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Background: Although the use of e-mental health interventions and their evaluation is already well advanced in countries such as the United States and Australia, research in this area is s...

OBJECTIVES: We combined multimodal functional magnetic resonance imaging (fMRI) and structural magnetic resonance imaging to probe abnormalities in brain circuits underpinning episodic memory performance deficits in patients with bipolar disorder (BD). METHODS: We acquired whole-brain fMRI data in 21 patients with BD and a matched group of 20 healthy controls during a non-verbal episodic memory task, using abstract shapes. We also examined density of gray matter, using voxel-based morphometry (VBM), and integrity of connecting fiber tracts, using diffusion tensor imaging (DTI) and tract-based spatial statistics, for areas with significant activation differences. RESULTS: Patients with BD remembered less well than controls which shapes they had seen and had lower activation levels during the encoding stage of the task in the anterior cingulate gyrus, the precuneus/cuneus bilaterally, and the left lingual gyrus, and higher activation levels during the retrieval stage in the left temporo-parietal junction. Patients with BD showed reduced gray matter volumes in the left anterior cingulate, the precuneus/cuneus bilaterally, and the left temporo-parietal region in comparison with controls. DTI revealed increased radial, axial, and mean diffusivity in the left superior longitudinal fascicle in patients with BD compared with controls. CONCLUSIONS: Changes in task-related activation in frontal and parietal areas were associated with poorer episodic memory in patients with BD. Compared with data from single imaging modalities, integration of multimodal neuroimaging data enables the building of more complete neuropsychological models of mental disorders.

BACKGROUND: Bipolar affective disorder (BD) is often associated with cognitive dysfunction in executive domains. However the biological underpinnings of cognitive deficits in BD are not sufficiently understood. A growing body of evidence indicates a loss of microstructural integrity in various white matter (WM) fiber tracts in BD. The aim of the current study was to assess potential links between WM structural abnormalities and cognitive performance in euthymic middle-aged BD patients (n=30) and matched healthy controls (n=32). METHODS: Diffusion tensor imaging (DTI) data was carried out with both voxelwise (tract based spatial statistics, TBSS) and region-of-interest (ROI) based analysis. We compared multiple indices of diffusion including fractional anisotropy (FA), radial (DR), axial (DA) and mean diffusivities (MD). RESULTS: Increased mean diffusivity was found in the fornix, anterior thalamic radiation, splenium and the truncus of the corpus callosum in BD patients compared with controls. These diffusion changes were significantly associated with poorer performance in executive tasks in BD patients. CONCLUSIONS: Our results indicate a direct link between executive cognitive functioning and abnormal WM microstructural integrity of fronto-limbic tracts in remitted BD patients, and add evidence to the neuronal disruption that underlies the residual symptomatology of BD.

In den letzten Jahren wird die Bedeutung der Person des Psychotherapeuten fur den Prozess und das Ergebnis von Psychotherapie vermehrt untersucht. Durch Therapeuteneffekte lassen sich in kontrollierten Studien etwa 5 % und in Versorgungsstudien etwa 17 % der Therapieerfolgsvarianz aufklaren. Die Identifikation einzelner erfolgsrelevanter Psychotherapeutenmerkmale gestaltete sich bisher schwierig. Der vorliegende Beitrag bietet einen Uberblick uber die Forschung zur Person des Psychotherapeuten und geht ihren Implikationen fur die Aus- und Weiterbildung von Psychotherapeuten nach. Ergebnisse aus kontrollierten Studien und der Versorgungsforschung werden referiert. Merkmale von Psychotherapeuten werden in Bezug auf den Therapieerfolg untersucht. Hierbei wird zwischen allgemeinen Personenmerkmalen und therapiebezogenen Merkmalen unterschieden. Die Bedeutung von Manualen und der Passung zwischen Patient und Therapeut wird herausgearbeitet. Nach der Beschreibung, wie sich die professionelle Entwicklung von Psychotherapeuten vollzieht, werden Masnahmen diskutiert, die die professionelle Entwicklung und Kompetenz von Psychotherapeuten fordern konnen, und solche, die moglicherweise bei anhaltend schlechten Therapieergebnisse ergriffen werden konnen. Besondere Bedeutung scheinen interpersonelle Fahigkeiten der Therapeuten zu haben. Im professionellen Entwicklungsverlauf kommt es bei Psychotherapeuten in der Regel zur Herausbildung eines zunehmend stabilen und optimistischen Selbstbilds. In der therapeutischen Tatigkeit wird bei erfahrenen Therapeuten die Intuition als komplexe und holistische Informationsverarbeitung wichtig. Bisher ungeklart ist die Frage, wie mit Psychotherapeuten, die anhaltend schlechte Behandlungsergebnisse erzielen, umgegangen werden sollte. Es bleibt noch sehr viel Forschungsarbeit, um gezielte Fordermasnahmen oder gar Selektionskriterien fur Psychotherapeuten zu entwickeln.

Item does not contain fulltext This is the first study to combine psychometric and functional neuroimaging methods to study altered patterns of autobiographical memory in bipolar disorder (BD). All participants were interviewed with an expanded version of the Bielefelder Autobiographical Memory Inventory (Bielefelder Autobiographisches Gedachtnis Inventar 2004;Lisse: Swets and Zeitlinger). We then acquired functional magnetic resonance imaging data during a task of individually designed autobiographical recall. Compared with healthy controls, BD patients reported a stronger emotionality of autobiographical memories and more frequent recollections of autobiographical events during their everyday life. Furthermore, they failed to deactivate areas in the cuneus and lingual gyrus and showed decreased activation in the inferior frontal and precentral areas compared with the control group. More frequent intrusions from a person's past, which had a neural correlate in the lack of deactivation in some default mode network areas in BD patients, may contribute to manic or depressive symptoms.

Major depressive disorders (MDD) are among the most debilitating diseases worldwide and occur with a high prevalence in elderly individuals. Neurodegenerative diseases (in particular Alzheimer's disease, AD) do also show a strong age-dependent increase in incidence and prevalence among the elderly population. A high number of geriatric patients with MDD show cognitive deficits and a very high proportion of AD patients present co-morbid MDD, which poses difficult diagnostic and prognostic questions. Especially in prodromal and in very early stages of AD, it is almost impossible to differentiate between pure MDD and MDD with underlying AD. Here, we give a comprehensive review of the literature on the current state of candidate biomarkers for MDD ("positive MDD markers") and briefly refer to established and validated diagnostic AD biomarkers in order to rule out underlying AD pathophysiology in elderly MDD subjects with cognitive impairments ("negative MDD biomarkers"). In summary, to date there is no evidence for positive diagnostic MDD biomarkers and the only way to delineate MDD from AD is to use "negative MDD" biomarkers. Because of this highly unsatisfactory current state of MDD biomarker research, we propose a research strategy targeting to detect and validate positive MDD biomarkers, which is based on a complex (genetic, molecular and neurophysiological) biological model that incorporates current state of the art knowledge on the pathobiology of MDD. This model delineates common pathways and the intersection between AD and MDD. Applying these concepts to MDD gives hope that positive MDD biomarkers can be successfully identified in the near future.

Various particles with sizes between 100 and 200 μm were encapsulated with waxes commonly used in technical coating applications. For this, a homogeneous mixture of molten paraffin and supercritical carbon dioxide was prepared in an autoclave and injected into the high-pressure fluidized bed through a nozzle from the bottom. Due to the different conditions in the mixing autoclave and the fluidized bed, the paraffin precipitated in the vicinity of the nozzle and adhered to the solid particles. A complete, thin, uniform, and solvent-free coating was produced. The use of two paraffins with different alkane compositions resulted in dissimilar spreads on glass beads due to their different glass transition temperatures. A smaller pressure drop across the nozzle led to more uniform and even coatings. Glass beads, ceramic spheres, potassium chloride, and lactose showed similar coating results, whereas different morphologies were observed with a plastic material, characterized by a rougher surface and a lower surface energy. The high quality of the coating was confirmed by standard dissolution tests with coated potassium chloride crystals and lactose agglomerates.

Objectives Neuroimaging studies in patients with bipolar disorder (BD) have indicated a number of structural brain changes, including reduced cortical thickness. However, the effects of the course of illness, clinical and cognitive variables on cortical thickness in BD patients have not yet been evaluated. Methods A total of 67 individuals (32 patients with euthymic BD and 35 healthy and age-matched controls) underwent 3D-anatomical magnetic resonance imaging (MRI). Whole-brain cortical thickness and group differences were assessed using the Freesurfer software. Course of disease variables, clinical and cognitive parameters were correlated with cortical thickness measures. Results We found reduced cortical thickness in BD patients compared with controls in the frontal and temporal lobes and in several limbic areas. We also report significant associations between cortical thickness and age of disease-onset, speed of cognitive processing, executive function and depression severity in BD patients. Conclusions Cortical thickness reduction across frontal and limbic areas is a structural correlate of affective symptom severity and cognitive impairments in BD as well of age of disease-onset. We may assume that frontal lobe structural abnormalities are present in bipolar disorder, and might lead to dysfunctional cognitive functioning. The causality and functional relevance beyond mere correlation, however, is yet to be established. Our findings encourage further longitudinal studies in BD patients and in healthy at-risk subjects in order to discern the temporal order and development of morphological changes and clinical symptoms.

In this study, we sought to examine the intrinsic functional organization of the episodic memory network during rest in bipolar disorder (BD). The previous work suggests that deficits in intrinsic functional connectivity may account for impaired memory performance. We hypothesized that regions involved in episodic memory processing would reveal aberrant functional connectivity in patients with bipolar disorder. We examined 21 patients with BD and 21 healthy matched controls who underwent functional magnetic resonance imaging (fMRI) during a resting condition. We did a seed-based functional connectivity analysis (SBA), using the regions of the episodic memory network that showed a significantly different activation pattern during task-related fMRI as seeds. The functional connectivity scores (FC) were further correlated with episodic memory task performance. Our results revealed decreased FC scores within frontal areas and between frontal and temporal/hippocampal/limbic regions in BD patients in comparison with controls. We observed higher FC in BD patients compared with controls between frontal and limbic regions. The decrease in fronto-frontal functional connectivity in BD patients showed a significant positive association with episodic memory performance. The association between task-independent dysfunctional frontal-limbic FC and episodic memory performance may be relevant for current pathophysiological models of the disease. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Item does not contain fulltext The apolipoprotein E epsilon4 allele is a well established genetic risk factor for sporadic Alzheimer's disease. It is associated with structural and functional brain changes in healthy young, middle-aged and elderly subjects. In the current study, we assessed the impact of the ApoE genotype on brain macro- and microstructure, cognitive functioning and brain activity in fifty healthy young subjects (25 ApoE epsilon4 (epsilon4+) carriers and 25 non-carriers (epsilon4-), mean age 26.4+/-4.6years). We used diffusion tensor imaging (DTI) and voxel based morphometry (VBM) to assess brain structure, an extensive neuropsychological battery to test cognitive functioning and event-related functional magnetic resonance imaging (fMRI) to capture brain activity during episodic memory encoding and retrieval. ApoE epsilon4 carriers differed from non-carriers in fMRI activations but not in cognitive performance nor in brain micro- and macrostructure. These results suggest functional alterations in the episodic memory network that are modulated by the epsilon4 allele and might precede clinical or structural neurodegeneration.

Background Episodic memory deficits affect the majority of patients with bipolar disorder (BD). Aims The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI). Methods 26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test. Results Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters. Limitations We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group. Conclusions The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.

The current study provides a complete MRI analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical magnetic resonance imaging data sets, obtained at 3 Tesla, from three different subject groups: 25 SZ patients, 29 first-degree relatives and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition towards hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.

Item does not contain fulltext In this study, we investigate whether aberrant integrity of white matter (WM) fiber tracts represents a genetically determined biological marker of schizophrenia (SZ), and its relation with clinical symptoms. We collected brain DTI data from 28 SZ patients, 18 first-degree relatives and 22 matched controls and used voxel-based analysis with tract-based spatial statistics (TBSS) in order to compare fractional anisotropy (FA) between groups. Mean voxel-based FA values from the entire skeleton of each group were compared. We did a multiple regression analysis, followed by single post-hoc contrasts between groups. FA values were extracted from the statistically significant areas. The results showed significantly smaller FA values for SZ patients in comparison with controls in cortico-spinal tracts, in commissural fibers, in thalamic projections, in association fibers and in cingulum bundles. A significant increase of FA in SZ patients in comparison with healthy controls was only found in the arcuate fasciculus. Relatives had intermediate values between patients and controls which were deemed significant in the comparison to patients and controls in association fibers, arcuate fasciculus and cingulum bundles. Lower FA values in association fibers were significantly associated with predisposition toward hallucinations (in SZ patients and relatives), with higher PANSS scores of positive symptoms and with duration of illness (SZ patients). Our results suggest that clinical and subclinical presentations of psychotic symptoms are associated with aberrant integrity of multiple WM tracts. This association may represent an endophenotype of schizophrenia, since it is present in unaffected relatives as well. Such endophenotypes may serve as quantitative traits for future genetic studies and as candidate markers for early and preclinical identification of subjects at risk.

a Laboratory of Neuroscience, Dept. of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe Univ., Frankfurt/Main, Germany b Brain Imaging Center, Goethe Univ., Frankfurt/Main, Germany c School of Psychology, Cardiff University, United Kingdom d MRC Centre for Neuropsychiatric Genetics & Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, United Kingdom