Ceramide levels in blood plasma correlate with major depressive disorder severity and its neutralization abrogates depressive behavior in mice.

Major depressive disorder (MDD) is a severe disease of unknown pathogenesis that will affect ∼10% of people during their lifetime. Therapy for MDD requires prolonged treatment and often fails, predicating a need for novel treatment strategies. Here, we report increased ceramide levels in the blood plasma of MDD patients and in murine stress-induced models of MDD. These blood plasma ceramide levels correlated with the severity of MDD in human patients and were independent of age, sex, or body mass index. In addition, intravenous injection of anti-ceramide antibodies or neutral ceramidase rapidly abrogated stress-induced MDD, and intravenous injection of blood plasma from mice with MDD induced depression-like behavior in untreated mice, which was abrogated by ex vivo preincubation of the plasma with anti-ceramide antibodies or ceramidase. Mechanistically, we demonstrate that ceramide accumulated in endothelial cells of the hippocampus of stressed mice, evidenced by the quantitative measurement of ceramide in purified hippocampus endothelial cells. We found ceramide inhibited the activity of phospholipase D (PLD) in endothelial cells in vitro and in the hippocampus in vivo and thereby decreased phosphatidic acid in the hippocampus. Finally, we show intravenous injection of PLD or phosphatidic acid abrogated MDD, indicating the significance of this pathway in MDD pathogenesis. Our data indicate that ceramide controls PLD activity and phosphatidic acid formation in hippocampal endothelial cells and thereby mediates MDD. We propose that neutralization of plasma ceramide could represent a rapid-acting targeted treatment for MDD.

Cancer Patients' Age-Related Benefits from Mobile Neurofeedback-Therapy in Quality of Life and Self-efficacy: A Clinical Waitlist Control Study.

Electroencephalographic neurofeedback (EEG NF) can improve quality of life (QoL) and reduce distress by modifying the amplitude of selected brain frequencies. This study aims to investigate the effects of NF therapy on QoL and self-efficacy in cancer patients and to explore age-related reactions. In a waitlist control paradigm, psychometric data (EORTC QLQ-C30, General Self-Efficacy Scale) of 20 patients were collected at three different time points, each five weeks apart. An outpatient 10-session NF intervention (mobile) was conducted between the second and third measurement point. QoL and self-efficacy changed significantly over time (QoL: F(2,36) = 5.294, p < .05, η2 = .227; Self-efficacy: F(2,26) = 8.178, p < .05, η2 = .386). While QoL increased in younger patients, older patients initially showed a decrease in QoL, which then increased during intervention. Younger patients did not differ from older patients in QoL in both waitlist control (T0-T1) and intervention phase (T1-T2). QoL in older patients significantly differed between waitlist control and intervention phase (Z = - 2.023, p < .05, d = 1.085). Self-efficacy increased in both age categories. Younger and older patients did not differ in self-efficacy in waitlist control, but in intervention phase (F(1,16) = 7.014, p < .05, η2 = .319). The current findings suggest that NF therapy is a promising treatment modality for improving QoL in cancer patients. Our study reveals NF being a tool to influence self-efficacy, which should receive more appreciation in clinical care. However, the effect of NF in different age groups as well as the influence on further cancer-related symptoms should be investigated in future research.

Amygdalar nuclei and hippocampal subfields on MRI: Test-retest reliability of automated volumetry across different MRI sites and vendors.

BACKGROUND: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. METHODS: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1-90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. RESULTS: Significant MRI site and vendor effects (p â€‹< â€‹.05) were found in a few subfields/nuclei for the ε, while extensive effects were found for the DICE score of most subfields/nuclei. Reliability was strongly influenced by volume, as ε correlated negatively and DICE correlated positively with volume size of structures (absolute value of Spearman's r correlations >0.43, p â€‹< â€‹1.39E-36). In particular, volumes larger than 200 â€‹mm3 (for amygdalar nuclei) and 300 â€‹mm3 (for hippocampal subfields, except for molecular layer) had the best test-retest reproducibility (ε â€‹< â€‹5% and DICE â€‹> â€‹0.80). CONCLUSION: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Theory of mind, emotion recognition, delusions and the quality of the therapeutic relationship in patients with psychosis - a secondary analysis of a randomized-controlled therapy trial.

BACKGROUND: Cognitive models of psychosis postulate an important role of Theory of mind (ToM) in the formation and maintenance of delusions, but research on this plausible conjecture has gathered conflicting findings. In addition, it is still an open question whether problems in emotion recognition (ER) are associated with delusions. We examined the association of problems in ToM and ER with different aspects of delusions in a large sample of patients with psychosis enrolled in a therapy trial. This also enabled us to explore the possible impact of ToM and ER on one part of patients' social life: the quality of their therapeutic relationship. METHODS: Patients with psychotic disorders and delusions and/or hallucinations (n = 185) and healthy controls (n = 48) completed a ToM picture sequencing task and an ER task. Subsequently, patients were enrolled in a randomized-controlled Cognitive Behavior Therapy (CBT) trial (ISRCTN29242879). Patients and therapists rated the quality of the therapeutic relationship during the first five sessions of therapy. RESULTS: In comparison to controls, patients were impaired in both ToM and ER. Patients with deficits in ER experienced more severe delusional distress, whereas ToM problems were not related to delusions. In addition, deficits in ER predicted a less favorable therapeutic relationship and interactional problems viewed by the therapist. Impaired ER also moderated (increased) the negative influence of delusions on the therapeutic relationship and interactional difficulties viewed by the therapist. CONCLUSIONS: Cognitive models on the formation and maintenance of delusions should consider ER as a potential candidate that might be related to the formation and maintenance of delusional distress, whereas problems in ToM might not be directly related to delusions and secondary dimensions of delusions. In addition, problems in ER in patients with psychosis might have an impact on the quality of the therapeutic relationship and patients with problems in ER are more likely to be viewed as problematic by their therapists. Nevertheless, training ER might be a way to improve the quality of the therapeutic relationship and potentially the effectiveness of CBT or other interventions for patients with psychosis.

Problems in measuring the JTC-bias in patients with psychotic disorders with the fish task: a secondary analysis of a baseline assessment of a randomized controlled trial.

BACKGROUND: The jumping to conclusions bias (JTC) is considered to be an important causal factor in theoretical models for the formation and maintenance of delusions. However, recent meta-analytic findings show a rather equivocal pattern of results regarding associations between JTC and delusions. Thus, the present study aims to investigate in a large sample whether the JTC-bias is more pronounced in patients with psychotic disorders in comparison to controls and whether the JTC bias is associated with a more severe delusional conviction, persecutory delusions, and positive symptoms in general. METHODS: Patients with psychotic disorders (n = 300) enrolled in a therapy trial and healthy controls (n = 51) conducted a variant of the beads task (fish task) as a measure for the JTC-bias at the start of the trial. Further, clinical interviews were used to assess patients' delusional severity and delusional conviction. RESULTS: There were no statistically significant differences between patients with psychotic disorders (with 53% displaying the JTC-bias) and controls (41%). Furthermore, there were no statistically significant correlations between JTC measures and persecutory delusions, delusional conviction, and positive symptoms. CONCLUSIONS: We found no differences in JTC between patients with psychotic disorders and healthy controls, which is in part in line with meta-analytic findings using a wide range of JTC task variants. Interestingly, patients with psychotic disorders displayed JTC rates commonly found in the literature, while healthy control subjects showed an unexpectedly high level of JTC. The task variant we used in the present study (fish task) is discussed as a potential reason for our results, as it may induce a more deliberative reasoning style in controls as compared to the traditional beads task. Furthermore, possible implications for the measurement of the JTC-bias, in general, are discussed. TRIAL REGISTRATION: ISRCTN29242879 ( isrctn.com ), date of registration: April 12th 2006, retrospectively registered.

Test-retest reliability of the default mode network in a multi-centric fMRI study of healthy elderly: Effects of data-driven physiological noise correction techniques.

Understanding how to reduce the influence of physiological noise in resting state fMRI data is important for the interpretation of functional brain connectivity. Limited data is currently available to assess the performance of physiological noise correction techniques, in particular when evaluating longitudinal changes in the default mode network (DMN) of healthy elderly participants. In this 3T harmonized multisite fMRI study, we investigated how different retrospective physiological noise correction (rPNC) methods influence the within-site test-retest reliability and the across-site reproducibility consistency of DMN-derived measurements across 13 MRI sites. Elderly participants were scanned twice at least a week apart (five participants per site). The rPNC methods were: none (NPC), Tissue-based regression, PESTICA and FSL-FIX. The DMN at the single subject level was robustly identified using ICA methods in all rPNC conditions. The methods significantly affected the mean z-scores and, albeit less markedly, the cluster-size in the DMN; in particular, FSL-FIX tended to increase the DMN z-scores compared to others. Within-site test-retest reliability was consistent across sites, with no differences across rPNC methods. The absolute percent errors were in the range of 5-11% for DMN z-scores and cluster-size reliability. DMN pattern overlap was in the range 60-65%. In particular, no rPNC method showed a significant reliability improvement relative to NPC. However, FSL-FIX and Tissue-based physiological correction methods showed both similar and significant improvements of reproducibility consistency across the consortium (ICC = 0.67) for the DMN z-scores relative to NPC. Overall these findings support the use of rPNC methods like tissue-based or FSL-FIX to characterize multisite longitudinal changes of intrinsic functional connectivity. Hum Brain Mapp 37:2114-2132, 2016. © 2016 Wiley Periodicals, Inc.

Occipital event-related potentials to addiction-related stimuli in detoxified patients with alcohol dependence, and their association with three-month relapse.

BACKGROUND: Understanding the biological underpinnings of relapse in alcohol dependency is a major issue in addiction research. Based on recent evidence regarding the relevance of occipital visual evoked response potentials (ERPs) in addiction research, and its significance for relapse research, we assessed occipital ERPs to alcohol- and non-alcohol-related stimuli in recently detoxified patients and controls. METHODS: Thirty recently detoxified patients with alcohol addiction, and 31 healthy control subjects, were assessed in a Go and a NoGo condition, each using three visual stimuli: tea, juice and beer. In the "Go" condition, subjects had to respond to the juice (12.5 %) and the beer stimulus (12.5 %), and ignore the tea picture (75 %). In the "NoGo" condition, subjects had to respond to the tea picture (75 %) and ignore the juice and the beer picture (12.5 % each). The subjects' EEGs were analyzed with regard to the occipital P100 and N170 ERP components. Patients were then evaluated for relapse 3 months after this initial assessment. RESULTS: P100 amplitudes differed between conditions and between stimuli, and we found a condition x electrode interaction. However, none of these P100 results involved group or relapse-status effects. N170 amplitudes in patients were elevated as compared to controls. Additionally, patients' heightened N170 amplitudes in response to the alcohol-related (beer) stimulus were found only under the NoGo condition, where subjects had to react to the frequent tea stimulus and ignore the beer and the juice stimuli, thus resulting in a condition x stimulus x group interaction. Patients reporting relapse in a 3-month follow-up assessment showed larger NoGo N170 alcohol cue-related ERP amplitudes and increased depression scores as compared to patients who stayed abstinent. Depression was related to shortened P100 latencies in patients, but unrelated to the N170 NoGo cue-reactivity effect. CONCLUSIONS: Our results indicate a sensitivity of occipital ERPs to addiction-related stimuli when these act as non-targets. Recently detoxified patients may be vulnerable to addiction-related cues when these occur outside the focus of directed attention, thereby circumventing intentional control processes. Furthermore, ERPs to addiction-related stimuli may be useful as a predictor of abstinence success in recently detoxified patients.

Longitudinal reproducibility of automatically segmented hippocampal subfields: A multisite European 3T study on healthy elderly.

Recently, there has been an increased interest in the use of automatically segmented subfields of the human hippocampal formation derived from magnetic resonance imaging (MRI). However, little is known about the test-retest reproducibility of such measures, particularly in the context of multisite studies. Here, we report the reproducibility of automated Freesurfer hippocampal subfields segmentations in 65 healthy elderly enrolled in a consortium of 13 3T MRI sites (five subjects per site). Participants were scanned in two sessions (test and retest) at least one week apart. Each session included two anatomical 3D T1 MRI acquisitions harmonized in the consortium. We evaluated the test-retest reproducibility of subfields segmentation (i) to assess the effects of averaging two within-session T1 images and (ii) to compare subfields with whole hippocampus volume and spatial reliability. We found that within-session averaging of two T1 images significantly improved the reproducibility of all hippocampal subfields but not that of the whole hippocampus. Volumetric and spatial reproducibility across MRI sites were very good for the whole hippocampus, CA2-3, CA4-dentate gyrus (DG), subiculum (reproducibility error∼2% and DICE > 0.90), good for CA1 and presubiculum (reproducibility error ∼ 5% and DICE ∼ 0.90), and poorer for fimbria and hippocampal fissure (reproducibility error ∼ 15% and DICE < 0.80). Spearman's correlations confirmed that test-retest reproducibility improved with volume size. Despite considerable differences of MRI scanner configurations, we found consistent hippocampal subfields volumes estimation. CA2-3, CA4-DG, and sub-CA1 (subiculum, presubiculum, and CA1 pooled together) gave test-retest reproducibility similar to the whole hippocampus. Our findings suggest that the larger hippocampal subfields volume may be reliable longitudinal markers in multisite studies.

The precuneus and the insula in self-attributional processes.

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p ≤ .001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations.

The impact of alcohol dependence on social brain function.

The impact of alcoholism (ALC) or alcohol dependence on the neural mechanisms underlying cognitive and affective empathy (i.e. the different routes to understanding other people's minds) in schizophrenic patients and non-schizophrenic subjects is still poorly understood. We therefore aimed at determining the extent to which the ability to infer other people's mental states and underlying neural mechanisms were affected by ALC. We examined 48 men, who suffered either from ALC, schizophrenia, both disorders or none of these disorders, using functional magnetic resonance imaging while performing on a mind reading task that involves both cognitive and affective aspects of empathy. Using voxel-based morphometry, we additionally examined whether between-group differences in functional activity were associated with deficits in brain structural integrity. During mental state attribution, all clinical groups as compared with healthy controls exhibited poor performance as well as reduced right-hemispheric insular function with the highest error rate and insular dysfunction seen in the schizophrenic patients without ALC. Accordingly, both behavioral performance and insular functioning revealed schizophrenia × ALC interaction effects. In addition, schizophrenic patients relative to non-schizophrenic subjects (regardless of ALC) exhibited deficits in structural integrity and task-related recruitment of the left ventrolateral prefrontal cortex (vlPFC). Our data suggest that ALC-related impairment in the ability to infer other people's mental states is limited to insular dysfunction and thus deficits in affective empathy. By contrast, mentalizing in schizophrenia (regardless of ALC) may be associated with insular dysfunction as well as a combination of structural and functional deficits in the left vlPFC.

Networks of Neuropsychological Functions in the Clinical Evaluation of Adult ADHD.

This study applied network analysis to explore the relations between neuropsychological functions of individuals in the clinical evaluation of attention-deficit/hyperactivity disorder (ADHD) in adulthood. A total of 319 participants from an outpatient referral context, that is, 173 individuals with ADHD (ADHD group) and 146 individuals without ADHD (n-ADHD group), took part in this study and completed a comprehensive neuropsychological assessment. A denser network with stronger global connectivity was observed in the ADHD group compared to the n-ADHD group. The strongest connections were consistent in both networks, that is, the connections between selective attention and vigilance, and connections between processing speed, fluency, and flexibility. Further centrality estimation revealed attention-related variables to have the highest expected influence in both networks. The observed relationships between neuropsychological functions, and the high centrality of attention, may help identify neuropsychological profiles that are specific to ADHD and optimize neuropsychological assessment and treatment planning of individuals with cognitive impairment.

Cognitive Underperformance in a Mixed Neuropsychiatric Sample at Diagnostic Evaluation of Adult ADHD.

(1) Background: The clinical assessment of attention-deficit/hyperactivity disorder (ADHD) in adulthood is known to show non-trivial base rates of noncredible performance and requires thorough validity assessment. (2) Objectives: The present study estimated base rates of noncredible performance in clinical evaluations of adult ADHD on one or more of 17 embedded validity indicators (EVIs). This study further examines the effect of the order of test administration on EVI failure rates, the association between cognitive underperformance and symptom overreporting, and the prediction of cognitive underperformance by clinical information. (3) Methods: A mixed neuropsychiatric sample (N = 464, ADHD = 227) completed a comprehensive neuropsychological assessment battery on the Vienna Test System (VTS; CFADHD). Test performance allows the computation of 17 embedded performance validity indicators (PVTs) derived from eight different neuropsychological tests. Further, all participants completed several self- and other-report symptom rating scales assessing depressive symptoms and cognitive functioning. The Conners' Adult ADHD Rating Scale and the Beck Depression Inventory-II were administered to derive embedded symptom validity measures (SVTs). (4) Results and conclusion: Noncredible performance occurs in a sizeable proportion of about 10% up to 30% of individuals throughout the entire battery. Tests for attention and concentration appear to be the most adequate and sensitive for detecting underperformance. Cognitive underperformance represents a coherent construct and seems dissociable from symptom overreporting. These results emphasize the importance of performing multiple PVTs, at different time points, and promote more accurate calculation of the positive and negative predictive values of a given validity measure for noncredible performance during clinical assessments. Future studies should further examine whether and how the present results stand in other clinical populations, by implementing rigorous reference standards of noncredible performance, characterizing those failing PVT assessments, and differentiating between underlying motivations.

It Takes Time: Vigilance and Sustained Attention Assessment in Adults with ADHD.

Objectives: The present study compares the utility of eight different tests of vigilance and sustained attention in the neuropsychological examination of adults with Attention-deficit/hyperactivity disorder (ADHD). Methods: Thirty-one adults diagnosed with ADHD performed eight tests for vigilance and sustained attention, spread over three assessment days. Results: Adults with ADHD showed cognitive impairments in most tests and test variables, even though their sensitivity differed greatly. No specific type of test variable stands out to be the most sensitive, and no evidence for a differential deterioration of performance over time was observed. Conclusion: This study underscores the role of vigilance and sustained attention tests in the assessment of adult ADHD. It is further concluded that summary scores over the entire test duration are sufficient, but that all variables of a test should be considered. Finally, we hypothesize that reassessment on a different day may benefit a more accurate clinical assessment of adults with ADHD, in order to adequately take intraindividual fluctuations and limitations regarding test reliability into account.

Impulsivity-related brain volume deficits in schizophrenia-addiction comorbidity.

Despite a high prevalence of schizophrenia patients with comorbid substance abuse, little is known about possible impacts on the brain. Hence, our goal was to determine whether addicted and non-addicted schizophrenic patients suffer from different brain deficits. We were especially interested to determine if grey matter volumes were affected by impulsivity. We hypothesized that (comorbid) substance abuse would be associated with enhanced impulsivity and that this enhanced impulsivity would be related to grey matter volume deficits in prefrontal areas. We employed a voxel-based morphometry approach as well as neuropsychological assessment of executive functions and trait impulsivity in 51 participants (age range 23-55). The schizophrenia group comprised 24 patients (12 patients with paranoid schizophrenia and 12 with additional comorbid substance use disorders). The comparison group comprised 27 non-schizophrenic individuals, matched by age and education (14 healthy individuals and 13 patients with substance use disorders). Total grey matter volume deficits were found in all patient groups as compared with healthy controls but were largest (~8%) in both addicted groups. While grey matter volume losses in lateral orbitofrontal and temporal regions were affected by schizophrenia, volume decreases of the medial orbitofrontal, anterior cingulate and frontopolar cortex were associated with addiction. Compared with non-addicted schizophrenics, comorbid patients showed significant volume decreases in anterior cingulate, frontopolar and superior parietal regions. Additionally, they showed an increased non-planning impulsivity that was negatively related to grey matter volumes in the same regions, except for parietal ones. The present study indicates severe grey matter volume and functional executive deficits in schizophrenia, which were only partially exacerbated by comorbid addiction. However, the relationship between non-planning impulsivity and anterior cingulate and frontopolar grey matter volumes points to a specific structure-function relationship that seems to be impaired in schizophrenia-addiction comorbidity.

Klotho KL-VS haplotype does not improve cognition in a population-based sample of adults age 55-87 years.

The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55-87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = - 0.042 (verbal fluency) and - 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI - 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55-65 years, 66-75 years, > 75 years). In the 66-75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

Accuracy and reproducibility of automated white matter hyperintensities segmentation with lesion segmentation tool: A European multi-site 3T study.

Brain vascular damage accumulate in aging and often manifest as white matter hyperintensities (WMHs) on MRI. Despite increased interest in automated methods to segment WMHs, a gold standard has not been achieved and their longitudinal reproducibility has been poorly investigated. The aim of present work is to evaluate accuracy and reproducibility of two freely available segmentation algorithms. A harmonized MRI protocol was implemented in 3T-scanners across 13 European sites, each scanning five volunteers twice (test-retest) using 2D-FLAIR. Automated segmentation was performed using Lesion segmentation tool algorithms (LST): the Lesion growth algorithm (LGA) in SPM8 and 12 and the Lesion prediction algorithm (LPA). To assess reproducibility, we applied the LST longitudinal pipeline to the LGA and LPA outputs for both the test and retest scans. We evaluated volumetric and spatial accuracy comparing LGA and LPA with manual tracing, and for reproducibility the test versus retest. Median volume difference between automated WMH and manual segmentations (mL) was -0.22[IQR = 0.50] for LGA-SPM8, -0.12[0.57] for LGA-SPM12, -0.09[0.53] for LPA, while the spatial accuracy (Dice Coefficient) was 0.29[0.31], 0.33[0.26] and 0.41[0.23], respectively. The reproducibility analysis showed a median reproducibility error of 20%[IQR = 41] for LGA-SPM8, 14% [31] for LGA-SPM12 and 10% [27] with the LPA cross-sectional pipeline. Applying the LST longitudinal pipeline, the reproducibility errors were considerably reduced (LGA: 0%[IQR = 0], p < 0.001; LPA: 0% [3], p < 0.001) compared to those derived using the cross-sectional algorithms. The DC using the longitudinal pipeline was excellent (median = 1) for LGA [IQR = 0] and LPA [0.02]. LST algorithms showed moderate accuracy and good reproducibility. Therefore, it can be used as a reliable cross-sectional and longitudinal tool in multi-site studies.

Does the cognitive dispute of psychotic symptoms do harm to the therapeutic alliance?

We examined whether the cognitive dispute of psychotic symptoms has a negative impact on the course of the therapeutic alliance. Sixty-seven patients with persistent psychotic symptoms received either cognitive behavioral therapy (CBT) or supportive therapy. Questionnaire-based alliance ratings were repeatedly obtained throughout the course of therapy. Patient and therapist alliance ratings were examined separately. Data analyses comprised repeated measurement analyses of variance and cluster analytic procedures. Neither patient nor therapist alliance ratings showed a differential course throughout the treatments. This was despite the implementation of disputing strategies in later stages of CBT. Irrespective of the treatment condition a cluster with a positive alliance rating and a cluster with a poorer rating were found for therapist and patient ratings, respectively. Baseline symptoms and insight differentiated between the types of clusters. In conclusion, CBT-specific interventions that challenge psychotic symptoms do not necessarily negatively influence the course of the alliance.

Clinical symptoms of major depression are associated with the intensity dependence of auditory event-related potential components.

The intensity (loudness) dependent amplitude change (IDAP) of the auditory event-related potential (ERP) has been shown to be associated with the outcome of treatment with selective serotonin reuptake inhibitors in major depression. The purpose of the present study is to evaluate associations between clinical symptoms of major depression and the IDAP as an indirect indicator of cortical serotonergic function. We assessed 40 in-patients suffering from a major depressive episode (DSM-IV) prior to antidepressant treatment. Psychometric characteristics of depression were assessed by means of psychiatric rating scales (CGI, HDRS, HAMA, STAI and BDI) and evaluated for associations with auditory evoked P1, N1, P2 as well as P1/N1 and N1/P2 peak to peak amplitude slopes. Our data revealed a positive correlation of the intensity dependent N1 amplitude slope with the degree of certain somatic symptoms of depression: loss of appetite and weight, insomnia, and sexual dysfunction. The results of our study might contribute to a more specific clinical basis in the differential indication of serotonergic versus noradrenergic antidepressants.

Cognitive bias modification as an add-on treatment in clinical depression: Results from a placebo-controlled, single-blinded randomized control trial.

BACKGROUND: Only 60% of depressed patients respond sufficiently to treatment, so there is a dire need for novel approaches to improve treatment effects. Cognitive Bias Modification (CBM) may be an effective and easily implemented computerized add-on to treatment-as-usual. Therefore, we investigated the effects of a positivity-attention training and a positivity-approach training compared to control trainings. METHODS: In a blinded randomized-controlled design, 139 depressed inpatients received either the CBM Attention Dot-Probe Training (DPT) or the CBM Approach-Avoidance Training (AAT), next to treatment as usual. N = 121 finished all four training sessions. Both trainings had an active and a control condition. In both active conditions, patients were trained to preferentially process generally positive pictures over neutral pictures. Depressive symptom severity was assessed before and after CBM, and positivity bias was measured at the start and end of each session. RESULTS: Clinician-rated depressive symptom severity decreased more in patients who received the active condition of the DPT or the AAT compared to patients in the control conditions. Significant change in positivity bias was found for the DPT (not the AAT), but did not mediate the effect of the training on depressive symptoms. CONCLUSIONS: The results suggest that both types of CBM (i.e., DPT and AAT) may provide a fitting add-on treatment option for clinical depression. The working mechanisms and optimal dose of CBM trainings, plus their possible combination, should be examined in more detail.

Negative schemata about the self and others and paranoid ideation in at-risk states and those with persisting positive symptoms.

BACKGROUND: The objective of this study is to test the conflicting theories concerning the association of negative self and other schemata and paranoid ideation. METHODS: A risk-based approach, including risk stratification, is used to gain insight into the association of the negative self and other schemata that may be shared by individuals or differentiate between individuals at clinical high risk (CHR) for a first-episode psychosis and those with full-blown psychosis. The dataset includes a sample of individuals at CHR (n = 137) and a sample of individuals with persisting positive symptoms (PPS, n = 211). The CHR sample was subdivided according to a prognostic index yielding 4 CHR sub-classes with increasing risk for transition to psychosis. RESULTS: Negative beliefs about the self were associated with paranoid ideation in CHR and a lower risk state. In the highest risk state and full-blown psychosis, there is an association with negative beliefs about others. CONCLUSION: These findings are in line with theories suggesting a switch from a predominantly activated negative self-schema to a malevolent others-schema in association with paranoid ideation along the risk-continuum. However, due to methodological limitations these results should be replicated by future studies.