • Etiology • Treatment – medication – psychosocial Pharmacotherapy of Autism • There are no treatments for autism per se • Treatment is therefore aimed at reduction of behaviours which interfere with the individual’s daily functioning • Goal of medication should be to enhance other treatments (behaviour modification, education, speech therapy,…) Interfering Behaviours Commonly Seen in Autism • Aggression • Inattention and hyperactivity • Anxiety/Ritualistic behaviour • Sleep Disturbances • Sensory Hypersensitivity Treatment of Aggression in Autism • Aggresssion, to others, to self, and to property, is a common problem in autism • Commonly associated with frustration and so probably best viewed as a problem of impulse control Interfering Behaviours Commonly Seen in Autism • Aggression • Inattention and hyperactivity • Anxiety/Ritualistic behaviour • Sleep Disturbances • Sensory Hypersensitivity Inattention and Hyperactivity in Autism • Common comorbid condition for pervasive developmental disorders and mental retardation (10% to 20% of children with MR have ADHD) Interfering Behaviours Commonly Seen in Autism • Aggression • Inattention and hyperactivity • Anxiety/Ritualistic behaviour • Sleep Disturbances • Sensory Hypersensitivity Anxiety in Autism • Can present as: – repetitive and ritualistic behaviour – phobias – difficulty with unpredictability – social withdrawal • Can be associated with aggression Alternative Therapies in Autism • • • • • • B-vitamins Vitamin A Vitamin C DMG (dimethylglycine) DMSA Secretin • Essentially all are lacking solid evidence for effectiveness • Medications should NOT be viewed as a treatment for developmental disorders • They should be viewed as a treatment which can make other interventions (education, behaviour therapy, speech therapy, etc) more effective by reducing behaviours which interfere with these therapies Psychosocial Treatments in Autism • Social skills training • Occupational therapy • Speech therapy