Neurobiological correlates of social functioning in autism

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Abstract

Although autism is defined by deficits in three areas of functioning (social, communicative, and behavioral), impairments in social interest and restricted behavioral repertoires are central to the disorder. As a result, a detailed understanding of the neurobiological systems subserving social behavior may have implications for prevention, early identification, and intervention for affected families. In this paper, we review a number of potential neurobiological mechanisms—across several levels of analysis—that subserve normative social functioning. These include neural networks, neurotransmitters, and hormone systems. After describing the typical functioning of each system, we review available empirical findings specific to autism. Among the most promising potential mechanisms of social behavioral deficits in autism are those involving neural networks including the amygdala, the mesocorticolimbic dopamine system, and the oxytocin system. Particularly compelling are explanatory models that integrate mechanisms across biological systems, such as those linking dopamine and oxytocin with brain regions critical to reward processing.

Introduction

Of all childhood psychiatric disorders, autism is among the most pervasive and earliest to emerge. Diagnostic criteria for autism include three broad areas of impairment (American Psychiatric Association, 2000). The first relates to social interaction, including deficits in expression and gesture, social and emotional reciprocity, and sharing of interest. A second area of impairment is in communication, including deficits in behaviors ranging from spoken language to symbolic play. The third includes restricted and stereotyped behavior, interests, and activities, and encompasses rigid preferences for routine as well as repetitive motor mannerisms. Although the features of autism are often referred to as a “triad of impairment” (Wing, 1981), social impairments may be foundational, as longitudinal studies suggest that early social deficits provide near perfect classification of later diagnosis (Dawson and Bernier, 2007, Osterling and Dawson, 1994). The term ‘autism spectrum disorder’ (ASD) is often used to encompass classic autism, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDDNOS; Dawson & Faja, 2008), and thus the diagnosis is characterized by a great deal of heterogeneity. Although autism is often considered a disorder of childhood due to the diagnostic requirement of impairment by age three, its effects persist throughout the lifespan.

Family studies reveal a strong genetic component for ASDs. Concordance among monozygotic twins ranges between 69 and 95%, whereas concordance among dizygotic twins ranges from 0 to 24% (Bailey et al., 1995, Folstein and Rutter, 1977, Ritvo et al., 1985, Steffenburg et al., 1989). However, despite the high heritabilities found in behavioral genetics studies, specific genes involved in the etiology of ASD have been elusive, although it is clear that the disorder is polygenic (Dawson & Faja, 2008). At present, some candidate genes include the serotonin transporter (5-HTT), engrailed 2 (En-2), and the oxytocin receptor (OXTR; Bartz and Hollander, 2008, Dawson, 2008). To date, much work remains to elucidate genetic characteristics of ASD, as well as biomarkers and endophenotypes that indicate specific genetic risk.

Before considering the biological bases of social impairments in ASD, it is useful to characterize such impairments behaviorally. Dawson and Bernier (2007) describe five particular areas of social functioning in which individuals differ from age-matched controls as early as preschool. The first, social orienting, refers to a tendency to direct attention spontaneously toward social stimuli (Dawson, Meltzoff, Osterling, Rinaldi, & Brown, 1998). Whereas typically developing children demonstrate attraction to social stimuli shortly after birth, children with ASD are less likely to look preferentially or orient toward social stimuli (e.g., hands clapping and a voice calling their name) than are controls (Osterling and Dawson, 1994, Swettenham et al., 1998).

Such deficits in social orienting are likely responsible in part for the second area of social impairment, joint attention (Dawson, Meltzoff, Osterling, Rinaldi, & Brown, 1998). The ability to share awareness with others by sharing, following, and/or directing attention typically emerges during the first year of life (Mundy, Sigman, Ungerer, & Sherman, 1986), and supports the development of subsequent linguistic and social skills (Dawson et al., 2004, Toth et al., 2006). Children with ASD show well-documented deficits in both initiation and following of joint attention, even after accounting for deficits in social orienting more generally (Colombi et al., 2009, Leekam et al., 2000, Leekam and Ramsden, 2006, Naber et al., 2008, Sullivan et al., 2007).

Intertwined with both social orienting and joint attention is processing of facial information, the third area of difficulty (Dawson & Bernier, 2007). Whereas typically developing infants look preferentially toward human faces with in the first minutes after birth (Goren, Sarty, & Wu, 1975), lack of attention to faces is among the earliest indicators of ASD (Osterling et al., 2002, Osterling and Dawson, 1994). Both children and adults with ASD use less holistic face processing strategies, placing relatively greater emphasis on featural (as opposed to configural) information (Deruelle et al., 2004, Rosset et al., 2008), and may also prioritize information from the mouth over that of the eyes, resulting in decreased accuracy and efficiency relative to controls during tasks of race recognition or matching based on expression, gaze direction, or sex (Deruelle et al., 2004, Joseph and Tanaka, 2003, Klin et al., 2002).

A fourth area of impairment is in motor imitation. Typically, infants are able to imitate others from a very young age, perhaps as early as a few weeks (Meltzoff & Moore, 1977). By the end of their first year, they are able to imitate behavior selectively and flexibly based upon complex social cues (Nielsen & Carpenter, 2008). Children with ASD, in contrast, show deficits in spontaneous and prompted imitation of basic hand, facial, and body movements, as well as simple actions on objects (Colombi et al., 2009, Rogers et al., 2003). They are also less likely to imitate the style with which an action is performed (Hobson & Hobson, 2008) and do not discriminate between “accidental” and “intentional” actions in their imitation, unlike children without the disorder (D'Entremont & Yazbek, 2007).

The final dimension of social deficit involves the degree to which individuals with ASD respond to emotional cues from others (Dawson & Bernier, 2007). At a basic level, those with ASD display difficulties in recognition of emotions based on visual and vocal cues (Golan, Baron-Cohen, Hill, & Golan, 2006). Interpersonally, individuals with ASD react differently to displays of distress by others (Sigman, Dissanyake, Corona, & Espinosa, 2003). In a number of studies assessing response to a feigned injury and consequent distress expressed by an experimenter, children with ASD looked less at the experimenter's face and supposed injury (Corona et al., 1998, Dawson et al., 2004). Children with ASD are also less likely than controls to provide a prosocial response during similar help-seeking paradigms (Bacon, Fein, Morris, Waterhouse, & Allen, 1998).

Following from this brief review, our goal in writing this paper is to review biological systems thought to subserve social functioning among individuals with and without ASD. From the discussion thus far, it is clear that ASD is characterized by early and pervasive deficits in social behavior. It is important to identify biological substrates of social functioning in ASD (and other disorders), as such knowledge may facilitate efforts at early detection, prevention, and intervention (Beauchaine, Neuhaus, Brenner, & Gatzke-Kopp, 2008). The following discussion is organized around multiple neurobiological levels of analysis that affect social behavior, including neural and hormonal influences. For each, we will focus on (1) functioning in the general population, and (2) functioning among individuals with ASD. As will become evident, the extent to which each system has been explored in ASD varies significantly. As a result, conclusions in many areas are premature and necessarily tentative.

Section snippets

The “social brain”

Nearly 20 years ago, Brothers (1990) identified a network of brain structures that have come to be known as the “social brain” (Zilbovicius et al., 2006). This network facilitates social cognition and behavior across a range of functions of varying complexity. Although the label “social brain network” is a useful heuristic by which to refer to these brain regions, it is somewhat misleading in that it exaggerates their functional specificity. Nonetheless, the network of structures and regions

Trait social affiliation

In contrast to the social brain model, in which a network of regions supports processing of socially-oriented information, are trait models of social behavior, which describe social functioning at the level of personality. Nearly all theories of personality structure posit a construct related to an individual's tendency to engage in and enjoy social relationships, often identified as a higher-order trait of “extraversion” or “reward dependence” (Buss and Plomin, 1984, Cloninger et al., 1993,

Additional neurotransmitters

Although not central to either of the frameworks discussed thus far, the roles of two additional neurotransmitter systems merit discussion. Both norepinephrine and serotonin contribute to social functioning among typical adults, and have consequently been the focus of investigation among individuals with ASD.

Conclusions and implications

Each of the models discussed in this review represents a system proposed to underlie normative social functioning in the general population, yet each provides insight at a different level of analysis, including genes, neurotransmitters, hormones, and neural organization and functioning. These models fall along a spectrum of specificity regarding the behaviors and functions they facilitate and/or predict. Whereas some attempt to account for precise behaviors that occur in discrete moments,

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