Gary Stobbe MD Clinical Associate Professor University of Washington Depts Of Neurology amp Psychiatry April 7 2017 Jameses Guys Conflicts of Interest Dr Stobbe has no conflicts of interest to disclose ID: 774702
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Slide1
Autism Into Adulthood:Striving for SuccessGary Stobbe, MDClinical Associate ProfessorUniversity of WashingtonDepts. Of Neurology & PsychiatryApril 7, 2017
“Jameses Guys”
Slide2Conflicts of Interest
Dr.
Stobbe
has no conflicts of interest to disclose
Slide3Objectives
Review ASD trajectories across the years of transition to adulthood
Discuss independent factors that influence adult outcomes in ASD
Define success as an adult with ASD and
identify barriers
to this success
Review key elements and strategies that can improve quality of life for adults with ASD and their families
Slide4Autism into Adulthood:
Background
“The Right Idea”
By F
orrest Sargent
Slide5DSM-5Autism Spectrum Disorders
Persistent Deficits in Social Communication and
Social Interaction
Restrictive/
Repetitive Patterns of Behaviors, Interests, or Activities
ASD
-Must be present in early childhood (age 8 or less)
-No sub-categories (with/without ID and/or language impairment)
Slide6- 50,000 individuals with ASD enter adulthood
i
n the US annually based on current CDC estimates
o
f 1 in 68 (Wang, 2014)
Slide7Adult ASD in Washington State
UW Medicine
A
dult
A
utism
C
linic
Opened
S
eptember 2012
Over 1000 unique patients seen since
opening
Over 1000 patient visits/year
ASD or related disorders
Representative sample
?
Slide8UW Medicine Adult Autism Clinic
Retrospective Chart review385 Individual patients selected randomly from a list of all patients in the clinic since its opening in August 2012 through June 2014Demographic dataPrimary and secondary diagnosis historyService utilizationMedication use at presentationEducation levelWork status (full, part, paid, volunteer)Living condition status (supported vs independent vs homeless)Communication ability (verbal, not-verbal, uses a device)
Tolson
, 2015
Slide9RESULTS: Clinical Care needs
CharacteristicPercentageASD diagnosis50%ASD with a genetic or other condition18%Seeking a diagnosis25%
CharacteristicPercentageWell-established care93%
RESULTS: Diagnostic Needs
Slide10Results: Seekers vs Non-Seekers
SeekingASDp valueAge in years29 (18.5)*22 (6)*<0.001In person visits 1.6 (1.8)*2.3 (2.3)*<0.01Phone visits 0 (0)*0 (1.9)*<0.001Independent Employment 36%13%<0.001Living Independently 41%8%<0.001Well established care 85%95%=0.002Behavioral Medication 46%75%<0.001Antispychotic 7% 38% <0.001Antidepressant 36% 52%<0.01
*Median (interquartile range)
Slide11Autism into Adulthood:
Outcome Trajectories
Andrew Mito
mitosanpaints.com
Slide12Outcome Trajectories
3-25% optimal outcome (Helt, 2008)Roughly 60% make progress but continue to require some types of supportApproximately 20% remain severely impacted requiring 24/7 support (Seltzer, 2004)
Slide13ASD Progress into Adulthood
Slide14Warning! Autistic Regression in Adulthood
Majority show
inprovement
in core symptoms and maladaptive behaviors
Warning – 10% worsen maladaptive behaviors, 15-25% worsen autistic
symptoms (Shattuck, 2007;
Howlin
, 2016)
Predictors of regression – undetermined
Permanency of regression - undetermined
Slide15Autism intoAdulthood:FactorsImpactingTrajectory
“Trash Guys”
by Wil
Kerner
w
ilspapercutouts.com
Slide16Factors Impacting Outcome
Intrinsic
Cognitive ability
Severity of core autistic deficits – communication, social, restricted interests (motivation
)
Medical health
(epilepsy, sleep disorders, “
syndromic
”)
Mental health
(depression, anxiety
)
Specific disruptive behaviors (hygiene, aggression, etc.)
Extrinsic
S
ocioeconomic
A
ccess to services/early intervention
“Case management”
(Myers, 2015)
Slide17Biology of Autism
80%
non-syndromic
– normal
gross motor
, minimal
dysmorphic
features, fewer neuro
co-morbidities
M:F ratio 5:1
More “high-functioning” outcomes
20%
syndromic
– often motor delay,
dymorphic
features, co-morbidity with intellectual disability/epilepsy
M:F ratio 1:1
Genetic (Fragile X, Down’s,
Rett’s
, etc.)
Acquired (premature birth, birth trauma, encephalitis, etc.)
Slide181999
2012
2009
2007
2013
2011
Collaborative Linkage Study of Autism
MIP (molecular inversion probe) Sequencing
Full Scale Exome Sequencing
Pilot
Exome Sequencing
Genome-Wide Associations
De Novo Copy Number Variations
2014
CHD8
gene
(Bernier, 2014)
The search for etiology…
The Search for Etiology
Slide192014
CHD8 gene
2014
2014
ADNP
gene
DYRK1A gene
2015
Rare, inherited mutations
16p11.2 CNV
POGZ gene
2014-2015
WAC
gene
2016
2016
1q21.1
CNV
2015
The search for etiology…
The Search for Etiology
Slide20From State &
Sestan
, 2012
Slide21ASD &
Genetic Landscape
Unknown
16p11.2
Syndromic
and other monogenic disorders
Fragile X (FMR1), Rett (MeCP2)…
Private and Recurrent CNVs15q11-13, 22q11…
De novo LGD (likely gene disrupting) mutationsDYRK1A, ADNP…
CHD8
Rare, inherited gene mutations
RIMS1, CUL7…
Courtesy of R. Bernier
Slide22Environmental Risk Factors
Toxic exposures during pregnancy:
Valproic
acid
SSRIs
Prenatal rubella
Misoprostol (ulcer treatment)
Chlorpyrifos
(insecticide)
Pollution (proximity to freeways,
amt
of traffic)
Agricultural
pesticides
Ultrasound
- link
to ASD
severity (Webb, 2016)
Increased paternal age
Interaction between exposures and genetic
background
Slide23Gender differences
Non-social traits less severe in idiopathic females
Less eccentric and peculiar interests (
Selzer
, 2004)
“My Little Pony vs. urinals”
Better social-communication abilities
social interest but poor social cognition
Heightened levels of anxiety
Better self-awareness
Social environment more
challenging
But, be aware of “
syndromic
” ASD
Slide24Adult Autism –
Neurologic and MedicalComorbidities
“Love in Action”
By Guy
McDonell
Slide25Epilepsy in Autism
22% of adults with autism (Bolton, 2011)
All seizure types (GTC and CPS most common)
Well-controlled in over half
Higher risk of co-morbidity with intellectual disability
EEG abnormalities common
44% focal, 12% generalized, 42% mixed (
Ekinci
, 2010)
Onset around time of
Dx
– increased likelihood of
syndromic
autism
AED choice influenced by ASD behaviors
Lamotrigine
,
valproic
acid,
oxcarbazepine
Slide26Epilepsy in Autism – Age of Onset
Bolton, 2011
Slide27Sleep Dysfunction in Autism
No studies in ASD adults
44-83% of ASD children with sleep dysfunction (
Miano
, 2010) – greater than other Dev. Disorders
Primarily insomnia (initiation, awakenings)
Other less common include nightmares, sleep apnea, sleep-related movement disorders, & circadian rhythm disorders
Treatment with melatonin improved total sleep time and daytime behavioral difficulties (Wright, 2010)
Slide28Motor Tic Disorders
Complex motor tics more common in ASD
Onset typically in childhood or adolescence but can also occur in adult years
Difficult to differentiate from stereotypies
Tics more likely worsened by stress/anxiety
Partial seizures also in differential
Slide29Health in ASD
Loss of adaptive skills after 30sPremature deathIncreased medical conditionsLower QoL than age matched DD ages 19-79 (interpret with caution – preliminary, small numbers, cohort effect?)
Geurtz
, IMFAR, 2014
Slide30Adult Autism –
Psychiatric Comorbidities
Slide31Mental Health in ASD
Inpatient hospitalization
tripled between 1999-2009 for adolescents with ASD (
Nayfack
, 2014)
Suicidal ideation
Suicide attempts 4-fold increase in ASD (
Croen
, 2014)
Depression and anxiety
increased in ASD vs. DD/non-ASD (
Gotham,
2014
)
Slide32Psychiatric Comorbidities in Autism
ADHDDepressive DisordersAnxiety DisordersBipolar DisorderObsessive-Compulsive DisorderPsychotic DisordersCatatonia
See Appendix Slides for details
Slide33General Considerations
ASD is a neurodevelopmental “substrate” enhancing likelihood of co-
occuring
mental health conditions
Atypical manifestation in ASD population
Self-injury, irritability, aggression, bizarre movements and behaviors
Overlap of ASD features and symptoms of other mental health disorders often delays recognition and treatment (
Bakken
, 2010)
Reverse of what is seen in childhood (mental health diagnoses “hiding” recognition of ASD)
Slide34Adult Autism –
Psychopharmacology
“Party Boy”
By Wil
Kerner
Wilspapercutouts.com
Slide35Psychopharmacology in Adult ASD
Systematic evidence of benefit lacking (Dove, 2012)
No FDA approved med for adults
aripiprazole
and
risperidone
approved in children
Atypical antipsychotics, SSRIs, and stimulants most commonly used (
Esbensen
, 2009)
80% of all adults on
psychotropics
Steady increase in use of
psychopharm
agents with age
Once on psychotropic, likely to stay on
Poly-pharmacy common (
Tsiouris
, 2013)
mean – 1.51 meds in adults with
ID/autism
Slide36Most Challenging Aspects of Pharmacotherapy
Identifying Target Symptoms
Narrowing target symptoms/expectations
Multiple symptom clusters occurring simultaneously
Measuring Response
High level of variability of response to medications
L
ess benefit and more adverse effects
Subjective (often from observer) assessment of benefit
Adverse Events
I
diosyncratic responses
are more common
Sensitivity of patients with ASD to side effects of
medications
Slide37Commonly Used Meds in Adult Autism
ADHD Meds
Stimulants – long acting preferred
Non-stimulants (amantadine, alpha-agonists)
Antidepressants
SSRIs most common
Antipsychotics
Risperidone and aripiprazole most studied (
Zuddas
, 2011)
Anxiolytics
Benzodiazepines (more commonly “prn” use; lorazepam for catatonia)
Beta-blockers
Mood stabilizers
AEDs (lamotrigine, oxcarbazepine) and lithium
Slide38Crisis Intervention
UWMAAC (Aug 2014 - July 2016) 17 male, 8 female (25.3 yo)32 events – 6 hospitalizations, 19 ED visits (including 3 SI), 7 police callsDx – ASD (81%), ID (52%), genetic (24%), CP (14%), anxiety (48%), depression (14%), psychosis (14%), OCD (10%), ADHD (10%), bipolar (5%), epilepsy (5%)Living – 64% living at home with parents Lessons Community mental health resources lackingDDA involvement early is essentialParents overwhelmed
Freed, 2016, personal communication
Slide39Adult ASD:
Defining Success
“Metal Sky”
By F
orrest Sargent
Slide40The ConnectionAmongOutcomes
Quality of life is interconnected with all aspects of health and community involvement
Roux et al, 2015
Slide41What is success as an adult with ASD?
Ultimately defined by happiness?
Trajectory influences definition
Community access
Health and wellness
Making friends
Education and employment
Slide42Defining Success
Parents in “Next Steps” class – asked “What are your long term goals for your son/daughter?”
Community access –
Live in a group home with a caretaker to oversee him and insure he is OK”
“Live independently and have positive social relationships
”
“Find permanent housing and learn to manage
money”
Health and wellness -
“Safe and well cared for, eating healthy food and functioning as independently as possible”
Slide43Defining Success(cont.)
Making Friends -
“More face-to-face in person rather than online over the computer”
“Make friends who are understanding and avoid people trying to take advantage of him”
“Possible relationship with a female partner”
Education and employment -
“A job that paid enough for him to live on with health care”
“A meaningful job challenging to him while he is able to support himself financially”
“Continue opportunities for learning”
Slide44Barriers to Success
Lack of adult providersPhysicians serving adults with ASD, only 20% received training during residency (Bruder, 2012)Parents view PCPs as unable to assist vast majority of autism-related problems (Carbone, 2013)Lack of transition tools for pediatric providersParents/caregivers delay; anxiety about future planningLack of identifying person responsible for transition Financial barriers
Transitions Clinical Report Authoring Group, 2011
Slide45Transition planning
Only 58% of youth with autism have a transition planRace disparity – 60% transition planning for whites, only 46% for blacksAs a result, over one-third of adults in their 20’s “disconnect” and do not participate in school or get a job (compared to 8% for learning disabled, emotional disturbance, or speech/language impairment)
Roux et al, 2015
Slide46Successful Transition – Importance of “Case Management”
National Longitudinal Transition
Study (NLTS-2)Household income and “case manager” at wave 1 influenced community participation as an adult (defined as ANY participation outside of school in prior 12 months)“case manager” at wave 1 influenced social participation as an adult (defined as ANY get together, social event, or phone call to friend in prior 12 months)
CP - “has youth participated in community activities in the last 12 months”SP – “get togethers, invitations, or phone calls in the last 12 months”
Myers, 2015
Slide47ASD Employment
Employment rates 4.1% - 11.8% regardless of ID (Taylor &
Selzer
, 2011)
Lower rates compared to other DDs (Shattuck, 2012)
Decline in employment status over time
Unemployment and under-employment
Taylor study (2014) - Greater vocational independence relates to -
subsequent reduction in autism symptoms
Reduced maladaptive behaviors
I
ncrease in ADLs
The reverse does
not
hold true – autism severity does
not
correlate with having a job
Conclusion - The job
is
the treatment!
Slide48ASD Employment
Factors influencing successful employment (Hedley, 2016)
Older age
Post-secondary education
Absence of co-morbidity
Receipt of support
To disclose or not disclose?
Disclosing – 3X more likely to be employed (
Ohl
, 2017)
Economic impact
Greater upfront cost in ASD vs other DD
Support increases # of weeks employed
(
Mavranezouli
,
2014
)
Slide492016 National Autism Indicators Report – Vocational Rehabilitation
60% leave VR with employment (> 90 days)
Admin/office job most common
Median weekly earnings - $160
Arizona
5
%
of VR users with ASD diagnosis
(11
th
nationally,
avg
3%)
73% of VR users enter during secondary school (1
st
nationally
)
Only 3
%
of VR users received job placement services
(
45
th
nationally
)
51
%
of VR users left with employment
(
42
nd
nationally)
The gap between hourly wages for workers with autism exiting VR and all workers was $8.21 ($8.25 vs $16.46)
Slide50Hyperfocused vs. Preferred Interests – when is it a good thing?
“special interest areas” Sciences, history & culture, animals, information and mechanical systems, belief systems, machines and technology Improves joint attention, social interaction, and anxiety 62% of adults feel focusing on preferred interests has helped not hindered success (majority of these individuals were high functioning and diagnosed as an adult)Only 10% felt their teachers were supportive of their preferred interests
Koenig, 2017
Slide51“Rock Alone”
By Forrest Sargent
“Not everything that steps out of line, and thus ‘abnormal,’must necessarily be ‘inferior.” - Quote of Hans Asperger, 1938 (from NeuroTribes by Steve Silberman)
Adult ASD –
Hope for Welcoming
Inclusion
Slide52Striving for a Meaningful Life
How can we improve opportunities for community access?
How do we creating a more welcoming community?
Slide53Slide54Thoughtfully Serving Across the Whole Spectrum
Slide55Slide56Thanks!
Contact
at:gastobbe@uw.edu
“Dumpling”
By F
orrest Sargent
Slide57References
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TL,
Helverschou
SB,
Eilertsen
DE, et al. Psychiatric disorders in adolescents and adults with autism and intellectual disability; a representative study in one county in Norway.
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I, Hutton J, et al. Features and correlates of epilepsy in autism.
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Boada
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Merchan
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McPheeters
ML, et al. Medications for adolescents and young adults with autism spectrum disorders: a systematic review.
Pediatrics
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Aman
AR,
Isik
U, et al. EEG abnormalities and epilepsy in autistic spectrum disorders: clinical and familial correlates.
Epilepsy
Behav
, 2010, 17: 178-82.
Esbensen
AJ,
G
reenberg JS, Seltzer MM, et al. A longitudinal investigation of psychoactive and physical
medicaltion
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Fink M & Taylor MA.
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g
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Slide58References (cont.)
Han S, Tai C, Jones C, et al. Enhancement of inhibitory neurotransmission by GABA-A receptors having
α
-2,3-subunits ameliorates behavioral deficits in a mouse model of autism.
Neuron
, 2014, 81(6): 1282-89.
Hardan
AY, Fung LK,
Libove
RA, et al. A randomized controlled pilot trial of oral N-
acetylcysteine
in children with autism.
Biol
Psych
, 2012, 71(11): 956-61
.
Hedley D,
Uljarevic
M, Cameron L, et al. Employment
programmes
and interventions targeting adults with autism spectrum disorder: a systematic review of the literature.
Autism
, 2016, DOI: 10.1177/1362361316661855
.
Helt
M, Kelly E,
Kinsbourne
N, et al. Can children with autism recover? If so, how?
Neuropsychology Review
, 2008, 18:339-66
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Henry
CA,
Steingard
R, Venter J, et al. Treatment outcome and outcome associations in children with pervasive developmental disorders treated with selective serotonin reuptake inhibitors: a chart review.
J Child
Adolesc
Psychopharmacol
, 2006, 16 (1-2): 187-95
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Howlin
P, Moss P. Adults with autism spectrum disorders.
Can J Psychiatry
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Howlin
P, Moss P. The association between cognitive ability and psychiatric problems in adults with ASD.
International Meeting for Autism Research,
2016 Annual Meeting, Baltimore, MD.
Hutton J, Goode S, Murphy M, et al. New-onset psychiatric disorders in individuals with autism.
Autism
, 2008, 12(4): 373-90.
Johnston K,
Dittner
A,
Bramham
J, et al. Attention deficit hyperactivity disorder symptoms in
adults
with autism spectrum disorders.
Autism Res
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.
Joshi G,
Biederman
J, Petty C, et al. Examining the comorbidity of bipolar disorder and autism spectrum disorders: a large controlled analysis of phenotypic and familial correlates in a referred population of youth with bipolar I disorder with and without autism spectrum disorders.
J
Clin
Psychiatry
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.
Koenig, KP & Williams, LH. Characterization and utilization of preferred interests: a survey of adults on the autism spectrum.
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Lugnegard
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I,
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O, Cheema N, et al. The cost-effectiveness of supported employment for adults with autism in the United Kingdom.
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S,
Bruni
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M, et al. Sleep in children with autism spectrum disorder: a questionnaire and
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Slide59References (cont.)
Myers E, Kobayashi A,
Stobbe
G, et al. Longitudinal measures of community and social participation in young adults with autism.
International Meeting for Autism Research
, poster, Toronto, 2012
.
Ohl
A,
Sheff
G, Little S, et al. Predictors of employment status among adults with autism spectrum disorder.
Work
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doi
: 10.3233/WOR-172492
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Rossignol
DA, Frye RE. Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis.
Mol
Psychiatry
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.
Roux, Anne M.,
Rast
, Jessica E., Anderson, K.A., and Shattuck, Paul T.
National Autism Indicators Report: Vocational Rehabilitation
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Russell AJ,
Mataix
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Seltzer MM, Shattuck P,
Abbeduto
L, et al. Trajectory of development in adolescents and adults with autism.
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Y, Dies KA, Holm IA, et al. Clinical genetic testing for patients with autism spectrum disorders.
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Sestan
N. The emerging biology of autism spectrum disorders.
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Slide60References (cont.)
Stobbe
G, Liu Y, Wu R, et al. Diagnostic yield of array comparative genomic hybridization in adults with autism spectrum disorders.
Genetics in Med
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JA, Kim SY, Brown WT, et al. Association of aggressive
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1 in 68: what do autism’s rising numbers
nean
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://
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Webb S, Garrison M, Bernier R, et al. Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound.
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Slide61Appendix Slides
Slide62ADHD
Can be present from early age
36.7% of ASD adults meet ADHD criteria (Johnston, 2012)
Neuropsych
shows similar deficits in selected attention, except - ADHD fast and inaccurate on attentional switching, while ASD is slower in response (reduced processing speed
)
Is inattention/hyperactivity due to ASD core deficit or ADHD?
Slide63Depression and Anxiety Disorders
Anxiety
Generalized and social anxieties most common (
Caamano
, 2013)
More common in higher functioning (increased self-awareness?)
Can manifest as increased motor function, aggression, sleep disturbance, obsessive behaviors
Further worsens social communication deficit
Depression vs. lack of motivation from ASD?
Slide64Bipolar Disorder
When do aggressive/
dysregulated
behaviors warrant an additional comorbid diagnosis in ASD?
Variable data regarding comorbidity of ASD and Bipolar
<1% of ASD
dx’ed
with bipolar by age 21 (Hutton, 2008)
30%
of
Bipolar 1 in childhood meet ASD criteria (Joshi, 2013
)
Differential
Oppositional Defiant
D
isorder
Intermittant
Explosive
D
isorder
Disruptive Mood
D
ysregulation Disorder
Slide65Obsessive-Compulsive Disorder
Overlap between OCD behaviors and ASD stereotypies/repetitive behaviors & restricted interested
Symptoms of OCD present in up to 67% of children with high-functioning ASD (
Caamano
, 2013)
25% of high-functioning adults meet ICD-10 criteria for OCD (Russell, 2005)
Slide66Psychosis in Adult ASD
Studies show psychosis in autism ranging 4.4% – 18% (Cooper, 2007;
Tsiouris
, 2011
)
Relation of ASD and schizophrenia remains controversial
Autism originally categorized as “childhood schizophrenia”
Psychosis more often mood-related?
Genetic overlap
Specific
microdeletions
/duplications (16p11.2, 22q11 –
velocardiofacial
syndrome –
DiGeorge
)
Slide67Catatonia in ASD
Cluster of abnormalities in speech, movement, and behavior
Elevated to a modifier in DSM-5
Estimated as high as 12-18%
Most commonly seen in mood disorders (Fink, 2003)
Emerges in teens; often gradual onset
Differential in situations of regression and loss of function
Diagnosis complicated by overlap with ASD features
Stereotypies, echolalia,
mutism
Effective treatments enhance GABA function
Benzodiazepines
ECT
Behavioral intervention
Slide68