Qingsen Ming

Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents

Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR “SS” genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions.

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder.

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.

Whole-brain resting-state functional connectivity identified major depressive disorder: A multivariate pattern analysis in two independent samples.

BACKGROUND there has been a recent increase in the use of connectome-based multivariate pattern analysis (MVPA) of resting-state functional magnetic resonance imaging (fMRI) data aimed at distinguishing patients with major depressive disorder (MDD) from healthy controls (HCs). However, the validity of this method needs to be confirmed in independent samples. METHOD we used resting-state fMRI to explore whole-brain functional connectivity (FC) patterns characteristic of MDD and to confirm the effectiveness of MVPA in distinguishing MDD versus HC groups in two independent samples. The first sample set included 29 MDD patients and 33 HCs and second sample set included 46 MDD patients and 57 HCs. RESULTS for the first sample, we obtained a correct classification rate of 91.9% with a sensitivity of 89.6% and specificity of 93.9%. For the second sample, we observed a correct classification rate of 86.4% with a sensitivity of 84.8% and specificity of 87.7%. With both samples, we found that the majority of consensus FCs used for MDD identification were located in the salience network, default mode network, the cerebellum, visual cortical areas, and the affective network. LIMITATION we did not analyze potential structural differences between the groups. CONCLUSION results suggest that whole-brain FC patterns can be used to differentiate depressed patients from HCs and provide evidence for the potential use of connectome-based MVPA as a complementary tool in the clinical diagnosis of MDD.

The interactive effect of the MAOA-VNTR genotype and childhood abuse on aggressive behaviors in Chinese male adolescents

Objective Gene–environment interactions that moderate aggressive behavior have been identified in association with the MAOA (monoamine oxidase A) gene. The present study examined the moderating effect of MAOA-VNTR (variable number of tandem repeats) on aggression behavior relating to child abuse among Chinese adolescents. Materials and methods A sample of 507 healthy Chinese male adolescents completed the Child Trauma Questionnaire-Short Form (CTQ-SF) and Youth Self-report of the Child Behavior Checklist. The participants’ buccal cells were sampled and subjected to DNA analysis. The effects of childhood abuse (CTQ-SF scores), MAOA-VNTR [high-activity allele (H) versus low-activity allele (L)], and their interaction in aggressive behaviors were analyzed by linear regression. Results Child maltreatment was found to be a significant independent factor in the manifestation of aggressive behavior, whereas MAOA activity was not. There was a significant interaction between MAOA-VNTR and childhood maltreatment in the exhibition of aggressive behaviors. In the context of physical or emotional abuse, boys in the MAOA-L group showed a greater tendency toward aggression than those in the MAOA-H group. Conclusion Aggressive behavior arising from childhood maltreatment is moderated by MAOA-VNTR, which may be differentially sensitive to the subtype of childhood maltreatment experienced, among Chinese adolescents.

Screen time on school days and risks for psychiatric symptoms and self-harm in mainland Chinese adolescents

Objective: To investigate associations of television and of video game or non-educational computer use (VG/CU) exposure volumes in a typical school day with psychiatric symptoms and suicidal ideation/self-injurious behavior (self-harm), in mainland Chinese adolescents. Methods: Secondary school pupils (N = 13,659; mean age: 15.18 ± 1.89) from 10 urban areas sampled from different regions of mainland China were recruited. The subjects were divided into the following four screen exposure volume groups for television and VG/CU respectively based on a self-administered questionnaire: 0 h/day, >0 to ≤1 h/day, >1 to ≤2 h/day, and >2 h/day. Demographic and psychiatric symptoms were recorded for each respondent. Odds ratios (ORs) and 95% confidence intervals (CIs) for several types of psychological problems and self-harm were calculated. Results: More than 2 h per school day television watching was associated with higher risk of depression in both boys (OR = 1.33, 95%CI: 1.02–1.73) and girls (OR = 1.62, 95%CI: 1.19–2.21), of anxiety in boys (OR = 1.43, 95%CI: 1.05–1.95), of general emotional, behavioral, and social problems (GEBSPs; OR = 1.55, 95%CI: 1.01–2.39), and of oppositional defiant problems (OR = 1.65, 95% CI: 1.09–2.50) in girls, compared with no television exposure. Conversely, television exposure of no more than 1 h per school day was associated with lower self-harm risk in boys (OR = 0.81, 95%CI: 0.67–0.99) compared with no television exposure. High school day VG/CU time (>2 h) compared with no VG/CU were associated with higher risks of anxiety (OR = 1.40, 95%CI: 1.06–1.86) and of attention deficit/hyperactivity problems (ADHPs; OR = 1.56, 95%CI: 1.02–2.38) in boys. And any school day VG/CU exposure was associated with higher risks of self-harm and all other psychiatric problems in boys and all psychiatric problems (including anxiety and ADHPs) in girls (ORs, 1.44–3.69), compared to no VG/CU exposure. Conclusion: For secondary school students, associations of psychiatric problems and self-harm were more strongly associated with exposure to VG/CU than with exposure to television. The findings suggest that VG/CU and television exposure on weekdays should be considered in psychiatric interventions for adolescents.

Dysfunctional feedback processing in adolescent males with conduct disorder.

Abnormalities in neural feedback-processing systems may play a role in the development of dysfunctional behavior in individuals diagnosed with conduct disorder (CD). The present study investigated the relation between CD adolescents and feedback processing by measuring event-related potentials (ERPs) in a single outcome gambling task, which included reward valence (loss and gain) and reward magnitude (10 and 50cents) as outcomes. N2 and P3 components have been established as effective indicators in studies of behavioral disinhibition, reward processing, and decision-making. Eighteen adolescent males (age: 13-17years) diagnosed with CD and 19 healthy age-matched male controls were recruited. Compared to healthy controls, CD individuals exhibited reduced N2 amplitudes in response to loss condition. There was also a significant decreased P3 amplitude in all conditions. The amplitudes of P3 were negatively correlated with impulsivity scores across both groups, and the amplitudes of N2 were positively correlated with impulsivity scores across both groups. Our findings suggest that adolescents with CD may be impaired in neural sensitivity feedback and the processing of environmental cues compared to healthy controls. Moreover, N2 and P3 may be reliable indices to detect different sensitivity in reward and punishment feedback processing.

A Functional Polymorphism of the MAOA Gene Modulates Spontaneous Brain Activity in Pons

Objective. To investigate the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Methods. Thirty-one healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H) completed the 11-item Barratt Impulsiveness Scale (BIS-11) questionnaire and were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software. ALFF data were related to BIS scores and compared between genotype groups. Results. Compared with the MAOA-H group, the MAOA-L group showed significantly lower ALFFs in the pons. There was a significant correlation between the BIS scores and the ALFF values in the pons for MAOA-L group, but not for the MAOA-H group. Further regression analysis showed a significant genotype by ALFF values interaction effect on BIS scores. Conclusions. Lower spontaneous brain activity in the pons of the MAOA-L male adolescents may provide a neural mechanism by which boys with the MAOA-L genotype confers risk for impulsivity and aggression.

State-Independent and Dependent Neural Responses to Psychosocial Stress in Current and Remitted Depression

OBJECTIVE Stress is a strong risk factor for major depressive disorder, while sensitization to stress in remitted individuals plays a key role in depression recurrence. The present study explored the state-independent (trait) and dependent (state) neural responses to psychosocial stress in major depressive disorder. METHOD Thirty-six patients with medication-naive first-episode current depression, 33 patients with remitted depression, and 36 demographically matched healthy control participants were administered the Montreal Imaging Stress Task during functional MRI. One-way analyses of variance were used to assess differences in stress responses in the three groups. RESULTS Both currently depressed and remitted patients exhibited higher stress levels and cortisol responses than control subjects. Compared with control subjects, both depressed and remitted patients exhibited reduced activation in the ventromedial prefrontal cortex and increased activation in the precuneus. The stress-induced ventromedial prefrontal cortex activation changes negatively correlated with cortisol increases in all three groups. Additional increased activations were found in the dorsolateral prefrontal cortex and bilateral striatum in remitted patients compared with control subjects, and activation in these regions correlated inversely with depressive symptoms in the remitted group. CONCLUSIONS These findings provide novel evidence regarding the trait and state markers of depression on neural responses to psychosocial stress. Regional activation changes in the ventromedial prefrontal cortex and precuneus may reflect the trait markers of depression. Hyperactivation in the dorsolateral prefrontal cortex and striatum may represent a state-dependent compensatory mechanism during depression remission.

Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder.

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients.

Electrophysiological responses of feedback processing are modulated by MAOA genotype in healthy male adolescents.

A functional polymorphism in the promoter region of the monoamine oxidase A (MAOA) gene is closely related to aggression. Although previous studies suggested that impaired ability of feedback processing might be associated with aggressive behaviour, studies concerning the MAOA gene-related aggression rarely focused on the link between MAOA gene and feedback processing. We therefore sought to investigate the effect of MAOA genotype on electrophysiological responses of feedback processing in 72 healthy male adolescents during a simple monetary gambling task. Feedback processing was investigated by measuring the feedback-related negativity (FRN) and the P300 as electrophysiological markers. We observed a decreased electrophysiological response of the loss-gain difference waves from 250 to 350 ms (dFRN) in individuals with the lower activity alleles (MAOA-L) during the task, an effect that was driven primarily by the considerably altered response to monetary gains. The reduced dFRN in MAOA-L group might indicate poor ability to learn from feedback, which is followed by adjusting future behaviour. And MAOA-L carriers exhibited lower P300 compared with subjects with higher activity alleles (MAOA-H), which suggested fewer attentional resources were allocated to feedback processing. In addition, MAOA-L carriers demonstrated higher aggression and the aggression were inversely correlated with dFRN across two groups; further analyses suggested that dFRN mediated the MAOA genotype-aggression relationship. Consequently, we concluded that it might be the altered feedback processing that makes MAOA-L carriers more vulnerable to aggressive behaviour.