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Table 1 LEAP summary of study protocol, by schedule

From: The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders

Level IA/OA Domain/task Time point Schedulea
A B C D
Clinical diagnosis
 Level 1 IA Autism Diagnostic Interview-Revised (ADI-R)c Base Pb Pb Pb Pb
 Level 1 IA Autism Diagnostic Observation Schedule (ADOS or ADOS-2)c Base & FU Sb Sb Sb Sb
Dimensional measures of ASD symptoms
 Level 2 OA Social Responsiveness Scale-2nd Edition (SRS-II)c Base & FU S & Pb S & P P P
 Level 2 OA Repetitive Behaviour Scale-Revised (RBS-R)c Base & FU Pb P P P
 Level 2 OA Short Sensory Profile (SSP)c Base & FU Pb P P P
 Level 2 OA Children’s Social Behaviour Questionnaire (CSBQ)c
Adults’ Social Behaviour Questionnaire (ASBQ)c
Base & FU
S & Pb
P
P
P
 Level 2 OA Autism Quotient (AQ), AQ-Adol, AQ-Childc Base & FU S & Pb P P P
 Level 2 OA Aberrant Behaviour Checklist FU Pb P P P
 Level 2 OA Adult Routines Inventory (ARI) or
Childhood Routines Inventory-Revised (CRI-R)
FU S

P

P

P
 Level 2 OA Sensory Experiences Questionnaire—short version (SEQ 3.0) FU Pb P P P
 Level 2 OA Global Score of Change FU Pb Pb Pb Pb
Comorbidities
 Level 2 OA Development and Well-Being Assessment (DAWBA)c Base S & Pb S & P P P
 Level 2 OA Strengths and Difficulties Questionnaire (SDQ)c Base & FU S & Pb S & P P P
 Level 2 OA DSM-5 ADHD rating scalec Base & FU S & Pb P P P
 Level 3 OA Beck Anxiety Inventory (BAI) Base & FU S S P P
 Level 3 OA Beck Depression Inventory (BDI) Base & FU S S P P
Quality of life/adaptive behaviour
 Level 1 IA Vineland Adaptive Behaviour Scale-2nd Ed (VABS-2) Base & FU Pb Pb P P
 Level 2 OA Columbia Impairment Scale (CIS)c Base & FU S & Pb S & P P P
  OA Child Health and Illness Profile (CHIP-CE) or
World Health Organisation Quality of Life (WHOQOL-BREF)
Base & FU
S
P
P
P
Medical or psychiatric history
 Level 1 OA NIH ACE Subject Medical History Questionnairec Base S’ or Pb P P P
 Level 2 OA NIH ACE Family History Form Base S’ or Pb P P P
 Level 2 OA Medical Psychiatric History Perinatal Environmental Risk Questionnairec FU Pb P P P
 Level 2 OA Brief Life Events Questionnaire, anchored in pregnancy FU Pb P P P
 Level 2 OA Children’s Sleep Habits Questionnaire or
Adult version (FU only)
Base & FU
S
S & P
P
P
 Level 2 IA Family Medical History Interview FU S’ or Pb P P P
Cognitive and psychological profile
 Level 1 IA WASI or WISC / WAIS (4 subtests)c Base S S S S
 Level 1 IA WASI or WISC / WAIS (2 subtests)c FU S S S S
 Level 1 IA BPVS and RCPM Base & FU S S S S
 Level 2 OA HRS-MAT online adaptive IQ test FU S S S S
 Level 2 IA Probabilistic reversal learningc Base & FU S S S S
 Level 2 IA Spatial working memoryc Base & FU S S S S
 Level 2 IA Un/Segmented block design taskc Base S S S S
 Level 2 IA Animated shapes narratives taskc Base & FU S S S S
 Level 3 OA Empathy Quotient Base & FU S P
 Level 3 OA Systemising Quotient Base & FU S P
 Level 3 OA Child EQ-SQ Base & FU P
 Level 3 OA Toronto Alexithymia Scale (TAS) Base & FU S S P P
 Level 3 IA Reading the Mind in the Eyes task (RMET) Base & FU S S S S
 Level 3 IA Karolinska Directed Emotional Faces (KDEF) FU S S S S
 Level 3 IA Sandbox continuous false belief task Base & FU S S S S
Cognitive tests assessed as part of the eye-tracking battery:
 Level 3 IA Event memory task FU S S S S
 Level 3 IA Emotion matching task Base S S S S
 Level 3 IA Films expression task FU S S S S
 Level 3 IA Visual processing task FU S S S S
 Level 3 IA Change detection task Base or FU S S S S
Eye-tracking
 Level 2 IA Natural scenes: static and dynamicc Base & FU S S S S
 Level 2 IA Gap overlapc Base & FU S S S S
 Level 2 IA Implicit false beliefc Base & FU S S S S
 Level 2 IA Pupillary light reflexc Base & FU S S S S
 Level 3 IA Biological motion Base & FU S S S S
Neuroimaging
 Level 1 IA Structural MRIc Base & FU S S S S
 Level 1 IA FLAIR sequence or localiser sequence MRIc Base & FU S S S S
 Level 2 IA Diffusion tensor imaging (DTI)c Base & FU S S S S
 Level 2 IA Resting-state fMRIc Base & FU S S S S
 Level 2 IA Social/non-social reward fMRIc Base & FU S S S S
 Level 2 IA Animated shapes theory of mind fMRIc Base & FU S S S -
 Level 2 IA Flanker Go/No-Go taskc Base & FU S S - -
 Level 3 IA Hariri emotion processing fMRI Base & FU S S S -
EEG
 Level 2 IA Resting statec Base & FU S S S S
 Level 2 IA Auditory oddball taskc Base & FU S S S S
 Level 2 IA Upright-inverted Faces (gamma)c Base & FU S S S S
 Level 2 IA Social / non-social videosc Base & FU S S S S
Biological samples
 Level 2 IA Blood sample (for genomic analyses)c Base or FU S S S S
 Level 2 IA Saliva (for genomic analyses where blood samples cannot be obtained and for epigenetics)c Base & FU S S S S
 Level 2 IA Urine (at home, for biochemical biomarkers)c Base or FU S S S S
 Level 2 IA Hair roots (to generate iPSCs)c Base or FU S S S S
 Level 2 IA Head circumferencec, weightc, heightc Base & FU S S S S
Assessment of clinical symptoms and cognition in both biological parents
 Level 3 OA Social Responsiveness Scale (SRS-2) Base Pb Pb Pb Pb
 Level 3 OA DSM-5 ADHD rating scale Base Pb Pb Pb Pb
 Level 3 OA Beck Anxiety Inventory (BAI) Base Pb Pb Pb Pb
 Level 3 OA Beck Depression Inventory (BDI) Base Pb Pb Pb Pb
 Level 3 OA Adult Routines Inventory (ARI) FU Pb P P P
 Level 2 OA HRS-MAT online adaptive IQ test FU Pb P P P
  1. Level 1 measures are defined as the minimal data set that must be acquired for any one participant to be included in the ‘head count’. Level 2 measures are (a) central to primary and/or secondary study objectives, (b) suitable for the entire targeted participant age and ability range, and (c) have previously shown ASD case-control differences or have been validated in ASD group(s). Level 3 measures are measures that are either (a) more exploratory (e.g. related to novel/emerging hypotheses), (b) less central to the primary or secondary study objectives, and/or (c) only suitable for some schedules. Within each assessment module, in the order of assessments, level 1 and level 2 assessments should be administered before level 3 assessments. Level 3 measures are omitted first in the event of, e.g. participant fatigue or if assessments take considerably longer than average
  2. ADHD attention-deficit hyperactivity disorder, ASD autism spectrum disorder, Base baseline assessment wave, DSM Diagnostic and Statistical Manual of Mental Disorders, fMRI functional magnetic resonance imaging, FU follow-up assessment wave, IA investigator administered assessment at the institute, iPSCs induced pluripotent stem cells, NIH ACE US National Institutes of Health Autism Centers of Excellence, OA online assessment, P reported by parent, S self-reported, S’ self-reported in the TD adult group in which parents are not enrolled in the study, sMRI structural magnetic resonance imaging, TD typical development
  3. aSchedule A: adults with ASD or TD (aged 18–30 years, with IQ greater than 70); schedule B: adolescents with ASD or TD (aged 12–17 years, with IQ greater than 75); schedule C: children with ASD or TD (aged 6–11 years, with IQ greater than 75); schedule D: adolescents and adults with mild ID (with or without ASD) (aged 12–30 years, with IQ 50–74); schedule E: monozygotic or dizygotic twins (schedule E is not shown but is based on schedules A–C)
  4. bASD groups only
  5. cCore measures that were submitted to the European Medicines Agency for QA