Emily Neuhaus

Ten good reasons to consider biological processes in prevention and intervention research

Most contemporary accounts of psychopathology acknowledge the importance of both biological and environmental influences on behavior. In developmental psychopathology, multiple etiological mechanisms for psychiatric disturbance are well recognized, including those operating at genetic, neurobiological, and environmental levels of analysis. However, neuroscientific principles are rarely considered in current approaches to prevention or intervention. In this article, we explain why a deeper understanding of the genetic and neural substrates of behavior is essential for the next generation of preventive interventions, and we outline 10 specific reasons why considering biological processes can improve treatment efficacy. Among these, we discuss (a) the role of biomarkers and endophenotypes in identifying those most in need of prevention; (b) implications for treatment of genetic and neural mechanisms of homotypic comorbidity, heterotypic comorbidity, and heterotypic continuity; (c) ways in which biological vulnerabilities moderate the effects of environmental experience; (d) situations in which Biology x Environment interactions account for more variance in key outcomes than main effects; and (e) sensitivity of neural systems, via epigenesis, programming, and neural plasticity, to environmental moderation across the life span. For each of the 10 reasons outlined we present an example from current literature and discuss critical implications for prevention.

Familial and temperamental predictors of resilience in children at risk for conduct disorder and depression.

In this study, we evaluated predictors of resilience among 8- to 12-year-old children recruited from primarily low socioeconomic status neighborhoods, 117 of whom suffered from clinical levels of conduct problems and/or depression, and 63 of whom suffered from no significant symptoms. Tests of interactions were conducted between (a) paternal antisocial behavior and maternal depression and (b) several physiological indices of child temperament and emotionality in predicting (c) childrens conduct problems and depression. Both internalizing and externalizing outcomes among children were associated specifically with maternal melancholic depression, and not with nonmelancholic depression. In addition, low levels of respiratory sinus arrhythmia (RSA) among children conferred significant risk for depression, regardless of maternal melancholia, whereas high RSA offered partial protection. Furthermore, high levels of maternal melancholia conferred significant risk for child depression, regardless of paternal antisocial behavior, whereas low levels of maternal melancholia offered partial protection. Finally, low levels of electrodermal responding (EDR) conferred significant risk for conduct problems, regardless of paternal antisocial behavior, whereas high EDR offered partial protection. None of the identified protective factors offered complete immunity from psychopathology. These findings underscore the complexity of resilience and resilience-related processes, and suggest several potential avenues for future longitudinal research.

Neurobiological correlates of social functioning in autism

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.

The effects of allostatic load on neural systems subserving motivation, mood regulation, and social affiliation

The term allostasis, which is defined as stability through change, has been invoked repeatedly by developmental psychopathologists to describe long-lasting and in some cases permanent functional alterations in limbic-hypothalamic-pituitary-adrenal axis responding following recurrent and/or prolonged exposure to stress. Increasingly, allostatic load models have also been invoked to describe psychological sequelae of abuse, neglect, and other forms of maltreatment. In contrast, neural adaptations to stress, including those incurred by monoamine systems implicated in (a) mood and emotion regulation, (b) behavioral approach, and (c) social affiliation and attachment, are usually not included in models of allostasis. Rather, structural and functional alterations in these systems, which are exquisitely sensitive to prolonged stress exposure, are usually explained as stress mediators, neural plasticity, and/or programming effects. Considering these mechanisms as distinct from allostasis is somewhat artificial given overlapping functions and intricate coregulation of monoamines and the limbic-hypothalamic-pituitary-adrenal axis. It also fractionates literatures that should be mutually informative. In this article, we describe structural and functional alterations in serotonergic, dopaminergic, and noradrenergic neural systems following both acute and prolonged exposure to stress. Through increases in behavioral impulsivity, trait anxiety, mood and emotion dysregulation, and asociality, alterations in monoamine functioning have profound effects on personality, attachment relationships, and the emergence of psychopathology.

Sympathetic- and Parasympathetic-Linked Cardiac Function and Prediction of Externalizing Behavior, Emotion Regulation, and Prosocial Behavior Among Preschoolers Treated for ADHD

OBJECTIVE To evaluate measures of cardiac activity and reactivity as prospective biomarkers of treatment response to an empirically supported behavioral intervention for attention-deficit/hyperactivity disorder (ADHD). METHOD Cardiac preejection period (PEP), an index of sympathetic-linked cardiac activity, and respiratory sinus arrhythmia (RSA), an index of parasympathetic-linked cardiac activity, were assessed among 99 preschool children (ages 4-6 years) with ADHD both at rest and in response to behavioral challenge, before participants and their parents completed 1 of 2 versions of the Incredible Years parent and child interventions. RESULTS Main effects of PEP activity and reactivity and of RSA activity and reactivity were found. Although samplewide improvements in behavior were observed at posttreatment, those who exhibited lengthened cardiac PEP at rest and reduced PEP reactivity to incentives scored higher on measures of conduct problems and aggression both before and after treatment. In contrast, children who exhibited lower baseline RSA and greater RSA withdrawal scored lower on prosocial behavior before and after treatment. Finally, children who exhibited greater RSA withdrawal scored lower on emotion regulation before and after treatment. CONCLUSIONS We discuss these findings in terms of (a) individual differences in underlying neurobiological systems subserving appetitive (i.e., approach) motivation, emotion regulation, and social affiliation and (b) the need to develop more intensive interventions targeting neurobiologically vulnerable children.

Brief report: social skills, internalizing and externalizing symptoms, and respiratory sinus arrhythmia in autism.

Theoretical and empirical models describe respiratory sinus arrhythmia (RSA) as a peripheral biomarker of emotion regulation and social competence. Recent findings also link RSA to individual differences in social functioning within autism spectrum disorder (ASD). However, associations between RSA and symptoms of internalizing/externalizing psychopathology in ASD have not been explored. We assessed RSA, social functioning, and internalizing/externalizing symptoms among boys with and without ASD. Compared with controls, participants with ASD evidenced reduced parasympathetic cardiac control, which correlated with social behavior. Symptoms were associated with deficiencies in RSA, over-and-above the contribution of social functioning. These findings yield a more nuanced understanding of parasympathetic function in ASD, and suggest a role for integrative intervention strategies that address socioemotional difficulties.

Age-related abnormalities in white matter microstructure in autism spectrum disorders

Abnormalities in structural and functional connectivity have been reported in autism spectrum disorders (ASD) across a wide age range. However, developmental changes in white matter microstructure are poorly understood. We used a cross-sectional design to determine whether white matter abnormalities measured using diffusion tensor imaging (DTI) were present in adolescents and adults with ASD and whether age-related changes in white matter microstructure differed between ASD and typically developing (TD) individuals. Participants included 28 individuals with ASD and 33 TD controls matched on age and IQ and assessed at one time point. Widespread decreased fractional anisotropy (FA), and increased radial diffusivity (RaD) and mean diffusivity (MD) were observed in the ASD group compared to the TD group. In addition, significant group-by-age interactions were observed in FA, RaD, and MD in all major tracts except the brain stem, indicating that age-related changes in white matter microstructure differed between the groups. We propose that white matter microstructural changes in ASD may reflect myelination and/or other structural differences including differences in axonal density/arborization. In addition, we suggest that white matter microstuctural impairments may be normalizing during young adulthood in ASD. Future longitudinal studies that include a wider range of ages and more extensive clinical characterization will be critical for further uncovering the neurodevelopmental processes unfolding during this dynamic time in development.

Electrodermal responding predicts responses to, and may be altered by, preschool intervention for ADHD.

OBJECTIVES To evaluate electrodermal activity (EDA) as a prospective biomarker of treatment response, to determine whether patterns of EDA are altered by treatment, and to assess oppositional defiant disorder (ODD) as a possible moderator of trajectories in EDA after an empirically supported behavioral intervention for attention-deficit hyperactivity disorder (ADHD) in preschool. METHOD Nonspecific fluctuations (NSFs) in skin conductance, which index sympathetic nervous system activity, were assessed among 4-6 year old children with ADHD (n = 99) before they participated with their parents in 1 of 2 versions of the Incredible Years intervention. All were reassessed at posttreatment, and a subgroup (n = 49) were assessed again at 1-year follow-up. RESULTS No difference in pretreatment NSFs was observed between ADHD participants and a group of normal control children (n = 41). Nevertheless, among those with ADHD, fewer NSFs at pretest predicted poorer treatment response on 4 of 7 externalizing outcomes. Furthermore, treatment was associated with increasing NSFs across time, but not for those who scored high on ODD at pretest. CONCLUSIONS Low EDA appears to mark resistance to treatment among preschoolers with ADHD. Furthermore, although our study was not experimental, treatment was associated with longitudinal increases in EDA, which were not observed in a normal control group. This may suggest increased sensitivity to discipline, with positive implications for long term outcome. In contrast to treated participants as a whole, however, those who scored high on ODD at pretest exhibited reduced EDA over time. (PsycINFO Database Record

Electrodermal Response to Reward and Non‐Reward Among Children With Autism

Pervasive social difficulties among individuals with autism spectrum disorder (ASD) are often construed as deriving from reduced sensitivity to social stimuli. Behavioral and neurobiological evidence suggests that typical individuals show preferential processing of social (e.g., voices, faces) over nonsocial (e.g., nonvocal sounds, images of objects) information, whereas individuals with ASD may not. This reduction in sensitivity may reflect disrupted reward processing [Dawson & Bernier, ], with significant developmental consequences for affected individuals. In this study, we explore effects of social and monetary reward on behavioral and electrodermal responses (EDRs) among 8‐ to 12‐year‐old boys with (n = 18) and without (n = 18) ASD, with attention to the potential moderating effects of stimulus familiarity. During a simple matching task, participants with and without ASD had marginally slower reactions during social vs. nonsocial reward, and boys with ASD had less accurate responses than controls. Compared to baseline, reward and non‐reward conditions elicited more frequent and larger EDRs for participants as a whole, and both groups showed similar patterns of EDR change within reward blocks. However, boys with and without ASD differed in their EDRs to non‐reward, and response amplitude was correlated with social and emotional functioning. These findings provide some support for altered reward responding in ASD at the autonomic level, and highlight the discontinuation of reward as an important component of reward‐based learning that may play a role in shaping behavior and guiding specialized brain development to subserve social behavior and cognition across the lifespan. Autism Res 2015, 8: 357–370.

Face processing among twins with and without autism: social correlates and twin concordance

Autism spectrum disorder (ASD) has a strong heritable basis, as evidenced by twin concordance rates. Within ASD, symptom domains may arise via independent genetic contributions, with varying heritabilities and genetic mechanisms. In this article, we explore social functioning in the form of (i) electrophysiological and behavioral measures of face processing (P1 and N170) and (ii) social behavior among child and adolescent twins with (N = 52) and without ASD (N = 66). Twins without ASD had better holistic face processing and face memory, faster P1 responses and greater sensitivity to the effects of facial inversion on P1. In contrast, N170 responses to faces were similar across diagnosis, with more negative amplitudes for faces vs non-face images. Across the sample, stronger social skills and fewer social difficulties were associated with faster P1 and N170 responses to upright faces, and better face memory. Twins were highly correlated within pairs across most measures, but correlations were significantly stronger for monozygotic vs dizygotic pairs on N170 latency and social problems. We suggest common developmental influences across twins for face processing and social behavior, but highlight (i) neural speed of face processing and (ii) social difficulties as important avenues in the search for genetic underpinnings in ASD.