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The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants

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Title: The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants
Language: English
Authors: Paterson, Sarah J., Wolff, Jason J., Elison, Jed T., Winder-Patel, Breanna, Zwaigenbaum, Lonnie, Estes, Annette, Pandey, Juhi, Schultz, Robert T., Botteron, Kelly, Dager, Stephen R., Hazlett, Heather C., Piven, Joseph, Piven, J., Hazlett, H. C., Chappell, C., Dager, S., Estes, A., Shaw, D., Botteron, K. N., McKinstry, R. C., Constantino, J., Pruett, J., Schultz, R. T., Paterson, S., Zwaigenbaum, L., Elison, J., Evans, A. C., Collins, D. L., Pike, G. B., Fonov, V., Kostopoulos, P., Das, S., Gerig, G., Styner, M., Gu, H.
Source: Journal of Autism and Developmental Disorders. Jul 2019 49(7):2849-2863.
Availability: Springer. Available from: Springer Nature. 233 Spring Street, New York, NY 10013. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-348-4505; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 15
Publication Date: 2019
Sponsoring Agency: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
Contract Number: R01HD055741
HD055741S1
K01MH101653
Document Type: Journal Articles
Reports - Research
Descriptors: Autism, Pervasive Developmental Disorders, Infants, At Risk Persons, Personality, Age Differences
DOI: 10.1007/s10803-019-04003-2
ISSN: 0162-3257
Abstract: The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive--classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD.
Abstractor: As Provided
Entry Date: 2019
Accession Number: EJ1220871
Database: ERIC
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  Value: <anid>AN0137289979;aut01jul.19;2019Jul04.04:41;v2.2.500</anid> <title id="AN0137289979-1">The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants </title> <p>The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive—classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD.</p> <p>Keywords: Temperament; Infancy; Autism spectrum disorder</p> <p>The members of the IBIS Network group are listed in the acknowledgements.</p> <p>Infant siblings of children with autism spectrum disorder (ASD) are themselves at elevated risk for the disorder, and consequently have proven valuable for prospective studies of early developmental trajectories associated with a later diagnosis of ASD. Prospective longitudinal study designs also enable comparisons between high-risk infants who receive a diagnosis at 24 months (HR Pos) with those who do not (HR Neg). Several such studies have examined temperament in infant siblings of children with a diagnosis of ASD, seeking in part to investigate whether observable differences are present prior to the consolidation of ASD symptoms (Bolton et al. [<reflink idref="bib4" id="ref1">4</reflink>]; Clifford et al. [<reflink idref="bib9" id="ref2">9</reflink>]; del Rosario et al. [<reflink idref="bib10" id="ref3">10</reflink>]; Garon et al. [<reflink idref="bib17" id="ref4">17</reflink>], [<reflink idref="bib18" id="ref5">18</reflink>]; Zwaigenbaum et al. [<reflink idref="bib59" id="ref6">59</reflink>]).</p> <hd id="AN0137289979-2">Theoretical Approaches to Temperament</hd> <p>Temperament can be thought of as early emerging individual differences in "activity, affectivity, attention, and self-regulation" that have a biological basis, and are influenced by genetics and the environment (Shiner et al. [<reflink idref="bib55" id="ref7">55</reflink>], p. 437). Temperament differences are evident early in life, and play an important role in cognition and learning throughout development (Rothbart and Putnam [<reflink idref="bib48" id="ref8">48</reflink>]). A number of models of temperament have given rise to different measurement approaches but they are all grounded in the broad definition above (see, for example, Bieberich and Morgan [<reflink idref="bib2" id="ref9">2</reflink>]; Buss and Plomin [<reflink idref="bib7" id="ref10">7</reflink>]; Goldsmith et al. [<reflink idref="bib20" id="ref11">20</reflink>]; Rothbart and Bates [<reflink idref="bib45" id="ref12">45</reflink>]; Rothbart and Derryberry [<reflink idref="bib46" id="ref13">46</reflink>]; Thomas and Chess [<reflink idref="bib56" id="ref14">56</reflink>]). Rothbart's approach (Rothbart and Derryberry [<reflink idref="bib46" id="ref15">46</reflink>]) defines temperament as individual differences in regulation and reactivity and has a strong emphasis on neurobiological underpinnings and regulation.</p> <p>As noted above, because models of temperament fit a general overarching definition, many share consistent underlying factors (Zentner and Bates [<reflink idref="bib58" id="ref16">58</reflink>]). These factors include <emph>approach</emph> or <emph>surgency</emph>, which captures an individual's tendency to approach new people and things, and <emph>negative affect</emph>, which captures fear, sadness and anger. Some others include <emph>effortful control</emph> or <emph>regulatory capacity</emph>, which captures an individual's ability to adapt to their environment and regulate their emotions or activity level. Although the traits are relatively stable, each can be demonstrated through different behaviors at different stages of development as infants' capabilities change. Behaviors underlying surgency are evident from 2 to 3 months of age (Rothbart [<reflink idref="bib44" id="ref17">44</reflink>]) and negative affect is first seen stemming from the inability to disengage attention before 4 months (Johnson et al. [<reflink idref="bib22" id="ref18">22</reflink>]). Some aspects of effortful control emerge at the end of the first year of life and continue to develop throughout childhood (Kochanska et al. [<reflink idref="bib24" id="ref19">24</reflink>]; Rothbart and Bates [<reflink idref="bib45" id="ref20">45</reflink>]).</p> <p>In this study, we adopt the model of temperament devised by Rothbart and colleagues (Rothbart and Derryberry [<reflink idref="bib46" id="ref21">46</reflink>]) because of its wide use in the infancy field and its emphasis on biological bases (Rothbart and Putnam [<reflink idref="bib48" id="ref22">48</reflink>]; Rothbart & Derryberry [<reflink idref="bib46" id="ref23">46</reflink>]; Shiner and Caspi [<reflink idref="bib54" id="ref24">54</reflink>]; see Nigg [<reflink idref="bib35" id="ref25">35</reflink>] for a full review), enabling us to examine established constructs early in development that may inform underlying mechanisms of neural development.</p> <hd id="AN0137289979-3">Temperament in High-Risk Siblings</hd> <p></p> <hd id="AN0137289979-4">High-Risk Siblings at 6–7 Months</hd> <p>Findings about temperament early in the first year have been mixed. A study by Clifford et al. ([<reflink idref="bib9" id="ref26">9</reflink>]) examined infants at High Risk (HR) for ASD, and found that 7-month-old infants at high risk for ASD who later develop ASD (HR Pos) are higher in surgency behaviors than those who do not develop ASD (HR Neg), though they score lower on the approach subscale than infants with ASD. When the Low Risk ASD-Negative (LR Neg) group and the High Risk (HR) sibling groups were compared, the HR group as a whole also scored lower on surgency. In another study, del Rosario et al. ([<reflink idref="bib10" id="ref27">10</reflink>]) examined growth of temperament over time in high-risk siblings, and found that 6-month-old infants who developed ASD were more adaptable, less active, and more likely to approach than those who did not. The heightened approach behavior was similar to the increased surgency found in the HR Pos group by Clifford et al. ([<reflink idref="bib9" id="ref28">9</reflink>]). These findings of higher approach and adaptability at around 6 months are surprising at first glance, but Del Rosario et al. ([<reflink idref="bib10" id="ref29">10</reflink>]) suggest that this may reflect less inhibition of response to non-social objects, rather than more motivation for social approach, given that they used the Carey Temperament Scales (Carey and McDevitt [<reflink idref="bib8" id="ref30">8</reflink>]), which measure both social and non-social approach. They also suggest that adaptability might be high at 6 months given anecdotal reports from parents that their infants with ASD were passive or easy to manage (see Zwaigenbaum et al. [<reflink idref="bib59" id="ref31">59</reflink>]).</p> <hd id="AN0137289979-5">High-Risk Siblings at 12–14 Months</hd> <p>Whereas Clifford et al. ([<reflink idref="bib9" id="ref32">9</reflink>]) found that at 7 months, HR Pos infants were higher in surgency than HR Neg infants, they observed a reversal of this finding at 14 months, when lower surgency was found in both HR Pos and HR Neg infants compared to LR Neg controls. This study also found lower effortful control in all HR siblings relative to LR controls. Garon et al. ([<reflink idref="bib18" id="ref33">18</reflink>]) found that HR Pos infants at 12 months showed lower effortful control and higher negative affect than LR Controls, and that HR Pos infants had lower positive affect compared to HR Neg infants. In another study investigating high-risk siblings at 12 months of age, Zwaigenbaum et al. ([<reflink idref="bib59" id="ref34">59</reflink>]) found higher distress in ASD Pos infants relative to HR Neg and LR Neg groups.</p> <hd id="AN0137289979-6">High-Risk Siblings at 24 Months</hd> <p>At 24 months, a different and more consistent pattern is seen across studies. HR Pos children had lower effortful control than HR Neg children (Garon et al. [<reflink idref="bib17" id="ref35">17</reflink>], [<reflink idref="bib18" id="ref36">18</reflink>]) or controls, and also had higher negative affect than typically developing children (Clifford et al. [<reflink idref="bib9" id="ref37">9</reflink>]) and lower positive affect (Garon et al. [<reflink idref="bib18" id="ref38">18</reflink>]). Garon et al. found that HR Pos infants exhibited greater difficulty in controlling negative emotions and lower positive affect than LR infants and HR Neg infants. The two non-ASD groups were also slightly different from each other, with behavioral approach higher among HR Neg relative to low risk controls. For HR Pos infants, the behavioral approach factor score was lower relative to both HR Neg and LR controls. The HR Pos infants also differed from their HR Neg counterparts, with higher shyness and lower soothability (Clifford et al. [<reflink idref="bib9" id="ref39">9</reflink>]). Infants were also no longer higher than controls on approach behaviors or adaptability (del Rosario et al. [<reflink idref="bib10" id="ref40">10</reflink>]). In addition, Garon et al. ([<reflink idref="bib18" id="ref41">18</reflink>]) found that in LR infants, positive affect at 12 months was correlated with effortful control at 24 months, but this was not the case for children diagnosed with ASD. This suggests that positive affect may play an important role in the development of effective regulatory processes (Garon et al. [<reflink idref="bib18" id="ref42">18</reflink>]).</p> <p>Macari et al. ([<reflink idref="bib30" id="ref43">30</reflink>]) also examined the temperament of 24-month-olds with follow up in a sub-sample at 43 months of age. The sample differed from the aforementioned studies in that the children had been referred to a clinic with developmental concerns and later diagnosed with ASD. The children with ASD had lower surgency scores and poorer effortful control than comparison groups composed of typically developing children and those with developmental delay. Children with ASD also had higher emotional negativity on the TBAQ (similar to negative affectivity on the ECBQ/IBQ) than typically developing children. In addition, ASD severity from the ADOS was predicted by changes in temperament scores between 24 months and 43 months. Those children who demonstrated an increase in perceptual sensitivity over this time period had more severe ASD symptoms.</p> <p>Taken together, these studies suggest that after the first year of life and through to age two, infants who go on to receive a diagnosis of ASD have higher negative affect, lower effortful control and lower surgency than those who do not. However, findings across studies are less clear at 6 months with reports of both increased surgency, and increased passivity in infants later diagnosed with ASD (Zwaigenbaum et al. [<reflink idref="bib59" id="ref44">59</reflink>]; Clifford et al. [<reflink idref="bib9" id="ref45">9</reflink>]; del Rosario et al. [<reflink idref="bib10" id="ref46">10</reflink>]).</p> <hd id="AN0137289979-7">The Impact of Temperament on Early Autism Symptoms</hd> <p>Despite early differences in temperament in infants at high risk for ASD, it is unclear whether these differences are an indicator of ASD risk status, distinct from classic signs of ASD, or reflect the emerging symptoms of ASD. It is possible that temperament differences observed in infants are better explained as prodromal ASD (Bryson et al. [<reflink idref="bib6" id="ref47">6</reflink>]). Some studies have found very little correlation between ADOS social affect scores and temperament scores at 24 months (Macari et al. [<reflink idref="bib30" id="ref48">30</reflink>]), although changes in perceptual sensitivity between 24 and 48 months predicted symptom severity in the ASD-positive group at 48 months. Garon et al. ([<reflink idref="bib18" id="ref49">18</reflink>]), found some evidence that positive affect temperament factors at 12 months, in addition to IQ and sex, were associated with ASD symptoms at 36 months in their sample. Furthermore, lower IQ and effortful control at 24 months predicted symptoms at 36 months.</p> <p>The inconsistent findings concerning the relationship between temperament and symptoms from these toddler studies may be due to the nature of the participants assessed. In the Macari study, the participants are drawn from a sample of infants with concerns and in the Garon et al. study they are high risk siblings. It is possible that these two groups may follow very different developmental trajectories.</p> <p>Focusing on temperament in infants at high risk for ASD provides the opportunity to investigate measurable developmental features prior to the consolidation of core ASD symptoms (Zwaigenbaum et al. [<reflink idref="bib59" id="ref50">59</reflink>]). For example, differences in temperament seen via difficulty in focusing attention might mean that infants at high risk for ASD miss important social cues early in development, such as eye contact from a social partner, that in turn could lead to further social deficits associated with ASD. These subtle differences, which might amplify over time, provide an alternative window for us to investigate ASD early in development, rather than focusing only on ASD diagnostic features. Differences that are captured on temperament scales at 6 or 12 months of age, such as fussiness, may be evident before the classic signs of ASD, which are often only clearly seen after the first birthday or later (Brian et al., [<reflink idref="bib5" id="ref51">5</reflink>]; Estes et al. [<reflink idref="bib14" id="ref52">14</reflink>]; Ozonoff et al. [<reflink idref="bib36" id="ref53">36</reflink>]). Other differences before the first birthday may also include motor or attentional skills (Flanagan et al. [<reflink idref="bib16" id="ref54">16</reflink>]; Maestro et al. [<reflink idref="bib31" id="ref55">31</reflink>]). By including performance on the Autism Observational Scales for Infants (AOSI) (Bryson et al. [<reflink idref="bib6" id="ref56">6</reflink>]) in our analysis, we can examine the relationship between temperament and early autism signs.</p> <hd id="AN0137289979-8">The Current Study</hd> <p>The current study makes use of a large longitudinal sample of infants at high and low risk for ASD seen at 6, 12, and 24 months to examine early temperament characteristics in relation to risk and diagnostic status. Based on patterns emerging from studies of toddlers and infants at risk for ASD, we hypothesized that infants who later met criteria for ASD would demonstrate lower regulatory capacity, lower surgency later in infancy, and more negative affect than their typically developing peers. It was expected that these differences would be evident as early as 6 months of age and increase over the course of early development as the core behavioral symptoms of ASD emerged and the ASD phenotype becomes more pronounced (Brian et al. [<reflink idref="bib5" id="ref57">5</reflink>]; Estes et al. [<reflink idref="bib14" id="ref58">14</reflink>]; Ozonoff et al. [<reflink idref="bib36" id="ref59">36</reflink>]). In addition, we carried out exploratory analyses to examine: (<reflink idref="bib1" id="ref60">1</reflink>) whether individual differences in temperament could be explained by differences in early features of ASD, and (<reflink idref="bib2" id="ref61">2</reflink>) relations of verbal and nonverbal skills to temperament.</p> <hd id="AN0137289979-9">Method</hd> <p></p> <hd id="AN0137289979-10">Participants</hd> <p>Data were collected from a sample of 282 infants who were at high risk for ASD (by virtue of having an older sibling with the disorder) as part of a larger network study of infant brain and behavioral development, the Infant Brain Imaging Study (IBIS), conducted at four clinical sites across the USA. ASD in older siblings was determined, prior to the infant enrolling in the study, using the Social Communication Questionnaire (SCQ) (Rutter et al. [<reflink idref="bib50" id="ref62">50</reflink>]) and then the Autism Diagnostic Interview—Revised (ADI-R; Lecouteur et al. [<reflink idref="bib26" id="ref63">26</reflink>]); and confirmed with a reported diagnosis of ASD from a community provider. A group of 114 low-risk infants also screened with the SCQ, who had typically developing older siblings and no first degree relative with ASD, also took part in the study. Low-risk infants were recruited from many sources including: flyers in the community, advertisements in parenting magazines, and outreach at parent events. Exclusionary criteria for both the high-risk and low-risk groups included the following: (<reflink idref="bib1" id="ref64">1</reflink>) diagnosis or physical signs of genetic conditions (e.g., Fragile X syndrome), (<reflink idref="bib2" id="ref65">2</reflink>) significant medical or neurological conditions affecting growth, development, or cognition (e.g., seizure disorder, congenital heart disease), (<reflink idref="bib3" id="ref66">3</reflink>) sensory impairments such as vision or hearing loss, (<reflink idref="bib4" id="ref67">4</reflink>) low birth weight (< 2000 g) or prematurity (< 37 weeks gestation), (<reflink idref="bib5" id="ref68">5</reflink>) evidence for significant perinatal brain injury from exposure to in utero neurotoxins (e.g., alcohol, selected prescription medications), (<reflink idref="bib6" id="ref69">6</reflink>) non-English speaking families, (<reflink idref="bib7" id="ref70">7</reflink>) evidence for contraindication for MRI (e.g., metal implants), (<reflink idref="bib8" id="ref71">8</reflink>) adopted children, and (<reflink idref="bib9" id="ref72">9</reflink>) family history of first degree relative with intellectual disability, psychosis, schizophrenia, or bipolar disorder. Participants included in the present study also had: (<reflink idref="bib1" id="ref73">1</reflink>) complete developmental and diagnostic assessment at age 24 months and (<reflink idref="bib2" id="ref74">2</reflink>) parent-report assessment of temperament at 6 and/or 12 months of age. The majority of participants (74%) contributed temperament data at both time points. There were no group differences in proportion of missing data. See Table 1 for participant characteristics.</p> <p>Study sample characteristics</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left"><p>HR Pos<sup>a</sup></p></th><th align="left"><p>HR Neg<sup>b</sup></p></th><th align="left"><p>LR Neg<sup>c</sup></p></th><th align="left"><p><italic>p</italic><sup>1</sup></p></th><th align="left"><p>Group differences</p></th></tr></thead><tbody><tr><td align="left"><p>Total sample</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p><italic>n</italic></p></td><td align="left"><p>61</p></td><td align="left"><p>221</p></td><td align="left"><p>114</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Sex (% male)</p></td><td align="left"><p>78.7</p></td><td align="left"><p>57</p></td><td align="left"><p>59.6</p></td><td align="left"><p>0.008</p></td><td align="left" /></tr></tbody></table> </ephtml> </p> <p>Study sample characteristics</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left"><p>Mean (SD)</p></th><th align="left"><p>Mean (SD)</p></th><th align="left"><p>Mean (SD)</p></th><th align="left" /><th align="left" /></tr></thead><tbody><tr><td align="left" colspan="6"><p>Time 1</p></td></tr><tr><td align="left"><p><italic>n</italic></p></td><td align="left"><p>48</p></td><td align="left"><p>167</p></td><td align="left"><p>109</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Age (months)</p></td><td align="left"><p>6.45 (0.59)</p></td><td align="left"><p>6.6 (0.74)</p></td><td align="left"><p>6.68(0.74)</p></td><td align="left"><p>0.460</p></td><td align="left" /></tr><tr><td align="left"><p> Sex (% male)</p></td><td align="left"><p>81.25</p></td><td align="left"><p>57.74</p></td><td align="left"><p>59.63</p></td><td align="left"><p>0.01</p></td><td align="left" /></tr><tr><td align="left"><p> Mullen ELC<sup>2</sup></p></td><td align="left"><p>95.7 (12.6)</p></td><td align="left"><p>97.6 (12.3)</p></td><td align="left"><p>100.90 (10.5)</p></td><td align="left"><p>< 0.001</p></td><td align="left"><p>a < b, a < c</p></td></tr><tr><td align="left"><p> Mullen VDQ<sup>3</sup></p></td><td align="left"><p>87.9 (16.3)</p></td><td align="left"><p>87.2 (17.37)</p></td><td align="left"><p>90.8 (15.7)</p></td><td align="left"><p>0.202</p></td><td align="left" /></tr><tr><td align="left"><p> Mullen NVDQ<sup>3</sup></p></td><td align="left"><p>98.4 (20.5)</p></td><td align="left"><p>101 (19.4)</p></td><td align="left"><p>105.5 (15.1)</p></td><td align="left"><p>0.042</p></td><td align="left" /></tr><tr><td align="left"><p> AOSI</p></td><td align="left"><p>10.59 (4.09)</p></td><td align="left"><p>9.88 (4.43)</p></td><td align="left"><p>8.07 (3.23)</p></td><td align="left"><p>0.000</p></td><td align="left"><p>a > c, b > c</p></td></tr><tr><td align="left" colspan="6"><p>Time 2</p></td></tr><tr><td align="left"><p><italic>n</italic></p></td><td align="left"><p>56</p></td><td align="left"><p>202</p></td><td align="left"><p>100</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Age (months)</p></td><td align="left"><p>12.66 (0.62)</p></td><td align="left"><p>12.55 (0.595)</p></td><td align="left"><p>12.61 (0.71)</p></td><td align="left"><p>0.639</p></td><td align="left" /></tr><tr><td align="left"><p> Sex (% male)</p></td><td align="left"><p>78.57</p></td><td align="left"><p>55.67</p></td><td align="left"><p>60</p></td><td align="left"><p>0.008</p></td><td align="left" /></tr><tr><td align="left"><p> Mullen ELC<sup>2</sup></p></td><td align="left"><p>93.5 (14.6)</p></td><td align="left"><p>100.45 (12.5)</p></td><td align="left"><p>105.53 (12.0)</p></td><td align="left"><p>< 0.001</p></td><td align="left"><p>a < b< c</p></td></tr><tr><td align="left"><p> Mullen VDQ<sup>3</sup></p></td><td align="left"><p>80.20 (17.8)</p></td><td align="left"><p>90.50 (16.9)</p></td><td align="left"><p>96.40 (15.7)</p></td><td align="left"><p>< 0.001</p></td><td align="left"><p>a < b, a < c</p></td></tr><tr><td align="left"><p> Mullen NVDQ<sup>3</sup></p></td><td align="left"><p>102.10 (18.4)</p></td><td align="left"><p>107.70 (17)</p></td><td align="left"><p>117.00 (11.5)</p></td><td align="left"><p>0.001</p></td><td align="left"><p>a < b< c</p></td></tr><tr><td align="left"><p> AOSI</p></td><td align="left"><p>7.23 (4.01)</p></td><td align="left"><p>5.06 (3.51)</p></td><td align="left"><p>4.06 (3.08)</p></td><td align="left"><p>0.000</p></td><td align="left"><p>a > c, a > b</p></td></tr><tr><td align="left" colspan="6"><p>Time 3</p></td></tr><tr><td align="left"><p><italic>n</italic></p></td><td align="left"><p>18</p></td><td align="left"><p>46</p></td><td align="left"><p>22</p></td><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Age (months)</p></td><td align="left"><p>24.43 (0.12)</p></td><td align="left"><p>24.47 (0.08)</p></td><td align="left"><p>24.62 (0.14)</p></td><td align="left"><p>0.502</p></td><td align="left" /></tr><tr><td align="left"><p> Sex (% male)</p></td><td align="left"><p>94.4</p></td><td align="left"><p>56.5</p></td><td align="left"><p>77.3</p></td><td align="left"><p>0.009</p></td><td align="left" /></tr><tr><td align="left"><p> Mullen ELC<sup>2</sup></p></td><td align="left"><p>82.29 (20.8)</p></td><td align="left"><p>102.48 (14.08)</p></td><td align="left"><p>110.62 (11.6)</p></td><td align="left"><p>< 0.001</p></td><td align="left"><p>a < b< c</p></td></tr><tr><td align="left"><p> Mullen VDQ<sup>3</sup></p></td><td align="left"><p>73.12 (26.82)</p></td><td align="left"><p>98.76 (18.18)</p></td><td align="left"><p>108.15 (15.23)</p></td><td align="left"><p>< 0.001</p></td><td align="left"><p>a < b< c</p></td></tr><tr><td align="left"><p> Mullen NVDQ<sup>3</sup></p></td><td align="left"><p>91.35 (12.42)</p></td><td align="left"><p>102.7 (15.83)</p></td><td align="left"><p>106.98 (13.45)</p></td><td align="left"><p>0.003</p></td><td align="left"><p>a < b, a < c</p></td></tr><tr><td align="left"><p> ADOS severity</p></td><td align="left"><p>6.05 (1.49)</p></td><td align="left"><p>1.61 (.912)</p></td><td align="left"><p>1.51 (1.05)</p></td><td align="left"><p>0.000</p></td><td align="left"><p>a < b, a < c</p></td></tr><tr><td align="left"><p> ADI-R Total</p></td><td align="left"><p>16.65 (9.39)</p></td><td align="left"><p>7.67 (5.40)</p></td><td align="left"><p>6.07(5.62)</p></td><td align="left"><p>0.000</p></td><td align="left"><p>a > b, a > c</p></td></tr></tbody></table> </ephtml> </p> <p> <sups>a</sups> <emph>HR Pos</emph> high risk positive group, <sups>b</sups><emph>HR Neg</emph> high risk negative group, <sups>c</sups><emph>LR Neg</emph> low risk negative group <sups>1</sups>Omnibus ANOVA (age, Mullen, AOSI) and Fisher's exact tests (sex) <sups>2</sups>Mullen Early Learning Composite standard score <sups>3</sups>Mullen Verbal Developmental Quotient and Nonverbal Developmental Quotient</p> <hd id="AN0137289979-11">Procedure</hd> <p>Parents of all infants provided written informed consent prior to their child's participation in the study. Study procedures were approved by the institutional review boards at each site.</p> <p>Direct assessment of infants was carried out at ages 6, 12, and 24 months to assess behavioral and cognitive development, and signs of ASD. Parent report of infant development was obtained through interview and questionnaire at ages 6 and 12 months. All infants, both low risk and high risk, were seen at 24 months of age, at which time they underwent gold standard diagnostic assessment for ASD by research-reliable examiners using both the Autism Diagnostic Interview-Revised (ADI-R) (Lecouteur et al. [<reflink idref="bib26" id="ref75">26</reflink>]) and Autism Diagnostic Observation Schedule (ADOS) (Lord et al. [<reflink idref="bib28" id="ref76">28</reflink>]). Diagnostic classification was determined by expert clinical judgment based on these and all other available cognitive and behavioral assessment data using DSM-IV-TR criteria. This classification was confirmed by a senior clinical psychologist or psychiatrist blinded to risk group. For more details, see Estes et al. ([<reflink idref="bib14" id="ref77">14</reflink>]). Only infants not classified as ASD were included in the low risk group and in this study. There is a strong body of literature to support the choice of 24 months as a point of diagnostic classification (see Estes et al. [<reflink idref="bib14" id="ref78">14</reflink>], for a full discussion), and these infants will also be followed in further studies.</p> <hd id="AN0137289979-12">Developmental and Autism Measures</hd> <p>Developmental level was assessed at each visit by a trained clinician using the Mullen Scales of Early Learning (Mullen [<reflink idref="bib33" id="ref79">33</reflink>]). A verbal developmental quotient (VDQ) and nonverbal developmental quotient (NVDQ) was calculated for each child.</p> <p>Early Autism features were examined using the Autism Observation Scale for Infants (AOSI) (Bryson et al. [<reflink idref="bib6" id="ref80">6</reflink>]). This is a direct clinical assessment, which includes 16 items that capture: visual tracking and attention disengagement, coordinated eye gaze and action, imitation, affective responses, early social-communication, behavioral reactivity, and sensorimotor development. Each child received a total score, with higher scores reflecting more ASD features.</p> <hd id="AN0137289979-13">Temperament Measures</hd> <p>Infant temperament was assessed by the Infant Behavior Questionnaire-Revised (IBQ-R) (Gartstein and Rothbart [<reflink idref="bib19" id="ref81">19</reflink>]), which parents completed before the 6- and 12-month visits to the laboratory. The IBQ-R consists of a series of 191 questions about the frequency and type of behaviors infants were observed to engage in during the preceding one to 2 weeks. For example, parents were asked, "When visiting a new place how often did the baby show distress for the first few minutes?" or "When being dressed or undressed during the last week, how often did the baby coo or vocalize?" Responses were made using a 7-point Likert-type scale ranging from "never" to "always". From these questions, 14 subscales, and 3 factor scores (surgency, negative affect and regulatory capacity) were calculated (Gartstein and Rothbart [<reflink idref="bib19" id="ref82">19</reflink>]; Gartstein personal communication). The <emph>surgency</emph> factor encompasses approach, activity level, vocal reactivity, smiling and laughter, high intensity pleasure, and perceptual sensitivity. The <emph>negative affect</emph> factor encompasses sadness, fear, distress to limitations, and negatively loading on falling reactivity. The <emph>regulatory capacity</emph> factor encompasses duration of orienting, low intensity pleasure, soothability, and cuddliness. Internal consistency for the subscales ranges from.70 to.89 (Gartstein and Rothbart [<reflink idref="bib19" id="ref83">19</reflink>]). The three factor scores were calculated by transforming raw subscale scores into z-scores and summing them into factors according to guidance provided by the authors of the IBQ-R (Gartstein and Rothbart [<reflink idref="bib19" id="ref84">19</reflink>]; Gartstein personal communication).</p> <p>At 24 months, a subgroup of participants (<emph>n</emph> = 86) completed the Early Childhood Behavior Questionnaire (ECBQ) (Putnam et al. [<reflink idref="bib41" id="ref85">41</reflink>]), which is an upward extension of the IBQ-R. This also gives rise to three factor scores: <emph>surgency</emph> (impulsivity, activity level, high intensity pleasure, sociability, positive anticipation), <emph>negative affectivity</emph> (discomfort, fear, sadness, frustration, soothability, motor activation, perceptual sensitivity, shyness), and <emph>effortful control</emph> (inhibitory control, attention shifting, low-intensity pleasure, cuddliness, attention focusing). The ECBQ factors were used for the 24-month point in our longitudinal analysis, as proposed by Putnam et al. ([<reflink idref="bib42" id="ref86">42</reflink>]). The ECBQ is moderately stable over time and Chronbach alphas for subscales range from 0.60 to 0.89 at 24 months (Putnam et al. [<reflink idref="bib41" id="ref87">41</reflink>]). The ECBQ was only available for a subset of participants as it was added to our assessment battery partway through the study. The general pattern of the subscales is similar to the IBQ-R, though soothability moves from regulatory capacity to negative affectivity, and additional constructs such as impulsivity and attention focusing appear in the 24-month scale. There is good longitudinal consistency across the IBQ-R and ECBQ, with scores on all temperament factors strongly correlated across the measures (Putnam et al. [<reflink idref="bib42" id="ref88">42</reflink>]).</p> <hd id="AN0137289979-14">Analytic Approach</hd> <p>For all analyses in this paper, we divided infants into 3 groups: infants at high risk for ASD who met criteria for ASD at 24 months based on clinical best estimate using all available clinical information (<emph>HR Pos</emph>, <emph>n</emph> = 61), those at high risk for ASD who did not meet criteria (<emph>HR Neg</emph>, <emph>n</emph> = 221), and infants at low risk without ASD (<emph>LR Neg</emph>, <emph>n</emph> = 114). Low-risk infants who met ASD criteria (<emph>n</emph> = 4) were not included in the analyses.</p> <p>For our primary set of analyses, we employed linear mixed models for each of three temperament factors (surgency, regulatory capacity (effortful control), and negative affect). Given that the IBQ-R and ECBQ both provide z-scores based on the same scale of measurement and are designed to reflect uniform constructs (Putnam et al. [<reflink idref="bib42" id="ref89">42</reflink>]), these scores were combined within a single analytic. Model predictors included group (HR Pos, HR Neg, and LR Neg), time (<reflink idref="bib6" id="ref90">6</reflink>, 12, and 24 months of age), and the interaction of group × time. Sex and overall cognitive ability on the MSEL were also included as covariates, given differences in sex ratio and cognitive ability among diagnostic groups. Bonferroni adjusted pairwise-comparisons were generated following significant omnibus results for group effects only. For those analyses where significant group differences were found, we also conducted analyses of group differences in the subscales that make up each temperament factor to see which subscales might be contributing to the differences. For temperament subscale analyses, the effect of group (HR Pos, HR Neg, and LR Neg), on temperament scores was examined separately at each time point (<reflink idref="bib6" id="ref91">6</reflink>, 12, and 24 months of age) using ANOVA, with Bonferroni adjusted pairwise-comparisons generated following significant omnibus results. All secondary analyses of subscales were FDR corrected for multiple comparisons (Benjamini and Hochberg [<reflink idref="bib1" id="ref92">1</reflink>]).</p> <p>In a secondary exploratory analysis, we examined whether early behavioral signs of ASD, as measured by scores on the AOSI (Bryson et al. [<reflink idref="bib6" id="ref93">6</reflink>]), might account for differences seen in temperament between groups given possible overlap between constructs. In order to do this, we repeated the previously described analysis with the addition of AOSI scores at ages 6 and 12 months as a covariates. In addition, we conducted regression analyses to examine the relationship between 6-month autism signs and later temperament to investigate this further. For each group, we examined whether 6- and 12-month AOSI scores predicted variance in each of the temperament factors at 12 months, accounting for 6-month temperament in the model. We ran a regression model for surgency, negative affect and regulatory control separately. In the first model we measured the effect of 6-month AOSI, and in the second model whether 12-month AOSI scores contributed additional variance above the baseline 6-month AOSI scores.</p> <p>Each of the temperament factors from the IBQ at ages 6 and 12 months to VDQ and NVDQ were assessed using Pearson correlations FDR corrected for multiple comparisons (Benjamini and Hochberg [<reflink idref="bib1" id="ref94">1</reflink>]).</p> <hd id="AN0137289979-15">Results</hd> <p></p> <hd id="AN0137289979-16">Subject Characteristics</hd> <p>Mean ages and Mullen Early Learning Composite Scores (MSEL ELC) are presented in Table 1, along with Mullen Nonverbal and Verbal Developmental Quotients and AOSI scores, which were used in exploratory analyses. Groups did not differ by age of assessment at the 6 month, 12 month, or 24 month visits, <emph>F</emph>(<reflink idref="bib2" id="ref95">2</reflink>, 348) = 1.68, <emph>p </emph>= 0.187, <emph>F</emph>(<reflink idref="bib2" id="ref96">2</reflink>, 387) =. 847, <emph>p </emph>= 0.419, <emph>F</emph>(<reflink idref="bib2" id="ref97">2</reflink>, 84) = 0.696, <emph>p </emph>= 0.502 respectively. As expected, MSEL ELC scores differed significantly by group at the 6 month timepoint, <emph>F</emph>(<reflink idref="bib2" id="ref98">2</reflink>, 321) = 4.142, <emph>p </emph>= 0.017 and at 12 months, <emph>F</emph>(<reflink idref="bib2" id="ref99">2</reflink>, 356) = 16.26, <emph>p </emph>< 0.001. Post hoc pairwise comparisons indicated that at 6 months the HR Pos group scored significantly lower on the MSEL ELC than the LR Neg group. At 12 months all groups differed from each other, with the LR Neg group scoring highest on the MSEL ELC followed by the HR Neg group then the HR Pos group. At 24 months, the HR Pos and HR Neg group differed on the MSEL ELC, and the HR Pos and LR Neg group also differed on this measure, with the HR Pos group scoring lower than the LR Neg group. The HR Pos group also scored lower on the MSEL ELC than the HR Neg group.</p> <hd id="AN0137289979-17">Temperament Factors</hd> <p>Longitudinal temperament data for HR Pos, HR Neg, and LR Neg groups are presented in Fig. 1 and descriptive data for each time point are presented in Table 2.</p> <p>Graph: Fig. 1Estimated marginal means for primary temperament factors</p> <p>Cross-sectional Means by Group for Infant Behavior Questionnaire-Revised (IBQ-R) and Early Childhood Behavior Questionnaire (ECBQ)</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2"><p>IBQ-R Factor Score (z)</p><p>ECBQ Factor Score (z)</p></th><th align="left" colspan="2"><p>HR Pos<sup>a</sup></p></th><th align="left" colspan="2"><p>HR Neg<sup>b</sup></p></th><th align="left" colspan="2"><p>LR Neg<sup>c</sup></p></th><th align="left" rowspan="2"><p>Group differences</p></th></tr><tr><th align="left"><p>Mean</p></th><th align="left"><p>SE</p></th><th align="left"><p>Mean</p></th><th align="left"><p>SE</p></th><th align="left"><p>Mean</p></th><th align="left"><p>SE</p></th></tr></thead><tbody><tr><td align="left" colspan="8"><p>Time 1 (6 months)</p></td></tr><tr><td align="left"><p> Surgency</p></td><td char="." align="char"><p>− 0.14</p></td><td char="." align="char"><p>0.56</p></td><td char="." align="char"><p>− 0.07</p></td><td char="." align="char"><p>0.33</p></td><td char="." align="char"><p>0.74</p></td><td char="." align="char"><p>0.36</p></td><td align="left"><p>a < b</p></td></tr><tr><td align="left"><p> Negative affect</p></td><td char="." align="char"><p>0.66</p></td><td char="." align="char"><p>0.41</p></td><td char="." align="char"><p>0.09</p></td><td char="." align="char"><p>0.24</p></td><td char="." align="char"><p>− 0.39</p></td><td char="." align="char"><p>0.25</p></td><td align="left" /></tr><tr><td align="left"><p> Regulatory capacity</p></td><td char="." align="char"><p>− 1.0</p></td><td char="." align="char"><p>0.42</p></td><td char="." align="char"><p>0.19</p></td><td char="." align="char"><p>0.21</p></td><td char="." align="char"><p>0.17</p></td><td char="." align="char"><p>0.21</p></td><td align="left"><p>a < b, a < c</p></td></tr><tr><td align="left" colspan="8"><p>Time 2 (12 months)</p></td></tr><tr><td align="left"><p> Surgency</p></td><td char="." align="char"><p>− 1.86</p></td><td char="." align="char"><p>0.53</p></td><td char="." align="char"><p>− 0.02</p></td><td char="." align="char"><p>0.28</p></td><td char="." align="char"><p>1.23</p></td><td char="." align="char"><p>0.36</p></td><td align="left"><p>a < c, a < b, b < c</p></td></tr><tr><td align="left"><p> Negative affect</p></td><td char="." align="char"><p>0.74</p></td><td char="." align="char"><p>0.39</p></td><td char="." align="char"><p>0.23</p></td><td char="." align="char"><p>0.199</p></td><td char="." align="char"><p>− 0.49</p></td><td char="." align="char"><p>0.27</p></td><td align="left"><p>a > c</p></td></tr><tr><td align="left"><p> Regulatory capacity</p></td><td char="." align="char"><p>− 0.68</p></td><td char="." align="char"><p>0.33</p></td><td char="." align="char"><p>− 0.09</p></td><td char="." align="char"><p>0.18</p></td><td char="." align="char"><p>0.44</p></td><td char="." align="char"><p>0.24</p></td><td align="left"><p>a < c</p></td></tr><tr><td align="left" colspan="8"><p>Time 3 (24 months)</p></td></tr><tr><td align="left"><p> Surgency</p></td><td char="." align="char"><p>− 0.43</p></td><td char="." align="char"><p>0.32</p></td><td char="." align="char"><p>0.09</p></td><td char="." align="char"><p>0.21</p></td><td char="." align="char"><p>0.04</p></td><td char="." align="char"><p>0.38</p></td><td align="left" /></tr><tr><td align="left"><p> Negative affectivity</p></td><td char="." align="char"><p>0.60</p></td><td char="." align="char"><p>0.55</p></td><td char="." align="char"><p>0.02</p></td><td char="." align="char"><p>0.24</p></td><td char="." align="char"><p>− 0.69</p></td><td char="." align="char"><p>0.38</p></td><td align="left" /></tr><tr><td align="left"><p> Effortful control</p></td><td char="." align="char"><p>− 1.25</p></td><td char="." align="char"><p>0.47</p></td><td char="." align="char"><p>0.43</p></td><td char="." align="char"><p>0.25</p></td><td char="." align="char"><p>0.15</p></td><td char="." align="char"><p>0.32</p></td><td align="left" /></tr></tbody></table> </ephtml> </p> <p> <sups>a</sups> <emph>HR Pos</emph> high risk positive group, <sups>b</sups><emph>HR Neg</emph> high risk negative group, <sups>c</sups><emph>LR Neg</emph> low risk negative group</p> <p>For surgency, there was a significant effect of group, <emph>F</emph>(<reflink idref="bib2" id="ref100">2</reflink>, 342.9) = 13.4, <emph>p </emph>< 0.001, and cognitive ability, <emph>F</emph>(<reflink idref="bib1" id="ref101">1</reflink>, 208.3) = 4.0, <emph>p </emph>= 0.047, but no main effect of time, <emph>F</emph>(<reflink idref="bib2" id="ref102">2</reflink>, 240.4) = 1.5, <emph>p </emph>= 0.23. There was a significant interaction between time and group, <emph>F</emph>(<reflink idref="bib4" id="ref103">4</reflink>, 241.0) = 4.1, <emph>p </emph>= 0.003. For the effect of group, post hoc tests revealed that all three groups significantly differed from one another, with the LR Neg group scoring highest on surgency (HR Pos < HR Neg < LR Neg). In addition, higher cognitive ability led to higher scores on surgency. For group × time interaction, post hoc tests indicated that the HR Pos group significantly differed from the LR Neg group in terms of trajectory over the interval from 6 to 24 months of age, with the HR Pos group showing initially lower but increasing surgency and the LR Neg group showing the reverse of this pattern. Scores for the HR Neg group were relatively stable over time and intermediate to the other groups (see Fig. 1).</p> <p>For negative affect, there was also a significant effect of group, <emph>F</emph>(<reflink idref="bib2" id="ref104">2</reflink>, 308.1) = 6.1, <emph>p </emph>= 0.002, but no effect of time, <emph>F</emph>(<reflink idref="bib2" id="ref105">2</reflink>, 181.1) = 0.17, <emph>p </emph>= 0.84, cognitive ability, <emph>F</emph>(<reflink idref="bib1" id="ref106">1</reflink>, 358.0) = 1.5, <emph>p</emph> = 0.22, or interaction between time and group <emph>F</emph>(<reflink idref="bib4" id="ref107">4</reflink>, 180.4) =.16, <emph>p </emph>= 0.96. Post hoc analyses for negative affect indicated that the HR Pos group had higher scores than the LR Neg group, but not the HR Neg group. In addition, the LR Neg group and the HR Neg group did not differ from each other.</p> <p>For regulatory capacity, there was also a significant main effect of group on the longitudinal profile, <emph>F</emph>(<reflink idref="bib2" id="ref108">2</reflink>, 320.9) = 8.6, <emph>p </emph>< 0.001, but no effect of time, <emph>F</emph>(<reflink idref="bib2" id="ref109">2</reflink>, 169.8) = 1.3, <emph>p </emph>= 0.29, cognitive ability, <emph>F</emph>(<reflink idref="bib1" id="ref110">1</reflink>, 375.4) = 1.6, <emph>p </emph>= 0.21, or interaction between time and group <emph>F</emph>(<reflink idref="bib4" id="ref111">4</reflink>, 169.0) = 1.9, <emph>p </emph>= 0.11. Post hoc analysis for the effect of group indicated that the HR Pos group scored significantly lower on regulatory capacity than either HR Neg or LR Neg groups, and that these latter groups did not differ significantly from one another. The effect of sex was not significant in any model, (<emph>p</emph> > 0.250).</p> <hd id="AN0137289979-18">Temperament Subscale Scores</hd> <p>We also investigated whether individual subscales contributed to the significant differences we found between groups. (See Fig. 2 for figures showing means and standard deviations for all raw scores on each of the subscales and Online Appendix A for tables showing group differences.)</p> <p>Graph: Fig. 2a Temperament subscale scores for infant behavior questionnaire-revised (IBQ-R) by diagnostic group. b Temperament subscale scores for early childhood behavior questionnaire (ECBQ) by diagnostic group</p> <p>Group differences in surgency at 6 months were driven by significant differences in the following subscale scores: vocal reactivity, <emph>F</emph>(<reflink idref="bib2" id="ref112">2</reflink>, 324) = 6.45, <emph>p</emph> = 0.002), and smiling and laughter <emph>F</emph>(<reflink idref="bib2" id="ref113">2</reflink>, 324) = 7.54, <emph>p</emph> = 0.001, with HR Pos infants exhibiting less smiling and laughter than their HR Neg and LR Neg peers. There was a different pattern at 12 months. Differences between groups were seen in all the subscales that make up surgency, except response to high pleasure. The HR Neg group was lower than the LR Neg group in perceptual sensitivity, <emph>F</emph>(<reflink idref="bib2" id="ref114">2</reflink>, 358) = 3.40, <emph>p </emph>= 0.034, and activity level, <emph>F</emph>(<reflink idref="bib2" id="ref115">2</reflink>, 358) = 4.07, <emph>p</emph> = 0.018. The HR Pos group were lower in approach than the LR Neg group, <emph>F</emph>(<reflink idref="bib2" id="ref116">2</reflink>, 358) = 5.12, <emph>p</emph> = 0.006, and also lower than the HR Neg group. The HR Pos group also had lower scores than both the LR Neg and HR Neg groups for vocal reactivity <emph>F</emph>(<reflink idref="bib2" id="ref117">2</reflink>, 358) = 16.18, <emph>p</emph> < 0.001 and smiling and laughter, <emph>F</emph>(<reflink idref="bib2" id="ref118">2</reflink>, 358) = 11.68, <emph>p</emph> < 0.001. At 24 months, differences were seen in positive anticipation and sociability that are part of the surgency factor, with the HR Pos group scoring lower than the HR Neg group and the LR Neg group.</p> <p>Significant differences in regulatory capacity subscales at 6 months were seen in low intensity pleasure, <emph>F</emph>(<reflink idref="bib2" id="ref119">2</reflink>, 322) = 5.82, <emph>p</emph> = 0.003, again with the HR Pos infants exhibiting less response to low intensity pleasure than their HR Neg and LR Neg peers (see Online Appendix B). No specific subscales stood out for effortful control at 12 months, despite group differences in this factor.</p> <p>At 12 months, differences were seen in sadness, <emph>F</emph>(<reflink idref="bib2" id="ref120">2</reflink>, 358) = 3.31, <emph>p</emph> = 0.038, and falling reactivity, <emph>F</emph>(<reflink idref="bib2" id="ref121">2</reflink>, 358) = 3.31, <emph>p</emph> = 0.038, in the negative affect factor, with the HR Neg group having higher sadness scores than the LR Neg group. For falling reactivity, the HR Pos group had poorer scores than the LR Neg infants and the HR Neg infants also had poorer scores than the low risk negative infants. At 24 months, there were also differences in discomfort, frustration, and sadness, with the HR Pos group having higher reports of all these behaviors than LR Neg infants (see Online Appendix A).</p> <hd id="AN0137289979-19">The Effect of AOSI Scores on Temperament</hd> <p>In order to investigate whether differences in temperament could be explained in part by emerging signs of ASD, scores from the AOSI were added to our analytic models. The effect of diagnostic group and time on temperament factors was examined with AOSI scores at 6 and 12 months included as a covariates. There was a main effect of AOSI for regulatory capacity, <emph>F</emph>(<reflink idref="bib1" id="ref122">1</reflink>, 523.0) = 5.4, <emph>p</emph> = 0.02, and surgency, <emph>F</emph>(<reflink idref="bib1" id="ref123">1</reflink>, 487.0) = 22.9, <emph>p</emph> < 0.001, but not negative affect, <emph>F</emph>(<reflink idref="bib1" id="ref124">1</reflink>, 533.9) = 0.1, <emph>p</emph> = 0.76, such that AOSI scores contributed to variance in regulatory capacity and surgency scores, with a pattern of those infants with poorer AOSI scores also having lower regulatory capacity and surgency scores. The main effect of group remained significant in each of these three models. For surgency, the interaction of group × time was no longer significant with the addition of control for AOSI score, <emph>F</emph>(<reflink idref="bib2" id="ref125">2</reflink>, 300.9) = 1.0, <emph>p</emph> = 0.37. Including AOSI scores in the model for surgency appeared to mitigate differences in slope while not impacting the level or intercept of scores for groups across the age interval (with HR Pos < HR Neg < LR Neg).</p> <p>In addition, we investigated the relationship between early autism signs and temperament at 12 months of age using linear regression for each temperament factor: surgency, regulatory capacity, and negative affect. The results were mixed across groups and across temperament factors (see Online appendix B). In the Low-Risk group, 12-month AOSI score significantly contributed to variance in surgency at 12 months, controlling for temperament at 6 months <emph>(B</emph> = − 208, <emph>t</emph> = − 2.12, <emph>p</emph> = 0.04). In the HR Neg group, AOSI scores only made a contribution to variance in regulatory capacity, controlling for temperament at 6 months (<emph>B</emph> = − 0.133, <emph>SE</emph> = 0.049, <emph>t</emph> = − 2.734, <emph>p</emph> < 0.01). Negative affect at 12 months was not related to AOSI score at 12 or 6 months in any of the three groups. It is of note that for the HR Pos group, AOSI score had no impact on any temperament outcomes at 12 months.</p> <p>In order to examine whether verbal or nonverbal ability and temperament were related early in development we examined correlations between Mullen NVDQ and VDQ and temperament in each group with correction for multiple comparisons. As shown in Online Appendix C, in the HR Pos group, NVDQ was not correlated with any temperament measures but VDQ at 12 months was correlated with regulatory control at 12 months. However, this did not survive FDR correction. In the HR Neg group, VDQ at 6 months was significantly associated with surgency at 6 months, and at 12 months. In addition, NVDQ was significantly correlated with surgency at 6 months. In the LR Neg group, VDQ was correlated with surgency at 6 months.</p> <hd id="AN0137289979-20">Discussion</hd> <p>The results of the current study suggest that by 6 months of age, high-risk infant siblings who went on to meet diagnostic criteria for ASD at 24 months of age exhibit different parent-reported temperament characteristics than high and low risk infants without ASD. This suggests that temperament differences are an early emerging feature of ASD. Differences between groups are seen in all three temperament factors, with differences between HR positive and negative infants most pronounced for surgency and regulatory capacity.</p> <p>In addition, we examined the degree to which early manifestations of ASD symptomatology might overlap with or explain temperament characteristics using the AOSI at 6 and 12 months. Early ASD signs as measured by the AOSI made no contribution to 12-month temperament scores in the HR Pos group. Finding group differences as early as 6 months in all aspects of temperament provides a promising avenue for the examining possible mechanisms underlying the development of ASD.</p> <hd id="AN0137289979-21">Did Temperament Differ by Diagnostic Group?</hd> <p>Previous work has demonstrated that many ASD behaviors, such as social communication deficits, emerge in the second year of life (Brian et al. [<reflink idref="bib5" id="ref126">5</reflink>]; Estes et al. [<reflink idref="bib14" id="ref127">14</reflink>]; Ozonoff et al. [<reflink idref="bib36" id="ref128">36</reflink>]) after temperament differences may already be apparent. Indeed, we found that regulatory capacity and surgency differ at 6 months in high-risk infants later classified as ASD as compared to those infants who did not receive the diagnosis. Those infants with a sibling with ASD, but who were not classified as ASD, the HR Neg group, fell between the HR Pos and LR Neg groups on surgency at 6 and 12 months, but had scores like the LR Neg group for regulatory capacity and negative affect.</p> <hd id="AN0137289979-22">Surgency</hd> <p>In typical development, approach behaviors captured by the surgency factor, are evident at around 2 to 3 months of age (Rothbart [<reflink idref="bib44" id="ref129">44</reflink>]). Infants in the HR Pos group in the current study were exhibiting fewer behaviors that contribute to surgency at 6 months (see Online Appendix A). These behaviors, such as smiling and vocal reactivity, could be construed as important foundations for social interaction (Garon et al. [<reflink idref="bib17" id="ref130">17</reflink>]), although lower vocal reactivity could also reflect the presence of early language difficulties in the HR Pos group. The group differences found by del Rosario et al. ([<reflink idref="bib10" id="ref131">10</reflink>]) using the Carey scales, and by Clifford et al. ([<reflink idref="bib9" id="ref132">9</reflink>]) (using the IBQ-R) were based in approach behaviors.</p> <p>Contrary to our findings, some studies have reported increased approach behaviors or surgency behaviors at 6 months in high risk infants who go on to develop ASD. One such study suggests that these infants might be highly motivated by novel non-social objects rather than social stimuli and therefore might approach them more often than an infant following a more typical trajectory (del Rosario et al. [<reflink idref="bib10" id="ref133">10</reflink>]). However, because this study used a different temperament scale, the Carey Scales, it may be capturing slightly different aspects of approach behavior.</p> <p>The current findings of decreased surgency on the IBQ-R at 12 months are similar to those found with a sample of infants at 14 months of age (Clifford et al. [<reflink idref="bib9" id="ref134">9</reflink>]). Infants who go on to develop ASD might exhibit fewer behaviors that contribute to surgency early in development for a number of reasons. For example, they may be less inclined to vocalize and engage socially, either because they are less intrinsically socially motivated, or because of developmental delays, as reflected by our MSEL data. Verbal ability was marginally correlated with surgency at 12 months in the HR Pos group. However, it did not survive correction for multiple comparisons. The HR Pos infants could also have lower surgency scores because they are beginning to exhibit other signs of the ASD phenotype, such as repetitive motor behaviors (Elison et al. [<reflink idref="bib13" id="ref135">13</reflink>]; Wolff et al. [<reflink idref="bib57" id="ref136">57</reflink>]), indicating a more limited behavioral repertoire. Excess restricted and repetitive behavior may interfere with opportunities for social and other engagement, thus hindering the expression or development of behaviors contributing to surgency. This is supported by findings suggesting a negative relationship between repetitive behaviors and social engagement or social skills in toddlers (Wolff et al. [<reflink idref="bib57" id="ref137">57</reflink>]) and school-age children with ASD (Lee et al. [<reflink idref="bib27" id="ref138">27</reflink>]). Increased repetitive and stereotyped motor behavior is seen in ASD-positive high risk infants as young as 12 months, both when these behaviors are coded from videotape using the Repetitive and Stereotyped Movement Scales (RSMS) (Morgan et al. [<reflink idref="bib32" id="ref139">32</reflink>]), and by parent report of similar behaviors using the Repetitive Behavior Scales–Revised (RBS-R) (Bodfish et al. [<reflink idref="bib3" id="ref140">3</reflink>]; Wolff et al. [<reflink idref="bib57" id="ref141">57</reflink>]). Alternatively, there may also be a tendency for low surgency and restricted patterns of behavior to occur in the same infants.</p> <hd id="AN0137289979-23">Regulatory Capacity</hd> <p>Regulatory capacity also appears to be affected as early as 6 months of age in infants who go on to develop ASD, remaining significantly lower in that group. No differences were seen between the LR Neg and HR Neg infants in our sample. For those infants with a diagnosis of ASD, VDQ at 12 months was correlated with regulatory control at 6 and 12 months suggesting that for children in the HR Pos group better control of emotions and attention could perhaps influence verbal skills, or better verbal skills might support better emotional control. The HR Pos infants are having difficulties with regulation throughout their early development, something that distinguishes them from those infants at risk who do not receive a diagnosis (HR Neg), as in other studies by Garon et al. ([<reflink idref="bib17" id="ref142">17</reflink>], [<reflink idref="bib18" id="ref143">18</reflink>]) and del Rosario et al. ([<reflink idref="bib10" id="ref144">10</reflink>]). In addition, children with ASD differ from children with developmental delay in effortful control at 24 months (Macari et al. [<reflink idref="bib30" id="ref145">30</reflink>]). These early differences in regulatory capacity and effortful control likely have cascading effects on behavior later in development (Kochanska et al. [<reflink idref="bib24" id="ref146">24</reflink>]; Rothbart et al. [<reflink idref="bib47" id="ref147">47</reflink>]), manifesting in difficulties in attending and regulating emotions, both skills that can be impacted in older children with ASD and can have an effect on later adaptive outcomes (Macari et al. [<reflink idref="bib30" id="ref148">30</reflink>]). These differences also provide us with useful clues as to possible neurobiological mechanisms that might contribute to the development of ASD, for example, the anterior attention system (Posner and Rothbart [<reflink idref="bib40" id="ref149">40</reflink>]), and systems underlying emotion regulation, such as the limbic system (Panksepp [<reflink idref="bib39" id="ref150">39</reflink>]; Rothbart and Bates [<reflink idref="bib45" id="ref151">45</reflink>]).</p> <hd id="AN0137289979-24">Negative Affect</hd> <p>Differences were also found between groups in negative affect. In typically developing infants, negative affect is evident first as frustration and then later as fear and anxiety between 7 and 10 months (Rothbart [<reflink idref="bib43" id="ref152">43</reflink>]). We find differences in negative affect between the HR Pos group and the LR Neg group, with the HR Pos group exhibiting greater negativity throughout the age span at 6, 12, and 24 months. This had been found in several other studies, but only at later time points (Clifford et al. [<reflink idref="bib9" id="ref153">9</reflink>]; del Rosario et al. [<reflink idref="bib10" id="ref154">10</reflink>]; Garon et al. [<reflink idref="bib18" id="ref155">18</reflink>]; Macari et al. [<reflink idref="bib30" id="ref156">30</reflink>]; Zwaigenbaum et al. [<reflink idref="bib59" id="ref157">59</reflink>]). Work with typically developing infants suggests that negative affect contributes to the later ability to regulate emotions and social and motivational behaviors (DeYoung [<reflink idref="bib11" id="ref158">11</reflink>]; Evans and Rothbart [<reflink idref="bib15" id="ref159">15</reflink>]). This fits with our findings that HR Pos infants have both high negative affect and difficulty with regulatory control, i.e., regulating emotions or attention, but we cannot determine the direction of this relationship.</p> <p>An overall pattern of poor regulatory capacity, lower surgency, and increased negative affect was reported by the parents of high-risk children who later developed ASD. This pattern fits with the characterization of two-year-olds with ASD by Garon et al. ([<reflink idref="bib17" id="ref160">17</reflink>], [<reflink idref="bib18" id="ref161">18</reflink>]) and Macari et al. ([<reflink idref="bib30" id="ref162">30</reflink>]), who found more negativity and difficulty with emotional control in children who received a diagnosis of ASD, as well as results from del Rosario et al. ([<reflink idref="bib10" id="ref163">10</reflink>]), who found increased negative affect and lower effortful control in their infants with ASD at age two.</p> <hd id="AN0137289979-25">Differences Across the Age Span</hd> <p>All of the temperament differences found at 6 months persisted into the second year of life. By 12 months of age, there appears to be greater consensus in the pattern of temperament results seen across studies of infants at risk for ASD than is evident at 6 months of age. At earlier time points, some studies report greater approach (Clifford et al. [<reflink idref="bib9" id="ref164">9</reflink>]; del Rosario et al. [<reflink idref="bib10" id="ref165">10</reflink>]) whereas others suggest infants are more inhibited and passive (Zwaigenbaum et al. [<reflink idref="bib59" id="ref166">59</reflink>]). When early behavior is coded in the laboratory at 6 months of age during a cognitive assessment, differences in social behavior such as social smiling and social vocalization are not yet evident (Ozonoff et al. [<reflink idref="bib36" id="ref167">36</reflink>]). Nevertheless, we find differences in parent report of these behaviors reflected in temperament ratings in the present study. It is possible that parent-report measures might better reflect aggregate behavior over time and across multiple contexts. Indeed, Ozonoff et al. ([<reflink idref="bib37" id="ref168">37</reflink>]) report that parent concerns at 12 months are predictive of later outcome, suggesting that reports of temperament may well be useful guideposts for researchers. Questions on temperament scales do not require fine-grained behavioral coding but may nonetheless pick up meaningful differences early in development. In line with several previous studies, at 12 months our sample of infants demonstrated decreased surgency or approach, regulatory capacity, and increased negativity when compared with typically developing infants. The increasing consistency in findings seen across studies around the first birthday could suggest that constructs of temperament become more ingrained at 12 months of age. At this time, infants may behave more consistently, or parents are better able to discern clear patterns in their infants' behavior. These findings could also be a reflection of truly diverging patterns of temperament profiles, reflecting real differences in the expression of temperament between 6 and 12 months, such that there is a noticeable change in temperament in infants who go to develop ASD sometime at the end of the first year of life. We found a group × time interaction for surgency. Surgency increased in those infants with ASD between 12 and 24 months, but was still markedly lower than that of other groups. Surgency decreased in the LR Neg group during this time. The increase in surgency in our HR Pos group, seen between 12 and 24 months, although still much lower than in the HR Neg and LR Neg groups, could be due to an increase in vocalization and smiling that was more obvious to parents in this period for this group. Although not statistically significant, we see decreases in surgency, in the HR Pos group between 6 and 12 months. It may be that this decrease reflects changes in underlying cognitive or neurobiological mechanisms, which drive behaviors such as approach and vocal reactivity. This hypothesis needs to be further investigated in the high-risk group, and we are currently collecting data at a greater number of time points between 3 and 24 months in order to construct more detailed trajectories.</p> <hd id="AN0137289979-26">Emerging Autism Symptoms</hd> <p>When early signs of autism, as captured by AOSI scores at 6 and 12 months, were included in our analyses, the findings reported above still held. However, there was an effect of AOSI on both surgency and regulatory capacity. This could mean that some of the differences seen in temperament characteristics overall could be accounted for by differences in AOSI scores. This is not surprising given that many of the constructs captured by the AOSI are similar to those measured by the IBQ-R and ECBQ. For example, attention is measured by both the AOSI, in switching attention between objects, and by the regulatory capacity factor of the IBQ-R, by duration of orienting. Surgency from the IBQ-R encompasses vocalizations and smiling (see Online Appendix for a list of IBQ-R/ECBQ subscale scores), as do two items from the AOSI. However, these shared behaviors across measures of temperament and ASD signs, for example smiling or attention switching, do not rule out the possibility that temperament differences in children at risk for ASD could be precursors to later ASD. They are included on the AOSI precisely because they are good early indicators of ASD risk. For example, difficulty switching attention differentiates between groups, but is not a diagnostic criterion (Elison et al. [<reflink idref="bib12" id="ref169">12</reflink>]; Landry and Bryson [<reflink idref="bib25" id="ref170">25</reflink>]). It is also important to note that the AOSI is an early screener but is not a diagnostic tool.</p> <hd id="AN0137289979-27">HR Neg Infants</hd> <p>For some aspects of temperament, our data suggest that HR Neg infants fall between HR Pos infants and LR Neg controls. It may be that these infants are exhibiting a shared temperament endophenotype that is present at a milder level among unaffected family members. Studies of older children and adults report that personality traits are shared across the family later in development (Murphy et al. [<reflink idref="bib34" id="ref171">34</reflink>]). Indeed, one of the characteristics of the broader autism phenotype is an aloof personality style, which could be seen as low surgency (Losh and Piven [<reflink idref="bib29" id="ref172">29</reflink>]). The HR Neg group is similar to the LR Neg group in their regulatory capacity at 6 months but show a non-statistically significant decline at 12 months, not seen in the LR Neg group. This might suggest that the HR Neg infants are demonstrating some mild aspects of the ASD phenotype, having difficulties with emotion regulation and attention, but are not exhibiting the significant impairments seen in HR Pos infants.</p> <p>These early differences in temperament are important because they can impact later development either directly or indirectly. It is likely differences will impact later behavior directly by changing the learning opportunities available to the infant. For example, if the child is less likely to approach, he or she will have less exposure to social stimuli. In addition, temperament differences can impact behavior and psychopathology indirectly by changing the way in which adults interact with the infant, altering their experiences (Sanson et al. [<reflink idref="bib52" id="ref173">52</reflink>]). The current study cannot address these pathways, but it does highlight the importance of early differences.</p> <hd id="AN0137289979-28">Limitations</hd> <p>The present study reports data from only a small subsample of infants at age 24 months, so conclusions across the entire age range should be interpreted with caution. We are continuing to collect more data from 2- and 3-year-olds. While there is evidence that the IBQ-R and ECBQ measure the same constructs, the use of data from both sources to gauge change over time may introduce measurement bias. Data at age 24 months in relation to 6 and 12-month data should be considered with this potential bias in mind given that convergent validity between the IBQ-R and ECBQ was not directly evaluated in this sample.</p> <p>Caution should also be exercised in interpreting results based on measures collected through parental report. While use of parent report is common, it is important to be aware of the differences in the reporting of temperament characteristics between parents of low risk infants versus parents who already have a child with ASD. Parents with an older child with ASD may be more knowledgeable of, or more attentive to, different behaviors, and are likely to be reporting temperament in comparison to some of the atypical behaviors they see in the other child (Zwaigenbaum et al. [<reflink idref="bib59" id="ref174">59</reflink>]). If their infant has slightly more approach behaviors than their child with ASD, they might score them artificially higher on approach. In contrast, a parent of a typically developing older child is likely to be comparing their infant's behavior to more "typical" behavior patterns. This potential source of bias should be considered in evaluating findings for the LR Neg group relative to HR groups. In addition, we should be cognizant of the characteristics of parents themselves, because their contribution to the child's temperament might be both genetic and through the environment they provide, and reflected in responses to the questionnaire (del Rosario et al. [<reflink idref="bib10" id="ref175">10</reflink>]; Rothbart and Bates [<reflink idref="bib45" id="ref176">45</reflink>]). We know, for example, that parents of children with ASD are at higher risk for depression and anxiety, and that these conditions could bias ratings of their child's behavior (Ingersoll and Hambrick [<reflink idref="bib21" id="ref177">21</reflink>]).</p> <p>In this study, we consider infants only from multiplex families, which means that it will be important to replicate this work in a more diverse sample of infants with and without ASD. We know that there are differences in the behavioral presentation of infants from simplex and multiplex families (Pandey [<reflink idref="bib38" id="ref178">38</reflink>]) and infants who are ascertained from community referred samples versus prospective high-risk cohorts. Infants from community samples may demonstrate more severe ASD symptoms and poorer adaptive skills (Sacrey et al. [<reflink idref="bib51" id="ref179">51</reflink>]).</p> <p>Although ASD classification is likely to remain quite stable beyond 24 months for the majority of our participants (Jones and Klin [<reflink idref="bib23" id="ref180">23</reflink>]; Rozga et al. [<reflink idref="bib49" id="ref181">49</reflink>]; Shen et al. [<reflink idref="bib53" id="ref182">53</reflink>]), it is possible that some children in our sample might change diagnostic status as they get older. Given known variability in onset patterns associated with ASD, some children not meeting diagnostic criteria at age 2 may do so at later ages, while some in the HR Pos group may lose or change their diagnosis over time. This means that the pattern of group differences in temperament we see here could change if we use a classification made at 36 months or later. Following infants through to older ages in future work will allow us to address this. Another useful extension of this work would be to include infants with other developmental disorders, which would allow us to tease apart which aspects of the early temperament profile are specific to the emergence of ASD and not just due to underlying global developmental issues.</p> <hd id="AN0137289979-29">Conclusions</hd> <p>This study of a large group of infants at risk for ASD who did and did not meet criteria for ASD in comparison with a group of typically developing infants at 6, 12, and 24 months of age, has enabled us to characterize emerging differences in temperament. We observed that, in the first year of life, infants who go on to develop ASD demonstrate poorer regulatory control, less surgency and greater negative affect, even when early markers of ASD are taken into account. This suggests that although there is likely some overlap between early temperament and early signs associated with ASD, differences in temperament may be evident before the core symptoms of ASD have emerged. Targeting the early development of temperament in ASD for further study may be important for several reasons. Doing so may uncover early indicators of risk before other behavioral differences are clear. Alternatively, ASD could be investigated as a disorder that arises out of temperamental differences, with differences in regulatory capacity, surgency, and negative affect preceding a cascade of behavioral changes that lead to the consolidation of core symptoms. Features of temperament might also represent potentially actionable targets for pre-symptomatic or prodromal intervention.</p> <hd id="AN0137289979-30">Funding</hd> <p>This study was funded by National Institutes of Health (R01-HD 055741, R01-HD055741-S1, K01-MH101653) and the Simons Foundation (SFARI Grant 140209) and Autism Speaks.</p> <hd id="AN0137289979-31">Acknowledgments</hd> <p>This study was supported by Grants from NIH/NIHCD (R01-HD055741, HD055741-S1) Autism Speaks, and the Simons Foundation to J. Piven and K01-MH101653 to J. Wolff. We sincerely thank our IBIS families for participating in this research. We are grateful to Robert Emerson for helpful comments on an earlier version of this manuscript.</p> <p>* IBIS Network: The IBIS (Infant Brain Imaging Study) Network is an NIH funded Autism Centers of Excellence project and consists of a consortium of 8 Universities in the U.S. and Canada. Clinical Sites: University of North Carolina: J. Piven (IBIS Network PI), H.C. Hazlett, C. Chappell; University of Washington: S. Dager, A. Estes, D. Shaw; Washington University: K. N. Botteron, R. C. McKinstry, J. Constantino, J. Pruett; Children's Hospital of Philadelphia: R. T. Schultz, S. Paterson; University of Alberta: L. Zwaigenbaum; University of Minnesota: J. Elison. Data Coordinating Center: Montreal Neurological Institute: A.C. Evans, D. L. Collins, G. B. Pike, V. Fonov, P. Kostopoulos, S. Das. Image Processing Core: New York University: G. Gerig; University of North Carolina: M. Styner. Statistical Analysis Core: University of North Carolina: H. Gu.</p> <hd id="AN0137289979-32">Author Contributions</hd> <p>SJP, AE, LZ, RTS, JP, HCH, SRD, KB, JJW, JTE and JPn, contributed to the concept and design of the study, provided feedback, and reviewed the manuscript. SJP and JJW performed statistical analyses and interpreted the data. SJP, JJW, JTE, BWP, and JPn contributed to drafting and revising of the manuscript.</p> <hd id="AN0137289979-33">Compliance with Ethical Standards</hd> <p></p> <hd id="AN0137289979-34">Conflict of interest</hd> <p>All authors declare that they have no conflicts of interest.</p> <hd id="AN0137289979-35">Ethical Approval</hd> <p>All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.</p> <hd id="AN0137289979-36">Informed Consent</hd> <p>Informed consent was obtained from all individual participants included in the study.</p> <hd id="AN0137289979-37">Electronic supplementary material</hd> <p>Graph: Supplementary material 1 (DOCX 34 kb)</p> <p>Graph: Supplementary material 2 (DOCX 16 kb)</p> <p>Graph: Supplementary material 3 (DOC 99 kb)</p> <hd id="AN0137289979-38">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0137289979-39"> <title> References </title> <blist> <bibl id="bib1" idref="ref60" type="bt">1</bibl> <bibtext> Benjamini Y, Hochberg Y. 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  Data: The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants
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  Data: <searchLink fieldCode="AR" term="%22Paterson%2C+Sarah+J%2E%22">Paterson, Sarah J.</searchLink><br /><searchLink fieldCode="AR" term="%22Wolff%2C+Jason+J%2E%22">Wolff, Jason J.</searchLink><br /><searchLink fieldCode="AR" term="%22Elison%2C+Jed+T%2E%22">Elison, Jed T.</searchLink><br /><searchLink fieldCode="AR" term="%22Winder-Patel%2C+Breanna%22">Winder-Patel, Breanna</searchLink><br /><searchLink fieldCode="AR" term="%22Zwaigenbaum%2C+Lonnie%22">Zwaigenbaum, Lonnie</searchLink><br /><searchLink fieldCode="AR" term="%22Estes%2C+Annette%22">Estes, Annette</searchLink><br /><searchLink fieldCode="AR" term="%22Pandey%2C+Juhi%22">Pandey, Juhi</searchLink><br /><searchLink fieldCode="AR" term="%22Schultz%2C+Robert+T%2E%22">Schultz, Robert T.</searchLink><br /><searchLink fieldCode="AR" term="%22Botteron%2C+Kelly%22">Botteron, Kelly</searchLink><br /><searchLink fieldCode="AR" term="%22Dager%2C+Stephen+R%2E%22">Dager, Stephen R.</searchLink><br /><searchLink fieldCode="AR" term="%22Hazlett%2C+Heather+C%2E%22">Hazlett, Heather C.</searchLink><br /><searchLink fieldCode="AR" term="%22Piven%2C+Joseph%22">Piven, Joseph</searchLink><br /><searchLink fieldCode="AR" term="%22Piven%2C+J%2E%22">Piven, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hazlett%2C+H%2E+C%2E%22">Hazlett, H. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Chappell%2C+C%2E%22">Chappell, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Dager%2C+S%2E%22">Dager, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Estes%2C+A%2E%22">Estes, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Shaw%2C+D%2E%22">Shaw, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Botteron%2C+K%2E+N%2E%22">Botteron, K. N.</searchLink><br /><searchLink fieldCode="AR" term="%22McKinstry%2C+R%2E+C%2E%22">McKinstry, R. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Constantino%2C+J%2E%22">Constantino, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Pruett%2C+J%2E%22">Pruett, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Schultz%2C+R%2E+T%2E%22">Schultz, R. T.</searchLink><br /><searchLink fieldCode="AR" term="%22Paterson%2C+S%2E%22">Paterson, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Zwaigenbaum%2C+L%2E%22">Zwaigenbaum, L.</searchLink><br /><searchLink fieldCode="AR" term="%22Elison%2C+J%2E%22">Elison, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Evans%2C+A%2E+C%2E%22">Evans, A. C.</searchLink><br /><searchLink fieldCode="AR" term="%22Collins%2C+D%2E+L%2E%22">Collins, D. L.</searchLink><br /><searchLink fieldCode="AR" term="%22Pike%2C+G%2E+B%2E%22">Pike, G. B.</searchLink><br /><searchLink fieldCode="AR" term="%22Fonov%2C+V%2E%22">Fonov, V.</searchLink><br /><searchLink fieldCode="AR" term="%22Kostopoulos%2C+P%2E%22">Kostopoulos, P.</searchLink><br /><searchLink fieldCode="AR" term="%22Das%2C+S%2E%22">Das, S.</searchLink><br /><searchLink fieldCode="AR" term="%22Gerig%2C+G%2E%22">Gerig, G.</searchLink><br /><searchLink fieldCode="AR" term="%22Styner%2C+M%2E%22">Styner, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Gu%2C+H%2E%22">Gu, H.</searchLink>
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  Data: <searchLink fieldCode="SO" term="%22Journal+of+Autism+and+Developmental+Disorders%22"><i>Journal of Autism and Developmental Disorders</i></searchLink>. Jul 2019 49(7):2849-2863.
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  Data: Springer. Available from: Springer Nature. 233 Spring Street, New York, NY 10013. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-348-4505; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
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  Data: 15
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  Label: Publication Date
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  Data: 2019
– Name: SourceSuprt
  Label: Sponsoring Agency
  Group: SrcSuprt
  Data: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
– Name: NumberContract
  Label: Contract Number
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  Data: R01HD055741<br />HD055741S1<br />K01MH101653
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Autism%22">Autism</searchLink><br /><searchLink fieldCode="DE" term="%22Pervasive+Developmental+Disorders%22">Pervasive Developmental Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Infants%22">Infants</searchLink><br /><searchLink fieldCode="DE" term="%22At+Risk+Persons%22">At Risk Persons</searchLink><br /><searchLink fieldCode="DE" term="%22Personality%22">Personality</searchLink><br /><searchLink fieldCode="DE" term="%22Age+Differences%22">Age Differences</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-019-04003-2
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The present study investigated the relationship between infant temperament characteristics and autism spectrum disorder (ASD) risk status. Temperament was examined at 6, 12, and 24 months in 282 infants at high familial risk for ASD and 114 low-risk controls using the Infant Behavior Questionnaire-Revised and Early Childhood Behavior Questionnaire. Infants were divided into three groups at 24 months: High-Risk Positive--classified as ASD (HR Pos), High-Risk Negative (HR Neg), and Low-Risk Negative (LR Neg). At 6 and 12 months HR Pos infants exhibited lower Surgency and Regulatory Capacity than LR Neg infants. By 12 months they also demonstrated increased Negative Affect. Group differences remained, when early signs of ASD were controlled for, suggesting that temperament differences could be useful targets for understanding the development of ASD.
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  Label: Entry Date
  Group: Date
  Data: 2019
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  Label: Accession Number
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  Data: EJ1220871
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        Value: 10.1007/s10803-019-04003-2
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      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 15
        StartPage: 2849
    Subjects:
      – SubjectFull: Autism
        Type: general
      – SubjectFull: Pervasive Developmental Disorders
        Type: general
      – SubjectFull: Infants
        Type: general
      – SubjectFull: At Risk Persons
        Type: general
      – SubjectFull: Personality
        Type: general
      – SubjectFull: Age Differences
        Type: general
    Titles:
      – TitleFull: The Importance of Temperament for Understanding Early Manifestations of Autism Spectrum Disorder in High-Risk Infants
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            NameFull: Paterson, Sarah J.
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            NameFull: Wolff, Jason J.
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      – PersonEntity:
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    IsPartOfRelationships:
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          Dates:
            – D: 01
              M: 07
              Type: published
              Y: 2019
          Identifiers:
            – Type: issn-print
              Value: 0162-3257
          Numbering:
            – Type: volume
              Value: 49
            – Type: issue
              Value: 7
          Titles:
            – TitleFull: Journal of Autism and Developmental Disorders
              Type: main
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