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Interactive effect of BDNF rs10835210 polymorphism and childhood maltreatment on cognitive functioning in Chinese

Linjun Jiang^1,2, Dongmei Wang^3,4, Yang Tian^1,2

¹State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Road, Chaoyang District, Beijing, 100101, China.

European Archives of Psychiatry and Clinical Neuroscience

|June 28, 2025

Abstract

Background:

Patients with methamphetamine use disorder (MUD) are known to experience cognitive dysfunction. Our previous study was the first to demonstrate the negative impact of childhood maltreatment (CM) on cognitive function in MUD patients. Extensive research has highlighted the crucial role of brain-derived neurotrophic factor (BDNF) gene polymorphisms in cognitive function. However, whether genetic variations in BDNF interact with environmental factors such as CM to influence cognition remains unclear. Therefore, this study aimed to investigate the potential interaction between BDNF gene polymorphism and CM in affecting cognitive function among MUD patients.

Methods:

We recruited 558 MUD patients and 459 healthy controls, assessed cognitive function using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) and CM using the Chinese version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in all participants, and genotyped all patients and 158 healthy controls for the BDNF rs10835210 polymorphism.

Results:

CM negatively affected cognitive performance in both MUD patients and healthy controls, especially in visuospatial/constructional abilities (HC: FDR p < 0.001), attention (HC: FDR p = 0.008; MUD: FDR p < 0.001), and RBANS total score (HC: FDR p < 0.001; MUD: FDR p = 0.006). Furthermore, a significant interaction between CM and the BDNF rs10835210 polymorphism on attention (FDR p = 0.006) was observed in MUD patients, but not in healthy controls. Post hoc analyses revealed that among carriers of the BDNF rs10835210 A allele, MUD patients with CM had lower RBANS attention scores (FDR p < 0.001) than those without CM. In contrast, no significant simple main effect of CM on RBANS attention was found among MUD patients carrying BDNF rs10835210 CC genotype.

Conclusions:

Our findings suggest that CM impairs multiple aspects of cognitive function in MUD patients. Moreover, the BDNF gene rs10835210 polymorphism mediates the effect of CM on cognitive function in this population.

Insights

Childhood maltreatment (CM) impairs cognitive function in methamphetamine use disorder (MUD) patients. The BDNF gene rs10835210 polymorphism influences how CM affects attention in MUD patients.

Area of Science:

Neuroscience
Genetics
Psychiatry

Background:

Methamphetamine use disorder (MUD) is linked to cognitive dysfunction.
Childhood maltreatment (CM) exacerbates cognitive deficits in MUD patients.
Brain-derived neurotrophic factor (BDNF) gene polymorphisms are crucial for cognitive function.

Purpose of the Study:

To investigate the interaction between BDNF gene polymorphism and CM in MUD patients' cognitive function.
To determine if BDNF rs10835210 genotype modifies the impact of CM on cognition.
To explore the specific cognitive domains affected by this interaction.

Main Methods:

Recruited 558 MUD patients and 459 healthy controls.
Assessed cognitive function using the Repeated Battery for the Assessment of Neuropsychological Status (RBANS).
Evaluated CM using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) and genotyped BDNF rs10835210 polymorphism.

Main Results:

CM negatively impacted cognitive performance, particularly attention, in both MUD patients and controls.
A significant interaction between CM and BDNF rs10835210 polymorphism on attention was found in MUD patients.
MUD patients with the BDNF rs10835210 A allele and CM showed significantly lower attention scores.

Conclusions:

Childhood maltreatment significantly impairs cognitive function in MUD patients.
The BDNF rs10835210 polymorphism plays a mediating role in the effect of CM on cognitive function, specifically attention, in MUD patients.

Read full analysis

Keywords:

BDNF rs10835210 Childhood maltreatment Cognitive function Gene–environment interaction Methamphetamine use disorder

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