Index

AAV-PHP.B,

634

ABA

. See Applied behavior analysis

ABC-CT

. See Autism Biomarkers Consortium for Clinical Trials

Abdominal migraines,

52

Aberrant behavior,

238, 479, 627

Aberrant Behavior Checklist (ABC),

418

Aberrant Behavior Checklist Social Withdrawal scale,

39

Acetaminophen

overdose,

506

prenatal exposure,

189, 191

Acupuncture,

481

AD

. See Alzheimer’s disease

Adaptive functioning

comorbidities and,

137

ESDM approach to,

560

measurement of,

131–132, 133

Adeno-associated virus (AAV) gene therapy,

615–616, 619–620, 628, 630, 634–635

ADHD. See Attention-deficit/hyperactivity disorder

ADOS

. See Autism Diagnostic Observation Schedule

Advanced age

grandparental age,

196–197

maternal age,

195–198, 195

paternal age,

196–198, 197

Advancing Social-communication And Play (ASAP),

579

AFQ056 (mavoglurant),

270

Age

advanced age as risk factor,

195–198, 195, 197

of diagnosis,

102–103

Aggression

behavioral interventions,

570–572

experimental therapeutics for,

463–464, 497, 509, 510–511, 512

FXS and,

267, 269

neurobiology of,

357, 497

as pharmacotherapy adverse effect,

60, 426–427, 459–460

pharmacotherapy for,

60–61, 269, 271, 430, 433, 440–446, 442

psychiatric assessment of,

42, 45, 47, 52, 56

Agomelatine,

431

AIMS-2-Trials

. See Autism Innovated Medicine Studies (AIMS)-2-Trials

Air pollution,

192–193, 212, 213

Allergies,

52, 145, 146

α₂-Adrenergic antagonist

. See Mirtazapine

α-Adrenergic agonists,

58, 62–63, 456, 457–461. See also Clonidine; Guanfacine

Alzheimer’s disease (AD),

508

Amantadine,

58, 65, 463–464

American Academy of Child and Adolescent Psychiatry,

36

American Academy of Neurology,

80–81, 83, 265

American Academy of Pediatrics

genetic testing guidelines,

254–255, 265

screening guidelines,

35, 79, 80–81

American College of Medical Genetics and Genomics,

80–81, 254

American Indians,

102

AMPA receptors,

505–506, 507, 513, 520

Amphetamine,

62, 456, 457–458. See also Stimulants

Amygdala,

349–363

about,

349

appetite regulation and,

323

development,

353–355

functions,

352–353

impulsivity and,

324

oxytocin and,

486

structure and connectional system,

350–352, 350, 354–355, 357

vasopressin and,

496

volume of,

367–368

Amyloidosis,

632

Anatomic dysphoria,

92–93

Anatomy and imaging

. See Functional magnetic resonance imaging; Neuroanatomical findings; Neurodevelopment; Positron emission tomography

Anavex 2-73,

272, 313

Angelman syndrome

assessment plan,

55

genetic testing,

86, 310

neurotransmission function studies,

394

PET studies,

385

stem cell gene therapy studies,

621

Angiomyolipomas (AMLs),

280, 284

Animal models,

207–221

about

background and overview,

207–208

conclusion,

217–218

key points,

218

recommended reading,

218

experimental therapeutic studies,

485–486, 497, 519–520

gene therapy studies,

620–621, 630, 631, 634, 636–637

genetic model advancements,

209–212, 210

G×E interactions,

156, 157, 212–215, 213

neurobiology studies,

270, 352

neurogenetic pathways research,

257–258, 258

nonrodent models,

215–217, 240

oxidative stress studies,

513–515

rodent models,

210, 211. See also Mouse models; Rat models

toxicant studies,

239–241

validity and,

207–208, 211–212

Antecedent-behavior-consequence format,

557–558, 559–560, 589–590

Antibrain autoantibodies,

51

Antidepressants

prenatal exposure risks,

187–189, 188

TCAs,

417, 431–432. See also Clomipramine

Anti-DNase B,

55

Antihistamines,

312

Anti-inflammatory treatment,

58, 64, 532

Anti-influenza medication,

58, 65, 463–464

Antipsychotics,

439–453

about

background and overview,

439

conclusion,

450

future directions,

450

key points,

450

recommended reading,

451

adverse drug effects,

449–450

atypical antipsychotics,

58, 60–61, 440–448. See also Atypical antipsychotics

conventional antipsychotics,

439–440

for hyperactivity symptoms,

466

newer antipsychotics,

448

Antisense oligonucleotides (ASOs),

628, 630–631

Antistreptococcal antibodies,

55

Antistreptolysin O-antibody,

55

Anxiety and anxiety disorders

differential diagnosis,

54

digital biomarkers,

109, 112–113

ethical considerations for interventions,

110–111, 113–114

neurobiology of,

490, 497, 630

prevalence,

43, 268

psychiatric assessment of,

42

syndromic causes,

268, 320

treatment,

64, 270, 569–572, 630

trigger analysis,

114

Apgar score,

194

Appetite regulation,

319, 322–324

Applied behavior analysis (ABA)

about,

543, 544–545

challenges for,

590

comprehensive treatment models,

590–591

early intervention models,

545–551, 555–563. See also Early intensive behavioral interventions; Early Start Denver Model

for feeding difficulties,

146

focused intervention approaches,

589–590

past psychiatric history,

50

principles,

557, 589

Applied α-[11C]methyl-L tryptophan (AMT),

391–392, 393, 395

Arbaclofen,

519–527

about,

519, 520

animal models,

519–520

clinical pharmacology,

520–521

clinical trials,

522–525

neurophysiological and psychophysical studies,

521–522, 522

Aripiprazole,

269

Arrhythmias,

279

ASAP

. See Advancing Social-communication And Play

Ascorbic acid,

480

ASD

. See Autism spectrum disorder

Asenapine,

448

Asian and Asian Americans,

102

ASOs

. See Antisense oligonucleotides

Assessment and evaluation

. See Digital biomarkers; Epidemiology; Gender identity development; Neurological assessment; Pediatric Assessment; Psychiatric assessment; Race/ethnicity disparities; Sexual identity development

Asthma,

52

Astrocytes,

395

Atomoxetine,

455, 461–463

Attention-deficit/hyperactivity disorder

acetaminophen exposure and,

191

comorbidities,

36, 45–46, 81, 110, 256, 266–267, 269–270

differential diagnosis,

54

genetics and,

159, 298

hyperactivity,

431, 455–471. See also Hyperactivity

prevalence,

16, 45–46, 110

social-communicative impairment and,

137

treatment,

62–63, 65, 269–270, 431, 461, 508

Attractiveness,

497–498

Atypical antipsychotics

about,

58, 60–61, 440–448, 466

adverse effects,

449

aripiprazole,

61, 442, 446–447, 449

clozapine,

440–441, 449

indications,

269–270, 466

lurasidone,

61, 442, 447–448

olanzapine,

442, 444–445, 449

paliperidone,

448

quetiapine,

445, 449

risperidone,

61, 441–444, 442, 448, 449–450

ziprasidone,

445–446, 449

Atypical Rett syndrome,

307, 309, 310

Auditory stimulus, electrophysiological studies of,

226

Augmented reality technology,

118–119

Autigender,

93

Autism and Developmental Disabilities Monitoring (ADDM) Network,

18

Autism Biomarkers Consortium for Clinical Trials (ABC-CT),

648–650, 650

Autism Diagnostic Interview–Revised/Social Communication Questionnaire,

131, 650

Autism Diagnostic Observation Schedule (ADOS),

80, 131, 418, 650

Autism Innovated Medicine Studies (AIMS)-2-Trials,

646–647

Autism spectrum disorder (ASD)

advocacy

. See Patient advocacy groups

assessment and evaluation

. See Digital biomarkers; Epidemiology; Gender dysphoria; Gender identity development; Neurological assessment; Pediatric assessment; Psychiatric assessment; Race/ethnicity disparities; Sexual identity development

behavioral and educational interventions

. See Behavioral interventions; Developmental, Individual Difference, Relationship-Based Model; Early Start Denver Model; Language and communication interventions; Parent-implemented approaches; School-based interventions

causes

. See Animal models; Electrophysiological studies; Epigenomics; Genetics and genomics; Immune dysregulation; Risk factors; Syndromic ASD

consortiums

. See Consortiums

experimental treatments

. See Arbaclofen; Cannabis and cannabinoids; Complementary and integrative approaches; N-acetylcysteine studies; Oxytocin; Vasopressin

future treatment developments

. See Gene therapy; Patient advocacy groups; Transcranial magnetic stimulation

heritability of,

155–156, 156–157, 179, 289–290. See also Epigenomics; Genetics and genomics

historical context,

253–254, 260–261

imaging and anatomy

. See Functional magnetic resonance imaging; Neuroanatomical findings; Neurodevelopment; Positron emission tomography

neurodiversity and,

655–658, 656, 662–663

perspectives,

655–666, 656

psychiatric medications

. See Pharmacotherapy

target and comorbid symptoms

. See Comorbidities and associated symptoms; Diet and nutrition

Autistic disturbance of affective contact,

253

Autistic Pride Day,

656, 657

Autoimmune disorders,

53, 236, 532

Autonomic system monitoring,

113

Autonomic testing,

84

Autumn season births,

189–190

AVPR1A gene,

496, 498

Baby Siblings Research Consortium,

544–545

Baclofen,

519–520, 520

Bacterial infections,

51, 55, 191

Balovaptan,

58, 63–64, 498–500, 499

Basal nucleus,

350–351

BASIS

. See British Autism Study of Infant Siblings

Behavioral Intervention for Young Children With Autism: A Manual for Parents and Professionals (Maurice),

549

Behavioral interventions,

543–554

about

background and overview,

543–544

conclusion,

550–551

key points,

551

recommended reading,

551

applied behavior analysis,

543, 544–545. See also Applied behavior analysis; Early intensive behavioral interventions; Early Start Denver Model

DIR model

. See Developmental, Individual Difference, Relationship-Based model

for FXS,

269

historical context,

543–544

language and communication interventions,

587–600. See also Language and communication interventions

neurobiology of,

489

outcomes,

549

parent participation,

548, 550, 592–596

pharmacotherapy as adjunct to,

439

school-based,

575–585. See also School-based interventions

Behavioral rigidity,

41–42, 320

Behavioral shaping,

546

Benign extra-axial fluid of infancy,

370

Binocular rivalry,

522, 522

Biomarkers,

109–124, 648–649. See also Digital biomarkers

Biomedical treatments,

475, 476. See also Complementary and integrative approaches

Bipolar disorder,

45, 52, 159, 508

Birth cohort surveys,

14–16, 16–17

Birth weight,

187, 193, 320

Black Americans,

102. See also Race/ethnicity disparities

Blood pressure monitoring,

112–113

Bodily synchrony deficits,

556

Body mass index (BMI),

145, 190, 294, 295

Body temperature monitoring,

112, 113, 117

Borderline personality disorder (BPD),

49

Brain Power Autism System,

118

Brain stimulation techniques,

603–604. See also Transcranial magnetic stimulation

Brain structure and connectivity

. See also Neuroanatomical findings; Neurodevelopment

cellular composition,

340–342, 341

cellular morphology,

342–343

cell volumes,

342

copy number variants’ effect on,

294–295

electrophysiology in ASD,

223–233. See also Electrophysiological studies

functional connectivity,

284, 295, 404–406

sexual dimorphism,

355, 371

size,

339–340

volume of,

366

Breathing irregularities,

312

Brexpiprazole,

448

British Autism Study of Infant Siblings (BASIS),

645

Building Up Food Flexibility and Exposure Treatment Program,

146

Bumetanide,

59, 65–66, 603

Buspirone,

395, 417, 425, 427, 432

Cambridge Neuropsychological Test Automated Battery (CANTAB),

49

Cannabidiol (CBD),

59, 66, 271, 481, 531, 533–534, 536–537, 538

Cannabidivarin (CBDV),

531, 534, 536–537

Cannabinoid type 1 and type 2 (CB1 and CB2) receptors,

530, 532, 533–534, 535

Cannabis and cannabinoids,

529–540

about

background and overview,

59, 66, 529–530

conclusion,

538

key points,

538

recommended reading,

538

clinical trials,

534, 535–537, 538

epigenetics and,

180

mechanism of action,

530–533, 531

phytocannabinoids,

533–534. See also Cannabidiol; Cannabidivarin

Cannabis indica,

533

Cannabis ruderalis,

533

Cannabis sativa,

533

Carbamazepine,

312

Carbetocin,

328–329

Caregivers

. See Parent-implemented approaches

Cariprazine,

448

Case evaluation,

6–8. See also Epidemiology

Casein-free diet,

145–146, 480

Catechins,

272

Caudate nucleus,

268, 367

Causes

. See Animal models; Electrophysiological studies; Epigenomics; Genetics and genomics; Immune dysregulation; Risk factors; Syndromic ASD

CBD

. See Cannabidiol

CBDV

. See Cannabidivarin

CD38 gene,

486

Celiac disease,

53

Cell transplantation,

619–620

Cellular environment,

177

Centers for Disease Control and Prevention (CDC),

6, 8–9, 14, 18, 529

Cerebellum,

368

Cerebral palsy (CP),

519, 521

Cerebrospinal fluid (CSF),

369–371, 489

Cesarean delivery,

189, 190

Charlotte’s Web preparation of CBD oil,

534, 538

CHD8 gene,

618

Chelation,

481

Chemokine dysregulation,

236–238, 238

Childhood apraxia of speech,

292

Childhood Autism Rating Scale (CARS),

131

Childhood-onset schizophrenia,

54

Child Neurology Society,

80–81, 83

Children’s Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CY-BOCS-PDD),

41, 418

Chimeric antigen receptor T-cell therapies,

616

Choreoathetosis syndrome,

296

CHRNA7 gene,

299

Chromatin,

176

Chromatin loops,

175

Chromodomain helicase DNA-binding protein 1-like gene (CHD1L),

297–298

Chromosomal microarrays,

55, 85, 158–161, 209–210, 254, 290

Chronic fetal hyperinsulinemia,

190

Chronic inflammation,

506–508, 515

Cisgender persons,

92

Citalopram,

60, 419, 426, 427–428

Classroom SCERTS Intervention (CSI),

580, 592

Clinical Global Impression Scale–Improvement (CGI-I),

417–418, 650

Clobazam,

521–522

Clomipramine,

417, 424, 427, 431–432, 461

Clonidine,

63, 269–270, 458–459

Clustered regularly interspaced short palindromic repeats (CRISPR)-based therapeutics,

616–619, 634–635

CM-AT,

58, 64, 479

CNVs

. See Copy number variants

Coaching

augmented reality technology for,

118

of caregivers and parents,

560–562, 593–594

distance coaching,

561–562, 578, 580

gender identity and,

97

for school-based interventions,

578, 580, 581

Cognitive-behavioral therapy,

42

Cognitive style,

658–660

Cognitive traits

copy number variants’ effect on,

292, 293, 297

rigidity,

41–42, 320

as strengths,

658–660, 659–660

Cohen syndrome,

158

Coherence electroencephalographic studies,

228

Communicating hydrocephalus,

369–370

Communication deficits

. See Language and communication deficits; Social-communicative impairment

Comorbidities and associated symptoms,

43–50

aggression,

45. See also Aggression

anxiety,

43. See also Anxiety and anxiety disorders

bipolar spectrum disorders,

45

depression,

43–45. See also Depression

DSM-5 on,

81

DSM-IV on,

254

hyperactivity,

45–46. See also Hyperactivity

impulse-control disorders and behavioral addictions,

45–48

irritability,

42, 45

learning disabilities,

49–50

personality disorders,

48–49

self harm,

44, 45. See also Self-injurious behaviors

social communication deficits,

137–138. See also Social-communicative impairment

substance use disorders,

48, 52

syndromic causes,

253–263. See also Syndromic ASD

Comparative genomic hybridization array testing,

85, 85

Complementary and integrative approaches,

475–483

about

background and overview,

475, 476

conclusion,

481

future directions,

481

key points,

481–482

recommended reading,

482

diet,

145–146, 390

rationale for,

476–477, 477

treatments,

145–146, 390, 477–481

Complete blood count,

55

Comprehensive metabolic panel,

55

Comprehensive treatment models (CTMs),

590–591. See also Early Start Denver Model

Compulsive behaviors,

48, 456

Congenital anomalies,

294

Connective tissue dysplasia,

268

Consortiums,

643–654

ABC-CT,

648–650

about

background and overview,

643–644

conclusion,

647

key points,

652

recommended reading,

653

AIMS-2-Trials,

646–647

European autism interventions,

644–646, 648–649

Interactive Autism Network,

650–652

Constipation,

52, 145, 313

Construct validity,

208, 211

Coordination testing,

82

Copper,

480

Copy number variants (CNVs)

about

background and overview,

289–290, 617

conclusion,

300

key points,

300

recommended reading,

301

ASD model based on,

299–300

brain structure and connectivity,

294–295, 296–297

genetic testing for,

85

neurological symptoms,

294

non-CNS malformations,

294

1q21.1 BP4-BP5 deletions and duplications,

291, 293, 296–298

15q13.3 BP4-BP5 deletions,

291, 298–299

16p11.2 BP4-BP5 deletions and duplications,

290–295, 291–293

16p11.2 linking genes,

295–296, 297

studies,

158–161, 159–160

Cord complications,

190

Core symptom burden,

131–132

Cornelia de Lange syndrome,

158

CORO1A gene,

296, 297

Corpus callosum,

339–340, 343, 371

Cortex

brain connectivity,

343–344

neuron morphology,

342–343

sexual dimorphism,

371

Cortical dysplasias,

279

Cortical tubers,

278–279, 283

CP

. See Cerebral palsy

Cranial nerve evaluation,

82

C-reactive protein (CRP),

55

Cri du Chat syndrome,

260

CRISPR-based therapeutics,

616–619, 634–635

CTMs

. See Comprehensive treatment models

CYP2C19 enzyme,

428, 534

Cysteine,

505–506

Cytochrome P450 system,

417, 534

Cytokine dysregulation,

51, 236–238, 238, 532

Danio rerio (zebrafish),

215–216

DECIPHER,

159

Deep brain stimulation (DBS),

390

Deep machine learning,

114, 115, 116, 120, 121, 229–230

Default mode network,

405–406

Delayed language,

588

Dendrites and dendritic spines,

342–343

Dental pitting,

279

Denver Model intervention approach,

556. See also Early Start Denver Model

Depression

family history,

52

maternal risk factor,

187–189

NAC as treatment for,

508

prevalence,

43–44

Desipramine,

431

Developmental, Individual Difference, Relationship-Based (DIR) model,

565–573

about

background and overview,

565–566

conclusion,

572

key points,

572–573

recommended reading,

573

illustrative observations,

568–569, 570–571

implementation,

567, 569–572

principles,

567, 569–572

progress measurements,

567

Developmental assessment,

36, 80–81

Developmental disabilities,

460

Developmental language disorders,

54

Dextromethorphan,

58, 65

Diabetes,

53, 189, 193–194, 195

Diagnostic and Statistical Manual of Mental Disorders (DSM)

DSM-IV,

254

DSM-IV-TR,

81, 456

DSM-5

autism spectrum disorder classification,

254

comorbidity guidelines,

81

diagnostic criteria,

36, 37, 38, 131, 259, 588

severity specifiers,

131–132, 133

Diet and nutrition

about

background and overview,

143

conclusion,

146–147

key points,

147

recommended reading,

147

BMI and weight,

145, 190, 294, 295

diet trends,

145–146, 390, 480

epigenomics and,

177

feeding difficulties,

144–146, 267, 294, 295, 313

gastrointestinal symptoms,

146

glucose metabolism studies on,

390

interventions,

146

nutritional supplements,

146, 478, 479–480

olfactory sensitivity,

144–145

selective eating,

143

taste sensitivity,

144–145

Diffusion tensor imaging (DTI),

366, 368–369

Digital biomarkers,

109–124

about

background and overview,

109–110

future directions,

120–121, 121

key points,

122

recommended reading,

122

augmented reality technology use,

118–119

ethics of,

110–111

passive analysis technologies,

119–120

physiological monitoring,

111–115, 111, 113, 116, 117–118, 228–229. See also Electrophysiological studies

precautions,

110

studies using,

117–118

for TSC,

284

virtual reality technology use,

119, 119

voice recognition devices,

114–117, 116

DIR model

. See Developmental, Individual Difference, Relationship-Based (DIR) model

Discrete trial training (DTT),

545, 546, 547, 589–590

Discrimination skills,

548–549

Diuretics,

59, 65–66, 603

Divarinic acid,

533

DNA methylation

. See also Epigenomics

environmental conditions and,

175–177

neurodevelopment and,

178–180

Docosahexaenoic acid (DHA),

465, 478

Dolphin animal models,

240

Dopamine,

391, 456

Dopamine receptors,

417, 444, 445, 508. See also Risperidone

Dravet syndrome,

534, 538, 631

Drooling,

449–450

Drugs

. See Pharmacotherapy

Duchenne muscular dystrophy,

158

Duloxetine,

430–431

Dysarthria with phoneme imprecision,

292

Dysmorphic features,

81, 294, 320

Early intensive behavioral interventions (EIBI),

545–551

about

background and overview,

545–546

conclusion,

550–551

key points,

551

recommended reading,

549, 551

curriculum scope and sequence,

548–549

framework,

546

instructional format,

546–548

parent participation,

548, 550

progress measurements,

548

seminal research,

549–550

Early Start Denver Model (ESDM),

555–563

about

background and overview,

555–557

future directions,

561–562

key points,

562

recommended reading,

562

child-directed play-based routines,

558–559

cost effectiveness,

561

curriculum scope and sequence,

569

for FXS,

269

implementation,

557–560

joint activity routine,

559–560

parent participation,

560–561, 594–595

past psychiatric history,

50

progress measurements,

557–558, 560

seminal research,

560–561, 591

Eating disorders,

47–48, 294, 295

Echolalia,

588–589

Eclectic preschool classrooms,

581

ECT

. See Electroconvulsive therapy

EDA (electrodermal activity),

111–112, 111, 117–118

Educational and behavioral interventions

. See Behavioral interventions; Developmental, Individual Difference, Relationship-Based Model; Early Start Denver Model; Language and communication interventions; School-based interventions

Effortless Assessment of Risk States (EARS),

120

EIBI

. See early intensive behavioral interventions

Eicosapentaenoic acid (EPA),

478

EIVI

. See Early intensive behavioral interventions

Electroconvulsive therapy (ECT),

603

Electrodermal activity (EDA),

111–112, 111, 117–118

Electroencephalography,

83–84, 223–224, 648–650

Electromyography,

84

Electrophysiological studies,

223–233

about

background and overview,

83–84, 223–224

conclusions,

230

key points,

230–231

recommended reading,

231

coherence analysis,

228

early detection,

229–230

epilepsy in ASD,

224–225

event-related potentials in ASD,

225–227

on facial processing,

228–229

spectral domain and oscillations of ASD,

227

Embedded Figures Test,

659, 659

Emergency department evaluation,

56–57

Emotional development deficits,

38, 353, 565–573. See also Developmental, Individual Difference, Relationship-Based model

Empatica E4 wristband,

117–118

Empowered Brain,

118

ENCODE,

166

Endogenous proteins,

635

Enhanced milieu teaching (EMT),

595

Enhanced perceptual functioning,

658

Environmental toxins

about

background and overview,

235–236, 237

conclusion,

245–246

key points,

246

epigenomics and,

197–198, 239–240

immune dysregulation and,

245–246

polybrominated diphenyl ethers as,

239–245

Eosinophilic esophagitis (EoE),

145, 146

EPA

. See Eicosapentaenoic acid

Epidemiology,

5–33

about

background and overview,

5, 156

conclusion,

19

key points,

19

recommended reading,

20

birth cohort surveys,

14–16, 16–17

case definition,

6

case evaluation,

6–8

case identification or ascertainment,

6, 7

cross-sectional survey issues,

14, 15

diagnostic substitution,

12–14

prevalence survey methodology,

5–8, 7

prevalence survey systematic review,

8–12, 10–11, 26–33

race/ethnicity status,

16, 18–19. See also Race/ethnicity disparities

referral statistics,

12, 13

repeated survey issues,

14

socioeconomic status,

16, 18–19, 102

time trend interpretation,

12–16

Epigenome-wide association studies (EWASs),

179–180, 181

Epigenomics,

175–184

about

background and overview,

175–176, 617

conclusion,

180

future directions,

166

key points,

182

recommended reading,

182

advanced parental age and,

197

as CIM treatment rationale,

476–477

definitions,

175

dysregulation,

179–180, 181

environment and,

176–179, 197–198, 239–240

neurodevelopment and,

178–179

Rett syndrome and,

309

therapeutic editing of,

618–619

Epilepsy

copy number variants’ effect on,

294, 298

diagnosis,

224

genetics of,

225, 296

neurological assessment,

83–84

past medical history,

51

pathophysiology,

533

prevalence,

83–84, 224–225

in TSC,

279, 282–284

treatment,

284, 506, 533, 538

Erythrocyte sedimentation rate,

55

Escitalopram,

60, 312, 419, 428

ESDM

. See Early Start Denver Model

Estrogen,

327

Ethical issues,

110–111

European Autism Interventions—A Multicentre Study for Developing New Medications (EU-AIMS),

644–646, 648–649

European Babysibs Autism Research Network,

645

Evaluation and assessment

. See Digital biomarkers; Epidemiology; Gender identity development; Neurological assessment; Pediatric assessment; Psychiatric assessment; Race/ethnicity disparities; Sexual identity development

Event-related potentials (ERPs),

224, 225–227, 228–229

Everolimus,

284–285

EWASs

. See Epigenome-wide association studies

Excitatory/inhibitory (E/I) imbalance,

532–533

Executive functioning training,

42

Exercise,

480

Experimental treatments,

58–59. See also Arbaclofen; Cannabis and cannabinoids; Complementary and integrative approaches; N-acetylcysteine studies; Oxytocin; Vasopressin

Expressive language,

589. See also Language and communication deficits

External hydrocephalus,

369–370

Extra-axial fluid cerebrospinal fluid,

370–371

Extrapyramidal symptoms,

449–450

Eye contact

clinical presentation,

37

eye tracking monitoring,

114–115, 648–650

gaze detection,

114

treatment,

63

Face validity,

208

Facial angiofibromas,

279

Facial expression recognition

clinical presentation,

37–39

neurobiology of,

228–229, 352–353, 402–403, 403

Failure to thrive,

294

Family history,

52–53, 81

Fear detection,

498–500

Fecal incontinence,

52

Feeding difficulties,

144–146, 267, 294, 295, 313

Fenfluramine,

418

Fetal distress,

190

Fetal growth restriction,

194–195, 194

Fetal infections,

194–195

Fevers,

112

Fibrous cephalic plaques,

279

¹⁸F-labeled fluorodopa (FDOPA),

391

“Floor time,”

567, 568, 570–572

Floreo’s Platform,

119

[¹¹C]Flumazenil PET study,

394

[¹⁸F]-Fluorodeoxyglucose PET studies,

377, 379, 380–383, 388

Fluoxetine,

58, 59–60, 381, 388, 420–421, 426, 428–429

Fluvoxamine,

60, 421–422, 426, 429–430

FMR1

. See Fragile X mental retardation 1 gene

fMRI

. See Functional magnetic resonance imaging

FMRP

. See Fragile X mental retardation protein

Focused intervention (FI) approaches,

589–590

Folic acid deficiency,

179, 189, 192

Folinic acid,

480

Food

. See Diet and nutrition

Food allergies,

52, 145–146, 480

Food motivation,

322–324

Food neophobia,

144

Fractional anisotropy (FA),

369

Fragile X-associated primary ovarian insufficiency,

269

Fragile X-associated tremor ataxia syndrome (FXTAS),

266, 269, 272

Fragile X DNA testing,

85, 85, 254, 265, 269

Fragile X mental retardation 1 gene (FMR1)

about,

156–157, 255–256, 265–266

animal models,

216, 217, 258

gene therapy and,

628, 630

genetic testing for,

85, 85, 265

glucose metabolism and,

389

Fragile X mental retardation protein (FMRP)

about,

156–157, 255–256, 258, 265–266

animal models,

258

gene therapy and,

628, 630

phenotype,

267

Fragile X syndrome (FXS),

265–275

about

background and overview,

255–256, 256, 265–267

conclusion,

272

key points,

272

recommended reading,

272–273

advanced maternal and paternal age risk factor,

197

arbaclofen and,

519, 522–523, 524, 525

assessment plan,

55

clinical presentation,

267–268

comorbidity,

266, 267

diagnostic criteria,

259, 268–269

differential diagnosis,

268

electrophysiological studies of,

225–226

genetic testing,

85, 85, 86, 254, 265, 269

genetics of,

156–157. See alsoFMR1; FMRP

glucose metabolism studies,

389

prevalence,

50, 158, 265–266

treatment,

260, 268–272, 627

Free radicals,

513

Functional abdominal pain,

52

Functional connectivity studies,

404–406

Functional language units,

590

Functional magnetic resonance imaging (fMRI),

401–409

about

background and overview,

401–402

conclusion,

406

future directions,

403, 406, 407

key points,

406

recommended reading,

406–407

early localization studies,

402–404, 403

functional connectivity studies,

404–406

social-communicative impairments and,

136

Fusiform face area (FFA),

402–403, 403

FXS

. See Fragile X syndrome

FXTAS

. See Fragile X-associated tremor ataxia syndrome

GABAergic neurotransmission,

225, 357, 519–520, 520, 521–522, 532–533

GABA receptors,

357, 394, 520, 627

Gaboxadol,

272

GABRB3 gene,

394

Gait evaluation,

82–83

Galvanic skin response (GSR),

111–112, 111

Ganaxolone,

627

Gastrointestinal disorders and symptoms,

51–52, 53, 146

Gc protein-derived macrophage activating factor (GcMAF),

532

Gender dysphoria

about

background and overview,

91, 92–93

conclusion,

97–98

key points,

98

recommended reading,

98

assessment perspectives,

94–95

collaborative treatment approach,

95–97

minority status and,

94

Gender identity development

about

background and overview,

91

conclusion,

97–98

key points,

98

recommended reading,

98

collaborative ASD treatment,

95–97

definitions,

92

gender dysphoria assessment,

94–95

minority status and,

94

process of,

92–93

Gene panel testing,

85, 85

Gene therapy

about

background and overview,

615–616, 627–630, 630

conclusion,

636–637

key points,

637

recommended reading,

637

adeno-associated virus,

615–616, 619–620, 628, 630, 634–635

antisense oligonucleotides,

628, 630–631

clinical viral vector gene therapy trials,

635–636

cost effectiveness,

637

foreign vs. endogenous proteins,

635

lentivirus,

628, 632–633, 634

modes of action,

629

nonviral vector molecular approaches,

628, 630–632

protein expression type,

635

RNA interference,

628, 630, 631–632

route of administration,

629, 635

safety and side effects,

628

stem cells and,

615–625. See also Stem cell gene therapy

viral vector gene therapy,

615–616, 619–620, 628, 630, 632–636, 633

Genetics and genomics,

155–173

about

background and overview,

155, 254–255, 616–619

conclusion,

86–87, 166

future directions,

166–168, 167

key points,

87, 168

recommended reading,

168

additive effects,

266

advanced parental age,

196–197

animal model advancements,

209–215, 210. See also Animal models

assessment plan,

55

copy number variation,

158–161, 159–160, 289–304. See also Copy number variants

of epilepsy,

225, 296

genome-wide association studies,

209, 210

genome-wide screenings,

158–159

G´E interactions,

156, 157, 212–215, 213

heritability evidence,

155–156, 156–157, 179

medical genetic workup,

84–86, 85

of PWS,

326

social-communicative impairments and,

129–131, 134–137

symptom cluster associations,

128

syndromic forms of ASD,

156–158, 158

of vasopressin receptors,

496

whole-exome sequencing,

55, 85, 86, 161–163, 162, 164, 209–210

whole-genome sequencing,

85, 86, 163–166, 165, 209–210

Genome-wide association studies (GWASs),

209, 210

Genome-wide screenings,

158–159

Geriatrics,

57

Gestational age,

192–193, 194

Gestational diabetes,

189, 190

Gesture use deficits,

38–39, 588, 592

GFCF diet

. See Gluten-free casein-free diet

Ghrelin,

323

Gingival fibromas,

279

Glass Enterprise Edition,

118–119

Glucocorticoid replacement therapy,

327

Glucose metabolism studies,

379, 380–387, 388–390

Glutamatergic agents,

58, 64–65. See also Arbaclofen; Memantine; N-acetylcysteine (NAC) studies

Glutamatergic signaling,

357, 463, 505–508, 507, 512–513, 532–533, 644

Glutathione (GSH),

505–506

Gluten-free casein-free (GFCF) diet,

145–146, 480

Google Cardboard,

119

G-protein-coupled receptors (GPCRs),

494, 530, 533

Grandparental age,

196–197

Group interventions

Early Start Denver Model,

561

narrative-based,

592

social skills training,

592

Growth failure,

306, 307, 312–313

Growth hormone therapy,

327

GSH

. See Glutathione

GSR. Galvanic skin response

Guanfacine,

62–63, 269–270, 458, 459–461

GWASs

. See Genome-wide association studies

Hair pulling,

65, 508

Haloperidol,

432, 440, 444–445, 449–450

Hamartin (TSC1) gene,

277, 278, 283, 389–390

Hanen Centre More Than Words program,

594

Haploinsufficiency,

296, 297, 299, 618

Head circumference measurements,

81

Hearing evaluation,

83

Heart rate variability (HRV),

112–113

Height,

294

Helminth worms,

532

Heritability,

155–156, 156–157, 179, 289–290. See also Epigenomics; Genetics and genomics

High-frequency rTMS,

608–609, 608

Hippocampus,

351, 367–368, 485

Hispanic/Latinx Americans,

102. See also Race/ethnicity disparities

Histaminergic H₁ receptors,

444, 445. See also Risperidone

Histone posttranslational modification,

175, 176

Hoarding,

41

Horseback riding,

480

HRV

. See Heart rate variability

HydroCel net,

649

“Hygiene” hypothesis,

532

Hyperactivity,

455–471

about

background and overview,

455

conclusion,

466

key points,

466–467

recommended reading,

467

α₂-adrenergic agonists for,

458–461

amantadine for,

58, 65, 463–464

atomoxetine for,

455, 461–463

atypical antipsychotics for,

269–270, 466

gene therapy for,

630

as memantine adverse effect,

464

NAC for,

65, 509

naltrexone for,

464–465

NMDA receptor agonists for,

463–464

omega-3 fatty acids for,

465–466

prevalence,

45–46

stimulants for,

62–63, 456–458

TCAs for,

431

Hyperphagia,

319, 322–324

Hyperprolactinemia,

449

Hypersensitivity,

630

Hyperserotonemia,

416

Hypersexuality,

48

Hypersystemizing,

659–660, 660

Hypertension,

190, 193–194, 459–460

Hypomelanotic macules,

279

Hypopigmentation,

279, 320, 321

Hypoxia,

190–191

IAN

. See Interactive Autism Network

ID

. See Intellectual disability

Idiopathic psychosis,

295

IEP

. See Individualized Education Program

IGF-1

. See Insulin-like growth factor 1

Iloperidone,

448

Imaging and anatomy

. See Functional magnetic resonance imaging; Neuroanatomical findings; Neurodevelopment; Positron emission tomography

Imitation deficits,

556

Immune dysregulation

about

background and overview,

235–236, 237

conclusion,

245–246

key points,

246

recommended reading,

246

cytokine dysregulation,

236–238, 238

endocannabinoids and,

530–532

environmental toxins and,

239–245

global,

236, 238

past medical history,

51

stem cell gene therapy for,

620

Immunoglobulin levels,

236

Implementation fidelity,

577

Impulsivity

in PWS,

324

prevalence,

47–48

treatment,

63, 65

Inattention,

45–46, 52, 431, 456

Inborn error of metabolism,

83

Incidental teaching,

545–546, 547

Individualized Education Program (IEP),

50, 53

Individuals with Disabilities Education Act (U.S., 1990),

16

Induced pluripotent stem cells (iPSCs),

367, 644

Induction gene therapy models,

620–621

Infantile encephalopathy,

310

Infantile spasms,

389

Infections,

51, 55, 189, 191, 194–195, 241

Inflammation

about,

235

chronic inflammation,

506–508, 515

cytokine dysregulation,

236–238

inflammatory markers and immune assessment,

55

neuroinflammation studies,

387, 395

past medical history,

51

Inositol,

480

Insistence on sameness,

40–41, 42

Insomnia,

417, 459–460

Insula,

322–324, 351

Insulin-like growth factor 1 (IGF-1),

313

Intellectual disability (ID)

causes,

255, 256, 257

copy number variants and,

159, 298

differential diagnosis,

54

epilepsy association,

224

FXS and,

267, 268

megalencephaly association,

366

prevalence,

49–50, 259–260, 268, 280–281

stimulant use and,

456

treatment,

543

TSC association,

280–281

Interactive Autism Network (IAN),

650–652

Interests, of autistic individuals,

661

International Classification of Functioning,

656, 659, 662

International Standards for Cytogenomic Arrays,

159

Internet addiction,

47, 110

Interoception,

324–325, 571

Interpersonal-Psychological Theory of Suicide (IPTS),

44–45

Intraindividual strengths,

658–662

Intrinsic (task-free) functional connectivity studies,

405–406

Intuitive Physics Test,

660, 660

In vitro fertilization,

189–190

iPSCs

. See Induced pluripotent stem cells

IQ scores,

49–50, 271, 292, 293, 299–300

Iron,

480

Irritability

about,

45

as clonidine adverse effect,

458

FDA-approved medications for,

441, 446

rigidity and,

42

treatment,

59–62, 65, 66, 430, 432, 441, 443–444, 446–448, 509, 512

Irritable bowel syndrome,

52

Janssen Autism Knowledge Engine (JAKE) system,

117–118

Joint attention, symbolic play, engagement, and regulation (JASPER),

569, 578–579, 591–592, 594–595

Joint attention skills,

544, 577–579, 588, 589

KCTD13 gene,

295, 297

Ketogenic diet,

390

Kidney problems,

280, 294, 506

Kinesigenic dyskinesia,

296

Klinefelter syndrome,

309

Kynurenine pathway,

395

Labor, prolonged,

190

LAM

. See Lymphangioleiomyomatosis

Lamotrigine,

58, 62, 312

Landau-Kleffner syndrome,

225

Language and communication deficits

about,

588–589

copy number variants’ effect on,

292, 293, 295, 297

delayed language,

588

prelinguistic,

588

repetitive speech behaviors,

588–589

social communication deficits,

127–141. See also Social-communicative impairment

treatment

. See Language and communication interventions

Language and communication interventions,

587–600

about

background and overview,

587–589

conclusion,

595–596

key points,

596

recommended reading,

596–597

behavioral interventions,

545–546, 548–549, 589–591. See also Applied behavior analysis

for minimally verbal children,

595

narrative interventions,

592

parent-implemented approaches,

592–595

pharmacotherapy,

270, 430, 431

social communication approaches,

591–592

Language ENvironment Analysis (LENA),

115

L-carnosine,

480

Lead exposure,

83, 192

Learning disabilities,

49–50, 54

Learning Experiences and Alternate Program for Preschoolers and Their Parents (LEAP) model,

580–581

LENA

. See Language ENvironment Analysis

Lennox-Gastault syndrome,

538

Lentivirus-based virus,

628, 632–633, 634

Level of support severity index,

132, 133

Levetiracetam,

58, 62, 312

Linking genes,

295–296, 297

Lipid-based nanoparticles,

632

Lipid metabolism,

465

Local processing bias,

658

Longitudinal European Autism Project,

645

Loss of function (lof) mutations,

157, 159, 160, 161, 162, 295–296, 617–618

Lovastatin,

271

Low birth weight,

187, 193, 320

Low-frequency rtms,

606–608, 608

Luxturna,

619

Lyme disease markers,

55

Lymphangioleiomyomatosis (LAM),

280

Macaca mulatta (rhesus macaque monkeys),

217

Machine learning,

114, 115, 116, 120, 121, 229–230

Macrocephaly,

81, 366–368

MAGEL2 gene,

321, 326

Magnetic resonance imaging (MRI),

84, 366, 369. See also Functional magnetic resonance imaging

Making a Difference: Behavioral Intervention for Autism (Maurice),

549

Male Rett encephalopathy,

309–310

Manage Eating Aversions and Low intake plan,

146

Manganese deficiency,

192

MAPK3 gene,

292, 295–296, 297

Marine animal models,

240

Martial arts,

480

Maternal risk factors

. See also Perinatal environment

advanced age,

195–198, 195

infections,

189, 195

maternal diabetes,

189, 195

maternal metabolic syndrome,

193–194

nutrition,

194–195

perinatal bleeding,

190

Maternal uniparental disomy (mUPD),

320–321

Mavoglurant (AFQ056),

270

MAZ gene,

296, 297

MC4R (melanocortin 4 receptor),

328

M-CHAT

. See Modified Checklist for Autism in Toddlers

MDMA (3,4-methylenedioxymethamphetamine),

489

Mechanistic target of rapamycin (mTOR) inhibitors,

627

MECP2

. See Methyl-CpG binding protein 2 gene

MECP2 duplication syndrome,

631

Medicaid waivers,

106

Medical genetic workup,

55, 84–86, 85

Medical transition,

91–92

Medications

. See Pharmacotherapy

Megalencephaly,

366–368

Melanocortin 4 receptor (MC4R),

328

Melanocortin stimulation hormones (MSH),

328

Melatonin,

270, 477

Memantine,

58, 64–65, 463, 464

Mental status examination,

81

Mercury exposure,

236

MERS-R

. See Montefiore-Einstein Rigidity Scale–Revised

Mesenchymal stem cells (MSCs),

616, 620

Metabolic testing,

83

Metabotropic glutamate receptor 5 (mGluR5),

270, 394, 507, 519, 627

Metals (toxic),

83, 191–192

Metformin,

271–272

Methyl B₁₂ (methylcobalamin),

478

Methyl-CpG binding protein 2 gene (MECP2),

305, 308–311, 389, 628, 631

3,4-Methylenedioxymethamphetamine (MDMA),

489

Methylphenidate,

58, 62, 456, 457–459. See also stimulants

mGluR5

. See Metabotropic glutamate receptor 5

mGluR theory,

519

Microarray panels,

55, 85, 158–161, 209–210, 254, 290

Microbiome treatments,

479

Microcephaly,

81

Microglia,

395

Micronutrients,

479–480

MicroRNAs,

631

Microsatellites,

496

Minimally verbal children,

595

Minocycline,

270–271

Minority stress,

94. See also Race/ethnicity disparities

Mirtazapine,

417, 425, 427, 432

Modified Checklist for Autism in Toddlers (M-CHAT),

79

Monogenic ASD,

630

Montefiore-Einstein Rigidity Scale–Revised (MERS-R),

42

Mood disorders

. See Anxiety and anxiety disorders

Mood stabilizers and anticonvulsants,

58, 61–62. See also Lamotrigine; Levetiracetam; Valproate

More Than Words program,

594

Mosaicism,

267

Mother–infant bonding symptoms,

63–64

Motor skills,

82, 292, 293

Mouse models

background and overview,

211

experimental therapeutic studies,

485–486, 497

gene therapy studies,

620–621, 630, 631, 634

genetic studies,

209, 210, 211

neurogenetic pathways research,

257–258, 258

oxidative stress studies,

513–515

toxicant studies,

239–241

Movement sensors,

113–114

MRI

. See Magnetic resonance imaging

MSCs

. See Mesenchymal stem cells

MSEL

. See Mullen Scales of Early Learning

mTOR complex 2,

631

mTOR inhibitors

. See Mechanistic target of rapamycin inhibitors

Mullen Scales of Early Learning (MSEL),

281, 284, 418

Multiple sclerosis,

519

mUPD

. See Maternal uniparental disomy

Muscarinic receptors,

444

Muscle biopsy,

84

Music therapy,

480–481

Mycoplasma pneumoniae infections,

51, 55

N-acetylcysteine (NAC) studies,

505–518

about

background and overview,

58, 65, 505

conclusion,

515

key points,

515–516

recommended reading,

516

for acetaminophen overdose,

506

chemistry and pharmacology,

505–506, 506

clinical trials,

509, 510–511, 512

glutamatergic signaling,

505–506, 507, 512–513

mechanism of action,

512–515

medical indications,

506–508, 507

neurological indications,

508–509

oxidative stress and,

513–515, 514

risperidone as adjunctive treatment with,

509, 512

Nagalase,

532

Naltrexone,

464–465

Nanoparticle delivery systems,

621–622

Narrative interventions,

592

National Center for Complementary and Integrative Health (NCCIH),

475

National Institutes of Health,

628

Native Americans,

102

Naturalistic developmental-behavioral intervention (NDBI),

555, 556, 590–591

Naturalistic social communication intervention,

578

Natural products,

475, 476. See also Complementary and integrative approaches

NCCIH

. See National Center for Complementary and Integrative Health

NDBI

. See Naturalistic developmentalbehavioral intervention

NDD

. See Neurodevelopmental disability

Necdin,

321, 325

Neonatal encephalopathy,

310

Nerve conduction studies,

84

NET

. See Norepinephrine transporter

Neuroanatomical findings,

339–347

about

background and overview,

339

conclusion,

344

key points,

344

recommended reading,

344–345

amygdala,

349–363. See also Amygdala

in ASD,

268

brain size,

339–340

cellular composition,

340–342, 341

cellular morphology,

342–343

cell volumes,

342

cortical connectivity,

343–344

FXS,

268

structural imaging on,

365–375. See also Structural imaging research

Neurodevelopment

about

conclusion,

357

key points,

357–358

recommended reading,

358

of amygdala,

353–355

antidepressant prenatal exposure and,

187–189

copy number variants’ effect on,

294–295, 296–297

CSF and,

369

depression and,

188–189

environmental toxin exposure and,

236, 237, 239–243, 244–245

gene therapy timing and,

636–637

neuropathology of ASD,

355–357

serotonin and,

415

stem cell gene therapy studies,

620–621

Neurodevelopmental disability (NDD),

298

Neurodiversity,

655–658, 656, 662–663

Neurofibromatosis,

50

Neuroinflammation studies,

387, 395

Neurological assessment,

80–83, 86–87

Neurological examination,

81

Neurological workup,

83–84

Neurotransmitter function studies,

384–386, 391–394, 393

NIBS techniques

. See Noninvasive brain stimulation techniques

NMDA receptors,

463–464, 505–506, 507, 513

Noncoding RNA,

175

Nonheritable risk factors,

185–205

about

background and overview,

185–187

conclusion,

198

future directions,

198–199

key points,

199

recommended reading,

199

evidence,

185–186

parental risk factors,

195–198, 195, 197

perinatal,

193–195, 194

prenatal and maternal conditions,

187–193, 188–189

Nonhuman primates,

217

Noninvasive brain stimulation (NIBS) techniques,

604, 609–610. See also Transcranial magnetic stimulation

Nonpsychotic personality disorders,

52

Nonsyndromic ASD,

254, 257–260

Nonviral vector-based therapies,

628, 630–632

Norepinephrine transporter (NET),

416–417

Normative modeling,

645

Nose temperature monitoring,

112

Nucleus accumbens,

487, 508

Nuedexta,

58, 65

Nutrition

. See Diet and nutrition

Obesity

appetite regulation and,

324

copy number variants’ effect on,

292–294

diet and nutrition,

145

FXS and,

267

maternal risk factor,

189, 193–194

in PWS,

319

obsessive-compulsive disorder (OCD),

46–47, 54, 320, 508

obsessive-compulsive personality disorder (OCPD),

48–49, 53

occupational therapy,

549

¹⁵O-labeled water PET,

383–384, 390–391

Olfactory sensitivity,

144–145

Olivetolic acid,

533

Omega-3 fatty acids,

465–466, 477–478

Onasemnogene abeparvovec (Zolgensma),

635–636, 637

1q21.1 BP4-BP5 deletions and duplications,

291, 293, 296–298

15q11-13 region,

394

15q11.2-13 deletions,

320–321

15q13.3 BP4-BP5 deletions,

291, 298–299

16p11.2 BP4-BP5 deletions and duplications,

290–295, 291–293

16p11.2 linking genes,

295–296, 297

Operant techniques,

546

Orbitofrontal cortex (OFC),

322–324, 351

Oscillations of electroencephalographic signals,

227

Oxidative stress,

478, 513–515, 514

OXT gene,

486

OXTR gene,

486, 496

Oxytocin,

485–491

about

background and overview,

58, 63

conclusion,

489–490

future directions,

488–489

key points,

490

recommended reading,

491

animal models,

485–486

anxiety and,

490

genetic studies,

486

intervention studies,

487–488

PET studies on,

386, 392, 394

for PWS,

327–329

restricted and repetitive behaviors,

490

sensory sensitivity,

490

single-dose studies,

486–487

social communication and,

485–486, 488, 490

P50 suppression,

226

Pancreatic digestive enzymes,

479

Paradoxical functional facilitation,

660–661, 661

Parent-implemented approaches

about,

592–593

coaching and,

560–562, 593–594

DIR model,

565–573. See also Developmental, Individual Difference, Relationship-Based model

early intensive behavioral interventions,

548, 550

Early Start Denver Model,

560–561, 594–595

efficacy studies,

462–463, 593–596

parent-implemented language intervention,

270, 271

video teleconferencing and,

594

Parent-implemented language intervention (PILI),

270, 271

Paroxetine,

422, 430

Partial effectiveness trial,

576

Passive analysis technologies,

119–120

Past medical history,

51–52

Past psychiatric history,

50

Paternal age,

196–198, 197

Patient advocacy groups,

667–675

about

background and overview,

667, 668

key points,

674–675

clinical care and co-learning through,

673–674, 674

clinical trial execution and,

671–672, 673

clinical trial readiness and,

669–673, 670

future research directions,

668–669, 668–669

organizations and resources,

671–672

preclinical development,

669

regulatory approval and,

673

Patisiran,

622, 632

PBDE exposure

. See Polybrominated diphenyl ether exposure

PCB exposure

. See Polychlorinated biphenyl exposure

PECS

. See Picture Exchange Communication System

Pediatric assessment,

79–80, 81, 86–87

Pediatric autoimmune neuropsychiatric disorders,

51

Pediatric screening guidelines,

35

Peer engagement,

580

Perceived burdensomeness,

44–45

Perinatal environment

epigenomics and,

177–178, 179

family history,

53

fetal growth restriction,

194–195, 194

G×E animal studies,

212–213

low birth weight,

187, 193, 320

perinatal bleeding,

190

preterm birth,

193–194, 194

Peripheral blood mononuclear cell (PBMC) cytokine responses,

236

Peripheral temperature monitoring,

112, 113

Periungual fibromas,

279

Perivascular lymphocytic cuffs,

238

Personality traits,

662

Pervasive developmental disorder,

298

Pervasive developmental disorder not otherwise specified,

52, 254

PET

. See positron emission tomography

Pharmacotherapy,

57–66

about

background and overview,

35–36, 58–59

conclusion,

66–67

key points,

67

anticonvulsants and mood stabilizers,

58, 61–62. See also Lamotrigine; Levetiracetam; Valproate

anti-inflammatory treatment,

58, 64, 532

anti-influenza medication,

58, 65, 463–464

antipsychotic agents,

58, 60–61, 439–453. See also Antipsychotics

cannabinoids,

59, 66, 529–540. See also Cannabis and cannabinoids

diuretic,

59, 65–66

diuretics,

603

glutamatergic agents,

58, 64–65. See also Arbaclofen; Memantine; N-acetylcysteine (NAC) studies

oxytocin,

58, 63, 485–491. See also Oxytocin

pancreatic enzyme,

58, 64

serotonergic medications,

415–437. See also Serotonergic medications

stimulants and α-adrenergic agents,

58, 62–63, 269–270, 456, 457–461. See also Clonidine; Guanfacine

vasopressin,

58, 63–64, 493–503. See also Vasopressin

Phelan-McDermid syndrome,

86, 158

Phobias,

43, 144, 533

Phosphatase and tensin homolog gene (PTEN),

631

Physics test,

660, 660

Physiological monitoring,

111–115, 111, 113, 116, 117–118

Phytocannabinoids,

533–534

Pica,

83

Picture Exchange Communication System (PECS),

50, 590–591

Pimavanserin,

448

Pivotal response training (PRT),

590–591, 594–595

Placental problems,

194–195

Pluripotent stem cells,

367, 644

Point mutations,

617–619

Pollutant exposure,

192–193, 212, 213, 236, 239–245

Polybrominated diphenyl ether (PBDE) exposure,

236, 239–243, 244–245

Polychlorinated biphenyl (PCB) exposure,

236, 239, 243, 244–245

Polycystic kidney disease,

280

Polysomnography (sleep study),

84

Porcine whipworm,

532

Positron emission tomography (PET),

377–400

about

background and overview,

377–378

conclusion,

395

future directions,

395–396

key points,

396

recommended reading,

396

cerebral blood flow studies,

383–384, 390–391

glucose metabolism studies,

379, 380–383, 388–390

methodology,

378–379

neuroinflammation studies,

387, 395

neurotransmitter function studies,

384–386, 391–394, 393

Prader-Willi critical region (PWCR),

320–321, 326

Prader-Willi syndrome (PWS),

319–335

about

background and overview,

319–320

conclusion,

329

key points,

329–330

recommended reading,

330

ASD commonalities,

325–327

assessment plan,

55

behaviors,

322–325

clinical features,

320, 322–325

genetic mutations,

320–321, 326

management,

327–329

neurobiology and pathophysiology,

321–322

neurotransmission function studies,

394

oxytocin efficacy studies,

488

PET studies,

385

Prairie voles,

485

Predictive validity,

208

Preeclampsia,

193–194

Prefrontal cortex (PFC)

α₂-adrenergic agonists and,

458

appetite regulation and,

322–324

epilepsy and,

533

impulsivity and,

324

Prelinguistic communication deficits,

588

Prenatal environment,

177, 191, 236

Preterm birth,

193–194, 194

Prevalence surveys

. See Epidemiology

Probiotics,

479

Problematic internet use,

47

Progesterone hormone treatment,

189–190

Programing for generalization,

546, 548

Prompting and fading,

545, 546

Prosody,

39, 114–115, 588

Provisional Rett syndrome,

307

PRRT2 gene,

296

PRT

. See Pivotal response training

Psoriasis,

53

Psychiatric assessment,

35–57

about

background and overview,

35–37

conclusion,

66–67

key points,

67

recommended reading,

67

clinical presentation and course of illness,

37–43, 38. See also Gender identity development; Race/ethnicity disparities; Sexual identity development

emergency department evaluation,

56–57

family history,

52–53, 81

geriatric considerations,

57

impression,

53–54

past medical history,

51–52

past psychiatric history,

50

plan,

54–56

psychiatric hospitalization evaluations,

56–57

social history,

53

Psychiatric Genomics Consortium study,

290

Psychiatric treatments

behavioral and educational

. See Behavioral interventions; Developmental, Individual Difference, Relationship-Based (DIR) model; Early Start Denver Model; Language and communication interventions; School-based interventions

experimental treatments

. See Arbaclofen; Cannabis and cannabinoids; Complementary and integrative approaches; N-acetylcysteine (NAC) studies; Oxytocin; Vasopressin

future directions

. See Gene therapy; Patient advocacy groups; Transcranial magnetic stimulation

psychiatric medications

. See Pharmacotherapy

PTEN.

See Phosphatase and tensin homolog gene

PWS

. See Prader-Willi syndrome

Pyramidal neurons,

342–343

Race/ethnicity disparities

about

background and overview,

101, 102

conclusion,

106

key points,

106

recommended reading,

107

causes of,

103–105, 104

detection of,

101–103, 103

gender identity and,

94

prevalence estimates,

16, 18–19

psychiatric hospitalization risk factor,

56

reduction of,

105–106

sexual identity and,

94

Rapamycin,

260, 278

Rapid Interactive Screening Test for Autism in Toddlers,

80

Rat models,

211–212, 241, 621, 636

R-baclofen (arbaclofen),

65, 519–527. See also Arbaclofen

RBRs

. See Restricted and repetitive behaviors

Reactive oxygen species (ROS),

513–515

Receptive language,

589. See also Language and communication deficits

Reciprocal social behavior deficits,

127–128, 556. See also Social-communicative impairment

Recombinant AAVs (rAAVs),

634

Reflux,

145

“Refrigerator mother” theory,

185

Reinforcers,

545, 546, 547

Relationship-based intervention model,

565–573. See also Developmental, Individual Difference, Relationship-Based model

Remaking Recess,

580

Renal angiomyolipomas,

280

Renal problems,

280, 294, 506

Repetitive and Stereotyped Movements Scale,

40

Repetitive Behavior Scale–Revised,

41, 418

Repetitive sensory and motor behaviors,

40

Repetitive speech behaviors,

588–589

Repetitive transcranial magnetic stimulation (rTMS),

604, 606–611, 607–608

Research registry,

650–652

Research Units on Pediatric Psychopharmacology (RUPP) Autism Network trial,

457

Resilience, of autistic individuals,

662

Resting-state functional connectivity studies,

405–406

Restricted and repetitive behaviors (RRBs)

caudate nucleus volume and,

268, 367

clinical presentation,

39–41, 42

measurement of variation,

133

oxytocin,

490

in PWS,

320, 326

symptom clusters associated with,

128

treatment,

59–60, 63–64, 65, 429, 431, 509, 512, 519–520

Retinal hamartomas,

279

Rett syndrome (RTT),

305–317

about

background and overview,

256, 257, 305

conclusion,

313

key points,

314

recommended reading,

314

assessment plan,

55

clinical presentation,

305–307

diagnostic criteria,

307, 308

DSM-5 exclusion,

254

DSM-IV diagnosis,

254

environmental toxin exposure and,

239–240

epidemiology,

197, 305

gene therapy studies,

620–621

genetics,

157, 176–177, 308–310

genetic testing,

86, 310

glucose metabolism and,

389

management,

312–313

neurobiology and pathophysiology,

310–311

prevalence,

50

treatment,

260, 627

Reward circuitry,

295

Rhabdomyomas,

279–280

Rhesus macaque monkeys (Macaca mulatta),

217

Rheumatic fever,

51

Rheumatoid arthritis,

53

Rigidity,

41–42, 64

Risk factors

epigenomics,

174–184. See also Epigenomics

genetics,

155–173. See also Genetics and genomics

maternal,

189, 190, 193–198, 195

nonheritable,

185–205. See also Nonheritable risk factors

Risperidone,

269, 432, 509, 512

RNA interference (RNAi) therapy,

628, 630, 631–632

Roadmap Epigenomics,

166

Rolandic epilepsy,

294

RRBs

. See Restricted and repetitive behaviors

rTMS

. See Repetitive transcranial magnetic stimulation

RTT

. See Rett syndrome

Sarizotan,

312

Savant talents,

660–661, 661

S-baclofen,

519–520, 520

SCERTS model

. See Social Communication, Emotional Regulation, and Transactional Support model. See also Classroom SCERTS Intervention

Schizophrenia

differential diagnosis,

54

family history,

52

genetics,

159, 290, 291, 291, 295, 296–297, 298

glucose metabolism studies on,

388–389

NAC as treatment for,

508

School-based interventions,

575–585

about

background and overview,

575–576

conclusion,

581–583

key points,

583

recommended reading,

583

challenges,

576–577, 578

joint attention interventions,

577–579

peer-mediated interventions,

579, 580–581

research in schools,

575–577

social skills interventions,

579–581

teacher- and paraprofessional-mediated interventions,

577–580

training recommendations,

581

Scoliosis,

312, 320

Screenings,

6–8, 35–36, 79–80, 229, 544–545. See also Epidemiology

Seaside Therapeutics studies,

523–524

Secretin,

481

Sedation,

450, 458, 459

SEGAs

. See Subependymal giant cell astrocytomas

Seizures

copy number variants and,

294

FXS and,

267

glucose metabolism and,

389

NAC as treatment for,

506

past medical history,

51

Rett syndrome and,

307, 312

rTMS adverse effect,

609

treatment,

61–62, 66

Selective eating,

143

Selective mutism,

54

Selective norepinephrine reuptake inhibitors,

461–463

Selective responding,

547, 548

Selective serotonin reuptake inhibitors (SSRIs)

about,

57–60, 58, 416, 427–430

citalopram,

60, 419, 426, 427–428

escitalopram,

60, 312, 419, 428

fluoxetine,

58, 59–60, 381, 388, 420–421, 426, 428–429

fluvoxamine,

60, 421–422, 426, 429–430

paroxetine,

422, 430

prenatal exposure risks,

187

sertraline,

270, 312, 422–423, 426, 430

Self development,

571

Self-help skills (hand washing, dressing, safety skills),

549

Self-injurious behaviors (SIBs)

guanfacine adverse effect,

459–460

NAC efficacy,

509

prevalence,

44, 45

treatment,

60–61

Sensory processing,

54, 82, 144, 324–325, 490

Sequential Oral Sensory Approach to Feeding,

146

Serotonergic medications,

415–437

about

background and overview,

415–417

conclusion,

433

future directions,

433–434

key points,

434

recommended reading,

434

clinical trials,

417–419, 419–425

5-HT receptors,

312, 392–393, 444, 445

serotonin modulators,

417, 432–433, 471. See also Buspirone; Mirtazapine

side effects,

426–427

SNRIs,

416–417, 430–431. See also Venlafaxine

SSRIs,

57–60, 58, 416, 427–430. See also Selective serotonin reuptake inhibitors

TCAs,

417, 431–432. See also Clomipramine

Serotonin

metabolism,

415–416

neurotransmission,

391–394, 393, 416–417

Serotonin-norepinephrine reuptake inhibitors (SNRIs),

416–417, 430–431

Serotonin transporter (SERT),

416–417

Serotonin transporter–linked polymorphic region (5-HTTLPR),

416

Sertraline,

270, 312, 422–423, 426, 430

[¹⁸F]Setoperone,

392–393

Sex steroid replacement therapy,

327

Sexual identity development

about

background and overview,

91

conclusion,

97–98

key points,

98

recommended reading,

98

collaborative ASD treatment,

95–97

definitions,

93

development process,

92–93

minority status and,

94

Shagreen patches,

279

Shaping (behavioral shaping),

546

Siblings,

53

SIBs

. See Self-injurious behaviors

Sign language,

50

Simons Searchlight,

159

Single nucleotide polymorphism (SNP),

85, 85, 86, 209, 496–497

siRNAs,

631

Skin biopsy,

84

Skin examination,

81

Skin picking,

65, 324–325, 326

Sleep disturbances and disorders

assessment and evaluation,

84

copy number variants’ effect on,

298

family history,

53

FXS and,

267

guanfacine adverse effect,

459–460

past medical history,

52

in Rett syndrome,

312

serotonin and,

416

treatment,

63, 270, 417

Sleep study (polysomnography),

84

Small-molecule drugs,

627–628

Smart glasses,

118–119

Smart-home devices,

117

Smartphone technology,

115, 120, 121

Smartwatch-based sensors,

120

Smith-Magenis syndrome,

158

sMRI (structural MRI),

366, 369

SNORD116 gene,

321

SNRIs

. See Serotonin-norepinephrine reuptake inhibitors

Social anxiety,

39, 268

Social Communication, Emotional Regulation, and Transactional Support (SCERTS) model,

592. See also Classroom SCERTS Intervention

Social Communication Questionnaire,

39

Social-communicative impairment (SCI),

127–141

about

background and overview,

127–128

key points,

138–139

recommended reading,

139

behavioral interventions,

549, 589, 591–592. See also Joint attention, Symbolic play, Engagement, and Regulation

clinical presentation,

36–39

comorbidity,

137–138, 268

copy number variants’ effect on,

292, 293

FXS and,

268

genetic studies and,

486

longitudinal course,

132–134, 134–135

neurobiology of,

134–137, 352, 353, 494, 495, 497–500, 499

oxytocin and,

485–486, 488, 490

PWS and,

326–327

reciprocal social behavior deficits,

127–128, 556

school-based interventions,

579–581

subclinical impairments,

129–131, 130

symptom clusters associated with,

128

treatment,

63–64, 65, 66, 431, 479

variation distribution,

129, 130

variation measurement,

131–132, 133

Social development,

544–545, 556–557

Social history,

53

Social isolation, suicide risk factor,

44–45

Social motivation deficits,

42

Social motivation hypothesis,

557, 558

Social phobias,

533

Social Responsiveness Scale (SRS),

131

Social Responsiveness Scale–2,

39

Social withdrawal,

39

Socioeconomic status,

16, 18–19, 102

Sodium valproate,

312

Somatic mosaicism,

309

Special interests, of autistic individuals,

661

Spectral electroencephalographic composition,

227

Speech analysis,

114–115, 116

Speech-generating devices (SGDs),

595

Speech impairments and delays

copy number variants and,

292, 293, 298

FXS and,

267

past psychiatric history,

50

sound production deficits,

588

treatment,

65, 430

Speech production in preverbal children,

589

Speech recognition devices,

114–117, 116

Spinal muscular atrophy type I,

631

Spontaneous electroencephalogram (EEG),

224

SRS

. See Social Responsiveness Scale

SSADH

. See Succinic semialdehyde dehydrogenase deficiency

SSRIs

. See Selective serotonin reuptake inhibitors

Stem cell gene therapy,

615–625

about

background and overview,

615–619

conclusion,

621

future directions,

621–622, 644

key points,

622

recommended reading,

622

implementation,

619–621

preclinical studies,

620–621

Stereotypic movements,

456, 466, 509, 512

Stimulants,

58, 62–63, 269–270, 456, 457–461. See also Clonidine; Guanfacine

Stimulus overselectivity,

547

Strengths, of autistic individuals,

662–663

Streptococcal infections,

51

Structural imaging research,

365–375

about

background and overview,

365–366

conclusion,

371

future directions,

367

key points,

371–372

recommended reading,

372

cerebellum,

368

cerebrospinal fluid,

369–371

macrocephaly/megacephaly,

366–368

sex differences in brain structure,

371

subcortical structures,

367–368

white matter morphology,

368–369

Structural MRI (sMRI),

366, 369

Subarachnoid fluid collections,

370

Subcortical tubers,

278–279

Subependymal giant cell astrocytomas (SEGAs),

278–279, 283, 284

Subependymal nodules (SENs),

278–279

Substance use disorders,

48, 52

Succinic semialdehyde dehydrogenase deficiency (SSADH),

394

Suicide ideation,

44–45

Sulforaphane,

478–479

Superior temporal gyrus,

487

Supplements,

479–480

Support severity index, for level of support,

132, 133

Survey methodology,

6–8. See also Epidemiology

Symbolic play,

569–572

Sympathetic nervous system monitoring,

111–112

Syndromic ASD,

253–263. See also Copy number variants; Fragile X syndrome; Prader-Willi syndrome; Rett syndrome; Tuberous sclerosis complex

about

background and overview,

253–255

conclusion,

260–261

future directions,

257–260, 258

key points,

261–262

recommended reading,

262

genetics and genomics,

156–158, 158

monogenetic syndromes,

255–258, 256, 258

targeted treatments,

260

Synthetic nanoparticle delivery systems,

621–622

Systemic inflammation,

51

Systemizing,

659–660, 660

Tactile defensiveness,

144

Taeniopygia guttata (zebra finch),

216–217

TANDs

. See TSC-associated neuropsychiatric disorders

Tantrums,

42

TAOK2 knockout,

295, 296, 297

Target and comorbid symptoms

. See Comorbidities and associated symptoms; Diet and nutrition; Social-communicative impairment

Task-based functional connectivity studies,

404–405

Task-free (intrinsic) functional connectivity studies,

405–406

Taste sensitivity,

144–145

TEACCH

. See Treatment and Education of Autistic and Related Communication Handicapped Children

Teaching Developmentally Disabled Children: The Me Book (Lovaas),

549

Technology

. See Digital biomarkers

Temperature monitoring,

112, 113, 117

Tendon reflexes,

82

Teratogens,

189

Testosterone,

327

Δ⁹-tetrahydrocannabinol (THC),

533

Texture refusal,

144

TGF-α

. See Transforming growth factor α

TGF-β

. See Transforming growth factor β

Thalamus,

393

“Theory of mind” tasks,

353

Theta burst stimulation (TBS) paradigm,

606, 609, 610

Thwarted belongingness,

44–45

Thyroid hormone replacement therapy,

327

Thyroid levels,

55

Tianeptine,

418

Tic disorders,

459

Timothy syndrome,

86

TMS

. See Transcranial magnetic stimulation

Topiramate,

312

Toxic metals,

83, 191–192

Transcranial magnetic stimulation (TMS),

603–614

about

background and overview,

59, 603–604

conclusion,

611

future directions,

609–610

key points,

611

recommended reading,

611–612

investigative studies,

605–606

limitations and concerns,

610–611

repetitive transcranial magnetic stimulation,

604, 606–611, 607–608

safety and side effects,

609

Transcription activator-like effectors,

616

Transcriptional regulation,

177

Transforming growth factor α (TGF-α),

241–243, 244

Transforming growth factor β (TGF-β),

238

Transgender persons,

92

Translational research,

667, 668

Translocator protein (TSPO),

395

Traumatic brain injury,

508–509

Trazodone,

312, 417, 433

Treatment and Education of Autistic and Related Communication Handicapped Children (TEACCH),

50, 581

Treatments

behavioral and educational

. See Behavioral interventions; Developmental, Individual Difference, Relationship-Based model; Early Start Denver Model; Language and communication interventions; School-based interventions

experimental treatments

. See Arbaclofen; Cannabis and cannabinoids; Complementary and integrative approaches; N-acetylcysteine (NAC) studies; Oxytocin; Vasopressin

future directions

. See Gene therapy; Patient advocacy groups; Transcranial magnetic stimulation

psychiatric medications

. See Pharmacotherapy

Trichotillomania,

65, 508

Trichuris suis ova (TSO),

58, 64, 532

Tricyclic antidepressants (TCAs),

417, 431–432. See also Clomipramine

Trofinetide,

313, 627

Tryptophan,

392, 395

TSC

. See Tuberous sclerosis complex

TSC1 (hamartin) gene,

277, 278, 283, 389–390

TSC2 (tuberin) gene,

277, 278, 283, 284, 389–390

TSC-associated neuropsychiatric disorders (TANDs),

279

TSPO (translocator protein),

395

Tuberin (TSC2) gene,

277, 278, 283, 284, 389–390

Tuberous sclerosis complex (TSC),

277–288

about

background and overview,

256–257, 256, 277

conclusion,

285

key points,

285

recommended reading,

285

ASD determinants,

282–284

ASD prevalence,

281

ASD profile,

281–282

assessment plan,

55

diagnostic criteria,

277–278

genetics,

157, 225, 277, 278, 283, 284

genetic testing,

86

glucose metabolism and,

389–390

intellectual disability prevalence,

280–281

mechanisms,

278

prevalence,

50, 158

systemic manifestations,

278–280

treatment,

66, 260, 284–285, 627

Twin studies,

130, 134–135, 138, 155–156, 156, 185, 192, 455

Type 1 diabetes mellitus,

53

Ubiquitin-protein ligase e3A (UBE3A) gene,

321

UCLA Young Autism Project,

549

Ulcerative colitis,

53

Underweight,

292–294

VABS

. See Vineland Adaptive Behavior Scale

Valproate,

58, 61–62, 513

Valproic acid,

189

Vasopressin,

493–503

about

background and overview,

58, 63–64, 493–494, 495

conclusion,

500–501

key points,

501

recommended reading,

501

animal studies,

497

behavioral studies,

494–497

clinical studies,

497–500, 499

genetic studies,

496–497

receptors,

494–500, 495

Venlafaxine,

417, 423, 426, 431

Ventral amygdalofugal system,

352

Ventral temporal cortex,

402

Video teleconferencing,

594

Vineland Adaptive Behavior Scale (VABS),

39, 418

Viral infections,

191, 241

Viral vector gene therapy,

615–616, 619–620, 628, 630, 632–636, 633

Virtual reality technology,

119, 119

Vitamin B₆/magnesium,

480

Vitamin D,

55, 480

Vitamin/mineral supplements,

146, 478, 479–480

Vocal characteristics,

38

Vocal imitation,

589

Voice recognition systems,

114–117, 116

Weak central coherence,

658

Weight gain,

449. See also Obesity

West syndrome,

225

White matter morphology,

368–369

Whole-exome sequencing (WES),

55, 85, 86, 161–163, 162, 164, 209–210

Whole-genome sequencing (WGS),

85, 86, 163–166, 165, 209–210

Wisconsin Card Sorting Task,

41

World Health Organization,

662

Wristbands,

112, 117–118

X-chromosome inactivation (XCI),

309

Yale-Brown Obsessive Compulsive Scale (Y-BOCS),

418

Zebra finch (Taeniopygia guttata),

216–217

Zebrafish (Danio rerio),

215–216

Zinc,

480

Zinc deficiency,

192

Zinc fingers,

616

Zolgensma (onasemnogene abeparvovec),

635–636, 637

Zolpidem,

312