attention deficit hyperactivity disorder ( adhd ) and autism spectrum disorders ( asd ) are 2 different disorders with important impacts on the lives of children . the frequently seen attention deficit hyperactivity disorder may lead to lack of school success and to disruptive behavior . although there is no specific known cause of this disorder , multiple factors in its pathophysiology have been implicated . this group is associated with certain risk factors such as mutated or variant genes , advanced father s age , prematurity , and birth complications [ 46 ] . recently , there have been papers on the association of adhd in children with increased thickness of carotid intima media . children with adhd and with asd have higher body mass index ( bmi ) than controls , and this increased bmi increases the risk for cardiovascular disease . furthermore , co - deficiency of vitamin b12 and vitamin d in both adhd and asd has recently been reported and claimed as a possible risk factor for both disorders . deficiency of vitamin b12 and vitamin d has been implicated as a factor increasing the risk for cardiovascular disease [ 914 ] . when one looks at the situation in terms of all predisposing factors , it is evident that adhd and asd are accompanied by an increased risk of cardiovascular disease . when platelets are more active , the risk of atherothrombosis is higher , and outcomes are worse . platelet activity has been related to acute vascular events , and the administration of anti - platelet agents is a class i recommendation for treatment and secondary prevention of coronary artery disease ( cad ) . in addition , many recent studies have correlated platelet activity with development and progression of atherosclerosis . platelet functions have been determined to be associated with the risk of adverse events in different types of cad . tests for measuring platelet function are currently available , but most are expensive and are only used for research , not routine clinical practice . the mean platelet volume ( mpv ) is a simple indicator of platelet size , which may represent platelet activity and be associated with plaque burden , morphology , progression , and vulnerability in vascular endothelial tissue . larger platelets are younger , contain more alpha granules , have more expression of adhesion receptors , and are more metabolically and enzymatically active ; therefore , they possess more marked thrombogenic features . a recent meta - analysis in adults has strongly suggested an association between mpv and cad . the specific features , frequent lack of nutritional factors such as vitamins b12 and d , and high levels of oxidative stress in adhd and asd have led us to think that these disorders may be a risk factor for cardiovascular disease . the purpose of our study was to assess the risk of cardiovascular disease in subjects with adhd and asd by determining the values of mpv , a predictor of cardiovascular disease , in both adhd and asd patients and in healthy controls . the study included patients aged 318 years with adhd and with asd , and healthy controls , in the van region of turkey . the patients were divided into 2 groups based on diagnosis : the adhd group and the asd group . the study plan was approved by the ethics committee of the medical school , yznc yil university , and was made according to the ethics principles of the declaration of helsinki . after informing each patient or each patient s family about the study , the patient or the family provided signed informed consent . the sampling groups of the study included children and adolescents presenting to the pediatric psychiatry outpatient clinic of the van regional training and research hospital , who had received the diagnoses of adhd or asd in the period between february and july 2014 . the diagnosis of asd was made according to the dsm-5 and dsm-4 tr diagnostic criteria based on asd - diagnostic interview and the childhood autism rating scale ( cars ) . the diagnosis of adhd was based on dsm-5 and dsm-4 tr diagnostic interview and on the evaluation of the scale for screening / evaluation for disruptive behavior disorders filled in by the family and the teacher . after measuring the weight and height of the patients , their blood samples were collected . the criteria for exclusion from the study were : comorbidity , a diagnosed genetic or metabolic disorder , history of head trauma or surgery , use of any vitamins , infection during the time of presentation , another chronic disorder , and long - term use of drugs . we tested the renal and hepatic function of patients and controls , and those with abnormal values were excluded from the study ( the values of these tests have not been demonstrated in the study ) . the control group comprised normal subjects who had presented to the pediatric endocrinology outpatient clinic for a developmental check - up . the controls matched the study group patients with regard to age and sex , they did not have the diagnostic criteria for adhd or asd , did not have a chronic disorder , and were not taking vitamins of any kind . measurements of biochemical parameters , serum electrolyte levels , renal and hepatic functions , calcitriol , and vitamin b12 levels were made at the central laboratory of the medical school using the architect ci-16200 ( abbott diagnostics , abbott park , il ) and the chemiluminescent method . ferritin levels were determined in the biochemistry laboratory of the medical school hospital using the immulite 2000 ( siemens healthcare diagnostics , los angeles , ca ) and the chemiluminescent method . hematological tests that measured hemoglobin , platelets , white blood cells ( wbc ) , and mpv were performed using the cell - dyn ruby analyzer ( abbott diagnostics ) . the results obtained in the groups are expressed as mean  standard deviation and minimum and maximum values . in the comparison of continuous variables between the groups , one - way anova was used for normally - distributed variables and the kruskal - wallis h test and the chi - square test were used for the non - normally distributed and non - parametric variables . the study included a total of 79 children and adolescents aged 218 years ( 32 females and 47 males ) . of these subjects , 36 were in the adhd group , 18 in the asd group , and 25 in the control group . the comparison of the groups in terms of age , weight , and height is shown in tables 1 and 2 . there was no significant difference between the groups in terms of age , sex , weight , or height . there was no significant difference between the groups in terms of any hematological parameters ( p>0.05 ) . a significant difference was present between the groups in terms of vitamin d , vitamin b12 , and ferritin levels ( table 5 ) . the lowest vitamin b12 level was determined in the asd group , whereas the vitamin b12 level in the adhd group was markedly lower than that in the control group . the ferritin level was highest in the asd group and lowest in the control group . the correlation analyses within each group showed no statistically significant difference between the groups , but in the adhd group there was a negative correlation between vitamins b12 and d and mpv ( p<0.05 ) . in the control group , a significant negative correlation was present between mpv and serum folate levels ( p : 0.003 ) . the partial correlation analysis of the adhd group showed that mpv in particular was negatively correlated to vitamin d but not to vitamin b12 ( p : 0.03 , 0.424 , respectively ) ( table 6 ) . in this prospective case - control study , the risk of cardiovascular disease was assessed in children with adhd and with asd by determining the mpv levels . in the literature , furthermore , in our study , the association between vitamins b12 and d and mpv was assessed for the first time . we found no significant difference in mpv values between asd , adhd , and the control groups , but we determined that in the asd and adhd groups , the levels of vitamins b12 and d were significantly lower than those in the control group . in the adhd group , there was a significantly negative correlation between vitamins b12 and d and mpv . the partial correlation analysis showed that vitamin d particularly had an effect on mpv . the only study in the literature assessing the association between adhd and mpv is by yorbik et al . , who found increased levels of mpv in children aged 616 years and adolescents with adhd , but concluded that the reason for and the importance of increased mpv should be clarified by further studies . this finding may be due to the limited number of patients studied . in order to verify this finding , further studies with larger patient one important finding in our study was the impact of vitamin d on mpv , particularly in the adhd group . we showed that there was a negative correlation between mpv and vitamins d and b12 . in the partial correlation analysis indicating that when vitamin b12 was taken as the controlling factor there was a significant negative correlation between mpv and vitamin d , but when vitamin d was taken as the controlling factor there was no significant correlation between vitamin b12 and mpv . adhd is considered to share the same etiologies with asd , since asds also exist frequently in the states that commonly exist with adhd . therefore , factors playing roles in the etiology of asd also have to be well understood to clarify the etiology of adhd . attention deficit hyperactivity disorder is less prevalent in geographical regions with hot climate and longer hours of sunlight . the next question to be answered is whether vitamin d deficiency is frequent in adhd . many studies have reported that vitamin d deficiency is frequently seen both in adhd and asd , and that in children with these disorders , the levels of vitamins b12 and d are much lower than in controls . the relevant studies have also reported that vitamin d is a requirement for normal cerebral homeostasis , cellular differentiation during cerebral development , axonal growth , stimulation of neurotrophic factors , modulation of the production of cerebral reactive oxygen species , and stimulation of glutathione , which is a potent anti - oxidant that plays a role in the synthesis and repair of dna , whereby vitamin d down - regulates excitotoxicity [ 2527 ] . hence , failures in these mechanisms caused by vitamin d deficiency may lead to behavior disorders as seen in adhd and asd . as a matter of fact , in our study , vitamin d deficiency was frequently determined as a comorbidity as well as an etiologic factor in both adhd and asd patients . after considering all these data , the next question to be answered is whether there is an association between vitamin d and cardiovascular disease . in the cardiovascular system , the endothelial cells , cardiomyocytes , and vascular smooth muscle cells carry the vitamin d receptor gene ( vdr ) , which interacts with vitamin d. it has been reported that when cardiomyocytes are incubated with active vitamin d , cellular proliferation is inhibited , cardiomyocyte formation is increased , the anti - apoptotic effect is induced , and the expression of genes involved in cell cycle is reduced . it has been reported that in cases of vitamin d deficiency , there is an increase of inflammatory cytokines released by active macrophages ( il-1 beta , il-6 , tnf - alpha ) induced by interferon - gamma release from th1 cells , which causes increased oxidation of ldl , and the subsequent destabilization and tearing of the atheroma plaque leads to increased risk of thrombosis . a recent comprehensive study has reported that vitamin d deficiency accompanies hypertension , high blood glucose levels , cardiovascular disease , and metabolic syndrome ( 11 ) . both adhd and asd may accompany increased risk for cardiovascular disease due to the presence of vitamin b12 and d deficiency and their own characteristics . the lack of a difference in mpv between the patient groups and control group may be due to the limited number of patients studied .  the vitamin d deficiency , particularly in the adhd group , may have contributed to the elevated mpv level in the study by yoruk et al . further studies on larger patient populations are required for verification of the presented data .
backgroundthe purpose of this study was to assess the values of the mean platelet volume ( mpv ) in children with attention deficit hyperactivity disorder ( adhd ) and with autism spectrum disorders ( asds ) to determine the risk of cardiovascular disease in these 2 disorder groups.material/methodsthe study included a total of 79 patients with adhd or asds and controls in the van region of turkey . 
 the control group included subjects of matching age and sex with no adhd , asds , or chronic disease and taking no vitamins . 
 the hematological parameters of the patients , including mpv , vitamin b12 , and vitamin d , were assessed.resultsthe study included a total of 79 children and adolescents aged 218 years ( 32 females and 47 males ) . 
 of the patients , 36 were in the adhd group , 18 in the asds group , and 25 in the control group . 
 there was no statistically significant difference in hematological parameters between the groups , but there were significant differences in terms of vitamin d and vitamin b12 . 
 the patient groups showed lower levels of vitamin b12 and vitamin d. in the adhd group , there was a negative correlation between both vitamins and mpv ( p<0.05 ) . 
 partial correlation analysis of the adhd group showed that mpv in particular was negatively correlated to vitamin d , and not to vitamin b12 ( p : 0.03).conclusionsboth adhd and asds may accompany increased risk for cardiovascular disease due to the presence of vitamin b12 and d deficiency and their own characteristics . 
 therefore , these disorders should be closely followed up .