Effects of Left Versus Right Dorsolateral Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation on Affective Flexibility in Healthy Women: A Pilot Study.

OBJECTIVE: To determine the antidepressant mechanism of action for repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) in healthy women. Our primary hypothesis was that a single session of left DLPFC rTMS, compared with a session of right DLPFC rTMS, would result in better (reduced) negative nonaffective switch costs in healthy women. BACKGROUND: The antidepressant mechanism of action for rTMS is not clear. It is possible that rTMS to the DLPFC improves emotion regulation, which could be a part of its antidepressant mechanism. METHODS: Twenty-five healthy women were randomized to receive left high-frequency (HF) rTMS versus right HF rTMS in one session and then contralateral stimulation during a second session. Emotion regulation was assessed via switch costs for reappraisal of negatively valenced information on an affective flexibility task. RESULTS: For negative nonaffective switch costs, the interaction effect in the two-way ANOVA was not significant (F1,19=3.053, P=0.097). Given that left HF rTMS is the approved treatment for depression, post hoc t tests were completed with particular interest in the left-side findings. These tests confirmed that negative nonaffective switch costs significantly improved immediately after left rTMS (t1,19=2.664, P=0.015) but not right rTMS. CONCLUSIONS: These findings suggest that left DLPFC HF rTMS may lead to antidepressant effects by improving the regulation of emotion.

Deep brain stimulation in the treatment of depression.

Major depressive disorder is a worldwide disease with debilitating effects on a patient's life. Common treatments include pharmacotherapy, psychotherapy, and electroconvulsive therapy. Many patients do not respond to these treatments; this has led to the investigation of alternative therapeutic modalities. Deep brain stimulation (DBS) is one of these modalities. It was first used with success for treating movement disorders and has since been extended to the treatment of psychiatric disorders. Although DBS is still an emerging treatment, promising efficacy and safety have been demonstrated in preliminary trials in patients with treatment-resistant depression (TRD). Further, neuroimaging has played a pivotal role in identifying some DBS targets and remains an important tool for evaluating the mechanism of action of this novel intervention. Preclinical animal studies have broadened knowledge about the possible mechanisms of action of DBS for TRD, Given that DBS involves neurosurgery in patients with severe psychiatric impairment, ethical questions concerning capacity to consent arise; these issues must continue to be carefully considered.

El trastorno depresivo mayor es una enfermedad a nivel mundial que deteriora la vida del paciente. Los tratamientos habituales incluyen farmacoterapia, psicoterapia y terapia electroconvulsive, Ya que muchos pacientes no responden a estos tratamientos se ha generado la investigación de otras alternatives de intervención terapéutica. La estimulación cerebral profunda (ECP) es una de estas modalidades, Esta terapia se empleó inicialmente con éxito para el tratamiento de trastornos motores y luego se ha extendido al tratamiento de trastornos psiquiátricos, Aunque la ECP todavía es un tratamiento naciente, en los ensayos preliminares en pacientes con depresión resistente al tratamiento (DRT) se ha demostrado su prometedora eficacia y seguridad, Además, las neuroimágenes han jugado un papel central en la identificación de algunos blancos para la ECP y se mantienen como una importante herramienta para la evaluación del mecanismo de acción de esta nueva intervención. Los estudios animates preclínicos han ampliado el conocimiento sobre los posibles mecanismos de acción de la ECP para las DRT. Dado que la ECP involucra neurocirugía en pacientes con deterioro psiquiátrico grave, surgen aspectos éticos respecto a la capacidad de consentir y estos temas deben ser tomados en cuenta con mucho cuidado.

L'épisode dépressif caractérisé est une pathologie mondiale aux effets débilitants sur la vie des patients. La pharmacothérapie, la psychothérapie et l'électroconvulsivothérapie sont des traitements courants. De nombreux patients ne répondent pas à ces traitements, ce qui a conduit à la recherche de traitements alternatifs. La stimulation cérébrale profonde (SCP) en est un. Elle a d'abord été utilisée avec succès pour le traitement des dyskinésies et a depuis été élargie au traitement des troubles psychiatriques. Bien que la SCP soit encore un traitement récent, des études préliminaires chez des patients déprimés résistants au traitement (DRT) ont montré une efficacité et une sécurité prometteuses. De plus, la neuro-imagerie a joué un rôle pivot dans l'identification des cibles pour la SCP et reste un outil important pour évaluer le mécanisme d'action de cette nouvelle technique. Des études précliniques chez l'animal ont élargi la connaissance sur les mécanismes d'action possibles de la SCP pour les DRT. La SCP impliquant un geste de neurochirurgie chez des patients ayant un trouble psychiatrique sévère, des questions éthiques se posent quant à la capacité de consentement des patients. Ces questions doivent continuer à être soigneusement prises en considération.

The importance of quality of life in patients with alcohol abuse and dependence.

LEARNING OBJECTIVES: After participating in this educational activity, the reader should be better able to identify the instruments that are currently being used to measure quality of life (QoL) in alcohol abuse and dependence; determine the impact of alcohol abuse and dependence on QoL; and evaluate the impact of treating alcohol abuse and dependence on QoL. OBJECTIVE: Quality of life, which consists of the physical, mental, and social domains, has been shown to be negatively affected by alcohol abuse and dependence. This review aims to examine QoL in alcohol abuse and dependence by reviewing the instruments used to measure it and by analyzing the impact of alcohol abuse and dependence and of treatment on QoL. METHODS: Studies were identified using a database search of PubMed and PsycINFO from the past 40 years (1971-2011) using the following keywords: abuse OR dependence, OR use AND alcohol, AND Quality of Life, QoL, Health-related quality of life, HRQOL. Two authors agreed independently on including 50 studies that met specific selection criteria. RESULTS: Although several global measures of QoL have established reliability and validity, many alcohol-specific measures of QoL have not yet been validated. Nevertheless, QoL has been shown to be significantly impaired in those with alcohol abuse and dependence, particularly in the domains of mental health and social functioning, the very areas that show the greatest improvement with abstinence and its maintenance. Moreover, the literature demonstrates the utility of using QoL measures throughout assessment and treatment as a motivational tool and as a marker for treatment efficacy. CONCLUSIONS: Measuring and monitoring QoL during assessment and treatment can add important value to patient recovery, for QoL improves with treatment and successful abstinence. Therefore, targeted, disease-specific assessments of QoL are warranted to address the impairments in the physical, mental, and social domains in alcohol abuse and dependence, thereby improving long-term outcomes.

Quality of life in borderline personality disorder.

OBJECTIVE: To review the literature on quality of life (QoL) in borderline personality disorder (BPD) by examining the use of QoL instruments, the extent of QoL impairments in BPD, and the impact of treatment on QoL in BPD. METHODS: Studies were identified through PubMed and PsycINFO searches for articles from 1980 to 2011 using the following keywords: quality of life OR health-related quality of life OR QOL OR HRQOL AND borderline personality disorder. We focused our search on studies that actually measured QoL. Two authors agreed independently on including 25 studies that met specific selection criteria. RESULTS: The data on QoL in BPD are still sparse, with high heterogeneity in the instruments used to measure QoL, which decreases the comparability of existing studies. EQ-5D, WHOQOL, SF-36, Satisfaction Profile, and Q-LESQ have been utilized as QoL measures in BPD research. The reviewed studies uniformly demonstrated grave impairments in QoL of BPD patients. The available evidence indicates that BPD treatments improve not only psychiatric symptoms but also QoL, as shown by psychotherapy and pharmacotherapy studies. Nevertheless, it remains unclear whether current treatments are able to restore QoL to community norms. CONCLUSIONS: QoL is gaining more importance as an outcome measure of psychiatric interventions. Research evidence confirms that QoL is seriously impaired in BPD and that QoL improves with treatment. Further research is needed to build a consensus on the utilization of QoL measures and to improve their validity in BPD. More importantly, future studies need to develop and test interventions to improve QoL in BPD.

Does the physical disector method provide an accurate estimation of sensory neuron number in rat dorsal root ganglia?

The physical disector is a method of choice for estimating unbiased neuron numbers; nevertheless, calibration is needed to evaluate each counting method. The validity of this method can be assessed by comparing the estimated cell number with the true number determined by a direct counting method in serial sections. We reconstructed a 1/5 of rat lumbar dorsal root ganglia taken from two experimental conditions. From each ganglion, images of 200 adjacent semi-thin sections were used to reconstruct a volumetric dataset (stack of voxels). On these stacks the number of sensory neurons was estimated and counted respectively by physical disector and direct counting methods. Also, using the coordinates of nuclei from the direct counting, we simulate, by a Matlab program, disector pairs separated by increasing distances in a ganglion model. The comparison between the results of these approaches clearly demonstrates that the physical disector method provides a valid and reliable estimate of the number of sensory neurons only when the distance between the consecutive disector pairs is 60 microm or smaller. In these conditions the size of error between the results of physical disector and direct counting does not exceed 6%. In contrast when the distance between two pairs is larger than 60 microm (70-200 microm) the size of error increases rapidly to 27%. We conclude that the physical dissector method provides a reliable estimate of the number of rat sensory neurons only when the separating distance between the consecutive dissector pairs is no larger than 60 microm.

Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study.

PURPOSE: Evaluation of treatment effects in malignant brain tumors is challenging because of the lack of reliable response predictors of tumor response. This study examines the predictive value of positron emission tomography (PET) using [18F] fluorothymidine (FLT), an imaging biomarker of cell proliferation, in patients with recurrent malignant gliomas treated with bevacizumab in combination with irinotecan. PATIENTS AND METHODS: Patients with recurrent malignant gliomas treated with biweekly cycles of bevacizumab and irinotecan were prospectively studied with FLT-PET at baseline, after 1 to 2 weeks, and after 6 weeks from start of treatment. A more than 25% reduction in tumor FLT uptake as measured by standardized uptake value was defined as a metabolic response. FLT responses were compared with response as shown by magnetic resonance imaging (MRI) and patient survival. RESULTS: Twenty-one patients were included, and 19 were assessable for metabolic response evaluation with FLT-PET. There were nine responders (47%) and 10 nonresponders (53%). Metabolic responders survived three times as long as nonresponders (10.8 v 3.4 months; P = .003), and tended to have a prolonged progression-free survival (P = .061). Both early and later FLT-PET responses were more significant predictors of overall survival (1 to 2 weeks, P = .006; 6 weeks, P = .002), compared with the MRI responses (P = .060 for both 6-week and best responses). CONCLUSION: FLT-PET as an imaging biomarker seems to be predictive of overall survival in bevacizumab and irinotecan treatment of recurrent gliomas. Whether FLT-PET performed as early as 1 to 2 week after starting treatment is as predictive as the study indicates at 6 weeks warrants further investigation.

18F-FDOPA PET imaging of brain tumors: comparison study with 18F-FDG PET and evaluation of diagnostic accuracy.

UNLABELLED: We evaluated the amino acid and glucose metabolism of brain tumors by using PET with 3,4-dihydroxy-6-(18)F-fluoro-l-phenylalanine ((18)F-FDOPA) and (18)F-FDG. METHODS: Eighty-one patients undergoing evaluation for brain tumors were studied. Initially, 30 patients underwent PET with (18)F-FDOPA and (18)F-FDG within the same week. Tracer kinetics in normal brain and tumor tissues were estimated. PET uptake was quantified by use of standardized uptake values and the ratio of tumor uptake to normal hemispheric tissue uptake (T/N). In addition, PET uptake with (18)F-FDOPA was quantified by use of ratios of tumor uptake to striatum uptake (T/S) and of tumor uptake to white matter uptake. The accuracies of (18)F-FDOPA and (18)F-FDG PET were determined by comparing imaging data with histologic findings and findings of clinical follow-up of up to 31 mo (mean, 20 mo). To further validate the accuracy of (18)F-FDOPA PET, (18)F-FDOPA PET was performed with an additional 51 patients undergoing brain tumor evaluation. RESULTS: Tracer uptake in tumors on (18)F-FDOPA scans was rapid, peaking at approximately 15 min after intravenous injection. Tumor uptake could be distinguished from that of the striatum by the difference in peak times. Both high-grade and low-grade tumors were well visualized with (18)F-FDOPA. The sensitivity for identifying tumors was substantially higher with (18)F-FDOPA PET than with (18)F-FDG PET at comparable specificities, as determined by simple visual inspection, especially for the assessment of low-grade tumors. Using receiver-operating-characteristic curve analysis, we found the optimal threshold for (18)F-FDOPA to be a T/S of greater than 1.0 (sensitivity, 96%; specificity, 100%) or a T/N of greater than 1.3 (sensitivity, 96%; specificity, 86%). The high diagnostic accuracy of (18)F-FDOPA PET at these thresholds was confirmed with the additional 51 patients (a total of 81 patients: sensitivity, 98%; specificity, 86%; positive predictive value, 95%; negative predictive value, 95%). No significant difference in tumor uptake on (18)F-FDOPA scans was seen between low-grade and high-grade tumors (P = 0.40) or between contrast-enhancing and nonenhancing tumors (P = 0.97). Radiation necrosis was generally distinguishable from tumors on (18)F-FDOPA scans (P < 0.00001). CONCLUSION: (18)F-FDOPA PET was more accurate than (18)F-FDG PET for imaging of low-grade tumors and evaluating recurrent tumors. (18)F-FDOPA PET may prove especially useful for imaging of recurrent low-grade tumors and for distinguishing tumor recurrence from radiation necrosis.