Abnormal functional connectivity between the anterior cingulate and the default mode network in drug-naïve boys with attention deficit hyperactivity disorder.

A previous study indicated that adults with attention deficit hyperactivity disorder (ADHD) had a decreased anti-correlation between the dorsal anterior cingulate cortex (dACC) and the default mode network (DMN). In this study, we investigated whether children with ADHD also show a decreased anti-correlation between the dACC and the DMN. We also explored the developmental characteristics of the resting-state functional connectivity (RSFC) of the dACC with the DMN in children with ADHD. Resting-state functional magnetic resonance imaging scans were obtained from a 3T scanner in 19 drug-naïve boys with ADHD and 23 controls. Compared with normal controls, the dACC in boys with ADHD showed a significantly decreased negative RSFC with the DMN, including the dorsomedial prefrontal cortex and the posterior cingulate cortex. The RSFC strength between the dACC and the posterior cingulate cortex showed a significantly negative correlation with age in normal controls, but not in boys with ADHD. This decreased anti-correlation may suggest an abnormal balance or interaction between attentional and intrinsic thoughts. Our age-related analysis suggested an abnormal development pattern of the dACC-DMN interaction in ADHD.

Mindfulness-Based Cognitive Therapy Regulates Brain Connectivity in Patients With Late-Life Depression.

Late-life depression (LLD) is an important public health problem among the aging population. Recent studies found that mindfulness-based cognitive therapy (MBCT) can effectively alleviate depressive symptoms in major depressive disorder. The present study explored the clinical effect and potential neuroimaging mechanism of MBCT in the treatment of LLD. We enrolled 60 participants with LLD in an 8-week, randomized, controlled trial (ChiCTR1800017725). Patients were randomized to the treatment-as-usual (TAU) group or a MBCT+TAU group. The Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to evaluate symptoms. Magnetic resonance imaging (MRI) was used to measure changes in resting-state functional connectivity and structural connectivity. We also measured the relationship between changes in brain connectivity and improvements in clinical symptoms. HAMD total scores in the MBCT+TAU group were significantly lower than in the TAU group after 8 weeks of treatment (p < 0.001) and at the end of the 3-month follow-up (p < 0.001). The increase in functional connections between the amygdala and middle frontal gyrus (MFG) correlated with decreases in HAMA and HAMD scores in the MBCT+TAU group. Diffusion tensor imaging analyses showed that fractional anisotropy of the MFG-amygdala significantly increased in the MBCT+TAU group after 8-week treatment compared with the TAU group. Our study suggested that MBCT improves depression and anxiety symptoms that are associated with LLD. MBCT strengthened functional and structural connections between the amygdala and MFG, and this increase in communication correlated with improvements in clinical symptoms. Randomized Controlled Trial; Follow-Up Study; fMRI; Brain Connectivity.

Converging evidence implicates the dopamine D3 receptor gene in vulnerability to schizophrenia.

The dopamine D3 receptor has been implicated in the pathophysiology of schizophrenia (SZ). A glycine-to-serine polymorphism at codon 9 of the dopamine D3 receptor gene (DRD3), rs6280, has been widely studied for its association with SZ, but with conflicting results. Altered levels of DRD3 mRNA have also been reported in SZ compared with normal controls. Moreover, it has been suggested that DRD3 is subject to recent positive selection in European populations. To explore the potential role of DRD3 in SZ from these various aspects, we conducted a threefold study. First, we tested the genetic association of rs6280 with SZ in 685 SZ patients and 768 normal controls. Second, we examined DRD3 mRNA levels in peripheral leukocytes in a subset of 37 patients and 37 controls. Finally, we investigated the possible recent positive selection on DRD3 in an East Asian population. Consequently, we observed that the genotypic distribution of rs6280 was nominally associated with SZ (P = 0.045), with the ancestral CC genotype being significantly over-represented in SZ patients. DRD3 mRNA levels were significantly lower in patients than in controls (P = 5.91E-5). The derived C-allele of rs6280 might have been subject to recent positive selection (P < 0.001) in the East Asian population. Taken together, our results suggest that DRD3, a gene possibly under natural selection, might be involved in vulnerability to SZ in the Han Chinese population. These findings may further add to the body of data implicating DRD3 as a schizophrenia risk gene.

Enhanced resting-state brain activities in ADHD patients: a fMRI study.

Resting-state functional MRI (fMRI) could be an advantageous choice for clinical applications by virtue of its clinical convenience and non-invasiveness. Without explicit stimulus, resting-state brain activity patterns cannot be obtained using any model-driven method. In this study, we advanced a measure named resting-state activity index (RSAI) to evaluate the resting-state brain activities. Using RSAI, we first investigated the resting-state brain activity patterns in normal adolescents to test the validity of this RSAI measure. Then we compared the resting-state brain activity patterns of Attention deficit hyperactivity disorder (ADHD) patients to those of their matched controls. According to the resultant brain activity patterns, we suggest that RSAI could be an applicable measure to evaluate resting-state brain activities. As compared to the controls, the ADHD patients exhibited more significant resting-state activities in basic sensory and sensory-related cortices. This finding was in accordance with ADHD symptoms of inattention.

Asymmetry of prefrontal cortical convolution complexity in males with attention-deficit/hyperactivity disorder using fractal information dimension.

BACKGROUND AND PURPOSE: Prefrontal cortex, known to be a crucial region for the function of attention, is generally thought to be largely associated with the pathogenesis of attention-deficit hyperactivity disorder (ADHD). Most previous structural imaging studies of ADHD reported abnormality of grey matter volume in prefrontal region. However, volume measure is affected by the size of the interrogated brain, which may cause the inconsistence of the volume based findings. The purpose of the current paper is to use a scale-free measure, fractal information dimension (FID), to assess the prefrontal cortical convolution complexity and asymmetry in ADHD patients. METHODS: MRI scans from 12 boys with ADHD and 11 controls were carefully processed. Prefrontal cortex was outlined manually. FIDs of bilateral prefrontal cortical surface were examined in each case. Group differences of the bilateral prefrontal cortical convolution complexities and the asymmetry pattern were statistically tested. RESULTS: We found a left-greater-than-right prefrontal cortical convolution complexity pattern in both groups. However, compared with healthy controls, the left prefrontal cortical convolution complexities of ADHD patients were significantly reduced, resulting in significant reduction of the normal left-greater-than-right cortical convolution complexity asymmetry pattern. CONCLUSION: This study confirms and extends the existing anatomical knowledge about the brains of people with ADHD. The cortical convolution analysis method may also be applied to quantitatively assess changes in other neuropsychiatric syndromes as well.

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, [corrected] and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.

Abnormal neural activity in children with attention deficit hyperactivity disorder: a resting-state functional magnetic resonance imaging study.

In this study, a newly reported regional homogeneity approach was used to analyze blood oxygen level-dependent functional magnetic resonance imaging data on resting state in boys with attention deficit hyperactivity disorder. Boys with attention deficit hyperactivity disorder showed decreased regional homogeneity in the frontal-striatal-cerebellar circuits, but increased regional homogeneity mainly in the occipital cortex. Our findings are consistent with the hypothesis of abnormal frontal-striatal-cerebellar circuits in attention deficit hyperactivity disorder. The regional homogeneity approach may be a potentially useful method in exploring the pathophysiology of attention deficit hyperactivity disorder.

Altered resting-state functional connectivity patterns of anterior cingulate cortex in adolescents with attention deficit hyperactivity disorder.

Dorsal anterior cingulate cortex (dACC) has been found to function abnormally in attention deficit hyperactivity disorder (ADHD) patients in several former functional MRI (fMRI) studies. Resting-state low-frequency fluctuations (LFFs) of blood oxygen level-dependent (BOLD) fMRI signals have been proved to be quite informative. This study used resting-state LFFs to investigate the resting-state functional connectivity pattern differences of dACC in adolescents with and without ADHD. As compared to the controls, the ADHD patients exhibited more significant resting-state functional connectivities with the dACC in bilateral dACC, bilateral thalamus, bilateral cerebellum, bilateral insula and bilateral brainstem (pons). No brain region in the controls was found to exhibit more significant resting-state functional connectivity with the dACC. We suggest these abnormally more significant functional connectivities in the ADHD patients may indicate the abnormality of autonomic control functions in them.

[A preliminary study on the attentional networks of attention deficit hyperactivity disorder].

OBJECTIVE: To investigate the efficiency of the three attentional networks in attention deficit hyperactivity disorder (ADHD). METHODS: Subjects were 25 children, aged 7 to 12 years, with DSM-IV ADHD and 25 non-ADHD controls matched by age, sex and IQ. Attentional networks tests were performed in all the subjects on an IBM compatible computer. RESULTS: No differences were found between the ADHD children and the normal controls in alerting and orienting effects. However, ADHD children had a significantly larger executive control effect than their normal counterparts. The general accuracy of the ADHD children was significantly lower than that of the normal controls. CONCLUSION: ADHD children may have impairments in their executive control network of attention.

Local synchronization and amplitude of the fluctuation of spontaneous brain activity in attention-deficit/hyperactivity disorder: a resting-state fMRI study.

Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging (RS-fMRI) data. Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder (ADHD) remains unknown. In this study, we applied ReHo and ALFF to 23 medication-naïve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis. Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD. We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipito-cerebellar circuitry, while the ALFF method showed a difference only in the right occipital area. When a larger smoothing kernel and a more lenient threshold were used for ALFF, more overlapped regions were found between ALFF and ReHo, and ALFF even found some new regions with group differences. The ADHD symptom scores were correlated with the ReHo values in the right cerebellum, dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group, while no correlation was detected between ALFF and ADHD symptoms. In conclusion, ReHo may be more sensitive to regional abnormalities, at least in boys with ADHD, than ALFF. And ALFF may be complementary to ReHo in measuring local spontaneous activity. Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.

MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia.

MicroRNAs (miRNAs) are short, non-coding RNAs that regulate the stability and translation of mRNA targets. Increasing evidence suggests that miRNAs could be involved in the initiation and progression of neuropsychiatric disorders. Prior to this study, six miRNAs had been reported to show a significantly abnormal expression level in schizophrenic brains. Also, common single nucleotide polymorphisms within two miRNA transcripts have shown genetic associations with schizophrenia. However, it remains largely unknown whether variants in these miRNA genes and/or in their target sites are associated with schizophrenia. Here, we selected the above eight miRNAs, plus 15 of their experimentally validated target sites, as candidate susceptibility factors for schizophrenia, for mutation screening and further association studies in Chinese case-control samples. We identified a new potentially functional variant ss178077483 located in the pre-mir-30e, which was strongly associated with schizophrenia (allelic P=0.00017; genotypic P=0.00015), with an odds ratio of 4.952 (95% confidence interval: 1.887-12.998). We also demonstrated that this new variant ss178077483, combined with mir-30e rs7556088 and mir-24-MAPK14 rs3804452, showed a weak gene-gene interaction for schizophrenia risk (P=0.001). In addition, analysis of gene expression demonstrated that expression of the mature mir-30e in the peripheral leukocytes was significantly higher in patients' group than in the control group (P=6.79e-7).This is the first study to indicate that mir-30e ss178077483 plays a role in schizophrenia susceptibility. It suggests that the contribution of mir-30e to the processes that lead to schizophrenia should be further investigated.

Abnormal resting-state functional connectivity patterns of the putamen in medication-naïve children with attention deficit hyperactivity disorder.

Structural and functional alterations of the putamen have been reported in patients with attention deficit hyperactivity disorder (ADHD), but the functional relationships between this area and other brain regions are seldom explored. In the present study, seed-based correlation analyses were performed in the resting-state functional magnetic resonance imaging (fMRI) data to examine the differences in functional connectivity of the putamen between medication-naïve children with ADHD and normal children. Positive functional connectivity with the putamen-ROIs was seen in bilateral sensorimotor area, prefrontal cortex, insula, superior temporal gyrus and subcortical regions and negative functional connectivity was located in bilateral parietal and occipital cortex as well as clusters in the frontal, middle temporal cortex and cerebellum. Group comparison showed that decreases in functional connectivity with the putamen-ROIs were observed in ADHD relative to the controls, except for the right globus pallidus/thalamus, which showed increased positive connectivity with left putamen-ROI. For children with ADHD, areas exhibiting decreased positive functional connectivity with left putamen-ROI were seen in right frontal and limbic regions, and regions showing decreased negative connectivity with the putamen-ROIs were observed in areas belonging to the default mode network (for left putamen-ROI, including right cerebellum and right temporal lobe; for right putamen-ROI, including left cerebellum and right precuneus). The above results suggest that abnormal functional relationships between the putamen and the cortical-striatal-thalamic circuits as well as the default mode network may underlie the pathological basis of ADHD.

Fisher discriminative analysis of resting-state brain function for attention-deficit/hyperactivity disorder.

In this study, a resting-state fMRI based classifier, for the first time, was proposed and applied to discriminate children with attention-deficit/hyperactivity disorder (ADHD) from normal controls. On the basis of regional homogeneity (ReHo), a mapping of brain function at resting state, PCA-based Fisher discriminative analysis (PC-FDA) was trained to build a linear classifier. Permutation test was then conducted to identify the brain areas with the most significant contribution to the final discrimination. Experimental results showed a correct classification rate of 85% using a leave-one-out cross-validation. Moreover, some highly discriminative brain regions, like the prefrontal cortex and anterior cingulate cortex, well confirmed the previous findings on ADHD. Interestingly, some important but less reported regions such as the thalamus were also identified. We conclude that the classifier, using resting-state brain function as classification feature, has potential ability to improve current diagnosis and treatment evaluation of ADHD.