The last 25 years have witnessed tremendous changes in our ability to detect autism very early in life and provide interventions that can significantly influence children's outcomes. It was once questioned whether autism could be recognized before children had developed language and symbolic play skills; now changes in early behaviors, as well as structural brain changes, have been documented in infants 6–12 months of age who later develop autism. Advances in brain imaging and genetics offer the possibility of detecting autism before the syndrome is fully manifest, thereby reducing or preventing symptoms from developing. Whereas the primary mode of behavioral intervention a few decades ago relied on operant conditioning, recent approaches integrate the methods of applied behavioral analysis within a developmental, relationship-focused intervention model that are implemented by both parents and clinicians. These interventions have been found to have positive effects on children's developmental trajectory, as measured by both behavioral and neurophysiological assessments. Future approaches will likely combine both behavioral and pharmacological treatments for children who have less robust responses to behavioral interventions. There has been a paradigm shift in the way that autism is viewed, evolving from a lifelong condition with a very poor prognosis to one in which significant gains and neuroplasticity is expected, especially when the condition is detected early and appropriate interventions are provided. The grand challenge for the future is to bridge the tremendous gap between research and the implementation of evidence-based practices in the broader community, both in the United States and worldwide. Significant disparities in access to appropriate health care for children with autism exist that urgently require advocacy and more resources.

Evidence suggests that the left frontal region is specialized for the expression of positive emotions, such as joy, whereas the right frontal region is specialized for certain negative emotions, such as distress. We previously reported that infants of mothers with depressive symptoms exhibited atypical patterns of frontal electroencephalographic (EEG) activity. We now extend these findings by examining the combined influence of maternal depression and attachment security on the infant's behavior and brain activity. Participants were 26 infants, 11–17 months of age, and their mothers. Twelve mothers reported elevated levels of depressive symptoms. Attachment behavior was observed in the traditional Strange Situation. While left and right, frontal and parietal EEG was recorded, infants were exposed to a baseline and three emotion-eliciting conditions (play with mother, stranger approach, maternal separation). During baseline and the condition designed to elicit positive emotion (play with mother), securely attached infants of symptomatic mothers exhibited reduced left frontal brain activity, compared to securely attached infants of nonsymptomatic mothers. During maternal separation, the most robust finding was that infants of symptomatic mothers, regardless of their attachment classification, exhibited reduced right frontal activity and lower levels of behavioral distress. The results suggest that both the mother's emotional well-being and her attachment relationship with her infant can influence infant frontal brain activity and affective behavior.

The effectiveness of imitating an autistic child's actions as a means for promoting social responsiveness and creative toy play was explored. Fifteen autistic children between the ages of 2 and 6 years and their mothers were assessed before and after a 2-week period during which they engaged in imitative play for 20 minutes per day. At the pre-intervention assessment, autistic children's gaze at mother's face was of longer duration, and their toy play was more creative during imitative play than during a free play session. At the post-intervention assessment, significant cumulative increases in duration of gaze at mother's face and creative toy play were found. Children's positive behavior changes were not found to be a function of developmental level of imitative ability, play skills, Vineland social age, IQ, or severity of autistic symptoms. Instead, the majority of children showed positive responses to this interactive strategy, regardless of these individual characteristics.

Dramatic changes take place in the neural physiology and emotional behavior of the human infant during the first 2 years of life. Evidence suggests that certain variations in the infant's early social environment, such as disturbances in mother-infant interaction that are associated with maternal depression, influence the development of biological systems related to the expression and regulation of emotion, particularly those systems involved in frontal lobe, autonomic, and adrenocortical functioning. In this essay, we provide an overview of the links between maternal depression and disruptions in early social and emotional development, and we highlight parallels between disturbances in biological systems found in depressed adults and those found in infants of mothers experiencing depression. We then discuss the possibility of sensitive periods for the enduring influences of maternal depression on the emotional development of these children and for increased risk for affective disorder. Finally, we point to directions for further research on the nature of the intergenerational transmission of emotional disturbance.

Currently, the heterogeneity in the developmental trajectories of autism spectrum disorders (ASD) is poorly understood. Preschool children with ASD participating in a longitudinal study received a battery of neurocognitive tasks that measured the learning of reward associations (Lrn-Rew), spatial working memory (SpatWM), and imitation from memory and novelty preference (Mem/Nov), as well as a measure of nonverbal problem-solving ability (NVDQ). Growth curve analyses via HLM were used to predict the variability in growth rates between age 4 to age 6.5 in Vineland Socialization and Communication scores. Individual differences in both Lrn-Rew and Mem/Nov were significantly related to Socialization and Communication growth rates above and beyond NVDQ, whereas SpatWM was not. Thus, specific aspects of neurocognitive functioning appear to be important predictors of developmental variability during the preschool years in children with ASD. We speculate that these findings support the combined role of ventromedial prefrontal and medial temporal lobe systems in the early pathogenesis of ASD and may be useful in predicting developmental trajectory. The benefits and challenges of assessing specific neurocognitive functions in children with autism is discussed with regard to general cognitive/developmental ability and the behavioral requirements of most assessment settings. (JINS, 2008, 14, 956–966.)

Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.

This study examines the relation between the longitudinal course of maternal depression during the child's early life and children's psychophysiology and behavior at age 6.5 years. One hundred fifty-nine children of depressed and nondepressed mothers were followed from infancy through age 6.5 years. Growth mixture modeling was used to identify classes of depressed mothers based on the longitudinal course of the mother's depression. School-aged children of chronically depressed mothers were found to have elevated externalizing behavior problems, decreased social competence, reduced frontal brain activation (EEG power), and higher respiratory sinus arrhythmia reactivity. Children of mothers with decreasing and stable mild depression were found to have increased hyperactivity and attention problems compared to children of nondepressed mothers. Contextual risk factors were found to mediate the relation between maternal depression and child behavioral outcomes.

Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual–spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.The writing of this paper and the studies reported herein were funded by a grant from the National Institute of Child Health and Human Development (NICHD Grant U19HD34565), which is part of the NICHD Collaborative Program of Excellence in Autism, and a center grant from the National Institute of Mental Health (NIMH Grant U54MH066399), which is part of the NIH STAART Centers Program.

Achieving progress in understanding the cause, nature, and treatment of autism requires an integration of concepts, approaches, and empirical findings from genetic, cognitive neuroscience, animal, and clinical studies. The need for such integration has been a fundamental tenet of the discipline of developmental psychopathology from its inception. It is likely that the discovery of autism susceptibility genes will depend on the development of dimensional measures of broader phenotype autism traits. It is argued that knowledge of the cognitive neuroscience of social and language behavior will provide a useful framework for defining such measures. In this article, the current state of knowledge of the cognitive neuroscience of social and language impairments in autism is reviewed. Following from this, six candidate broader phenotype autism traits are proposed: (a) face processing, including structural encoding of facial features and face movements, such as eye gaze; (b) social affiliation or sensitivity to social reward, pertaining to the social motivational impairments found in autism; (c) motor imitation ability, particularly imitation of body actions; (d) memory, specifically those aspects of memory mediated by the medial temporal lobe–prefrontal circuits; (e) executive function, especially planning and flexibility; and (f) Language ability, particularly those aspects of language that overlap with specific language impairment, namely, phonological processing.

In a recent article, Cowan, Harter, and Kandel (2000) concluded that much of the success and excitement engendered by modern neuroscience can be attributed to the incorporation of several previously independent disciplines into one intellectual framework. During the 1950s and 1960s, neuroanatomy, neurochemistry, neuropharmacology, and neurophysiology, disciplines that had largely functioned in a separate and distinct fashion, gradually merged into a unified field of neuroscience. The penultimate step in the coalescence of neuroscience occurred in the early 1980s, when neuroscience integrated with molecular biology and molecular genetics. The confluence of these fields enabled scientists to understand the genetic basis of neurological diseases for the first time without requiring foreknowledge of the underlying biochemical abnormalities. The final phase of the merger of neuroscience into a single discipline took place in the mid-1980s, when cognitive psychology joined with neuroscience, leading to the formation of cognitive neuroscience.

Research suggests that disruptions in early caretaking can have long-term effects on the hypothalamic–pituitary–adrenal (HPA) axis, which mediates the stress response. Children of depressed mothers are at increased risk for developing internalizing problems in part because of disruptions in their caretaking environment. The present study investigated whether children of depressed mothers exhibit elevated salivary cortisol levels. Salivary cortisol samples were collected from 45 7- to 8-year-old children of mothers with a history of depression and 29 children of nondepressed mothers. Samples were collected soon after arrival to the laboratory and after a mild laboratory stressor and at home after wakeup and before bedtime. Children who had elevated levels of internalizing symptoms and whose mothers had a history of depression showed elevated laboratory baseline cortisol levels. Children who were reported to have clinically significant internalizing symptoms were also more likely to show an elevated stress response to a mild laboratory stressor. When the longitudinal history of maternal depression was examined, maternal depression during the child's first 2 years of life was the best predictor of elevations in baseline cortisol at age 7 years. This study provides evidence that internalizing symptoms exist in conjunction with a more reactive hormonal stress system in children of depressed mothers. The results also provide preliminary evidence that exposure to maternal depression in the first 2 years of life may be related to children's cortisol levels later in life.

Previous work based on observations of home videotapes indicates that differences can be detected between infants with autism spectrum disorder and infants with typical development at 1 year of age. The present study addresses the question of whether autism can be distinguished from mental retardation by 1 year of age. Home videotapes of first birthday parties from 20 infants later diagnosed with autism spectrum disorder, 14 infants later diagnosed with mental retardation (without autism), and 20 typically developing infants were coded by blind raters with respect to the frequencies of specific social and communicative behaviors and repetitive motor actions. Results indicated that 1-year-olds with autism spectrum disorder can be distinguished from 1-year-olds with typical development and those with mental retardation. The infants with autism spectrum disorder looked at others and oriented to their names less frequently than infants with mental retardation. The infants with autism spectrum disorder and those with mental retardation used gestures and looked to objects held by others less frequently and engaged in repetitive motor actions more frequently than typically developing infants. These results indicate that autism can be distinguished from mental retardation and typical development by 1 year of age.

Individuals with autism have difficulty integrating information and generalizing previously learned concepts to new situations. It was hypothesized that these problems result from an underlying impairment in category formation. Persons with autism may not abstract a summary representation (a prototype) during category learning and, instead, may form categories by memorizing a list of rules. Children with autism, Down syndrome, and normal development participated in one set of category learning tasks that could be solved using a rule-based approach and a second set of tasks in which there was no rule that defined category membership (prototype tasks). In the rule-based tasks, all groups were successful at using a rule to learn a new category. In the prototype tasks, only the typically developing children were able to learn a new category. Neither the persons with autism nor the persons with Down syndrome appeared to develop a prototype during category learning. These data suggest that persons with autism and Down syndrome have difficulty categorizing new information by forming prototypes and, instead, tend to rely on a rule-based approach to learning.

This article provides a targeted review of the scientific literature on the effects of experience on early brain and behavioral development and later outcome as it pertains to risk for some forms of child psychopathology. It is argued that ample evidence exists indicating that the prenatal and early postnatal years likely represent a sensitive period with respect to the effects of stress on the developing nervous system and behavioral outcome, and with respect to the long-term beneficial effects of early interventions on brain and behavioral development for some genetically based disorders, such as phenylketonuria and autism. Moreover, evidence suggests that parental mental health during the first years of life has a significant influence on early brain activity and behavior, and long-term behavioral outcome. It is concluded that, although prevention and early intervention efforts should not exclusively focus on the earliest years of development, such efforts should begin during this period. By directing such efforts toward promoting optimal prenatal and infant–toddler development, the long-term negative consequences of factors that have their greatest influences during early development and which set the stage for future development can be minimized or avoided entirely. Several recommendations for public policy and future research pertaining to the effects of early experience on child outcome are offered.

In previous studies, infants of depressed mothers have been found to exhibit reduced left frontal brain electrical activity (EEG). The left frontal region has been hypothesized to mediate social approach behaviors and positive affective expression. These findings raise important questions about the cause and nature of atypical EEG patterns in infants of depressed mothers. The present study begins to address some of these questions by examining whether or not variations in patterns of frontal brain activity in infants of depressed and nondepressed mothers are related to variations in infant behavior as observed in naturalistic situations. If such relations exist, are they specific to certain behaviors hypothesized to be mediated by the frontal region (i.e., positive approach behaviors)? Frontal and parietal brain electrical activity was recorded from 14- to 15-month old infants of depressed versus nondepressed mothers during a baseline condition and during conditions designed to elicit interest and positive affect. Infant behavior was observed in naturalistic play conditions, with and without mother, on a separate day from EEG testing. Mothers provided information on infant temperament. Infants of depressed mothers showed less affection and touching of their mothers. For infants of depressed mothers only, reduced left frontal brain activity was found to be related to lower levels of affection toward mother, but not to infant temperament. Furthermore, increased generalized frontal activation was found to be related to higher levels of negative affect, hostility, and tantrums and aggression. Relations between infant brain activity and behavior were not found for parietal EEG activity. These results suggest that infant frontal electrical brain activity is related to variations in infant behavior, especially those involved in positive affiliative behavior and the expression and regulation of negative affect. The nature and cause of atypical patterns of brain activity and question of whether such atypical patterns of frontal brain activity predispose infants to affective disorders in later life are discussed.