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Differential Diagnosis in Psychosis and Autism

Abigail Donovan, MD Director, First Episode and Early Psychosis Program

Associate Director, Acute Psychiatry Service Massachusetts General Hospital Assistant Professor of Psychiatry

Harvard Medical School

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Disclosures

Neither I nor my spouse/partner has a relevant financial relationship with a commercial interest

to disclose.

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Historical Perspective

Bleuler used the term “autism” to describe a symptom of

schizophrenia

Kanner used the same term to

describe a childhood develop-mental

disorder

Autism was considered a

subset of childhood onset

schizophrenia

Kolvin & Rutter made the distinction

between psychosis with onset in early childhood (ASD) &

psychosis with onset in

adolescence (SCZ)

DSM-III formally

separated autism from

schizophrenia

Coming full

circle?

1911

1943

1950-1960s

1970s

1980

2017

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Multiple Levels of Overlap

• Brain pathology: – Structural and functional abnormalities in the

cerebellum, insular cortex, fusiform gyrus

• Genetics: shared deletions, mutations, CNVs – NRXN1, CNTNAP2, 22q11, 1q21, 15q13

• Environmental risks: – Advanced paternal age, maternal infection/immune

activation

• Pathogenesis: – Neurodevelopmental disorders- atypical brain

development around the time of symptom onset

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Symptom Overlap

• Social deficits – Both disorders have impaired social cognition,

including Theory of Mind1

• Cognitive deficits – Abstract reasoning, working memory, processing

speed, executive function2

• Language deficits – Decreased verbal communication/output3,

pragmatic language deficits

1. Lugnegard et al. Schiz Res 2013; 277-284. 2. Goldstein et al. Arch Clin Neuropsychology 2002; 461-475. 3. Fitzgerald Clinical Neuropsychiatry 2012; 171-176.

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Comorbidity

• Reports on prevalence are variable

• Patients with ASD:

– with psychosis: 3-16%1-4

– with schizophrenia: 0.6-3.4%5,6

• Patients with schizophrenia:

– with PDD NOS: 20-50%7-9

– with ASD: 0-11%7-9

1. Larsen Eur Child Adolesc Psychiatry 1997;181-90. 2. Wing Psychol Med 1981;115-29. 3. Wolff Psychol Med 1980;85-100. 4. Tsakanikos J Autism Dev Disord 2006;1123-9. 5. Volkmar Am J Psychiatry 1991;1705-7. 6. Mouridsen J Psychiatr Pract 2008;5-12. 7. Solomn Schizophrenia Research 2011;146-51. 8. Waris Eur Child Adolesc Psychiatry 2013;217-223. 9. Rapoport J Am Acad Child Adolesc Psychiatry 2009; 10-18.

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Psychosis

SCZ

ASD

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Is it really psychosis?

• Patients with ASD may report symptoms that sound psychotic, but really aren’t

– Auditory hallucinations

– Paranoia

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“Auditory Hallucinations”

ASD

• Hyperacusis

• May explain internal ambivalence

• May perceive own thoughts as a voice: “concrete externalization”1

• Frequently experienced as part of oneself

Psychosis

• Frequently derogatory

• Highly suggestive AH:

• Running commentary

• Two voices conversing

• Experienced as foreign to oneself, outside one’s head

• No insight- perceived as real

1. Dossetor DR Clin Child Psychol Psychiatry 2007; 537-548.

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“Paranoia”

ASD

• Children who have been bullied may be more apt to be suspicious of others

• Paranoia limited to social situations, esp with known perpetrators

• Not a delusional perception but a fear based in reality

Psychosis

• Unrelated to prior social experiences

• May involve vague or unknown perpetrators

• May involve bizarre plots

• Present throughout the day in a variety of contexts

• No insight

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Psychosis

SCZ

ASD

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Case

• 11 yo f diagnosed with ASD at age 6

• Started 5th grade at her public school with an IEP

• Experiencing profound academic stress

• Parents going through contentious divorce

• She developed AH of several voices mocking her, experienced as real, present 24/7

• Symptoms resolved with intensive treatment, risperidone and modified IEP, and she was able to return to school at prior level of functioning

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ASD with Psychosis

• Premorbid ASD - chronic social, cognitive and behavioral deficits

• Followed by later emergence of new psychotic symptoms – Brief reactive psychosis- stress induced psychosis

– Mood disorder with psychotic features

• Accompanied by functional impairment – Typically mild to moderate

– Always time limited

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ASD with Psychosis

• Stress-induced psychosis in ASD1

– “Micro-episodes” of psychosis: brief and transient

– Triggered by stress, resolve when stress is absent

• ASD patients are at 3x greater risk for having isolated psychotic symptoms2

• ASD patients display psychotic symptoms with stress or anxiety3

1. Tantam D et al. Br Med Bull 2009; 41-62. 2. Sullivan et al. J Amer Acad Child Adolesc Psychiatry 2013; 806-814. 3. Solomon et al. J Autism Dev Disord 2008; 1474-1484.

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Psychosis

SCZ

ASD

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Is it ASD or Schizophrenia?

Features of ASD

Impairment in non-verbal

communication

Lack emotional reciprocity

Stereotyped language

Features of Schizophrenia

Flat affect

Social withdrawal

Alogia

Cochran DM et al. Child Adolesc Psychiatric Clin N Am; 2013:609-627.

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How do you distinguish?

• Developmental history is critical

• ASD symptoms are present from an early age

– May become more prominent over time

• SCZ symptoms emerge after grossly normal development

– Followed by gradual, persistent functional decline

– Then emergence of positive symptoms

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Social Deficits

ASD

• Present from early childhood

• May be socially motivated, but clumsy

• May be verbal but inappropriate

Schizophrenia

• Develop after a period of normal functioning

• Lack of social motivation

• Withdrawal from friends and family

• Paucity of speech/content

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Case

• 24 yo male with ASD, limited social function, good academic function

• Just started first year of business school- developed difficulty with concentration and memory

• Withdrew from family and few friends • Developed PI (being followed by CIA) and AH • Calling police several times a day, eventually

hospitalized • Stabilized on olanzapine but continued to have

functional impairment and unable to return to school

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ASD with Schizophrenia

• Rare but real

• Premorbid ASD - chronic social, cognitive and behavioral deficits

• Followed later in development by further functional decline (social and cognitive)

• Then, emergence of new psychosis – True AH, paranoia, delusions, disorganization

– DSM 5: “prominent delusions or hallucinations must be present for one month”

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ASD with Schizophrenia

Key aspects of differential (with brief reactive psychosis):

• Onset may be influenced by stress, but symptoms are not solely stress dependent

• Functional impairment

– Additional impairment from baseline- typically severe

– Chronic- patients do not return to baseline

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Conclusion

• Substantial symptom overlap and true comorbidity between ASD, psychosis and schizophrenia

• Accurate diagnosis can be made by:

– Careful, detailed symptom history

– Developmental history- timing of onset of symptoms

– Functional assessment over time

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Thank you!