Correlation analysis between fractional anisotropy (FA) and behavioral measures within the Internet addiction disorder (IAD) group.

<p>To aid visualization, regions showing significant correlations (red) are thickened using the tbss_fill script implemented in FSL. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030253#pone-0030253-g002" target="_blank">Figure 2A</a> shows FA values in the left genu of the corpus callosum correlates negatively with the Screen for Child Anxiety Related Emotional Disorders (SCARED) (r = −0.621, <i>p</i> = 0.008). <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030253#pone-0030253-g002" target="_blank">Figure 2B</a> shows FA values in the left external capsule correlates negatively with the Young's Internet addiction scale (YIAS) (r = −0.566, <i>p</i> = 0.018).</p

Assays of copy number in <i>SHANK2</i> and <i>SHANK3</i> genes.

<p>The copy number states of five segments in ASD patients were shown in five panels. Panel A: exon7 of <i>SHANK2</i>; Panel B: intron16-exon17 of <i>SHANK2</i>. Panel C: exon25 of <i>SHANK2</i>; Panel D: exon6 of <i>SHANK3</i>; Panel E: exon22 of <i>SHANK3</i>. Each column indicates a patient. All ASD cases showed two copy of <i>SHANK2/SHANK3.</i></p

Linkage disequilibrium block of <i>NLGN4</i> gene.

<p>The color of each square from light to dark represents the level of LD from low to high. White: complete recombination; blue: partial linkage; red: complete linkage.</p

The distribution of allele frequencies for 6 SNPs in <i>NLGN4</i> gene.

<p>*P value not corrected for the multiple testing.</p

Group differences in diffusivity indices from volume-of-interests (corrected for age).

<p>*<i>p</i><0.05/22≈0.002 (ANCOVA with age as a covariate variable, Bonferroni corrected for multiple comparisons).</p><p>Abbreviation. WM: white matter; CON: controls; IAD: Internet addiction disorder; Da: axial diffusivity; Dr: radial diffusivity; MD: mean diffusivity; R: right; L: left. SD: standard deviation.</p

Lack of Association between NLGN3, NLGN4, SHANK2 and SHANK3 Gene Variants and Autism Spectrum Disorder in a Chinese Population

<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication, absence or delay in language development, and stereotyped or repetitive behaviors. Genetic studies show that neurexin-neuroligin (NRXN-NLGN) pathway genes contribute susceptibility to ASD, which include cell adhesion molecules <i>NLGN3</i>, <i>NLGN4</i> and scaffolding proteins <i>SHANK2</i> and <i>SHANK3</i>. Neuroligin proteins play an important role in synaptic function and trans-synaptic signaling by interacting with presynaptic neurexins. Shank proteins are scaffolding molecules of excitatory synapses, which function as central organizers of the postsynaptic density. Sequence level mutations and structural variations in these genes have been identified in ASD cases, while few studies were performed in Chinese population. In this study, we examined the copy numbers of four genes <i>NLGN4, NLGN3, SHANK2,</i> and <i>SHANK3</i> in 285 ASD cases using multiplex fluorescence competitive polymerase chain reaction (PCR). We also screened the regulatory region including the promoter region and 5′/3′ untranslated regions (UTR) and the entire coding region of <i>NLGN4</i> in a cohort of 285 ASD patients and 384 controls by direct sequencing of genomic DNA using the Sanger method. DNA copy number calculation in four genes showed no deletion or duplication in our cases. No missense mutations in <i>NLGN4</i> were identified in our cohort. Association analysis of 6 common SNPs in <i>NLGN4</i> did not find significant difference between ASD cases and controls. These findings showed that these genes may not be major disease genes in Chinese ASD cases.</p> </div

Neuroanatomical regions with reduced FA in adolescents with Internet addiction disorder relative to normal controls. (<i>p</i><0.01, TFCE corrected).

<p>Abbreviation. MNI: Montreal Neurological Institute; WM: white matter; R: right; L: left.</p><p>Note. Coordinates for the peak voxels are displayed.</p

Demographic information of the participants involved in this study.

<p>(YIAS = Young's Internet Addiction Scale, BIS-11 = Barratt Impulsiveness Scale-11, TMDS = Time Management Disposition Scale, SDQ-P = Strengths and Difficulties Questionnaire parent version, SDQ-C = Strengths and Difficulties Questionnaire children version, FAD = McMaster Family Assessment Device).</p>a<p>The value was obtained by two-tailed Pearson Chi-square () test.</p>b<p>The value was obtained by two-sample two-tailed -test.</p><p>Demographic information of the participants involved in this study.</p

Disrupted Brain Functional Network in Internet Addiction Disorder: A Resting-State Functional Magnetic Resonance Imaging Study

<div><p>Internet addiction disorder (IAD) is increasingly recognized as a mental health disorder, particularly among adolescents. The pathogenesis associated with IAD, however, remains unclear. In this study, we aim to explore the encephalic functional characteristics of IAD adolescents at rest using functional magnetic resonance imaging data. We adopted a graph-theoretic approach to investigate possible disruptions of functional connectivity in terms of network properties including small-worldness, efficiency, and nodal centrality on 17 adolescents with IAD and 16 socio-demographically matched healthy controls. False discovery rate-corrected parametric tests were performed to evaluate the statistical significance of group-level network topological differences. In addition, a correlation analysis was performed to assess the relationships between functional connectivity and clinical measures in the IAD group. Our results demonstrate that there is significant disruption in the functional connectome of IAD patients, particularly between regions located in the frontal, occipital, and parietal lobes. The affected connections are long-range and inter-hemispheric connections. Although significant alterations are observed for regional nodal metrics, there is no difference in global network topology between IAD and healthy groups. In addition, correlation analysis demonstrates that the observed regional abnormalities are correlated with the IAD severity and behavioral clinical assessments. Our findings, which are relatively consistent between anatomically and functionally defined atlases, suggest that IAD causes disruptions of functional connectivity and, importantly, that such disruptions might link to behavioral impairments.</p></div

Between-group differences in terms of clinical and behavioral measures.

<p>(YIAS = Young's Internet Addiction Scale, BIS-11 = Barratt Impulsiveness Scale-11, TMDS = Time Management Disposition Scale, SDQ-P = Strengths and Difficulties Questionnaire parent version, SDQ-C = Strengths and Difficulties Questionnaire children version, FAD = McMaster Family Assessment Device).</p