Objective: Evaluation of intellectual disability and behavioral characteristics in autistic subjects using standardized psychological assessment tools
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Western Psychological Services • N/A
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Partek • N/A
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Assembled autistic cohort of 13 subjects (4-62 years, 9 males, 4 females) and control cohort of 14 subjects (4-64 years, 9 males, 5 females). Originally 38 brains were assigned (20 autistic, 18 control).
Note: Final cohort reduced to 27 brains after applying exclusion criteria
“The autistic cohort study consisted of 13 subjects (4–62 years of age), including 9 males (69%) and 4 females (31%), while the control cohort consisted of 14 subjects (4–64 years of age)”
Collected medical records of autistic subjects after their deaths, consisting of psychological, behavioral, neurological and psychiatric evaluation reports.
Note: Records obtained postmortem
“The source of our clinical data was the medical records of the autistic subjects, which consisted of psychological, behavioral, neurological and psychiatric evaluation reports. All of the records were obtained after the subjects' deaths.”
Administered ADI-R to each donor family as a standardized assessment tool to confirm autism diagnosis on a postmortem basis. Assessment based on four domains: (a) qualitative abnormalities in reciprocal social interaction; (b) qualitative abnormalities in verbal and nonverbal communication; (c) restricted, repetitive and stereotyped patterns of behavior; and (d) abnormality of development evident at or before 36 months.
Note: All 13 autistic subjects met ADI-R criteria for autism. Two cases were excluded based on ADI-R results: one diagnosed with atypical autism and one that did not meet ADI-R criteria.
“The Autism Diagnostic Interview-Revised (ADI-R) was administered to each donor family as a standardized assessment tool in order to confirm the diagnosis on a postmortem basis. Inclusion of the subject in this study was based on a summary of scores of four domains”
For subjects with available intellectual evaluation data, administered Wechsler Intelligence Scale for Children III and Woodcock-Johnson Tests of Achievement-Revised to assess intellectual disability.
Note: Eight of 13 autistic subjects were diagnosed with intellectual disability, usually in the range from mild to severe (61%)
“For some subjects, the intellectual evaluation was available and was based on the Wechsler Intelligence Scale for Children III and the Woodcock-Johnson Tests of Achievement-Revised”
Recorded psychiatric disorders, neurological symptoms, seizure history, and age of seizure onset for each subject. Documented behavioral characteristics including self-injurious behavior, aggression, hyperactivity, obsessive compulsive disorder, depression, and mania.
Note: Six of 13 autistic subjects had seizures (46%). Behavioral disorders noted: self-injurious behavior (6 cases, 46%), aggression (4 cases, 31%), hyperactivity (3 cases, 23%), obsessive compulsive disorder (2 cases, 12%), depression and mania (1 case each)
“Six of 13 autistic subjects had seizures (46%). Several forms of challenging behaviors and behavioral disorders were noted, including self-injurious behavior (six cases, 46%), aggression (four cases, 31%), hyperactivity (three cases, 23%)”
Applied exclusion criteria to reduce cohort from 38 to 27 brains. Excluded two autistic cases based on ADI-R results (one atypical autism, one not meeting criteria). Excluded five additional autistic cases: one due to severe postmortem autolytic changes, three due to severe global hypoxic encephalopathy related to mechanism of death, one due to multiple microinfarcts. Excluded four control brains due to severe postmortem autolysis.
Note: Exclusion criteria applied to ensure neuronal loss, changes of neuronal size and shape, and gliosis did not mask developmental alterations associated with autism
“Based on the results of the ADI-R, two cases were excluded, including one case diagnosed with atypical autism, and one that did not meet ADI-R criteria. Based on postmortem evaluation, five more autistic cases were excluded”
For three of the 13 autistic subjects, identified high-confidence copy number variations using quantiSNAP and Partek HMM computational algorithms. Results posted on ATP portal by The Center for Applied Genomics, Toronto.
Note: Copy number variations detected in three autistic subjects did not differ from commonly observed variations, except for loss of 25,505 kb within NPSR1 gene at 7p15-p14 detected in 22-year-old autistic male (B-6337)
“For three of the 13 autistic subjects, the list of high-confidence copy number variations identified both by quantiSNAP and Partek HMM computational algorithm was posted on the ATP portal”
13 autistic subjects and 14 control subjects. Originally 38 brains (20 autistic, 18 control) were assigned but reduced to 27 after applying clinical and neuropathological exclusion criteria.