Neurotrophic Factors, Impulsivity, and Reward Sensitivity in Children With Internet Gaming Disorder

Investigation of the Relationship Between Serum BDNF and GDNF Levels and Impulsivity, Reward/Punishment Sensitivity in Children Diagnosed With Internet Gaming Disorder

Research and knowledge regarding the neurobiology of behavioral addictions and Internet Gaming Disorder (IGD) remain limited compared to substance and alcohol use disorders. However, IGD is increasingly causing significant functional impairment, particularly in the child and adolescent population. The primary objective of this study is to measure the serum levels of Brain-Derived Neurotrophic Factor (BDNF) and Glial-Derived Neurotrophic Factor (GDNF)-both known for their roles in neurogenesis and neuroprotective effects-in a patient group aged 10-14 and a healthy control group. Additionally, this study aims to investigate the relationship between these neurotrophic factor levels and disease severity, as well as various behavioral and emotional parameters measured through psychometric assessments, to identify differences between the patient and healthy populations.

Researchers will compare IGD patient group with healthy control group, both aged 10-14.

Participants and their parents will be asked to fill self-report measures and serum samples of participants will be collected for BDNF and GDNF level measurements.

The main questions of the study are:

• Is there a difference in serum BDNF and GDNF levels between IGD patient group and healthy controls?
• Is there a relation between serum BDNF and GDNF levels and IGD severity?
• Is there a difference in impulsivity, reward/punishment sensitivity between IGD patient group and healthy controls
• Is there a relation between serum BDNF and GDNF levels and impulsivity, reward/punishment sensitivity scores in IGD patient group?

Between May 2026 and December 2026, informed consent and assent will be obtained from participants and their parents/legal guardians after a comprehensive explanation of the study objectives, psychometric scales, and psychiatric evaluation protocols. This research is designed as a cross-sectional case-control study. The patient group will include children and adolescents diagnosed with Internet Gaming Disorder (IGD) according to DSM-5 criteria. The control group will consist of age- and gender-matched individuals attending psychiatry or pediatric outpatient clinics or volunteers who meet the control inclusion criteria and have provided written informed consent.

The primary investigator will conduct clinical psychiatric interviews with all participants in both the case and control groups to verify eligibility and diagnostic status. The following psychometric instruments will be administered:

For children (Case and Control groups): Internet Gaming Disorder Scale-Short Form (IGDS9-SF), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), UPPS-P Impulsive Behavior Scale for Children (C-UPPS-P), Screen for Child Anxiety Related Emotional Disorders (SCARED) - Child Form, and Children's Depression Inventory (CDI).

For parents (Case and Control groups): SCARED - Parent Form, and the Turgay DSM-IV-based Screening and Assessment Scale for Disruptive Behavior Disorders (Turgay ADHD Scale).

Joint Assessments: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) and a sociodemographic data form will be administered to both the children and their parents by the researcher.

For biochemical analysis, peripheral venous blood samples will be collected from all participants following a 10-12 hour fasting period between 09:00 and 12:00. Samples will be drawn into gold-top (serum separator) tubes and transported within 2-3 hours to the Brain and Neurodegenerative Diseases Research Laboratory at Istanbul University-Cerrahpaşa, Institute of Neurological Sciences, Department of Neuroscience. Blood tubes will be centrifuged at 5000 rpm for 10 minutes. The separated serum will be aliquoted into 1.5 ml microcentrifuge tubes and stored at -80°C until the final analysis. Once the sample collection phase is complete, serum BDNF and GDNF levels will be determined using Human BDNF (ELH-BDNF-1, RayBiotech) and Human GDNF (ELH-GDNF-1, RayBiotech) ELISA kits. ELISA assays will be conducted strictly following the manufacturers' protocols at the aforementioned laboratory.

Inclusion Criteria:

For IGD Patient Group:

Age: Being between 10 and 14 years of age. Literacy: Ability to read and write fluently. Informed Consent: Voluntary participation with written informed consent obtained from both the participants and their parents/legal guardians after a comprehensive briefing on the study procedures and scales.

Diagnostic Criteria: Meeting the DSM-5 diagnostic criteria for Internet Gaming Disorder (IGD) and scoring above the clinical cutoff on the Internet Gaming Disorder Scale-Short Form (IGDS9-SF).

For Healthy Control Group:

Age: Children between 10 and 14 years of age. Literacy: Ability to read and write fluently. Clinical Status: No history or current diagnosis of any neuropsychiatric disorder, confirmed through clinical psychiatric assessment.

Informed Consent: Voluntary participation with written informed consent obtained from both the participants and their parents/legal guardians after a comprehensive briefing on the study procedures and scales.

Exclusion Criteria:

Comorbid Psychiatric Disorders: Meeting the DSM-5 diagnostic criteria for Autism Spectrum Disorder, Schizophrenia, Bipolar I Disorder, or Bipolar II Disorder.

Cognitive and Neurological Impairment: Having a moderate to severe intellectual disability and/or a neurological disease in either the child or the caregiver that would impede the ability to understand instructions or provide reliable responses during the interview.

Lack of Informed Consent: Refusal to participate voluntarily or failure to sign the informed consent/assent form by the children or their parents/legal guardians after receiving a detailed explanation of the study's purpose and the assessment scales to be administered.