This case report delves into the increasing prevalence of autism cases, particularly focusing on the city of Pelotas, Brazil, and its multidisciplinary autism center, Doutor Danilo de Moura Rolim. The study aims to examine hair cortisol levels in 36 children diagnosed with autism, exploring their association with functionality. Sociodemographic data were gathered through interviews and standardized instruments. Hair cortisol levels were determined using liquid chromatography coupled with mass spectrometry. Results indicated elevated cortisol levels in 88.8% of the sample, particularly in severe autism cases, highlighting a moderate positive correlation between cortisol levels and autism severity. Additionally, a strong negative correlation was observed between cortisol levels and functionality, emphasizing the potential impact of chronic stress on functionality in children with autism. Despite some limitations, this study underscores the importance of considering chronic stress in the assessment and treatment of autism, urging a multidimensional approach for improved understanding and therapeutic interventions aimed at enhancing the well-being of affected children.

• Autism; Cortisol; Functionality

Campelo G, Rech CL, Amantea S (2023) Stress and Functionality Levels in a Sample of Patients with Autism Spectrum Disorder. Ann Pediatr Child Health 2023; 11(5): 1317.

ASD: Autism Spectrum Disorder ACTH: Adrenocorticotropin

Over the past decade, most research in autism spectrum disorder (ASD) has emphasized ASD as a neurodevelopmental condition. Changes in routine may generate high levels of stress in children with ASD, further affecting social functioning. A 2020 study showed that cortisol levels were positively associated with the presence of stereotypic behaviors in children with autism. Recently, the determination of hair cortisol levels has been recognized as a good quantitative biomarker.

As time progresses, it is possible to observe an increasingly higher number of autism cases. The city of Pelotas, in the southern region of the state of Rio Grande do Sul, Brazil, is home to the multidisciplinary autism center, Doutor Danilo de Moura Rolim, Within this establishment, we conducted evaluations on a 36 children diagnosed with autism, to determine hair cortisol levels and, if possible, verify its association with functionality.

An interview was conducted with the legal guardian and 3 standardized instruments were applied. The first instrument collected sociodemographic data such as age of the child and mother, sex (male or female), marital status of the legal guardian (married or living common law, single, divorced, or widowed).

The second instrument consisted of the validated Brazilian Portuguese version of the Childhood Autism Rating Scale (CARS), which seeks to determine the degree of autism in patients, with two possible classifications: mild-moderate autism and severe autism [1].

The third instrument was the validated Brazilian Portuguese version of the Pediatric Evaluation Disability Inventory (PEDI), which aims to measure functional status in three domains: self care, mobility, and social function [2].

Regarding capillary cortisol assessment, liquid chromatography coupled with mass spectrometry was used to determine hair cortisol levels. Hair samples were cut with surgical scissors as close as possible to the scalp from an occipital position, as it is least subject to environmental action and considered an optimal region for collection. The procedure had to obtain approximately 25 g of hair. The samples were placed in aluminum foil and envelopes individually to avoid contamination and sent to a central laboratory for testing within a maximum of 24 hours after collection.

The analysis was performed by liquid chromatography coupled with mass spectrometry using the Nexera-i LC-2040C Plus system coupled to a triple quadrupole mass spectrometer LCMS-8045 (Shimadzu®, Kyoto, Japan). The reference values used to characterize normality were based on data from Raul et al. and are shown in Table 1.

Mean participant age was 4 years and 9 months (n=36), and most participants were boys (80.6%). Cortisol levels ranged from 71 to 256 pg/mg of hair (Figure 1), and elevated cortisol levels were found in 88.8% of the sample, which is above the method’s reference limit [3].

Figure 1: Concentrations of hair cortisol in the sample of children with ASD

When comparing data from the CARS with hair cortisol levels, we found that children with severe autism also had increased cortisol levels. According to Pearson’s correlation, there was a moderate positive correlation between the CARS score and cortisol [4](r= 0.396).

When comparing data from the PEDI domains (self-care, mobility, and social function) with hair cortisol levels, children with lower scores on the social function domain also had increased cortisol levels [4].

To control for the biological behavior of the sample, which was obtained by convenience, we evaluated the correlation between the CARS and PEDI scores. Pearson’s correlation identified a strong negative correlation between the PEDI social function domain and CARS (r= -0.854) and the PEDI self-care domain and CARS (R = -0.670) and a moderate negative correlation between the PEDI mobility domain and CARS (r = -0.523). The higher the PEDI score, the lower the CARS score [4] (Figure 2).

Figure 2: Bivariate analysis of the CARS score in relation to the PEDI score in a sample of children with autism. The higher the PEDI score, the lower the CARS score. Children with mild-moderate ASD have greater functioning in self-care, mobility, and social function

The present case report provides a valuable opportunity to examine the clinical implications and lessons learned in the context of evaluating hair cortisol levels in children with ASD. By investigating the association between cortisol levels and functionality in children with ASD, relevant considerations arise that can inform clinical practice and future research.

Hair cortisol refers to the levels of cortisol present in the hair, which can provide a measure of exposure to chronic stress. Recent studies suggest that elevated hair cortisol levels are associated with autism in children.

Our sample consisted mainly of boys (80.6%), which is in accordance with the literature, as ASD tends to affect more boys than girls [5]. The levels of hair cortisol found in this study were higher than those found in other studies [6], suggesting that it may act as a good marker for chronic stress.

The role of cortisol in autism was assessed to evaluate whether there is an association between some of the related behavioral disorders and a chronically increased level of activation and hyperarousal, which can result in elevated cortisol levels. Eleven studies assessed baseline levels of cortisol, ACTH, or response to dexamethasone. Five studies using blood measurements of cortisol or ACTH found no differences between participants with autism and controls, which suggests that baseline levels of cortisol functioning are not greatly altered in autism. The largest study, involving 48 participants with autism, found significantly increased ACTH levels and normal cortisol levels in these patients7 . Plasma ACTH was established as a good marker for acute stress. Cortisol, on the other hand, has a longer half-life and a significantly longer latency to respond to stress, providing a better measure for baseline stress levels [7]. Therefore, rather than providing evidence for a chronic hyperarousal state, these results suggest that people with autism have an increased stress response to experimental procedures such as blood draw. It is interesting, however, that two studies showed that some patients with autism have abnormal cortisol suppression [8].

Although studies using hair cortisol to assess stress and functionality levels in patients with ASD are scarce, hair cortisol has been used in other studies to assess chronic stress [9]. For patients with autism, this opens up a range of interesting study perspectives, as signs of chronic stress were observed in our study sample.

By assessing degree of functioning in our series of patients, we found that patients with autism and higher cortisol levels have decreased functionality, suggesting that this may affect the performance of activities of daily living, instrumental activities of daily living, and sensory activities related to the disorder. Functionality is lower in the most stressed ASD [10].

Any type of physical or mental stress can lead to an increase in cortisol. However, the type of situation that triggers a stress response can vary from person to person. People with autism often react abnormally to environmental changes or to new situations that may not be stressful for others. Studies on the oscillation of cortisol levels in children with autism have presented conflicting results, which may be partly explained by the fact that different methodologies were used and measurements were taken at different moments during the day, as well as by inadequate handling of collection conditions [11]. A recently published study using a peer interaction paradigm found higher cortisol levels in many children with autism [12]. This is a significant concern, as chronic elevations of cortisol can have detrimental effects on brain development. Prolonged, elevated cortisol levels were associated with a reduced size of some brain regions, such as the hippocampus, in individuals without autism [11]. High cortisol levels have been linked to other adverse associations, including low parent-child attachment security [12].

This study has some limitations. One would be the lack of a control group, which would have been an interesting evaluation strategy. The other limitation was due to the COVID-19 pandemic, data collection may have been compromised by the impact of the pandemic on patients with autism, as well as the difficulty of collecting samples in this environment. Despite the limitation, the cortisol levels found in our sample were considerably higher than those found in the literature.

In summary, this case report expands our understanding of the relationship between cortisol levels, the severity of autism, and social functionality in children with ASD. The clinical implications underscore the relevance of considering chronic stress as part of the assessment and treatment of patients with ASD. From the lessons learned, we recognize the need for an integrated and multidimensional approach to comprehend and address the complexities of ASD. In the future, further investigations can deepen this understanding and explore therapeutic approaches aimed at reducing stress and enhancing the well-being of these children.

The multidisciplinary autism center, Doutor Danilo de Moura Rolim, Pelotas/Brazil

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