2026 ECNP Congress

PS03-3150

Nerve growth factor levels in peripheral blood of children with attention deficit hyperactivity disorder: a meta-analysis

Danail Minchev — A. Stoynova, I. Pikova, B. Georgieva, T. Vachev · Faculty of Biology- "Paisii Hilendarski" University of Plovdiv, Department of Human Anatomy and Physiology, Plovdiv, Bulgaria

2026 ECNP Congress

Introduction: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by persistent inattention and/or hyperactive-impulsive behavior [1]. ADHD is a highly heritable disorder with a multifactorial etiology, involving genetic and environmental factors [2]. Considering the importance of nerve growth factor (NGF) for normal CNS development and function, a better understanding of its levels in peripheral blood may help elucidate the intricate processes underlying ADHD.

Aim: This study aims to integrate experimental data on NGF levels in the peripheral blood (whole blood, serum, or plasma) of children with ADHD through a comprehensive meta-analysis.

Methods: This study strictly follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [3]. Initially, a thorough search of the literature available at the WoS database was performed with the following query: ALL=((nerve growth factor OR NGF) AND (Attention Deficit Hyperactivity Disorder OR ADHD OR Attention Deficit) AND (blood OR serum OR plasma) AND (patient OR patients OR children)).

The following inclusion criteria were applied without time restrictions:

  1. Reported quantitative data on NGF levels in peripheral blood from human participants.

  2. Reported sample sizes, means, and standard deviations.

  3. Provided sufficient statistical data (sample sizes, medians, interquartile ranges, p-values) when means and standard deviations were unavailable.

  4. Included comparisons between probands with ADHD and typically developing controls.

Data analyses were performed using the meta package (version 7.0-0) for R (version 4.3.2).

Results: The initial search generated a list with 25 articles. After screening titles and abstracts, 13 studies were selected for full-text review. Of these, seven did not meet the inclusion criteria. Data were successfully extracted from the six remaining studies: Gunay et al. (2014), Bilgic et al. (2016), Gumus et al. (2022), Yurteri et al. (2019), Chang et al. (2020), and Gul et al. (2024).

The analysis included 344 children with ADHD and 219 healthy controls. A random-effects model revealed that NGF levels were higher in children with ADHD compared to their matched controls (Hedges’ g = 0.94; 95%-CI [-0.07; 1.95]; p = 0.067). Between-study heterogeneity was high (Q(5) = 102.6, p < 0.001; tau² = 1.38 [0.57; 12.37]; I² = 95.1% [91.8%; 97.1%]). The effect sizes of two studies could be considered disproportionately large. Their removal substantially reduced the initial Q value to 4.99, revealing them as significant sources of heterogeneity. This heterogeneity may be attributed to between-study discrepancies in patient demographics or diagnostic criteria. No publication bias was detected by the funnel plot asymmetry evaluation (t = 0.56, p = 0.606) and the Spearman’s test for correlation between years of publication and effect sizes (r = -0.60, p = 0.241).

Discussion: To our knowledge, this is the first meta-analysis to integrate literature data on NGF levels in the peripheral blood of ADHD children. Our results suggest a tendency for NGF dysregulation, although the observed effects cannot be deemed statistically significant. Given the essential role of NGF in CNS development, the better characterization of its expression patterns may allow a more precise understanding of ADHD.

Conclusion: Based on the integrated data provided, we can suggest a tendency for dysregulation of NGF in ADHD.

References

  1. American Psychiatric Association, 2013. Diagnostic and statistical manual of mental disorders, fifth ed. American Psychiatric Association Publishing, Washington.
  2. Faraone, S.V., Larsson, H., 2019. Genetics of attention deficit hyperactivity disorder. Mol. Psychiatry 24 (4), 562-575.
  3. Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., PRISMA Group, 2009. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6 (7), e1000097. The authors declare no conflicts of interest. This abstract was supported by the Bulgarian National Science Fund, Grant No. КП-06-М91/5 (BG-175467353-2025-07-0019-C01): Comparative analysis of inflammatory factors in individuals with overweight and obesity.