White Matter Abnormalities in Late Onset First Episode Mania: A Diffusion Tensor Imaging Study.

INTRODUCTION: A first manic episode after 50 years of age is uncommon. Late Onset Mania might be indicative of abnormalities in white matter, probably related to vascular, degenerative, or inflammatory processes. OBJECTIVE: To determine if patients with late onset mania have reduced white matter integrity according to Magnetic Resonance Diffusion Tensor Imaging (DTI) and structural MRI. METHODS: Twenty-two patients with late onset mania (>50 years old) and 22 age-paired healthy subjects were included in the study. Fractional anisotropy (FA) was used as a quantitative measure of white matter integrity. Fazekas scale was assessed also to measure white matter abnormalities in the FLAIR sequence. The Frontal Assessment Battery, COGNISTAT and Trail making test A and B were used as cognitive measurements. RESULTS: According to DTI, commissural connections (left corpus callosum), and limbic connections (right and left uncinate fasciculus) were different between the patients and the comparison group. Fractional anisotropy values in the left corpus callosum showed significant correlations with neuropsychological measures, and with the Fazekas scale score. According to Fazekas scale, a pathological score in the FLAIR sequence was significantly more frequent in the patients as compared to the comparison group. CONCLUSIONS: Patients with first episode mania in late life have relevant white matter abnormalities not explained by age, affecting interhemispheric and fronto-limbic networks probably related to executive functioning and emotional processing, at the level of the corpus callosum and the uncinate fasciculus. The etiology of this white matter loss of integrity in patients with late-onset mania is yet to be explored.

Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.

BACKGROUND: Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. METHODS: Twenty-three antipsychotic naïve subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. RESULTS: Higher levels of γ-aminobutyric acid (P<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both γ-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest. CONCLUSIONS: This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of γ-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response.

Selected Gray Matter Volumes and Gender but Not Basal Ganglia nor Cerebellum Gyri Discriminate Left Versus Right Cerebral Hemispheres: Multivariate Analyses in human Brains at 3T.

Interest in the lateralization of the human brain is evident through a multidisciplinary number of scientific studies. Understanding volumetric brain asymmetries allows the distinction between normal development stages and behavior, as well as brain diseases. We aimed to evaluate volumetric asymmetries in order to select the best gyri able to classify right- versus left cerebral hemispheres. A cross-sectional study performed in 47 right-handed young-adults healthy volunteers. SPM-based software performed brain segmentation, automatic labeling and volumetric analyses for 54 regions involving the cerebral lobes, basal ganglia and cerebellum from each cerebral hemisphere. Multivariate discriminant analysis (DA) allowed the assembling of a predictive model. DA revealed one discriminant function that significantly differentiated left vs. right cerebral hemispheres: Wilks' λ = 0.008, χ(2) (9) = 238.837, P < 0.001. The model explained 99.20% of the variation in the grouping variable and depicted an overall predictive accuracy of 98.8%. With the influence of gender; the selected gyri able to discriminate between hemispheres were middle orbital frontal gyrus (g.), angular g., supramarginal g., middle cingulum g., inferior orbital frontal g., calcarine g., inferior parietal lobule and the pars triangularis inferior frontal g. Specific brain gyri are able to accurately classify left vs. right cerebral hemispheres by using a multivariate approach; the selected regions correspond to key brain areas involved in attention, internal thought, vision and language; our findings favored the concept that lateralization has been evolutionary favored by mental processes increasing cognitive efficiency and brain capacity.

Abnormal white matter integrity in antipsychotic-naïve first-episode psychosis patients assessed by a DTI principal component analysis.

INTRODUCTION: Diffusion tensor imaging (DTI) studies in patients with schizophrenia have shown abnormalities in the microstructure of white matter tracts. Specifically, reduced fractional anisotropy (FA) has been described across multiple white matter tracts, in studies that have mainly included patients treated with antipsychotic medications. OBJECTIVE: To compare FA in antipsychotic-naïve patients experiencing a first episode of psychosis (FEP) to FA in healthy controls to demonstrate that the variance of FA can be grouped, in a coincidental manner, in four predetermined factors in accordance with a theoretical partition of the white matter tracts, using a principal components analysis (PCA). METHODS: Thirty-five antipsychotic-naïve FEP patients and 35 age- and gender-matched healthy controls underwent DTI at 3T. Analysis was performed using a tract-based spatial statistics (TBSS) method and exploratory PCA. RESULTS: DTI analysis showed extensive FA reduction in white matter tracts in FEP patients compared with the control group. The PCA grouped the white matter tracts into four factors explaining 66% of the total variance. Comparison of the FA values within each factor highlighted the differences between FEP patients and controls. DISCUSSION: Our study confirms extensive white matter tracts anomalies in patients with schizophrenia, more specifically, in drug-naïve FEP patients. The results also indicate that a small number of white matter tracts share common FA anomalies that relate to deficit symptoms in FEP patients. Our study adds to a growing body of literature emphasizing the need for treatments targeting white matter function and structure in FEP patients.

Global diffusion tensor imaging derived metrics differentiate glioblastoma multiforme vs. normal brains by using discriminant analysis: introduction of a novel whole-brain approach.

BACKGROUND: Histological behavior of glioblastoma multiforme suggests it would benefit more from a global rather than regional evaluation. A global (whole-brain) calculation of diffusion tensor imaging (DTI) derived tensor metrics offers a valid method to detect the integrity of white matter structures without missing infiltrated brain areas not seen in conventional sequences. In this study we calculated a predictive model of brain infiltration in patients with glioblastoma using global tensor metrics. METHODS: Retrospective, case and control study; 11 global DTI-derived tensor metrics were calculated in 27 patients with glioblastoma multiforme and 34 controls: mean diffusivity, fractional anisotropy, pure isotropic diffusion, pure anisotropic diffusion, the total magnitude of the diffusion tensor, linear tensor, planar tensor, spherical tensor, relative anisotropy, axial diffusivity and radial diffusivity. The multivariate discriminant analysis of these variables (including age) with a diagnostic test evaluation was performed. RESULTS: The simultaneous analysis of 732 measures from 12 continuous variables in 61 subjects revealed one discriminant model that significantly differentiated normal brains and brains with glioblastoma: Wilks' λ = 0.324, χ(2) (3) = 38.907, p < .001. The overall predictive accuracy was 92.7%. CONCLUSIONS: We present a phase II study introducing a novel global approach using DTI-derived biomarkers of brain impairment. The final predictive model selected only three metrics: axial diffusivity, spherical tensor and linear tensor. These metrics might be clinically applied for diagnosis, follow-up, and the study of other neurological diseases.

Glutamate levels in the associative striatum before and after 4 weeks of antipsychotic treatment in first-episode psychosis: a longitudinal proton magnetic resonance spectroscopy study.

IMPORTANCE: Increased glutamate levels in the right associative striatum have been described in patients during a first episode of psychosis. Whether this increase would persist after effective antipsychotic treatment is unknown. OBJECTIVES: To compare the glutamate levels in antipsychotic-naive patients with first-episode psychosis in the right associative striatum and right cerebellar cortex using proton magnetic resonance spectroscopy before and 4 weeks after antipsychotic treatment and to compare these results with normative data from sex-matched healthy control subjects. DESIGN, SETTING, AND PARTICIPANTS: Before-after trial in an inpatient psychiatric research unit among 24 antipsychotic-naive patients with first-episode psychosis and 18 healthy controls matched for age, sex, handedness, and cigarette smoking. INTERVENTIONS: Participants underwent 2 proton magnetic resonance spectroscopy studies: patients were imaged at baseline and after 4 weeks of antipsychotic treatment, while controls were imaged at baseline and at 4 weeks after the baseline measurement. Patients were treated with oral risperidone (open label) for 4 weeks with dosages that were titrated on the basis of clinical judgment. MAIN OUTCOMES AND MEASURES: Glutamate levels were estimated using LCModel (version 6.2-1T) and were corrected for the cerebrospinal fluid proportion within the voxel. RESULTS: Patients with first-episode psychosis had higher levels of glutamate in the associative striatum and the cerebellum during the antipsychotic-naive condition compared with controls. After clinically effective antipsychotic treatment, glutamate levels significantly decreased in the associative striatum, with no significant change in the cerebellum. No differences in glutamate levels were observed between groups at 4 weeks. CONCLUSIONS AND RELEVANCE: Increased glutamate levels observed at baseline in patients with first-episode psychosis normalized after 4 weeks of clinically effective antipsychotic treatment. These results provide support for the hypothesis that improvement in clinical symptoms might be related to a decrease in glutamate levels.

Gender and age groups interactions in the quantification of bone marrow fat content in lumbar spine using 3T MR spectroscopy: a multivariate analysis of covariance (Mancova).

INTRODUCTION: There is an age-related conversion of red to yellow bone marrow in the axial skeleton, with a gender-related difference less well established. Our purpose was to clarify the variability of bone marrow fat fraction (FF) in the lumbar spine due to the interaction of gender and age groups. METHODS: 44 healthy volunteers (20 males, 30-65 years old and 24 females, 30-69 years old) underwent 3T magnetic resonance spectroscopy (MRS) and conventional MRI examination of the lumbar spine; single-voxel spectrum was acquired for each vertebral body (VB). After controlling body mass index (BMI), a two-way between-groups multivariate analysis of covariance (MANCOVA) assessed the gender and age group differences in FF quantification for each lumbar VB. RESULTS: There was a significant interaction between gender and age group, p=.017, with a large effect size (partial η(2)=.330). However the interaction explained only 33% of the observed variance. Main effects were not statistically significant. BMI was non-significantly related to FF quantification. CONCLUSIONS: Young males showed a high FF content, which declined in the 4th decade, then increased the next 3 decades to reach a FF content just below the initial FF means. Females' FF were low in the 3rd decade, depicted an accelerated increase in the 4th decade, then a gradual increase the next 3 decades to reach a FF content similar to males' values. Our findings suggest that quantification of bone marrow FF using MRS might be used as a surrogate biomarker of bone marrow activity in clinical settings.

Feasibility of in vivo quantitative magnetic resonance imaging with diffusion weighted imaging, T2-weighted relaxometry, and diffusion tensor imaging in a clinical 3 tesla magnetic resonance scanner for the acute traumatic spinal cord injury of rats: technical note.

STUDY DESIGN: Prospective longitudinal study. OBJECTIVE: To verify the feasibility of performing in vivo quantitative magnetic resonance imaging evaluation of moderate traumatic spinal cord injury (SCI) in rats using a clinical 3T scanner. SUMMARY OF BACKGROUND DATA: Animal models of human diseases are essential for translational medicine. Potential treatments of SCI are evaluated in 2 ways: anatomical and functional. Advanced magnetic resonance sequences allow a noninvasive assessment of the spinal cord depicting both. This study describes and validates a very reproducible, feasible, affordable, and reliable method, designed to be applied in commercial 3T equipment, using a novel stereotactic device for spinal cord, leading to a readily available assessment of the progression of damage generated after traumatic SCI in rats. METHODS: Four Long-Evans female rats were injured with a New York University weight-drop device to produce the SCI by contusion at thoracic level 10. All animals were placed in a fixation system, using a commercial wrist antenna to obtain magnetic resonance imaging data of the relaxometry time, apparent diffusion coefficient, and fractional anisotropy. Three sets of data obtained before SCI and 1 and 4 weeks after injury were compared. RESULTS: The data showed a progressive decline in fractional anisotropy measurements after SCI comparing baseline versus the 1-week period (P < 0.001) and baseline versus the 4-week period (P < 0.019), with a significant progressive increase in apparent diffusion coefficient values and T2 after SCI only in the baseline versus the 4-week period (P < 0.045 and P < 0.024, respectively). CONCLUSION: Our results helped us to validate a novel method to acquire highly reproducible and reliable quantitative biomarkers of traumatic SCI in vivo by using a 3T clinical MR scanner coupled with a novel stereotactic device for rats. LEVEL OF EVIDENCE: N/A.

Striatal glutamate and the conversion to psychosis: a prospective 1H-MRS imaging study.

Increased glutamate levels in the associative-striatum have been described in subjects at ultra-high risk for psychosis (UHR); nevertheless, it is unclear whether this abnormality predicts the conversion to psychosis. Nineteen subjects at UHR and 26 controls were studied using proton magnetic resonance spectroscopy. Subjects at UHR were clinically followed for 2 yr. Seven UHR subjects (37%) transitioned to a psychotic disorder and the remaining 12 did not exhibit psychotic symptoms at the most recent follow-up. The psychosis transition group had higher glutamate levels compared to both non-transition and control groups (p = 0.02 and p < 0.01, respectively; effect size 1.39). These pilot findings suggest that the conversion to psychosis is associated with increased glutamate levels in the associative-striatum.

Diagnostic performance of regional DTI-derived tensor metrics in glioblastoma multiforme: simultaneous evaluation of p, q, L, Cl, Cp, Cs, RA, RD, AD, mean diffusivity and fractional anisotropy.

OBJECTIVES: Almost a dozen diffusion tensor-imaging (DTI) variables have been used to evaluate brain tumours with scarce information about their diagnostic ability. We aimed to perform a comprehensive evaluation of tensor metrics reported in the last decade. METHODS: Retrospective case control study performed in 14 patients with glioblastoma multiforme (GBM) and 28 controls. Conventional brain MR sequences and image postprocessing of DTI allowed the calculation of: MD, FA, p, q, L, Cl, Cp, Cs, RA, RD and AD, classified into five regions: normal appearance white matter (NAWM), immediate and distant oedema, enhancing rim and cystic cavity. ANOVA and AUROC analyses were performed. RESULTS: ANOVA depicted a significant difference among all metrics (p < 0.05). RA had the highest performance in the NAWM and cystic cavity; immediate and distant zones of oedema were best diagnosed by RD and Cp respectively; q was the best biomarker of the enhancing rim zone; p < 0.001 for all metrics. CONCLUSIONS: FA and MD, accepted biomarkers of brain injury, were surpassed by other metrics. RA, together with Cs, Cl and CP, might be the new leaders in the evaluation of brain tumours. DTI tensor metrics depict different clinical applicability at each tumour region.

Diffusion tensor imaging-derived measures of fractional anisotropy across the pyramidal tract are influenced by the cerebral hemisphere but not by gender in young healthy volunteers: a split-plot factorial analysis of variance.

BACKGROUND: Diffusion tensor imaging (DTI) permits quantitative examination within the pyramidal tract (PT) by measuring fractional anisotropy (FA). To the best of our knowledge, the inter-variability measures of FA along the PT remain unexplained. A clear understanding of these reference values would help radiologists and neuroscientists to understand normality as well as to detect early pathophysiologic changes of brain diseases. The aim of our study was to calculate the variability of the FA at eleven anatomical landmarks along the PT and the influences of gender and cerebral hemisphere in these measurements in a sample of young, healthy volunteers. METHODS: A retrospective, cross-sectional study was performed in twenty-three right-handed healthy volunteers who underwent magnetic resonance evaluation of the brain. Mean FA values from eleven anatomical landmarks across the PT (at centrum semiovale, corona radiata, posterior limb of internal capsule (PLIC), mesencephalon, pons, and medulla oblongata) were evaluated using split-plot factorial analysis of variance (ANOVA). RESULTS: We found a significant interaction effect between anatomical landmark and cerebral hemisphere (F (10, 32) = 4.516, P = 0.001; Wilks' Lambda 0.415, with a large effect size (partial η(2) = 0.585)). The influence of gender and age was non-significant. On average, the midbrain and PLIC FA values were higher than pons and medulla oblongata values; centrum semiovale measurements were higher than those of the corona radiata but lower than PLIC. CONCLUSIONS: There is a normal variability of FA measurements along PT in healthy individuals, which is influenced by regions of interest location (anatomical landmarks) and cerebral hemisphere. FA measurements should be reported for comparing same-side and same-landmark PT to help avoid comparisons with the contralateral PT; ideally, normative values should exist for a clinically significant age group. A standardized package of selected DTI processing tools would allow DTI processing to be routinely performed in clinical settings.

Secondary MRI-findings, volumetric and spectroscopic measurements in mesial temporal sclerosis: a multivariate discriminant analysis.

INTRODUCTION: Primary- and secondary MR findings, volumetric measurements and MR spectroscopy data of each hippocampus represent more a dozen of variables that radiologists should consider in a quantitative MR report of temporal lobe epilepsy (TLE). There is a paucity of data about the significance of secondary MR findings simultaneously evaluated with volumetry and MR spectroscopy. We analyzed the influence of qualitative-secondary MR findings simultaneously with quantitative (volumetry and spectroscopy) data in MRI positive- and negative patients with mesial temporal sclerosis (MTS). METHODS: Analytic and transversal study of 59 patients with TLE and suspiciousness of MTS. 13 variables were analyzed for each hippocampus: age, gender, cerebral hemisphere, temporal lobe atrophy, choroidal fissure dilatation, mamillary body atrophy, collateral white matter atrophy, fornix asymmetry; Naa/Cr, Cho/Cr, mI/Cr, Naa/(Cr+Cho); and hippocampus volume (mm3). Multivariate discriminant analysis (DA) was performed with the aim to identify specific morphologic and metabolic attributes in hippocampi with and without MTS. RESULTS: Discriminant function significantly differentiated the hippocampi with- and without MTS (Wilks' λ = 0.211, χ2 (11) = 116.072, p = < .001. The model explained 79.03% of the variation in the grouping variable. The pooled within-groups correlations showed the highest influence of discriminating function for the secondary MR findings over metabolite indices and hippocampal volumes, the overall predictive accuracy was 93.9%. DISCUSSION: Due of the large number of variables (qualitative and quantitative) to which a radiologist is exposed in a conventional hippocampal MR-report, such evaluation might benefit from the use of predictive models generated by unconventional statistical methods, such as DA.

Neural response to experimental heat pain in stable patients with schizophrenia.

Diminished pain sensitivity in schizophrenia has been reported in clinical studies. While the role of antipsychotic medications as a cause of the decrease in pain perception has been questioned, little is known about neural pain processing in treated schizophrenia patients. The aim of this pilot study was to examine the blood oxygen level-dependent (BOLD) changes induced by an experimental pain tolerance (endure) hot stimuli vs. non-painful stimuli in clinically stable patients with schizophrenia and in healthy controls. Twelve patients with schizophrenia, treated with risperidone and considered clinically stable, and 13 gender- and age-matched healthy controls were studied using painful and non-painful thermal stimuli in a periodic block design. BOLD changes were assessed using high field, 3 T functional Magnetic Resonance Imaging (fMRI). Pain tolerance in stable patients was not statistically different than healthy controls. Interestingly, patients showed higher activation in the primary somatosensory cortex (S1) and superior prefrontal cortex, and less activation in the posterior cingulate cortex and brainstem than controls. Our pilot study indicates that pain tolerance is similar in clinically stable patients and controls, although the neural processing of pain is not normalized with antipsychotic treatment.

Higher levels of glutamate in the associative-striatum of subjects with prodromal symptoms of schizophrenia and patients with first-episode psychosis.

The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ((1)H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a (1)H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.

In vivo 3T spectroscopic quantification of liver fat content in nonalcoholic fatty liver disease: Correlation with biochemical method and morphometry.

BACKGROUND & AIMS: The clinical application of liver fat quantification has increased in recent years, paralleling the epidemic increase in nonalcoholic fatty liver disease. The aim of this study was to perform a diagnostic evaluation of spectroscopy by comparing its measurement of total lipid content with that from liver biopsies and morphometry in normal subjects and patients with nonalcoholic fatty liver disease. METHODS: Patients with symptomatic cholelithiasis underwent 3T MR cholangiography with spectroscopic quantification of TLC. A laparoscopic cholecystectomy was performed on the day of admission, with liver samples taken during surgery. Microcolorimetric assessment quantified lipid content in liver samples and morphometric evaluation in stained slides. Statistical analysis included bivariate correlation, regression, and ROC analysis. RESULTS: The study was conducted in 18 patients, 5 men (mean age, 35.2+/-11.03 years; range, 27-54 years) and 13 women (mean age, 46.77+/-11.77 years; range, 21-61 years). Using a cut-off value >5% for fat content, 8 patients presented with steatosis and 10 patients presented with normal liver fat content. A significant correlation was observed between fat spectroscopy and lipid content (r=0.876, p<0.001). A lower and non-significant correlation was observed between lipid content and morphometry (r=0.190, p>0.05). CONCLUSIONS: The accuracy of spectroscopy in assessing fat concentration with a cut-off level of 7.48% was 100%. Spectroscopy showed a strong and significant correlation with lipid content. It may reliably replace liver biopsy for the assessment of liver fat content.

Functional magnetic resonance imaging response to experimental pain in drug-free patients with schizophrenia.

Clinical evidence suggests that there is decreased pain sensitivity in schizophrenia; however, the neurobiological mechanism of this decrease remains unknown. Using functional magnetic resonance imaging, we examined the blood oxygen level-dependent (BOLD) changes induced by experimental pain-tolerance (endure) hot stimuli vs. non-painful stimuli during an acute psychotic episode in 12 drug-free patients with schizophrenia and in 13 gender- and age-matched healthy controls. The analyses revealed that patients showed a greater BOLD response at S1 compared with controls but a reduced BOLD response in the posterior cingulate cortex (PCC), insula, and brainstem during pain-tolerance stimuli. Pain-tolerance temperature was higher in patients than in healthy controls. BOLD response in the insula positively correlated with unpleasantness and temperature in controls, but this effect was not observed in patients. S1 BOLD response positively correlated with unpleasantness in patients but not in controls. These initial results confirm that unmedicated patients with schizophrenia have a higher pain tolerance than controls, decreased activation in pain affective-cognitive processing regions (insula, PCC, brainstem), and an over-activation of the primary sensory-discriminative pain processing region (S1). These pilot results are the first to explore the mechanism driving altered pain sensitivity in schizophrenia.

[Glutamate increase in the associative striatum in schizophrenia: a longitudinal magnetic resonance spectroscopy preliminary study]. / Incremento del glutamato en el estriado de asociación en esquizofrenia. Resultados preliminares de un estudio longitudinal con espectroscopia con resonancia magnética.

OBJECTIVE: To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls. METHODS: Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr). RESULTS: The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions. CONCLUSIONS: Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.

Incremento del glutamato en el estriado de asociación en esquizofrenia. Resultados preliminares de un estudio longitudinal con espectroscopia con resonancia magnética / Glutamate increase in the associative striatum in schizophrenia: a longitudinal magnetic resonance spectroscopy preliminary study

Objetivo: Comparar los niveles de glutamato en el núcleo caudado dorsal, región rica en dopamina, y el cerebelo, región pobre en dopamina, en pacientes con esquizofrenia, durante un episodio psicótico agudo, después de recibir tratamiento antidopaminérgico (risperidona) y en controles sanos. Métodos: Se incluyeron 14 pacientes con esquizofrenia aguda sin tratamiento y 14 controles sanos. A los pacientes se les realizaron dos estudios de espectroscopia por resonancia magnética de protones (ERM1H). El primero antes de tratamiento y el segundo a las seis semanas de tratamiento efectivo. Los controles fueron evaluados en una ocasión. Los niveles de glutamato fueron normalizados con la concentración de creatina. Resultados: Los niveles de glutamato/creatina fueron mayores en el caudado dorsal de los pacientes previo a tratamiento (t=-2.16, p=0.03) y después del tratamiento en comparación con los controles (t=2.12, p=0.04). Los niveles de glutamato en el cerebelo no cambiaron con el tratamiento y fueron iguales a los controles. Conclusiones: Nuestros resultados indican que el incremento delglutamato en el caudado dorsal se encuentra en relación con la enfermedad y no cambia después de seis semanas de tratamiento antipsicótico efectivo. Más aún, la ausencia de diferencias en el cerebelo sugiere que el incremento del glutamato presente en la esquizofrenia se podría relacionar a regiones con abundante inervación dopaminérgica.

OBJECTIVE: To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls. METHODS: Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr). RESULTS: The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions. CONCLUSIONS: Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.