Leire Zubiaurre-Elorza

Decreased Regional Brain Volume and Cognitive Impairment in Preterm Children at Low Risk

OBJECTIVE: To investigate whether preterm children with low risk for neurodevelopmental deficits show long-term changes in gray matter (GM) and white matter (WM) volumes compared with term children and to relate these changes to cognitive outcome. METHODS: MRI was used to evaluate 20 preterm children who were determined to be at low risk for neurodevelopmental deficits and were born between 30 and 34 weeks’ gestational age without major neonatal morbidity or cerebral pathology in the neonatal period and 22 matched, term control subjects. Volumetric images were analyzed by means of voxel-based morphometry to identify regional cerebral alterations. Children also underwent cognitive and behavioral/emotional assessments. RESULTS: Preterm children showed global and regional GM volume reductions in several brain areas, including temporal and parietal lobes and concomitant WM volume reductions in the same areas, although only the left temporal regions achieved statistical significance. Global intellectual performance in the preterm group was significantly decreased compared with control subjects. Neither behavioral nor emotional problems were found in the preterm group. In the whole sample, we found a positive correlation between GM volume bilaterally in the middle temporal and in the postcentral gyri with IQ. Positive correlations were observed between GM and gestational age at birth in parietal and temporal cerebral regions and with WM in parietal regions. CONCLUSION: Preterm birth has an important impact on the neurodevelopmental and cognitive outcome of children at 9 years of age, being a risk factor for decreased regional cortical GM and WM even in preterm children with low risk for neurodevelopmental deficits.

Hormone-treated transsexuals report less social distress, anxiety and depression.

INTRODUCTION The aim of the present study was to evaluate the presence of symptoms of current social distress, anxiety and depression in transsexuals. METHODS We investigated a group of 187 transsexual patients attending a gender identity unit; 120 had undergone hormonal sex-reassignment (SR) treatment and 67 had not. We used the Social Anxiety and Distress Scale (SADS) for assessing social anxiety and the Hospital Anxiety and Depression Scale (HADS) for evaluating current depression and anxiety. RESULTS The mean SADS and HADS scores were in the normal range except for the HAD-Anxiety subscale (HAD-A) on the non-treated transsexual group. SADS, HAD-A, and HAD-Depression (HAD-D) mean scores were significantly higher among patients who had not begun cross-sex hormonal treatment compared with patients in hormonal treatment (F=4.362, p=.038; F=14.589, p=.001; F=9.523, p=.002 respectively). Similarly, current symptoms of anxiety and depression were present in a significantly higher percentage of untreated patients than in treated patients (61% vs. 33% and 31% vs. 8% respectively). CONCLUSIONS The results suggest that most transsexual patients attending a gender identity unit reported subclinical levels of social distress, anxiety, and depression. Moreover, patients under cross-sex hormonal treatment displayed a lower prevalence of these symptoms than patients who had not initiated hormonal therapy. Although the findings do not conclusively demonstrate a direct positive effect of hormone treatment in transsexuals, initiating this treatment may be associated with better mental health of these patients.

Effects of androgenization on the white matter microstructure of female-to-male transsexuals. A diffusion tensor imaging study

Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.

Cortical Thickness in Untreated Transsexuals

Sex differences in cortical thickness (CTh) have been extensively investigated but as yet there are no reports on CTh in transsexuals. Our aim was to determine whether the CTh pattern in transsexuals before hormonal treatment follows their biological sex or their gender identity. We performed brain magnetic resonance imaging on 94 subjects: 24 untreated female-to-male transsexuals (FtMs), 18 untreated male-to-female transsexuals (MtFs), and 29 male and 23 female controls in a 3-T TIM-TRIO Siemens scanner. T1-weighted images were analyzed to obtain CTh and volumetric subcortical measurements with FreeSurfer software. CTh maps showed control females have thicker cortex than control males in the frontal and parietal regions. In contrast, males have greater right putamen volume. FtMs had a similar CTh to control females and greater CTh than males in the parietal and temporal cortices. FtMs had larger right putamen than females but did not differ from males. MtFs did not differ in CTh from female controls but had greater CTh than control males in the orbitofrontal, insular, and medial occipital regions. In conclusion, FtMs showed evidence of subcortical gray matter masculinization, while MtFs showed evidence of CTh feminization. In both types of transsexuals, the differences with respect to their biological sex are located in the right hemisphere.

Effects of Cross-Sex Hormone Treatment on Cortical Thickness in Transsexual Individuals

INTRODUCTION Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively. AIM A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. METHODS This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values. MAIN OUTCOME MEASURES Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. RESULTS After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles. CONCLUSIONS Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system.

Cortical Thickness and Behavior Abnormalities in Children Born Preterm

Aim To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. Methods We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). Results We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. Interpretation The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems.

Thalamic changes in a preterm sample with periventricular leukomalacia: correlation with white-matter integrity and cognitive outcome at school age

Introduction:Thalamic abnormalities have been well documented in preterms with periventricular leukomalacia (PVL), although their contribution to long-term cognitive dysfunctions has not been thoroughly investigated.Results:Significant differences between groups were observed for global thalamic volume. Neuropsychological assessments showed that preterms with PVL scored within the normal range, although significantly below controls in the full intelligence quotient and the specific cognitive domains of processing speed and working memory. Correlations of several thalamic regions with Working Memory Index and FIQ were found in the PVL group. Moreover, thalamic atrophy correlated with white-matter (WM) damage indexes (fractional anisotropy and radial diffusivity) assessed by diffusion tensor imaging.Discussion:The findings suggest that thalamic damage is a common correlate of WM microstructural alterations and might be involved in the cognitive deficits seen in premature infants with PVL at school age.Methods:We analyzed the impact of PVL-associated thalamic injury on cognitive status at school age and its correlation with WM integrity as measured by magnetic resonance imaging techniques. Thalamic volume and shape of 21 preterm children with PVL were compared with those of 11 preterm children of similar gestational age and birth weight with no evidence of focal WM abnormality.

Gray Matter Volume Decrements in Preterm Children With Periventricular Leukomalacia

Periventricular leukomalacia (PVL) is the prototypic lesion in the encephalopathy of prematurity. Although PVL is identified by targeting cerebral white matter (WM), neuropathological and MRI studies document gray matter (GM) loss in cortical and subcortical structures. This study aimed to investigate the distribution of GM changes in children with a history of premature birth and PVL. Voxel-based morphometry was used to examine regional GM abnormalities in 22 children with a history of preterm birth and PVL. Preterms with PVL were compared with 22 terms and 14 preterms without PVL of similar GA and birth weight. GM and WM global volumetric volumes were found to decrease in comparison with both control groups. Regional GM volume abnormalities were also found: compared with their term peers, preterm children with PVL showed several regions of GM reduction. Moreover, PVL differed from preterms without PVL in the medial temporal lobe bilaterally, thalamus bilaterally, and caudate nuclei bilaterally. In addition, in our preterm sample with PVL, birth weight showed a statistical significant correlation with decreased GM regions. In conclusion, the voxel-based morphometry methodology revealed that PVL per se does involve GM reductions.

Anterior cingulate and paracingulate sulci morphology in patients with schizophrenia

The anterior cingulate cortex is a cerebral region engaged in several emotional and cognitive functions. The aim of this study was to investigate possible anterior cingulate and paracingulate sulcal abnormalities in schizophrenia. Twenty-three patients with DSM-IV diagnoses of schizophrenia were compared with 23 healthy subjects matched for age, gender, and parental socioeconomic status. Magnetic resonance images were used to explore the morphology of these regions, with volume and maximum depth being measured by an automated method of sulcal recognition. Additionally, voxel-based morphometry (VBM) was performed to analyze possible reduction in gray and white matter of the anterior cingulate region. A smaller volume of the left anterior cingulate sulcus (ACS) was observed in patients with schizophrenia when compared with healthy controls. Furthermore, female patients showed a reduction in volume of the left ACS and an increase of the right paracingulate sulcus (PCS) compared to female controls. There was also a significant relationship between the depth of right PCS and neuroleptic exposure. VBM analysis showed a reduction in left anterior cingulate gray matter. These findings provide further evidence of left anterior middle frontal cortex abnormalities in schizophrenia. In addition, the results suggest gender differences in the structural abnormalities of the illness.

Magnetic resonance imaging study of cerebral sulci in low-risk preterm children.

Premature birth is associated with several brain dysfunctions including changes in the normal pattern of sulcal development. Previous studies on sulcal abnormalities were performed in subjects with perinatal brain complications. We selected a sample of preterm subjects with a low risk of neurodevelopmental abnormalities with the aim of investigating the effects of prematurity per se. Surface and maximum depth measures of four sulci that develop at different gestational ages were obtained using Anatomist/Brain Visa 3.0.2 software. The sulci measured were the olfactory sulcus (16 weeks), the parieto‐occipital sulcus (22–23 weeks), the superior temporal sulcus (32 weeks) and the orbitofrontal sulcus (36–39 weeks). The sample comprised 17 low‐risk preterms (mean gestational age: 32 weeks) and 16 full‐term children who were matched for age at scan, gender, handedness and socio‐cultural status. Analysis of surface variance showed a significant group effect (P < 0.015), as well as an interaction between the type of sulcus and group (P < 0.001). The superior temporal sulcus surface was inferior in the low‐risk preterm group compared to controls. Our findings suggest that even without perinatal complications, premature birth affects sulcal morphology.