Impulsive Internet Game Play Is Associated With Increased Functional Connectivity Between the Default Mode and Salience Networks in Depressed Patients With Short Allele of Serotonin Transporter Gene

Abstract

Problematic Internet game play is often accompanied by major depressive disorder (MDD). Depression seems to be closely related to altered functional connectivity (FC) within (and between) the default mode network (DMN) and salience network. In addition, serotonergic neurotransmission may regulate the symptoms of depression, including impulsivity, potentially by modulating the DMN. We hypothesized that altered connectivity between the DMN and salience network could mediate an association between the 5HTTLPR genotype and impulsivity in patients with depression. A total of 54 participants with problematic Internet game play and MDD completed the research protocol. We genotyped for 5HTTLPR and assessed the DMN FC using resting-state functional magnetic resonance imaging. The severity of Internet game play, depressive symptoms, anxiety, attention and impulsivity, and behavioral inhibition and activation were assessed using the Young Internet Addiction Scale (YIAS), Beck Depressive Inventory, Beck Anxiety Inventory (BAI), Korean Attention Deficit Hyperactivity Disorder scale, and the Behavioral Inhibition and Activation Scales (BIS-BAS), respectively. The SS allele was associated with increased FC within the DMN, including the middle prefrontal cortex (MPFC) to the posterior cingulate cortex, and within the salience network, including the right supramarginal gyrus (SMG) to the right rostral prefrontal cortex (RPFC), right anterior insular (AInsular) to right SMG, anterior cingulate cortex (ACC) to left RPFC, and left AInsular to right RPFC, and between the DMN and salience network, including the MPFC to the ACC. In addition, the FC from the MPFC to ACC positively correlated with the BIS and YIAS scores in the SS allele group. The SS allele of 5HTTLPR might modulate the FC within and between the DMN and salience network, which may ultimately be a risk factor for impulsive Internet game play in patients with MDD.

Keywords: Internet gaming disorder; default mode network; major depressive disorder; salience network; serotonin transporter gene.

Figure 1

Comparing brain functional connectivity of brain areas between the SS and SL + LL allele groups. Default mode network.middle prefrontal cortex (DMN.MPFC) to posterior cingulate cortex (DMN.PCC): t = 2.42, FDRq = 0.02; left salience network.anterior insular (SAL.AInsula) to right rostral prefrontal cortex (SAL.RPFC): t = 2.42, FDRq = 0.02; right SAL.AInsula (SAL.AInsula) to right SAL supramarginal gyrus (SAL.SMG): t = 2.40, FDRq = 0.02; right SAL.SMG to right SAL.RPFC: t = 2.02, FDRq < 0.05; SAL.ACC to left SAL.RPFC: t = 2.15, p = 0.04; DMN.MPFC to anterior cingulate cortex (SAL.ACC): t = 2.61, FDRq = 0.01.

Figure 2

Correlation between clinical scales and brain connectivity in all patients with major depressive disorder (MDD) and Internet gaming disorder (IGD). (A) Correlation between the BAS scores and the Young Internet Addiction Scale (YIAS) scores in all patients with MDD with IGD (r = 0.63, p < 0.01), (B) correlation between the YIAS scores and FC between anterior cingulate cortex (ACC) to middle prefrontal cortex (MPFC) in all Patients with MDD with IGD (r = 0.58, p < 0.01), (C) correlation between the BAS scores and FC between ACC to MPFC in all patients with MDD with IGD (r = 0.42, p < 0.01), (D) correlation between the Beck Depressive Inventory (BDI) scores and FC between PCC to MPFC in all patients with MDD with IGD (r = 0.51, p < 0.01).

Figure 3

Correlation between clinical scales and brain connectivity in the SS allele and SL + LL allele groups. (A) Correlation between the BAS and Young Internet Addiction Scale (YIAS) scores in the SS allele group (r = 0.68, p < 0.01), (B) correlation between the BIS scores and FC from anterior cingulate cortex (ACC) to middle prefrontal cortex (MPFC) in SS allele group (r = 0.48, p = 0.01), (C) correlation between the YIAS scores and FC from ACC to MPFC in SS allele group (r = 0.64, p < 0.01).