Developmental psychopathology applies developmental concepts to the study of neurodevelopmental disorders. The relationship of disordered to non-disordered behaviour is considered, as are the early origins of maladaptive behaviours that may not appear in clinical form until adolescence or adulthood. Knowledge of normal development is utilized to study children whose development is atypical, in order to understand the natural history of their disorder and establish the developmental trajectory of that particular condition. Conversely, the investigation of such deviant behaviour associated with a particular disorder is considered in regard to our understanding of normal development. For example, attention-deficit hyperactivity disorder has been investigated as a disorder of executive functions of the prefrontal cortex, and autistic disorder as a disorder of social cognition and communication. In both instances, new knowledge about brain functions has been derived from these formulations. Among the neurodevelopmental disorders, the age of recognition varies, multiple causes are involved, and many transformations in behaviour may occur in determining their complex course. The goal is to understand the mechanisms and processes through which risk factors lead to the emergence of a disorder. Disordered behaviour is not viewed as a static condition, but is considered as part of a dynamic transactional engagement. Behaviour and development are viewed within a social context, and the transactional nature of interactions is considered from infancy through adulthood to understand these processes.

Attention-deficit hyperactivity disorder, pervasive developmental disorders, obsessive-compulsive disorder, Tourette’s syndrome, and childhood-onset schizophrenia are developmental neuropsychiatric disorders under active investigation and each is reviewed in the respective chapters. Their developmental psychopathology is investigated by addressing the origins and course of individual patterns of behavioural maladaptation in each of these disorders and determining their genetic bases, thought to be complex, and involving more than one gene. Information derived from genetics, developmental psychology, clinical psychology, psychiatry, sociology, physiological sciences, neurosciences, and epidemiology is included in the description of each of these disorders.

The interrelationship of the various child neuropsychiatric disorders is an important consideration. Disorders may be risk factors for other conditions, so that attention-deficit disorder may be a risk factor for conduct disorder. In this instance, the child’s behaviour affects the adult and the transactional interactions between child and adult may result in further disruptive behaviours. Moreover, there may be a developmental basis for disorders whose full presentation is not evident until later in life, as is the case with schizophrenia—generally considered to be a disorder of late adolescence or early adult life, but with origins in the developmental period.⁽³⁾ Some disorders may have co-occurring diagnoses that influence their outcome, as in Tourette’s syndrome, where co-occurring conditions may determine the behavioural presentation. In Tourette’s syndrome, obsessive-compulsive symptoms may be an aspect of ‘pure’ Tourette’s syndrome, while co-occurring disruptive behaviour may be secondary to co-occurring attention-deficit disorder. Social and behavioural dysfunction in children with Tourette’s syndrome is largely ADHD-specific. Children with TS alone have a different social-emotional profile.^(4,5,6) Compulsive behaviours may not only interfere with the normal routines for the affected child but also become particularly problematic for their impact on other family members.

Particular patterns of behaviour, temperament, and psychopathology may be associated with specific chromosomal and genetic disorders.^(2,5,7,8,9) The term ‘behavioural phenotype’ was introduced by Nyhan in 1972^(7,10) to describe patterns of unusual behaviour that are so characteristic that they suggest a specific neurogenetic disorder. Nyhan described stereotypical patterns of behaviour occurring in syndromic fashion in sizeable numbers of affected individuals with a given syndrome, and observed that these patterns seemed self-programmed. In these children, he proposed that it is reasonable to hypothesize that their behaviours are associated with an abnormal neuroanatomy and that such stereotypical patterns of unusual behaviour could reflect the presence of structural deficits in the central nervous system. Recent developments in the neurosciences provide a means to investigate the biological bases of behavioural phenotypes. Behavioural assessments, neuropsychological testing, and neuroimaging procedures, carried out in well-characterized genetic syndromes, are being utilized to understand pathways from genes to cognition and complex behaviours in these conditions.

Comprehensive study of children with different neurogenetic disorders may increase our appreciation for the relative contribution of genetic variables in the pathogenesis of specific, affective, and behavioural disorders. Behavioural phenotypes have been studied most extensively in Down syndrome (language),⁽¹¹⁾ fragile × syndrome (gaze aversion, hyperkinesia, autistic-like behaviour),⁽¹²⁾ Williams syndrome (sociability, hyperverbal behaviour, and visuospatial deficits),^(13,14) Lesch-Nyhan syndrome (compulsive self-injury and aggression),^(15,16,17) and Prader-Willi syndrome (hyperphagia, obsessive-compulsive behaviour).^(13,18,19) The number of identifiable behavioural phenotypes is growing with careful observations of behaviours in neurogenetic disorders.^(8,9) Besides behaviours, particular temperamental features have also been considered in these disorders. However, when studying temperament, the appropriate measures must be chosen. For example, when Down syndrome, proposed to be linked to a particular temperament, was studied using temperamental clusters of easy temperament, slow to warm-up, and difficult temperament, Gunn et al.⁽²⁰⁾ demonstrated both easy and difficult temperament in children with Down syndrome; therefore, a typical temperamental pattern among these three categories was not demonstrated. However, when a more comprehensive assessment was carried out in other syndromes⁽²¹⁾ (that included the personality factors of extraversion,
agreeableness, conscientiousness, emotional stability, and openness, along with motor activity and irritability), specific personality phenotypes were identified. These were differentially related to parental behaviours and family context in Prader-Willi, fragile X, and Williams syndromes. Moreover, isolated special abilities, as in calculation and in music,⁽²²⁾ are recognizable that might be considered as phenotypes and linked to the proposed modular organization of the central nervous system. Finally, physical and behavioural phenotypes are not only identified in neurogenetic syndromes but also in those caused by environmental events, such as intrauterine exposure to alcohol: namely, the foetal alcohol syndrome. Because alcoholism is a familial disorder, there may vulnerability to its effects resulting in a severe presentation in some individuals and less severe presentation in others.⁽²³⁾

Both traditional Mendelian laws of inheritance (Lesch-Nyhan syndrome) and non-traditional inheritance have been identified in conditions with behavioural phenotypes. Among the non-traditional forms of inheritance are triplet repeat amplification (fragile × syndrome), microdeletion or contiguous gene deletion (Williams syndrome), imprinting (Prader-Willi syndrome), transcriptional derepression (Rett’s syndrome), and excessive gene dosage (Down syndrome). A key finding is the recognition that mutations of single genes can lead to complex behavioural symptoms, especially if the affected protein is essential for the expression or processing of multiple ‘downstream’ genes.

Behavioural phenotypes are also discussed in relation to intellectual disability in Chapter 10.5.1.

Neurobehavioural teratology investigates abnormal development of the nervous system and of cognition and complex behaviour that results from prenatal environmental insults. Neurobehavioural research addresses the prevalence of cognitive behavioural disorders in exposed individuals and the consequences of the brain insult on other developing brain systems, to identify risks for functional or behavioural deficits. Investigators focus on cognitive behavioural deficits and their underlying anatomy and embryology. Assessment emphasizes not only IQ but also neuropsychological profiles, because learning disability or difficulty in visuomotor integration may be evident in children who function in the low to average range of general mental ability.

The natural history of intrauterine drug exposure on motor, cognitive, emotional, and social behaviour is an area of growing concern. Multiple drug exposures during pregnancy are common among substance-abusing mothers. Of syndromes associated with intrauterine substance abuse, alcohol abuse has been studied the most extensively. Subsequently, retinoids, anticonvulsants (lithium, tegretol, and valproic acid), and the selective serotonin-reuptake inhibitors have also been studied. Other teratogens do not lead to major malformations of the nervous systems but they do compromise its integrity (for example, lead, heroin, methadone), and are associated with neurotoxic damage or effects on neurochemical systems.

The greatest period of vulnerability to drugs in a human pregnancy is during the period of embryogenesis (days 14 to 60). During embryogenesis, many neurobehavioural teratogens (for instance, retinoids and ethanol) produce syndromes with abnormalities that involve craniofacial, neural, and major organ systems. Behavioural abnormalities without detectable physical abnormality can occur when the insult occurs during the foetal period. The extent of malformation is stage-specific and dose-dependent, with outcomes ranging from death with malformation, malformation and survival, effects on growth, and cognitive-neuropsychological or behaviour disorder. The same exposure to alcohol needed to produce cognitive behavioural change in the foetal period would generally cause malformation if it occurred during embryogenesis. The term ‘developmental toxicology’ is sometimes used if the insult occurs in the postnatal period.

There may be a genetic vulnerability that influences the extent of expression of response to environmental toxins in an individual. A common family of regulatory genes is involved in the formation of structures of the face, head, hindbrain, parts of the heart, and thymus gland, all of which share a common origin from neural crest cells (anterior neural tube). These regulatory genes, known as HOX genes, provide rules for assembling various structures and for determining particular anatomical segments.⁽²⁴⁾ Homozygous HOXA1 mutations have been shown to disrupt human brainstem, inner ear, cardiovascular and cognitive development. Because the retinoid family is involved in controlling these HOX genes,⁽²⁵⁾ a similar pattern is produced by excessive retinoid administration, as in hypervitaminosis of vitamin A (retinol). Moreover, the enzyme alcohol dehydrogenase functions in the metabolism of both retinol and ethanol so that intoxicating levels of ethanol can competitively inhibit the metabolism of retinol and impact brain development. Thus, both genetic and teratogenetic agents may produce similar developmental abnormalities. Understanding these mechanisms helps to understand how an abnormal facial appearance may suggest an abnormal brain.

Children with the full foetal alcohol syndrome demonstrate prenatal and postnatal growth deficiency, microcephaly, infantile irritability, mild to moderate intellectual disability, and a characteristic facial appearance.⁽²³⁾ The extent of the abnormality depends on the time of maximal exposure to alcohol and the dose. Approximately half of those affected have co-ordination problems, are hypotonic, and have attention deficits. Between 20 and 50 per cent have other birth defects, including eye and ear anomalies and cardiac anomalies. Those children who do not show growth retardation or congenital anomalies may show more subtle changes, such as attention problems, disruptive behaviour, reduced speed of information processing, motor clumsiness, speech disorders, fine motor impairment, and learning problems, especially in mathematics.^(23,27) These findings have been documented in a prospective longitudinal study of the effects of prenatal alcohol exposure on a birth cohort of 500 offspring who were selected from 1529 consecutive pregnant women in prenatal care in community hospitals.⁽²⁸⁾ Dose-dependent effects are most clear from the neurobehavioural status of subjects when regular neuro-developmental evaluations are carried out from birth to age 14 years. The more subtle abnormalities are referred to as ‘foetal alcohol effects’, or alcohol-related neurodevelopmental disorder. The full range of disabilities is described as foetal alcohol spectrum disorder.⁽²⁷⁾
Subjects with average to above-average IQ may demonstrate neuropsychological deficits in complex attention, verbal learning, and executive functioning. Disruptive behaviour, attention-deficit disorder, anxiety disorder, and communication disorder have been described^(29,31,33) in children with foetal alcohol syndrome and foetal alcohol spectrum disorder who test in the low normal range and in the moderate to severe range of intellectual disability.

The behavioural phenotype is characterized by problems in cognitive functioning, academic problems in arithmetic, difficulty with abstractions, understanding cause and effect, and generalizing from one situation to another. Thus, inattention, poor concentration, impaired judgement, memory deficits, and problems in abstract reasoning are characteristic. Behavioural problems related to impulsivity and hyperactivity makes them vulnerable to later diagnoses of oppositional defiant and conduct disorder.^(27,30)

Foetal alcohol spectrum disorder is not only a childhood disorder; the cognitive and behavioural effects and psychosocial problems may persist throughout adolescence into adulthood.^(28,33) Although the facial features are not as distinctive after puberty and the growth deficiency is not as apparent as in the younger child, the central nervous system effects do persist throughout life. Approximately 50 per cent of those affected function as intellectually disabled persons. Moreover, adaptive behavioural problems in communication skills and in socialization are apparent in those with foetal alcohol spectrum disorder whose intelligence test scores are in the normal range.

Poor judgement, attention problems, distractibility, difficulty in recognizing common social cues, and problems in modulating mood continue as characteristic features. Family environmental problems often continue as risk factors for behavioural problems if there is a lack of stability in family life. In one follow-up study⁽³⁴⁾ that used structured interviews with non-intellectually disabled affected subjects, the most common diagnoses were alcohol or drug dependence, mood disorders, and personality disorders (especially passive aggressive or antisocial). Further follow-up is needed to investigate the mechanisms involved in these psychiatric presentations, and particularly in determining the pathways leading to alcoholism.

Foetal alcohol syndrome is a common cause of neuropsychiatric disorders, with a worldwide incidence of approximately 1.9 in 1000 live births. When foetal alcohol syndrome and alcohol-related neurodevelopmental disorder are considered together, the combined rate in one study conducted in the United States was 9.1 in 1000.⁽³⁵⁾ Despite its frequency and severity, the syndrome may go unrecognized because physicians may not systematically enquire about alcohol use and may not recognize the spectrum of the effects of prenatal alcohol exposure on neurodevelopment.

The amount and pattern of alcohol consumption and the trimester of use during pregnancy, especially if during critical periods of brain development, are major factors in determining outcome. Binge drinking patterns with high blood concentrations are especially deleterious. Rapid changes in alcohol concentrations in the blood and central nervous system cause apoptotic damage (cell degeneration) in developing neurons and other cells in rat models.⁽³⁶⁾ Microcephaly is commonly reported in foetal alcohol syndrome and suggests an underdevelopment of the brain. Neuropathological studies demonstrate the underdevelopment or absence of the corpus callosum and enlarged lateral ventricles. Dendritic changes have been observed in animals with prenatal exposure to alcohol; these changes were correlated with decreased learning ability. Magnetic resonance imaging studies have documented brain abnormalities in foetal alcohol syndrome, particularly in midline frontal structures such as the corpus collosum.^(37,38) Research to identify specific polymorphisms contributing to foetal alcohol spectrum disorder is at an early stage. Polymorphisms of only one of the genes for the alcohol dehydrogenase enzyme family, the ADH1B, have been demonstrated to contribute to vulnerability.⁽³⁹⁾