Neurodevelopmental Disorders



Neurodevelopmental disorders form a new section in DSM-5 (American Psychiatric Association 2013), grouping conditions with very early onset. Consistent with the overall organization of DSM-5, they are all placed in the single list of all diagnoses. The neurodevelopmental disorders are characterized by a variety of developmental deficits that lead to impairment in functioning in multiple domains. The disorders included are intellectual disabilities, communication disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, specific learning disorder, and motor disorders.


Clinical Description

DSM-5 replaced the diagnosis of mental retardation (coded on Axis II in DSM-IV [American Psychiatric Association 2000]) with the term intellectual disability (also referred to as intellectual developmental disorder, the ICD-11 term). Intellectual disability was the preferred nomenclature used by many experts and advocates since the mid 2000s, as well as in a federal statute. The DSM-5 diagnosis of intellectual disability (ID) requires deficits in general mental abilities; deficits in adaptive functioning compared with peers of similar age, gender, and culture; and onset in the developmental period. Clinical assessment and standardized testing are both necessary in making the diagnosis of ID. Individuals with ID have IQ scores of two or more standard deviations below the mean (IQ of 65–75 or lower). Adaptive functioning is subdivided into three domains: conceptual (language, math, reading, writing, reasoning, knowledge, memory); social (empathy, social judgment, interpersonal communication, awareness of social and legal rules, friendships); and practical (abilities in self-care, employment, money management). Severity levels of ID are now classified by adaptive functioning rather than IQ, as was done in DSM-IV. Clinical features of the four levels of severity are listed in Table 3–1.

TABLE 3–1. Clinical features of intellectual disability





Percentage of intellectual disability population





Predominant socioeconomic class


Less low

Even distribution

Even distribution

Academic level achieved by adulthood

4th to 6th grade

2nd grade

Below 1st grade

Below 1st grade


Concrete and limited

More limited

Single words and phrases



Can acquire skills for minimum wage work

Rote work under protected conditions

Simple skills




Mostly living in highly structured and closely supervised settings

Mostly living in highly structured and closely supervised settings


Able to make change

Able to make small change

Able to use coin machines

Dependent on others for money exchange

Budget planning with effort or assistance

Usually able to manage pocket money

Dependent on others for money management

Dependent on others for money management


Prevalence of ID in the United States ranges from 1% to 3%, depending on age, how ID is defined, methods used for diagnosis, and the population being evaluated. All levels of severity of ID are more common in males (approximately 30% more common in males), but this difference decreases as severity of ID increases.


Of children and adolescents with ID, 30%–50% have a comorbid psychiatric disorder (Munir 2016). This rate is significantly higher than in youngsters of normal intelligence, in part because neurobiological and psychosocial causes of ID place the child at greater risk of psychiatric disorder. Almost every diagnostic category in psychiatry is represented. Prevalence estimates of comorbid conditions vary because of the challenge of distinguishing symptoms due to ID from those of a separate condition. Factors that increase the risk of psychiatric comorbidity include severity of disability, lower adaptive functioning, language impairment, poor socialization, lower socioeconomic status, and being cared for by a single parent.

The most common presentation is a constellation of symptoms that includes impulsivity, irritability, hyperactivity, short attention span, and language delay. The prevalence of attention-deficit hyperactivity disorder (ADHD) in individuals with ID is between 4% and 11%, similar to that in the general population. Symptoms of ADHD can be observed even in nonverbal children. However, in children with ID, inattention may be a sign of developmentally inappropriate expectations rather than ADHD. Frustration and limited expressive and receptive language may lead to aggressive temper outbursts.

Autism spectrum disorder (ASD) is the second most common co-occurring disorder for individuals with ID (Matson and Shoemaker 2009). There is much overlap in ID and ASD. Approximately 30%–40% of persons with ID have ASD, and 70% of persons with ASD have ID. Both ID and ASD can be caused by congenital rubella syndrome, tuberous sclerosis complex, and phenylketonuria. Some symptoms seen in ASD, including self-injurious behaviors, social isolation, and communication deficits, also may be found in persons with severe ID. ASD is diagnosed when there is evidence of severe social impairment relative to the patient’s developmental level. Stereotypic movements, including hand shaking or waving, body rocking, head banging, mouthing of objects, self-biting, picking at skin, and self-hitting, are among the more common behavioral presentations in individuals with ID, especially those with more severe impairment. Pica, rumination, cluttering, stuttering, and other language and speech disorders occur at increased rates in association with ID.

Depression can be a complication of ID (e.g., in response to extra burdens, poor self-image, and social stigmatization) or simply a coincidence, and occurs at a rate similar to or higher than that in the general population (Hurley 2006). Depression is probably underdiagnosed in persons with ID, given the reliance on the individual to express internal thoughts and feelings. Behaviors, such as aggression, may be attributed incorrectly to the ID, instead of to depressed mood. Depression in verbal, mildly intellectually disabled individuals presents more similarly to that in typically developing peers, although the patient’s reports may be more concrete. The diagnosis in moderately or severely intellectually disabled youth, however, requires observation in several settings. Occasionally, pharmacological or behavioral treatment is undertaken without a confirmed diagnosis of depression, with the hope that symptoms will improve. Rarely, individuals with ID may have rapid-cycling bipolar mood disorders. Suicidal ideation and behavior may occur among intellectually disabled individuals, but completed suicides are less prevalent than in typically developing youth.

Twenty-five percent of youth with ID have significant symptoms of anxiety. Diagnoses include generalized anxiety disorder, phobias, panic disorder, posttraumatic stress disorder, and obsessive-compulsive disorder (OCD). Fears of failing and loss of caregivers are among the environmental factors that increase the vulnerability of persons with ID to anxiety disorders. As in individuals affected by depression, patients with ID may not have the cognitive or verbal skills to describe specific cognitive or emotional symptoms, increasing the clinician’s reliance on behavioral observation and report of caregivers.


Intellectual disability results from psychosocial, biological, and environmental factors. In approximately 30% of cases, the etiology is unknown. Both biological and social factors influence risk for ID of unknown cause. Risk factors for ID of unknown etiology include low birth weight; male gender; mothers of African American, Latina, or Asian ethnicity; older mothers; lower level of maternal education; lower socioeconomic status; multiple births; or second or later birth order.

Most ID is idiopathic, associated with sociocultural or psychosocial disadvantage. Intellectual and adaptive deficits are presumed to be determined by the interaction of a polygenic mechanism and social factors (Table 3–2).

TABLE 3–2. Psychosocial causes of intellectual disability



Disease and infection

Inadequate preventive care and medical treatment

Sociocultural deprivation

Parental factors

Limited intelligence and education

Psychiatric disorders

Inadequate help-seeking behavior

Lack of psychosocial stimulation

Poor parenting skills

Child abuse and neglect

Lack of community programs

Early identification and diagnosis

Early intervention and infant stimulation

Specialized education

Vocational training and independent living

Intellectual disability of moderate, severe, or profound severity is less likely to be idiopathic. ID is associated with more than 200 recognized syndromes. Known biomedical etiologies are identified in 60%–90% of cases of severe or profound ID (Table 3–3). Virtually all types of genetic inheritance paradigms are represented when genetic causes of ID are considered (recessive, dominant, X-linked, single gene, polygenic).

TABLE 3–3. Biological causes of intellectual disability


Single gene defects (e.g., 22q11.2 deletion syndrome [velocardiofacial syndrome])

Inborn errors of metabolism (e.g., phenylketonuria)

Chromosomal abnormalities (e.g., fragile X syndrome, trisomy 21 [Down syndrome])

Polygenic inheritance


Maternal illness (e.g., diabetes, toxemia)

Maternal infection passed to fetus (e.g., rubella, cytomegalovirus, toxoplasmosis, syphilis, herpes, HIV)

Toxins (e.g., alcohol, tobacco, narcotics, lead, anticonvulsants)

Brain malformations

Extreme malnutrition

Intrauterine growth retardation

Gestational complications (e.g., placenta previa, umbilical cord prolapse, vaginal hemorrhages)


Extreme prematurity

Blood group incompatibility

Brain trauma

Cerebrovascular accident

Neonatal anoxia


Encephalopathy from hyperbilirubinemia

Infancy or childhood

Brain infection (e.g., meningitis, encephalitis)

Head trauma

Neurological disease

Brain tumor



Lead intoxication

Severe malnutrition

Down syndrome, the most common genetic cause of ID, occurs in about 1 of 1,000 births. Down syndrome is caused by a triplicate state of all or part of the critical region on chromosome 21, most often caused by errors in cell division of maternal origin. Risk increases with increase in maternal age. The phenotype is characterized by more than 80 features, including cognitive impairments (average IQ of 50), hypotonia, short stature, cardiac malformation, gastrointestinal malformation, distinctive facial appearance, and obesity. Individuals with Down syndrome can develop early-onset Alzheimer’s disease. Relative cognitive strengths include visual processing and relative weaknesses include language. A generalized deficit in executive function can lead to problems with attention, impulsivity, hyperactivity, and aggression. Social skills tend to be relatively stronger than other domains of adaptive functioning.

Fragile X syndrome (FXS), caused by trinucleotide expansion of the FMR1 gene, is the most common inherited cause of ID (1 in 4,000 males and 1 in 8,000 females). Characteristic physical stigmata—long face, prominent ears, prominent jaw, and macroorchidism (large testes)—are seen most clearly after puberty. Patients may have a high arched palate; hyperextensible finger joints; soft, velvetlike skin; and flat feet. The medical history may include seizures, recurrent infections, hernias, strabismus, or scoliosis. In some individuals with FXS, cognitive impairment may be absent. However, most affected males have moderate impairment, and affected females have mild impairment. Behavioral characteristics of individuals with FXS include hyperarousal, hyperactivity, social anxiety, shyness, and gaze aversion. Up to 25% of individuals with FXS meet criteria for autism (conversely, however, only 2% of individuals with autism have FXS). Other comorbid psychopathology includes schizotypal personality disorder and ADHD.

Course and Prognosis

The course of ID varies according to the etiology, severity, underlying genetic syndromes, and associated medical conditions. Medical care should address underlying conditions that can cause brain injury (e.g., shunting for hydrocephalus, diet for phenylketonuria). Associated medical conditions that compromise the child’s functioning can be prevented or adequately managed. Such conditions include seizures, otitis media, injury secondary to self-abusive behavior, and deafness and congenital cataracts (associated with Down syndrome). Treatment of comorbid psychiatric conditions can also influence the course (e.g., treatment of comorbid ADHD can enhance the ability to learn skills). Adaptive functioning outcome is also influenced by environmental variables, including parental intelligence, psychological resilience, and material resources, as well as community resources and barriers.

More severe levels of ID are diagnosed before the child is of school age, particularly when the ID is associated with a known phenotype or syndrome. In ID of moderate to mild severity, diagnosis is uncommon before age 5 years, rises sharply in the early school years, and peaks in the later school years. Higher observed prevalence during the school years is usually attributed to the adaptive and intellectual demands of school (especially for social interaction and abstract thinking). At all levels of severity, the normal sequence of cognitive developmental stages occurs, but the rate of developmental progress is slow and there is a ceiling on ultimate achievement. Delays in speech and language development may limit ability to express negative affect, leading to impulsive anger and low frustration tolerance. Insufficient financial resources, inappropriate or inadequate educational programming, and prejudices of communities and health care personnel can result in a wide variety of developmental, social, and medical complications. ID is not necessarily a lifelong affliction. Proper training that addresses clinical needs and uses the patient’s strengths can improve the level of functioning.

Evaluation and Differential Diagnosis

Intelligence tests are a necessary component of the diagnostic process (although there are potential challenges in using standardized tests in individuals with ID). The scores provide a general index of the individual’s developmental level. Test selection is based on age of the child and the child’s verbal ability. Tests measuring adaptive functioning vary in the domains assessed, child’s age, the identified informant, and setting of assessment. Table 2–7 (Chapter 2, “Evaluation and Treatment Planning”) lists individually administered tests of intellectual capacity, learning, and adaptive functioning. For very young children, the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) or the Denver Developmental Screening Test (DDST) may be used to estimate level of cognitive development. In 2015, the American Association on Intellectual Disability and Developmental Disabilities (AAIDD) published the Diagnostic Adaptive Behavior Scale (DABS), a test of adaptive functioning focused on diagnostic clarity.

Medical evaluation begins with a careful history that includes inquiry regarding potential familial disorders, neurophysiological insults, diseases with progressive deterioration, and seizure disorder. The physical examination should include a neurodevelopmental assessment of functional abilities and impairments and a search for abnormal neurological findings, dysmorphic features, or dermatological signs. Laboratory investigations are particularly important when there is no clear etiology for the ID. Genetic testing and recommendations are rapidly evolving. The American College of Medical Genetics and Genomics (ACMG) provides current guidelines for cytogenetic analysis in the diagnostic process ( Brain imaging may identify lesions that are surgically correctable or at least explanatory. If seizures are suspected, an electroencephalogram (EEG) is indicated. Individuals with ID require modifications in the standard psychiatric examination, according to their level of language and cognitive development. These patients often suffer from multiple disabilities and medical disorders that affect mood and behavior. Clinical assessment must be comprehensive and based on the patient’s presentation in multiple settings. Hyperactivity, aggression, sadness, lack of enthusiasm, excessive anxiety, and formal thought disorder are not primary features of ID and should lead to a full psychiatric evaluation, as should a significant change in mood, behavior, sleep, appetite, or level of adaptive functioning.

The differential diagnosis of ID includes environmental deprivation, learning disorders, autism spectrum disorder, communication disorders, borderline intellectual functioning, and impaired vision and/or hearing.


To address the multiple disabilities and complications associated with ID, developmentally sensitive multimodal treatment is optimal. The clinician should coordinate medical and psychiatric evaluations, parental guidance (support, education, behavior management, educational and environmental planning, long-term monitoring, and advocacy), and the standard therapies for concomitant psychiatric disorders. It is important to ensure the safety of the patient and those around him or her.

Behavior modification techniques, such as removing inappropriate attention; changing dysfunctional communication patterns (e.g., rewarding use of words or sign language); consistently applying social, self-care, academic, and vocational expectations; and structuring environmental contingencies, can reduce the frequency and severity of self-injury, stereotypies, pica, and asocial behavior. The behavioral program should be consistent and applied across settings, including home and school. Specialists may provide educational and developmental training to enhance speech and language; motor, cognitive, social, and occupational functioning; and adaptive skills such as toileting, dressing, grooming, and eating.

Developmentally oriented psychotherapeutic interventions may be effective in managing crises or in addressing long-term psychosocial goals. Therapy can focus on tangible objectives for the patient, including achieving greater independence, recognizing and expressing emotion, dealing with the reactions of others, developing social skills, and handling personal and practical challenges. Group therapy for adolescents and young adults can be useful for social skills training. Family therapy can focus on learning about the disability, emphasizing the patient’s strengths, reducing guilt and overprotection, and fostering greater independence.

Although no pharmacological treatments are available for ID per se, the frequency of comorbid psychiatric disorders may suggest the use of psychotropic medication. Treatment effects are often difficult to assess in developmentally disabled patients. Their impaired verbal skills may complicate the diagnostic process, measurement of efficacy, and detection of adverse effects. Heterogeneity among children with ID leads to variability in treatment effect. Youngsters with structural brain abnormalities often react differently to medications than do typically developing children, even when target symptoms are similar.

Before psychotropic medications are prescribed to individuals with ID, special considerations apply. Individuals with ID may have limited ability to communicate adverse effects, thus caregiver input is often necessary. Medications used for medical or neurological disorders associated with ID may have problematic side effects and/or ceilings on effectiveness and should be started at lower doses with more gradual increases. A significant change in the individual’s typical behavior warrants an investigation for a medical cause of discomfort. Medications typically used for ADHD are effective in the treatment of symptoms of impulsivity, hyperactivity, and inattention in ADHD in children with ID, although effect size is less and side effects are more prominent. Alpha-adrenergic agents also have shown to be effective in treating ADHD symptoms. Few studies exist on the psychopharmacological treatment of depression in these patients, but selective serotonin reuptake inhibitors (SSRIs) may improve mood, energy level, interest, and motivation. Individuals with ID may be more susceptible to behavioral activation with SSRI use. Mood lability and aggression can be treated with mood stabilizers and antipsychotics. Of the antipsychotics, the second-generation class of medications is generally preferred. Risperidone has been studied the most, showing positive effects on behaviors. However, weight gain and metabolic changes are also seen. Sleep disturbance is commonly seen in this population. Treating the sleep disturbance may indirectly yield improvement in behaviors. Melatonin has shown promising effects in small, open trials.


Clinical Description

DSM-5 communication disorders include language disorder, speech sound disorder, childhood-onset fluency disorder, and social (pragmatic) communication disorder. Communication disorders are deficits in speech, language, or communication abilities that interfere with academic or adaptive functioning. Speech is the expressive production of sounds and includes articulation, fluency, voice, and resonance. Language involves the effective, rule-governed use of a conventional system of symbols for communication. Communication includes verbal and nonverbal behavior that influences the behavior or ideas of other individuals. A child may have a disorder in more than one area of communication, and multiple cortical deficits are usually observed, particularly in sensory information processing and temporal auditory processing.


Speech and language disorders are evident in about 5% of the school-age population. Language disorders are more common in males and in children with psychiatric disorders, ID, or hearing impairment.


Many aspects of motor, sensory, and cognitive development must be intact for speech and language to develop normally. By age 5 years, children are expected to speak fluently and to comprehend speech. Adult articulation skills should be present by age 8 years. The range of normal functioning is broad, and development of language and speech skills continues for many years. Development of articulation and vocabulary is highly influenced by the child’s environment. Verbal and nonverbal communication skills include word finding (access and retrieval of verbal information), word relationships (semantics), sentence formation (syntax), along with giving and receiving feedback, following conversational structure and flow, responding to the context, adapting to meanings and external events (pragmatics), responding to one’s internal sense of events, and monitoring one’s own communication (metalinguistic skills). The development of these skills is a formidable task to achieve in 5 years.

The etiology of deficits is often unknown, but there is strong evidence for the heritability of expressive language disorders, both with and without articulation problems. Environmental factors also contribute and may include faulty speech models within the family and lack of stimulation of language. Hearing loss, even if mild, plays a significant role in the etiology of language and speech disorders. During the period of language development, fluctuating hearing capacity or degrees of hearing loss that are considered medically insignificant can diminish measured verbal IQ and academic performance. Even mild hearing loss (25–40 decibels) may delay development of articulation, expressive and receptive language, reading, and spelling.

Course and Prognosis

Relative deficits in articulation (speech sound production), expression (oral language production and use), and reception (comprehension) may be observable by age 2–3 years. Delays in speech and language frequently improve during development, so that early delays are not strongly predictive of subsequent psychiatric and learning disorders. Speech and language skills are eventually acquired in most cases, but other characteristics (concomitant psychiatric disorders, neuromotor problems, low IQ) may predict worse outcome.

Complications of speech and language disorders include progressive academic impairment, psychological distress, low self-esteem, anxiety regarding learning, and school dropout. Children with these disorders may have difficulty maintaining a conversation or expanding on a topic. Problems in social interactions may lead to peer problems and overdependence on family members. When frustrated, the young child may have tantrums or the older child may refuse to speak.

Evaluation and Differential Diagnosis

Multidisciplinary assessment is required to evaluate communication disorders. Specialized speech and language evaluation includes articulation, receptive skills (understanding single words, word combinations, and sentences), and expressive language skills (syntactic structures, vocabulary, and social appropriateness). The clinician may observe family characteristics and free speech between parents and child to assess social skills and nonverbal communication (vocalizations, gestures, and gazes). The clinician should obtain hearing acuity evaluation using audiometry or auditory evoked response (which does not require the child’s cooperation) and evaluate auditory attention (e.g., losing flow of conversation, inability to hear in a crowd, distractibility), discrimination, and memory. Nonverbal measures of IQ (see Table 2–7) are used in cases of suspected language delay.

Comorbid psychiatric disorders, including other developmental disorders, are common and should be carefully sought in the evaluation.

Differential diagnosis includes autism spectrum disorder, selective mutism, deafness, intellectual disability, medical and neurological disorders, and acquired aphasia. Children with a communication disorder may exhibit social awkwardness, resistance to change, and low frustration tolerance that approach the severity of ASD, but they have better social communication, empathic awareness, and abstraction than do children with ASD.


Hearing deficits should be addressed. Social involvement, imitation, and imaginative play are encouraged to increase verbal, communicative, and symbolic skills. Referral to a speech-language pathologist (SLP) for evaluation and ongoing therapy is essential. Psychiatric treatment of concurrent attentional, emotional, or behavior problems and educational management of academic skills disorders may be needed.

Specific Disorders

Language Disorder

Language disorder is characterized by persistent difficulties in the acquisition and use of language (spoken, written, signed, or other) due to deficits in language comprehension or production including reduced vocabulary, limited sentence structure, and impairments in discourse. This disorder includes both expressive and receptive language skills, which were classified as separate disorders in DSM-IV. Deficits result in limitations in communication, social participation, academic performance, and/or occupational function. Language disorder becomes evident in toddlerhood. There is early variability in prognosis, but function at age 4 years may be predictive of long-term prognosis. Children with receptive language difficulties have a poor prognosis compared with children who have only expressive deficits.

Speech Sound Disorder

Speech production requires both the knowledge of phonological speech sounds and the ability to move the jaw, tongue, and lips in coordination with breath to vocalize. In speech sound disorder (phonological disorder in DSM-IV), there are persistent difficulties with the production of speech sounds that interfere with speech intelligibility and cause limitations in communication, social participation, or academic achievement. This disorder may occur together with language disorder. It may be associated with other oral-motor skills deficits, including feeding problems. Speech sound disorder usually responds to speech therapy.

Childhood-Onset Fluency Disorder (Stuttering)

Stuttering is a disturbance of the normal fluency and time patterning of speech that is inappropriate for the age and language level of the individual. It may include sound or syllable repetitions, broken words, blocking, or tension in the production of words. Stuttering severity varies with the perceived stress of a situation, and fear and avoidance of speaking may develop. It typically begins by age 6 years, and 65%–85% of children with this disorder have full recovery. The severity of the disorder at age 8 years is predictive of persistence into adolescence or adulthood.

Speech therapy for stuttering, conducted by an SLP, involves intensive training of fluent speech skills; the fostering of self-esteem and social assertiveness; and the use of behavior therapy methods, such as modification of environmental and conversational factors that trigger stuttering, relaxation, role-playing, feedback, practice in speaking in different settings (e.g., reading aloud in a group, alone, in front of a classroom, on a telephone), and talking with different people (parents, relatives, friends, strangers). Education and counseling of family members regarding the disorder and ways to support the child’s speech efforts is advised.

Social (Pragmatic) Communication Disorder

Social (pragmatic) communication disorder (SCD), introduced in DSM-5, is characterized by persistent deficits in the social use of verbal and nonverbal communication as manifested by impairment in greeting or sharing information, in adjusting communication to match the social context and audience, in following the rules of conversation and storytelling (including reciprocity and using nonverbal cues), and in understanding nonliteral meanings of language or making inferences. Although syntax, word structure, and grammar of language are intact, pragmatics (i.e., the social use of language and communication) is impaired. These deficits in social communication result in impaired communication, social participation, relationships, and academic or occupational achievement.

A diagnosis of SCD should not be made in the presence of ID unless the social communication deficits are clearly in excess of the cognitive limitations. The diagnosis also cannot be made in very young children, because language development and acquisition of vocabulary typically are not sufficiently developed to assess social pragmatic deficits. Milder cases may not be recognized until adolescence.

A family history of ASD, communication disorders, or specific learning disorder increases the risk for SCD. It has been proposed that some of the children who were diagnosed under DSM-IV with pervasive developmental disorder not otherwise specified (PDD NOS) may now qualify for a diagnosis of SCD. SCD can be distinguished from autism spectrum disorder by the absence of current or previous history of repetitive or restricted patterns of behavior, interests, or activities. Other considerations in differential diagnosis are attention-deficit/hyperactivity disorder and social anxiety disorder. Because SCD is a new diagnosis, research (and even clinical experience) is lacking with regard to epidemiology, treatment, and prognosis.


Clinical Description

Autism spectrum disorder is a diagnostic category introduced in DSM-5 to replace the pervasive developmental disorders in DSM-IV: autistic disorder, Asperger’s disorder, PDD NOS, and childhood disintegrative disorder. This change was made because the separate diagnoses were not reliably made or consistent over time. The diagnostic criteria of ASD (Box 3–1) focus on impairment, relative to chronological and mental age, in two key areas: social interaction/communication and behavior, interests, and activities. Because ASD encompasses a broad range of clinical presentations, diagnostic specifiers are included to indicate level of severity; intellectual or language impairment; known associated medical, genetic, or environmental factors; comorbid neurodevelopmental, mental, or behavioral disorder; or catatonia. Although there is no longer a specific age-at-onset criterion, symptoms must be present in early childhood. Symptoms of ASD manifest most often in the second year of life. Individuals with milder ASD symptoms and normal IQ may first present for clinical attention in middle school or even in adolescence as their long-standing deficits become more salient with expectations for more advanced social functioning. A childhood history of completely normal social development, intact communication, and age-appropriate peer relationships precludes a later diagnosis of ASD.

Box 3–1 DSM-5 Diagnostic Criteria for Autism Spectrum Disorder

  1. Persistent deficits in social communication and social interaction across multiple contexts, as manifested by all of the following, currently or by history (examples are illustrative, not exhaustive; see text):

    1. Deficits in social-emotional reciprocity, ranging, for example, from abnormal social approach and failure of normal back-and-forth conversation; to reduced sharing of interests, emotions, or affect; to failure to initiate or respond to social interactions.
    2. Deficits in nonverbal communicative behaviors used for social interaction, ranging, for example, from poorly integrated verbal and nonverbal communication; to abnormalities in eye contact and body language or deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communication.
    3. Deficits in developing, maintaining, and understanding relationships, ranging, for example, from difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or in making friends; to absence of interest in peers.

  2. Restricted, repetitive patterns of behavior, interests, or activities, as manifested by at least two of the following, currently or by history (examples are illustrative, not exhaustive):

    1. Stereotyped or repetitive motor movements, use of objects, or speech (e.g., simple motor stereotypies, lining up toys or flipping objects, echolalia, idiosyncratic phrases).
    2. Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or nonverbal behavior (e.g., extreme distress at small changes, difficulties with transitions, rigid thinking patterns, greeting rituals, need to take same route or eat same food every day).
    3. Highly restricted, fixated interests that are abnormal in intensity or focus (e.g., strong attachment to or preoccupation with unusual objects, excessively circumscribed or perseverative interests).
    4. Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (e.g., apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement).

  3. Symptoms must be present in the early developmental period (but may not become fully manifest until social demands exceed limited capacities, or may be masked by learned strategies in later life).
  4. Symptoms cause clinically significant impairment in social, occupational, or other important areas of current functioning.
  5. These disturbances are not better explained by intellectual disability (intellectual developmental disorder) or global developmental delay. Intellectual disability and autism spectrum disorder frequently co-occur; to make comorbid diagnoses of autism spectrum disorder and intellectual disability, social communication should be below that expected for general developmental level.

Note: Individuals with a well-established DSM-IV diagnosis of autistic disorder, Asperger’s disorder, or pervasive developmental disorder not otherwise specified should be given the diagnosis of autism spectrum disorder. Individuals who have marked deficits in social communication, but whose symptoms do not otherwise meet criteria for autism spectrum disorder, should be evaluated for social (pragmatic) communication disorder.

Social deficits are the most consistent and reliable indication of ASD. Younger children fail to seek out peer interactions, whereas older individuals may express an interest in friendships and seek interpersonal experiences but lack the skills to initiate and maintain relationships. Individuals with ASD demonstrate persistent deficits in appreciating the feelings and thoughts of other people and in understanding the process and nuances of social communication. They prefer solitary games and relate to others primarily as “objects” in their play.

In many children with ASD, spoken language is either delayed or totally absent. Even in patients with normal language and IQ, deficits in pragmatic language are present, as seen in these patients’ inability to initiate or sustain reciprocal conversation. Communication may be characterized by echolalia, pronoun reversals, scripted or stereotyped phrases, and idiosyncratic meanings. Phonological (sound production) and syntactic (grammar) functions may be relatively spared, with more significant impairment of verbal semantics (sociocultural meanings) and pragmatics (rules of interpersonal exchange) and nonverbal aspects of communication (eye contact, facial expression, body language). Imaginative and symbolic functions (e.g., use of toys in play) are significantly impaired. Play is characterized by rituals, stereotypies, motor mannerisms, and preoccupations with parts of objects. Individuals with ASD are often cognitively rigid, finding it difficult to adjust to transitions between activities and unexpected changes in routine or in the environment and to compromise in social interactions. Some individuals with ASD are hypersensitive and may avoid sensory stimuli (certain tastes, loud sounds, textures of food or clothing).

Many individuals with ASD have subnormal intelligence, but a few show significant improvements in measured IQ with time or treatment. According to 2012 data from the Centers for Disease Control and Prevention (CDC), 31.6% of ASD patients had ID (IQ < 70), 24.5% had borderline intelligence (IQ 71–85), and only 43.9% had average to above average intelligence. Even in individuals with normal IQ, neuropsychological test results are often greatly scattered (often with discrepancies between verbal and nonverbal IQ) and inconsistent over time. Some individuals (known as savants) have unusual or special capacities in music, drawing, arithmetic, or calendar calculation.


Prevalence estimates of ASD vary widely. The most recent report from the CDC estimates national prevalence at 14.6 per 1,000 (1 in 68) 8-year-olds (Christensen et al. 2016). The reported overall prevalence rate has increased 123% from 2002 to 2010 but seems to have stabilized between 2010 and 2012. Increased prevalence estimates are likely due primarily to broader diagnostic criteria and increased awareness. There is a male predominance of 4 to 1. White children are more likely to be diagnosed with ASD than Hispanic or black children, though this is likely due to cultural or socioeconomic barriers to assessment and treatment.


ASD is a highly heritable condition with multiple implicated genes. The prevalence of autism in siblings is 4.5%. Monozygotic twins have a higher rate of concordance (60%–90%) than dizygotic twins, but it is not 100%, thus implicating the role of early environmental biological insults as well. There is no evidence that psychosocial factors or parenting patterns cause ASD.

A specific genetic cause of autism can be identified in about 15% of individuals, most often in those with profound or severe ID, developmental delays, or physical anomalies. Known medical causes include fragile X syndrome (5% of ASD individuals), tuberous sclerosis, and certain chromosomal abnormalities (15q11-13 maternal duplications; 16p11.2 duplications and deletions) (Volkmar et al. 2014). Seizure disorders appear in 20%–25% of patients with ASD (Volkmar et al. 2014). Neuroimaging studies demonstrate a wide range of structural and functional abnormalities but no consistent, diagnostic pattern.

Identified risk factors include advanced maternal or paternal age, a sibling with ASD, extremely premature birth, and closer spacing of pregnancies (Volkmar et al. 2014).

In multiple studies, the mumps, measles, and rubella (MMR) vaccine or the vaccine preservative thimerosal have not been found to increase the risk of ASD.

Course and Prognosis

ASD is often apparent in early infancy, but in some patients, the full disorder does not appear until after age 3 years. An initial period of seemingly normal development may be followed by developmental arrest or by regression with loss of previously developed abilities.

Children with ASD usually make gradual but erratic improvement, particularly during the school-age years. Occasionally patients make rapid unexplained developmental progress. Medical illness and environmental changes may precipitate behavioral dysregulation that may include compulsive, aggressive, or self-injurious behaviors, occasionally requiring pharmacological intervention. Adolescents may experience either continued developmental progress or behavioral deterioration. Conditions frequently comorbid with ASD include ADHD, anxiety, depression, motor incoordination, constipation, epilepsy, avoidant/restrictive food intake disorder, and sleep problems. DSM-5 allows a diagnosis of ADHD to be made in the presence of ASD, unlike DSM-IV.

Educational and supportive services have a marked beneficial effect. For the less severely impaired, treatment may lead to social skills and adaptations that permit employment and independent or group home living. Predictors of good adaptive outcome include higher IQ, better language skills (especially the ability to communicate verbally by age 5 years), greater social skills, and later appearance of symptoms.

Depending on severity, perhaps one-third of individuals with ASD are able to function independently as adults. However, even in these higher-functioning individuals, social deficits and cognitive rigidity may persist, making navigation of social interactions and life demands difficult, thereby increasing the likelihood of anxiety and depression.


The evaluation of the child with suspected ASD should be a thorough, multidisciplinary, collaborative process. The American Academy of Pediatrics recommends screening of all children for ASD at age 18 and 24 months. Examples of brief screening instruments that can be used by primary care physicians or nurses with very young children are the Checklist for Autism in Toddlers (CHAT), which includes parent interview and observations of the child (Scambler et al. 2001), and the Modified Checklist for Autism in Toddlers (M-CHAT-R; available at, which includes only parent interview. Early developmental, family, and medical histories are important. If ASD is suspected, the assessment should include a clinical evaluation by a child and adolescent psychiatrist, psychologist, or developmental pediatrician experienced in assessing children with ASD. In addition, it is important to assess language, cognition, social skills, and adaptive functioning. Testing by a speech and language pathologist can document abnormalities in abstract and pragmatic language, encoding of complex information, and attentional skills. The medical evaluation should screen for possible inborn metabolic, structural, or degenerative diseases or seizures. An EEG (indicated in the presence of seizure disorder or developmental regression), Wood’s lamp exam for tuberous sclerosis, and genetic testing are recommended to rule out medical etiologies (Volkmar et al. 2014). Audiological examination for possible deafness and examinations for other sensory deficits may be done. Patients who have a tendency to mouth objects should have serum lead levels drawn to check for lead intoxication. Psychological testing to assess cognitive ability and adaptive functioning and to establish the diagnosis of ASD may be indicated. Standardized diagnostic checklists (e.g., the Childhood Autism Rating Scale, Second Edition [CARS-2]) are based on clinical observation and parental recall of early behavior. The “gold standard” instruments for autism diagnosis in research are the Autism Diagnostic Interview, Revised (ADI-R), and the Autism Diagnostic Observation Schedule (ADOS), developed by Lord and colleagues. (CARS-2, ADI-R, and ADOS are available from Western Psychological Services; These instruments are not required for clinical diagnosis.

Differential Diagnosis

Rett syndrome occurs predominantly in females and includes deceleration of head growth, marked ID, hand-washing stereotypies, and loss of purposeful motor skills. Differential diagnosis also includes congenital deafness (but deaf children typically learn an alternative oral or sign language, lose their isolative behaviors, and develop expressive communication), congenital blindness (but blind children relate socially), developmental expressive and receptive language disorders (but children with these disorders are typically more sociable, communicate well in gestures, and do not have stereotypic and repetitive behavioral patterns), and juvenile-onset schizophrenia (distinguished by hallucinations, delusions, and thought disorder). Children with pure intellectual disability have a more even or global distribution of delays and fewer abnormalities in behavior or social relatedness. The differential diagnosis is particularly difficult in children with severe to profound ID. In very young children, reactive attachment disorder may be a consideration, but these cases are typically characterized by a history of severe neglect. In selective mutism the patient is able to speak in certain situations, such as at home or with familiar adults. Degenerative neurological diseases or Landau-Kleffner syndrome (acquired epileptic aphasia) may resemble ASD. Social (pragmatic) communication disorder overlaps with ASD in the domain of social interaction/communication but lacks past or current restricted and repetitive behavior or interests.


Patients fortunate enough to have early access to rigorous multimodal treatment show significant improvement. The milieu should be highly structured and should include special education, speech and language instruction, vocational training (for adolescents), and teaching of adaptive skills. Behavior therapy reduces unwanted symptoms; promotes speech, social interaction, and assertiveness; increases self-reliance and self-care skills; and facilitates exploration. Parent guidance is critical, both to provide education and to deal with emotional reactions such as guilt or denial. Parents can contribute to the child’s learning of language and self-care and adaptive skills, arrange for special education and for adjunctive services, and make long-term plans for the child. Training in behavior management skills is essential for a tolerable home environment and for maximizing the child’s potential.

Acute hospitalization or longer-term residential treatment may be needed in the context of severe aggression. Long-term outpatient follow-up is required, including periodic reassessment for seizures or mood or anxiety disorders.

Psychotropic medications may be used to ameliorate disruptive behavior or to treat coexisting psychiatric disorders. However, in the context of new or worsening aggression or self-injurious behavior, medication treatment should only occur after environmental stressors (e.g., changes in teacher, caregiver, routine, or environment) and medical etiologies (e.g., pain, infection) have been ruled out. Especially in nonverbal patients, physical discomfort can frequently be a cause for new or increased aggression or self-injurious behavior. Low doses of nonsedating antipsychotics, in conjunction with a highly structured treatment program, may help control behavioral symptoms, reduce excessive activity levels, and enhance the effect of behavior therapy. Controlled studies of atypical antipsychotics, such as risperidone, demonstrate clinical effectiveness with a relatively tolerable side-effect profile, although weight gain and metabolic syndrome are concerns in chronic use. The strongest evidence is for risperidone (McCracken et al. 2002) and aripiprazole (Owen et al. 2009) in reducing disruptive behavior and irritability (FDA-approved indications). Common side effects are sedation and weight gain. The risk of tardive dyskinesia may be higher in these patients because of the length of treatment and perhaps biological vulnerability. The α2-adrenergic receptor agonist clonidine has also demonstrated efficacy in treating irritability and aggression (Fung et al. 2016).

In patients with comorbid ADHD, one may consider stimulant medications, atomoxetine, or an α2 agonist such as guanfacine (Scahill et al. 2015) or clonidine. SSRIs are sometimes effective in reducing comorbid anxiety or depressive symptoms in patients with ASD, though one should titrate cautiously and monitor for agitation or behavioral activation.


Clinical Description

The syndrome of hyperactivity, impulsivity, and inattention was historically labeled “minimal brain damage,” “minimal brain dysfunction,” “hyperkinetic syndrome,” “hyperactivity,” or “ADD.” The prior diagnostic term, attention-deficit disorder (ADD), is no longer correct but is often used in the lay media, sometimes to refer to inattentive ADHD, and sometimes for the entire syndrome.

DSM-5 made few changes to ADHD, which was moved to the new neurodevelopmental disorders section (see Box 3–2 for DSM-5 criteria). Because of low reliability and longitudinal instability, the DSM-IV subtypes have been replaced by similar “presentations”: combined (meeting criteria for both inattention and hyperactivity–impulsivity), predominantly inattentive, and predominantly hyperactive/impulsive. Children with the predominantly inattentive presentation tend to be described as “daydreamers” or “spacey,” more often have comorbid anxiety and depression, are more likely to be neglected by peers, have fewer conduct and behavior problems, and present less frequently to psychiatric settings than do those with the combined presentation. The predominantly hyperactive/impulsive group consists largely of very young children for whom the inattention criteria are not yet developmentally appropriate. Longitudinal follow-up studies have found that for the majority of these children, the criteria for combined type/presentation are eventually met.

Box 3–2 DSM-5 Diagnostic Criteria for Attention-Deficit/Hyperactivity Disorder

  1. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development, as characterized by (1) and/or (2):

    1. Inattention: Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities:
      Note: The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility, or failure to understand tasks or instructions. For older adolescents and adults (age 17 and older), at least five symptoms are required.

      1. Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or during other activities (e.g., overlooks or misses details, work is inaccurate).
      2. Often has difficulty sustaining attention in tasks or play activities (e.g., has difficulty remaining focused during lectures, conversations, or lengthy reading).
      3. Often does not seem to listen when spoken to directly (e.g., mind seems elsewhere, even in the absence of any obvious distraction).
      4. Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (e.g., starts tasks but quickly loses focus and is easily sidetracked).
      5. Often has difficulty organizing tasks and activities (e.g., difficulty managing sequential tasks; difficulty keeping materials and belongings in order; messy, disorganized work; has poor time management; fails to meet deadlines).
      6. Often avoids, dislikes, or is reluctant to engage in tasks that require sustained mental effort (e.g., schoolwork or homework; for older adolescents and adults, preparing reports, completing forms, reviewing lengthy papers).
      7. Often loses things necessary for tasks or activities (e.g., school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones).
      8. Is often easily distracted by extraneous stimuli (for older adolescents and adults, may include unrelated thoughts).
      9. Is often forgetful in daily activities (e.g., doing chores, running errands; for older adolescents and adults, returning calls, paying bills, keeping appointments).

    2. Hyperactivity and impulsivity: Six (or more) of the following symptoms have persisted for at least 6 months to a degree that is inconsistent with developmental level and that negatively impacts directly on social and academic/occupational activities:
      Note: The symptoms are not solely a manifestation of oppositional behavior, defiance, hostility, or a failure to understand tasks or instructions. For older adolescents and adults (age 17 and older), at least five symptoms are required.

      1. Often fidgets with or taps hands or feet or squirms in seat.
      2. Often leaves seat in situations when remaining seated is expected (e.g., leaves his or her place in the classroom, in the office or other workplace, or in other situations that require remaining in place).
      3. Often runs about or climbs in situations where it is inappropriate. (Note: In adolescents or adults, may be limited to feeling restless.)
      4. Often unable to play or engage in leisure activities quietly.
      5. Is often “on the go,” acting as if “driven by a motor” (e.g., is unable to be or uncomfortable being still for extended time, as in restaurants, meetings; may be experienced by others as being restless or difficult to keep up with).
      6. Often talks excessively.
      7. Often blurts out an answer before a question has been completed (e.g., completes people’s sentences; cannot wait for turn in conversation).
      8. Often has difficulty waiting his or her turn (e.g., while waiting in line).
      9. Often interrupts or intrudes on others (e.g., butts into conversations, games, or activities; may start using other people’s things without asking or receiving permission; for adolescents and adults, may intrude into or take over what others are doing).

  2. Several inattentive or hyperactive-impulsive symptoms were present prior to age 12 years.
  3. Several inattentive or hyperactive-impulsive symptoms are present in two or more settings (e.g., at home, school, or work; with friends or relatives; in other activities).
  4. There is clear evidence that the symptoms interfere with, or reduce the quality of, social, academic, or occupational functioning.
  5. The symptoms do not occur exclusively during the course of schizophrenia or another psychotic disorder and are not better explained by another mental disorder (e.g., mood disorder, anxiety disorder, dissociative disorder, personality disorder, substance intoxication or withdrawal).

Specify whether:

Combined presentation: If both Criterion A1 (inattention) and Criterion A2 (hyperactivity-impulsivity) are met for the past 6 months.

Predominantly inattentive presentation: If Criterion A1 (inattention) is met but Criterion A2 (hyperactivity-impulsivity) is not met for the past 6 months.

Predominantly hyperactive/impulsive presentation: If Criterion A2 (hyperactivity-impulsivity) is met and Criterion A1 (inattention) is not met for the past 6 months.

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Nov 25, 2018 | Posted by in PSYCHIATRY | Comments Off on Neurodevelopmental Disorders
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