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Psychiatric Comorbidity in Children, Adolescents, and Adults with Autism
Janet Lainhart, MD Professor-Department of Psychiatry Faculty Member – Waisman Center, Laboratory for Brain Imaging & Behavior Laboratory University of Wisconsin-Madison
The Problem: Striking Manifestations across the Lifespan, Ability and Disability, Cause Unknown
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Challenge to Neuroscience
Autism: the fastest growing developmental disability. There are no biological markers of autism. There is no way to prevent the disorder or complications of the disorder. There are no specific treatments based on the underlying neurobiology of the disorder because the neural basis of autism and its complications is unknown.
The Clinical Problem Identification of infants at risk for autism and young children early in the course of the disorder is important. Providing early intensive intervention is important.
*But it is also important to understand the neural basis of autism and its complications in older children, adolescents, and adults with the disorder. --the majority are currently destined to live with significant lifelong impairment. --1/3rd may worsen over time rather than remain stable or improve. Science, June 2005
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The Clinical problem There is substantial evidence that autism is a disorder of brain connectivity.
.
Science, June 2005
The Clinical Problem We and others have found widespread but not uniformly diffuse microstructural abnormalities in white matter. Abnormalities of cortical and subcortical gray matter are also observed..
Neural networks involved in social communication and social interaction and repetitive behaviors appear to be involved.
Brain networks involved in attention, motor activity, emotional regulation and control, and compulsive behaviors may also be or become involved.
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onset:Tantrums 70 60 50
Cumulative Percent
40
Group
30
Autism
20
n=46 10
Language-Impaired
0
n=9
> 97
6 -9 61 t on m
t on m
hs
hs
hs
s
s th on m
0 -6 37
t on m
th on m
6 -3 13
12 0-
Age Severe Tantrums Started
Cumulative age at onset: Unsettled sleep pattern 70
60
50
Cumulative Percent
40
Group 30
Autism n=46
20 Language-Impaired 10
n=16 > s th
th on
s th
th on m
m
on m
6 -9
0 -6
97
61
37
on
th on m
m
6 -3
12
13
0-
s
s
s
Age Atypical Sleep Patterns Started
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Cumulative age at onset: Atypical eating patterns 80 70 60 50
Cumulative Percent
40
Group 30 Autism 20
n=50
10
Language-Impaired
0
n=6
6 -9 61
0 -6 37
t on m
t on m
t on m
th on m
6 -3 13
12 0-
hs
hs
hs
s
Age Atypical Eating Pattern Started
Cumulative age at onset: Self Injurious behavior 40
30
Cumulative Percent
20
Group Autism 10
n=20 Language-Impaired n=5
0 61
37
13
1 0-
96 m
m
t on
t on
t on
th on
m
m
60
36
2
hs
hs
hs
s
Age Self-Injurious Behavior Started
5
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Cumulative age at onset: Aggression
Cumulative Percent
40
30
20
Group Autism
10
n=24 Language-Impaired
0
n=8
> 97 on th s
s th on m
s th on m
m
6 -9 61
0 -6 37
s th on m
s th on m
6 -3 13
12 0-
Age Aggressive Behavior Started
Autistic children have more abnormal behaviors 40
30
20
Group
Percent
10
Non-Autism Control 0
Autism s or vi ha be al ic s or yp vi at 5 ha be al ic s or yp vi at 4 ha be al ic s or yp vi at 3 ha be al ic or yp vi at ha 2 be al ic or yp vi at ha 1 be al ic yp at
no
ng si is M
a at D
Total Number of Atypical Behaviors
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What is observed Pushing Hitting
Specific Behaviors Underlying Deficits
From: Behavioral Issues In Autism Eds. Schopler & Mesibov 1994. Plenum Press, NY
Causes of emotional and behavioral problems in autism - 1 Particularly impairing core features of the disorders difficulty communicating with and understanding others; social impairment; repetitive behaviors
Cognitive impairments deficits in complex information processing; theory of mind deficits; executive dysfunction; deficits in central coherence; specific learning disabilities
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How to diagnose co-morbid psychiatric disorders in autistic individuals 1. Understand the core and associated features of autism well, and how their manifestation change over the lifespan. 2. Understand the other co-morbid conditions well. 3. Understand the patient’s “best baseline”, and how he/she has changed over time. 4. Get information from an informant who has known the patient well for a long time.
Causes of New or Worsened Emotional and/or Behavioral Problems in Autism - 2 MEDICAL DISORDERS seizures; other acute and chronic illnesses
PSYCHIATRIC DISORDERS depression; anxiety; attention deficit; hyperactivity; bipolar disorder; obsessivecompulsive disorder; psychotic disorders
DIMENSIONAL TRAITS (at baseline: IQ etc.) LEARNED BEHAVIORS LIFE EXPERIENCES related to autism and other life experiences
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How common are other psychiatric conditions in individuals with ASD? N=109 children with autism (community
ascertained; Boston and Utah) 5-17 years (mean 9.2, s.d. 2.7), mostly males all with at least some language Full Scale IQs 42-141 (mean 82.5, s.d. 23.4) Parent Interview, present and lifetime disorders, by a clinician Impairment above and beyond core features of autism
Lifetime Prevalence of DSM-IV Disorders in the Boston/Utah Sample • Major depressive disorder 10.1% (13.8%) • Depression, NOS • Bipolar I Disorder • Bipolar II Disorder • Schizophrenia
2.8% 1.9% 0.9% 0 (Leyfer et al., JADD, 2006)
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Lifetime Prevalence of DSM-IV Disorders in the Boston/Utah Sample • • • • •
Specific phobic disorder 44.3% Social phobic disorder 7.5% Separation anxiety disorder 11.9% Generalized anxiety disorder 2.4% (n=41) Panic disorder 0
• Other Impairing Non-DSM Anxiety-like Syndromes – Transition-change Anxiety Syndrome – Focused Anxiety Syndrome (Leyfer et al., JADD, in press)
Lifetime Prevalence of DSM-IV Disorders in the Boston/Utah Sample • Obsessive compulsive disorder
37.2%
• Oppositional defiant disorder (n = 86) 7.0% (4.6%) • ADHD (n=85) – Inattentive – Combined – Hyperactive
30.5%
(24.7%)
20 % 7.0% 3.5% (Leyfer et al., JADD, in press)
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Number of Co-morbid Lifetime Psychiatric Disorders • Utah/Boston sample – Only 27.5% had no co-morbid disorder – 22% had 1 co-morbid disorder – 30% had 2 co-morbid disorders – 20.5% had 3 or more co-morbid disorders
Aggression Pushing Hitting
Specific Behaviors Underlying Deficits
Poor Social Judgment Unawareness of Feelings of Self & Others Sensory Misperceptions Impaired Cognitive Processing at baseline Major Depression New Psychosocial Stressor From: Behavioral Issues In Autism Eds. Schopler & Mesibov 1994. Plenum Press, NY
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Do Any Medication Treat Core Features of Autism-spectrum disorders? No medication “cures” autism or completely eliminates core features of autism. But a number of medications may have a mild to modest effect on some features of autism. Social deficits Communication deficits Stereotyped repetitive behaviors
What Associated features of ASD may be helped by medication and other interventions? Depression Anxiety ADD/ADHD Other psychiatric disorders Atypical behaviors that are not part of any co-morbid disorders
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Medications Commonly Used in Autism and Side Effects Stimulants: Attentional deficits, hyperactivity, (executive function defects) Serotonin-reuptake inhibitors: depression, anxiety, compulsive-like repetitive behaviors incl. repetitive question-asking, transition/change-related anxiety (social behaviors, communication). Atypical Neuroleptics: nonspecific serious behavioral problems – tantrums, aggression, self-injurious behavior.
What has gone awry in brain development in ASD? The power of brain imaging to understand autism spectrum disorder and its complications.
Source: Abidskov & Bigler (2010)
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Translational Research – hope for the future
Use variation in clinical manifestations to drive the discovery of the brain-basis of ASD and its complications. Use variations in brain structure, microstructure, and functional connectivity to drive the discovery of new gene variants and other factors involved. Understand defects in molecular pathways. Develop new biology-based treatments that target molecular abnormalities, aberrant brain structure & function, and the clinical and day-to-day problems they cause.
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WAISMAN CENTER Laboratory for Brain Imaging & Behavior UNIVERSITY OF WISCONSIN McLEAN Hospital / HARVARD UNIVERSITY Neurostatistics Lab UNIVERSITY OF UTAH Scientific Computing & Imaging Institute (SCI) and Eccles Institute of Human Genetics BRIGHAM YOUNG UNIVERSITY Neuropsychology, Brain Imaging & Behavior Lab
Our research is supported by: P30 HD003352-45 (Waisman Center Core Grant) from the Eunice Kennedy Shriver, National Institute of Child Health & Human Development (NICHD) NICHD T32 HD07489 Waisman Center Postdoctoral Training Award and The Hartwell Foundation fellowship (Brittany Travers) RO1 MH080826,RO1 MH084795, and KO8 MH092697 from the National Institute Of Mental Health
Thank you 30
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