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.     

The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study

Background

Diffusion tensor imaging (DTI) has been shown to be sensitive in detecting white matter differences between sexes. Before cross-sex hormone treatment female to male transsexuals (FtM) differ from females but not from males in several brain fibers. The purpose of this paper is to investigate whether white matter patterns in male to female (MtF) transsexuals before commencing cross-sex hormone treatment are also more similar to those of their biological sex or whether they are more similar to those of their gender identity.

Method

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

Results

MtF transsexuals differed from both male and female controls bilaterally in the superior longitudinal fasciculus, the right anterior cingulum, the right forceps minor, and the right corticospinal tract.

Conclusions

Our results show that the white matter microstructure pattern in untreated MtF transsexuals falls halfway between the pattern of male and female controls. The nature of these differences suggests that some fasciculi do not complete the masculinization process in MtF transsexuals during brain development.     

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

Background

Voxel-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.

Methods

A 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.

Results

A 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.

Conclusions

Meta-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.     

Voxel based morphometric and diffusion tensor imaging analysis in male bipolar patients with first-episode mania

Objectives

Structural abnormality of both gray and white matter has been detected in patients with bipolar disorder (BD). But results were greatly inconsistent across studies which were most likely attributed to heterogeneous populations as well as processing techniques. The present study aimed to investigate brain structural and microstructural alterations in a relative homogenous sample of bipolar mania.

Methods

3D T1-weighted magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were conducted in 18 patients with BD and 27 healthy volunteers. Gray matter (GM) and white matter (WM) differences were evaluated using voxel-based morphometry (VBM) and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI, respectively.

Results

Patients with BD had a larger volume of GM in the left thalamus and bilateral basal ganglia, including the bilateral putamen and extending to the left claustrum, as well as reduced FA values in the left posterior corona radiata.

Conclusions

By combined analysis, alterations in subcortical GM areas and part of the corresponding association fiber area were detected. Compared with observations in homogeneous samples, our findings indicate that disruption of the limbic network may be intrinsic to BD.     

A voxel-based morphometric MRI study of stabilized obsessive-compulsive adolescent patients

Background

The aim of this study was to determine whether treated stabilized adolescents with obsessive-compulsive disorder (OCD) present brain structure differences in comparison with healthy control subjects.

Methods

Twenty-seven adolescents with already-treated OCD and 27 healthy controls matched by age, sex and estimated intellectual level were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 1.5 T scanner and analyzed using optimized voxel-based morphometry (VBM).

Results

Compared with controls, stabilized patients with OCD did not present any statistical differences in the whole brain. However, a small volume correction analysis yielded significant results that survived correction for multiple comparisons, showing decreased white matter (WM) volume in a small area of the parietal cortex (t = 3.39, p = 0.045 FWE (family wise error)-corrected) of OCD patients in comparison with healthy controls. There was no significant correlation between decreased WM volume in the parietal cortex and obsessive-compulsive symptomatology.

Conclusion

There were no global significant differences in either gray matter (GM) or WM. Small differences were found between adolescent patients with stabilized OCD and healthy controls as regards in WM volume in right parietal areas. The parietal lobe may play a role in the pathophysiology of OCD, even in clinically stabilized patients.     

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.     

Where (in the brain) do semantic errors come from?

Background

Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone.

Methods

A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits.

Results

Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37.

Conclusion

Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.     

Correlating 3T MRI and histopathology in patients undergoing epilepsy surgery

Purpose

To investigate whether specific semi-quantitative 3T MRI parameters are associated with particular histological features in temporal lobe specimens in epilepsy surgery patients whose conventional MRI scan appeared normal. These MRI techniques have the potential to visualise subtle structural abnormalities currently undetected on conventional MRI; but correlation between pre-operative in vivo MRI and histopathology is needed to understand the basis of these MRI abnormalities. Predicting subtle histopathology with semi-quantitative MRI techniques could contribute to pre-surgical evaluation of epilepsy patients.

Materials and methods

MRI techniques: normalised FLAIR signal intensity (nFSI), grey matter probability and diffusion tensor imaging (DTI) were correlated with quantitative histopathological measures: NeuN (neuronal nuclear antigen); GFAP (glial fibrillary acidic protein) and MBP (myelin basic protein) field fractions and stereological neuronal densities obtained in grey and white matter regions in twenty-four patients who underwent anterior temporal lobe resections.

Results

There were no significant correlations between the histopathological measurements and MRI values in grey or white matter in macroscopically normal appearing tissue.

Conclusion

Findings suggest that in macroscopically normal appearing tissue, the studied semiquantitative MRI measurements are not significantly related to the measures of gliosis, neuronal loss/gain and myelin used in the current study. Studies of macroscopically abnormal tissue as well as improvements to the MRI techniques may increase the sensitivity of future correlative studies to improve our understanding of the histopathological basis of MRI signal characteristics.     

Disrupted regional homogeneity in treatment-resistant depression: a resting-state fMRI study

Background

Using a newly developed regional homogeneity (ReHo) approach, we were to explore the features of brain activity in patients with treatment-resistant depression (TRD) in resting state, and further to examine the relationship between abnormal brain activity in TRD patients and specific symptom factors derived from ratings on the Hamilton Rating Scale for Depression (HRSD).

Methods

24 patients with TRD and 19 gender-, age-, and education-matched healthy subjects participated in the fMRI scans.

Results

1.

Compared with healthy controls, decreased ReHo were found in TRD patients in the left insula, superior temporal gyrus, inferior frontal gyrus, lingual gyrus and cerebellum anterior lobe (culmen) (p < 0.05, corrected).

2.

Compared with healthy controls, increased ReHo were found in the left superior temporal gyrus, cerebellum posterior lobe (tuber), cerebellum anterior lobe (culmen), the right cerebellar tonsil and bilateral fusiform gyrus (p < 0.05, corrected).

3.

There was no correlation between the ReHo values in any brain region detected in our study and the patients' age, years of education, illness duration, HRSD total score and its symptom factors.

Limitation

The influence of antidepressants to the brain activity in TRD patients was not fully eliminated.

Conclusions

The pathogenesis of TRD may be attributed to abnormal neural activity in multiple brain regions.     

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.     

A primary study of diffusion tensor imaging-based histogram analysis in vascular cognitive impairment with no dementia

Purpose

This study performed diffusion tensor imaging (DTI) histogram analysis and voxel-based analysis (VBA) to detect white matter (WM) damage in patients with vascular cognitive impairment with no dementia (VCIND) and to determine correlations between DTI histogram-derived measures and cognitive dysfunction in these patients.

Materials and methods

Among patients with subcortical ischemic vascular disease, 18 patients with VCIND were selected along with 18 age- and sex-matched cognitive-normal subjects. Both groups underwent magnetic resonance and DTI scans, and fractional anisotropy (FA) changes in VBA between the two groups were assessed. Further, mean diffusivity (MD) and FA histograms of WM and normal-appearing WM (NAWM) in each subject were evaluated.

Results

Compared to control, the VCIND group showed lower FA values throughout the brain. FA and MD histogram patterns of WM and NAWM were significantly different between the groups. Significant differences were found in all DTI histogram-derived measures, except in the mean FA peak height of WM and mean MD peak location of NAWM. Neuropsychological results (z-scores) were found to be significantly correlated with mean FA peak location, average MD, mean MD peak location of WM, and mean FA peak height, average MD, mean MD peak location of NAWM.

Conclusions

Results of VBA and diffusion tensor imaging-based histogram analysis suggest that VCIND patients have more severe damage in WM and NAWM than the control. Thus, the severity of damage in WM and NAWM may be related with cognitive dysfunction in VCIND patients, and DTI histogram analysis can help in further understanding VCIND.     

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.     

White matter pathways associated with working memory in normal aging

Introduction

Previous studies by our group have found that white matter integrity as determined by Diffusion Tensor Imaging (DTI) is associated with working memory decline. It has been proposed that subtle white matter integrity loss may lead to the disruption of working memory in particular because it relies on the dynamic and reiterative activity of cortico-cortical pathways.

Methods

DTI and working memory measurement were acquired for 99 adults from our GENIE study of healthy middle aged and elderly individuals. Voxel-based statistics were used to identify clusters of voxels in mean diffusivity images specifically associated with variations in working memory performance. Tractography then identified the cortico-cortical white matter pathways passing through these clusters, between the temporal, parietal and frontal cortices.

Results

Significant clusters were identified which were associated with working memory in the white matter of the temporal and frontal lobes, the cingulate gyrus, and in the thalamus. The tracts that passed through these clusters included the superior parietal lobule pathway, the medial temporo-frontal pathway, the uncinate fasciculus, the fronto-parietal fasciculus, and the cingulum.

Conclusions

Significant clusters were identified in the white matter that were associated with working memory performance. Tractography performed through these clusters identified white matter fiber tracts which pass between grey matter regions known to be activated by working memory tasks and also mirror working memory pathways suggested by previous functional connectivity imaging.     

Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder

Background

The polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions. Here we sought to investigate the influence of CACNA1C polymorphism on key subcortical brain structures implicated in the pathophysiology of BD.

Methods

Structural magnetic resonance imaging scans were acquired from 41 euthymic patients with BD and 40 healthy controls, who were also genotyped for the CACNA1C rs1006737 polymorphism. The effect of diagnosis, genotype and their interaction was examined in predefined volumes of interest in the basal ganglia, hypothalamus and amygdala extracted using SPM5.

Results

Carriers of the CACNA1C rs1006737 risk allele showed increased grey matter density in the right amygdala and right hypothalamus irrespective of diagnosis. An interaction between genotype and diagnosis was observed in the left putamen which was smaller in BD patients carrying the risk allele than in healthy controls.

Conclusions

: The CACNA1C rs1006737 polymorphism influences anatomical variation within subcortical regions involved in emotional processing.     

Human amygdala responses during presentation of happy and neutral faces: correlations with state anxiety

Background

Previous functional imaging studies demonstrating amygdala response to happy facial expressions have all included the presentation of negatively valenced primary comparison expressions within the experimental context. This study assessed amygdala response to happy and neutral facial expressions in an experimental paradigm devoid of primary negatively valenced comparison expressions.

Methods

Sixteen human subjects (eight female) viewed 16-sec blocks of alternating happy and neutral faces interleaved with a baseline fixation condition during two functional magnetic resonance imaging scans.

Results

Within the ventral amygdala, a negative correlation between happy versus neutral signal changes and state anxiety was observed. The majority of the variability associated with this effect was explained by a positive relationship between state anxiety and signal change to neutral faces.

Conclusions

Interpretation of amygdala responses to facial expressions of emotion will be influenced by considering the contribution of each constituent condition within a greater subtractive finding, as well as 1) their spatial location within the amygdaloid complex; and 2) the experimental context in which they were observed. Here, an observed relationship between state anxiety and ventral amygdala response to happy versus neutral faces was explained by response to neutral faces.     

A comparative study of cognition and brain anatomy between two neurodevelopmental disorders: 22q11.2 deletion syndrome and Williams syndrome

Background

22q11.2 deletion syndrome (22q11DS) is associated with intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies comparing cognition and neuroanatomical characteristics of 22q11DS with other syndromes to investigate if the cognitive strengths and difficulties and neuroanatomical differences associated with 22q11DS are specific to the syndrome. Hence, it is difficult to know if the observed features of 22q11DS are simply due to a non-specific effect of having a genetic disorder or are specific to 22q11DS.

Methods

In this study, cognition and brain anatomy of 12 children with 22q11DS were compared to 12 age, gender and full scale IQ (FSIQ) matched children with William syndrome (WS) in order to investigate which cognitive and neuroanatomical features are specific to 22q11DS. We chose WS since the literature suggests that both groups have areas of physical/cognitive/behavioural overlap but as yet there has been no direct comparison of the two groups.

Results

Despite being matched on FSIQ the WS group had significantly greater impairment than those with 22q11DS on tests of Performance IQ, while performing significantly better on tasks measuring verbal, social and facial processing skills. Moreover there were significant differences in brain anatomy. Despite similar overall brain volumes, midline anomalies were more common among the 22q11DS group, and regional differences such as increased striatal volumes and reduced cerebellar volumes in the 22q11DS group were detected.

Conclusions

These findings suggest that although the behavioural phenotype is similar in some aspects there are key differences in cognition and neuroanatomy between the two groups. Different neuropsychological profiles need to be considered when designing educational frameworks for working with these children.     

Acute vagus nerve stimulation using different pulse widths produces varying brain effects

Background

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies.

Methods

Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 μs, 250 μs, or 500 μs). The data were analyzed with SPM2.

Results

Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs.

Conclusions

The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.     

Acute cigarette smoke exposure reduces clot lysis -- association between altered fibrin architecture and the response to t-PA

Background

Enhanced thrombolysis is a proposed mechanism for reduced mortality in cigarette smokers with STEMI (“smoker's paradox”). The mechanisms remain unclear but studies suggest fibrin architecture (FA) may affect thrombolysis. Our group has previously shown that acute cigarette smoke exposure (CSE) alters FA. This study was done to evaluate the association between FA, thrombolysis and CSE.

Methods and Results

Otherwise healthy smokers (n = 22) were studied before and after smoking two cigarettes. Non-smokers (n = 22) served as controls. Two ex-vivo models were used to evaluate clot lysis of venous blood and these data were compared to FA as determined by SEM. In the first model, clot lysis in a glass tube at 60 minutes after addition of t-PA was measured. The second model quantified lysis utilizing thromboelastography. With the latter, after a clot reached maximum strength, t-PA was added and clot lysis at 60 min was noted. SEM studies were performed on platelet poor plasma mixed with thrombin and FA was examined at 20 K.Clot lysis was similar in both groups except that post-smoking, TEG showed a significantly lower lysis compared to pre- and non-smoking clots. SEM analysis showed significantly thinner fibers and denser clots post-smoking.

Conclusions

Venous clots from smokers failed to show an enhanced lysis when exposed to t-PA. In fact, acute CSE was associated with changes in FA and increased resistance to thrombolysis. These findings in part may explain enhanced thrombogenicity but suggest that mechanisms other than enhanced fibrinolysis are likely to be responsible for “smoker's paradox.”     

Visuo-motor integration in humans: Cortical patterns of response lateralisation and functional connectivity

Purpose

We assessed response and functional connectivity patterns of different parts of the visual and motor cortices during visuo-motor integration with particular focus on the intraparietal sulcus (IPS).

Methods

Brain activity was measured during a visuo-motor task in 14 subjects using event-related fMRI. During central fixation, a blue or red target embedded in an array of grey distractors was presented for 250 ms in either the left or right visual hemifield. After a delay, the subjects were prompted to press the upper or lower response button for targets in the upper and lower hemifield with the left or right thumb for blue and red targets, respectively. The fMRI responses were evaluated for different regions of interests (ROIs), and the functional connectivity of the IPS subregions with these ROIs was quantified.

Results

In an anterior IPS region and a region in the anterior premotor cortex, presumably the frontal eye fields (FEF), visually driven responses were dominant contralateral to both visual stimulus and effector. Thus, the anterior IPS combines, in contrast to the posterior IPS and the occipital cortex, response properties of cortex activated by visual input and by motor output. Further, functional connectivity with the motor areas was stronger for the anterior than for the posterior IPS regions.

Discussion

Anterior IPS and FEF appear to be of major relevance for relating visual and effector information during visuo-motor integration. Patient studies with the devised paradigm are expected to uncover the impact of pathophysiologies and plasticity on the observed cortical lateralisation patterns.     

White matter hyperintensities in affected and unaffected late teenage and early adulthood offspring of bipolar parents: A two-center high-risk study

Background

White matter hyperintensities (WMHs) are among the most replicated neuroimaging findings in bipolar disorder (BD). It is not clear whether these lesions are an artifact of comorbid conditions, or whether they are directly associated with the disorder, or even represent biological risk factor for BD.

Methods

To test whether WMHs meet criteria for an endophenotype of BD, we conducted a high-risk design study and recruited 35 affected, 44 unaffected relatives of bipolar probands (age range 15-30 years), matched by age and sex with 49 healthy controls without any personal or family history of psychiatric disorders. The presence of WMHs was determined from Fluid Attenuated Inversion Recovery (FLAIR) scans acquired on a 1.5 Tesla scanner using a validated semi-quantitative scale.

Results

We found mostly low grade WMHs in all groups. The proportion of WMH-positive subjects was comparable between the unaffected high-risk, affected familial and control groups.

Conclusion

White matter hyperintensities did not meet criteria for an endophenotype of BD. Bipolar disorder in young subjects without comorbid conditions was not associated with increased rate of WMHs.