Evidence for fractional anisotropy and mean diffusivity white matter abnormalities in the internal capsule and cingulum in patients with obsessive-compulsive disorder

Background

There is evidence to suggest that obsessive–compulsive disorder (OCD) is associated with structural abnormalities in cortico–striato–thalamic circuits, yet the extent of white matter abnormalities is not well established. In this study, we used diffusion tensor imaging (DTI) to examine white matter integrity in specific regions of interest (ROIs) in patients with OCD.

Methods

Patients with OCD and sex-, age- and IQ-matched healthy controls underwent DTI. The primary objective was to explore whether patients with OCD had white matter abnormalities in the anterior limb of the internal capsule (ALIC), the uncinate fasciculus, the genu of the corpus callosum and the cingulum. The secondary objective was to evaluate the relation between fractional anisotropy and mean diffusivity in these ROIs and other clinical variables (including age at onset of OCD, OCD severity and levels of depressive and anxiety symptomatology) in patients with OCD.

Results

There were 15 patients and 17 controls enrolled in our study. Compared with healthy controls, patients with OCD showed increased fractional anisotropy in bilateral regions of the ALIC adjacent to the body of the caudate, as well as decreased fractional anisotropy in the right anterior limb near the head of the caudate. Patients also had decreased mean diffusivity in the body of the right cingulum and the left anterior cingulum compared with controls. Correlational analyses revealed significant associations of fractional anisotropy and mean diffusivity in select circuits with OCD, depression and anxiety severity scores.

Limitations

Inclusion of patients with OCD receiving pharmacotherapy may have been a limitation. In addition, the patients were heterogeneous in terms of their obsessive–compulsive symptom profiles; we did not distinguish between different obsessive–compulsive symptom dimensions.

Conclusion

The study results provide further evidence for OCD-related white matter abnormalities in the ALIC and cingulum, consistent with a corticostriatal model of OCD.     

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

Background

Abnormalities in the corpus callosum have long been implicated in schizophrenia. Previous diffusion tensor imaging (DTI) studies in patients with different durations of schizophrenia yielded inconsistent results. By comparing patients with different durations of schizophrenia, we investigated if white matter abnormalities of the corpus callosum emerge at an early stage in the illness or result from pathological progression.

Methods

We recruited patients with first-episode schizophrenia, patients with chronic schizophrenia and age-, sex-and handedness-matched healthy controls. We used 2 DTI techniques (voxel-based and fibre-tracking DTI) to investigate differences in corpus callosum integrity among the 3 groups.

Results

With both DTI techniques, significantly decreased fractional anisotropy values were identified in the genu of corpus callosum in patients with chronic schizophrenia, but not first-episode schizophrenia, compared with healthy controls.

Limitations

This study was cross-sectional, and the sample size was relatively small.

Conclusion

Abnormalities in the genu of the corpus callosum might be a progressive process in schizophrenia, perhaps related to disease severity and prognosis.     

Impaired interhemispheric connectivity in medication-naive patients with major depressive disorder

Background

Abnormalities in the anterior interhemispheric connections provided by the corpus callosum (CC) have long been implicated in major depressive disorder (MDD). The purpose of this study was to investigate interhemispheric connectivity in medication-naive patients with MDD by measuring fractional anisotropy in the CC with diffusion tensor imaging (DTI) techniques.

Methods

We obtained DTI scans from medication-naive patients with MDD and from matched healthy controls. Fractional anisotropy values were compared using semiautomatic region of interest methods to localize the regional CC differences between these 2 groups.

Results

We enrolled 27 patients and 27 controls in our study. Fractional anisotropy values were significantly lower in the anterior genu of the CC in the MDD group than in the control group (p = 0.009, corrected); results were not significantly different in any other CC subregions.

Limitations

As patients with MDD were already experiencing acute episodes, future studies of individuals at risk for MDD are warranted to elucidate the interhemispheric connectivity abnormalities associated with the predisposition to MDD.

Conclusion

The findings demonstrate abnormalities in the structural integrity of the anterior genu of the CC in medication-naive individuals with MDD, which may contribute to impairment of interhemispheric connectivity in patients with this disorder.     

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder

Objective

Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD.

Methods

Thirty-two right-handed patients with PD [11 men, 21 women; 40.34±13.17 (mean±SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity.

Results

Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum.

Conclusion

This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.     

Altered white matter tract property related to impaired focused attention,sustained attention,cognitive impulsivity and vigilance in attention-deficit/hyperactivity disorder

Background

The neural substrate for clinical symptoms and neuropsychological performance in individuals with attention-deficit/hyperactivity disorder (ADHD) has rarely been studied and has yielded inconsistent results. We sought to compare the microstructural property of fibre tracts associated with the prefrontal cortex and its association with ADHD symptoms and a wide range of attention performance in youth with ADHD and healthy controls.

Methods

We assessed youths with ADHD and age-, sex-, handedness-, coil- and intelligence-matched controls using the Conners’ Continuous Performance Test (CCPT) for attention performance and MRI. The 10 target tracts, including the bilateral frontostriatal tracts (caudate to dorsolateral prefrontal cortex, ventrolateral prefrontal cortex and orbitofrontal cortex), superior longitudinal fasciculus (SLF) and cingulum bundle were reconstructed using diffusion spectrum imaging tractography. We computed generalized fractional anisotropy (GFA) values to indicate tract-specific microstructural property.

Results

We included 50 youths with ADHD and 50 healthy controls in our study. Youths with ADHD had lower GFA in the left frontostriatal tracts, bilateral SLF and right cingulum bundle and performed worse in the CCPT than controls. Furthermore, alteration of the right SLF GFA was most significantly associated with the clinical symptom of inattention in youths with ADHD. Finally, youths with ADHD had differential association patterns of the 10 fibre tract GFA values with attention performance compared with controls.

Limitations

Ten of the youths with ADHD were treated with methylphenidate, which may have long-term effects on microstructural property.

Conclusion

Our study highlights the importance of the SLF, cingulum bundle and frontostriatal tracts for clinical symptoms and attention performance in youths with ADHD and demonstrates the involvement of different fibre tracts in attention performance in these individuals.     

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder

Background

Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear.

Methods

We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI).

Results

We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls.

Limitations

The major limitation of our study is the small number of patients with bipolar disorder.

Conclusion

Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.     

White matter microstructure in patients with obsessive-compulsive disorder

Background

Previous diffusion tensor imaging (DTI) studies in patients with obsessive–compulsive disorder (OCD) have reported inconsistent findings, and it is not known whether observed findings are related to abnormalities in axonal structure or myelination.

Methods

In this DTI study, we investigated fractional anisotropy, as well as axial and radial diffusivity, in 21 patients with OCD and 29 healthy controls.

Results

We found decreased fractional anisotropy in the body of the corpus callosum in the OCD group, which was underpinned by increased radial diffusivity.

Limitations

The cross-sectional design was the main limitation.

Conclusion

Our findings of increased radial diffusivity provide preliminary evidence for abnormal myelination in patients with OCD.     

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Background

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence.

Methods

DTI was performed in 78 healthy subjects aged 8–21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence.

Results

In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age.

Conclusions

These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.     

Whole-Brain Diffusion-Tensor Changes in Parkinsonian Patients with Impulse Control Disorders

Background and Purpose

The aim of this study was to determine the changes in diffusion-tensor images associated with medication-related impulse control disorder (ICD) in Parkinson''s disease (PD) patients undergoing chronic dopamine-replacement therapy.

Methods

Nineteen PD patients, comprising 10 with ICD (PD-ICD) and 9 without ICD (PD-nonICD), and 18 age-matched healthy controls (HCs) with no cognitive or other psychiatric disorders were analyzed. All subjects underwent 3-T magnetic resonance diffusion-tensor imaging. For all PD patients, clinical data on PD duration, antiparkinsonian medication dosages, Unified Parkinson''s Disease Rating Scale and Mini-Mental State Examination were collected. Whole-brain voxel-based measures of fractional anisotropy (FA) and mean diffusivity (MD) were analyzed.

Results

In comparison with HCs, the PD-nonICD subjects had low FA at the bilateral orbitofrontal areas. While the PD-ICD subjects exhibited no such difference, their FA was significantly elevated at the anterior corpus callosum. Analysis of FA between the two PD groups revealed that FA in the anterior corpus callosum, right internal capsule posterior limbs, right posterior cingulum, and right thalamic radiations were significantly higher (corrected p<0.05) in the PD-ICD than in the PD-nonICD patients. MD did not differ between the PD-ICD and PD-nonICD groups in any brain regions.

Conclusions

The PD-ICD patients appear to have relatively preserved white-matter integrity in the regions involved in reward-related behaviors compared to PD-nonICD patients. Further investigation is required to determine whether the difference in FA between PD-ICD and PD-nonICD patients reflects microstructural differences in the pathological progression of PD or is secondary to ICD.     

Lower white matter microstructure in the superior longitudinal fasciculus is associated with increased response time variability in adults with attention-deficit/hyperactivity disorder

Background

Response time variability (RTV) is consistently increased in patients with attention-deficit/hyperactivity disorder (ADHD). A right-hemispheric frontoparietal attention network model has been implicated in these patients. The 3 main connecting fibre tracts in this network, the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the cingulum bundle (CB), show microstructural abnormalities in patients with ADHD. We hypothesized that the microstructural integrity of the 3 white matter tracts of this network are associated with ADHD and RTV.

Methods

We examined RTV in adults with ADHD by modelling the reaction time distribution as an exponentially modified Gaussian (ex-Gaussian) function with the parameters μ, σ and τ, the latter of which has been attributed to lapses of attention. We assessed adults with ADHD and healthy controls using a sustained attention task. Diffusion tensor imaging–derived fractional anisotropy (FA) values were determined to quantify bilateral microstructural integrity of the tracts of interest.

Results

We included 100 adults with ADHD and 96 controls in our study. Increased τ was associated with ADHD diagnosis and was linked to symptoms of inattention. An inverse correlation of τ with mean FA was seen in the right SLF of patients with ADHD, but no direct association between the mean FA of the 6 regions of interest with ADHD could be observed.

Limitations

Regions of interest were defined a priori based on the attentional network model for ADHD and thus we might have missed effects in other networks.

Conclusion

This study suggests that reduced microstructural integrity of the right SLF is associated with elevated τ in patients with ADHD.     

Microstructural abnormalities of the brain white matter in attention-deficit/hyperactivity disorder

Background

Attention-deficit/hyperactivity disorder (ADHD) is an early-onset neurodevelopmental disorder with multiple behavioural problems and executive dysfunctions for which neuroimaging studies have reported a variety of abnormalities, with inconsistencies partly owing to confounding by medication and concurrent psychiatric disease. We aimed to investigate the microstructural abnormalities of white matter in unmedicated children and adolescents with pure ADHD and to explore the association between these abnormalities and behavioural symptoms and executive functions.

Methods

We assessed children and adolescents with ADHD and healthy controls using psychiatric interviews. Behavioural problems were rated using the revised Conners’ Parent Rating Scale, and executive functions were measured using the Stroop Colour-Word Test and the Wisconsin Card Sorting test. We acquired diffusion tensor imaging data using a 3 T MRI system, and we compared diffusion parameters, including fractional anisotropy (FA) and mean, axial and radial diffusivities, between the 2 groups.

Results

Thirty-three children and adolescents with ADHD and 35 healthy controls were included in our study. In patients compared with controls, FA was increased in the left posterior cingulum bundle as a result of both increased axial diffusivity and decreased radial diffusivity. In addition, the averaged FA of the cluster in this region correlated with behavioural measures as well as executive function in patients with ADHD.

Limitations

This study was limited by its cross-sectional design and small sample size. The cluster size of the significant result was small.

Conclusion

Our findings suggest that white matter abnormalities within the limbic network could be part of the neural underpinning of behavioural problems and executive dysfunction in patients with ADHD.     

Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression

Background

Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes.

Methods

Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography.

Results

Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts.

Limitations

Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used.

Conclusion

Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive–emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies.     

Preoperative Weakness and Demyelination of the Corticospinal Tract in Meningioma Patients : Changes in Diffusion Parameters Using Diffusion Tensor Imaging

Objective

Differentiation of demyelination in white matter from axonal damage can be determined using diffusion tensor imaging (DTI). In this study using meningioma patients an attempt was made to evaluate the relationship between preoperative weakness and the changes of diffusion parameters in the corticospinal tract (CST) using DTI.

Methods

Twenty-six patients with meningioma were enrolled in this study. Eleven of them suffered from objective motor weakness and were classified as Group 1. The remaining 15 patients did not present motor weakness and were classified as Group 2. Fiber tractography and CST diffusion parameters were obtained using DTIStudio. The ratios (lesion side mean value/contralateral side mean value) of CST diffusion parameters were compared with 1.0 as a test value using a one-sample t-test.

Results

In Group 1, fractional anisotropy (FA), tensor trace (TT), and radial diffusivity (RD, λ2 and λ3) of the CST were significantly different between two hemispheres, but axial diffusivity (AD, λ1) of the CST was not significantly different between two hemispheres. In Group 2, FA and λ3 of CST did not differ significantly between the hemispheres. In Group 2, TT, λ1, and λ2 of CST in the ipsilateral hemisphere were significantly higher than those of the unaffected hemisphere. However, the differences were small.

Conclusion

Motor weakness was related to a low FA and high TT resulting from increased RD of the CST fibers. CST diffusion changes in patients with weakness are similar to those for demyelination.     

Microstructural Changes of Anterior Corona Radiata in Bipolar Depression

Objective

In bipolar disorder, dysregulation of mood may result from white matter abnormalities that change fiber tract length and fiber density. There are few studies evaluating the white matter microstructural changes in bipolar I patients (BD) with depressive episodes. The present study aimed to evaluate anterior corona radiata in BD patients with depressive episode using Diffusion Tensor Imaging (DTI).

Methods

Twenty-one patients with bipolar depression and 19 healthy controls were investigated and groups were matched for age and gender. Diffusion-weighted echoplanar brain images (DW-EPI) were obtained using a 1.5 T MRI scanner. Regions of interest (ROIs) were manually placed on directional maps based on principal anisotropy. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of white matter were measured in the anterior corona radiata (ACR) bilaterally by diffusion tensor imaging.

Results

There was not a significant difference between groups of age and gender (p>0.05). Significantly lower FA was observed in bilateral ACR in bipolar patients with depression compared with healthy individuals. And there is significantly higher ADC values in the left frontal corona radiate in bipolar patients.

Conclusion

White matter abnormalities can be detected in patients with BD using DTI. The neuropathology of these abnormalities is unclear, but neuronal and axonal loss, myelin abnormalities and reduced white matter fiber density are likely to be relevant.     

Methamphetamine Enhances the Development of Schizophrenia in First-Degree Relatives of Patients With Schizophrenia

Objective:

Although there is some evidence that methamphetamine (MA) abuse may play a causative role in the development of schizophrenia, studies directly linking these 2 are rare.

Methods:

In our study, the effect of MA abuse on the development of schizophrenia was investigated in 15 MA abusers who are offspring of patients with schizophrenia and 15 siblings of MA abusers without a history of drug abuse. Cognitive deficits and resting-state brain function were evaluated in all participants. Correlations between cognitive deficits and schizophrenia development were investigated.

Results:

Significantly more cognitive impairments were observed in MA abusers, compared with their siblings without a history of drug use. Significant abnormalities in regional homogeneity (ReHo) signals were observed in resting brain in MA abusers. Decreased ReHo was found to be distributed over the bilateral cingulate gyrus, right Brodmann area 24, and bilateral anterior cingulate cortex. Seven MA abusers were diagnosed with schizophrenia, while 1 control sibling was diagnosed with schizophrenia during the 5-year follow-up. The cognitive scores correlated with the development of schizophrenia in MA abusers.

Conclusion:

Our study provides direct evidence for the causative role of MA use in the etiology of schizophrenia and highlights the role of MA-induced brain abnormalities in cognitive deficiency and development of schizophrenia.     

White-matter abnormalities in adolescents with long-term inhalant and cannabis use: a diffusion magnetic resonance imaging study

Background

There is growing evidence that inhalants are neurotoxic to white matter, yet limited work has been conducted to investigate the neurobiologic effects of long-term exposure among adolescent users, despite inhalant use being most prominent during this developmental period.

Methods

We used diffusion tensor imaging to examine white-matter integrity in 11 adolescents who used inhalants, 11 matched cannabis users and 8 drug-naive controls.

Results

Although both groups of drug users had white-matter abnormalities (i.e., lower fractional anisotropy), abnormalities were more pronounced in the inhalant group, particularly among early-onset users.

Limitations

The findings of this study should be considered in light of its small sample size, cross-sectional design and the complex psychosocial background of long-term inhalant users.

Conclusion

White-matter abnormalities may underpin long-term behavioural and mental health problems seen in individuals with long-term inhalant use.     

Lateralization of Hypoglycemic Encephalopathy: Evidence of a Mechanism of Selective Vulnerability

Background

One of the characteristics of hypoglycemic encephalopathy (HE) is selective vulnerability of different brain regions.

Case Report

We observed a patient with unilateral HE affecting the right internal capsule and the subcortical white matter. The patient had a preexisting stroke in the opposite hemisphere. The hemisphere that was affected by HE exhibited greater regional blood flow (single positron-emission tomography) and higher fractional anisotropy (diffusion-tensor imaging) than the unaffected hemisphere.

Conclusions

This case suggests that the degree of metabolism required to maintain the function of brain structures and neuronal integrity is an important factor determining the selective vulnerability in HE.     

Cognitive impairment with and without depression history: an analysis of white matter microstructure

Background

Mild cognitive impairment (MCI) and late-life depression are clinical syndromes that often co-occur and may represent an early manifestation of neurodegenerative disease. The present study examined white matter microstructure in patients with MCI with and without a history of major depression compared with healthy controls.

Methods

Older adults with MCI and no history of major depression (MCI), adults with MCI and euthymic major depression (MCI-MD) and healthy controls underwent comprehensive medical, psychiatric and neuropsychological assessments. Participants also underwent diffusion tensor imaging, which was analyzed using tract-based spatial statistics. White matter hyperintensity (WMH) burden and medical burden were also quantified.

Results

We enrolled 30 participants in the MCI group, 36 in the MCI-MD group and 22 in the control group. Compared with controls, participants in the MCI group had significantly reduced fractional anisotropy (FA) in the corpus callosum, superior longitudinal fasciculus (SLF), corona radiata and posterior thalamic radiation. Participants in the MCI-MD group had significantly reduced FA in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiation, sagittal striatum, fornix, SLF, uncinate fasciculus and right cingulum compared with controls. No significant differences in FA were observed between the MCI and MCI-MD groups. Participants in the MCI-MD group had greater medical burden (p = 0.020) and WMH burden than controls (p = 0.013).

Limitations

Study limitations include the cross-sectional design and antidepressant medication use.

Conclusion

To our knowledge, this study is the first to compare white matter microstructure in patients with MCI with and without a history of major depression and suggests that a common underlying structural white matter change may underpin cognitive impairment in both MCI groups. Further research is needed to delineate the pathophysiological mechanisms underlying these microstructural changes.     

Alterations of white matter integrity in adults with major depressive disorder: a magnetic resonance imaging study

Objective

The purpose of our study was to investigate alterations of white matter integrity in adults with major depressive disorder (MDD) using magnetic resonance imaging (MRI).

Methods

We performed diffusion tensor imaging with a 3T MRI scanner on 45 patients with major depression and 45 healthy controls matched for age, sex and education. Using a voxel-based analysis, we measured the fractional anisotropy (FA), and we investigated the differences between the patient and control groups. We examined the correlations between the microstructure abnormalities of white matter and symptom severity, age of illness onset and cumulative illness duration, respectively.

Results

We found a significant decrease in FA in the left hemisphere, including the anterior limb of the internal capsule and the inferior parietal portion of the superior longitudinal fasciculus, in patients with MDD compared with healthy controls. Diffusion tensor imaging measures in the left anterior limb of the internal capsule were negatively related to the severity of depressive symptoms, even after we controlled for age and sex.

Conclusion

Our findings provide new evidence of microstructural changes of white matter in non–late-onset adult depression. Our results complement those observed in late-life depression and support the hypothesis that the disruption of cortical– subcortical circuit integrity may be involved in the etiology of major depressive disorder.Medical subject headings: depressive disorder, major; magnetic resonance imaging; brain diseases     

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

Background

Many 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.

Method

A 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.

Results

We 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.

Limitations

The 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.

Conclusion

Voxel-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 is strong evidence for the involvement of these neural circuits in the pathology of MDD.