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International Journal of Developmental Disabilities logoLink to International Journal of Developmental Disabilities
. 2023 May 25;71(1):159–167. doi: 10.1080/20473869.2023.2213923

Evaluation of procalcitonin and C-reactive protein levels in children with autism spectrum disorder and attention deficit hyperactivity disorder

Öznur Adıgüzel Akman 1,✉, Erman Esnafoglu 2
PMCID: PMC11774147  PMID: 39882415

Abstract

Inflammation is thought to play a role in the etiopathogenesis of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Procalcitonin (PCT) is an inflammatory biomarker released by thyroid parafollicular cells. CRP is systemic biomarker of inflammation. In this study, the hypothesis that PCT and C-reactive protein (CRP) might be indicators of increased inflammatory response was tested. For this purpose, PCT and CRP as well as other simple inflammatory markers were evaluated in children with ASD and ADHD. A total of 33 ASD, 36 ADHD, and 31 healthy controls were included in the study, who were similar in terms of gender and age. PCT, CRP, sedimentation and hemogram parameters (Neutrophil Lymphocyte Ratio) were measured in children aged 5-15 years. PCT and CRP values were found to be statistically significantly higher in ASD and ADHD children compared to healthy controls (p < 0.05). A positive correlation was found between PCT and CRP values (r: 0.358; p < 0.001). No significant correlations were found between disorder severity scale scores and PCT and CRP values (p > 0.05 for both). Accordingly, it is suggested that inflammation plays a role in the etiopathogenesis of these disorders. PCT and CRP may be used as inflammation markers.

Keywords: procalcitonin, c-reactive protein, inflammation, autism spectrum disorder, attention deficit and hyperactivity disorder

Introduction

Inflammation is the physiological response to tissue damage initiated by the organism against exogenous and endogenous stimuli. This response occurs at cellular and humoral level and is necessary for the continuation of life. The aim is to repair cellular injury caused by the stimulant, to ensure removal from the environment of necrotic cells and tissues forming as a result of damage to the cell, and to prevent harmful effects on the organism by limiting the bacteria or stimulant. Natural immunity comprises the immune system provided by non-specific cells meeting an antigen and present in the organism before the antigen. The secondary defense system occurs through specific immune mechanisms and ensures immunity specific to the microorganism is acquired at humoral and/or cellular level within a certain period based on the primary and secondary response of the organism to the antigen (Kushener 1993, Kılınçturgay 1994).

Many studies to date have shown immune abnormalities and inflammation in the etiopathogenesis of neurodevelopmental disorders like autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) (Vargas et al. 2005, Hoekstra 2019). The results of these studies observed cytokine and chemokine production through microglial and astrocyte activation in the brain (Siniscalco et al. 2013, Donfrancesco et al. 2020). The high rates of comorbidity for inflammatory and autoimmune diseases in both disorder groups lead to consideration that chronic neuroinflammation may play a role in the etiology (Hoekstra 2019, Leffa et al. 2018).

ASD is a neurodevelopmental disorder beginning in the early stage of development characterized by inadequate social communication and interaction (not sharing mutual feelings, inadequate eye contact and body language, etc.) and limited repetitive behavior patterns (repeated motor movements, echolalia, inability to tolerate changes, etc.) (APA 2013). The etiology is still not clearly or fully known. In recent times, increasing ASD prevalence was reported on a global scale and 1 in 68 children are diagnosed with ASD (Ning et al. 2019). The overall ASD prevalence per 1,000 children aged 8 years was 27.6 (one in 36) (Maenner 2023). Autism patients have neuroglial system activation in brain tissue and cerebrospinal fluid (CSF), indicating neuroimmune abnormalities (Pardo et al. 2005).

ADHD is another neurodevelopmental disorder characterized by ongoing lack of attention and/or hyperactivity-impulsivity. Symptoms begin before 12 years of age and it affects nearly 5% of children in more than one environment. It may lead to significant levels of disruption in lifelong social, academic and professional functioning (Anand et al. 2017). Though it is known that higher rates of genetic factors are present, genetic transition alone is inadequate to explain the etiology. It is thought to have a multifactorial background linked to the interaction of environmental, biological and genetic factors with each other (Faraone et al. 2005).

Procalcitonin (PCT) is released by parafollicular C cells in the thyroid. It cannot be easily identified due to low concentrations under normal physiological conditions. It is a marker playing a role in inflammation. In pathologic situations PCT is released by parenchymal cells in a variety of organs like the liver, kidney, fat and muscle and a significant degree of increased circulation concentration allows easy detection (Ge et al. 2019).

C-reactive protein (CRP) is an acute phase reactant protein synthesized by the liver when body tissue is injured (Ge et al. 2019). Plasma CRP concentration increases during inflammatory situations, a property allowing its use for clinical purposes for a long time. The rapid increase in synthesis within a few hours after tissue injury or infection contributes to host defense and was shown to be a part of the innate immune response (Black et al. 2004).

Inflammation has an important place in the pathogenesis of neurodevelopmental disorders. Immune system abnormalities are frequently seen in these disorders. Therefore, it may be important to demonstrate the presence and severity of inflammation in these disorders. The increase in other simple inflammatory markers with PCT may primarily indicate inflammation. These parameters can indicate the severity of inflammation. In conclusion, in this study, we aimed to show whether inflammation is present in the pathogenesis of these disorders with these parameters and to evaluate the relationship of these parameters with disorder severity. To the best of our knowledge, PCT levels have not been previously investigated in neurodevelopmental disorders. Thus, for the first time in the literature, PCT levels in these disorders and the correlations with other inflammation markers were investigated. In this respect, this study may contribute to elucidating the relationship between inflammation and neurodevelopmental disorders.

Materials and methods

Participants

The research was performed in Ordu University Education and Research Hospital. Participants attended the child and adolescent psychiatry outpatient clinic. A total of 33 ASD, 36 ADHD, and 31 healthy controls were included in the study.

The ADHD group comprised those aged 5-15 years who were diagnosed with ADHD and did not have any other psychiatric diagnosis. The ASD group was formed of those who were diagnosed with ASD according to DSM 5 criteria in the same age range and did not have any additional psychiatric diagnosis. The participants in the control group were selected from those who applied to the pediatric healthy child follow-up outpatient clinic. Detailed psychiatric examination and family interviews were held. Accordingly, the control group included participants who did not have any psychiatric diagnosis. Psychiatric examinations, family interviews and data collection were performed by specialist child and adolescent psychiatrists. Subjects outside this age group, who did not want to participate, with any systemic disease, with acute or chronic infection, and with additional neurological disease (epilepsy, cerebral palsy, tumor, sensory defects) or psychiatric disease (mental inadequacy, bipolar disorder, schizophrenia) were excluded from the study.

Data collection

All participants completed the detailed sociodemographic data form created by the researchers. The DSM-IV-Based Screening and Evaluation Scale for Conduct Disorders in Children and Adolescents (Turgay ADHD scale) was used for clinical severity in the ADHD group and the Childhood Autism Rating Scale (CARS) was used for clinical severity in the ASD group. The sociodemographic form and scales were completed with the parents during face-to-face interviews.

The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, DSM-5 (K-SADS-PL-DSM-5-T) was applied by a specialist child psychiatrist. Thus, the diagnosis was confirmed and the presence of comorbid conditions was investigated. Parents of all participants included in the research signed the ‘informed consent form’ containing information relating to the study and stating they participated voluntarily. The study was permitted by Ordu University Faculty of Medicine Ethics Committee (Decision no: 2020/68). Written consent was obtained from the families of the participants. The study was conducted in accordance with the ethical rules stated in the Declaration of Helsinki.

Samples were taken from patient and control groups and hemogram parameters, CRP, PCT and sedimentation values were measured on the same day as routine. Samples were collected in the morning before breakfast and 5 mL venous blood was placed in gel-barrier tubes under sterile conditions.

Instruments

Sociodemographic data form

This data form was prepared by the researchers. It included questions related to patient name-surname, sex, date of birth, age (months, years), assessment data, address information, communication information, type and time of birth, age at symptom onset, history of intense antibiotic use, history of psychotropic medication use, frequent infections, other psychiatric disorders apart from ASD or ADHD, special education received, duration of breastfeeding, height-weight information, infection in the mother during pregnancy, age of mother-father when pregnant with the patient, and any chronic disease that may be related to infection in the mother or father.

Turgay DSM-IV-based child and adolescent behavior disorders screening and rating scale (Turgay ADHD scale)

This scale, developed by Atilla Turgay in 1995 based on DSM-IV diagnostic criteria, aims to identify the presence of ADHD and behavior problems in children and adolescents. The scale comprises a total of 41 items, with 9 items about attention deficit, 9 items about hyperactivity and impulsivity, 8 items about oppositional defiance disorder and 15 items about symptoms of conduct disorder. Items are given points from 0-3 according to the clinical status of the patient. If 6 out of the 9 items for the attention deficit and hyperactivity and impulsivity subdimensions receive 2 or 3 points, the diagnostic criteria are accepted as being met (Turgay 1995). Turkish validity and reliability for this test was done by Ercan et al. (2001).

Childhood autism Rating scale (CARS)

The Childhood Autism Rating Scale is used in many pediatric psychiatry clinics to differentiate children with autism diagnosis and autistic disorder from other developmental disorders. The scale is completed during interviews with the family and in line with information obtained as a result of observing the child. CARS was developed in 1971 by Schopler et al. The Turkish adaptation, validity and reliability of this test was investigated by Sucuoglu et al. (1996). The scale comprises a total of 15 items under the headings of relationship with people, mimicry, emotional response, use of the body, use of objects, reaction to change, visual responses, listening responses, use of taste, smell and touch, fear/irritability, verbal communication, non-verbal communication, impact on behavior, level of mental response and general observations. Children receiving 30 or more points on the scale are considered to have autistic disorder. Those with points from 30-36 are considered to have mild-moderate severity autism, while points from 37-60 are accepted as indicating severe autism. CARS was shown to have high specificity and sensitivity to differentiate children with autism disorder from children with mental retardation, developmental delay or atypical autism-pervasive developmental disorder (Perry et al. 2005, Esnafoglu and Ayyıldız 2017).

Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version, DSM-5 (K-SADS-PL-DSM-5-T)

The Turkish adaptation of this semi-structured interview form, updated according to DSM-V diagnostic criteria by Kaufman et al. (2016), was performed by the researchers. After differences in the translated and re-translated texts and functionality of the interview form were assessed with pilot interviews with parents and children, the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version DSM-5 5 November 2016- Turkish version (K-SADS-PL-DSM-5-T) gained its final form. The first section of the interview form comprises an unstructured interview to obtain general information about sociodemographic data relating to child and family, complaints, development stages and health status, and functionality at home and in school. The second section assesses more than 200 symptoms with questions and the third section comprises evaluation and observation to confirm the DSM-V diagnosis. Each section is given points individually; however, results are based on clinician observation. The Turkish adaptation validity and reliability of this test was performed by Unal et al. (2019).

Measurement of inflammatory parameters

PCT measurement

Blood samples were processed within 30 min of collection. Plasma was separated by centrifugation at 4000 rpm for 10 min. After this procedure, it was routinely measured in the hospital lab on the same day. Samples taken for PCT measurement were studied with the electrochemiluminescence method with a Roche kit in a Roche Cobas 6000 E601 hormone device. Reference interval was taken as 0-0.046 ng/mL.

CRP measurement

Blood samples taken from the patients were routinely measured in the hospital laboratory on the same day. Samples taken for CRP measurement were centrifuged in a Rotofix 32 brand cooled centrifuge at 4000 rpm for 10 min. The serum obtained was studied with the immunoturbidimetric method using a Roche Cobas 6000 c501 biochemical device. Reference values were taken as 0-0.5 mg/dL.

Data analysis

The raw data were entered into the SPSS 22 program. The chi-square test was applied to categoric variables. The distribution of numerical data was researched with Shapiro Wilk normality tests. Numerical data with normal distribution had the Student t test used for two-way groups, while the Mann-Whitney U test was used for data without normal distribution. Numerical data with normal distribution are given as mean ± SD, while data without normal distribution are given as median (min-max). Comparisons between three groups used the ANOVA test for data with normal distribution and the Kruskal Wallis test for data without normal distribution. General significance was accepted as p < 0.05. Two-way comparisons after the ANOVA test used the Bonferroni correction. Accordingly p < 0.016 was accepted as significant. The Spearman and Pearson tests were used for correlation analysis.

Results

Comparison of sociodemographic data for the subjects is presented in Table 1. There were no significant differences between the groups in terms of sex, age and BMI. Birth features, psychomotor development, age of symptom onset and psychometric test points are presented in Table 1.

Table 1.

Characteristic features of the groups.

  ASD (n = 33) ADHD (n = 36) CONTROL (n = 31) P
Sex (F/M) 8/25 7/29 12/19 0.1901
Age (median) (min-max) 6.5
(5-15)		 7.5
(5-14)		 7
(5-14)		 0.4202
BMI (Mean ± SD)
(min-max)		 17.59 ± 2.33
(13.81-22.22)		 17.97 ± 2.86
(13.6-27.4)		 18.42 ± 2.78
(12.9-26.6)		 0.4743
CARS scores (min-max) 47.06 ± 7.42 (33-60) - - -
Atilla Turgay
(attention deficit subscale)
(min-max)		 - 17.05 ± 4.83
(12-27)		 - -
Atilla Turgay
(hyperactivity subscale)
(min-max)		 - 19.69 ± 4.66
(12-27)		 - -
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Note:

1

chi-square test (X2 test).

2

Kruskal-Wallis test.

3

One-Way ANOVA test.

ASD: Autism Spectrum Disorder.

ADHD: Attention Deficit Hyperactivity Disorder.

BMI: Body Mass Index.

Biochemical parameters of participants

Procalcitonin

The median PCT values measured were 0.037 (0.02-0.175) ng/ml in the ASD group, 0.034 (0.02-0.196) ng/ml in the ADHD group and 0.028 (0.005-0.165) ng/ml in the control group. There was a statistically significantly difference between the control and patient groups for PCT values (p < 0.05). The PCT values in the groups are given in Table 2. The distribution of PCT within the groups is shown in Figure 1.

Table 2.

Comparison of inflammatory parameters between groups.

  ASD n = 33 ADHD n = 36 Control n = 31 P
Median (min-max) Median (min-max) Median (min-max)
CRP (mg/dl) 0.1
(0.04-0.81)		 0.1
(0.06-0.49)		 0.06
(0.05-0.29)		 0.004*
PCT (ng/ml) 0.037
(0.02-0.175)		 0.034
(0.02-0.196)		 0.028
(0.005-0.165)		 0.003*
NLR 0.96
(0.15-3.52)		 1.09
(0.53-4.33)		 1.26
(0.58-7)		 0.067*
Sedimentation
(mm/hr)		 8
(1-33)		 5.5
(2-31)		 8
(3-40)		 0.309*
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*

Kruskal–Wallis test. p˂0.05 significant.

ASD: Autism Spectrum Disorder.

ADHD: Attention Deficit Hyperactivity Disorder.

CRP: C-Reactive Protein.

PCT: Procalcitonin.

NLR: Neutrophil-Lymphocyte Ratio.

Figure 1.

Figure 1.

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Distribution of PCT values between groups.

Of ASD patients, 39% (n = 13) had PCT values above normal limits. For the ADHD group, 28% (n = 10) and for the control group, 8% (n = 3) had high values for PCT. When the ASD and control group were compared in terms of PCT levels, the PCT values in the ASD group were identified to be significantly high (p = 0.003).

When the ADHD and control groups were compared, the PCT values of the ADHD group were significantly high (p = 0.003). There was no statistical significance found between the PCT values for the ASD and ADHD groups (p = 0.890). According to Spearman correlation analysis between CARS and PCT in the ASD group, there was no significant correlation between CARS with PCT values (r: ‐0.066; p = 0.717).

In the ADHD group, according to Spearman correlation analysis, there was no significant correlation between the Atilla Turgay attention deficit subscale and PCT (r: ‐0.29; p = 0.866). There was no significant correlation between the Atilla Turgay hyperactivity subscale with PCT (r: −0.182; p = 0.289).

The results of Spearman correlation analysis found significant positive correlation between CRP and PCT for all subjects (r: 0.358; p˂0.001). Since these two parameters are indicators of inflammatory response, a positive correlation was found between them. However, these significant correlations were not identified when the groups were assessed in each group (p > 0.05).

CRP

Since the CRP values did not show normal distribution, the difference between the groups was evaluated with the Kruskal Wallis test. Median CRP value was 0.1 (0.04-0.81) mg/dl in patients with ASD, while it was 0.1 (0.06-0.49) mg/dl in ADHD patients and 0.06 (0.05-0.29) mg/dl in the control group. When the control and patient groups are compared, CRP values were found to display statistically significant differences between the groups (p < 0.05) (Table 2). The distribution of CRP values in the groups is shown in Figure 2. Of ASD patients, 9% (n = 3) had CRP values above normal limits. CRP values were within the reference interval in the ADHD and control groups.

Figure 2.

Figure 2.

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Distribution of CRP values between groups.

When the ASD and control groups are compared in terms of CRP measurements, CRP values were found to be significantly higher in the ASD group (p = 0.008). When the ADHD and control group are compared, CRP levels were found to be significantly higher in the ADHD patients (p = 0.002). When the ASD and ADHD groups are compared, there was no statistically significant difference found in terms of CRP levels (p = 0.985).

Within the ASD group, according to Spearman correlation analysis between the CARS score for disorder severity and CRP, there was no significant correlation found (r: 0.123; p = 0.495).

According to Spearman correlation analysis between the Atilla Turgay attention deficit subscale and CRP within the ADHD group, there was no significant correlation between scale total points and CRP levels (r: ‒0.288; p = 0.089). There was a mild negative correlation between the hyperactivity subscale with CRP (r: ‒0.33; p = 0.049).

Neutrophil-Lymphocyte ratio (NLR) and sedimentation

Significant differences were not found between the groups for the other inflammatory parameters of NLR and sedimentation (p > 0.05). The distribution of NLR and sedimentation values between the groups is shown in Figure 3.

Figure 3.

Figure 3.

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Comparison of NLR and sedimentation values between groups.

Discussion

According to our results, PCT and CRP levels were statistically significantly higher in children with ASD and ADHD compared to the healthy control group. Accordingly, our study supports the role of inflammation in the pathogenesis of both disorders. However, no relationship was found between these inflammatory parameters and the severity of these disorders. Both of these are considered to be neurodevelopmental disorders. Both are most common in childhood and may show some common clinical features. They can also often be seen together as comorbidities. Both disorders have multiple intersections in their pathogenesis (Craig et al. 2015, Antshel and Russo 2019, Hours et al. 2022). For example, inflammation, infection, and neurodevelopmental abnormalities are seen in the pathogenesis of both disorders. Therefore, in this study, we aimed to evaluate these two disorders, which are common in childhood, together. In addition, children without ASD comorbidity in addition to ADHD were selected in this study. The ASD group comprised children with ASD who did not show obvious signs of ADHD. This was done to assess the pure impact of both disorders.

PCT is a calcitonin prohormone released by hepatocytes, renal cells, myocytes, adipocytes, neurons and leukocytes (de Campos et al. 2015). Increased PCT level is the best marker of sepsis. It is reported in other situations related to the inflammatory response like trauma, major surgery, heart surgery and heat exhaustion; as a result, it is not specific to infection (Vincent 2000). CRP is a very sensitive systemic marker of inflammation and tissue injury. It was the first acute phase protein identified and was named CRP due to the precipitation of C-polysaccharide. The acute phase response includes non-specific physiological and biochemical reactions against tissue injury, infection, inflammation and malignant neoplasm. Controlling cytokines sourced in injured tissue is regulated by hepatocytes, especially (Pepys and Hirschfield 2003).

In recent times, the effect of inflammation in the pathogenesis of neurodevelopmental disorders like autism and ADHD has become a research topic (Anand et al. 2017, Sajid et al. 2017, Yin et al. 2020). In addition, there are studies about the role of inflammation in the etiology of other neurodevelopmental disorders such as specific learning disabilities (SLD) and tic disorders (Yektas et al. 2022, Parker-Athill et al. 2015).

In a study, PCT values measured in 34 schizophrenia patients and 24 healthy controls had higher rates in schizophrenia patients compared to controls (Varun et al. 2018). According to this study, 32.3% of schizophrenia patients had high CRP, while 30.7% had high PCT. In our study, PCT values were high in 39% of ASD patients, 28% of the ADHD group and 8% of the control group. Another study compared the PCT values of 45 chronic schizophrenia patients, 45 healthy controls and 30 sepsis patients (de Campos et al. 2015). PCT has not been investigated so far in all neurodevelopmental disorders of childhood.

In our study, the CRP levels were significantly higher in the ASD group compared to controls. Again in the ADHD group, the CRP values were also statistically significantly high when compared to controls. However, when the correlation of CRP values with symptom severity is assessed, no significant correlation could be shown between ASD symptoms and CRP values in our study. In the ADHD group, there was no correlation between disorder severity and CRP. Another study investigated the effect of maternal CRP levels on development of ADHD in children and did not find a significant correlation between maternal CRP levels with the occurrence of ADHD (Chudal et al. 2020). According to a recent meta-analysis study evaluating inflammatory parameters in ADHD patients, no significant difference was found in terms of CRP, IL-1β, IL-10 and interferon-γ levels in ADHD children. This suggests that individuals with ADHD tend to have high IL-6 levels and low TNF-a levels (Misiak et al. 2022). In our study, CRP levels were statistically significantly higher in the ADHD group than in the controls. However, CRP levels in the ADHD group were within the reference ranges. The results of this study suggest that there are contradictions regarding the effect of CRP on ADHD. Another study showed that CRP levels were high in children with ADHD (Chang et al. 2020). This study is also compatible with our study.

According to the results of a review assessing 9 meta-analysis studies comprising ASD and control groups, the peripheral CRP levels of individuals with ASD were found to be significantly high (Yin et al. 2020). The results of this study support the results of our study. Another study including 39 autistic and 39 control subjects identified higher hs-CRP levels in autistic children compared to the control group. These levels were reported to be associated with autism severity (Khakzad et al. 2012). In our study, no relationship was found between CRP levels with ASD severity; however, while increases at minimal level in hs-CRP levels were sensitive, our study measured peripheral CRP levels. Accordingly, in spite of the similar numbers of subjects in the control and patient groups, sensitive measurement was not performed so sufficient elevation may not have been identified. In a meta-analysis study investigating CRP levels in a total of 5258 children with ASD and their mothers, children with ASD had higher CRP levels (Nadeem et al. 2020).

In the literature, it appears that neutrophil lymphocyte ratio (NLR), assessed as a marker of inflammation, was researched in ADHD patients (Avcil 2018, Önder et al. 2021). NLR can be easily calculated from hemogram analyses. High NLR is reported to be associated with increased CRP and cytokines. For this reason, NLR is commonly used as a marker for systemic inflammation (Karageorgiou et al. 2019). A study examining NLR, platelet lymphocyte ratio (PLR) and monocyte lymphocyte ratio (MLR) in 70 controls and 82 ADHD patients found the NLR, PLR, MLR, monocyte platelet volume (MPV) and neutrophil counts were significant high, while the lymphocyte count was significantly low in the ADHD group compared to the control group (Avcil 2018). The results of another study measuring NLR in 100 ADHD and 99 control subjects supported these findings (Önder et al. 2021). In our study, NLR measurements were performed; however, there was no significant correlation in terms of NLR between both the ASD and ADHD groups compared to controls. The contradiction between these results may be related to the low patient numbers in our study compared to the other studies. In another study, in which 100 patients between the ages of 7 and 12 who were not using drugs were examined, NLR, MPV, and MLR were measured with complete blood count in order to examine the inflammatory pathogenesis. In this study, monocyte levels were higher in both ADHD groups and SLD. No significance was found for other peripheral inflammatory markers, including NLR. The relationship between inflammatory parameters and disease severity could not be demonstrated (Yektas et al. 2022). The results of this study also support the results of our study from the point of view of NLR.

PCT and CRP are inflammatory biomarkers that can be easily and routinely measured. Much information indicates that these two parameters reflect systemic inflammation (Pfäfflin and Schleicher 2009, Kargaltseva et al. 2019) Therefore, these two parameters can easily illustrate inflammation seen in neurodevelopmental disorders such as ASD and ADHD. In further studies, the effect of treatment of these disorders on PCT and CRP as well as other inflammatory parameters should be investigated. At this stage, PCT and CRP measurements will contribute to the understanding of inflammatory processes in the pathogenetic mechanism.

Limitations

This study has some limitations. Firstly, the lack of adequate subject numbers reduces the significance. More accurate results may be reached if subjects were included in greater numbers. In addition, the number was small because we tried to select patients without comorbidities. Additionally, the effect of medication use on these inflammation parameters is not known. The subjects participating in the study were using psychopharmacological treatment. Treatment of the patients could not be stopped because it would be unethical. Psychopharmacological drugs may also have an effect on PCT (de Campos et al. 2015). However, studies about the possible effects of antipsychotic drugs on CRP (Diaz et al. 2010) were found; hence, these effects had to be ignored. Parameters like antinuclear antibody (ANA) and rheumatoid factor (RF), that can be used to assess systemic inflammation and autoimmunity, in addition to inflammatory cytokines were not assessed in this study. Though acute infection that may impact the study parameters was questioned by the psychiatrist, subjects were not assessed by a pediatrist, which represents a limitation. In our study, routinely-examined CRP measurements were used to assess patient groups, assessment of hs-CRP may provide more accurate results.

The etiopathogenesis of neurodevelopmental disorders like ASD and ADHD still cannot be clearly explained. In our study, the PCT and CRP values in these disorder groups were examined. According to the results of this study, it cannot be said that CRP is increased in neurodevelopmental disorders. However, it can be said that there is a tendency toward elevated CRP. Identifying other factors associated with inflammation may help explain the inflammatory mechanisms in the pathogenesis. Further study is needed to explore the correlations of PCT and CRP levels with disorder severity, symptom profile and treatment response.

Conclusions

Our study is the first to assess PCT and CRP together in children with ASD and ADHD. As a result of comparisons, PCT and CRP levels in children diagnosed with ASD and ADHD were found to be significantly high compared to the control group. Additionally, positive correlations were identified between CRP and PCT values. No significant correlation could be shown between CRP and PCT values with disorder severity. These findings lead to consideration of the role of inflammation in the etiopathogenesis of neurodevelopmental disorders like ASD and ADHD.

According to the results of this study, it is difficult to say that these inflammatory parameters can be used for diagnostic purposes. However, if the obstacles mentioned in the limitations are resolved, a re-evaluation can be made. This study may trigger further research about this subject. PCT and CRP may also reflect existing inflammation in ASD and ADHD.

Acknowledgements

We are grateful to our patients, their families, and the laboratory team in our hospital for routine biochemical analyses.

Disclosure statement

No potential conflict of interest was reported by the authors.

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