Social functioning and facial expression recognition in children with neurofibromatosis type 1.

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Journal of Intellectual Disability Research

doi: 10.1111/jir.12248

282 VOLUME

60 PART 3 pp 282–293 MARCH 2016

Social functioning and facial expression recognition in children with neurofibromatosis type 1 T. Allen,1 V. W. Willard,2 L. M. Anderson,1 K. K. Hardy3 & M. J. Bonner4 1 Duke University, Psychology and Neuroscience, Durham, NC, United States 2 St. Jude Children’s Research Hospital, Psychology, Memphis, TN, United States 3 Children’s National Medical Center, Center for Neuroscience and Behavioral Medicine, Washington, DC, United States 4 Duke University Medical Center, Psychiatry, Durham, NC, United States

Abstract Background This study examined social functioning and facial expression recognition (FER) in children with neurofibromatosis type 1 (NF1) compared to typically developing peers. Specifically, the current research aimed to identify hypothesised relationships between neurocognitive ability, FER and social functioning. Method Children, ages 8 to 16, with NF1 (n = 23) and typically developing peers (n = 23) were recruited during regularly scheduled clinic visits and through advertisements on an institutional clinical trials website, respectively. Participants completed a measure of FER, an abbreviated intelligence test and questionnaires regarding their quality of life and behavioural functioning. Parents were also asked to complete questionnaires regarding the social– emotional and cognitive functioning of their child. Results As expected, there were significant differences between children with NF1 and typically developing peers across domains of social functioning and FER. Within the sample of children with NF1, there were no significant associations observed between cognitive measures, social functioning and facial recognition skills.

Correspondence: Taryn Allen, PhD., Duke University, Psychology and Neuroscience, Durham, NC, United States (e-mail: [email protected]).

Conclusion Children with NF1 exhibited high rates of social impairment and weak FER skills compared to controls. The absence of associations between FER with cognitive and social variables, however, suggests something unique about this skill in children with NF1. Theoretical comparisons are made to children with autism spectrum disorders, as this condition may serve as a potentially useful model in better understanding FER in children with NF1. Keywords neurocognitive functioning, neurofibromatosis type 1, social functioning Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder with a prevalence rate of approximately 1 in 3000 (National Institute of Neurological Disorders and Stroke 2007). Hallmark features of the disease include the presence of café-aulait spots, neurofibromas, optic gliomas and osseous dysplasias (NINDS 2007). Children with NF1 also experience significant neurocognitive deficits (Hyman et al. 2006). Intellectual decrements have been reported in approximately 40% of children with NF1 (North et al. 1997). While studies have found impairment in both verbal and nonverbal processes, deficits in the latter have been considered a primary feature of this disease (Clements-Stephens et al. 2008). In particular, research indicates robust impairments in visuospatial processing and perceptual reasoning ability (Hyman et al. 2006).

© 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd


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60 PART 3 MARCH 2016

283 T. Allen et al. • Social functioning in neurofibromatosis type 1

Further, children with NF1 show significant impairment in working memory and executive domains, including sustained attention and planning (Hyman et al. 2006), which resembles the cognitive profile of individuals with attention deficit/hyperactivity disorder (ADHD). Indeed, high rates of comorbid ADHD have been reported in children with NF1 (Maunter et al. 2002). While cognitive functioning in children with NF1 has been extensively studied, less is understood about their social functioning. The data on social functioning in children with NF1 has largely characterised their social profile and perceived skills. Research has indicated that children with NF1 have low levels of social acceptance, are frequently rejected by their peers (Johnson et al. 1999), are less likely to be chosen as a best friend, have fewer reciprocal friendships and are generally less wellliked than their peers (Noll et al. 2007). Further, data from peers suggest that children with NF1 have a social reputation characterised by sensitivity, isolation and weak leadership potential (Noll et al. 2007). These findings are consistent with parent- and teacher-reported social impairments (Noll et al. 2007). The social difficulties put children with NF1 at an increased risk for adjustment problems later in life (Brendgen et al. 2002). There has been a growing body of literature comparing the social difficulties associated with NF1 to autism spectrum disorders (ASD). Indeed, studies suggest a relatively high prevalence of children with NF1 fall in the severe range on the Social Responsiveness Scale (SRS), a well-validated screener for ASD (Garg et al. 2012; Walsh et al. 2012). Moreover, in a recent two-part study by Plasschaert and colleagues (2015), 63% of their sample of children with NF1 exhibited clinically relevant symptoms on the SRS, and among a subsample referred for an ASD evaluation (n = 31), 27 received an ASD diagnosis. The phenotype of children with NF1 and comorbid ASD is distinct, reflecting primary impairments in social-communication with fewer restrictive/repetitive behaviours. To better understand the social profile of children with NF1, Huijbregts and de Sonneville (Huijbregts & De Sonneville 2011) examined facial expression recognition (FER) and social skills in children with NF1 compared to a control group of siblings and friends. Results indicated that children with NF1 exhibited significantly poorer FER than controls, which uniquely contributed to parent-rated deficits in

peer relations. In addition, a composite score of general cognitive ability predicted social responsiveness; however, the independent associations between intellectual functioning and FER were not examined in their sample of children with NF1. In other clinical samples, deficits in out-ofcontext FER have been associated with deficits in nonverbal cognitive abilities, such as visuospatial impairment in survivors of pediatric brain tumours (Bonner et al. 2008) and deficits in attention among children with ADHD (Shin et al. 2008). These are particularly relevant findings given that these neurocognitive domains are often affected in children with NF1 (Payne et al. 2013). This raises the question of whether weaknesses in FER may relate to these neurocognitive impairments in NF1. The current study aimed to further explore social functioning and FER ability in children with NF1, compared to a comparison group of peers without NF1. In addition, we sought to examine the relationship among FER with parent-rated cognitive functioning within a sample of children with NF1 and a control comparison group. It was hypothesised that children with NF1 would make significantly more errors on a FER task and exhibit weaknesses in interpersonal and emotional functioning compared to a control group of children without medical problems. In addition, it was hypothesised that there would be significant associations between neurocognitive ability, FER and social functioning.

Methods Participants Children with NF1 (n = 23) and healthy peers (n = 23) between the ages of 8 and 16 were recruited from an academic medical centre in the Southeast. This age group was selected because it afforded a broad developmental range, while still ensuring that children would understand and be able to complete the study questionnaires. All subjects spoke English. Children with evidence of extensive visual impairment were excluded from the study (as determined by medical record data). Further, community controls were without a history of any major mental or physical illness (e.g. ADHD, diabetes, asthma; per parent report). While there was no exclusion criterion based on intellectual



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functioning, all participants (in NF1 and control groups) had estimated full scale IQs greater than 70 and did not meet DSM-IV criteria for an intellectual disability (by history). Control participants were matched based on chronological age. This study was approved by the Institutional Review Board. Among participants with NF1 who were approached for this study, 24 (96%) out of 25 child– parent dyads agreed to participate. Following consent, one participant with NF1 declined to complete the questionnaires because of time constraints. Among the community control sample, all participants (100%) who attended their research appointment completed the study.

Procedures Participants with neurofibromatosis type 1 Eligible participants and a guardian were identified by the attending pediatric neurologist or physician assistant and approached by a research assistant during a regularly scheduled clinic appointment. The study rationale and procedure were explained to the guardian and patient, after which consent and assent (for children age 12 years and older) was obtained according to IRB-approved methods. Children and guardians completed all study procedures in approximately 40 min (see Measures below) on the same day as their clinic visit. Typically developing peers Typically developing peers were recruited through advertisements on a clinical trials website maintained by the medical centre. Parents contacted a member of the research team by phone, and study aims and procedures were explained. During an in-person appointment, study consent and assent were obtained according to IRB-approved methods; children and parents went on to complete questionnaire and neurocognitive measures in the same research visit (see Measures below).

Measures Wechsler Abbreviated Scale of Intelligence (WASI) (Wechsler 1999) The Wechsler scales are commonly used standardised intelligence tests for children and adults. The WASI is a brief measure of intelligence

that can be used with individuals aged 6 to 89 years, and is highly correlated with full-length measures of IQ (Wechsler 1999). A two-subtest option which allows for estimation of a full-scale IQ (FSIQ-2) was used for the current study (reliability coefficients range = 0.93–0.98). Diagnostic Analysis of Nonverbal Accuracy – Revised (DANVA2) (Nowicki 1997) The DANVA2 is a 48-item task of FER, containing two subtests: Adult Faces (DANVA2-AF) and Child Faces (DANVA2-CF). Each subtest contains 24 photographs of male and female actors expressing one of four emotions: Happy, sad, angry or fearful, which are expressed at a high (overt) or low intensity (subtle). Participants are shown photographs, one at a time, and asked to identify the emotion expressed, according to the four choices listed above. Scoring is based on the number of errors made; scores are also calculated for the number of high- and low-intensity errors. The DANVA2-AF has an internal consistency between α = 0.64–0.77, and a test–retest reliability of r = 0.84. The DANVA2-CF has an internal consistency of α = 0.76, and a test–retest reliability of r = 0.74.

Child Behaviour Checklist (CBCL) (Achenbach 1991) The CBCL is a widely used parent-rated measure of child behavioural problems and competencies, for ages 4 to 18 years. For full scales, the internal consistency ranges from α = 0.78 to 0.97, and test–retest reliability ranges from r = 0.95 to 1.00. The Social Problems, Social Competence, Internalising Problems and Externalising Problems subscales were used in this study.

Pediatric Quality of Life Inventory (PedsQL) (Varni et al. 2001) The PedsQL is a 23-item questionnaire completed separately by parents (PedsQL – Parent; 8 to 12 or 13 to 18 year old) and children (PedsQL; ages 8–12) or teens (PedsQL; ages 13–18). The questionnaire measures physical, emotional, social and school functioning using a 5-point Likert scale, with strong internal consistency (α = 0.88 child-report, 0.89 parent-report).



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Emory Dyssemia Index (EDI) (Love et al. 1994) The EDI is a 42-item parent-rated questionnaire measuring expressive and receptive nonverbal difficulties. Items are rated for frequency of occurrence on a 1–4 Likert scale. Scores include a total EDI score and seven subscales: gaze and eye contact, space and touch, facial expressions, paralanguage, objects, social rules and norms, and nonverbal receptivity. Test retest reliabilities for total EDI score and subscales range from 0.63 to 0.86. Conners Parent Rating Scale – Third Edition (CPRS) (Conners 2008) The CPRS is parent-reported questionnaire measure of children and adolescent attention and behavioural functioning along six subscales: Inattention, Hyperactivity/Impulsivity, Learning Problems, Executive Functioning, Aggression and Peer/Family Relations. The CPRS has high internal validity (α = 0.80–0.91) and test– retest reliability (r = 0.76–0.85) for each subscale. The Inattention and Executive Functioning scales were used for the current study.

Analytical plan Preliminary analyses Normality checks, assessing skew and kurtosis were run prior to analyses. Descriptive statistics were computed for demographic variables. A series of preliminary independent-sample t-tests and chisquare analyses were conducted to examine expected group differences in intellectual ability, parent-rated academic and physical functioning, and demographic traits (age, race, sex) between children with NF1 and typically developing peers.

Hypothesis testing Between-groups comparisons To conserve power and account for shared variance between measures of the same construct, three multivariate analyses of covariance (MANCOVA) were performed to test our first hypothesis that there are significant differences between groups on measures of social functioning (i.e. parent- and childrated social functioning from the PedsQL, the Social Problems subscale from the CBCL and the EDI total score), FER (i.e. child and adult z-scores from the

DANVA2; errors on high and low intensity faces) and emotional functioning (i.e. parent- and child-rated emotional functioning from the PedsQL, and Internalising and Externalising subscales from the CBCL). For all analyses, estimated IQ was included as a covariate. Within-group correlations for children with neurofibromatosis type 1and community controls Correlational analyses examined the association between FER scores, behavioural data of social functioning, and parent-rated neurocognitive abilities Specifically, analyses included FER skills by parentrated cognitive functioning (i.e. parent-rated Inattention and Executive Functioning from the CPRS), FER skills by parent- and child-rated social functioning (i.e. social functioning on the PedsQL and CBCL Social Problems and Social Competence scales) and parent-rated cognitive functioning (i.e. parent-rated Inattention and Executive Functioning from the CPRS) by parent- and child-rated social functioning (i.e. social functioning on the PedsQL and CBCL Social Problems and Social Competence scales). Given that multiple analyses were conducted, the Hochberg modified Bonferroni procedure(Hochberg 1988) was used to guard against inflated Type I error rate.

Results Preliminary analyses Preliminary screening of skewness and kurtosis indicated normally distributed data. A significant difference between the sample of children with NF1 and typically developing peers was found with regard to the racial make-up of the sample; no other demographic differences were observed (Table 1). Independent-samples t-tests confirmed significant differences in estimated IQ [t(39) = 5.0, P < 0.001], in addition to parent-rated school [t(38) = 4.2, P < 0.001] and physical functioning [t(39) = 5.8, P < 0.001] on the PedsQL. These results (Fig. 1) are consistent with previous research, indicating lower IQ and academic and physical functioning in children with NF1 (Noll et al. 2007). Further, correlational analyses revealed a significant relationship between IQ and outcome variables of the proposed multivariate analyses (e.g. social functioning



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Figure 1 Comparison of children with NF1 and typically developing peers on estimated IQ and parentrated physical and school functioning.

variables, FER, emotional–behavioural functioning) among the sample as a whole (i.e. NF1 and controls; it was not correlated in NF1 subjects alone). As such, estimated IQ was used as a covariate in each of the multivariate models described below.

Multivariate analyses of variance

developing peers and after accounting for IQ, children with NF1 had significantly lower parent- and child-rated social functioning per the PedsQL [F(1, 39) = 20.8, P < 0.001; F(1, 39) = 7.4, P < 0.01, respectively], and greater social problems according to the CBCL [F(1, 39) = 19.3, P < 0.001]. No differences were reported between groups regarding nonverbal social communication skills, per the EDI [F(1, 39) = 2.0, NS].

Social functioning The multivariate model of social functioning indicated significant differences between groups (T2 = 1.1, P < 0.001; Table 2). Specifically, compared to typically

Facial expression recognition As expected, the multivariate test of differences in FER scores was also significant (T2 = 3.4, P < 0.01; Table 2).

Table 1 Demographic information

NF1 M ± SD Age Gender Male Female Race Caucasian African–American Other

Healthy n (%)

12.11 ± 2.24

M ± SD

Test statistic* n (%)

12.9 ± 1.94

0.78 1.42

15 (65.2) 8 (34.8)

11 (47.8) 12 (52.2)

17 (73.9) 6 (26.1) 0 (0)

13 (56.5) 4 (17.4) 6 (26.1)

6.93†

*Test statistic is Student’s t-test for age and chi-square for gender and race. † p < 0.05. M, mean; SD, standard deviation.



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Table 2 Group comparisons on study measures: Social Functioning, FER and Emotional Functioning

NF1

Controls M ± SD

**Social Functioning **Parent PedsQL – Socialb *Child PedsQL – Socialb **CBCL Social Problemsc EDI Total scorec *DANVA Facial Recognition *Child z-score **Child low-intensity errors Child high-intensity errors *Adult z-score **Adult low-intensity errors *Adult high intensity errors **Emotional Functioning **Parent PedsQL – Emotionb Child PedsQL – Emotionb *CBCL Internalisingc *CBCL Externalisingc

57.1 ± 22.50 60.3 ± 25.47 62.7 ± 7.78 84.0 ± 40.05

91.5 ± 12.19 83.3 ± 12.40 51.9 ± 3.67 65.2 ± 18.01

0.3 ± 0.99 3.2 ± 1.84 0.9 ± 1.25 0.4 ± 1.02 4.4 ± 1.18 1.6 ± 1.53

0.6 ± 0.52 0.4 ± 0.61 1.3 ± 0.77 0.2 ± 1.05 1.2 ± 1.54 3.2 ± 1.47

58.4 ± 21.02 57.9 ± 18.73 60.2 ± 10.88 49.9 ± 9.63

85.4 ± 14.92 66.5 ± 13.35 47.6 ± 12.33 47.1 ± 9.77

Legend: *p ≤ .01, **p ≤ .001, 2 a Multivariate test statistics are Hotellings T , whereas univariate test statistics are F values. b Scale Score, range 0 to 100. c T-scores: M = 50, SD = 10; M, mean; SD, standard deviation; PedsQL, Pediatric Quality of Life Inventory; CBCL, Child Behaviour Checklist; EDI, Emory Dyssemia Index; DANVA, Diagnostic Analysis of Nonverbal Accuracy; FER, facial expression recognition.

Relative to peers, children with NF1 had significantly weaker recognition of child faces [F(1, 37) = 8.2, P < .01] and adult faces [F(1, 37) = 3.8, P < 0.05]. Relatively poor FER scores by the sample of children with NF1 is largely a reflection of significant weaknesses on the low intensity conditions for adult [F(1, 37) = 3.8, P < 0.05] and child faces [F(1, 37) = 8.2, P < .01]. In contrast, children with NF1 made significantly fewer errors identifying emotions on high intensity adult faces compared to typically developing peers [F(1, 37) = 6.2, P < 0.01]. There were no differences between groups in their ability to identify high intensity child faces [F (1, 37) = 0.7; NS].

displayed more internalising problems [F(2, 39) = 5.9, P < 0.01], and externalising problems [F(2, 39) = 4.0, P < 0.05] on the CBCL than typically developing peers. However, no between-group differences were observed for child-rated emotional functioning per the PedsQL [F(2, 39) = 1.5, NS] (Table 2).

Correlations As previously described, correlation analyses examined the association between FER scores, behavioural data of social functioning and parentrated neurocognitive abilities. Results are presented by participant sample.

Emotional functioning Finally, the model of child emotional functioning was significant (T2 = 0.7, P < 0.01; Table 2). Specifically, parents reported that children with NF1 had lower overall emotional functioning according to scores on the PedsQL [F(2, 39) = 12.4, P < 0.001], and also

Neurofibromatosis type 1 participants Among the sample of children with NF1, there were no significant relationships between FER ability with either cognitive variables or behavioural measures of social functioning, or between measures of social



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functioning and parent-rated inattention/executive functioning among children with NF1. The only notable finding was a trend between parent-rated Social Problems and Inattention in children with NF1 (r = 0.44, P = 0.06), indicating that more inattention was related to greater social problems. Correlations for the NF1 participants are summarised in Table 3. Control participants Among the control group, there were no relationships between FER with measures of neurocognitive functioning, or FER and measures of social functioning among controls. A significant association was observed between parent-rated Social Problems of the CBCL with (a) Executive Functioning of the CPRS (r = 0.76, P < 0.001) and (b) Inattention (r = 0.71, P ≤ 0.001), such that greater perceived cognitive impairments were associated with more social problems. Further, in the control group, while failing to meet statistical significance, there was also a strong trend between Executive Functioning of the CPRS and parent-rated social quality of life, per the PedsQL (r = 0.45, P ≤ 0.06), such that greater reported executive deficits were associated with worse social quality of life. Correlations for the control group are summarised in Table 4.

Discussion The current study examined social functioning and FER ability in children with NF1 as compared to typically developing peers. As hypothesised, parents rated children with NF1 as having more social problems and lower overall social functioning compared to typically developing children; this is consistent with the child self-report ratings of social functioning. Parents also rated their child with NF1 as having more difficulty with overall emotional functioning and displaying more internalising and externalising behaviours than the comparison group. In contrast, self-report ratings did not suggest a significant difference in emotional functioning (per the PedsQL) between children with NF1 and the control sample. This may partially reflect the fact that the control sample of children in the current study self-reported their emotional functioning to be considerably lower than has been reported in healthy participants in the literature (i.e. 66.5 in the current study versus 80.86 in the literature; Varni, Burwinkle, Katz, Meeske & Dickinson, 2002), and also than the parent-proxy ratings in the current study. Given evidence of social problems, it is not surprising that children with NF1 also made significantly more errors in FER on low-intensity

Table 3 Correlationsa between social problems and competency with neurocognitive ability, social functioning and FER: NF1 participants

1. 2. 3. 4. 5. 6. 7. 8. 9.

DANVA2 Adult Score DANVA2 Child Score FSIQ CPRS Inattention CPRS Executive Functioning CBCL Social Problems CBCL Social Competence TM PedsQL Child-rated Social Functioning TM PedsQL Parent-rated Social Functioning

1.

2.

3.

— .38 .36 .04 .32 .35 .16 .05 .27

— .18 .06 .31 .36 .01 .26 .05

— .15 .15 .10 .16 .01 .27

4.

— .63** .44† .32 .12 .08

5.

6.

7.

8.

— .41 .32 .21 .42

— .25 .19 .46*

— .18 .27

— .43+

Legend: *P < .05, **P < .01. † P < .10 – trend; DANVA2, Diagnostic Analysis of Nonverbal Accuracy – Second Edition; FSIQ, Full Scale Intelligence Quotient; CPRS, TM Conners Parent Rating Scale – Third Edition; CBCL, Child Behaviour Checklist; PedsQL , Pediatric Quality of Life Inventory. a For each set of analyses, P-values were compared with criterion values calculated according to the Hochberg modified Bonferroni procedure to control for familywise error rate. This procedure requires the ordering of P-values from highest to lowest, with the most significant value compared to a criterion alpha value of .05/1 (.05), the second to an alpha of .05/2 (.025), the third to an alpha of .05/3 (.017), the fourth to an alpha of .05/4 (.0125), the fifth to an alpha of .05/5 (.01) and the sixth to an alpha of .05/6 (0.008).



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Table 4 Correlationsa between social problems and competency with neurocognitive ability, social functioning and FER: healthy controls

1. 2. 3. 4. 5. 6. 7. 8. 9.

DANVA2 Adult Score DANVA2 Child Score FSIQ CPRS Inattention CPRS Executive Functioning CBCL Social Problems CBCL Social Competence TM PedsQL Child-rated Social Functioning TM PedsQL Parent-rated Social Functioning

1.

2.

3.

— .24 .21 .04 .11 .16 .01 .14 .09

— .04 .13 .01 .15 .01 .20 .02

— .48* .42† .36† .15 .34 .06

4.

— .79*** .71** .24 .38 .35

5.

— .76*** .43† .14 .45†

6.

— .29 .23 .74***

7.

8.

— .00 .20

— .34

Legend: *P < .05, **P < .01, ***P < .001; † P < .10 – trend; DANVA2, Diagnostic Analysis of Nonverbal Accuracy – Second Edition; FSIQ, Full Scale Intelligence Quotient; CPRS, TM Conners Parent Rating Scale – Third Edition; CBCL, Child Behaviour Checklist; PedsQL , Pediatric Quality of Life Inventory. a For each set of analyses, P-values were compared with criterion values calculated according to the Hochberg modified Bonferroni procedure to control for familywise error rate. This procedure requires the ordering of P-values from highest to lowest, with the most significant value compared to a criterion alpha value of .05/1 (.05), the second to an alpha of .05/2 (.025), the third to an alpha of .05/3 (.017), the fourth to an alpha of .05/4 (.0125), the fifth to an alpha of .05/5 (.01) and the sixth to an alpha of .05/6 (0.008).

child and adult faces than the control sample. This suggests that children with NF1 have difficulty deciphering relatively ambiguous facial expressions. The ability to detect more nuanced facial expressions requires a child to perceive and decode multiple details simultaneously (e.g. integrating information from upper and lower halves of the face), which is often a more demanding task than interpretation of a high-intensity emotional expression. It is possible that the cognitive limitations of children with NF1, as described in previous studies (Hyman et al. 2006; Clements-Stephens et al. 2008), preclude accurate perception and/or interpretation of subtle facial affect. Indeed, Boni and colleagues suggested that cognitive impairment may be responsible for similar deficits in low-intensity FER among children with sickle cell disease who had cerebral infarcts (Boni et al. 2001). However, cognitive functioning was not uniformly related to FER in this study, and IQ was used as a covariate, it cannot fully explain the between group differences in FER in this case. It is possible that verbal and nonverbal IQ play different roles in FER – an effect that would have been washed out by using a full scale score – however it is also possible that FER difficulties in NF1 may be driven by other psychosocial or neurobiological factors. It is well recognised that emotional awareness and FER develop early in infancy, and generally improve

with age, resulting from improved efficiency of processing and increased experience or socialisation (e.g. Leppanen & Nelson, 2009). This normative developmental process is partially moderated by parent-child interactions (Daly, Abramovitch, & Pliner, 1980), and any deficit in parental emotion identification can predispose a child (via shared genetic and environmental mechanisms) to weaknesses in social cognitive skills (e.g. Bolte & Poustka, 2003; Gokcen, Bora, Erermis, S., Kesikci, Aydin, C. 2009). In the context of a hereditary disorder like NF1, it is possible that parents’ own socio-emotional symptoms (e.g. weak emotion identification skills) may impede their child’s ability to decode facial expressions because of modelling and heritability factors. While data regarding parental social functioning and FER was not available in the current study, a better understanding of the child’s microsystem on his social behaviour may elucidate factors that underlie social impairment in NF1. A second hypothesis includes the possibility that the development of emotion recognition skills may be fundamentally different for some children with NF1 compared to their healthy peers. Aligned with the social-motivation theory in ASD, children who are less motivated or rewarded by social stimuli may pay less attention to verbal and nonverbal affective



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cues (e.g. smiling, tone of voice) during social interactions in infancy (Dawson, Webb, & McPartland, 2005). If children are not actively attuned to facial expressions and affective speech early in development because it is inherently less rewarding, the wiring of neural circuits responsible for social/affective processing may be impacted as development proceeds (Dawson et al. 2005). Over time, this may lead to weak FER skills and generalised difficulties socialising with peers. While this theory has not been evaluated in children with NF1, it is widely discussed in the ASD literature and deserves attention given the overlapping social phenotypes observed between these populations. While children with NF1 performed poorly on low intensity child and adult FER tasks, they made significantly fewer errors than typically developing peers in their identification of high-intensity adult faces. This finding may relate to different patterns of socialisation between groups. Specifically, it is possible that children with NF1 may have more contact with adults, such as through frequent encounters with medical professionals or attention from caretakers who routinely address these children’s needs. Indeed, nurses and family caretakers have been cited as the most important source of support for youth with chronic illnesses, rather than same-aged friends (Graetz et al. 2000; Kyngas & Rissanen 2001). In addition, as discussed earlier, prior research suggests that children with NF1 have difficulties forming friendships, have fewer friendships and are more frequently rejected by their peers (North et al. 1997; Johnson et al. 1999). It is possible that this leads them to spend more time with adults relative to typically developing peers. While there is no known empirical data to suggest that FER is directly linked to the ratio of adult versus peer interactions, there is evidence that suggests life experiences influences emotional facial processing (e.g. for review see Lewis & Saarni, 1985; Pollack & Pawan, 2002). In addition to between-group differences, the current study explored the relationship between social deficits and ratings of neurocognitive functioning within the NF1 sample and control group. Among the control group, there was a significant relationship between parent-rated inattention and parent-rated social problems and a trend between parents’ ratings of executive

functioning and the child’s social quality of life. In other words, perceived higher order cognitive capacities (i.e. attention and executive functioning) were related to adaptive social behaviour. In contrast to the relationships observed between social and cognitive functioning in the control group, there were limited associations between assessment measures in children with NF1. In fact, the only notable outcome was a trend between parent-rated inattention and social problems, such that higher levels of inattention were associated with greater levels of social difficulty. The absence of significant associations between neurocognitive ratings and measures of social functioning or FER in the NF1 group is contrary to our hypotheses and is in contrast to recent literature. For example, Martin and colleagues reported that Verbal IQ significantly predicted adaptive social behaviour in children with NF1 (Martin et al. 2012). Further, Huijbregts and de Sonneville found that measures of executive ability were related to parent-reported social skills in children with NF1 (Huijbregts & De Sonneville 2011). A similar pattern of functioning – whereby stronger neurocognitive abilities are associated with better social functioning and FER – has also been shown in other child clinical populations (e.g. ADHD (Singh et al. 1998), paediatric brain tumour survivors (Bonner et al. 2008) that are marked by similar social and neurocognitive profiles as children with NF1. Traditionally, research has suggested that higherand lower-order cognitive abilities are implicated in adaptive social behaviour, of which FER is a component (Crick & Dodge 1994). As previously described, the control group generally followed this expected pattern, in which greater social difficulty is associated with weaker executive and attention processes. This pattern did not hold true, however, for children with NF1. There are several explanations that may account for the lack of association between measures of social and cognitive functioning. It is possible that this discrepancy relates to the limited cognitive measures used in this study. Specifically, the current study relied on a single parent-reported measure of attention and executive functioning, and did not incorporate performance-based assessments of cognitive ability. Indeed, previous research has shown relatively modest correlations between parent-



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ratings of executive functioning with objective tasks (Naglieri et al. 2005). Thus, it is possible with more extensive and task-based cognitive data a clearer picture of the relationship between social and cognitive functioning may emerge. However, it is also possible that there is something unique about the development of social information processing in children with NF1 that would lead to a different pattern of association between neurocognitive abilities and social outcomes than anticipated. That is, even with an extensive cognitive battery measuring multiple aspects of executive functioning, null associations between cognitive, social and FER variables may have persisted. Drawing from preliminary imaging data from individuals with NF1, anomalies in the superior temporal gyrus and fusiform gyrus may relate to social–emotional deficits in this population. These regions of the brain are important for processing auditory and visual information relevant to social–emotional stimuli and then communicating with the prefrontal cortex, which composites information to enable social–emotional understanding. As previously suggested by research, there may be dysfunction in the connection between these temporal/temporo-occipital regions and the prefrontal structures underlying deficits in social cognition observed in individuals with NF1 (Pride et al. 2014). This is in contrast to children with ADHD, for example, in which dysfunction in the frontostriatal pathway is widely implicated in both social impairment and executive dysfunction (Uekermann et al. 2010). While neurobiological research on social functioning in NF1 is in its infancy, it is important to consider the complexity of neurocircuitry potentially involved in social behaviour in this group, particularly in light of the lack of significant findings in this study. As the field works to better understand the neurobiology of social impairment in NF1, it may be useful to draw upon better-established neurobiological models from other clinical samples. One useful model may come from the literature on children with autism, given overlapping social phenotypes in NF1 and ASD (Garg et al. 2012; Walsh et al. 2012). Neurobiological research of social– emotional functioning in ASD has implicated both structural anomalies – such as those in the in superior temporal gyrus and fusiform gyrus (Hubl et al. 2003) – and functional connectivity dysfunction – such as

between the superior temporal regions and the prefrontal regions (Wicker et al. 2007) – which are also observed in NF1. In addition, there is literature that suggests early dysfunction in the amygdala may relate to deficits in FER in children with an ASD (Grelotti et al. 2002). Specifically, decreased amygdala activity may impede activation of the fusiform gyrus – which is also implicated in FER in patients with NF1 – via functional connections between these structures, resulting in poor FER skills. It is not known whether similarities in neuronal dysfunction between ASD and NF1 relate to a shared biologic/genetic mechanism that is directly linked to FER skills in both groups, or whether the dysfunctional circuitry and impairment in FER is secondary to shared deficits in social motivation, or another behavioural process, in these two populations. Regardless, a better understanding the aetiology of social difficulties and FER deficits in children with NF1 may have important implications for interventions, which makes this a valuable area for future research.

Limitations and future directions The results of this study need to be considered in the context of its limitations. This study is limited by a small sample recruited from a single institution. This may have restricted our ability to detect effects in some instances, and limited our choice of analytical techniques (e.g. could not examine predictors, mediators or moderators). Larger, multi-centre studies can provide further data to support these results. Despite the small sample, we identified marked social impairments in the sample of children with NF1, compared to typically developing peers. Although the groups were not matched for gender, having a comparison group is a particular strength of this study, as prior studies of social functioning in children with NF1 (Huijbregts & De Sonneville 2011; Martin et al. 2012) have lacked a strong comparison sample, if any at all. Another limitation is the fact that the findings from this study were based on outcomes from brief structured assessments (e.g. DANVA2) and self- and parent-reported questionnaires. Thus, it is not known whether weak FER ability or social functioning translate into poor peer relations, which could be addressed with future sociometric research. Limitations of the DANVA2 (e.g. the lack of



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normative data on accuracy by emotion, and the fact the faces were not judged by FACS standards, introducing some potential overlap between facial displays) also precluded a more in-depth analysis of FER, including understanding the differences between groups by emotion, which would have added depth to our understanding of social–emotional functioning in NF1. Ultimately, the current study affords important preliminary data regarding deficits in FER in children with NF1, and adds to the growing body of literature on social functioning in this population. However, there is a need for further investigation into these cognitive and social processes – including research on mediating and moderating variables of social outcomes – as these types of data will provide greater insight into potential mechanisms for social interventions in this particular population. By understanding the variables contributing to poor social outcomes in children with NF1, we can better tailor intervention approaches and ultimately help improve the quality of life in this group of children.

Acknowledgements None declared.

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Accepted 28 October 2015


Language in young children with neurofibromatosis-1: relations to functional communication, attention, and social functioning.

emotional problems in Israeli children with neurofibromatosis type 1.

Activity and participation in children with neurofibromatosis type 1.

Adaptive behavior in young children with neurofibromatosis type 1.

Circle of Willis abnormalities in children with neurofibromatosis type 1.

Muscle weakness in children with neurofibromatosis type 1.

Are muscles weaker in children with neurofibromatosis type 1?

Motor problems in children with neurofibromatosis type 1.

Optic gliomas in children with neurofibromatosis type 1.

[Phenotypic and genetic features in neurofibromatosis type 1 in children].

Diffusion tensor imaging of neurofibromatosis bright objects in children with neurofibromatosis type 1.

Cognitive functioning in young children with type 1 diabetes.

Non-functioning pituitary macroadenoma in a child with neurofibromatosis type 1.

Use of 3D faces facilitates facial expression recognition in children.

Constipation in adults with neurofibromatosis type 1.

Hemostasis and Type 1 Neurofibromatosis.

[Neurofibromatosis type 1].

Language and social functioning in children and adolescents with epilepsy.

Facial Expression Recognition in Children with Cochlear Implants and Hearing Aids.

Relationship between cognitive dysfunction, gait, and motor impairment in children and adolescents with neurofibromatosis type 1.

Equatorial Staphyloma Associated with Neurofibromatosis Type 1.

Becker's nevus with neurofibromatosis type 1.

MRI features of plexiform neurofibromas involving the liver and pancreas in children with neurofibromatosis type 1.

Anisometropia in children with neurofibromatosis type 1 and unilateral optic glioma.