Although there is high co-occurrence between ASD and ADHD, the nature of this co-occurrence remains unclear. Our study aimed to examine the underlying relationship between ASD and ADHD symptoms in a combined sample of children with a primary clinical diagnosis of ASD or ADHD.n = 303) or ADHD (n = 319) for a total of 622 participants. Parents of these children completed the social communication questionnaire (SCQ), a measure of autism symptoms, and the strengths and weaknesses of ADHD and normal behavior (SWAN) questionnaire, a measure of ADHD symptoms. A principal component analysis (PCA) was performed on combined SCQ and SWAN items, followed by a profile analysis comparing normalized component scores between diagnostic groups and gender.Participants included children and youth (aged 3-20 years) with a clinical diagnosis of ASD ), with no overlap between SCQ and SWAN items in the components. Children with ASD had higher component scores in social-communication and RRBI than children with ADHD, while there was no difference in inattentive and hyperactive/impulsive scores between diagnostic groups. Males had higher scores than females in social-communication, RRBI, and hyperactivity/impulsivity components in each diagnostic group.We did not formally assess children with ASD for ADHD using our research-criteria for ADHD, and vice versa. High rates of co-occurring ADHD in ASD, for example, may have inflated component scores in inattention and hyperactivity/impulsivity. A disadvantage with using single informant-based reports  is that ASD and ADHD symptoms may be difficult to distinguish by parents, and may be interpreted differently between parents and clinicians.ASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. High levels of inattention and hyperactivity/impulsivity were seen in both ASD and ADHD in our clinical sample. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Females also had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-specific phenotypes related to the two conditions. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are both relatively common neurodevelopmental conditions , 2. DespOne possible explanation for the co-occurrence between ASD and ADHD is that they share common etiologies . EvidencDespite evidence of possible shared etiologies between ASD and ADHD, our understanding of the underlying relationship of combined ASD and ADHD behavior symptoms is limited. Delineating the relationship between core domains of different neurodevelopmental conditions can help us better understand the nature of their co-occurrence. If the core domains underlying ASD and ADHD overlap, this could suggest either that (1) the two disorders share a common latent phenotypic construct, or (2) there is substantial measurement error or reporting bias.A common latent phenotypic construct is found when item responses on a questionnaire are so highly correlated that they represent a common underlying domain. For example, if certain ASD and ADHD questionnaire items are highly correlated, they may load together in a principal component analysis and reveal a common underlying ASD/ADHD domain. A common ASD/ADHD domain might mean that certain ASD and ADHD traits are actually shared between the two disorders. Reporting bias can be observed when the same informant reports on both disorders, i.e., high scores on one disorder may bias an informant to rate an individual high (or low) on another disorder. A common latent phenotypic construct and measurement error may suggest an artificial co-occurrence between the two disorders. In contrast, if ASD and ADHD are associated with independent latent phenotypic constructs, this could suggest a “true” comorbidity in which measurement structure has no influence on the covariation between the two disorders.Factor analysis techniques are data reduction techniques that decompose symptoms into their underlying constructs or dimensions. One commonly used factor analysis technique is principal component analysis (PCA). The underlying dimensions that are extracted in PCA are referred to as components . It is wacross the two diagnostic groups. Furthermore, gender-specific phenotypes of ASD and ADHD have been proposed [across gender [To our knowledge, only four studies to date have examined the latent constructs of combined ASD and ADHD symptoms in the same sample. One study used a clinical sample of children with ADHD , one useproposed , 23, ands gender .The aims of our study were (i) to determine the principal components of combined ASD and ADHD symptoms in a clinical sample of children with a primary diagnosis of ASD or ADHD and (ii) to investigate whether there are differences in component scores across diagnosis and gender.Children and youth (aged 3-20 years) with a clinical diagnosis of ASD or ADHD were recruited via the Province of Ontario Neurodevelopmental Disorders (POND) Network, Canada. Participants were included if they had a primary clinical diagnosis of ADHD or ASD, and participants and their caregivers had sufficient English comprehension to complete required testing. Participants in the current study were enrolled between 2012-2017. Ethics approval was received from each participating institution’s ethics review board.Children with a primary diagnosis of ASD that were enrolled in the study had previously received a clinical diagnosis of autism, Asperger’s disorder/syndrome, or PDD-NOS by either a psychiatrist, clinical psychologist, developmental pediatrician, pediatrician, family physician or pediatric neurologist. Likewise, children with a primary clinical diagnosis of ADHD had previously received the diagnosis by either a psychiatrist, clinical psychologist, developmental pediatrician, pediatrician, family physician, or pediatric neurologist. Upon study enrollment, previous clinical diagnoses of ASD were confirmed using the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) , 25 and n = 101; ADHD: n = 106). We also excluded non-verbal children (n = 35) as these children by necessity had questions 2-7 incomplete on the SCQ. This resulted in a complete dataset of n = 303 in the ASD group and n = 319 in the ADHD group.A total of 439 ASD participants and 425 ADHD participants had both the ASD symptom (SCQ) and the ADHD symptom (SWAN) measures completed by their caregivers. Those with any missing data on either the SWAN or SCQ were excluded  , a 40-itADHD symptoms were assessed using the strengths and weaknesses of ADHD symptoms and normal behavior rating scale (SWAN) , an 18-iIQ was assessed with age-appropriate Weschler or Stanford-Binet scales. When more than one IQ score was available for a participant, the most recent IQ assessment was used. Adaptive functioning was assessed with the adaptive behavior assessment system (ABAS) first or second edition , 35. TheThe level of agreement beyond chance between ASD or ADHD caseness and having a clinical diagnosis of ASD or ADHD as noted by the parent or caregiver was calculated for children with a primary diagnosis of ADHD and ASD, respectively, using Cohen’s kappa.To remove redundant items, kappa was calculated between pairs of SCQ items (SCQ2-SCQ40) and between pairs of SWAN items (SWAN1-SWAN18). A kappa above 0.80 is considered “strong agreement”  and thisThe correlation between SCQ and SWAN variables was examined using a correlation matrix. Tetrachoric and Pearson correlations were used to examine correlations between dichotomous (SCQ) and continuous (SWAN) variables, respectively. Biserial correlations were used to examine correlations between SCQ and SWAN items.The following sets of items had very high correlations (> 0.80): SCQ 3 and 7; SCQ 28 and 30; SCQ 35 and 39; and SWAN 10 and 11. In all cases, the second question in the pair was excluded from further analysis to reduce multicollinearity . SCQ9 and SCQ23 were also removed from the combined SCQ-SWAN analysis as they had a low Kaiser-Meyer-Olkin (KMO) (< 0.85) . The KMOWe chose to use a PCA instead of an exploratory factor analysis as it is a simpler data reduction technique to use as a first step in understanding underlying ASD and ADHD dimensions. All principal component analyses were performed using R v3.5.1. Component scores were generated in R.χ (1225) = 25,880, p < 0.01, indicating that the data were suitable to be used in a PCA.We performed a PCA on SCQ items combined with SWAN items in the combined clinical sample of children with ASD and ADHD. The KMO = 0.92 was “superb” , indicatFor all PCAs, an oblique rotation (oblimin) was used to permit components to correlate with one another. To select the most appropriate principal components solution for each analysis, we considered the following criteria: (1) eigenvalues, (2) scree plots, (3) percentage of variance explained, (4) minimum number of item cross-loadings, and (5) clinical interpretability of the components.After a component solution was derived, correlations between components were examined. We defined correlation coefficients of 0.10-0.29 as small, 0.30-0.49 as medium and ≥ 0.50 as large .Before we could use the component scores of our combined ASD-ADHD sample PCA in a profile analysis, we needed to be confident that the components of our ASD sample and ADHD sample were similar. A PCA of the SCQ and SWAN items was performed separately in the ASD and ADHD samples. The PCAs of the ASD and ADHD samples were then compared on the number of components, the composition of the components, variance explained, and correlations between the components.When ASD and ADHD PCAs were performed separately they revealed similar components  were used to determine specifically which groups were different for each symptom component.Profile analysis was conducted in SPSS version 22  using thp = 0.02) and ABAS composite scores for all domains (p < 0.01).ASD participants from the complete dataset did not differ from those with missing data in terms of age, gender, SCQ score, SWAN inattention score, and SWAN hyperactivity/impulsivity score .ADHD participants from the complete dataset did not differ from those with missing data in terms of gender, SCQ score, SWAN inattention score, SWAN hyperactivity/impulsivity score, IQ, and ABAS scores  for children with a primary diagnosis of ASD. The level of agreement between ASD caseness and having a co-occurring ASD diagnosis was also “slight” [κ = 0.07) for children with a primary diagnosis of ADHD. Most cases of ADHD or ASD identified by questionnaires were not reflected in co-occurring clinical diagnoses.While 53.14% of children with a primary diagnosis of ASD met the threshold for ADHD caseness on the SWAN, only 18.97% were listed as having a known secondary ADHD diagnosis. While 13.48% of children with a primary diagnosis of ADHD met the threshold for ASD caseness on the SCQ, only 1.36% were listed as having a known secondary ASD diagnosis. The level of agreement between ADHD caseness and having a co-occurring ADHD diagnosis by caregiver report was “slight” [In the combined sample of clinically diagnosed ASD and ADHD participants, a PCA was conducted on the 34 SCQ and 17 SWAN items with oblique rotation on the 622 children with a primary clinical diagnosis of ASD or ADHD. The scree plot showed an inflection occurring after 4 points, which explained 55% of the variance. All 4 components had an eigenvalue greater than 1. A four-component solution was chosen based on the scree plot, eigenvalues, proportion of explained variance, and clinical interpretability of the components.Item loadings are shown in Table The “social-communication” component had a moderate correlation with the “RRBI” component (0.41), and low correlations with the “inattentive” and “hyperactivity/impulsivity” components, . The “RRBI” component had a low correlation with the “hyperactivity-impulsivity” component (0.17) and minimal correlation with the “inattentive” component (< 0.01). The “hyperactivity-impulsivity” component showed a moderate correlation with the “inattentive” component (0.34).The sum of the normalized component scores for each domain for each participant is shown in Fig. p < 0.001) or by gender (F (1620) = 613.63, p < 0.001), and there was no interaction between diagnosis and gender (F (1618) = 0.91, p = 0.34) with regard to overall levels of all four combined components. The tests of levels indicate that across all four components, there was a higher overall level of total scores in children in ASD than ADHD and in males than females. The test of parallel lines was significant for symptom components by diagnosis (F (3618) = 139.93, p < 0.001) and for symptom components by gender (F (3616) = 2.64, p = 0.05), but not for the interaction between symptom components by diagnosis by gender (F (3616) = 0.07, p = 0.97). The test of parallel lines indicates that the groups are not parallel by diagnosis, meaning that ADHD is not simply a milder version of ASD with lower levels of all symptom domains. Similarly, genders are not parallel, indicating that females are not scoring equally lower in all domains compared to males. The test of flatness was significant for diagnosis (F (31854) = 88.72, p < 0.001), but not for gender (F (31854) = 2.06, p = 0.10) and there was no interaction between diagnosis and gender (F (31854) = 0.06, p = 0.98). The test of flatness indicates that the diagnostic groups have significantly different amounts of one or more symptom components than that of other symptom components. The non-significant effect of gender and the interaction term indicates that it is the diagnosis, more so than gender, that drives the differences in the individual levels of the four symptom components.Overall, mean levels were not equal by diagnosis (F (1620) = 174.26, p < 0.01) and RRBI (F (1618) = 258.96, p < 0.01) component scores between the two diagnostic groups, there was no significant difference in inattentive (F (1618) = 5.67, p = 0.02) or hyperactive/impulsive (F (1618) = 0.31, p = 0.58) component scores between diagnostic groups. Males had higher social-communication (F (1618) = 9.10, p < 0.01), hyperactivity/impulsivity (F (1618) = 9.00, p < 0.01), and RRBI (F (1618) = 10.60, p < 0.01) component scores than females within each diagnostic group. There was no significant difference between males and females in inattentive (F (1618) = 0.93, p = 0.34) component scores.A profile plot comparing component scores between diagnostic groups and genders across the components is shown in Fig. High rates of co-occurrence between ASD and ADHD have been reported , 6. To dIn our sample, while 53.14% of children with a primary diagnosis of ASD met the threshold for ADHD caseness on the SWAN, only 18.97% were listed as having a known co-occurring ADHD diagnosis. While 13.48% of children with a primary diagnosis of ADHD met the threshold for ASD caseness on the SCQ, only 1.36% were listed as having a known co-occurring ASD diagnosis. This suggests that co-occurring ASD in children with ADHD (and vice versa) may be under-identified and highlights the importance of assessing for co-occurring symptomatology in this population. Since the SCQ and SWAN were filled out by caregivers it is also important to consider that rates of ASD and ADHD caseness on the SCQ and SWAN, respectively, may have been overrepresented in our sample.Even though ASD has an earlier age of onset than ADHD, studies have shown that many children with ASD are first diagnosed with having ADHD, subsequently leading to a delay in a diagnosis of ASD , 42. ThiWhen conducting a PCA on combined ASD and ADHD symptom measures in a sample of children with a primary diagnosis of ASD or ADHD, we found no overlap between ASD and ADHD items comprising the components. SCQ items loaded onto two ASD components  and SWAN items loaded onto two ADHD components (inattention and hyperactivity/impulsivity). Therefore, the explanation for the co-occurrence between the two disorders cannot simply be due to an overlap in their core domains. Also, there were low correlations between domains, so it is not a matter of scoring high on all components, which might reflect reporting bias. This suggests that the measurement structure cannot explain the covariation between the two disorders in clinical samples. We cannot assess “true comorbidity” based on the present findings since parent report bias has not been addressed in this study.Our findings are in contrast to the study by Martin et al.  which foInterestingly, our PCA of ASD children  across traditional ASD and ADHD diagnostic boundaries. This notion is also supported by recent neuroimaging studies in children with ASD and ADHD –55. In tWe also found that females had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity domains. This suggests that there may be gender-related phenotypes associated with the two neurodevelopmental disorders. A “female phenotype” of ASD has been proposed in the literature , one aspInterestingly, when looking at factor scores across genders in their combined ASD-ADHD symptom analysis, Martin et al.  did not n = 303) and ADHD (n = 319). The primary clinical diagnoses of all the study participants were also confirmed with valid and reliable measures: the PICS for ADHD [The strengths of our study include the large sample size of participants with ASD . Children with incomplete rating scales had significantly lower IQ and ABAS scores, which likely resulted in a biased sample of participants for our PCA.Finally, we combined two different rating scales with continuous (SWAN) and dichotomous (SCQ) variables in the PCA. It is therefore unclear to what extent our findings might be influenced by items from the same questionnaire grouping together as a result of being in the same measurement scale. It would be interesting to conduct a PCA on ASD and ADHD items from the same questionnaire, such as the child behavior checklist (CBCL); however, such questionnaires are typically based on broad DSM-based criteria and as such do not adequately capture ASD symptomatology.ASD and ADHD items loaded on separate components in our sample, suggesting that the measurement structure cannot explain the covariation between the two disorders in clinical samples. Our results also show that high levels of inattention and hyperactivity/impulsivity are seen in both ASD and ADHD. This supports the need for a dimensional framework that examines neurodevelopmental domains across traditional diagnostic boundaries. Clinically, this emphasizes the importance of careful screening for social communication difficulties and RRBIs in children presenting with high levels of inattention and hyperactivity/impulsivity. Moreover, females had lower component scores across social-communication, RRBI, and hyperactivity/impulsivity than males, suggesting that there may be gender-related phenotypes in the two neurodevelopmental conditions. An increasing amount of literature suggests that females show fewer observable difficulties than males, secondary to their tendency to “camouflage” or compensate for difficulties. This highlights the need for careful screening of ASD symptomatology in females, especially those with ADHD.Additional file 1: Table S1. Comparison of complete versus missing data for ASD study sample. Table S2. Comparison of complete versus missing data for ADHD study sample. Table S3. Pattern matrix of PCA loadings of SCQ and SWAN items in ASD sample. Table S4. Pattern matrix of PCA loadings of SCQ and SWAN items in ADHD sample.


Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. Chiari malformations (CM), first described approximately a hundred years ago, refer to a spectrum of hindbrain malformations characterized by cerebellar herniation through the foramen magnum. We present the case of a 28-year-old woman with ADHD and concurrent Chiari malformation type I (CM-I) that was diagnosed by CT scan. There is growing evidence supporting the role of the cerebellum and its associated structures in the pathophysiology of ADHD. Thus, a cerebellar malformation such as CM may impact neurological circuitry in a manner favoring the development of a neuropsychiatric disorder such as ADHD. Our case highlights the need for further studies pertaining to the role of the cerebellum in the pathophysiology of ADHD and the importance of considering the presence of CM when evaluating a patient with ADHD. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity . ReporteChiari malformations (CM), first described approximately a hundred years ago, refer to a spectrum of hindbrain malformations characterized by cerebellar herniation through the foramen magnum, resulting in compression of the caudal brainstem and upper cervical spinal cord as well as obstruction of normal cerebrospinal fluid (CSF) flow through the fourth ventricle. Possible CM aetiologies include genetic predisposition, congenital anomalies, and acquisition through trauma or illness . Four tyThe case we describe here is one of only three reported individual cases described in the English literature of a co-occurrence of ADHD and CM-I.The patient is a 28-year-old Caucasian college student, who was referred by her primary care practitioner to our outpatient clinic in September 2018 for evaluation and treatment of ADHD.She had been diagnosed with ADHD at age 12 by a pediatrician and a psychologist in the context of poor academic performance, concentration difficulties, attention deficits, distractibility, impulsivity, and lack of organizational skills. At that time, the patient almost failed her first year of high school and began a trial of psychostimulants. By age 28, she had tried several long-acting formulations of methylphenidate as well as a norepinephrine reuptake inhibitor, all of which increased her anxiety in social gatherings and resulted in significant dysphoria. At the time of her consultation, she was not on any medication.She had no pertinent medical or surgical history, except for a concussion at age 15. Her mother had been diagnosed with depression and anxiety and her brother with borderline personality disorder.One month prior to her consultation, the patient experienced a significant concussion accompanied by migraines, nausea, vomiting, and ataxia. An emergency physician prescribed a cerebral CT scan. While the results excluded hemorrhage, ischemia, or space-occupying lesions, they indicated a downward displacement of the cerebellar tonsils compatible with CM type I.At the time of presentation to our clinic, most of her symptoms of concussion had subsided with the exception of dizziness during physical exercise. The patient was mainly preoccupied with symptoms of ADHD, which were evaluated with the clinical interview and the adult ADHD self-report scale (ASRS) . Our conIn the months following her initial evaluation, the patient proved to be extremely sensitive to the side effects of stimulants, limiting the possibility of using the usual therapeutic dose range. She is currently stabilized on 10 mg of lisdexamfetamine dimesylate daily. At this dose, her ASRS score was 51. She notes some improvement in organisation but continues to have significant difficulties with concentration and impulsivity as of July 2019.Our case report of co-occurring ADHD and CM-I is one of only three cases described in the English literature. One other case occurred in a 10-year-old male who exhibited autism spectrum disorder (ASD), ADHD, and CM-I, and the third occurred in a 10-year-old male with a nonsense hemizygous mutation of the TBL1X gene, central congenital hypothyroidism, hearing loss, attention deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), encopresis, and CM-I , 12. TheCM consists of the herniation of the cerebellar tonsils, through the foramen magnum resulting in alteration and compression of postero-inferior cerebellar structures. Cerebellar findings, notably smaller cerebellar volumes, are amongst some of the earliest reported differences noted in ADHD . VariatiA review of the prevalence of psychiatric disorders in a sample of 86 children with a formal diagnosis of CM-I revealed elevated rates of psychiatric diagnoses, including ADHD (22.1%), anxiety (12.8%), and depression (10.5%) when compared to published norms in the general population .Changes in the cerebellum and associated structures have also been linked with ASD, as was highlighted in the case report by Osuagwu and colleagues . Their aFurthermore, structural and functional imaging studies have shown evidence of altered brain volumes in ADHD leading to dysfunction in fronto-subcortical pathways . A recenUnfortunately, the absence of studies examining the association between ADHD and the different types of CM is a significant limitation of the available literature; it would be interesting to explore the relationship of severity of one condition and its correlation with that of the other. Additionally, an examination of the order of onset of cerebllar malformations and ADHD would inform the directionality of a causal relationship between the two conditions.This case report suggests a potential link between CM and ADHD which may itself be, in part, a result of cerebellar dysfunction. Imaging might not be appropriate in every case of ADHD but may be considered when the clinical signs and symptoms of CM are present such as headaches, neck pain, dizziness, and visual disturbances. These observations add to data suggesting that the cerebellum and its associated neural networks may play a role in the pathophysiology of ADHD.


Attention-Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are two of the most frequently-observed neurodevelopmental disorders. Autistic traits are detected frequently in children who have ADHD. This study aimed to examine autism symptoms in children diagnosed with ADHD and their parents; and also, to investigate parental risk factors that increase autistic traits in children. Besides the risk factors related to pregnancy, birth and developmental history were examined.Two groups were created consisting of 66 children diagnosed with ADHD and 33 children not diagnosed with ADHD and their parents. Autism symptoms were screened with the Autism Behavior Checklist (ABC) in children, and Autism Spectrum Quotient (AQ) in parents. Also, Adult ADD/ADHD DSM-IV Based Diagnostic Screening and Rating Scale and Wender Utah Rating Scale (WURS) were used to determine ADHD symptoms in parents.It was determined that there were more autism symptoms in children who were diagnosed with ADHD than in the control group without ADHD. There were more autistic symptoms in boys and the presence of Oppositional Defiant Disorder (ODD). Although there were more ADHD symptoms in the parents of children diagnosed with ADHD, it was determined that they did not differ from parents in the control group in terms of autism symptoms. It was also determined that maternal and paternal ADHD symptoms were predictive for autism symptoms in children. It was also shown that maternal smoking during pregnancy is associated with more autistic traits.ASD and ADHD show high levels of comorbidity. The etiology remains unclear. Both ADHD and ASD show strong hereditary transition. We found that maternal and paternal ADHD symptoms predict autism symptoms in children with ADHD. However, more studies are needed to reveal the etiology. Attention-Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are two of the most frequent neurodevelopmental disorders detected in children . The preThe diagnostic criteria of DSM-IV-TR would not allow the diagnosis of ASD and ADHD together in the same case, which caused that ASD and ADHD were examined separately for some time. Recent studies have revealed that ADHD symptoms accompany autism, and autism symptoms accompany ADHD frequently, and there are clinical, genetic and neuropsychological overlapping points between autism and ADHD . In thisADHD and ASD show a high level of inherited transition. We have very little knowledge of the reasons for the relation between ADHD and ASD. According to the results of studies conducted on genetics for this subject, it is considered that the same genetic areas might be influenced by the autism and ADHD comorbidity . In a twThe results differ in studies that investigate the relation between ADHD subtype and autistic symptoms. In some studies, autistic symptoms were determined to be more frequent in combined type ADHD; in some other studies, no significant differences were detected between ADHD subgroups . AlthougADHD shows a strong familial transition. While the incidence of ADHD being detected in at least one child of the ADHD-diagnosed parents is 50%; the family of a child diagnosed with ADHD being affected by ADHD is 25% . AccordiIn a study that investigated the psychopathologies of families of children diagnosed with ADHD, significant relations were detected between adult-onset psychiatric disorders  and childhood ADHD; however, no relations were detected between childhood-onset psychiatric disorders . The mother’s having ADHD showed a stronger relationship than the father’s having ADHD .The diagnosis of ADHD might delay the diagnosis of ASD. In a study conducted with 1496 children diagnosed with ASD, it was shown that nearly 20% of the cases were diagnosed with ASD after being diagnosed with ADHD. It was determined that those diagnosed with ADHD were diagnosed with ASD after 3 years on average . In anotThe aim of the present study was to examine the autistic traits of children diagnosed with ADHD and their parents, and to determine whether there is a relation between autistic traits in children and autism symptoms in parents. In addition, risk factors increasing autism symptoms related to pregnancy, birth and developmental history were also examined.The present study is a descriptive study in which autistic traits and ADHD symptoms are investigated with appropriate scales in children, adolescents and parents.A total of 66 ADHD patients  and their parents who applied to Trakya University Medical Faculty Child and Adolescent Psychiatry Clinic between November 2017–May 2018 were included in our study as ADHD group; and 33 children  without ADHD diagnosis and their parents were included as the control group. A detailed psychiatric interview was made with all participants by the researcher. The diagnosis of ADHD was made according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5), and ASD was excluded according to DSM 5. Children with a total ABC score of 68 or more have a high probability of being autistic. Therefore, they were excluded from the study. Intellectual functioning was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R). Participants whose total Intelligence Quotient (IQ) score were above 80 were included in the study. Having important medical, neurological and genetic diseases in both groups and having bipolar disorder, psychosis, important medical, neurological and genetic diseases in the parents were determined as exclusion criteria. Since the present study was a family study, the children who were adopted were not included in the study.ADHD group cases met the diagnostic criteria with 34% attention-deficit predominant type ADHD, 12% hyperactivity / impulsivity predominant type ADHD, and 54% combined ADHD. Three cases in girls and 14 cases in males were diagnosed with ODD and one case was diagnosed with Conduct Disorder according to DSM-IV-Based Child and Adolescent Behavior Disorders Screening and Rating Scale.p > 0.05) and gender (p = 0.744). In the ADHD group, the education level of the parents and monthly income were found to be significantly lower than in the control group (p < 0.005) .No problem at birth was detected in the control group. In the ADHD group, 4 cases had asphyxia, 1 case had a traumatic delivery, 1 case had premature rupture of membranes, 1 case had an infection, 20 cases had jaundice, and 1 case had asphyxia and jaundice. When ADHD and control groups were compared in terms of problems at birth, there were significantly more problems in the ADHD group compared to the control group , and 15 items investigating Behavioral Disorders. The scale is filled by the mothers, fathers and teachers of children, who are suspected of having ADHD. Each item is rated between 0 and 3 . For ADHD diagnosis, at least 6 of the 9 items investigating attention-deficit or hyperactivity and impulsivity must be rated as 2 or 3 .This is a family report scale consisting of a total of 57 items and five sub-scales  . It is uThe original English version was developed by Atilla Turgay. It is in the form of a self-report scale to screen attention-deficit, hyperactivity and impulsivity in adults according to DSM-IV diagnostic criteria. It consists of 48 items and 3 subscales rated between 0 and 3. The attention-deficit section consists of 9 items, the hyperactivity/impulsivity section consists of 9 items, and the ADHD-related characteristics section consists of 30 items on the scale. In the attention-deficit or hyperactivity/impulsivity section, it is accepted that there is a low-level attention-deficit or hyperactivity/impulsivity symptom in those who receive scores below 3; there is a moderate-level attention deficit or hyperactivity/impulsivity symptom in those who receive a score between 3.01 and 10.99; and there is a high-level attention deficit or hyperactivity/impulsivity symptom in those who receive scores above 11. Those who receive scores between 0 and 12.99 in the ADHD-related behavior section have a low-level, those who receive scores between 13 and 35 have moderate-level, and those who receive a score between 35 and 75 have high-level characteristics that are stated in the scale. Those who score less than 20 on the entire scale show low ADHD symptoms; those who score between 20 and 59 show moderate ADHD symptoms; and those who score more than 59 show high ADHD symptoms. The Turkish validity and reliability study was conducted by Günay et al. .This scale questions ADHD symptoms in childhood retrospectively, and consists of 25 items and five subscales . It is aIt is a self-report scale of 50 items measuring autistic features in individuals with normal intelligence, and was developed by Baron Cohen. It consists of 5 subscales. Each of the subscales  consists of ten items. The increase in the total score indicates that the autistic symptoms are high. In its Turkish validity and reliability study, the cut-off point was found 26 [p ≤ 0.05.Mean, standard deviation, median, frequency and ratio values were used in descriptive statistics of the data. The Kruskal-Wallis and Mann-Whitney U and Wilcoxon tests were used to analyze the quantitative data. In the analysis of the qualitative independent data, the Chi-square test was used. Spearman correlation analysis was employed for correlation analysis. Statistical Package for the Social Science (SPSS) 22.0 database program was used in the analyses. The statistical level of significance was determined as p > 0.05). It was observed that the ADHD group started later to establish a two-word sentence compared to the control group (p < 0.001).In the ADHD group, time to start sitting was 6.3 ± 1.2 months and in the control group it was 6.3 ± 0.7 months. Time to start walking was 12.3 ± 2.1 months in the ADHD group, and 12.5 ± 1.9 months in the control group. The mean time for saying the first words was 12.33 ± 4.5 months in the ADHD group, and 11.7 ± 4.5 in the control group. The time to start forming two-word sentences was 22.2 ± 4.9 months in the ADHD group and, 17.1 ± 4.6 months in the control group. When the ADHD group and the control group were compared regarding the development history, there was no significant difference between the two groups in terms of sitting, walking and saying the first words. (p = 0.027). In the presence of ODD, ABC scores were determined higher (p = 0.001). There was no significant difference between ADHD subgroups , and ABC sensory, relating, body and object use and language subscale scores and the total score (p > 0.05). Only in the combined ADHD subgroup, the ABC social skills subscale score was significantly higher than attention-deficit predominant and hyperactivity/impulsivity predominant type (p = 0.02).When the ADHD group and the control group were compared in terms of ABC scores, the ADHD group’s all subscale scores and total scores were found significantly higher than those of the control group Table . In the p > 0.05). The ADHD group fathers’ WURS inattentiveness, irritability, depression and behavioral problems/impulsiveness subscale scores and total scores were significantly higher than those of the control group. In the ADHD and control group, fathers’ WURS school problems scores did not differ significantly (p > 0.05). The Adult ADHD scale, attention-deficit, hyperactivity/impulsivity and associated features subscale scores and total scores of the mothers in the ADHD group were found to be statistically higher than the mothers in the control group. In the Adult ADHD scale, attention-deficit, hyperactivity/impulsivity and associated features subscale scores and total scores of the fathers in the ADHD group were found to be significantly higher than the fathers in the control group. The total AQ score of the mothers in the ADHD group was found to be 19.9 ± 4.4, and the total AQ score of the mothers in the control group was 19.9 ± 4.9. While the total AQ score of the fathers in the ADHD group was 20.9 ± 4.7, total AQ score of the control group fathers were 21.1 ± 4.5. No statistically significant difference was determined between the AQ subscales and total scores of the parents in both groups (p > 0.05)  Table .Table 3p > 0.05)  Table .Table 4p = 0.031). There was no relationship between infection, drug use and having an illness in pregnancy and ABC scores (p > 0.05). The mean total ABC score was found to be higher in children who had problems at birth. No correlation was found between low birth weight, prematurity, and total ABC score (Table In both groups, the ABC total score was significantly higher in the children of mothers who smoked during pregnancy than the children of non-smokers (s p > 0.0. The meaIn our study, we used ABC to screen the autism symptoms in children. All subscale and total scores of ABC were higher in the ADHD group. In the ADHD group, the total ABC score was found to be higher in boys than in girls. As a result of our study, it was determined that there are more autism symptoms in children with ADHD. This result is consistent with other studies investigating autism symptoms in children with ADHD , 27, 28.Autism symptoms are seen more in ADHD children accompanied by ODD . In our Specific speech and language problems are common in ASD and ADHD. Delay in speech development, which is one of the defining features of autism, is common in individuals with ADHD . In addiADHD and autism are two neurodevelopmental disorders with a high hereditary transition. Some studies have reported that ADHD and autism pass from mother to child, and some studies have reported they pass from the father. Fewer studies have found no evidence of inheritance from mother or father . A totalIn our study, autistic traits in parents were examined with AQ which is a scale that investigates the broad autism phenotype characteristics. In our study, no significant difference was found between the ADHD and control group parents in terms of autistic traits. In a study conducted with 334 subjects examining adult population autism and ADHD symptoms, a significant correlation was found between ADHD symptoms and autism symptoms. A relationship was determined between attention-deficit and high total ADHD scores and deficits in communication and social skills [As a result of the Spearman correlation analysis, it was found that there was a significant correlation among parental attention-deficit and hyperactivity symptoms and autism symptoms in children. No correlation was determined between the AQ and ABC. According to these results, it is thought that maternal and paternal ADHD symptoms predict the autism symptoms of the child. The finding that ADHD symptoms in parents are associated with autism symptoms in children is consistent with the results of similar studies in the literature. In a study conducted with the families of 121 children diagnosed with autism, or autism and ADHD, autism and ADHD scores of the parents showed a significant correlation. A strong relationship was found between the autism scores of the mother and father and the autism symptoms of the child. It was determined that autism symptoms in parents do not predict the symptoms of ADHD in the child, but the ADHD symptoms in the mother predict autism symptoms in the child [The effect of prenatal and postnatal risk factors on autistic symptoms in ADHD patients was investigated. It was found that autism symptoms are higher in children whose mothers smoke during pregnancy. Researches show that maternal smoking during pregnancy, prenatal exposure to alcohol, young maternal age and maternal stress increase the risk for ADHD in children . In an AThere are some limitations to our study. The low number of sampling is thought to limit the generalizability of the results. Also, there was a gender imbalance between the participants. It is known that clinical applications are more frequent in boys with ADHD, therefore; this may be the reason. The second limitation is that all ADHD cases were under medical treatment. Treatment may have effects on ADHD symptoms and, on autism symptoms, and the severity of symptoms. The third limitation is that the data about the children were obtained from the families, mostly from the mothers. The fourth limitation is that the ADHD and autistic traits in parents were evaluated by self-report scales in our study. Due to the lack of structured psychiatric interviews, it was interpreted whether there was evidence for ADHD and autism. It was not diagnostic. The final limitation is that there were multiple comparisons that made statistical management difficult. There are also some strengths in our study. Our study was a family study involving fathers; however, mostly, only mothers were included since there were difficulties in the participation of fathers in the family studies . Also, fIn summary, it was found in the present study that children with ADHD had more autistic traits than non-ADHD controls. There was a correlation among the autism symptoms in children and parental ADHD symptoms. No significant difference was found between the parents of children with ADHD and parents of the control group in terms of autism symptoms. A relationship was determined between autistic traits in children and maternal smoking during pregnancy and the presence of natal and postnatal problems. It is considered that determining the relation between ADHD and autistic traits will help identify the difficulties that might be experienced in the social and communicative field and organize treatment plans for this condition.


Bartonella species are fastidious Gram negative vector-borne bacteria with a wide range of mammalian reservoirs. While it is understood that some species Bartonella are human pathogens, the extent of human exposure to Bartonella species (both pathogenic and non-pathogenic) has yet to be fully understood. To this end, residual sera from participants enrolled in undifferentiated fever studies in Cambodia, Ghana, Laos, and Peru were screened for the presence of IgG antibodies against B. quintana and B. henselae, using the FOCUS diagnostics Dual Spot- Bartonella IgG Immunofluorescence assay. Forty-eight patients with suspected or confirmed B. bacilliformis exposure or infection in Peru, were screened to assess cross-reactivity of the FOCUS assay for IgG against other Bartonella species. Ten of 13 patients with confirmed B. bacilliformis infection were Bartonella-specific IgG positive and overall, 36/48 of the samples were positive. Additionally, 79/206, 44/200, 101/180, and 57/100 of samples from Peru, Laos, Cambodia, and Ghana, respectively were Bartonella-specific IgG positive. Further, ectoparasites pools from Cambodia, Laos, and Peru were tested using quantitative real-time PCR (qPCR) for the presence of Bartonella DNA. Of the sand-fly pools collected in Peru, 0/196 were qPCR positive; 15/140 flea pools collected in Cambodia were qPCR positive; while 0/105 ticks, 0/22 fleas, and 0/3 louse pools collected in Laos tested positive for Bartonella DNA. Evidence of Bartonella in fleas from Cambodia supports the possibility that humans are exposed to Bartonella through this traditional vector. However, Bartonella species were not found in fleas, ticks, or lice from Laos, or sandflies from Peru. This could account for the lower positive serology among the population in Laos and the strictly localized nature of B. bacillformis infections in Peru. Human exposure to Bartonella species and Bartonella as a human pathogen warrants further investigation. Bartonella species are fastidious, Gram negative, vector-borne bacteria. Classically, three Bartonella species have been identified as causing human bartonellosis, B. bacilliformis, B. quintana, and B. henselae, however a growing number of Bartonella species are being implicated in human disease. The genus grew from just one member with the discovery of B. bacilliformis in 1909, to five members in 1993, when the Bartonella and Rochalimaea genera were united as well as a chronic condition (verruga peruana). B. quinpectively. More reven death.Bartonella species as human pathogens, the true extent of human exposure and disease associated with this genus is not fully understood per manufacturer’s instructions. Positive and negative controls were included on each slide. Samples were screened at a 1:64 dilution and a positive result was recorded if a 1+ apple green fluorescence was observed for the Bartonella quintana and/or Bartonella henselae antigens. Slides were reviewed by at least two researchers and samples were considered positive only if both researchers agreed.Human sera from undifferentiated fever studies conducted in Cambodia, Ghana, Laos, and Peru were tested for the presence of IgG antibodies targeting B. henselae and B. quintana, however, those individuals infected with B. quintana and B. henselae show high IgG cross-reactivity on testing and there is well documented, albeit variable, cross-reactivity in patients infected with numerous other Bartonella species, aiding in the diagnosis of Bartonellosis in these patients. . Samples were storred at - 700C until use.One-hundred and ninety-nine serum samples were collected by the Microbiology Laboratory/Lao-Oxford-Mahosot Hospital-Wellcome Trust Research Unit in July and August of 2014 after written consent from inpatients undergoing investigation for the etiology of fever at Mahosot Hospital in Vientiane Capital of Laos. SamplesB. bacilliformis in Huancambamba Province. Samples were collected from patients with suspected B. bacilliforms infections. Thirteen of the suspected cases were confirmed by PCR, culture, and/or identification of B. bacilliforms in blood smears. Samples were screened to assess the extent of the exposure to B. bacilliformis and to assess the ability of the assay to detect anti-B. bacilliformis IgG antibodies. Further, 206 serum samples collected between 2008 and 2015 from individuals with undifferentiated fever in the Amazonas, Junín, Cusco, and Loreto Regions of Peru were screened for the presence of IgG antibodies to Bartonella species were collected from November of 2015 through January of 2016 using combing/brushing technique from dogs, cats, rats and mice found in Rantanakiri and Stung Treng Provinces. Of those 14 pools of location  . Fleas C. felis fleas or Heterodoxus spiniger lice, while 210 Rhipacephalus sanguineus ticks were pooled. DNA was extracted and stored as described in In Laos, fleas, ticks and lice were collected in March of 2018 from dogs in Vientiane City and pooled based on species and host, resulting in 22 flea pools, 106 tick pools, and 3 louse pools. Flea and louse pools contained 2-20 individual 0C until DNA was extracted. DNA were extracted using DNeasy blood and tissue kit  following a protocol modified from the manufacturer’s instructions  Excel. Minimum infection rate (MIR) was caculated: .This study was approved by the Naval Medical Research Center Institutional Review Board in compliance with all applicable federal regulations governing the protection of human studies .For Ghana, the protocol was also approved by the Noguchi Memorial Institute for Medical Research (NMIMR) IRBFor Laos, ethical approval was granted by the National Ethics Committee for Health Research (Lao PDR) and the Oxford Tropical Research Ethics Committee (UK).Bartonella species were detected in febrile patients admitted to Mahosot Hospital with homes in Borikhamxay (3/11), Champassack (1/1), Luangnamtha (2/3), Luangphrabang (1/6), Oudomxay (1/2), Vientiane Capital (25/135), Vientiane Province (9/32), Xaiyabuly (1/2), and Xiengkhuang (1/4) provinces, but not in Attapeu, Huaphan, and Sekong Provinces where only one sample was tested from each. The overall sero-positive rate in Peru was slightly higher with 38% of samples collected from patients with undifferentiated fevers from the Amazonas (2/3), Junin (29/69), Cusco (24/66), and Loreto (24/68) regions of Peru positive for IgG antibodies against Bartonella species. Of the 180 serum samples from febrile patients tested in Cambodia 56% (101) were positive including samples from Kampong Speu (26/42), Kandal (12/22), Kratie (11/15), Rattankiri (3/13), Stung Treng (3/7), and Svay Rieng (46/81) provinces. While in Ghana, 57% of the samples were positive for IgG antibodies wherein (2/3) and (55/96) of samples from febrile patients from the Eastern and Greater Accra region were positive, respectively, while the single sample from the Ashanti region was negative.  for those without antibodies aganist Bartonella species.  serum samples from patients with confirmed B. bacilliformis infection were positive for IgG antibodies to Bartonella species. Interestingly, 75% (36/48) of individuals with suspected B. bacilliformis infection were positive for IgG antibodies to Bartonella species.Separately, serum samples from patients with confirmed or suspected Bartonella species DNA included C. felis, P. irritans, and X. cheopis. Pools from ticks (0/106), fleas (0/22), and lice (0/3) collected from dogs in Vientiane Capital of Laos were all negative for Bartonella species DNA. Further, none of the 196 pools of sandflies collected in Ancash and Cajamarca regions of Peru were positive for Bartonella species DNA. . Surprisingly, no flea pools collected from cats in the same provinces were positive. Flea species positive for Bartonella species are increasingly common and recent studies have highlighted the widespread nature of Bartonella species (both human pathogens and non-human pathogens) infecting vectors such as fleas, ticks, lice and small mammal reservoir hosts worldwide  in Cambodia.orldwide . The molom 7-10% . Our datBartonella species DNA. Previous studies in Laos found evidence of Bartonella species in fleas (including fleas collected from dogs) with positivity rates ranging from 3.3- 33%, but these studies were outside of Vientiane Capital and there is evidence that levels of infection in rodents are significantly lower in human settlements, or infection with,  in Spain. In thisrtonella . In this in 2014 . Higher Bartonella species in Peru is unique as the Bartonella species of major importance, B. bacilliformis, which causes both acute and chronic infections, is found only in the Andes Mountain range, and thought to be vectored by sandflies of these individuals at the 1:64 screening dilution. Not only does this indicate high infection rates, but that the FOCUS test has high cross-reactivity to Bartonella species indicating positivity on a FOCUS test would not be limited to B. quintana or B. henselae infections. Examination of the serologic evidence from a larger subset of individuals, those suspected of B. bacilliformis infection during the 2003 outbreak, shows widespread exposure to Bartonella (likely B. bacilliformis), with 75% of individuals seropositive, while B. bacilliformis was only identified by smear, PCR or culture for 27% of individuals. This indicates that smear, PCR, and culture may currently miss a large portion of infected individuals, or that many of these individuals had prior exposure, but not active infection. Given the cross-reactivity observed among known Bartonella species in serological assays, including the FOCUS IFA used in this study, the study participants may have been exposed to Bartonella species that have yet to identified or characterized, or even those that do not cause illness in humans.Finally, exposure to sandflies. Since tBartonella species in humans, animals, and vectors in countries such as those included in this study, but also in countries and regions where knowledge of these agents is lacking.This highlights the need for more in depth investigations into the Bartonella species DNA was not identified in any sandfly pools from the endemic areas of Ancash and Cajamarca. Interestingly, all previous studies have found low levels of B. bacilliformis infection of sandflies ranging from 0.5-2.8 %(L. verrucarum is considered a known vector of B. Bacilliformis, other sandfly species have been implicated as possible vectors including L. maranosesis and L. robusta, both of which were included in this study, however the mechanisms by which B. bacilliformis is transmitted by sandflies is still lacking (Bartonella species in sandflies from endemic areas provides more insight into the epidemic nature of B. bacilliformis, and possibly B. ancashensis, for which a vector has yet to be identified (B. bacilliformis could be driven by asymptomatic carriers and immediate transmission between persons via sandflies. Studies have shown that outbreaks occur within families and members of a household are 2.6 times more likely to contract B. bacilliformis than neighbors (B. bacilliformis is known to occur, with up to 40% of individuals in a post-exposure setting positive by qPCR (B. bacilliformis in individuals with undifferentiated fever endemic areas is consistent with previous studies of post-exposure or endemic asymptomatic populations which found seropositivity rates between 19-67% (B. bacilliformis, as seen during the outbreak, as well as other Bartonella species including those which are not known to be human pathogens. Nevertheless, this data combined with previous reports indicates exposure to Bartonella in Peru is of continuing importance.Further, 0.5-2.8 %. While L lacking . The absentified . Outbreaeighbors . Additio by qPCR . The sern 19-67% . Our datBartonella species is extensive and that Bartonella species may be the cause of undifferentiated fever in a subset of the individuals from these studies. These data taken along with previous work indicate that Bartonella species are likely an under-represented as cause of human disease around the world.This study combined with previous data indicates that human exposure to


Attention deficit hyperactivity disorder (ADHD) shows high heritability in formal genetic studies. In our review article, we provide an overview on common and rare genetic risk variants for ADHD and their link to clinical practice.The formal heritability of ADHD is about 80% and therefore higher than most other psychiatric diseases. However, recent studies estimate the proportion of heritability based on singlenucleotide variants (SNPs) at 22%. It is a matter of debate which genetic mechanisms explain this huge difference. While frequent variants in first mega-analyses of genome-wideassociation study data containing several thousand patients give the first genome-wide results, explaining only little variance, the methodologically more difficult analyses of rare variants are still in their infancy. Some rare genetic syndromes show higher prevalence for ADHD indicating a potential role for a small number of patients. In contrast, polygenic risk scores (PRS) could potentially be applied to every patient. We give an overview how PRS explain different behavioral phenotypes in ADHD and how they could be used for diagnosis and therapy prediction.Knowledge about a patient’s genetic makeup is not yet mandatory for ADHD therapy or diagnosis. PRS however have been introduced successfully in other areas of clinical medicine, and their application in psychiatry will begin within the next years. In order to ensure competent advice for patients, knowledge of the current state of research is useful forpsychiatrists. Attention deficit hyperactivity disorder (ADHD) is a developmental disorder with symptoms of inattentiveness, impulsiveness, and hyperactivity, which leads to impairments in everyday life and manifests before the age of 12. The developmental trajectory shows a typical course of clinical symptoms, e.g., decrease of hyperactivity, occurrence of comorbid disorders, e.g., addiction and depression, as well as economic costs and social impairments . The extEarly on, clinicians noticed that ADHD-typical behavior occurs frequently in syndromic disorders, e.g., Klinefelter syndrome, Williams syndrome, fragile X syndrome, or tuberous sclerosis . The higThere are several ways to investigate the heritability of ADHD. A classical strategy makes use of twin studies, due to the possibility of assessing the genetic effect (heritability) of the disorder. According to a recent meta-analysis of twin studies, the heritability of ADHD is estimated at 77–88% .2 snp = 22%) in a range comparable to previous estimates of h2 snp for ADHD in studies with fewer subjects  [By means of genome-wide complex trait analysis (GCTA), thousands of individuals are examined for hundreds of thousands of single-nucleotide polymorphisms (SNPs) and thus provide a measure of heritability, the so-called SNP-based heritability. A recent mega-analysis estimates SNP-based heritability h 10–28%) . The pro–28% . Th 10–28%)  which inIn addition to the relationship between the number of subjects and the allele frequency of the SNPs, other DNA variants, such as copy number variations (CNV), may explain the missing heritability. CNVs are sections of DNA that either occur in multiple copies or deletions of certain chromosomal sections. CNVs occur at different frequencies but are quite common in patients with ADHD. Small CNVs of only a few kilobases are not detected with the necessary accuracy by GWAS, yet make up the considerably larger part of the genetic variability in ADHD. Large CNVs (> 500 kb) with a frequency of less than 1% can only be detected using sufficiently large sample sizes. In order to be able to map all possible CNVs, whole-genome sequencing (WGS) would be the method of choice.p ≤ 5 × 10−8) by significantly increasing the number of cases and control numbers .Until the late 2000s, candidate gene studies on small samples were the method of choice for testing genetic associations. Genes coding for components of the monoamine transmitter systems was first investigated in ADHD. However, none of the candidate genes was replicated by larger genome-wide studies. A summary of these studies can be found in authoritative reviews , 12, 13.GFOD1) and cadherin 13 (CHD13) [GFOD1 is expressed in the frontal cortex; the exact function of the gene is not yet known [CDH13 encodes for a calcium-dependent cell-cell adhesion protein that influences neuronal development and synaptic plasticity [Cdh13, mice showed hyperlocomotion and learning deficits [CHD13 is associated with, e.g., autism, schizophrenia, bipolar disorder, and depression [CDH13 an interesting candidate gene for ADHD.A study of 909 parent-child trios with ADHD-affected children revealed strong genetic associations of the genes glucose-fructose oxidoreductase domain-containing 1 ( (CHD13) –17 with et known . CDH13 easticity . In a kndeficits . These fpression , make CDn = 2627 ADHD subjects, n = 2531 controls) is adhesion-G protein-coupled-receptor-L3 , a brain-specific G protein-coupled receptor with cell adhesion function [ADGRL3 was confirmed as an ADHD candidate locus in two other independent case-control studies, by association of one haplotype in ADGRL3 [adgrl3 leads to a reduction of dopaminergic neurons in the ventral diencephalon and a hyperactive/impulsive phenotype [Adgrl3-knockout mice, an increase in reward motivation and activity level as well as other ADHD-analogous behaviors was observed—parallel to dysregulation of the dopamine transporter [Another ADHD candidate gene found in a large family by linkage analysis and replicated in parallel in a global case-control study  could be identified [DUSP6 regulates the synaptic transmitter dopamine, while MEF2C is primarily associated with autism and intelligence impairment [r = 0.64) of ADHD and bipolar disorder [In the most recent and comprehensive meta-analysis of ADHD GWAS data sets to date , 12 genomic loci with genome-wide significance (entified •. The 12disorder .r = 0.81) between early childhood and adult ADHD arguing that these are indeed covering the same clinical phenotype. An additional meta-analysis of ADHD over the entire life span in children and adults revealed nine genes significantly associated with ADHD over the life span. This underscores how GWAS can contribute to clinical questions about differences between childhood and adult manifestations of ADHD.A recent meta-analysis in more than 17,000 cases showed a high overlap in genetic correlation between children and adults as well as continuous measures as well as categorical ADHD definition . There, The association of genetic syndromes with ADHD in childhood has been known for a while. Chromosomal aberrations have been frequently found in ADHD and other developmental disorders .FMR1 gene, which encodes the RNA-binding protein, called fragile X mental retardation protein (FMRP). Exaggerated glutamatergic excitation and reduced GABA-signaling have been discussed as main mechanisms for FXS.Fragile X syndrome (FXS) is one of the most frequent genetic syndromes associated with ADHD. Based on parent or teacher reports, 59% of boys with FXS meet diagnostic behavioral criteria for either ADHD-inattentive type only (31.5%), ADHD-hyperactive type only (7.4%), or ADHD-combined type (14.8%) [NF1) is characterized by different tumors in the eyes, the skin, and the central nervous system. The NF1 locus is situated on chromosome 17q11.2. About one third is accompanied by ADHD symptoms during childhood [NF1 might stem from lesions in the basal ganglia.Neurofibromin 1 (hildhood . The neuTuberous sclerosis complex (TSC) is an autosomal dominant hereditary disorder associated with brain malformations and tumors, skin lesions, and mostly benign tumors in other organ systems, often clinically characterized by epileptic seizures and cognitive impairment. ADHD prevalence in TSC patients has been ranging from about 30 to 60% •.The sexual aneuploidies Turner syndrome and Klinefelter syndrome have been associated with ADHD as well. In patients suffering from Klinefelter syndrome, the rate of ADHD is as high as 63% . In our Limk1 leads to hyperactivity and impaired spatial learning in knockout mice.Williams-Beuren syndrome (WBS) is a microdeletion on chromosome 7 and is associated with a typical set of symptoms ranging from special facial features (“elf-like”) to pulmonal and cardiovascular anomalies. On a behavioral level, they are characterized as being “hypersocial.” Almost two thirds of WBS show symptoms of ADHD . The delCOMT gene which is a bottleneck for the catecholamine neurotransmission.Velo-cardio-facial/DiGeorge syndrome (22q11 deletion syndrome) is associated with cardiovascular abnormalities and a variety of psychiatric disorders . PreviouWhile these syndromes are rare, they should be known to the adult psychiatrist because most patients come into contact with the medical system due to the complex comorbidities, e.g., heart disorder in 22q11. However, there are no studies looking at the behavioral trajectory of these genetic syndromes and associated ADHD in adults. Nevertheless, recent polygenic risk analyses suggest that a significant part of the heredity of ADHD is caused by rare variants . Rare vaA study in more than 2800 children with ADHD found an accumulation of large and rare CNVs in the 15q13.3 locus. Although still rare, the frequency of 0.6% results in a relatively high effect size with an odds ratio of 2.2, which is significantly higher than any single locus in ADHD-GWAS .Initial studies examining CNVs in ADHD case samples focused on children but not on adults. However, due to the small sample size and evolving methodology, the results are inconsistent. A British and an Icelandic study of children found a disproportionately high level of rare, large CNVs in ADHD patients compared to healthy controls , 39. DupFurther genome-wide studies on ADHD in childhood investigated the overall burden of rare, large CNVs in patients compared to healthy subjects. They provide some evidence of an accumulation of rare variants in childhood ADHD –42. NeveNPY) had been deleted in a ∼ 3 Mb duplication on chromosome 7p15.2–15.3. Interestingly, this was associated with an increased NPY plasma concentration in affected family members [In a genome-wide screening for CNVs in a cohort of 99 children and adolescents with severe ADHD, seven syndrome-associated CNVs were identified. The gene coding for neuropeptide Y  deletions in ten cases and one control, GRM7 deletions in six cases, and GRM8 deletions in eight cases and no controls.In a larger whole-genome CNV study with 1013 cases of ADHD and 4105 healthy children of European descent, CNVs affecting metabotropic glutamate receptor genes were enriched across all cohorts . The stun = 70), where rare variants in the regions inherited by affected members were tested in a large (n > 9000) independent cases and controls sample. This led to the identification of AAED1, which interacts with the protein kinase C-alpha-binding protein (PICK1). PICK1 is a regulator of dopamine transporter trafficking dopaminergic neurons.An innovative approach was used in a linkage analysis of three German ADHD families , also seems to have a large share in the unexplained genetic variability of ADHD. A recent study with 123 ADHD patients and 82 healthy controls by means of complete exome sequencing shows that within the group of ADHD patients, a strongly increased number of amino acid altering SNVs with rare allelic frequency (< 0.1%) are observed . AnotherShould the knowledge about these rare variants lead to clinical sequencing tests in ADHD patients? So far, this cannot be recommended as these variants still seem to be rare, and complete genome sequencing is expensive. However it can be considered in patients with comorbid intellectual disability.A polygenic risk score (PRS) uses the summary statistics of SNP results from large GWAS to predict clinically significant variables. The idea of the PRS is to provide genetic risk prediction, given the large set of SNPs for each individual, and use it as a predictive tool for a specific trait •. An indPRS provide interesting insights into the dimensional structure of ADHD: A PRS of ADHD risk variants is correlated with attention deficits in the general population  supportiApart from these more theoretical insights, PRS can be applied to more clinical questions: ADHD comes with a high burden of comorbid disorders which can be studied in large epidemiological samples like the UK Biobank sample. In more than 135,000 participants, an ADHD PRS was highly linked to depression, anxiety, alcohol intake, risk-taking, and negatively to verbal-numerical reasoning. While this gives general insight into the genetic structure of these traits, it should be kept in mind that ADHD and other disorders are probably underdiagnosed in this large sample •.ADHD in childhood, but in some parts in adulthood, too, is tightly linked to school achievement. In studies looking at the link between ADHD PRS and educational achievement or even intelligence, it is clear that PRS predicts educational achievement •. InterePRS can even contribute to the highly debated question, what defines a “persister” versus a remitter (from childhood ADHD) in patients? A recent population-based cohort correlated an ADHD PRS to ADHD symptom trajectories between ages 4 and 17 . The ADHStudies using a PRS from other psychiatric disorders, e.g., a schizophrenia risk PRS, predicted ADHD and oppositional defiant disorder in a large sample of children (ALSPAC) . PRS scoAnother study investigated the relationships of PRS of psychiatric disorders and substance (ab-)use. Using PRS for cross-disorder psychopathology (CROSS) from 2573 European-American participants and information on liability to alcohol, cannabis, cocaine, nicotine, and opioids, the authors identified negative association with cannabis and positive association with nicotine use for ADHD that did not survive after correction for multiple testing; however, in the other psychiatric disorders, statistically relevant patterns between substance and disorder-specific PRS could be identified . These sIn a study which looked at socioeconomic variables like employment, individual income, and household wealth, an ADHD PRS was associated with more negative outcomes in these variables and increased the likelihood of receiving social security disability benefits, unemployment or worker compensation .However, application of PRS in clinical practice comes with some drawbacks, e.g., most GWAS concentrate on populations of European ancestry. The application in other areas of clinical medicine led to severe problems in interpretation of results •.While these applications of PRS for understanding ADHD are exciting, it should be kept in mind that PRS typically explain only about 5.5% in variance •. In an The findings of recent years indicate that there is a specific genetic basis for ADHD in children and adults that not only increases the risk of the disorder but also the risk of other independent psychiatric diagnoses and socially relevant measures such as school and learning outcomes •. How caA general finding from the last 20 years of ADHD psychiatric genetics is that risk genes involved in the regulation of catecholaminergic genes have not been reliably replicated. Genetic findings show that ADHD is more than a simple “catecholaminergic disorder.” The genome-wide loci affected by ADHD often have a general function in areas such as “neurite outgrowth,” “synaptic plasticity,” or “glutamatergic signal transmission” •, 62, 63Another field that could see an earlier clinical application of genetics is the prediction of pharmacotherapy, the so-called pharmacogenomics. Initial studies on pharmacogenomics in ADHD looked at common candidate genes such as the dopamine transporter . Since tThe application of genomic methods for differential or primary diagnosis of psychiatric disorders does not play a role in clinical medicine so far. Since the explained variance is still too low, other factors for therapy prediction and diagnosis will play a greater role in individual cases. At present, patient treatment does not focus on genetic testing but on an exact clinical diagnosis. Nevertheless, in the future, psychiatrists will have to deal with the fact that some of their patients are diagnosed with a rare variant (SNV or CNV). Currently, it can be stated that beyond already defined genetic syndromes , there is no proven rare variant that determines or predicts ADHD.PRS are not yet helpful in differential diagnosis either; however, it is to be expected that this will change in the upcoming years. For example, the PRS for breast cancer has been combined with conventional risk factors to identify 16% of the population who may benefit from an earlier screening (and 32% who may delay screening) . In coroIn general, the genetic disposition plays a major role in the pathogenesis of ADHD. On the one hand, knowledge and public discussion about this can counteract stigmatization of patients. Genetic causes are now accepted by many affected patients and their relatives as an explanatory model , 71. An


Background: Despite the stability of global vaccination coverage, over 19 million children worldwide do not currently receive basic vaccines. Over the past several years, there has been a dramatic drop in the number of vaccinated children worldwide. The implementation of the vaccination program and the scope of protection depend on the parents or legal guardians, who decide whether to vaccinate their child or not. Studies were conducted to assess parents’ knowledge, attitudes, and beliefs about vaccines, as well as the role of healthcare providers in parents’ decisions. Methods: A population survey was conducted in 2018–2019. Parents or legal guardians of the children were invited to participate in the study during their visits to the clinic for healthy or sick children. The method used in the research was a diagnostic survey. Results: According to the conducted research, men and women constituted 45% and 55% of participants, respectively. The average age of men was 44, while, for women, it was 41. Internal research showed that as much as 71% of parents declared the need for vaccination, although 41% of parents vaccinated their children according to the vaccination calendar. The most frequently mentioned concerns included the possibility of adverse vaccination reactions (22%), the occurrence of autism (7%), and child death (6%). General practitioners had, by far, the greatest impact on the use of protective vaccination in children (73% women and 80% men), although there were cases of discouraging the performance of compulsory vaccinations (41%), and mentioning a doctor (38%) or nurse (3%). Conclusions: Modifiable determinants of the negative attitude toward vaccinations are caused mainly by the lack of knowledge. These obstacles in vaccinations can be overcome by improving health education in terms of the vaccination program. The course of infectious diseases is not always mild, and there is always a risk of serious complications and even death, particularly in younger children. Therefore, the development of preventive vaccinations is considered as one of the greatest achievements of modern medicine. Vaccinations are currently the most effective method of preventing infectious diseases, reducing morbidity and the number of complications and deaths, and allowing complete elimination of the disease. According to the World Health Organization, vaccinations prevent 2–3 million deaths worldwide annually ,2,3. ProThe study aimed to assess parents’ knowledge, opinions, views, and attitudes about preventive vaccinations, as well as to analyze how healthcare providers impacted the parents’ decision-making.A population survey was conducted in the Podkarpackie Voivodeship in the Clinical Voivodeship Hospital in Rzeszow, the Healthcare Centre in Jarosław, and Primary Care facilities in Przemysl, Jarosław, and Rzeszow districts in 2018–2019. The main indicator of participation in the study was the age of children, which was between 10 and 14 years, since the majority of compulsory vaccinations were already carried out according to the current vaccination calendar. The Preventive Vaccination Programme (PSO) is the main source of recent information regarding vaccinations in Poland, and it is published annually by the Chief Sanitary Inspector. The Ministry of Health in Poland aims at the implementation of the compulsory vaccination scheme among children using free vaccines funded by the government budget using non–reimbursed combination vaccines and recommended vaccinations against certain infectious diseases included in services paid by caretakers. Doctors and hospital personnel are obligated to provide parents with detailed information regarding compulsory and accessible methods of immunoprophylaxis for their children. The current PSO includes following compulsory vaccines: Tuberculosis , diphtheria, pertussis, tetanus , measles, rubella, mumps , poliomyelitis , hepatitis B , and infections caused by Haemophilus influenzae B , as well as vaccinations against pneumococcal infections . The prevention is complemented by following recommended payable vaccines: Meningococcal infections, chickenpox, rotaviruses, hepatitis A, meningitis, influenza, and human papilloma virus. Parents or legal guardians of the children were invited to participate in the study during their visits to the clinic for healthy or sick children. Each invited person was informed about the purpose of the study. The respondents were given the opportunity to complete an online survey or its paper version.The study covered 2300 people residing in the Podkarpackie Voivodeship, 1265 women (55%) and 1035 men (45%). Most of the respondents lived in the city (68%), the remaining persons were rural residents (32%).The method used in the research was a diagnostic survey, and the technique used was surveying. The research tool was a survey questionnaire. The main part of the questionnaire included questions about parents’ knowledge of current vaccination schedules, vaccine side effects, the presence of contraindications for vaccination, the vaccination qualification procedure, and vaccination safety, as well as preferred sources of information and the role of healthcare professionals in providing information on vaccination and in deciding whether or not a child should be vaccinated. The questionnaire was verified by testing a group of 100 parents in Poland within a month.The study was approved by the WMU Bioethics Committee (KB 386/2009). Participation in this study was voluntary and anonymous, and respondents were informed of their right to refuse or withdraw from the study at any time. Every respondent was informed of the purpose of the study and the time of completion of the study.t-test or Mann–Whitney U test. A correlation was determined using Pearson’s test, while χ2 was used for comparison between groups. Significance was assessed at p < 0.05. The chi-square test was used to assess the diversity of opinions on vaccination safety in groups. The repeatability of responses to individual questions was assessed using Kappa Cohen statistics. Missing data were excluded from all analyses.All data obtained were collected and analyzed using Prism 4.0. Descriptive statistics were used to determine the percentages and 95% confidence interval (CI). Statistical characteristics of continuous variables were presented in the form of arithmetic means, standard deviations, and medians. Statistical characteristics of step and qualitative variables were presented in the form of numerical and percentage distributions using the Student’s p < 0.0001) and the level of education (p < 0.0001). Other descriptive statistics are included in According to the conducted research, women constituted 55% of participants (95% CI: 51–59), and men constituted 45% (95% CI: 42–51). The average age of men was 44, while for women, it was 41. Almost half of the surveyed women declared secondary education , vocational education, , or higher education . Also, in the case of men, secondary education predominated . Vocational education was declared by 37% of respondents (95% CI: 31–41), and higher education was declared by 20% (95% CI: 16–26). Vaccinations carried out negatively correlated with both the age of parents (p = 0.03).During the assessment of parents’ personal opinions about vaccinations, 71% (95% CI: 69–73) responded favorably, declaring the need to perform them, 18% (95% CI: 13–23) responded indifferently, and 11% (95% CI: 8–18) were against vaccinations. As many as 91% (95% CI: 88–92) of the respondents believed that vaccinations have a significant impact on the child’s health, including as many as 35% (95% CI: 23–37) who believed it is not a positive impact. More than half of the respondents believed that the State should not impose the obligation to vaccinate children  while, 44% of women and 41% of men (95% CI: 41–48) claimed that vaccinations should be voluntary, and 3% of women and 8% of men (95% CI: 1–19) had no opinion on this subject. A general practitioner had the greatest impact on a parent’s decision to vaccinate, with 73% of women and 80% of men (95% CI: 71–82) following their advice, 44% women and 41% of men claiming that vaccinations should be voluntary, and 3% of women and 8% of men having no opinion on the subject. Other parents declared completely independent decision–making . According to parents, their independent decision was mostly influenced by research , their own feelings and beliefs , friends and family experiences , their own experience , or possible side effects . As many as 41% (95% CI: 39–48) of parents admitted that they had encountered the situation of discouraging the performance of compulsory vaccinations, mentioning a doctor , friends and family , parents of children with vaccine adverse event , or a nurse . During the assessment of parents’ concerns about vaccinations, more than half  expressed concern about the allegedly harmful effects of vaccinations on their children’s health, and in particular, of adverse vaccination reactions , autism , and child death . According to the results of simple analysis, the level of confidence in vaccination safety was associated in a statistically significant way with a negative assessment of the occurrence of vaccination complications. Educated people perceived vaccinations as less safe than those with lower levels of education (p = 0.05).During the analysis of the vaccination system in the study group, it was found that 41% of parents (95% CI: 37–46) vaccinated their children according to the calendar, 41% (95% CI: 37–46) bought combination vaccines to reduce the number of pricks, and 18% (95% CI: 13–25) did not vaccinate their children at all. As many as 40% (95% CI: 39–44) of parents admitted that they refused specific vaccinations . During p = 0.05).During the analysis of the use of optional vaccines, it was found that only 28% (95% CI: 19–31) of surveyed parents confirmed the use of optional vaccines. The decision to buy the recommended vaccines was motivated by the fear of falling ill and complications after the disease , advertisements , or doctor’s recommendation . When buying a vaccine for their child, 74% of parents (95% CI: 71–79) took into account the price of the vaccine, 65% (95% CI: 63–72) took into account knowledge about the vaccine, and 58% (95% CI: 54–62) took into account several punctures at one visit and doctor’s recommendations . The most frequently mentioned optional vaccines given to children were the pneumococcal , rotavirus , meningococcal , and influenza  vaccines. The reason for not purchasing recommended vaccines were financial situation , fear of side effects , poor information , and doubts about the actual effectiveness of these vaccines . According to the results of simple analysis, the frequency of nonobligatory vaccinations for motivation was statistically significantly associated with a negative assessment of vaccination costs. People who considered vaccinations expensive were less likely to vaccinate their children with the recommended vaccine , staff courtesy by 81% (95% CI: 78–84), aesthetics of the rooms by 86% (95% CI: 79–89), office equipment with children’s accessories by 85% (95% CI: 80–88), interest in the child by 85% (95% CI: 80–88), efficiency of performing medical examination by 75% (95% CI: 70–80), efficiency of performing vaccination by 83% (95% CI: 80–88), and competence in providing information on vaccinations and possible complications by 75% (95% CI: 70–80). For the degree of satisfaction with the information received from the doctor about the vaccination schedule and vaccination effectiveness, the results were as follows: 36% of parents (95% CI: 26–41) were very satisfied, 46% were satisfied (95% CI: 42–50), and 18% were dissatisfied (95% CI: 10–22).The parents’ knowledge of preventive vaccinations was subsequently analyzed. The vast majority of surveyed parents  declared good knowledge of immunization issues, partial knowledge was declared by 22% of women and 34% of men (95% CI: 19–41), and 2% of women and 10% of men (95% CI: 1–16) did not have knowledge about preventive vaccinations. The information was provided mainly by doctors  .The study showed that 95% of women and 89% of men (95% CI: 84–98) considered vaccines as supplements that stimulate the immune system to raise immunity . Of the mild reactions that are likely to occur after vaccination, the most often mentioned were fever , redness , and edema  .As a contraindication for vaccination, the respondents mentioned the child taking an antibiotic , fever , and allergic reaction after previous vaccine . Vaccination qualification should be carried out by the doctor according to 97% of respondents (95% CI: 94–99), while 3% (95% CI: 1–4) believed that it should be done by parents. Most parents  claimed that unwanted vaccination reactions do not always occur in every child, and that this is an abnormal reaction of the body after vaccination. The most commonly reported symptoms of vaccine adverse event were respiratory symptoms , autism , and convulsions  .Of the participants, 74% of women and 61% of men (95% CI: 59–79) had heard of combination vaccines. According to them, combination vaccines are new generation vaccines , vaccines that reduce the number of punctures , vaccines immunizing against several infectious diseases simultaneously , and safer than traditional vaccines . In the studied group, there was a very strong positive linear relationship between the source of knowledge and knowing about preventive vaccinations (+0.993), meaning that people acquiring knowledge directly and from reliable sources, i.e., from medical personnel, presented a higher level of knowledge.The study attempted to analyze the occurrence of vaccine adverse events in the children of the respondents. According to 78% (95% CI: 75–81) of respondents, adverse vaccination reactions occurred. As many as 37% (95% CI: 35–39) did not remember the duration of the adverse vaccination reaction. In 8%, the vaccination reaction lasted 24 h; according to 12% (95% CI: 9–14), it could be observed for 3 days; according to 10% (95% CI: 7–11), it occurred for 7 days; 15% (95% CI: 14–17) replied that the symptoms lasted a few weeks; and 19% (95% CI: 15–20) reported that symptoms lasted a few years. The symptoms mentioned by parents were high fever , neurological disorders , autism , convulsions , and developmental disorder .Journal of the Ministry of Health, providing detailed instructions regarding particular vaccinations, the current epidemiological situation, and WHO recommendations. The Programme is published before 31st October in the year preceding the year of the Programme’s implementation. The scheme of obligatory and recommended vaccinations is implemented according to the Programme. The costs of vaccines and performing vaccinations are covered by the part of the government budget controlled by the Minister of Health. The obligatory preventive vaccinations of insured citizens are performed by the healthcare providers that have signed the contract with the National Health Fund. The costs of obligatory preventive vaccinations for uninsured citizens are fully covered by the government budget. Recommended vaccinations are voluntary and performed using fully payable vaccines recommended by the Chief Sanitary Inspector. Due to performing preventive vaccination, the hospital personnel are required to fulfill various law obligations. The performance of the obligatory preventive vaccination needs to be preceded with a medical examination in order to eliminate contraindications for the vaccination. The vaccination cannot be performed more than 24 h after the medical examination date indicated on the certificate. Obligatory vaccinations are performed by doctors, nurses, and midwives. Their duties include informing the patient or their legal guardian of the obligatory vaccination, as well as informing about recommended vaccinations. Moreover, the doctor who suspects or recognizes the occurrence of the adverse effect is obliged to report such event within 24 h to the District Sanitary Inspector [The introduction of common preventive vaccinations remains one of the greatest achievements in public healthcare history. Routine vaccinations during childhood are crucial for the health of individual people, as well as populational health. In Poland, preventive vaccinations are required by law. People temporarily present in Poland are also required, according to the law, to receive compulsory preventive vaccines included in the National Preventive Vaccination Programme. In case a person is not fully able to take legal action, their legal guardian is required to fulfill the obligation. The Chief Sanitary Inspector announces the Preventive Vaccination Programme for a given year in the nspector ,16,17,18The state of preventive vaccinations of children in Poland is satisfactory. The percentage of vaccinated children is higher than in many other countries of the European Union. It reaches the target values approved by the World Health Organization, the United Nations International Children’s Emergency Fund, and the United Nations Children’s Fund. Despite the majority of children being vaccinated, concerns regarding the safety and effectiveness of vaccines have caused growth in the number of unvaccinated children due to their parents and legal guardians avoiding fulfilling the vaccination obligation . The resThe individual research showed that, due to the high cost, only 28.4% of parents chose recommended or combined vaccines. It has been confirmed by the research conducted by Pomian–Osiak, which showed that the cost of combined vaccines was the reason of performing free vaccinations . Also, KThe reason for avoiding the vaccination of children, according to numerous authors, is parents’ concerns. A review of the available literature showed that parents’ beliefs about the possibility of serious vaccination reactions are important factors strongly associated with vaccination fluctuations. Caregivers’ concerns mostly focus on the composition of vaccines, as well as on side effects usually associated with their own negative vaccination experience. The first results of the European project VACSATC, which aimed to track parents’ attitudes to vaccination in several European countries, carried out in 2008–2009, showed a generally positive attitude of parents toward vaccination in childhood vaccination programs ,22,23. TThe Lancet removed articles by Wakefield from their archive. Evidence supporting this concept was found to be false and manipulated, while Wakefield was found to be a fraudster in a court order [The lack of knowledge about the benefits of vaccination, as well as incorrect information published on the Internet, can influence the parents’ decision to not vaccinate their children. As studies have shown, parents’ fear may be due to the increasing activity of antivaccination movements and their frequent campaigns presenting vaccines as harmful. This has also been confirmed by data published by the Polish State Sanitary Inspectorate, which shows that, for every third unvaccinated child 32%), the parents’ decision was influenced by antivaccination movements ,20,23,30%, the part order ,34,35. Trt order ,37. In 1rt order ,24. As sParents have a responsibility to make decisions in the best interest of their children. Parents, taking into account medical advice and statistical information on risk and benefits, do not decide to vaccinate their child. The lack of sufficient information on preventive vaccinations often explains the lack of trust in childhood vaccination programs. Usually, it is a lack of knowledge about the etiology of infectious diseases that contributes to the development of so-called antivaccination movements. Various healthcare professionals play a key role in communication with parents. According to Facciola et al., only 18% of doctors favored recommended vaccinations, while 47.5% were opposed to vaccines .p = 0.03). More effective cooperation with the society is required, which can be achieved by providing reliable information and discussions. In this field, the educational role of medical personnel is of the utmost importance. Due to their direct contact with parents, medical workers are oriented in the current situation and have the possibility, as well as the obligation, of educating the concerned parents and caretakers [Insufficient contact with doctors and nurses, lack of reliable information from specialists regarding safety, mechanisms and effectivity of vaccinations, and negative attitude are important factors influencing parents’ attitude toward children vaccination, and they can even become the greatest obstacle in vaccination implementation ,24,38. Aretakers .Modifiable determinants of the negative attitude toward vaccinations are caused mainly by the lack of knowledge. These obstacles in vaccinations can be overcome by improving health education in terms of the vaccination program.The cost of combined and recommended vaccines is a significant financial obstacle for Polish parents. That should convince Polish legislators to take into consideration at least partial reimbursement of combined and recommended vaccines.Regular monitoring of parents’ attitudes toward the vaccination program will allow for the adjustment of educational programs to current needs.