Mingying Du

Is depression a disconnection syndrome? Meta-analysis of diffusion tensor imaging studies in patients with MDD

BACKGROUNDnMany studies using diffusion tensor imaging (DTI) have demonstrated impaired white matter integrity in patients with major depressive disorder (MDD), with significant results found in diverse brain regions. We sought to identify whether there are consistent changes of regional white matter integrity in patients with MDD, as shown by decreased fractional anisotropy in DTI.nnnMETHODnA systematic search strategy was used to identify relevant whole brain voxel-based DTI studies of patients with MDD in relation to comparison groups. Relevant databases were searched for studies published between January 1994 and February 2011 using combinations of the terms DTI or diffusion tensor; whole brain or voxel-based; and depress*. Using the studies that met our inclusion criteria, we performed a meta-analysis of the coordinates of decreased fractional anisotropy using the activation likelihood estimation (ALE) method, which detects 3-dimensional conjunctions of coordinates from multiple studies, weighted by sample size. We then used DTIquery software for fibre tracking to locate the fascicles involved in each region.nnnRESULTSnWe included 11 studies with a combined sample of 231 patients with MDD and 261 comparison participants, providing 50 coordinates of decreased fractional anisotropy. Our meta-analysis identified 4 consistent locations of decreased fractional anisotropy in patients with MDD: white matter in the right frontal lobe, right fusiform gyrus, left frontal lobe and right occipital lobe. Fibre tracking showed that the main fascicles involved were the right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, right posterior thalamic radiation and interhemispheric fibres running through the genu and body of the corpus callosum.nnnLIMITATIONSnThe number of studies included was relatively small, and the DTI data acquisition and analysis techniques were heterogeneous. The ALE method cannot handle studies with no significant group differences.nnnCONCLUSIONnVoxel-based analysis of DTI studies of patients with MDD consistently identified decreased fractional anisotropy in the white matter fascicles connecting the prefrontal cortex within cortical (frontal, temporal and occipital lobes) and subcortical areas (amygdala and hippocampus). This isstrong evidence for the involvement of these neural circuits in the pathology of MDD.

Voxelwise meta-analysis of gray matter reduction in major depressive disorder

BACKGROUNDnVoxel-based morphometry (VBM) has been widely used in studies of major depressive disorder (MDD) and has provided cumulative evidence of gray matter abnormalities in patients relative to controls. Thus we performed a meta-analysis to integrate the reported studies to determine the consistent gray matter alterations in MDD.nnnMETHODSnA systematic search was conducted to identify VBM studies which contrasted MDD patients against a comparison group. The coordinates of gray matter change across studies were meta-analyzed using the activation likelihood estimation (ALE) method hybridized with the rank-based Genome Scan Meta-Analysis (GSMA) to quantitatively estimate regional gray matter reductions in MDD.nnnRESULTSnA total of 20 VBM studies comparing 543 major depressive patients with 750 healthy control subjects were included. Consistent gray matter reductions in all MDD patients relative to healthy controls were identified in the bilateral anterior cingulate cortex (ACC), right middle and inferior frontal gyrus, right hippocampus and left thalamus.nnnCONCLUSIONSnMeta-analysis of all primary VBM studies indicates that significant gray matter reductions in MDD are localized in a distributed neural network which includes frontal, limbic and thalamic regions. Future studies will benefit from the use of a longitudinal approach to examine anatomical and functional abnormalities within this network and their relationship to clinical profile, particularly in first-episode and drug-naive MDD patients.

White matter deficits in first episode schizophrenia: An activation likelihood estimation meta-analysis

BACKGROUNDnDiffusion tensor imaging (DTI) has been widely used in psychiatric research and has provided evidence of white matter abnormalities in first episode schizophrenia (FES). The goal of the present meta-analysis was to identify white matter deficits by DTI in FES.nnnMETHODSnA systematic search was conducted to collect DTI studies with voxel-wised analysis of the fractional anisotropy (FA) in FES. The coordinates of regions with FA changes were meta-analyzed using the activation likelihood estimation (ALE) method which weighs each study on the basis of its sample size.nnnRESULTSnA total of 8 primary studies were selected, including 271 FES patients and 297 healthy controls. Among these studies, 52 regions showed reductions in the FA in FES while 2 regions had increased FA. Consistent FA reductions in the white matter of the right deep frontal and left deep temporal lobes were identified in all FES patients relative to healthy controls. Fiber tracking showed that the main tracts involved were the cingulum bundle, the left inferior longitudinal fasciculus, the left inferior fronto-occipital fasciculus and the interhemispheric fibers running through the corpus callosum.nnnCONCLUSIONSnThe current findings provide evidence confirming the lack of connection in the fronto-limbic circuitry at the early stages of the schizophrenia. Because the coordinates reported in the primary literature were highly variable, future investigations with large samples would be required to support the identified white matter changes in FES.

Brain grey matter abnormalities in medication-free patients with major depressive disorder: a meta-analysis.

BACKGROUNDnBecause cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment, inclusion of medicated patients may have biased previous meta-analyses of voxel-based morphometry (VBM) studies. A meta-analysis of VBM studies on medication-free MDD patients should be able to distinguish the morphological features of the disease itself from those of treatment.nnnMETHODnA systematic search was conducted for the relevant studies. Effect-size signed differential mapping was applied to analyse the grey matter differences between all medication-free MDD patients and healthy controls. Meta-regression was used to explore the effects of demographics and clinical characteristics.nnnRESULTSnA total of 14 datasets comprising 400 medication-free MDD patients and 424 healthy controls met the inclusion criteria. The pooled meta-analysis and subgroup meta-analyses showed robustly reduced grey matter in prefrontal and limbic regions in MDD. Increased right thalamus volume was only seen in first-episode medication-naive patients, and increased grey matter in the bilateral anterior cingulate cortex only in medication wash-out patients. In meta-regression analyses the percentage of female patients in each study was negatively correlated with reduced grey matter in the right hippocampus.nnnCONCLUSIONSnBy excluding interference from medication effects, the present study identified grey matter reduction in the prefrontal-limbic network in MDD. The subgroup meta-analysis results suggest that an increased right thalamus volume might be a trait directly related to MDD, while an increased anterior cingulate cortex volume might be an effect of medication. The meta-regression results perhaps reveal the structural underpinning of the sex differences in epidemiological and clinical aspects of MDD.

Grey matter reduction associated with posttraumatic stress disorder and traumatic stress.

In recent decades, many imaging studies have reported brain structural alterations in posttraumatic stress disorder (PTSD). However, due to differences in the selection of control subjects, it is difficult to conclude whether the observed alterations were related to disease or traumatic stress. The present study was to provide a quantitative voxelwise meta-analysis of grey matter (GM) changes in PTSD relative to either trauma-exposed controls without PTSD (TEC) or non-traumatised healthy controls (HC) separately and to conduct a systematic review of voxel-based morphometry (VBM) studies that compared trauma-exposed individuals with HC to explore the effect of traumatic stress. GM reduction was identified in the medial prefrontal cortex in PTSD compared to both TEC and HC. Additional GM reduction was also observed in PTSD in the left hippocampus, left middle temporal gyrus and right superior frontal gyrus compared with TEC. Additionally, GM decreased in the left occipital cortex in PTSD compared with HC. The present study delimited the significant differences among VBM results in PTSD research when different control groups were chosen.

The common traits of the ACC and PFC in anxiety disorders in the DSM-5: meta-analysis of voxel-based morphometry studies.

Background The core domains of social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder (PD) with and without agoraphobia (GA), and specific phobia (SP) are cognitive and physical symptoms that are related to the experience of fear and anxiety. It remains unclear whether these highly comorbid conditions that constitute the anxiety disorder subgroups of the Diagnostic and Statistical Manual for Mental Disorders – Fifth Edition (DSM-5) represent distinct disorders or alternative presentations of a single underlying pathology. Methods A systematic search of voxel-based morphometry (VBM) studies of SAD, GAD, PD, GA, and SP was performed with an effect-size signed differential mapping (ES-SDM) meta-analysis to estimate the clusters of significant gray matter differences between patients and controls. Results Twenty-four studies were eligible for inclusion in the meta-analysis. Reductions in the right anterior cingulate gyrus and the left inferior frontal gyrus gray matter volumes (GMVs) were noted in patients with anxiety disorders when potential confounders, such as comorbid major depressive disorder (MDD), age, and antidepressant use were controlled for. We also demonstrated increased GMVs in the right dorsolateral prefrontal cortex (DLPFC) in comorbid depression-anxiety (CDA), drug-naïve and adult patients. Furthermore, we identified a reduced left middle temporal gyrus and right precentral gyrus in anxiety patients without comorbid MDD. Conclusion Our findings indicate that a reduced volume of the right ventral anterior cingulate gyrus and left inferior frontal gyrus is common in anxiety disorders and is independent of comorbid depression, medication use, and age. This generic effect supports the notion that the four types of anxiety disorders have a clear degree of overlap that may reflect shared etiological mechanisms. The results are consistent with neuroanatomical DLPFC models of physiological responses, such as worry and fear, and the importance of the ventral anterior cingulate (ACC)/medial prefrontal cortex (mPFC) in mediating anxiety symptoms.

Quantitative Prediction of Individual Psychopathology in Trauma Survivors Using Resting-State fMRI

Neuroimaging techniques hold the promise that they may one day aid the clinical assessment of individual psychiatric patients. However, the vast majority of studies published so far have been based on average differences between groups. This study employed a multivariate approach to examine the potential of resting-state functional magnetic resonance imaging (MRI) data for making accurate predictions about psychopathology in survivors of the 2008 Sichuan earthquake at an individual level. Resting-state functional MRI data was acquired for 121 survivors of the 2008 Sichuan earthquake each of whom was assessed for symptoms of post-traumatic stress disorder (PTSD) using the 17-item PTSD Checklist (PCL). Using a multivariate analytical method known as relevance vector regression (RVR), we examined the relationship between resting-state functional MRI data and symptom scores. We found that the use of RVR allowed quantitative prediction of clinical scores with statistically significant accuracy (correlation=0.32, P=0.006; mean squared error=176.88, P=0.001). Accurate prediction was based on functional activation in a number of prefrontal, parietal, and occipital regions. This is the first evidence that neuroimaging techniques may inform the clinical assessment of trauma-exposed individuals by providing an accurate and objective quantitative estimation of psychopathology. Furthermore, the significant contribution of parietal and occipital regions to such estimation challenges the traditional view of PTSD as a disorder specific to the fronto-limbic network.

Functional MRI reveals different response inhibition between adults and children with ADHD

OBJECTIVEnAttention-deficit hyperactivity disorder (ADHD) has been recognized as a disorder of executive function, and a number of functional MRI (fMRI) studies have been conducted to investigate the altered brain activation patterns between ADHD patients and healthy controls. However, the findings across different studies have been inconsistent, and the different neural mechanisms between adults and children with ADHD remain unclear. The aim of this study was to perform a meta-analysis of fMRI studies to further investigate and compare the abnormalities in adults and children with ADHD during motor response inhibition.nnnMETHODnActivation likelihood estimation (ALE) was used to investigate brain activation differences between ADHD patients and controls, and a subtraction meta-analysis was performed to compare adult and child patients.nnnRESULTSnTwenty-three studies met the inclusion criteria. Meta-analysis using ALE detected significantly decreased activation during response inhibition in ADHD in the supplementary motor area, insula, caudate, and precentral gyrus, as well as increased activation in the postcentral gyrus, inferior frontal gyrus, and precuneus. The activation decreases in the right caudate were greater in child ADHD patients than adult ADHD patients.nnnCONCLUSIONSnThis meta-analysis identified dysfunction in several areas of the motor inhibition network that may play a role in the abnormal neural mechanisms of response inhibition in ADHD. The comparison of child and adult subgroups raises the possibility that the persistence of functional abnormalities of the caudate may be an important factor in whether ADHD persists.

Altered functional connectivity in the brain default-mode network of earthquake survivors persists after 2 years despite recovery from anxiety symptoms

Although acute impact of traumatic experiences on brain function in disaster survivors is similar to that observed in post-traumatic stress disorders (PTSD), little is known about the long-term impact of this experience. We have used structural and functional magnetic resonance imaging to investigate resting-state functional connectivity and gray and white matter (WM) changes occurring in the brains of healthy Wenchuan earthquake survivors both 3 weeks and 2 years after the disaster. Results show that while functional connectivity changes 3 weeks after the disaster involved both frontal-limbic-striatal and default-mode networks (DMN), at the 2-year follow-up only changes in the latter persisted, despite complete recovery from high initial levels of anxiety. No gray or WM volume changes were found at either time point. Taken together, our findings provide important new evidence that while altered functional connectivity in the frontal-limbic-striatal network may underlie the post-trauma anxiety experienced by survivors, parallel changes in the DMN persist despite the apparent absence of anxiety symptoms. This suggests that long-term changes occur in neural networks involved in core aspects of self-processing, cognitive and emotional functioning in disaster survivors which are independent of anxiety symptoms and which may also confer increased risk of subsequent development of PTSD.

Microstructural brain abnormalities in medication-free patients with major depressive disorder: a systematic review and meta-analysis of diffusion tensor imaging.

Background Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.