Pervasive microstructural abnormalities in autism: a DTI study

Background

Recent studies have reported abnormal functional connectivity patterns in the brains of people with autism that may be accompanied by decreases in white matter integrity. Since autism is a developmental disorder, we aim to investigate the nature and location of decreases in white and grey matter integrity in an adolescent sample while accounting for age.

Methods

We used structural (T₁) imaging to study brain volumetrics and diffusion tensor imaging (DTI) to investigate white and grey matter integrity in people with autism. We obtained magnetic resonance images for adolescents aged 12–18 years with high-functioning autism and from matched controls. Fractional anisotropy and mean diffusivity, as well as grey and white matter volumetrics were analyzed.

Results

There were 17 participants with autism and 25 matched controls included in this study. Participants with autism had lower fractional anisotropy in the left and right superior and inferior longitudinal fasciculus, but this effect was not significant after adjusting for age and intelligence quotient (IQ). The kurtosis of the white matter fractional anisotropy probability distribution was higher in this participant group, with and without adjustment for age and IQ. Most notably, however, the mean diffusivity levels were markedly increased in the autism group throughout the brain, and the mean diffusivity probability distributions of both grey and white matter were shifted toward a higher value, particularly with age and IQ adjustment. No volumetric differences in grey and white matter were found.

Limitations

We corrected for age and IQ using a linear model. The study was also limited by its sample size, investigated age range and cross-sectional design.

Conclusion

The findings suggest that autism is characterized by a generalized reduction of white matter integrity that is associated with an increase of interstitial space. The generalized manifestation of the white matter abnormalities provides an important new perspective on autism as a connectivity disorder.     

Disruption of brain white matter microstructure in women with anorexia nervosa

Background

The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa.

Methods

Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD.

Results

We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; p_FWE < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (p_FWE < 0.05), accompanied by decreased FA and increased RD and AD.

Limitations

Limitations include our modest sample size and cross-sectional design.

Conclusion

Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in body–energy–balance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa.     

Evidence From Structural and Diffusion Tensor Imaging for Frontotemporal Deficits in Psychometric Schizotypy

Background:

Previous studies of nonclinical samples exhibiting schizotypal traits have provided support for the existence of a continuous distribution of psychotic symptoms in the general population. Few studies, however, have examined the neural correlates of psychometric schizotypy using structural and diffusion tensor imaging (DTI).

Methods:

Healthy volunteers between the ages of 18 and 68 were recruited from the community and assessed using the Schizotypal Personality Questionnaire and received structural and DTI exams. Participants with high (N = 67) and low (N = 71) psychometric schizotypy were compared on gray and white matter volume, and cortical thickness in frontal and temporal lobe regions and on fractional anisotropy (FA) within 5 association tracts traversing the frontal and temporal lobes.

Results:

Higher levels of schizotypy were associated with lower overall volumes of gray matter in both the frontal and temporal lobes and lower gray matter thickness in the temporal lobe. Regionally specific effects were evident in both white matter and gray matter volume of the rostral middle frontal cortex and gray matter volume in the pars orbitalis. Moreover, relative to individuals who scored low, those who scored high in schizotypy had lower FA in the inferior fronto-occipital fasciculus as well as greater asymmetry (right > left) in the uncinate fasciculus.

Conclusions:

These findings are broadly consistent with recent data on the neurobiological correlates of psychometric schizotypy as well as findings in schizotypal personality disorder and schizophrenia and suggest that frontotemporal lobe dysfunction may represent a core component of the psychosis phenotype.Key words: schizotypy, MRI/DTI, healthy subjects     

Alterations in White Matter Evident Before the Onset of Psychosis

Background

Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.

Methods

Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.

Results

At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.

Conclusions

People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.     

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.     

Visual search for feature conjunctions: an fMRI study comparing alcohol-related neurodevelopmental disorder (ARND) to ADHD

Background

Alcohol-related neurodevelopmental disorder (ARND) falls under the umbrella of fetal alcohol spectrum disorder (FASD). Diagnosis of ARND is difficult because individuals do not demonstrate the characteristic facial features associated with fetal alcohol syndrome (FAS). While attentional problems in ARND are similar to those found in attention-deficit/hyperactivity disorder (ADHD), the underlying impairment in attention pathways may be different.

Methods

Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) was conducted at 3 T. Sixty-three children aged 10 to 14 years diagnosed with ARND, ADHD, and typically developing (TD) controls performed a single-feature and a feature-conjunction visual search task.

Results

Dorsal and ventral attention pathways were activated during both attention tasks in all groups. Significantly greater activation was observed in ARND subjects during a single-feature search as compared to TD and ADHD groups, suggesting ARND subjects require greater neural recruitment to perform this simple task. ARND subjects appear unable to effectively use the very efficient automatic perceptual ‘pop-out’ mechanism employed by TD and ADHD groups during presentation of the disjunction array. By comparison, activation was lower in ARND compared to TD and ADHD subjects during the more difficult conjunction search task as compared to the single-feature search. Analysis of DTI data using tract-based spatial statistics (TBSS) showed areas of significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the right inferior longitudinal fasciculus (ILF) in ARND compared to TD subjects. Damage to the white matter of the ILF may compromise the ventral attention pathway and may require subjects to use the dorsal attention pathway, which is associated with effortful top-down processing, for tasks that should be automatic. Decreased functional activity in the right temporoparietal junction (TPJ) of ARND subjects may be due to a reduction in the white matter tract’s ability to efficiently convey information critical to performance of the attention tasks.

Conclusions

Limited activation patterns in ARND suggest problems in information processing along the ventral frontoparietal attention pathway. Poor integrity of the ILF, which connects the functional components of the ventral attention network, in ARND subjects may contribute to the attention deficits characteristic of the disorder.     

White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study

Background

Psychosis onset is characterized by white matter and electrophysiologic abnormalities. The relation between these factors in the development of illness is almost unknown. We studied the relation between white matter volumes and P300 in prodromal psychosis.

Methods

We assessed white matter volume (detected using magnetic resonance imaging) and electrophysiologic response during an oddball task (P300) in healthy controls and individuals at high clinical risk for psychosis (with an “at-risk mental state” [ARMS]).

Results

We included 41 controls and 39 patients with an ARMS in our study. A psychotic disorder developed in 26% of the ARMS group within the follow-up period of 2 years. The P300 amplitude was significantly lower in the ARMS group than in the control group. The ARMS group showed reduced volume of white matter underlying the left superior temporal gyrus and the left superior frontal gyrus and increased volume of white matter underlying the right insula and the right angular gyrus compared with controls. Relative to individuals who did not later become psychotic, the subgroup in whom psychosis subsequently developed had a smaller volume of white matter underlying the left precuneus and the right middle temporal gyrus and increased volume in the white matter underlying the right middle frontal gyrus. We observed a significant interaction in the right middle frontal gyrus: white matter volume was negatively associated with P300 amplitude in the ARMS group and positively associated with P300 amplitude in the control group.

Limitations

The voxel-based morphometry method alone cannot determine whether abnormal white matter volumes are due to an altered number of axonal connections or decreased myelination.

Conclusion

P300 abnormalities precede the onset of psychosis and are directly related to white matter alterations, representing a correlate of an increased vulnerability to disease.     

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.     

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     

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.     

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.     

A significant risk factor for poststroke depression: the depression-related subnetwork

Background

Despite being one of the direct causes of depression, whether stroke-induced neuroanatomical deterioration actually plays an important role in the onset of poststroke depression (PSD) is controversial. We assessed the structural basis of PSD, particularly with regard to white matter connectivity.

Methods

We evaluated lesion index, fractional anisotropy (FA) reduction and brain structural networks and then analyzed whole brain voxel-based lesions and FA maps. To understand brain damage in the context of brain connectivity, we used a graph theoretical approach. We selected nodes whose degree correlated with the Hamilton Rating Scale for Depression score (p < 0.05, false discovery rate–corrected), after controlling for age, sex, years of education, lesion size, Mini Mental State Examination score and National Institutes of Health Stroke Scale score. We used Poisson regression with robust standard errors to assess the contribution of the identified network toward poststroke major depression.

Results

We included 116 stroke patients in the study. Fourteen patients (12.1%) had diagnoses of major depression and 26 (22.4%) had mild depression. We found that lesions in the right insular cortex, left putamen and right superior longitudinal fasciculus as well as FA reductions in broader areas were all associated with major depression. Seventeen nodes were selected to build the depression-related subnetwork. Decreased local efficiency of the subnetwork was a significant risk factor for poststroke major depression (relative risk 0.84, 95% confidence interval 0.72–0.98, p = 0.027).

Limitations

The inability of DTI tractography to process fibre crossings may have resulted in inaccurate construction of white matter networks and affected statistical findings.

Conclusion

The present study provides, to our knowledge, the first graph theoretical analysis of white matter networks linked to poststroke major depression. These findings provide new insights into the neuroanatomical substrates of depression that develops after stroke.     

Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms

Background

22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia.

Methods

Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/?2 years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed.

Results

Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale.

Conclusion

Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms.

     

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.     

Progressive structural brain changes during development of psychosis

Background:

Ultra-high risk (UHR) for psychosis has been associated with widespread structural brain changes in young adults. The onset of these changes and their subsequent progression over time are not well understood.

Methods:

Rate of brain change over time was investigated in 43 adolescents at UHR for psychosis compared with 30 healthy controls. Brain volumes (total brain, gray matter, white matter [WM], cerebellum, and ventricles), cortical thickness, and voxel-based morphometry were measured at baseline and at follow-up (2 y after baseline) and compared between UHR individuals and controls. Post hoc analyses were done for UHR individuals who became psychotic (N = 8) and those who did not (N = 35).

Results:

UHR individuals showed a smaller increase in cerebral WM over time than controls and more cortical thinning in the left middle temporal gyrus. Post hoc, a more pronounced decrease over time in total brain and WM volume was found for UHR individuals who became psychotic relative to controls and a greater decrease in total brain volume than individuals who were not psychotic. Furthermore, UHR individuals with subsequent psychosis displayed more thinning than controls in widespread areas in the left anterior cingulate, precuneus, and temporo-parieto-occipital area. Volume loss in the individuals who developed psychosis could not be attributed to medication use.

Conclusion:

The development of psychosis during adolescence is associated with progressive structural brain changes around the time of onset. These changes cannot be attributed to (antipsychotic) medication use and are therefore likely to reflect a pathophysiological process related to clinical manifestation of psychosis.     

White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study

Background

Some gray and white matter regions of the brain are sexually dimorphic. The best MRI technique for identifying subtle differences in white matter is diffusion tensor imaging (DTI). The purpose of this paper is to investigate whether white matter patterns in female to male (FtM) transsexuals before commencing cross-sex hormone treatment are more similar to that of their biological sex or to that of their gender identity.

Method

DTI was performed in 18 FtM transsexuals and 24 male and 19 female heterosexual controls scanned with a 3 T Trio Tim Magneton. Fractional anisotropy (FA) was performed on white matter fibers of the whole brain, which was spatially analyzed using Tract-Based Spatial Statistics.

Results

In controls, males have significantly higher FA values than females in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract.

Conclusions

Our results show that the white matter microstructure pattern in untreated FtM transsexuals is closer to the pattern of subjects who share their gender identity (males) than those who share their biological sex (females). Our results provide evidence for an inherent difference in the brain structure of FtM transsexuals.     

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.     

Longitudinal study of carbon monoxide intoxication by diffusion tensor imaging with neurospsychiatric correlation

Background

White matter damage is common after carbon monoxide (CO) intoxication, but in vivo follow-up studies about the mechanism of white matter damage are not possible in pathology series. Diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) can quantify diffusion parameters and volumetric changes in white matter that can be correlated with neuropsychological performances in longitudinal studies.

Methods

We examined 9 patients with CO intoxication using DTI, VBM and neuropsychologic tests at an average of 3 and 10 months after CO exposure. We used data from 18 age- and sex-matched controls for comparison.

Results

We found that cognitive recovery at 10 months after CO intoxication was not significant, although it was after 3 months. The neuropsychologic tests correlated better for the fibre tract of the semicentrum ovale and not the periventricular fibres. Diffusion measures suggest increases in fractional anisotropy, mean diffusivity and axial eigenvalues over time, while increases in radial eigenvalue were evident at 3 months compared with controls. Periventricular white matter atrophy was observed 10 months after CO intoxication

Limitations

Our study included few cases, and the interpretation of the putative changes on neuroimaging findings cannot be confirmed by histology.

Conclusion

Our study showed that the evolution of white matter injury in CO encephalopathy occurred over time. Cognitive recovery was not evident in the follow-up period because of white matter injuries.     

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.