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Clinical manifestations of children and adolescents with anxiety disorders with and without specific learning disorders

Annals of General Psychiatry volume 24, Article number: 17 (2025) Cite this article

Abstract

Background

Anxiety disorders (ADs) are common among children and adolescents and frequently co-occur with specific learning disorder (SLD). Approximately 20% of children with SLD meet criteria for ADs, while those with anxiety are six times more likely to have a premorbid SLD. The strong relationship between premorbid SLD and ADs underscores the importance of examining developmental trajectories and manifestations of neuropsychiatric conditions like ADs, particularly when SLD is present. In this context, this study investigates the clinical profiles of children and adolescents with a first diagnosis of an AD and a history of SLD compared to those with a first diagnosis of an AD without a history of SLD. The analysis focuses on various clinical characteristics, including developmental history, demographic aspects, age of anxiety onset, global functioning, types of ADs, self-report anxiety and depressive symptoms, and adaptive behavior. Additionally, the study aims to explore the relationship between anxiety symptoms and depressive symptoms, adaptive behavior, and age.

Methods

We conducted a cross-sectional, retrospective study with 78 participants from the Child and Adolescent Neuropsychiatry Unit, divided into two groups: those with ADs alone (Group AD, n = 42) and those with both ADs and premorbid SLD (Group AD + SLD, n = 36). We collected data on developmental history, demographic information, age of anxiety onset, global functioning, anxiety and depressive symptoms, and adaptive behavior.

Results

Our findings revealed that Group AD experienced more stressful life events and had higher cognitive levels, whereas Group AD + SLD showed a greater impairment in global functioning. Notably, Group AD exhibited lower social adaptive behavior and higher self-reported anxiety and depressive symptoms than Group AD + SLD, possibly indicating a greater awareness of their emotional distress.

Conclusions

These findings highlight the impact of premorbid neurodevelopmental disorders into clinical manifestations of psychopathological symptoms. In particular, results underline the importance of developing tailored clinical interventions for children with co-occurring ADs and learning difficulties, focusing more on their emotional awareness to better address the unique challenges posed by the comorbidity.

Background

Anxiety disorders (hereafter, ADs) often manifest as overwhelming and excessive feelings of apprehension, worry, and nervousness. These feelings are typically accompanied by physical symptoms such as an elevated heart rate, perspiration, and difficulties in concentration, triggered by perceived threats or stressors [1]. ADs encompass a spectrum of conditions, including Separation Anxiety Disorder, Selective Mutism, Specific Phobia, Social Anxiety Disorder (Social Phobia), Panic Disorder, Agoraphobia, Generalized Anxiety Disorder (hereafter, GAD), and other anxiety-induced and unspecified disorders [1]. In developmental ages, ADs rank among the most prevalent neuropsychiatric disorders, with estimates ranging from 9 to 32% [2,3,4]. These disorders significantly contribute to the overall health-related burden experienced by youths [5], leading to poor adaptive behaviors [6] and reduced quality of life [7].

A range of vulnerability factors contributes to the development of ADs in youths, including genetic predispositions (e.g., a family history of anxiety disorders), temperamental traits (e.g., behavioral inhibition, heightened emotional sensitivity), birth and/or life-events (e.g., weeks of gestation/obstetric complications [8]; adverse childhood events [9]). Notably, ADs often co-occur with premorbid neurodevelopmental conditions. Epidemiological studies reveal that around 40% of children with autism spectrum disorder [10], approximately 10–22% with intellectual disabilities [11], and roughly 20% with attention deficit/hyperactivity disorder (ADHD) [12] manifest anxiety symptoms or are associated with ADs. Similarly, around 20% of children and adolescents with specific learning disorders (SLD) meet diagnostic criteria for ADs [13], and approximately 70% of students with SLD experience significantly higher levels of anxiety compared to their peers [14]. In addition, ADs are more than twice as common among children with SLD compared to control groups [15,16,17]. On the other hand, a recent study [18] shows that youths with childhood-onset and adolescent-onset anxiety are six times more likely to exhibit a premorbid SLD than controls.

These findings raise important questions about the factors contributing to the increased vulnerability of children and adolescents with SLD to ADs [19]. One explanation proposes that a diagnosis of SLD may directly increase the risk of developing ADs as a secondary consequence of repeated school failure [19]. Another suggestion is that the strong relationship between premorbid SLD and ADs points to a shared developmental pathway, as emphasized by the “neurodevelopmental continuum model” [20,21,22]. According to this model, premorbid neurodevelopmental conditions and psychiatric disorders may exist on a continuum, suggesting overlapping etiological factors rather distinct separations between them [21]. This framework underlines the importance of examining developmental trajectories in individuals presenting with neuropsychiatric disorders such as ADs, particularly whether neurodevelopmental issues such as SLD are present. In addition, a developmental approach is particularly relevant to ADs [23], as they typically emerge early in life, often around the age of 11, compared to other psychopathological conditions [24].

Notably, these considerations suggest that, regardless of the theoretical framework used to interpret the association between SLD and ADs, early developmental processes and factors – including premorbid SLD – play a critical role in shaping an individual’s vulnerability and, consequently, their anxiety manifestations. Within this context, the need to better understand the impact of premorbid SLD on anxiety, related symptoms, and daily-life functioning became increasingly evident. Nevertheless, to date, the impact of a premorbid SLD on symptoms of ADs and strictly associated psychological correlates, such as depressive symptoms [25], as well as adaptive functioning has been overlooked.

To better understand how a premorbid SLD characterizes the clinical manifestations of ADs, we compared children and adolescents with a first diagnosis of an AD and a history of SLD to children and adolescents with a first diagnosis of an AD without a history of SLD. We focused on different clinical characteristics, listed as Research Questions (RQ):

  1. 1)

    RQ1: the developmental history (e.g., weeks of gestation, obstetric complications, neurodevelopmental/neuropsychiatric familiarity, stressful life-events and adverse childhood events; RQ1a), demographic aspects (e.g., age, cognitive level, RQ1b), age of anxiety onset (RQ1c) and global functioning (RQ1d);

  2. 2)

    RQ2: the types of ADs and self-report anxiety symptoms;

  3. 3)

    RQ3: the self-report depressive symptoms;

  4. 4)

    RQ4: the adaptive behavior (conceptual, social, and practical);

  5. 5)

    RQ5: the relationship between anxiety symptoms and depressive symptoms (RQ5a), adaptive behavior (RQ5b), and age (R5c).

Materials and methods

Participants and procedures

This is a cross-sectional study based on a retrospective chart review of children and adolescents with ADs referred for a clinical evaluation at the Child and Adolescent Neuropsychiatry Unit of the Bambino Gesù Children’s Hospital between January 2019 and December 2023. All children and adolescents received clinical evaluations according to the good clinical practice recommended by international guidelines for neuropsychiatric disorders according to present, past symptomatology, and neurodevelopmental history by a multi-specialized clinical team of child neuropsychiatrists and developmental psychologists.

Children and adolescents were selected accordingly to the following inclusion criteria: (i) a first diagnosis of ADs (i.e., GAD, Panic Disorder, Phobias/Specific Phobia, Agoraphobia, Social Anxiety Disorder, Separation Anxiety Disorder, Selective Mutism) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, DSM-5 [26] and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, DSM-5-TR [1]; (ii) a non-verbal Intelligence Quotient (nvIQ) above 85. The exclusion criteria were as follows: (i) having a comorbidity with other neuropsychiatric and/or neurodevelopmental disorders (e.g., mood disorders, obsessive compulsive disorder, autism spectrum disorder, ADHD) except for SLD; (ii) undergoing current CNS-active pharmacological treatment or psychotherapy programs; (iii) presenting a personal history of neurological, medical, genetic diseases.

The study cohort was composed of 78 Italian outpatients (42 females) aged 8 to 18 years who were evaluated at the Child and Adolescent Neuropsychiatry Unit of the Bambino Gesù Children’s Hospital (Rome, Italy). Based on their characteristics, the total sample was divided into two groups: 36 children and adolescents (23 females) received a first diagnosis of AD without a history of SLD (Group AD). While the remaining 42 children and adolescents (19 females) received a first diagnosis of AD in a previous history and/or current comorbid SLD (Group AD + SLD). All patients received a first prescription for cognitive-behavioral psychotherapy and parent-training.

All procedures performed in studies involving human participants were in accordance with the ethical standards (local ethical committee, 2541_OPBG_2021), with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The anonymity of the participants and the confidentiality of the data were guaranteed.

Clinical assessment

Clinical assessment was conducted by a child neuropsychiatrist and developmental psychologists, bringing specialized expertise to the evaluation of anxiety symptoms in children and adolescents, both with and without comorbid neurodevelopmental disorders. Clinicians were extensively trained in utilizing a range of structured and semi-structured neuropsychiatric and psychopathological diagnostic tools to ensure a comprehensive and accurate assessment.

Developmental history

Developmental history and information were collected via clinical examination by an experienced clinician. In the current study, we considered the following information: weeks of gestation (classified as “term birth” ≥ 37 weeks of gestations; or “preterm birth” < 37 weeks of gestations, according to WHO and International Federation of Gynecology and Obstetrics), obstetric complications (coded as 0 = no; 1 = yes), neurodevelopmental/neuropsychiatric familiarity (coded as 0 = no; 1 = yes), adverse childhood events (e.g., emotional/sexual-physical abuse; coded as 0 = no; 1 = yes), stressful life events (e.g., family bereavement; coded as 0 = no; 1 = yes) and age of anxiety onset (in years).

The presence of comorbid SLD (coded as 0 = no; 1 = yes) was determined through assessments of reading, writing, and arithmetic skills, or by reviewing previous clinical and psychometric evaluations. Developmental clinicians verified that the diagnosis of SLD (i.e., reading disorder, writing disorder, and/or math disorder) was made in accordance with either DSM-5 [26] or DSM-5-TR [1] criteria. Specifically, children and adolescents met the diagnostic criteria for reading, writing, and/or math disorder if their performance, in terms of accuracy and/or speed, was at least 1.5 standard deviations (SDs) below the school age-related mean on norm-referenced reading [27,28,29], writing [29, 30], and/or math [29, 31] assessments and significantly interfered with their functioning.

Non-verbal cognitive level

Non-verbal intelligence quotient (nvIQ) was assessed by using the Leiter International Performance Scale (Leiter-Revised or Leiter-3 [32], the Raven Progressive Matrices (Coloured Progressive Matrices – CPM; Standard Progressive Matrices – SPM; respectively [33, 34] or the Perceptual Reasoning Index of the Wechsler intelligence scales [35, 36]. Composite scores were analyzed (mean ± SD: 100 ± 15).

Evaluation of psychopathological disorders

Psychopathological disorders were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children Present and Lifetime Version DSM-5 (K-SADS-PL DSM-5) [37]. K-SADS-PL DSM-5 is a semi-structure interview that serves as a valuable tool for gathering information about the clinical history and developmental trajectories of primary psychopathological disorders according to DSM-5. This instrument not only relies on the input from the children and adolescents but also incorporates insights from their parents, enhancing the breadth and depth of information gathered.

The K-SADS-PL DSM-5 has a 3-point scale, whereby absent symptoms are coded as 0, subclinical symptoms are coded as 1, and clinical symptoms (e.g., symptoms severe and frequent enough to impair individuals’ functioning in multiple contexts) are coded as 2.

Global functioning

The assessment of global functioning, encompassing family, school, and social domains, was based on the Childhood Global Assessment Scale (C-GAS) [38]. This scale systematically evaluates functional impairment attributed to psychopathological disorders in the last 1 month, yielding a score spanning from 1 (requiring constant supervision) to 100 (exhibiting superior functioning above the norm across all domains), divided in 10 subscales (100 − 91: doing very well; 90 − 81: doing well; 80 − 71: doing all right; 70 − 61: some problems; 60 − 51: some noticeable problems; 50 − 41: obvious problems; 40 − 31: serious problems; 30 − 21: severe problems; 20 − 11: very severely impaired; 10 − 1: extremely impaired).

The participants’ C-GAS scores ranged from 52 to 70 and were analyzed as a categorical variable based on the established C-GAS subscales (coded as 0 = 60 − 51, some noticeable problems; 1 = 70 − 61, some problems).

Self-report anxiety symptoms

Self-reported anxiety symptoms were assessed using the Self-Report Form of Multidimensional Anxiety Scale for Children Second Edition (MASC-2) [39], a questionnaire that evaluates several anxiety dimensions in children and adolescents aged 8 to 19 years. By indexing the range and severity of anxiety symptoms, the MASC-2 aids in early identification, diagnosis, treatment planning, and monitoring of anxiety-prone youth. It is composed of 50 items, with responses scored as follows: 0 if the described situation never occurred, 1 point if it rarely occurred, 2 points if it sometimes occurred, and 3 points if it often occurred. Patients complete the questionnaire based on their experiences in the past weeks.

The questionnaire provides several subscales: Separation Anxiety; Generalized Anxiety; Social Anxiety (subfactors: Humiliation/Rejection; Performance Fears); Obsessive-compulsive; Physical Symptoms (subfactors: Panic; Tense/Restless); Harm Avoidance; and a MASC-2 Total Score scale.

Each raw score was converted into a standardized T-score using age- and sex-specific profile modules. According to the normative data, it was considered as “non-clinical” a T-score < 60; as “borderline” a T-score between 60 and 69; and as “clinically-relevant” a T-score > 69. Therefore, higher T-scores indicate higher levels of anxiety symptoms.

Self-report depressive symptoms

Self-reported depressive symptoms were assessed using the Self-Report Form of the Children’s Depression Inventory Second Edition (CDI-2) [40], a questionnaire that evaluates various dimensions of depressive functioning in children and adolescents aged 8 to 17 years. It is composed of 28 items, with responses scored as follows: 0 if the described situation never occurred, 1 point if it rarely occurred, 2 points if it sometimes occurred. Patient complete the questionnaire based on how she/he felt in the past weeks.

The questionnaire provides several subscales: Negative Mood/Physical Symptoms + Negative Self-esteem (Emotional Problems) and Ineffectiveness + Interpersonal Problems (Functional Problems), and a CDI-2 Total Score scale.

Each raw score was converted into a standardized T-score using age- and sex-specific profile modules. According to the normative data, it was considered as “non-clinical” a T-score < 60; as “borderline” a T-score between 60 and 69; and as “clinically-relevant” a T-score > 69. Therefore, higher T-scores indicate higher levels of depressive symptoms.

Adaptive behavior

The adaptive behavior was evaluated by using the Adaptive Behavior Assessment System Second Edition for Ages 5–21 (ABAS-II) [41], which provides a complete assessment of adaptive skills across the life span from 5 to 21 years. The ABAS-II investigates 10 areas of adaptive skills, covering 4 domains: Conceptual Adaptive Domain (subscales: Communication, Functional Academic, Self-direction), Social Adaptive Domain (subscales: Social and Leisure) and Practical Adaptive Domain (subscales: Community Use, Home Living, Health and Safety, Self-care), and a General Adaptive Composite. These domains include the practical and everyday skills needed to function, meet environmental needs, take care of oneself and interact with others effectively and independently.

According to the ABAS-II normative data, it was considered as “non-clinical” a composite score ≥ 85; as “borderline” a composite score between 84 and 71; and as “clinical” a composite score ≤ 70.

Sample size estimation

The sample size was calculated by a priori analysis in G*Power, version 3.1.9.7 (The G*Power Team, Düsseldorf, Germany). Difference in the T-scores of MASC-2 subscales (Separation Anxiety, Generalized Anxiety, Social Anxiety, Obsessive-compulsive, Physical Symptoms, Harm Avoidance) between Group AD and Group AD + SLD was considered. With an estimated expected effect size f = 0.30, α value = 0.05 (i.e., probability of false positives of 5%), and β = 0.80 (i.e., at least 80% power), a sample size of at least 76 children and adolescents was required for a MANOVA with two groups (Group AD vs Group AD + SLD) and 6 measurements (6 subscales; correlation among measures set at 0.80).

Statistical analysis

The data were first examined for assumptions of normality via Shapiro–Wilk test and homogeneity of variance via Levene’s test. As the distribution of the variables was found to be non-Gaussian, non-parametric tests were applied.

Chi-square (χ2) analyses were utilized to verify differences between the two groups on categorical variables (weeks of gestation; obstetric complications; neurodevelopmental/neuropsychiatric familiarity; stressful life events; adverse childhood events; C-GAS). Mann–Whitney U tests were used to test differences between the two groups (Group AD vs Group AD + SLD) on continuous variables (chronological age; nvIQ; age of anxiety onset).

Mann–Whitney U tests were also used to test differences between the two groups (Group AD vs Group AD + SLD) on self-report anxiety symptoms (MASC-2: Separation Anxiety, Generalized Anxiety, Social Anxiety, Obsessive-compulsive, Physical Symptoms, Harm Avoidance), self-report depressive symptoms (CDI-2: Negative Mood/Physical Symptoms, Negative Self-esteem, Ineffectiveness, Interpersonal Problems), and on adaptive behavior (ABAS-II: Conceptual Adaptive Domain, Social Adaptive Domain, and Practical Adaptive Domain).

In addition, to provide a comprehensive overview of results, frequencies and percentages of average and clinical (borderline and clinically-relevant) scores were calculated per each subscale for both groups and analyzed by mean of χ2. Odds Ratio (OR) and 95% confidence intervals (CI 95%) were reported.

Lastly, partial Spearman’s correlations (rho) were conducted to evaluate the relationship between anxiety symptoms (MASC-2 Subscales: Separation Anxiety, Generalized Anxiety, Social Anxiety, Obsessive-compulsive, Physical Symptoms, Harm Avoidance) and depressive symptoms (CDI-2 Subscales: Negative Mood/Physical Symptoms, Negative Self-esteem, Ineffectiveness, Interpersonal Problems), adaptive behavior (ABAS-II Domains: Conceptual Adaptive Domain, Social Adaptive Domain, Practical Adaptive Domain), and age.

Where appropriate, Bonferroni’s correction of the p-values was applied for multiple comparisons.

Statistical analyses were performed with Jamovi (version 2.4.5 released in 2024) and Jasp (version 0.18.3 released in 2024).

Results

Developmental history (RQ1a), chronological age and IQ (RQ1b), age of anxiety onset (RQ1c), and global functioning (RQ1d)

Table 1 compares Group AD vs Group AD + SLD in terms of week of gestations, obstetric complications, neurodevelopmental/neuropsychiatric familiarity, stressful life events, adverse childhood events, age, non-verbal cognitive level, age of anxiety onset, and C-GAS.

The results showed significant differences between groups in the occurrence of stressful life events (χ21 = 4.75, OR = 0.92, CI 95%: 0.24 − 0.05, p = 0.03), in the global functioning level, as measured by the C-GAS (χ21 = 8.62, OR = 10.43, CI 95%: 3.90–1.54, p = 0.003), and in the nvIQ (Mann–Whitney U = 558, p = 0.046). The incidence of stressful life events was higher in Group AD compared to Group AD + SLD. Conversely, a larger proportion of children and adolescents in Group AD + SLD had C-GAS scores that fell within the ‘Noticeable Problems’ range, compared to Group AD. Additionally, although both groups had average non-verbal cognitive levels, Group AD demonstrated a relatively higher nvIQ than Group AD + SLD.

No significant differences emerged between the two groups in terms of weeks of gestation (χ21 = 0.37, OR = 3.20, CI 95%: 0.63 − 0.11, p = 0.54), obstetric complications (χ21 = 1.84, OR = 12.83, CI 95%: 2.49–0.64, p = 0.18), neurodevelopmental/neuropsychiatric familiarity (χ21 = 2.47, OR = 1.22, CI 95%: 0.49 − 0.19, p = 0.12), adverse childhood events (χ21 = 1.98, OR = 1.71, CI 95%: 0.33 − 0.04, p = 0.16), chronological age (Mann–Whitney U = 683, p = 0.46), and age of anxiety onset (Mann–Whitney U = 567, p = 0.057).

Table 1 Description of groups in terms of developmental history, chronological age and cognitive level, age of anxiety onset and global functioning
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Characterization of anxiety manifestations (RQ2)

As shown in Table 2, both groups exhibited similar frequencies and percentages of diagnosed ADs, as well as subclinical and clinical symptoms, across all areas of anxiety assessed during the K-SADS-PL DSM-5 administration.

Table 2 Frequencies and percentages of diagnosed ADs and anxiety symptoms (categorized as subclinical and clinical based on K-SADS-PL DSM-5 symptom ratings) were calculated for each group
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Considering self-reported anxiety symptoms, assessed throughout MASC-2, results showed a significant difference between children and adolescents in the Group AD and those in the Group AD + SLD for the Generalized Anxiety (Mann – Whitney U = 485, p = 0.007), Obsessive-compulsive (Mann – Whitney U = 529, p = 0.023), Physical Symptoms (Mann – Whitney U = 392, p < 0.001), and Harm Avoidance subscales (Mann – Whitney U = 530, p = 0.023). In particular, children in the Group AD exhibited higher T-scores compared to children in the Group AD + SLD (see Table 3).

Results did not document a significant difference between children and adolescents in the Group AD and Group AD + SLD for the Separation Anxiety (Mann – Whitney U = 747, p = 0.93) and Social Anxiety (Mann – Whitney U = 561, p = 0.05).

After Bonferroni’s correction (p 0.05/6 comparisons ≤ 0.008), only significant differences for Generalized Anxiety and Physical Symptoms between the two groups were confirmed.

Table 4 shows frequencies and percentages of average and clinical (borderline and clinically-relevant) T-scores per each MASC-2 subscale for both groups. After Bonferroni’s correction (p 0.05/6 comparisons ≤ 0.008), significant differences in the distribution of average and clinical T-scores between groups were confirmed for the Generalized Anxiety (χ21 = 8.36, OR = 0.22, CI 95%: 0.08–0.64, p = 0.004) and Physical Symptoms (χ21 = 10.86, OR = 0.15, CI 95%: 0.05–0.50, p = 0.001), with higher occurrence of clinical scores in Group AD compared to Group AD + SLD. No further differences emerged (see Table 4).

Self-report depressive symptoms (RQ3)

Considering self-reported depressive symptoms, assessed throughout the CDI-2, results showed a significant difference between children and adolescents in the Group AD and those in the Group AD + SLD for the Negative Mood/Physical Symptoms (Mann – Whitney U = 536, p = 0.027). In particular, children in the Group AD exhibited higher T-scores compared to children in the Group AD + SLD (see Table 3).

Results did not document a significant difference between children and adolescents in the Group AD and Group AD + SLD for the Negative Self-esteem (Mann – Whitney U = 648, p = 0.28), Ineffectiveness (Mann – Whitney U = 595, p = 0.11), or Interpersonal Problems subscales (Mann – Whitney U = 603, p = 0.12).

After Bonferroni’s correction (p 0.05/4 comparisons ≤ 0.0125), no significant differences between the two groups remained.

Table 4 shows frequencies and percentages of average and clinical (borderline and clinically-relevant) T-scores per each CDI-2 subscale for both groups. After Bonferroni’s correction (p 0.05/4 comparisons ≤ 0.0125), significant difference in the distribution of average and clinical T-scores between groups emerged for the Ineffectiveness (χ21 = 12.81, OR = 0.17, CI 95%: 0.06–0.45, p < 0.001) and Interpersonal Problems subscales (χ21 = 11.38, OR = 0.18, CI 95%: 0.06–0.51, p < 0.001), with higher occurrence of clinical scores in Group AD compared to Group AD + SLD. No further differences emerged (see Table 4).

Parent-report adaptive behavior (RQ4)

Considering adaptive behavior, assessed throughout the ABAS-II, results showed a significant difference between children and adolescents in the Group AD and those in the Group AD + SLD for the Social Adaptive Domain (Mann – Whitney U = 563, p = 0.046). In particular, children in the Group AD exhibited lower composite scores compared to children in the Group AD + SLD (see Table 3).

However, results did not document a significant difference between children and adolescents in the Group AD and Group AD + SLD for the Conceptual Adaptive Domain (Mann – Whitney U = 698, p = 0.53) and for the Practical Adaptive Domain (Mann – Whitney U = 687, p = 0.48).

After Bonferroni’s correction (p 0.05/3 comparisons ≤ 0.0167), no significant differences between the two groups remained.

Table 4 shows frequencies and percentages of average and clinical (borderline and clinically-relevant) scores per each ABAS-II subscale for both groups. After Bonferroni’s correction (p 0.05/3 comparisons ≤ 0.0167), significant difference in the distribution of average and clinical T-scores between groups were confirmed for the Social Adaptive Domain (χ21 = 6.24, OR = 0.27, CI 95%: 0.09–0.76, p = 0.012), with higher occurrence of clinical scores in Group AD compared to Group AD + SLD. No further differences emerged (see Table 4).

Table 3 Mean ± SD of MASC-2 subscales, CDI-2 subscales, and ABAS-II domains for each group
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Table 4 Frequencies and percentages of average and clinical (borderline and clinically-relevant) scores on MASC-2 Subscales, CDI-2 Subscales, and ABAS-II Domains for both groups
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Relationship between anxiety symptoms and depressive symptoms (RQ5a), adaptive behavior (RQ5b), age (RQ5c)

With regard to Group AD, after Bonferroni’s correction for multiple comparisons (p 0.05/48 comparisons ≤ 0.001), results documented the following significant correlations (Table 5):

  • Generalized Anxiety subscale of MASC-2 significantly and positively correlated with age, meaning that T-scores in generalized anxiety increase with age (worse);

  • Social Anxiety subscale of MASC-2 significantly and positively correlated with Interpersonal Problems subscale of CDI-2 (p < 0.001), meaning that higher T-scores (worse) in social anxiety, higher T-scores (worse) in interpersonal problems;

  • Physical Symptoms subscale of MASC-2 significantly and positively correlated with Negative Mood/Physical Symptoms (p < 0.001); meaning that higher T-scores (worse) in physical symptoms, higher T-scores (worse) in negative mood and self-report physical symptoms.

Table 5 Correlations between scores of MASC-2 subscales, CDI-2 subscales, and ABAS-II domains for the group AD
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With regard to Group AD + SLD, after Bonferroni’s correction for multiple comparisons (p 0.05/48 comparisons ≤ 0.001), results documented the following correlations (Table 6):

  • Generalized Anxiety subscale of MASC-2 significantly and positively correlated with Negative Mood/Physical Symptoms (p < 0.001) and Ineffectiveness (p = 0.003) subscales of CDI-2, meaning that higher T-scores (worse) in generalized anxiety, higher T-scores (worse) in negative mood, self-report physical symptoms and ineffectiveness;

  • Physical Symptoms subscale of MASC-2 significantly and positively correlated with Negative Mood/Physical Symptoms (p < 0.001), Ineffectiveness (p < 0.001) subscales of CDI-2, meaning that higher T-scores (worse) in physical symptoms, higher T-scores (worse) in negative mood, self-report physical symptoms, and ineffectiveness;

No further significant correlations were found (p > 0.001).

Table 6 Correlations between scores of MASC-2 subscales, CDI-2 subscales, and ABAS-II domains for the group AD + SLD
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Discussion

The primary aim of this study was to explore the clinical characteristics of children and adolescents with a first diagnosis of ADs, with or without a history of SLD. Overall, our findings suggest that the clinical picture of patients with ADs at their first diagnosis may differ based on the presence or absence of premorbid neurodevelopmental conditions, such as SLD. Indeed, differences between patients with ADs with and without SLD occurred in the developmental history, global functioning, cognitive level, specific dimensions of self-reported anxiety and depressive symptoms, and the social domain of adaptive behavior.

When considering developmental history, patients with ADs are more likely to have experienced previous stressful life events (e.g., family bereavement) compared to those with both ADs and SLD. However, if a pre-existing SLD is conceptualized as a form of stressful life event that contributes to the onset of ADs, both groups may exhibit similar vulnerability profiles, except for the nature of these stressful experiences. This interpretation aligns with theoretical frameworks that posit ADs as a secondary consequence of SLD [14, 19]. Alternatively, it is plausible that SLD and ADs share neurodevelopmental predisposition and mechanisms that contribute to both conditions rendering anxiety an inherent aspect of their developmental trajectory [14, 19]. Although beyond the scope of the current study, future research should employ longitudinal designs to disentangle the specific contribution of premorbid SLD to the onset of ADs.

Notably, the clinical impact of a pre-existing neurodevelopmental disorder (i.e., SLD) and its combination with ADs emerge when considering global functioning impairment. Indeed, in the C-GAS, patients with both ADs and SLD exhibit a higher level of global functioning impairment compared to those without SLD. The current findings align with a recent study [22], which indicated that premorbid diagnosed neurodevelopmental disorders or self-reported neurodevelopmental difficulties tend to lead to poorer global functioning in children and adolescents at the onset of psychosis. In addition, the age of anxiety onset in patients with ADs (around 13 years old) appears slightly later, albeit not significantly different, compared to that in the patients with ADs and SLD (around 11 years old). This is likely because, already being under the care of healthcare services for learning disorders, they receive increased attention from professionals and are promptly identified. Concerning the cognitive phenotype, findings document that patients with ADs exhibit higher non-verbal cognitive abilities compared to patients with both ADs and SLD, although both groups remain within the average range.

Regarding the clinical phenotype, both groups exhibit a similar distribution in the types of anxiety diagnoses. Specifically, more than 60% of patients present GAD, around 10–20% exhibit social anxiety, and the remaining show separation anxiety and/or unspecified ADs. These findings align with the distribution of anxiety symptoms, as assessed during the administration of the semi-structured interview with both patients and their parents. Notably, despite a similar distribution of ADs between groups, neurovegetative dimensions (e.g., shortness of breath, dizziness/lightheadedness, and palpitations) and behavioral coping strategies (e.g., avoidance, obsessive rituals) associated with anxiety are reported more frequently and described in greater detail in our patients with ADs without SLD. Accordingly, from the administration of the semi-structured interview, a higher prevalence of subclinical panic symptoms (around 13%) emerged in patients with ADs without SLD compared than those with SLD (0%). Similarly, regarding the self-report questionnaire on the anxiety symptoms (MASC-2), patients with ADs without SLD are more likely to self-reporting generalized anxiety symptoms and physical sensations as well as harm avoidance behaviors compared to patients with ADs and SLD. Even when considering psychological correlates of anxiety, such as depressive symptoms, patients with ADs but without SLD are more likely to experience and report symptoms associated with negative mood/neurovegetative dimensions of depression (e.g., increase/decrease of appetite, increase/decrease of sleep, crying, etc.), feelings of self-ineffectiveness, and relationship problems compared to those with SLD. Regardless of the group, from correlation results emerged that greater self-perceived physical manifestations of anxiety are strongly associated with more self-reported negative mood and physical symptoms of depression. To sum up these results, patients with ADs alone exhibit a higher level of insight and physical and emotional distress perception compared to those with both ADs and SLD. However, those with ADs and premorbid SLD showed less perception of distress, and therefore reduced level of interoceptive self-awareness.

These results align with those of a previous meta-analysis, where the authors found a tendency for individuals with SLD to underreport symptoms of anxiety [14]. Although cautiously, these findings could be interpreted through a metacognitive approach. Mentalization (or reflective functioning), a subset of the metacognition construct, refers to the capacity to understand the self and others in terms of intentional mental states, such as feelings, desires, wishes, attitudes, and goals [42]. Research indicates that difficulties in mentalizing have been related to a wide array of cognitive-related problems, such as academic achievement [42], as well as to neurodevelopmental conditions such as ADHD [43] and SLD [44]. Additionally, evidence has revealed that children and adolescents with SLD experience problems with emotion recognition, identification and expression compared to controls [45], mirroring their poor mentalization, and pointed to a strong association between reading-related skills and empathic abilities [46]. Therefore, a possible explanation for these results could be a reduced capacity for mentalization in patients with both ADs and premorbid SLD. In other words, patients with both ADs and SLD appear to have a reduced capacity for mentalization compared to what would be expected in patients with psychopathological symptoms, such as AD, who typically have difficulty recognizing their own feelings and emotions [42]. To sum up, difficulties in metacognitive abilities may prevent patients with SLD and ADs from accurately interpreting their emotional states. Although speculatively, another possible explanation for the reduced insight and lower level of distress in patients with ADs and SLD could be related to the cognitive mechanisms underlying the interpretation of their anxiety. In this context, a recent study [47] compared children with SLD to typically developing controls, examining their attentional biases to general threats, reading-related stimuli, and SLD-related stereotypes. Results showed that children and adolescents with SLD exhibited top-down attentional control to specifically avoid reading-related stimuli, rather than hyper-vigilance to general threats, unlike the control group [47]. The authors interpreted these findings as reflecting a tendency of children and adolescents with SLD to be particularly triggered by disorder-congruent stimuli. Therefore, our findings suggest that patients with both SLD and ADs may interpret their emotional symptoms within the context of their learning disorders, minimizing anxiety symptoms unrelated to the academic challenges and leading to a reduced and biased perception of their daily non-academic distress. Further studies need to examine the contribution of mentalization abilities and cognitive interpretation to the manifestations of anxiety in children and adolescents with premorbid neurodevelopmental disorders, such as SLD.

Considering adaptive behavior, parents of patients with ADs without SLD are more likely to detect social adaptive impairments compared to those of patients with both ADs and SLD. In other words, the perception of anxiety on everyday social skills in parents of children and adolescents with only ADs is more pronounced than in those of children and adolescents with comorbid anxiety and SLD. Although speculatively, it is possible that, also in this case, parents of patients with ADs alone are more focused on the social consequences of anxiety, while in the case of SLD, parents may be less aware of the impact of learning difficulties on contexts unrelated to academic performance.

Closely related to these findings, the correlation results indicated that, in patients with ADs without SLD, social anxiety symptoms were perceived as a key and hindering factor. This was reflected in a strong association between severe self-reported social anxiety symptoms and significant interpersonal difficulties – an aspect already extensively documented [48, 49]. Whereas, in patients with ADs and SLD, greater self-reported physical manifestations of anxiety are significantly associated with severe ineffectiveness. It could be that in patients with ADs and SLD, the intensity of self-perceived anxiety manifestations may be associated with a sense of incapacity, learned through experienced repetitive negative situations [50]. Indeed, the presence of a SLD can be very challenging for a school child: in school environment, a child’s academic achievements is often under teachers’, parents’ and classmates’ judgments, and seen as the sole measure of their worth, despite their other non-academic talents [51]. Moreover, in patients with both ADs and SLD, the intensity of self-report generalized anxiety symptoms has a marked relation not only with negative mood/neurovegetative dimensions of depression but also with a greater sense of ineffectiveness. This is not trivial, as research had indicated that children with SLD found that most were burdened by feelings of ineffectiveness and that many believed that their situation would not improve [51] – which inevitably affect levels of anxiety and stress in this population. Future studies should examine the mediating/moderating factors that explain the association between anxiety symptoms and self-beliefs in order to support psychotherapists in their daily work.

Last, the correlation results indicated that, in patients with ADs without SLD, the intensity of self-report generalized anxiety symptoms increases positively with age. It is well-known that, if left untreated, ADs in young people often follow a chronic and unremitting course, increasing in severity with age [52]. Interestingly, previous research suggests are age-related differences in anxiety domains, with GAD and social anxiety being the most prevalent among adolescents and young adults, increasing in severity with age [53]. Future studies should focus on the developmental trajectories of anxiety manifestations in patients with ADs and a premorbid SLD compared to patients with ADs.

Overall, based on our findings, children and adolescents with solely ADs exhibit higher cognitive level and greater self-awareness of the emotional states that characterize their psychopathological condition (anxiety) and other correlated symptoms (depressive symptoms) as well, with negative influence on their interpersonal and social engagements. On the contrary, children and adolescents with ADs and a premorbid SLD tend to have a lower perception of self-efficacy and reduced awareness of their general emotional states, possibly due to their heightened focus on academic context. Current findings open new avenues for future research, which should focus on understanding the mechanisms underlying anxiety manifestations and their correlations with depressive symptoms and adaptive behaviors.

Although some caution is warranted given the small sample size of our participants, the results of our study suggest different clinical profiles based on the presence or absence of a history of neurodevelopmental disorders. This underscores the need for therapeutic interventions tailored to the clinical profile of the patient, considering not only the psychopathological symptoms (e.g., anxiety) but also the neurodevelopmental disorders (e.g., learning disorders). For example, it may be beneficial to support patients with ADs and a history of SLD within a cognitive-behavioral framework to enhance their ability to recognize and manage their emotions unrelated to academic achievements through psychoeducation, emotional literacy, behavioral techniques (e.g., Exposure and Response Prevention Technique), and a mentalization-based program.

Conclusions and future directions

Given the substantial impact of premorbid SLD on developmental trajectories of anxiety, a thorough clinical characterization of profile is paramount, as it provides essential guidance for the selection and implementation of appropriate treatments. These results need to be replicated, and combined with multi-level neuroscientific methods (genetic, neurobiological, behavioral assessment) to wholly describe the clinical profiles of children and adolescents with ADs. Of importance, longitudinal studies are mandatory to investigate the developmental trajectories of clinical phenotypes of these populations.

The significance of accurately describe the clinical picture of patients with ADs during childhood/adolescence cannot be overstated, as it enables the customization and enhancement of the quality of intervention programs.

Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We would like to thank all children, adolescents, and their families.

Funding

This study was supported by the Italian Ministry of Health with “Current Research” funds.

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Authors and Affiliations

  1. Child and Adolescent Neuropsychiatry Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Giulia Lazzaro, Domenica Bellantoni, Cristiana Varuzza, Stefano Vicari, Deny Menghini & Maria Pontillo

  2. Department of Life Science and Public Health, Catholic University of the Sacred Heart, Rome, Italy

    Stefano Vicari

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Contributions

Conceptualization, S.V., M.P. and D.M.; methodology, M.P., D.M., S.V., G.L. and D.B.; formal analysis, G.L. and D.B.; investigation, G.L., D.B. and C.V.; data curation, G.L., D.B. and C.V.; writing—original draft preparation, G.L., M.P., and D.M.; writing—review and editing, G.L., D.B., C.V., D.M., and S.V.; supervision, M.P., and D.M.; project administration, D.M. All authors have read and agreed to the published version of the manuscript.

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Lazzaro, G., Bellantoni, D., Varuzza, C. et al. Clinical manifestations of children and adolescents with anxiety disorders with and without specific learning disorders. Ann Gen Psychiatry 24, 17 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12991-025-00555-z

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Annals of General Psychiatry

ISSN: 1744-859X