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. Author manuscript; available in PMC: 2025 May 1.
Published in final edited form as: Autism. 2023 Sep 10;28(5):1216–1230. doi: 10.1177/13623613231195108

Changes in the Severity of Autism Symptom Domains are Related to Mental Health Challenges During Middle Childhood

Einat Waizbard-Bartov 1,2, Emilio Ferrer 1, Brianna Heath 2, Derek S Andrews 2, Sally Rogers 2, Connor M Kerns 3, Christine Wu Nordahl 2, Marjorie Solomon 2, David G Amaral 2
PMCID: PMC10924781  NIHMSID: NIHMS1921998  PMID: 37691349

Abstract

Introduction

Many autistic children experience changes in core symptom severity across middle childhood, when co-occurring mental health conditions emerge. We evaluated this relationship in 75 autistic children from 6-to-11-years-old.

Methods

Autism symptom severity change was evaluated for total autism symptoms using the autism diagnostic observation schedule (ADOS CSS), as well as social-communication symptoms (SA CSS) and restricted/repetitive behaviors (RRB CSS). Children were grouped based on their symptom severity change patterns. Mental health symptoms (ADHD, anxiety, disruptive behavior problems) were assessed via parental interview and questionnaire and compared across the groups.

Results

Co-occurring mental health symptoms were more strongly associated with change in SA or RRB severity than with total autism symptom severity. Two relevant groups were identified. The SA-Increasing-severity-group (21.3%) had elevated and increasing levels of anxiety, ADHD and disruptive behavior problems compared with children with stable SA severity. The RRB-Decreasing-severity-group (22.7%) had elevated and increasing levels of anxiety; 94% of these children met criteria for an anxiety disorder.

Conclusions

Autism symptom severity change during middle childhood is associated with co-occurring mental health symptoms. Children that increase in SA severity are also likely to demonstrate greater psychopathology, while decreases in RRB severity are associated with higher levels of anxiety.

Lay Abstract

For many autistic children, the severity of their autism symptoms changes during middle childhood. We studied whether these changes are associated with increasing mental health challenges such as anxiety and ADHD. Children who had worsening social-communication challenges had more anxiety and ADHD symptoms and disruptive behavior problems than other children. Children who decreased their restricted and repetitive behaviors, on the other hand, had more anxiety. We discuss why these changes in autism symptoms may lead to increases in other mental health concerns.

Introduction

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by the presence of two core symptom domains: social-communication challenges (SA) and restricted/repetitive behaviors (RRB) (APA, 2013). Autism may also be associated with several additional mental health conditions; 70% of autistic individuals have at least one co-occurring condition and 41% have two or more (Simonoff et al., 2008), making mental health challenges a common part of autistic life (Waizbard-Bartov, Fein, Lord, & Amaral, 2023). The most common co-occurring mental health conditions experienced by autistic individuals are attention-deficit hyperactivity disorder (ADHD), anxiety disorders and disruptive, impulse-control, and conduct disorders (Lai et al., 2019; Mutluer et al., 2022).

Many mental health challenges develop during middle childhood, starting around age 6-7 (Kessler et al., 2007). For neurotypical children, ADHD tends to emerge between ages 6 and 8 and anxiety disorders between ages 8 and 13 (Solmi et al., 2022; Visser et al., 2014). For autistic children, anxiety has been identified starting from the preschool years and across the duration of childhood (Vasa, Keefer, McDonald, Hunsche, & Kerns, 2020) while emotional difficulties (e.g., often feeling unhappy and downhearted) and hyperactivity are reported to emerge at around age 7 (Colvert et al., 2021).

Higher autism symptom severity has been associated with higher levels of emotional and behavioral problems (Colvert et al., 2021; Jang & Matson, 2015; Lindor et al., 2019; Simonoff et al., 2019) as well as clinically significant ADHD symptoms (Avni, Ben-Itzchak, & Zachor, 2018; Colvert et al., 2021; Hollingdale, Woodhouse, Young, Fridman, & Mandy, 2019; Zachor & Ben-Itzchak, 2019) and higher levels of social anxiety (Stark, Groves, & Kofler, 2022). Evaluating core symptom domains independently, similar associations emerge. More severe social communication symptoms (Duvekot, van der Ende, Verhulst, & Greaves-Lord, 2018) as well as RRB (Baribeau et al., 2020; Gotham et al., 2013) have been linked to higher anxiety levels. The nature of this relation, however, is not clear. It could be that having heightened levels of core symptoms contributes to children’s mental health symptoms. Alternatively, dealing with mental health challenges could impact children’s core symptom presentation. Moreover, while these studies depict a positive association between co-occurring psychopathology and autism severity levels, less is known about the relationship between psychopathology and autism severity change. One recent study found that as anxiety levels decreased during Cognitive-Behavioral Therapy, both social-communication challenges and RRB were also reduced (Fuselier et al., 2023).

Finally, individual characteristics, such as the birth-assigned sex of the individual, also influence total autism severity. For example, girls tend to decrease in autism symptom severity more than boys during childhood (Szatmari et al., 2015; Waizbard-Bartov et al., 2022; Waizbard-Bartov et al., 2020). Furthermore, decreases in autism severity are associated with having higher IQ (Hus, Gotham, & Lord, 2014; Solomon et al., 2018). However, it is not clear how characteristics such as IQ and birth-assigned sex are related to changes in the severity of the two core autism symptom domains. Cognitive ability, for one, has been found to moderate the relationship between change in social-communication symptoms and mental health. Sukhodolsky et al. (2008) showed that for children with typical-range IQ, greater impairment in social reciprocity was associated with more severe anxiety. The high rates of ASD and mental health co-occurrence make understanding the heterogeneity of symptom severity change in relation to mental health an important area for research (Pender, Fearon, Heron, & Mandy, 2020).

The current study is the third in a series evaluating change in the severity of autism symptoms in the children of the University of California (UC) Davis MIND Institute Autism Phenome Project (APP). We previously showed that about half of children experienced change in the severity of their autism symptoms during childhood: 46% during early childhood, from age 3 to 6 (Waizbard-Bartov et al., 2020) and 51% across the duration of childhood, from age 3 to 11 (Waizbard-Bartov et al., 2022). Of these, 28% showed change from age 6 to age 11, i.e., during middle childhood: 12% decreased in symptom severity while 16% increased. The goal of the current study was to focus on children’s autism symptom severity change during middle childhood and determine whether it was associated with the emergence of co-occurring mental health symptoms.

We evaluated the most common co-occurring mental health conditions in autistic individuals: ADHD, anxiety and disruptive behavior problems, as well as their additive impact using a general psychopathology measure. As the severity of social-communication symptoms and RRB may change differently across childhood (Kim et al., 2018; Waizbard-Bartov et al., 2022) change was analyzed for both the total autism symptoms score (ADOS CSS) as well as the two domain scores, separately (SA CSS and RRB CSS). We hypothesized that: 1) Increases in autism symptom severity (for ADOS CSS, SA CSS and RRB CSS) would be associated with increased mental health symptoms. Conversely 2) Decreases in autism symptom severity would be associated with fewer mental health challenges. 3) Change in the severity of the core symptom domains will show similar associations with mental health symptoms, and 4) The relationship between change in the severity of core symptoms and mental health challenges would be moderated by individual characteristics including sex and cognitive ability.

Methods

Participants

Participants enrolled in the longitudinal UC Davis MIND Institute APP when they were between 2 and 3.5 years of age (Time 1; T1). For a full description of the APP cohort see (Nordahl et al., 2021). In the present report, we focus on change in autism symptom severity during middle childhood based on information collected at the beginning (Time 3; T3, approximately age 6) and end (Time 4; T4, approximately age 11) of middle childhood.

The current study includes 75 children (15 girls) enrolled in the APP. These children are a subset of samples in previous publications (Waizbard-Bartov et al. (2020), N=125; Waizbard-Bartov et al. (2022), N=182), who completed behavioral evaluations of autism symptoms at T3 and T4 as well as for co-occurring mental health symptoms and IQ (Table 1; sample characteristics at T1 appear in Table S1). There were no differences between the current subsample (N=75) and the larger sample in any of the variables evaluated in the current study (p>0.05). The study was approved by the UC Davis Review Board and informed consent was obtained from the parent or guardian of each participant.

TABLE 1.

Sample characteristics

T3 T4
N 75
Female 15(20%)
Age 68.9(12) 136.3(10)
Autism symptom severity SA CSS 6.6(2.0) 7.3(1.8)
RRB CSS 8.5(1.5) 7.9(1.9)
Autism severity change SA CSS 0.72(2.1)
RRB CSS −0.57(1.7)
IQ 78(32) 81(31)
Psychopathology: CBCL Internalizing behaviors 58(9) 61(10)
DSM anxiety 55(7) 58(9)
Anxious/depressed 54(6) 60(9)
DSM ADHD 58(8) 61(8)
Attention problems 62(8) 66(10)
Externalizing behaviors 56(9) 56(9)
Total behavior problems 59(9) 63(9)
Psychopathology: ADIS/ASA CSR ------- 4.3(2.2)
Proportion with anxiety disorder ------- .73(.45)
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Note: means (SD)

Inclusion criteria for the study were based on the NIH Collaborative Programs of Excellence in Autism. Participants had received a diagnosis of ASD in the community that was confirmed by a licensed clinician at the MIND Institute using the Autism Diagnostic Interview-revised (ADI-R) and the Autism Diagnostic Observation Schedule-2 (ADOS-2) (Lord et al., 2000; Lord et al., 2012; Lord, Rutter, & Le Couteur, 1994). An ASD diagnosis was confirmed if they met the ADOS-2 cut off score for either autism or ASD and exceeded the ADI-R cutoff score for autism on either the Social or Communication subscales while being within two points of this criterion on the other subscale. Participants also needed to be English speaking, reside with at least one biological parent, be ambulatory and not be diagnosed with a severe motor, vision, hearing or chronic health issue that could hinder participation in the study. There was no community involvement in the design or interpretation of this study.

Measures

Standardized assessment measures in children:

Assessment of autism symptoms included:
Autism Diagnostic Observation Schedule-2: ADOS-2 (Lord et al., 2000; Lord et al., 2012)

The ADOS-2 (Lord et al., 2000; Lord et al., 2012) and Calibrated Severity Scores (Gotham, Pickles, & Lord, 2009) were used to evaluate autism symptoms across childhood. Autism symptom severity was also evaluated separately for social-communication symptoms (SA CSS) and restricted / repetitive behaviors (RRB CSS) (Hus et al., 2014). A detailed account of this measure and its use in the current study appears in Waizbard-Bartov et al. (2022).

Assessment of co-occurring mental health symptoms included:
Anxiety Disorders Interview Schedule–IV–Parent Interview: ADIS–P (Albano & Silverman, 1996); The Autism Spectrum Addendum (ASA) (Kerns, Renno, Kendall, Wood, & Storch, 2017)

The ADIS-P is a semi-structured parent interview aimed at assessing the presence of anxiety disorders in children. Assessments included four modules, each focused on a different childhood anxiety disorder: separation anxiety, social anxiety disorder, specific phobia and generalized anxiety disorder (these disorders were not substantially changed in the DSM-5 thus can be assessed using the DSM-IV-based measure). The Autism Spectrum Addendum (ASA) is a series of specific guidelines and prompts included in the ADIS-P to adapt it for use with autistic children. It includes five modules to assess distinct expressions of anxiety that often arise in ASD. These include: other social fear (i.e., social anxiety without a fear of negative evaluation), uncommon phobias, fear related to special interest areas, fear of change and negative reaction to change. The ADIS/ASA produces a Clinical Severity Rating (CSR) for each module, ranging from 0-8 and representing the child’s overall anxiety level and interference in life. A score of 4 on this scale is the cut-off for anxiety that is considered “clinically significant” with scores of 4 or higher signifying a potential anxiety diagnosis. Anxiety was measured using the ADIS/ASA in two ways: 1) the child’s highest CSR of all modules (for either DSM anxiety disorders or distinct anxiety characteristics of ASD) was used as an indicator of the child’s highest anxiety level, and 2) whether the child meets criteria for having an anxiety disorder based on the CSR (a binary “yes/no” score). All interviewers were trained to criterion, had achieved reliability on this instrument and attended weekly supervision meetings. The ADIS/ASA was administered at T4 and taken as an indication of the level of anxiety symptoms at the end of middle childhood.

Child Behavior Checklist/ 6–18 years (CBCL) (Achenbach & Ruffle, 2000)

The CBCL is a standardized, parent-report questionnaire assessing emotional and behavioral problems in children and adolescents. It has been validated for use with children diagnosed with ASD (Pandolfi, Magyar, & Dill, 2012). The CBCL includes “DSM-oriented” subscales aimed at capturing DSM-defined symptoms as well as norm-referenced T-Scores for specific syndrome subscales and broadband scales. Anxiety was measured using three CBCL scales: 1) internalizing behaviors broadband scale, 2) DSM anxiety scale, and 3) anxious/depressed syndrome subscale. ADHD was measured using two scales: 1) DSM ADHD scale, and 2) attention problems syndrome subscale. Disruptive behavior problems were measured using the externalizing behaviors broadband scale. The total behavior problems broadband scale was analyzed as an indicator of overall psychopathology. Clinically significant elevation in symptoms is indicated by T-scores of 64 and higher on broadband scales and 70 and higher on syndrome subscales.

Assessments of cognitive ability included:
Differential Abilities Scales-II (DAS-II) (Elliot, 2007)

The DAS-II assesses children’s cognitive abilities between 2.5 and 17 years of age in a standardized manner. Participants completed either the DAS-II Upper Early Years or the School Age forms. Sixteen children were not able to achieve basal scores, i.e., achieve a full-scale IQ>25 on the DAS-II at T3 and so were instead administered the Mullen Scales of Early Learning. DQ scores were used to calculate IQ scores. Seven children were not able to achieve basal scores on the DAS-II at T4. For statistical analyses, IQ scores <25 were converted to a score of 24. Two children did not complete IQ testing at T4 due to noncooperation.

Mullen Scales of Early Learning: MSEL (Mullen, 1995)

The MSEL measures cognitive and developmental functioning from infancy and up to 68 months of age in a standardized manner. Verbal, non-verbal and combined IQ were estimated by calculating ratio developmental quotient (DQ) scores, dividing average verbal, non-verbal and combined MSEL subscale age equivalents by chronological age. As a minority of participants achieved the lowest standard score, a ratio DQ was calculated (mental age/ chronological age * 100) to provide more specific individual estimates of cognitive ability (nonverbal, verbal and combined IQ).

Data analysis

The first part of the analysis employed methods used in previous publications (see Waizbard-Bartov et al. (2020) and Waizbard-Bartov et al. (2022) for a detailed description). In brief, autism symptom severity change across middle childhood (T3-T4) was evaluated for each child using three change scores: one for change in overall autism symptom severity (ADOS CSS), a second for change in social-communication symptoms (SA CSS) and a third for change in RRB (RRB CSS). The distribution of severity change scores appears in Supplemental Figure S1. The Reliable Change Index Statistic (RCI) (Jacobson & Truax, 1991) was used to determine statistically significant changes in severity across childhood (Table S2). The RCI indicated that changes of 2 ADOS CSS points, of 3 SA CSS points and of 2 RRB CSS points in either direction, constituted significant changes in CSS. Children were grouped based on their individual severity change patterns (decrease, increase or stable) for ADOS total, SA and RRB severity. Symptom severity levels, cognitive ability and sex composition were compared across groups.

The second part of the analysis evaluated co-occurring mental health symptoms for the established change groups. ADHD symptoms, anxiety symptoms, disruptive behavior problems and total psychopathology were compared across the groups at T3 and at T4 and within groups from T3-T4. For some mental health conditions, different measures capture distinct aspects of the condition. We thus used various measures and scales in order to have as much convergent information as possible to evaluate that condition. For example, anxiety was evaluated using two measures: the CBCL and the ADIS/ASA. ADHD, disruptive behavior problems and overall psychopathology were measured using the CBCL. For variables for which we had several measures and subscales (e.g., anxiety, ADHD) we used a MANOVA to evaluate group differences. This approach finds a linear combination of the various measures that maximizes differences between groups and allows examination of the unique contribution of each measure to the differences. Clinical thresholds were also used to evaluate significant elevation in symptom levels for the CBCL and the ADIS/ASA.

Results

Children in the study were divided into three groups based on their severity change pattern during middle childhood. We first evaluated groups of children with common change patterns in overall autism symptom severity (decreasing, increasing and stable severity levels). We found that the associations between change in total ADOS CSS and mental health symptoms were weak across these groups. There were minimal group differences in levels of anxiety, ADHD symptoms, disruptive behavior problems and overall psychopathology at T3 and T4, and either no or small within-group differences in mental health levels over time. See Supplementary Information. Next, we evaluated groups of children based on their severity change patterns from T3 to T4 in either of the two domain scores, SA CSS and RRB CSS. These analyses yielded stronger associations between symptom change and the emergence of psychopathology, described in greater detail below. Information about the ADOS, SA and RRB change groups at T1 and from T1-T3 appears in the Supplementary Information and in Tables S3 and S4. The overlap between children in the different change groups is described in Table S5 and Figure S2. All differences reported, both between-groups and within-groups, are statistically significant.

SA CSS change: comparing children that increased with children that remained stable

An analysis of children’s SA severity change resulted in the following two groups. The SA-Increasing-severity-group (N=16, 21.3%) included children that increased significantly in SA severity (by 3 or more SA CSS points). The SA-Stable-severity-group (N=57, 76%) comprised children that varied by 2 or less SA CSS points. As only two children significantly decreased in SA severity, they were not included in these analyses.

Characterizing the SA-CSS change groups

Concerning autism symptoms, the SA-Increasing-severity-group had a lower SA CSS compared to the SA-Stable-severity-group at T3 (Table S7; Table 2; Figure 1). But, from T3-T4 the SA-Increasing-severity-group greatly increased in SA CSS to have higher SA CSS at T4 compared to the SA-Stable-severity-group. Concerning cognitive ability, at T3 the SA-Increasing-severity-group had higher mean IQ than the SA-Stable-severity-group (Table S7). Both groups maintained stable IQ levels from T3-T4. Last, the SA change groups differed in birth-assigned sex composition: the SA-Increasing-severity-group was comprised only of boys (16 boys) while the SA-Stable-severity-group included all girls in the sample (42 boys, 15 girls) (Table S7; Table 2).

TABLE 2.

SA CSS and RRB CSS change groups

SA-I SA-S RRB-I RRB-S RRB-D
N,% 75=100% 16, 21.3% 59, 78.7% 7, 9.3% 51, 68% 17, 22.7%
Females N, %** 0, 0% 15, 100% * 0, 0% 13, 86.7% 2, 13.3%
ADOS Symptom Severity SA CSS T3 4.7(1.5) 7.1(1.8) * 5.9(2.5) 6.9(1.8) 6.2(2.2)
T4 ↑ 8.4(1.4) 7.1(1.7) * 6.3(2.3) ↑7.5(1.7) 7.1(2.0)
RRB CSS T3 8.3(1.1) 8.5(1.6) 6.0(2.5) +^ 8.8(1.1) 8.5(1.2)
T4 7.3(3.0) 8.1(1.4) 8.4(1.9) 8.6(1.2) ↓ 5.8(2.1) * +
ADOS Severity Change SA CSS T3-T4 3.8(0.7) 0.1(1.2) 0.4(1.6) 0.7(1.9) 0.9(2.8)
RRB CSS T3-T4 −1.1(2.3) −0.4(1.4) 2.4(0.8) −0.3(0.7) −2.8(1.3)
IQ T3 92(28) 74(32)* 82(34) 77(32) 81(31)
T4 92(27) 77(32) 79(35) 81(31) 82(33)
Psychopathology: CBCL Internalizing behaviors T3 61(10) 58(8) 56(12) 59(8) 59(9)
T4 66(7) 60(10)* 58(15) 60(10) 64(8)
DSM Anxiety T3 59(9) 54(6) 54(6) 55(6) 56(10)
T4 63(11) ↑ 58(8) 55(9) ↑58(8) 60(10)
Anxious/depressed T3 56(7) 54(6) 55(9) 54(5) 54(7)
T4 ↑ 65(9) ↑ 59(9) * 54(5) +^ ↑ 60(9) ↑ 62(10)
DSM ADHD T3 57(6) 59(8) 55(8) 59(8) 57(7)
T4 ↑ 65(9) 61(8) 61(10) 61(8) 62(8)
Attention problems T3 61(8) 63(8) 55(8) 63(7)^ 61(7)
T4 ↑ 70(12) 66(10) 63(10) 67(11) ↑66(8)
Externalizing behaviors T3 56(8) 56(9) 51(9) 57(9) 56(9)
T4 60(6) 55(10) * 56(8) 56(9) 56(10)
Total behavior problems T3 60(10) 58(9) 55(12) 59(8) 58(10)
T4 ↑ 69(5) 61(9) * 59(11) 62(9) ↑ 65(7)
Psychopathology: ADIS/ASA CSR T4 5.0(1.9) 4.2(2.2) 3.1(2.5) 4.2(2.4) 5.0(1.3)
Proportion with anxiety disorder T4 0.86(0.36) 0.70(0.46) 0.43(0.53) 0.70(0.47) 0.94(0.24) * +
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Notes: means(SD); * = Difference between SA-I and SA-S is p<0.05; * = Difference between RRB-D and RRB-S is p<0.05; + = Difference between RRB-D and RRB-I is p<0.05; ^ = Difference between RRB-S and RRB-I is p<0.05; ↑ = Increase from T3-T4 is p<0.05; ↓ = Decrease T3-T4 is p<0.05; ** percentage of all girls; Group names: SA-I = SA-Increasing-severity-group, SA-S = SA-Stable-severity-group, RRB-I = RRB-Increasing-severity-group, RRB-S = RRB-Stable-severity-group, RRB-D = RRB-Decreasing-severity-group.

Fig. 1.

Fig. 1

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Autism symptom trajectories across childhood. (A) The SA-Increasing-severity-group (SA-I) had lower SA severity compared to the SA-Stable-severity-group (SA-S) at T3. from T3-T4, however, the SA-Increasing-severity-group increased in SA severity to have a higher severity level compared to the SA-Stable-severity-group at T4. (B) The RRB-Increasing-severity-group (RRB-I) had the lowest RRB severity level at T3. From T3-T4 the RRB-Decreasing-severity-group (RRB-D) decreased in RRB severity to have a lower severity level compared to the other two groups at T4, while the RRB-Increasing-severity-group (RRB-I) increased in severity.

Summary

At T3, the SA-Increasing-severity-group had lower SA CSS and higher IQ compared to the SA-Stable-severity-group. This group increased in SA severity from T3-T4, to have higher SA CSS and borderline-higher IQ compared to the SA-Stable-severity-group at T4. No autistic girls (n=15) were included within the SA-Increasing-severity-group.

Co-occurring mental health conditions in the SA-CSS change groups

Anxiety

At T3, the MANOVA-based F test indicated that the SA-Increasing-severity-group and the SA-Stable-severity-group differed in CBCL DSM anxiety (yet a follow up t-test did not indicate significant group differences; see Supplementary Tables S6 and S7 for statistical results). Other CBCL anxiety scales did not differ (Table 2; Figure 2). From T3-T4 both groups increased in anxiety symptoms: the SA-Increasing-severity-group increased in anxious/depressed symptoms and the SA-Stable-severity-group increased in both anxious/depressed and DSM anxiety (Table S7). At T4, the SA-Increasing-severity-group had clinically elevated levels for the CBCL internalizing behaviors and the ADIS/ASA CSR and the SA-Stable-severity-group had borderline elevated ADIS/ASA CSR. The SA-Increasing-severity-group’s mean CBCL internalizing behaviors and anxious/depressed symptoms were also higher than the SA-Stable-severity-groups’, but DSM anxiety levels were similar.

Fig. 2.

Fig. 2

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Trajectories of CBCL anxious/depressed symptoms, DSM anxiety and internalizing behaviors for the (A) SA-Increasing-severity-group (SA-I) and (B) SA-Stable-severity-group (SA-S). The lower line (64) represents the clinical significance threshold for internalizing behaviors, the upper line (70) for anxious/depressed symptoms. (C) ADIS CSR medians for the SA change groups at T4. The dotted line (4) represents the clinical significance threshold. (D) Proportion of children in the SA change groups with anxiety disorder. Both the SA-Increasing-severity-group and SA-Stable-severity-group increased in anxious/depressed symptoms from T3-T4, and the SA-Stable-severity-group also increased in DSM anxiety. At T4, the SA-Increasing-severity-group had clinically elevated CBCL internalizing behaviors, its internalizing behaviors and anxious/depressed symptoms were higher than the SA-Stable-severity-groups’ and it had clinically elevated ADIS/ASA anxiety symptoms.

ADHD

There were no group differences at T3 in ADHD symptoms between the SA-Increasing-severity and SA-Stable-severity-groups (Tables S6 and S7). From T3-T4 the SA-Increasing-severity-group increased in CBCL DSM ADHD and attention problems while the SA-Stable-severity-group remained stable in both (Table 2; Figure 3). At T4 there were no group differences in attention problems, but the SA-Increasing-severity-groups’ mean level was clinically elevated.

Fig. 3.

Fig. 3

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Trajectories of CBCL DSM ADHD symptoms and attention problems for the (A) SA-Increasing-severity-group (SA-I) and (B) SA-Stable-severity-group (SA-S). The dotted line (70) represents the clinical significance threshold for attention problems. The SA-Increasing-severity-group increased from T3-T4 in CBCL DSM ADHD and attention problems, while the SA-Stable-severity-group remained stable. At T4, the SA-Increasing-severity-group had clinically elevated CBCL attention problems.

Disruptive behavior problems

At T3 there were no group differences in disruptive behavior problems (Table S7). But, by T4, the SA-Increasing-severity-group had higher disruptive behavior problems compared to the SA-Stable-severity-group (Table 2; Figure 4).

Fig. 4.

Fig. 4

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Trajectories of disruptive behavior problems (measured via CBCL externalizing behaviors) for the SA-Increasing-severity-group (SA-I) and SA-Stable-severity-group (SA-S). The dotted line (64) represents the clinical significance threshold. At T4 the SA-Increasing-severity-group had higher disruptive behavior problems compared to the SA-Stable-severity-group.

Overall psychopathology

At T3 there were no group differences in overall psychopathology (Table S7). From T3-T4 the SA-Increasing-severity-group increased in overall psychopathology to have a clinically elevated level at T4, that was also higher than the SA-Stable-severity-groups’ level (Table 2; Figure 5).

Fig. 5.

Fig. 5

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Trajectories of overall psychopathology (measured via CBCL total behavior problems) for the SA-Increasing-severity-group (SA-I) and SA-Stable-severity-group (SA-S). The dotted line (64) represents the clinical significance threshold. The SA-Increasing-severity-group increased from T3-T4 to have a clinically elevated overall psychopathology score at T4 that was higher than the SA-Stable-severity-groups’.

Summary

The SA-Increasing-severity-group demonstrated greater symptoms of anxiety, ADHD and overall psychopathology from T3-T4. The SA-Stable-severity-group increased in anxiety symptoms and had stable ADHD symptoms and overall psychopathology levels. At T4, the SA-Increasing-severity-group had clinically-elevated levels of anxiety, attention problems and overall psychopathology, while the SA-Stable-severity-group had borderline levels for anxiety and non-elevated ADHD symptoms and overall psychopathology level. Finally, at T4 the SA-Increasing-severity-group had higher anxiety symptoms, disruptive behavior problems and overall psychopathology than the SA-Stable-severity-group.

RRB CSS change: comparing children that increased, remained stable and decreased in severity

Evaluating children’s RRB severity change, three groups were defined: An RRB-Decreasing-severity-group (N=17, 22.7%) comprised children that significantly decreased in RRB severity (by 2 or more RRB CSS). An RRB-Stable-severity-group (N=51, 68%) included children that changed by 1 point or less, and an RRB-Increasing-severity-group (N=7, 9.3%) comprised children that significantly increased in RRB severity by 2 or more RRB CSS.

Characterizing the RRB-CSS change groups

At T3, the RRB-Increasing-severity-group had the lowest RRB severity, while the other two groups did not differ (Table S8; Table 2; Figure 1). From T3-T4 the RRB-Decreasing-severity-group decreased in RRB severity, while the RRB-Stable-severity-group remained stable and the RRB-Increasing-severity group trended towards increasing severity (the increase in RRB severity group likely did not reach statistical significance due to the small number of children in the group and thus low power to detect differences over time using t-tests). At T4 the RRB-Decreasing-severity-group had a lower RRB severity level compared to both other groups, which did not differ. There were no group differences in IQ at either T3 or T4 and groups did not change in IQ from T3-T4 (Table S8; Table 2). Last, there were no differences in birth-assigned sex between the RRB change groups (Table S8; Table 2).

Summary

At T3, the RRB-Increasing-severity-group had the lowest RRB severity level. The RRB-Decreasing-severity-group decreased in RRB severity from T3-T4 to have the lowest level at T4.

Co-occurring mental health conditions in the RRB-CSS change groups

Anxiety

There were no group differences in anxiety levels at T3 (Table S6 and S8). From T3-T4, the RRB-Decreasing-severity-group increased in CBCL anxious/depressed symptoms, and the RRB-Stable-severity-group increased in both CBCL anxious/depressed and DSM anxiety symptoms (Table 2; Figure 6). The RRB-Increasing-severity-group had stable anxiety levels. At T4, the RRB-Decreasing-severity-group had clinically elevated CBCL internalizing behaviors. The RRB-Increasing-severity-group, in comparison, had the lowest CBCL anxious/depressed symptoms. The three RRB change groups also differed at T4 in the ADIS CSR and proportion of children that met criteria for an anxiety disorder. The RRB-Decreasing-severity-group had a higher proportion of children (94%) that met criteria for an anxiety disorder than both other groups, which did not differ. The RRB-Decreasing-severity-group also had a clinically elevated ADIS/ASA CSR.

Fig. 6.

Fig. 6

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Trajectories of CBCL anxious/depressed symptoms, DSM anxiety and internalizing behaviors for the (A) RRB-Decreasing-severity-group (RRB-D) (B) RRB-Stable-severity-group (RRB-S) and (C) RRB-Increasing-severity-group (RRB-I). The lower line (64) represents the clinical significance threshold for internalizing behaviors, the upper line (70) for anxious/depressed symptoms. (D) Median ADIS CSR for the RRB change groups at T4. The dotted line (4) represents the clinical significance threshold. (E) Proportion of children in the RRB change groups with anxiety disorders. From T3-T4 the RRB-Decreasing-severity-group and RRB-Stable-severity-group increased in CBCL anxious/depressed symptoms, and the RRB-Stable-severity-group also increased in DSM anxiety. At T4 the RRB-Decreasing-severity-group had clinically elevated CBCL internalizing behaviors and ADIS/ASA CSR and included a higher proportion of children (94%) with anxiety disorders than both other groups. The RRB-Increasing-severity-group had the lowest CBCL anxious/depressed symptoms.

ADHD

At T3, the RRB change groups differed in CBCL attention problems (Tables S6 and S8; Table 2; Figure S3). Follow up comparisons showed that the RRB-Increasing-severity-group had lower attention problems than the RRB-Stable-severity-group. There were no differences between RRB change groups in DSM ADHD at T3. From T3-T4 the RRB decreasing-severity-group increased in attention problems while the other two groups remained stable. There were no group differences in ADHD symptoms at T4.

Disruptive behavior problems

There were no group differences in disruptive behavior problems or changes over time for the RRB change groups (Table S8; Table 2; Figure S4).

Overall psychopathology

There were no group differences in overall psychopathology at T3 (Table S8; Table 2; Figure 7). From T3-T4 the RRB-Decreasing-severity-group increased in overall psychopathology to have a clinically elevated level at T4, while the other groups remained stable. There were no significant differences at T4.

Fig. 7.

Fig. 7

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Trajectories of overall psychopathology (measured via CBCL total behavior problems) for the RBB change groups. The dotted line (64) represents the clinical significance threshold. The RRB-Decreasing-severity-group increased in overall psychopathology from T3-T4 to have a clinically elevated level at T4. Note: RRB-I = RRB-Increasing-severity-group, RRB-S = RRB-Stable-severity-group, RRB-D = RRB-Decreasing-severity-group.

Summary

From T3-T4 the RRB-Decreasing-severity-group increased in anxiety symptoms, attention problems and overall psychopathology. The RRB-Stable-severity-group increased only in anxiety symptoms. The RRB-Increasing-severity-group did not show increases in anxiety, ADHD or overall psychopathology levels. At T4, the RRB-Decreasing-severity-group had clinically elevated levels for anxiety (on both CBCL and ADIS/ASA) and for overall psychopathology, and it included the highest proportion of children (94%) meeting criteria for an anxiety disorder. The RRB-Increasing-severity-group had, by contrast, the lowest anxiety levels based on the CBCL and non-elevated levels based on the ADIS/ASA. The RRB-Stable-severity-group had non-elevated anxiety based on the CBCL and borderline levels based on the ADIS/ASA.

Discussion

Summary of Findings

The current study evaluated the relationship between change in autism symptom severity during middle childhood (from ages 6-to-11) and the occurrence of mental health symptoms. Change in overall autism symptom severity (ADOS CSS) was weakly related to increasing psychopathology during middle childhood. Because change in SA and RRB severity were often orthogonal, it proved more informative to evaluate them separately in relation to mental health challenges. Increases in the severity of social-communication symptoms were associated with increases in, and higher levels of, psychopathology during middle childhood. Decreases in RRB severity were associated with having higher and clinically significant anxiety levels later in childhood. The fact that change in the severity of the two core domains showed opposite associations with mental health symptoms was unexpected. Importantly, both domains were independently associated with the occurrence of mental health symptoms as there was only a 30% overlap between children that increased in SA severity and decreased in RRB severity (Table S5, Figure S2).

Why are increases in SA severity associated with more severe and increasing mental health symptoms?

During middle childhood, challenges including severe social-communication symptoms (Duvekot et al., 2018), reduced social competence or greater peer rejection (Hunsche et al., 2022) have all been associated with higher anxiety levels. Autistic youths with co-occurring ADHD and anxiety have greater social challenges than youths without such co-occurring conditions (McVey et al., 2018). These previous studies depict positive associations between co-occurring psychopathology and levels of social-communication symptoms and challenges, but not with change in autism symptoms. The current study thus extends previous results and is the first, to our knowledge, to demonstrate an association between co-occurring mental health symptoms and increases in the severity of social-communication difficulties for autistic children. These findings are in line with our hypothesis that increases in autism symptom severity would be associated with increased mental health symptoms.

While findings of associations between co-occurring mental health symptoms and changes in severity of social communication symptoms in autistic children are in line with past work, the nature or directionality of this relationship is unclear; Why are increases in social-communication symptoms and mental health challenges linked over time? One possibility is that children’s early elevated psychopathology prevents them from properly mastering social skills across childhood, leading to worsening social development with time. We gained a sense of this by analyzing CBCL scores at Time 1, when children were 3-years-old (analysis and data presented in Supplementary Information), where we found that the SA-Increasing-severity-group had clinically elevated levels for both externalizing and internalizing behaviors at T1. This is consistent with the literature. Neuropsychiatric comorbidities such as ADHD have been suggested to influence the development of autism impairments (Hawks & Constantino, 2020), and higher anxiety levels precede more severe social challenges later in childhood (Duvekot et al., 2018). Conversely, it is also possible that children’s increasing autism-related social-communication difficulties during middle childhood contribute to the emergence of their mental health challenges. Elevated autism symptoms, and specifically difficulties in the area of social skills, have been associated with (Spain, Sin, Linder, McMahon, & Happé, 2018) and suggested to lead to (Bellini, 2006; Stark et al., 2022) elevated levels of social anxiety. Moreover, this link may be moderated by reduced social competence (Stark et al., 2022) as well as children’s cognitive ability (Sukhodolsky et al., 2008). For children with typical-range IQ, having anxiety is associated with greater impairment in social reciprocity. The fact that children in the SA-Increasing-severity-group had typical-range IQ suggests that they are aware of their reduced social competence and added challenges (e.g., feel confused and embarrassed in social situations). This, in turn, could lead to feelings of anxiety and distress in social situations. These findings are in line with our prediction, that the relationship between change in children’s core symptoms and mental health challenges would be moderated by individual characteristics such as cognitive ability.

Why does decreasing RRB severity lead to high and increasing anxiety levels?

The literature consistently shows a relation between having more frequent and more severe RRB and elevated anxiety levels (Baribeau et al., 2020; Cashin & Yorke, 2018; Kim, Ahn, Lee, Ha, & Cheon, 2020; Rodgers, Riby, Janes, Connolly, & McConachie, 2012; Sukhodolsky et al., 2008). Whether having RRB contributes to having higher anxiety levels, or, whether individuals perform more RRB because they feel anxious (Jiujias, Kelley, & Hall, 2017) has never been clear. Anxiety has been identified as an intrinsic motivation for autistic individuals to perform RRB (Joosten, Bundy, & Einfeld, 2009) and performing RRB is linked with experiencing positive emotion (Mercier, Mottron, & Belleville, 2000). Autistic adults report that performing certain types of RRB acts as a self-regulation mechanism (Kapp et al., 2019), an idea also suggested by special education teachers of autistic children (Jaffey & Ashwin, 2022). These findings support the hypothesis that some forms of RRB can reduce anxiety and the increased arousal brought on by it (Spiker, Lin, Van Dyke, & Wood, 2012; Stratis & Lecavalier, 2013; Wood & Gadow, 2010). Despite this, autistic individuals might try to avoid performing RRB if they feel it conflicts with social expectations or can lead to negative reactions from others (Kapp et al., 2019; Wood & Gadow, 2010), such as stigmatization and bullying (Forrest, Kroeger, & Stroope, 2020).

We found that a decrease in RRB severity during middle childhood was related to higher levels of anxiety in late childhood. This is contrary to our prediction that decreases in autism symptom severity would be associated with having less mental health symptoms. However, if RRB function is viewed as a strategy for anxiety reduction, then elimination of this form of expression could indeed lead to increased anxiety. This position has previously been suggested (Jiujias et al., 2017), that if individuals are unable to or choose not to perform RRB, their absence can lead to heightened anxiety levels. Interestingly, we found that children that increased in RRB severity had fewer mental health challenges.

Our findings suggest that interventions focused on reducing RRB severity should be implemented cautiously, while monitoring children’s anxiety levels and providing them with alternative self-regulation strategies to prevent increases in anxiety. This is especially relevant as a child’s autism symptoms are predictive of receiving supportive services at school while their internalizing symptoms, such as anxiety, are not (Rosen, Spaulding, Gates, & Lerner, 2019). In addition, rather than target individuals, interventions focused on RRB can involve modifications to the environment, as to not provoke RRB and to encourage destigmatization of RRB (Kapp et al., 2019).

Using different measures to evaluate anxiety in children with autism

The CBCL has been validated for use with 6-to-18-year-old children with autism (Pandolfi et al., 2012). Its utility, however, differs based on children’s cognitive ability, and has been found to be better at identifying behavioral and emotional problems of autistic children without concurrent intellectual disability compared to those with intellectual disability (Dovgan, Mazurek, & Hansen, 2019). The ADIS/ASA, in comparison, has been successfully implemented with children of varied intellectual functioning (Kerns et al., 2020). We found that the CBCL identified emotional and behavioral problems, especially anxiety, in the SA-Increasing-severity-group which was characterized by cognitive ability in the average-range (IQ means: T3 & T4 = 92), while the ADIS/ASA indicated a borderline-clinical anxiety level for this group. Conversely, the ADIS/ASA identified clinically-significant anxiety symptoms in the RRB-Decreasing-severity-group which is also characterized by lower-than-average cognitive ability (IQ means: T3 = 81, T4 = 82), while the CBCL identified borderline-elevated levels of anxiety in this group. Thus, these measures’ differential functioning in detecting anxiety in our sample might be related to the children’s varied cognitive abilities. Alternatively, it could also be that this difference results from the types of anxiety evaluated by each measure. The CBCL targets only traditional forms of anxiety (e.g., separation anxiety) while the ADIS/ASA assesses a broader construct of anxiety including both traditional and distinct anxieties characteristic of youths with ASD (Kerns et al., 2014).

Limitations

In considering the conclusions of this study, it is important to point out certain limitations. First, the need for longitudinal behavioral data reduced our sample to 75 participants. This sample size limited our ability to evaluate subgroups and so our findings will need to be replicated and extended with larger samples. Second, while most measures in the study were used longitudinally, the ADIS/ASA was administered only at T4, restricting the longitudinal evaluation of anxiety. Also, we analyzed the ADIS in terms of each child’s highest CSR (the anxiety type with highest severity level), which does not account for type of anxiety or children who meet criteria for several anxiety disorders. Our sample size was not sufficient to evaluate specific types of anxieties within the groups. Third, both the CBCL and ADIS/ASA are based on parental report. Parental report can be unreliable and may be impacted by rater bias (Ozonoff, Li, Deprey, Hanzel, & Iosif, 2018). Specifically, parents might have generalized their child’s behavior from one aspect to the other, a bias known as the “halo effect” (Thorndike, 1920), reporting behaviors resulting from increases in autism severity as relating to increased psychopathology and vice versa. Fourth, several of the children did not achieve basal scores in cognitive assessments. Since, to our knowledge, there is currently no formal way to evaluate IQ scores <25, these participant’s scores were converted to a score of 24. Fifth, in the statistical models, we did not correct for multiple comparisons as any correction with this sample size would compromise the significance level of any individual analysis. This does, however, increase the risk of chance findings. Furthermore, it is important to make clear that this work describes patterns of associations which will need to be empirically tested in order to determine causality, as well as the possibility that a third factor might be impacting both change in autism symptoms and psychopathology levels. Last, our findings suggest that increasing SA severity during middle childhood is more characteristic of boys than girls. Our sample, however, included only 15 girls and only addressed birth-assigned sex (not gender identity). Future studies with larger numbers of girls are needed to comprehensively investigate this sex difference.

Conclusions

Our findings indicate a relationship between change in children’s autism symptom severity and increases in mental health challenges during middle childhood. Surprisingly, both increases and decreases in autism severity were associated with mental health symptoms, and these patterns differed between the two symptom domains. Children who increased in social-communication symptoms had higher and increasing psychopathology levels during middle childhood, while children who increased in RRB severity actually had more modest levels of mental health challenges. It was the children who decreased in RRB severity that had higher anxiety levels at age 11. Furthermore, change in the severity of core domains was more strongly associated with mental health symptoms than change in total autism severity. Our findings suggest that children’s mental health challenges should be evaluated in relation to other developmental processes such as change in core symptoms over time. This is especially important for adapting intervention and support to optimize outcomes across development.

Supplementary Material

1

Acknowledgments

The authors would like to thank the families and children who participate in the Autism Phenome Project and Girls with Autism Imaging of Neurodevelopment study.

Funding

Einat Waizbard-Bartov was supported by an Autism Speaks Predoctoral Fellowship grant #12841 during the preparation of this manuscript. This research was supported by grants from the NIH RO1MH128814 to Dr. Amaral and RO1MH127046 to Dr. Nordahl. This project was also supported by the MIND Institute Intellectual and Developmental Disabilities Research Center (P50HD103526). Dr. Solomon was supported by NIH grants R01 MH106518 and R01 MH103284. This research was supported by an Autism Center of Excellence grant awarded by the National Institute of Child Health and Development (NICHD) (P50 HD093079).

Footnotes

Declaration of conflicting interests

D. Amaral is on the Scientific Advisory Boards of Stemina Biomarkers Discovery, Inc. and Axial Therapeutics. Other authors declare no potential conflict of interest.

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NIHMS1921998-supplement-1.pdf (308KB, pdf)

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