Neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and monocyte to lymphocyte ratio in ADHD: a systematic review and meta-analysis

Abstract

IntroductionAttention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an unclear etiology. Systemic inflammation and immune dysregulation may play a role in the pathogenesis of ADHD. Morphology-derived parameters such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR), have been proposed as peripheral biomarkers of the immune-inflammatory process in various diseases. However, studies examining their role in ADHD remain inconclusive.MethodsA systematic review and a meta-analysis were conducted to evaluate the association between NLR, MLR, PLR and ADHD. Relevant articles were identified, screened, and assessed for quality according to PRISMA guidelines. Moreover, a qualitative and quantitative analyses were performed.ResultsThe review contained eight eligible studies, five of which were included in the meta-analysis. The meta-analysis showed that ADHD patients had higher NLR and PLR values compared to health controls. No significant difference in MLR value was observed between the two groups. Analysis in relation to ADHD subtypes showed no significant differences in inflammatory markers in any of the included studies as well. The influence of medical treatment on these ratios could not be adequately assessed due to limited data.ConclusionADHD patients exhibit higher NLR and PLR than healthy controls, which may indicate the potential immune-inflammatory involvement in this disorder. Further studies on inflammatory markers and ADHD, especially those considering the impact of treatment and clinical symptoms, are essential to comprehensively understand this association.

Inflammatory Hematological Ratios in Adolescents with Mental Disorders: A Scoping Review

“…Overall, a comparison of studies on IHRs in mental disorders between adolescents and adults indicates that the most reproducible abnormalities compared with healthy individuals in both age groups are NLR and (to a lesser extent) PLR increase in affective disorders [ 36 , 37 , 51 , 60 ], as well as NLR increase in schizophrenia spectrum disorders (first psychotic episode and schizophrenia) [ 25 , 33 , 56 ]. Comparison of studies of IHRs in ADHD between adolescents [ 46 , 47 ] and younger children [ 59 ] demonstrates an increase in NLR compared with healthy controls (although not in all studies) in both age groups. Thus, for those indications which were studied across various age groups (younger children, adolescents, adults), we did not find any age-related differences in the association between IHRs and mental disorder.…”

“…Several systematic reviews and meta-analyses have been published summarizing data on IHRs in mental disorders across various age groups, including children [ 25 , 59 ], adults [ 33 , 36 , 37 , 60 , 61 ], and mixed-age samples [ 38 ]. The majority of these studies focus on affective disorders in adult patients.…”

“…A meta-analysis of the results of 8 studies on IHRs in younger children with ADHD (mean age of participants of these studies varied from 8.3±1.7 to 10.33±3.15 years) demonstrated that they had higher NLR and PLR than healthy children (939 patients and 652 healthy children; SMD=0.49; 95% CI 0.15–0.82; p =0.004 and SMD=0.31; 95% CI 0.03–0.59, respectively), while no difference in MLR was observed [ 59 ]. The results of the studies in adolescents included in our review were inconsistent: one study demonstrated increased NLR and PLR in adolescents aged 12–17 years with ADHD [ 47 ], while another found no differences compared with healthy controls [ 46 ].…”