Fibroblast growth factor 21 associating with serotonin and dopamine in the cerebrospinal fluid predicts impulsivity in healthy subjects

Jinzhong Xu,Song Qian,Yuying Li,Yanlong Liu,Huai Li,Jue He,Li Chen,Wenhui Lin,Xiaokun Li,Hui Li,Lijing Chen,Yuncao Fan,Fan Wang,Haiyun Xu,Fenzan Wu

doi:10.1186/s12868-021-00676-7

Abstract

BackgroundImpulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. However, no biomarker of impulsivity available so far. This study explored the association between cerebrospinal fluid (CSF) fibroblast growth factor 21 (FGF21), a key hormonal mediator of the stress response, and impulsivity in healthy subjects.MethodsA total of 126 healthy persons subjected to surgery of anterior cruciate ligament were recruited in the present study. The impulsiveness of the subjects was evaluated by the Chinese version of the Barratt Impulsiveness Scale (BIS)-11 before surgery. CSF and blood samples of the subjects were collected before spinal anesthesia for surgery. The levels of FGF21, serotonin and dopamine in CSF and the level of FGF21 in blood of the subjects were measured by ELISA using commercial kits.ResultsNegative correlations were found between BIS-11 total score and either FGF21, serotonin or dopamine in CSF. However, BIS-11 total score was not correlated with FGF21 in blood. In addition, FGF21 was positively correlated with serotonin and dopamine in CSF, respectively. Multivariable linear regression models indicated that the decrease of FGF21 level associating with the decrease of serotonin and dopamine level in CSF contributed to the higher impulsivity. Furthermore, receiver operating characteristic curve (ROC) analysis indicated an important role of CSF FGF21 predicting high impulsivity.ConclusionsFGF21, serotonin and dopamine in CSF associate with impulsivity in opposite directions. The decrease of CSF FGF21 is related to higher impulsivity, and indicate that CSF FGF21 may predict impulsivity in healthy subjects.

Highlights

Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders
cerebrospinal fluid (CSF) serotonin and dopamine levels obtained in the subjects before the scheduled surgery of the cruciate ligament injury in the present study and in normal subjects could be comparable, and dopamine and serotonin levels as shown in Table 1 in the present study might be equal to the baseline levels of dopamine and serotonin in the healthy subjects
The decrease of fibroblast growth factor 21 (FGF21) contributed to the increase of impulsivity and the decrease of serotonin and dopamine in CSF Multivariable linear regression analysis was performed to evaluate the effect of CSF FGF21 on impulsivity, and the results showed that the decrease of CSF FGF21 contributed to the increase of impulsivity in an unadjusted model (Model 1), which suggested that every 0.084 pg/ ml decrease in CSF FGF21 may induce one unit increase of impulsivity

Summary

Introduction

Impulsivity is more commonly reported in subjects with mental disorders compared to healthy subjects, suggesting a potential application of impulsivity in predicting impulsivity-related mental disorders. No biomarker of impulsivity available so far. Impulsivity is a part of normal behavior and a potential shared pathological feature of mental disorders [2]. Xu et al BMC Neuroscience (2021) 22:68 subjects with conduct disorders, attention-deficit hyperactivity disorder (ADHD), disorders of personality, eating disorders, substance and alcohol abuse, psychotic disorders, bipolar disorders and dementia, suggesting the presence of a universal biological mechanism underlying the impulsivity in these mental and behavioral disorders [3,4,5,6]. It is very important to identify the subjects with high impulsivity tendency, and a biomarker of impulsivity will help to find, diagnose and treat the impulsivity-related mental disorders in the early stage in general population or currently healthy subjects. In order to pursue the biomarkers of impulsivity, a potential biomarker in CSF and blood was investigated

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Results

Discussion

Conclusion