Yüksek nötrofil-lenfosit oranı otizm spektrum bozukluğunu öngörebilir mi?
Amaç: Otizm spektrum bozukluğu (OSB), üzerinde en çok çalışılan nörogelişimsel bozukluklardan biri olmasına rağmen, etiyolojisi tam olarak aydınlatılamamıştır. OSB’nin altta yatan patofizyolojisinde nöroinflamasyonun rol oynadığına ilişkin çalışmalar ve bulgular giderek artmaktadır. Nötrofil-Lenfosit oranı (NLO) ve trombosit-lenfosit oranı (TLO) sistemik inflamasyonun göstergeleridir. Bu çalışmada, OSB’li çocuklarda sağlıklı kontrollere göre NLO ve TLO'yu değerlendirmeyi amaçladık. Yöntem: Bu çalışmada OSB tanısı olan 2-5 yaşları arasındaki çocukların tıbbi dosyaları gözden geçirilmiştir. Hasta grubu, daha öncesinde ilaç kullanımı olmayan ve tanı konulduğu bir ay içinde tam kan sayımı yapılan 64 çocuktan oluşmaktadır. Sağlam çocuk polikliniğinden psikiyatrik bozukluğu olmayan, yaş ve cinsiyetleri benzer 64 çocuk sağlıklı kontrol olarak çalışmaya alınmıştır. Sonuç: OSB’li çocuklarda, NLO anlamlı olarak yüksek bulunmuştur. Olgu grubunda, sağlıklı kontrollere kıyasla nötrofil sayısı daha yüksek, lenfosit ve trombosit sayısı daha düşük bulunmuştur. NLO değerlerinin OSB’yi yordadığı saptanmıştır. Tartışma:NLR yüksekliği OSB’nin etiyolojisinde nöroinflamasyon rolü olduğunu hipotezini desteklemektedir. Yeterli kanıt olmamakla birlikte küçük yaş döneminde yükselmiş NLR düzeylerinin OSB’de tarama ve erken müdahalede yorda- yıcı olabileceği görüşü yeni araştırmalara konu olabilir. Yaş ve alt grup dağılımı açısından benzer çocukları içeren daha büyük örneklemli uzun izlem çalışmaları OSB’nin etiyolojisinde inflamasyonun katkısını açıklayabilir. (Ana- dolu Psikiyatri Derg 2018; 19(6):607-614)
Does increased neutrophil-lymphocyte ratio predict autism spectrum disorder?
Objective: Although autism spectrum disorder (ASD) is one of the most studied neurodevelopmental disorders, itsetiology has not been fully elucidated. A growing body of evidence suggest the role of neuroinflammation in theetiology of ASD. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are markers of systemicinflammation. In this study, we aimed to evaluate NLR and PLR in children with ASD comparison to healthy controls.Methods: We reviewed the medical files of children with ASD in the ages of 2 to 5. The ASD group were consistedof drug-naïve 64 children who had complete blood count within a month of assessment. Age and sex matched 64healthy children without any psychiatric disorders were recruited from the healthy child outpatient unit of the hospital.Results: NLRs were significantly higher in ASD. Children with ASD had significantly higher neutrophil counts butlower platelet and lymphocyte counts compared to those of healthy controls. NLR was found to be a predictor ofASD. Conclusions: Increased NLRs support the hypothesis of the involvement of neuroinflammation in the under-lying physiopathology of ASD. Even though recent evidence is not enough to suggest that in young childrenincreased NLR levels may be used as screening and early intervention predictor, it should be kept in mind and mayinspire new studies. Further longitudinal studies with larger sample size and homogeneous groups regarding theage and subtypes may clarify the inflammatory involvement in ASD. (Anatolian Journal of Psychiatry 2018;19(6):607-614)
___
- American Psychiatric Association. Diagnostic and
Statistical Manual of Mental Disorders, 5th ed.
Arlington: American Psychiatric Publishing, 2013.
- Masi A, Glozier N, Dale R, Guastella AJ. The
immune system, cytokines, and biomarkers in
autism spectrum disorder. Neurosci Bull 2017;
33:194-204.
- Bilbo SD, Schwarz JM. The immune system and
developmental programming of brain and be-
havior. Front Neuroendocrinol 2012; 33:267-286.
- Yirmiya R, Goshen I. Immune modulation of
learning, memory, neural plasticity and neuro-
genesis. Brain Behav Immun 2011; 25:181-213.
- Depino AM. Peripheral and central inflammation
in autism spectrum disorders. Mol Cell Neurosci
2013; 53:69-76.
- Chess S. Follow-up report on autism in congenital
rubella. J Autism Child Schizophr 1977; 7:69-81.
- Greer MK, Lyons-Crews M, Mauldin LB, Brown III
FR. A case study of the cognitive and behavioral
deficits of temporal lobe damage in herpes
simplex encephalitis. J Autism Dev Disord 1989;
19:317-326.
- Yamashita Y, Fujimoto C, Nakajima E, Isagai T,
Matsuishi T. Possible association between con-
genital cytomegalovirus infection and autistic dis-
order. J Autism Dev Disord 2003; 33:455-459.
- Atladottir HO, Thorsen P, Ostergaard L, Schendel
DE, Lemcke S, Abdallah M, et al. Maternal
infection requiring hospitalization during preg-
nancy and autism spectrum disorders. J Autism
Dev Disord 2010; 40:1423-1430.
- Atladottir HO, Pedersen MG, Thorsen P, Morten-
sen PB, Deleuran B, Eaton WW, et al. Association
of family history of autoimmune diseases and
autism spectrum disorders. Pediatrics 2009;
124:687-694.
- Mostafa GA, Al Shehab A, Fouad NR. Frequency
of CD4+ CD25 high regulatory T cells in the
peripheral blood of Egyptian children with autism.
J Child Neurol 2010; 25:328-335.
- Ashwood P, Krakowiak P, Hertz-Picciotto I, Han-
sen R, Pessah IN, van de Water J. Altered T cell
responses in children with autism. Brain Behav
Immun 2011; 25:840-849.
- Ashwood P, Corbett BA, Kantor A, Schulman H,
Van de Water J, Amaral DG. In search of cellular
immunophenotypes in the blood of children with
autism. PLoS One 2011; 6:e19299.
- Mead J, Ashwood P. Evidence supporting an
altered immune response in ASD. Immunol Lett
2015; 163:49-55.
- Gladysz D, Krzywdzinska A, Hozyasz KK. Im-
mune abnormalities in autism spectrum disorders-
could they hold promise for causative treatment?
Mol Neurobiol 2018; doi: 10.1007/s12035-017-
0822-x. [Epub ahead of print]
- Meltzer A, Van de Water J. The role of the immune
system in autism spectrum disorder. Neuro-
psychopharmacology 2016; 42:284-298.
- Zahorec R. Ratio of neutrophil to lymphocyte
counts rapid and simple parameter of systemic
inflammation and stress in critically ill. Bratisl Lek
Listy 2001; 102:5-14.
- Balta S, Ozturk C. The platelet-lymphocyte ratio:
A simple, inexpensive and rapid prognostic
marker for cardiovascular events. Platelets 2014;
30:1-2.
- Kuyumcu ME, Yesil Y, Oztürk ZA, Kizilarslanoglu
C, Etgul S, Halil M, et al. The evaluation of neut-
rophil lymphocyte ratio in Alzheimer's disease.
Dement Geriatr Cogn Disord 2012; 34:69-74.
- Semiz M, Yıldırım O, Canan F, Demir S, Hasbek
E, Tuman TC, et al. Elevated neutrophil/lym-
phocyte ratio in patients with schizophrenia.
Psychiatr Danub 2014; 26:220-225.
- Kalelioglu T, Akkus M, Karamustafaalioglu N,
Genc AE, Cansız A, et al. Neutrophil-lymphocyte
and platelet-lymphocyte ratios as inflammation
markers for bipolar disorder. Psychiatry Res 2015;
228:925-927.
- Demir S, Atli A, Bulut M, Ibiloglu AO, Gunes M,
Kaya MC, et al. Neutrophil-lymphocyte ratio in
patients with major depressive disorder under-
going no pharmacological therapy. Neuropsychi-
atr Dis Treat 2015; 11:2253-2258.
- Hesapcioglu ST, Kasak M, Citak Kurt AN, Ceylan
MF. High monocyte level and low lymphocyte to
monocyte ratio in autism spectrum disorders. Int J
Dev
Disabil
2017;1-9
10.1080/20473869.2017.1371369.
- Savaşır I, Sezgin N, Erol N. Ankara Gelişim Tara-
ma Envanteri El Kitabı. Düzeltilmiş dördüncü
basım, Ankara: Rekmay, 2006.
- Durmazlar N, Ozturk C, Ural B, Karaagaoglu E,
Anlar B. Turkish children’s performance on Den-
ver II: effect of sex and mother’s education. Dev
Med Child Neurol 1998; 40:411-416.
- Sweeten TL, Posey DJ, McDougle CJ. High blood
monocyte counts and neopterin levels in children
with autistic disorder. Am J Psychiatry 2003;
160:1691-1693.
- Bodur S, Ceylan MF, Iseri E, Sener S, Yucel AA.
Serum neopterin levels in patients with autism. Int
J Dev Disabil 2014; 60:109-115.
- Zhao HX, Yin SS, Fan JG. High plasma neopterin
levels in Chinese children with autism spectrum
disorders. Int J Dev Neurosci 2015; 41:92-97.
- Owen JA, Punt J, Stranford SA, Jones PP, Kuby
J. Kuby Immunology. Seventh ed., New York:
W.H. Freeman, 2013.
- Bilbo SD, Block CL, Bolton JL, Hanamsagar R,
Tran PK. Beyond infection-Maternal immune
activation by environmental factors, microglial
development, and relevance for autism spectrum
disorders. Exp Neurol 2018; 299:241-251.
- Enstrom AM, Lit L, Onore CE, Gregg JP, Hansen
RL, Pessah IN, et al. Altered gene expression and
function of peripheral blood natural killer cells in
children with autism. Brain Behav Immun 2009;
23:124-133.
- Careaga M, Rogers S, Hansen RL, Amaral DG,
Van de Water J, Ashwood P. Immune endopheno-
types in children with autism spectrum disorder.
Biol Psychiatry 2017; 81:434-441.
- Bijl N, Thys C, Wittevrongel C, De la Marche W,
Devriendt K, Peeters H, et al. Platelet studies in
autism spectrum disorder patients and first-
degree relatives. Mol Autism 2015; 6:57. doi:
10.1186/s13229-015-0051-y. eCollection 2015.
- Wasilewska J, Kaczmarski M, Stasiak-Barmuta
A, Tobolczyk J, Kowalewska E. Low serum IgA
and increased expression of CD23 on B lympho-
cytes in peripheral blood in children with regres-
sive autism aged 3-6 years old. Arch Med Sci
2012; 8:324-331.
- Schopler E, Reichler R, DeVellis R, Daly K. To-
ward objective classification of childhood autism:
Childhood Autism Rating Scale (CARS). J Autism
Dev Disord 1980; 10:91-103.
- Ashwood P, Krakowiak P, Hertz-Picciotto I,
Hansen R, Pessah I, Van de Water J. Elevated
plasma cytokines in autism spectrum disorders
provide evidence of immune dysfunction and are
associated with impaired behavioral outcome.
Brain Behav Immun 2011; 25:40-45.
- Ferguson BJ, Marler S, Altstein LL, Lee EB,
Mazurek MO, McLaughlin A, et al. Associations
between cytokines, endocrine stress response,
and gastrointestinal symptoms in autism spec-
trum disorder. Brain Behav Immun 2016; 58:57-
62.
- Guloksuz SA, Abali O, Aktas Cetin E, Bilgic Gazi-
oglu S, Deniz G, Yildirim A, et al. Elevated plasma
concentrations of S100 calcium-binding protein B
and tumor necrosis factor alpha in children with
autism spectrum disorders. Rev Bras Psiquiatr
2017; 39:195-200.
- McBride PA, Anderson GM, Hertzig ME, Snow
ME, Thompson SM, Khait VD, et al. Effects of
diagnosis, race, and pubertal status on platelet
serotonin levels in autism and mental retardation.
J Am Acad Child Adolesc Psychiatry 1998;
37:767-779.
- Ritvo ER, Yuwiler A, Geller E, Ornitz EM, Saeger
K, Plotkin S. Increased blood serotonin and
platelets in early infantile autism. Arch Gen
Psychiatry 1970; 23:566-572.
- Geller E, Yuwiler A, Freeman BJ, Ritvo E. Platelet
size, number, and serotonin content in blood of
autistic, childhood schizophrenic and normal chil-
dren. J Autism Dev Disord 1988; 18:119-126.
- Anderson GM, Freedman DX, Cohen DJ, Hodel
EL, Volkmar FR, Paul R, et al. Whole blood
serotonin in autistic and normal subjects. J Child
Psychol and Psychiatry 1987; 28:885-900.