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Szeszko P.R.,Feinstein Institute for Medical Research | Szeszko P.R.,Yeshiva University | Narr K.L.,Laboratory of Neuroimaging | Phillips O.R.,Laboratory of Neuroimaging | And 7 more authors.
Schizophrenia Bulletin | Year: 2012

Identifying neurobiological predictors of response to antipsychotics in patients with schizophrenia is a critical goal of translational psychiatry. Few studies, however, have investigated the relationship between indices of brain structure and treatment response in the context of a controlled clinical trial. In this study, we sought to identify magnetic resonance (MR) imaging measures of the brain that predict treatment response in patients experiencing a first-episode of schizophrenia. Structural MR imaging scans were acquired in 39 patients experiencing a first-episode of schizophrenia with minimal or no prior exposure to antipsychotics participating in a double-blind 16-week clinical trial comparing the efficacy of risperidone vs olanzapine. Twenty-five patients were classified as responders by meeting operationally defined treatment response criteria on 2 consecutive study visits. Fourteen patients never responded to antipsychotic medication at any point during the clinical trial. MR imaging scans were also acquired in 45 age-and sex-matched healthy volunteers. Cortical pattern matching methods were used to compare cortical thickness and asymmetry measures among groups. Statistical mapping results, confirmed by permutation testing, indicated that responders had greater cortical thickness in occipital regions and greater frontal cortical asymmetry compared with nonresponders. Moreover, among responders, greater thickness in temporal regions was associated with less time to respond. Our findings are consistent with the hypothesis that plasticity and cortical thickness may be more preserved in responders and that MR imaging may assist in the prediction of antipsychotic drug response in patients experiencing a first-episode of schizophrenia. © 2010 The Author. Source


Lopes S.L.P.C.,Sao Paulo State University | Costa A.L.F.,City University of Sao Paulo | Cruz A.D.,Federal University of Fluminense | Li L.M.,Laboratory of Neuroimaging | De Almeida S.M.,University of Campinas
Dentomaxillofacial Radiology | Year: 2012

Objective: The aim of the present study was to describe the clinical and MRI findings of the temporomandibular joint (TMJ) in patients with major depressive disorders (MDDs) of the non-psychotic type. Methods: 40 patients (80 TMJs) who were diagnosed as having MDDs were selected for this study. The clinical examination of the TMJs was conducted according to the research diagnostic criteria and temporomandibular disorders (TMDs). The MRIs were obtained bilaterally in each patient with axial, parasagittal and paracoronal sections within a real-time dynamic sequence. Two trained oral radiologists assessed all images. For statistical analyses, Fisher's exact test and χ 2 test were applied (α 5 0.05). Results: Migraine was reported in 52.5% of subjects. Considering disc position, statistically significant differences between opening patterns with and without alteration (p=0.00) and between present and absent joint noises (p=0.00) were found. Regarding muscular pain, patients with and without abnormalities in disc function and patients with and without abnormalities in disc position were not statistically significant (p=0.42 and p=0.40, respectively). Significant differences between mandibular pathway with and without abnormalities (p50.00) and between present and absent joint noises (p=0.00) were observed. Conclusion: Based on the preliminary results observed by clinical and MRI examination of the TMJ, no direct relationship could be determined between MDDs and TMDs. © 2012 The British Institute of Radiology. Source


Bartzokis G.,University of California at Los Angeles | Bartzokis G.,Laboratory of Neuroimaging | Lu P.H.,University of California at Los Angeles | Amar C.P.,University of California at Los Angeles | And 9 more authors.
Schizophrenia Research | Year: 2011

Context: Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations. Objectives: Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N = 11; and RisO, N = 13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study. Main outcome measure: WM volume change scores. Results: WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function. Conclusions: The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions. © 2011. Source


Bartzokis G.,University of California at Los Angeles | Bartzokis G.,Laboratory of Neuroimaging | Lu P.H.,University of California at Los Angeles | Raven E.P.,University of California at Los Angeles | And 9 more authors.
Schizophrenia Research | Year: 2012

Context: Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in the treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. Objectives: Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. Design: Two groups of SZ subjects (RLAI, N. =. 9; and RisO, N. =. 13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and 6. months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. Main outcome measure: ICM volume change scores were adjusted for the change in the HCs. Results: ICM volume increased significantly (p. =. .005) in RLAI and non-significantly (p. =. .39) in the RisO groups compared with that of the healthy controls. A differential between-group treatment effect was at a trend level (p. =. .093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p. <. .05). Conclusions: The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action. © 2012 Elsevier B.V. Source


Raven E.P.,University of California at Los Angeles | Lu P.H.,University of California at Los Angeles | Tishler T.A.,University of California at Los Angeles | Heydari P.,University of California at Los Angeles | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2013

Background: Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain gray matter regions and may contribute to the risk of developing age-related diseases such as Alzheimer's disease (AD). Prior MRI studies demonstrated increased iron deposits in basal ganglia regions; however, the hippocampus (Hipp), which is heavily damaged in AD, and comparator regions that are resistant to AD damage, such as thalamus (Th), have rarely been examined. Objective: To assess iron levels and evidence of tissue damage in Hipp and Th of AD subjects and healthy controls. Methods: Thirty-one AD and sixty-eight healthy control subjects participated in this study. High-and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R2) was used as an index of tissue damage. Results: Compared with healthy controls, AD subjects had increased ferritin iron in Hipp (p = 0.019) but not Th (p = 0.637), and significantly decreased R2 in Hipp (p < 0.001) but not Th (p = 0.37). In the entire sample, FDRI and R2 were negatively correlated. Conclusion: The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD. © 2013-IOS Press and the authors. All rights reserved. Source

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