Yixiao Fu

Genetic influences on resting‐state functional networks: A twin study

Alterations in resting‐state networks (RSNs) are often associated with psychiatric and neurologic disorders. Given this critical linkage, it has been hypothesized that RSNs can potentially be used as endophenotypes for brain diseases. To validate this notion, a critical step is to show that RSNs exhibit heritability. However, the investigation of the genetic basis of RSNs has only been attempted in the default‐mode network at the region‐of‐interest level, while the genetic control on other RSNs has not been determined yet. Here, we examined the genetic and environmental influences on eight well‐characterized RSNs using a twin design. Resting‐state functional magnetic resonance imaging data in 56 pairs of twins were collected. The genetic and environmental effects on each RSN were estimated by fitting the functional connectivity covariance of each voxel in the RSN to the classic ACE twin model. The data showed that although environmental effects accounted for the majority of variance in wide‐spread areas, there were specific brain sites that showed significant genetic control for individual RSNs. These results suggest that part of the human brain functional connectome is shaped by genomic constraints. Importantly, this information can be useful for bridging genetic analysis and network‐level assessment of brain disorders. Hum Brain Mapp 36:3959–3972, 2015.

Fronto-limbic disconnection in depressed patients with suicidal ideation: A resting-state functional connectivity study

BACKGROUND Suicidal ideation (SI) is highly prevalent and a known symptom of Major Depressive Disorder (MDD), but its underlying biological mechanisms are relatively unknown. Several studies linked suicidal ideation to dysfunctional brain circuits, specifically fronto-limbic connections. The purpose of this work was to investigate fronto-limbic disconnection in MDD patients with or without SI. METHODS MDD patients with SI (SI, n=28) or without SI (NSI, n=20), identified by the Scale for Suicide Ideation and healthy controls (HCs, n=30) underwent resting-state functional MRI scanning. The functional properties of correlations in neural activity (intrinsic functional connectivity, iFC) of the rostral anterior cingulate cortex (rACC) were analyzed among the three groups. Furthermore, correlation analyses between iFC, SI severity and depression severity were performed. RESULTS We found that the SI group exhibited decreased iFC between the rACC, the orbitomedial prefrontal cortex and the right middle temporal pole compared to HCs and NSI groups. The NSI group showed decreased iFC between the rACC and the orbitomedial prefrontal cortex compared to HCs. In the SI group, iFC strength between the right rACC and the middle temporal pole positively correlated with SI severity. CONCLUSION Transdiagnostic and diagnosis-specific alterations of fronto-limbic iFC were found in MDD patients with or without SI. Disrupted fronto-limbic circuits may impact decision-making and emotional processing in SI. These results provide useful information about the pathophysiological mechanisms of MDD patients with SI.

Antidepressant Effects of Electroconvulsive Therapy Correlate With Subgenual Anterior Cingulate Activity and Connectivity in Depression.

AbstractThe mechanisms underlying the effects of electroconvulsive therapy (ECT) in major depressive disorder (MDD) are not fully understood. Resting-state functional magnetic resonance imaging (rs-fMRI) is a new tool to study the effects of brain stimulation interventions, particularly ECT. The authors aim to investigate the mechanisms of ECT in MDD by rs-fMRI.They used rs-fMRI to measure functional changes in the brain of first-episode, treatment-naive MDD patients (n = 23) immediately before and then following 8 ECT sessions (brief-pulse square-wave apparatus, bitemporal). They also computed voxel-wise amplitude of low-frequency fluctuation (ALFF) as a measure of regional brain activity and selected the left subgenual anterior cingulate cortex (sgACC) to evaluate functional connectivity between the sgACC and other brain regions.Increased regional brain activity measured by ALFF mainly in the left sgACC following ECT. Functional connectivity of the left sgACC increased in the ipsilateral parahippocampal gyrus, pregenual ACC, contralateral middle temporal pole, and orbitofrontal cortex. Importantly, reduction in depressive symptoms were negatively correlated with increased ALFF in the left sgACC and left hippocampus, and with distant functional connectivity between the left sgACC and contralateral middle temporal pole. That is, across subjects, as depression improved, regional brain activity in sgACC and its functional connectivity increased in the brain.Eight ECT sessions in MDD patients modulated activity in the sgACC and its networks. The antidepressant effects of ECT were negatively correlated with sgACC brain activity and connectivity. These findings suggest that sgACC-associated prefrontal-limbic structures are associated with the therapeutic effects of ECT in MDD.

Electroconvulsive Therapy-Induced Brain Structural and Functional Changes in Major Depressive Disorders: A Longitudinal Study

Background This study aimed to study the brain structural and functional changes after 8 courses of electroconvulsive therapy (ECT) on patients with major depressive disorder (MDD). Material/Methods MRI scans were performed on 12 depressive patients before and after 8 courses of ECT and compared with those of 15 normal controls. Data were analyzed by voxel-based morphometry (VBM) using SPM8 software. Functional MRI (fMRI) and regional homogeneity (ReHo) analyses were used to assess the functional changes after ECT. Results Grey matter volumes were smaller in the right cingulate gyrus of depressive patients before ECT compared with normal controls. After false discovery rate (FDR) correction, post-ECT grey matter volumes were increased in bilateral amygdala and hippocampus compared with pre-ECT. Resting-state ReHo maps showed significant differences in brain activity pre- and post-ECT. Compared with healthy controls, MDD patients treated with 8 courses of ECT showed higher ReHo values in the bilateral frontal lobe, bilateral parietal lobe, and right caudate nucleus. Decreased ReHo values were observed in the right medial temporal gyrus, right superior temporal gyrus, right cingulate gyrus, and left anterior cerebellar lobe. Conclusions Results suggested that there were both structural and functional differences between the brains of MDD patients and healthy controls. After ECT, both structural and functional changes occurred, but without complete recovery to normal. ECT may display effects through regulating other brain regions to compensate for the original defects.

Changes in the expression of hippocampal proteins in rats with recrudescence of morphine addiction

The high recrudescence rate of drug addiction has received attention worldwide and its mechanisms remain to be elucidated. This study aimed to analyse the disparate protein expression in the hippocampal tissue of rats with recrudescence of morphine addiction, as well as to provide clues for the exploration of the recrudescence mechanism. Sixteen male adult Sprague-Dawley rats were divided equally into the morphine and physiological saline groups. Effective nose pokes were determined as the main index. The proteins were separated using the immobilised pH gradient two-dimensional polyacrylamide gel electrophoresis (2-DE). Disparate protein spots were analysed using the PDQuest 2-DE software. Peptide dactylograms were obtained using the matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry. The effective nose poke counts of the morphine group significantly increased during addiction maturation compared with the saline group (P<0.001). The post-recrudescence nose poke counts of the morphine group significantly increased compared with those before recrudescence (P<0.001). Fifteen disparate proteins were identified according to the protein electrophoresis of the morphine and physiological saline groups, including three proteins associated with energy metabolism, two ionic channel regulatory proteins, one heat shock protein and one exogenous substance metabolic enzyme. The energy metabolism and expression of cell metabolism-related proteins decreased in the hippocampus of rats with morphine recrudescence.

Reorganization of Anatomical Connectome following Electroconvulsive Therapy in Major Depressive Disorder

Objective. Electroconvulsive therapy (ECT) is considered one of the most effective and fast-acting treatment options for depressive episodes. Little is known, however, about ECTs enabling brain (neuro)plasticity effects, particular for plasticity of white matter pathway. Materials and Methods. We collected longitudinal diffusion tensor imaging in the first-episode, drug-naïve major depressive disorder (MDD) patients (n = 24) before and after a predefined time window ECT treatment. We constructed large-scale anatomical networks derived from white matter fiber tractography and evaluated the topological reorganization using graph theoretical analysis. We also assessed the relationship between topological reorganization with improvements in depressive symptoms. Results. Our investigation revealed three main findings: (1) the small-worldness was persistent after ECT series; (2) anatomical connections changes were found in limbic structure, temporal and frontal lobes, in which the connection changes between amygdala and parahippocampus correlate with depressive symptom reduction; (3) significant nodal strength changes were found in right paralimbic network. Conclusions. ECT elicits neuroplastic processes associated with improvements in depressive symptoms that act to specific local ventral frontolimbic circuits, but not small-world property. Overall, ECT induced topological reorganization in large-scale brain structural network, opening up new avenues to better understand the mode of ECT action in MDD.

Regional Cortical Surface Area in Adolescents: A Preliminary MRI Twin Study of Genetic and Environmental Contributions

Cortical surface area (CSA) has particular relevance for understanding development, behavior, and the connection between brain structure and function. Little is known about genetic and environmental determinants of CSA during development. We utilized bivariate twin methods to identify global and regionally specific genetic factors which influence CSA in a preliminary sample of typically-developing adolescents, with hypotheses based on findings in middle-aged adults. Similar to previous findings, we observed high heritability for total CSA. There was also significant evidence for genetic influences on regional CSA, particularly when these were not adjusted for total CSA, with highest heritability in frontal cortex and relatively fewer genetic contributions to medial temporal cortical structures. Adjustment for total CSA reduced regional CSA heritability dramatically, but a moderate influence of genetic factors remained in some regions. Both global and regionally-specific genetic factors influence regional CSA during adolescence.

Twins methods quantitatively explore the genetic impact on children and adolescents brain gray matter volume

The gray matter volumes of 58 pairs of twins ranging in age from 12 to 18 were measured by MRI to explore the genetic and environmental impacts on gray matter volume in twin children and adolescents. By means of A/C/E structural equation modeling, it was found that the gray matter volume in children and adolescents was jointly affected by genetic (A: 0.89) and environmental factors while genetic factors play a greater role. The gray matter volume in frontal lobe, parietal lobe, occipital lobe and lateral temporal lobe was mainly affected by genetics (A: 0.7–0.89), where as the gray matter volume in medial temporal lobe and cingulate cortex was affected by both genetics and environment.

1393 – The study on validity and reliability of questionnaires related to family environment

Objectives To introduce some questionnaires related to family environment such as FAD-GFS (The General Functioning Scale of the MacMaster Family Activity Device), SLE (stressful life events), FSQ (Family Stresses Questionnaire), FLQ (Family Life Questionnaire), EFQ (Everyday Feelings Questionnaire) and evaluate their validity and reliability. Methods Using cross-sectional design. The general questionnaire, FAD-GFS, SLE, FSQ, FLQ, EFQ were used to collect information about family environment from 504 parents of only children FACESII-CV and Index of General Affect were used as scale of criteria related. Results The reliability and validity of FAD-GFS, SLE, FSQ, FLQ, EFQ is: Cronbach coefficient were 0.695 to 0.749; re-test reliability were 0.712 to 0.901; The scores of the scale in those questionnaires were correlated with each factor significantly and the coefficient of correlation is more than those between each factor of those scales. The correlation between the scores of FSQ, EFQ and the scores of Index of General Affect was-0.192, 0.539; The correlation between the scores of FAD-GFS, FLQ the score of total and three factor differently and the scores of family cohesion scores (FACESII-CV) was -0.423, 0.237, 0.514, 0.302, 0.210. Conclusion FAD-GFS, SLE, FSQ, FLQ, EFQ has good reliability and validity, in line with requirements of psychometric and is useful as a tool to evaluate the family environment.

1368 – Study on validity and reliability of the chinese version of parenting styles and dimensions questionnaire (PSDQ)

Objective To evaluate the validity and reliability of the Chinese version of PSDQ Parenting Styles And Dimensions Questionnaire, PSDQ. Methods 443 parents whose children aged 6 to 16 who lived in Chongqing were selected. 52 of them were retested 6 weeks later in order to assess the retest reliability. Determination of reliability include:internal consistency: to calculate Cronbach coefficient; coefficient of retest reliability: to calculate Person correlation of results of the results in every subscale in twice measurements of 52 parents. Determination of validity: content validity, structural validity, discriminant validity, confirmatory factor analysis. Results For each subscale and factor, the values of kappa for inter - rater reliability were 0.625 to 0.884 (p Conclusion Parenting Styles And Dimensions Questionnaire (PSDQ) has good reliability and validity, in line with requirements of Psychometric is useful as a tool to evaluate the parenting styles from parents.