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The current study examines whether facial emotion identification and family factors at preadolescence (age 11) predict psychotic experiences 5 years later during adolescence (age 16) and whether family factors may mediate the association between facial emotion identification and psychotic experiences. Data was obtained from the epidemiological cohort TRAILS (N = 2059). At preadolescence, a facial emotion identification test and three questionnaires to assess family functioning, perceived parenting styles and parenting stress, were administered. At adolescence, a questionnaire on psychotic experiences was administered. Facial emotion identification at preadolescence was not associated with psychotic experiences at adolescence, and the mediational role of family functioning was not further explored. However, increased overprotective parenting at preadolescence was associated with a higher frequency of psychotic experiences and delusions at adolescence. Future research may examine the mechanism behind the role of overprotective parenting on psychotic experiences during adolescence.

Normal-hearing listeners are less accurate and slower to recognize words with trial-to-trial talker changes compared to a repeating talker. Cochlear implant (CI) users demonstrate poor discrimination of same-gender talkers and, to a lesser extent, different-gender talkers, which could affect word recognition. The effects of talker voice differences on word recognition were investigated using acoustic noise-vocoder simulations of CI hearing. Word recognition accuracy was lower for multiple female and male talkers, compared to multiple female talkers or a single talker. Results suggest that talker variability has a detrimental effect on word recognition accuracy under CI simulation, but only with different-gender talkers.

In favorable listening conditions, cochlear-implant (CI) users can reach high speech recognition scores with as little as seven active electrodes. Here, we hypothesized that even when speech recognition is high, additional spectral channels may still benefit other aspects of speech perception, such as comprehension and listening effort. Twenty-five adult, postlingually deafened CI users, selected from two Dutch implant centers for high clinical word identification scores, participated in two experiments. Experimental conditions were created by varying the number of active electrodes of the CIs between 7 and 15. In Experiment 1, response times (RTs) on the secondary task in a dual-task paradigm were used as an indirect measure of listening effort, and in Experiment 2, sentence verification task (SVT) accuracy and RTs were used to measure speech comprehension and listening effort, respectively. Speech recognition was near ceiling for all conditions tested, as intended by the design. However, the dual-task paradigm failed to show the hypothesized decrease in RTs with increasing spectral channels. The SVT did show a systematic improvement in both speech comprehension and response speed across all conditions. In conclusion, the SVT revealed additional benefits in both speech comprehension and listening effort for conditions in which high speech recognition was already achieved. Hence, adding spectral channels may provide benefits for CI listeners that may not be reflected by traditional speech tests. The SVT is a relatively simple task that is easy to implement and may therefore be a good candidate for identifying such additional benefits in research or clinical settings.

This qualitative ethnographic study complements an epidemiological study on first episode psychosis in Vulindlela, a rural area in KwaZulu-Natal, South Africa. It focuses on two themes that emerged from our data: (1) the calling of the ancestors to become a traditional health practitioner and (2) ukuthwasa, the training to become a traditional health practitioner. The purpose of this study is to describe the ancestral calling, and to explore whether ukuthwasa may help with the management of mental disturbances, including unusual perceptual experiences. We also provide a discussion of the changing sociopolitical context of healing in KwaZulu-Natal, as a background to our study. In-depth interviews were conducted with 20 (apprentice) traditional health practitioners, formal health practitioners, patients and relatives recruited through local traditional health practitioners and a health care clinic. Our results show that the ancestral calling might announce itself with symptoms of mental illness including unusual perceptual experiences, for which some participants consider ukuthwasa as the only effective cure. We found indications that in some individuals successful completion of ukuthwasa might promote recovery from their illness and lead to a profession in which the unusual perceptual experiences become a legitimate and positively valued aspect. We suggest that – in this particular community today, which has been subject to several sociopolitical changes – ukuthwasa may be a culturally sanctioned healing process which moderates experiences that a Western psychiatric system might characterize as psychotic symptoms, providing some individuals with a lucrative and respected role in society.

BackgroundBullying and poor theory of mind (ToM) are both considered to negatively impact academic performance. However, it is unclear if they have separate effects.AimThe aim of the current study was to examine the potentially separate associations of bullying and ToM with academic performance.SampleA general population sample of 1,170 children aged 11–12 years.MethodsInformation on bullying, type of involvement (none, victim (only), bully (only), victim–bully (both)), ToM, and estimated intelligence was obtained at face-to-face assessments. Information on academic performance was obtained from Danish school registers.ResultsToM was positively associated with academic performance, and involvement in bullying was negatively associated with academic performance. Academic performance differed between types of involvement in bullying. Pairwise post hoc analyses showed that in the full sample, the only significant difference was between those not involved and those involved as victim (only). This was also the case for girls. Adjusting for potential shared variance with gender, estimated intelligence and ToM being victim (only) and victim–bully (both) were negatively associated with academic performance compared to no involvement. Thus, being a victim (or victim–bully) contributes negatively to academic performance beyond the effects of ToM and intelligence, and regardless of gender. Similarly, ToM remained positively associated with academic performance after adjusting for shared variance.ConclusionToM and involvement in bullying were both separately associated with later academic performance. These results remained even after adjusting for shared variance, and for shared variance with gender and estimated IQ.

Background\ud \ud The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.\ud \ud \ud Methods\ud \ud We fine-mapped the classical MHC (chr6: 29.6–33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10−6) and a candidate threshold (1.6 × 10−4).\ud \ud \ud Results\ud \ud No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97–0.99).\ud \ud \ud Conclusions\ud \ud We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

Objectives Despite the gains made by current first-line interventions for major depressive disorder (MDD), modest rates of treatment response and high relapse indicate the need to augment existing interventions. Following theory and initial research indicating the promise of mindful yoga interventions (MYIs), this study examines mindful yoga as a treatment of MDD.Methods/Design This randomized controlled trial uses a sample of young females (18-34 years) to examine the efficacy and cost-effectiveness of a 9-week manualized MYI added to treatment as usual (TAU) versus TAU alone. Primary outcome measures consist of clinician-administered (Hamilton Depression Rating Scale) and self-report (Depression-Anxiety-Stress Scales) measures of depression. Underlying mechanisms will be examined, including rumination, negative self-evaluation, intolerance of uncertainty, interoceptive awareness, and dispositional mindfulness. Assessments were conducted at preintervention and will be conducted at postintervention, 6-, and 12-month follow up.Results The baseline sample consists of 171 females (88 were randomized into the MYI), reporting a baseline M-age = 25.08 years (SDage = 4.64), MHamilton-depression = 18.39 (SDHamilton = 6.00), and a MDASS-depression = 21.02 (SDDASS = 9.36).Conclusion This trial will provide important information regarding the benefits of adding yoga-based interventions to TAU for young women with MDD and the mechanisms through which such benefits may occur.

BACKGROUND: Cognitive insight is defined as the ability to reflect upon oneself (i.e. self-reflectiveness), and to not be overly confident of one's own (incorrect) beliefs (i.e. self-certainty). These abilities are impaired in several disorders, while they are essential for the evaluation and regulation of one's behavior. We hypothesized that cognitive insight is a dynamic process, and therefore examined how it relates to temporal dynamics of resting state functional connectivity (FC) and underlying structural network characteristics in 58 healthy individuals.METHODS: Cognitive insight was measured with the Beck Cognitive Insight Scale. FC characteristics were calculated after obtaining four FC states with leading eigenvector dynamics analysis. Gray matter (GM) and DTI connectomes were based on GM similarity and probabilistic tractography. Structural graph characteristics, such as path length, clustering coefficient, and small-world coefficient, were calculated with the Brain Connectivity Toolbox. FC and structural graph characteristics were correlated with cognitive insight.RESULTS: Individuals with lower cognitive insight switched more and spent less time in a globally synchronized state. Additionally, individuals with lower self-reflectiveness spent more time in, had a higher probability of, and had a higher chance of switching to a state entailing default mode network (DMN) areas. With lower self-reflectiveness, DTI-connectomes were segregated less (i.e. lower global clustering coefficient) with lower embeddedness of the left angular gyrus specifically (i.e. lower local clustering coefficient).CONCLUSIONS: Our results suggest less stable functional and structural networks in individuals with poorer cognitive insight, specifically self-reflectiveness. An overly present DMN appears to play a key role in poorer self-reflectiveness.

(1) Background: The use of smartphone-based ecological momentary assessment (EMA) questionnaires in affective disorder research has rapidly increased. Though, a thorough understanding of experienced burden of and adherence to EMA is crucial in determining the usefulness of EMA. (2) Methods: Persons with current affective disorders (n = 100), remitted persons (n = 190), and healthy controls (n = 94) participated in a smartphone-based EMA two-week monitoring period. Our primary outcomes were (momentary) perceived burden of and adherence to EMA. (3) Results: In the whole sample, lower positive and higher negative affect were associated with slightly higher levels of perceived momentary burden (B = −0.23 [95%CI = −0.27−0.19], B = 0.30 [95%CI = 0.24−0.37], respectively). The persons with current affective disorders reported slightly higher levels of experienced momentary burden (Mdn = 1.98 [IQR = 1.28−2.57]), than the remitted persons (Mdn = 1.64 [IQR = 1.11−2.24]) and healthy controls (Mdn = 1.28 [IQR = 1.04−1.92]). Nevertheless, the persons with current affective disorders still showed very high adherence rates (Mdn = 94.3% [IQR = 87.9−97.1]), at rates on a par with the remitted persons (Mdn = 94.3% [IQR = 90.0−97.1]) and healthy controls (Mdn = 94.3% [IQR = 90.0−98.6]). (4) Discussion: Frequent momentary questionnaires of mental well-being are slightly more burdensome to the persons with current affective disorders, but this does not seem to have a negative impact on adherence. Their high rate of adherence to EMA—which was similar to that in remitted persons and healthy controls —suggests that it is feasible to apply (short-duration) EMA.

Humans experience a sense of self, which is proposed to emerge from the integration of intrinsic and extrinsic self-processing through the propagation of information across brain systems. Using a novel functional magnetic resonance imaging (fMRI) paradigm, we tested this hypothesis in a non-clinical sample by modulating the intrinsic and extrinsic self-relatedness of auditory action consequences in terms of identity and agency, respectively. In addition, the relevance of individual traits associated with altered self-experiences (e.g., psychosis-like experiences) was examined. The task-evoked fMRI results showed distinctive associations between the neural coding of identity and negative affect traits, and between agency and psychosis-like experiences. Most importantly, regarding the functional connectivity analysis, graph theoretical measures demonstrated that the simultaneous processing of identity and agency relies on the functional integration and segregation of default mode, sensorimotor, language, and executive brain networks. Finally, cross-network interactions mediated by executive and sensorimotor regions were negatively associated with psychosis-like experiences when the intrinsic and extrinsic self-relatedness of action consequences conflicted. These findings provide evidence that the self is a multidimensional phenomenon rooted in the functional interactions between large-scale neuronal networks. Such interactions may have particular relevance for self-experience alterations.

Background: Hostility and aggressive behavior in patients with psychotic disorders are associated with demographic and clinical risk factors, as well as with childhood adversity and neglect. Care needs are an essential concept in clinical practice; care needs in the domain of safety for others reflect the actual problem the patient has. Hostility, aggressive behavior, and associated care needs, however, are often studied in retrospect. Method: In a sample of 1,119 patients with non-affective psychotic disorders, who were interviewed three times over a period of 6 years, we calculated the incidence of hostility, self-reported maltreatment to others and care needs associated with safety for other people (safety-to-others). Regression analysis was used to analyze the association between these outcomes and risk factors. The population attributable fraction (PAF) was used to calculate the proportion of the outcome that could potentially be prevented if previous expressions of adverse behavior were eliminated. Results: The yearly incidence of hostility was 2.8%, for safety-to-others 0.8% and for maltreatment this was 1.8%. Safety-to-others was associated with previous hostility and vice versa, but, assuming causality, only 18% of the safety-to-others needs was attributable to previous hostility while 26% was attributable to impulsivity. Hostility, maltreatment and safety-to-others were all associated with number of unmet needs, suicidal ideation and male sex. Hostility and maltreatment, but not safety-to-others, were associated with childhood adversity. Neither safety-to-others, maltreatment nor hostility were associated with premorbid adjustment problems. Conclusion: The incidence of hostility, self-reported aggressive behaviors, and associated care needs is low and linked to childhood adversity. Known risk factors for prevalence also apply to incidence and for care needs associated with safety for other people. Clinical symptoms can index aggressive behaviors years later, providing clinicians with some opportunity for preventing future incidents.

Background Apathy, a common neuropsychiatric (NPS) in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD), is associated with structural and metabolic brain changes. However, functional connectivity changes across the brain in association with apathy remain unclear. In this study, graph theoretical measures of integration and segregation from resting state functional connectivity in MCI and AD patients with low depression scores, and healthy controls. Methods In MCI and AD patients with low depression scores, graph theoretical measures of integration and segregation were derived from resting state functional connectivity in patients, which were compared between those with apathy (NPS_A, n = 21) to those without NPS (NPS_None, n = 28) and those with NPS other than apathy (NPS_NA, n = 38). Additionally, the same measures were compared between AD patients and healthy controls (amyloid uptake below threshold levels). Results Altered whole brain global efficiency and reduced local efficiency were found in NPS_A compared to NPS_None and NPS_NA. In similar contrasts, apathy was associated with increased participation coefficient in the frontoparietal and cingulo-opercular template-based networks. A study-specific network definition also showed similar results. In comparison, AD patients showed higher modularity compared to controls at the whole brain level and higher participation coefficient in the ventral attention network. Limitations The severity and dimensions of apathy were not assessed. Conclusions Loss of segregation in the frontoparietal and cingulo-opercular network, which are involved in the control of goal-directed behavior, was associated with apathy in MCI/AD. The results also suggest that network-level changes in AD patients may underlie specific NPS.

INTRODUCTION: Type 2 diabetes (T2D) is a common comorbidity in patients with schizophrenia (SCZ). The underlying pathophysiologic mechanisms are yet to be fully elucidated, although it can be argued that shared genes, environmental factors or their interaction effect are involved. This study investigated the association between polygenic risk score of SCZ (PRSSCZ) and glycated haemoglobin (HbA1c) while adjusting for polygenic risk score of T2D (PRST2D), and clinical and demographic covariables. METHODS: Genotype, clinical and demographic data of 1129 patients with non-affective psychosis were extracted from Genetic Risk and Outcome of Psychosis (GROUP) cohort study. The glycated haemoglobin (HbA1c) was the outcome. PRS was calculated using standard methods. Univariable and multivariable linear regression analyses were applied to estimate associations. Additionally, sensitivity analysis based on multiple imputation was done. After correction for multiple testing, a two-sided p-value ≤.003 was considered to discover evidence for an association. RESULTS: Of 1129 patients, 75.8% were male with median age of 29 years. The mean (standard deviation) HbA1c level was 35.1 (5.9) mmol/mol. There was no evidence for an association between high HbA1c level and increased PRSSCZ (adjusted regression coefficient (aβ) = 0.69, standard error (SE) = 0.77, p-value = .37). On the other hand, there was evidence for an association between high HbA1c level and increased PRST2D (aβ = 0.93, SE = 0.32, p-value = .004), body mass index (aβ = 0.20, SE = 0.08, p-value = .01), diastolic blood pressure (aβ = 0.08, SE = 0.04, p-value = .03), late age of first psychosis onset (aβ = 0.19, SE = 0.05, p-value = .0004) and male gender (aβ = 1.58, SE = 0.81, p-value = .05). After multiple testing correction, there was evidence for an association between high HbA1c level and late age of first psychosis onset. Evidence for interaction effect between PRSscz and antipsychotics was not observed. The multiple imputation-based sensitivity analysis provided consistent results with complete case analysis. CONCLUSIONS: Glycemic dysregulation in patients with SCZ was not associated with PRSSCZ. This suggests that the mechanisms of hyperglycemia or diabetes are at least partly independent from genetic predisposition to SCZ. Our findings show that the change in HbA1c level can be caused by at least in part due to PRST2D, late age of illness onset, male gender, and increased body mass index and diastolic blood pressure. ispartof: Journal Of Psychosomatic Research vol:132 ispartof: location:England status: published

Lizard auditory papillae have proven to be an attractive object for modelling the production of spontaneous otoacoustic emissions (SOAE). Here we use an established model (Vilfan and Duke, 2008) and extend it by exploring the effect of varying the number of oscillating elements, the strength of the parameters that describe the coupling between oscillators, the strength of the oscillators, and additive noise. The most remarkable result is that the actual number of oscillating elements hardly influences the spectral pattern, explaining why spectra from very different papillar dimensions are similar. Furthermore, the spacing between spectral peaks primarily depends on the reactive coupling between the oscillator elements. This is consistent with observed differences between lizard species with respect to tectorial covering of hair cells and SOAE peak spacings. Thus, the model provides a basic understanding of the variation in SOAE properties across lizard species. (C) 2019 Elsevier B.V. All rights reserved.

BACKGROUND AND OBJECTIVE: Neurodegenerative diseases like Parkinson's disease often take several years before they can be diagnosed reliably based on clinical grounds. Imaging techniques such as MRI are used to detect anatomical (structural) pathological changes. However, these kinds of changes are usually seen only late in the development. The measurement of functional brain activity by means of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) can provide useful information, but its interpretation is more difficult. The scaled sub-profile model principal component analysis (SSM/PCA) was shown to provide more useful information than other statistical techniques. Our objective is to improve the performance further by combining SSM/PCA and prototype-based generalized matrix learning vector quantization (GMLVQ).METHODS: We apply a combination of SSM/PCA and GMLVQ as a classifier. In order to demonstrate the combination's validity, we analyze FDG-PET data of Parkinson's disease (PD) patients collected at three different neuroimaging centers in Europe. We determine the diagnostic performance by performing a ten times repeated ten fold cross validation. Additionally, discriminant visualizations of the data are included. The prototypes and relevance of GMLVQ are transformed back to the original voxel space by exploiting the linearity of SSM/PCA. The resulting prototypes and relevance profiles have then been assessed by three neurologists.RESULTS: One important finding is that discriminative visualization can help to identify disease-related properties as well as differences which are due to center-specific factors. Secondly, the neurologist assessed the interpretability of the method and confirmed that prototypes are similar to known activity profiles of PD patients.CONCLUSION: We have shown that the presented combination of SSM/PCA and GMLVQ can provide useful means to assess and better understand characteristic differences in FDG-PET data from PD patients and HCs. Based on the assessments by medical experts and the results of our computational analysis we conclude that the first steps towards a diagnostic support system have been taken successfully.

Maladaptive aggression, as present in conduct disorder (CD) and, to a lesser extent, oppositional defiant disorder (ODD), has been associated with structural alterations in various brain regions, such as ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), amygdala, insula and ventral striatum. Although aggression can be subdivided into reactive and proactive subtypes, no neuroimaging studies have yet investigated if any structural brain alterations are associated with either of the subtypes specifically. Here we investigated associations between aggression subtypes, CU traits and ADHD symptoms in predefined regions of interest. T1-weighted magnetic resonance images were acquired from 158 children and adolescents with disruptive behavior (ODD/CD) and 96 controls in a multi-center study (aged 8-18). Aggression subtypes were assessed by questionnaires filled in by participants and their parents. Cortical volume and subcortical volumes and shape were determined using Freesurfer and the FMRIB integrated registration and segmentation tool. Associations between volumes and continuous measures of aggression were established using multilevel linear mixed effects models. Proactive aggression was negatively associated with amygdala volume (b = -10.7, p = 0.02), while reactive aggression was negatively associated with insula volume (b = -21.7, p = 0.01). No associations were found with CU traits or ADHD symptomatology. Classical group comparison showed that children and adolescents with disruptive behavior had smaller volumes than controls in (bilateral) vmPFC (p = 0.003) with modest effect size and a reduced shape in the anterior part of the left ventral striatum (p = 0.005). Our study showed negative associations between reactive aggression and volumes in a region involved in threat responsivity and between proactive aggression and a region linked to empathy. This provides evidence for aggression subtype-specific alterations in brain structure which may provide useful insights for clinical practice.

Contains fulltext : 221358.pdf (Publisher’s version ) (Open Access) Many forensic psychiatric inpatients have difficulties regulating aggressive behavior. Evidence of effective aggression treatments is limited. We designed and investigated the effectiveness of a transdiagnostic application of a virtual reality aggression prevention training (VRAPT). In this randomized controlled trial at four Dutch forensic psychiatric centers, 128 inpatients with aggressive behavior were randomly assigned to VRAPT (N = 64) or waiting list control group (N = 64). VRAPT consisted of 16 one-hour individual treatment sessions twice a week. Assessments were done at baseline, post-treatment and at 3-month follow-up. Primary outcome measures were aggressive behavior observed by staff and self-reported aggressive behavior. Analysis was by intention to treat. This trial was registered in the Dutch Trial Register (NTR, TC = 6340). Participants were included between 1 March 2017, and 31 December 2018. Compared to waiting list, VRAPT did not significantly decrease in self-reported or observed aggressive behavior (primary outcomes). Hostility, anger control, and non-planning impulsiveness improved significantly in the VRAPT group compared to the control group at post-treatment. Improvements were not maintained at 3-month follow-up. Results suggest that VRAPT does not decrease aggressive behavior in forensic inpatients. However, there are indications that VRAPT temporarily influences anger control skills, impulsivity and hostility. 18 p.

In this study, we mathematically predict retinal vascular resistance (RVR) and retinal blood flow (RBF), we test predictions using laser speckle flowgraphy (LSFG), we estimate the range of vascular autoregulation, and we examine the relationship of RBF with the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC). Fundus, optical coherence tomography (OCT), and OCT-angiography images, systolic/diastolic blood pressure (SBP/DBP), and intraocular pressure (IOP) measurements were obtained float 36 human subjects. We modeled two circulation markers (RVR and RBF) and estimated individualized lower/higher autoregula tion limits (LARL/HARL), using retinal vessel calibers, fractal dimen- sion, perfusion pressure, and population-based hematocrit values. Quantitative LSFG waveforms were extracted from vessels of the same eyes, before and during IOP elevation. LSFG metrics explained most variance in RVR (R-2 =0.77/P = 6.9.10(-9)) and RBF (R-2 =0.65/P = 1.0.10(-6)), suggesting that the markers strongly reflect blood flow physiology. Higher RBF was associated with thicker RNFL (P = 4.0.10(-4)) and GCC (P = 0.003), thus also verifying agreement with structural measurements. LARL was at SBP/DBP of 105/65 mmHg for the average subject without arterial hypertension and at 115/75 mmHg for the average hypertensive subject. Moreover, during IOP elevation, changes in RBF were more pronounced than changes in RVR. These observations physiologically imply that healthy subjects are already close to LARL, thus prone to hypoperfusion. In conclusion, we modeled two clinical markers and described a novel method to predict individualized autoregulation limits. These findings could improve understanding of retinal perfusion and pave the way for personalized intervention decisions, when treating patients with coexisting ophthalmic and cardiovascular pathologies.NEW & NOTEWORTHY We describe and test a new approach to quantify retinal blood flow, based on standard clinical examinations and imaging techniques, linked together with a physiological model. We use these findings to generate individualized estimates of the autoregulation range. We provide evidence that healthy subjects are closer to the lower autoregulation limit than thought before. This suggests that some retinas are less prepared to withstand hypoperfusion, even after small intraocular pressure rises or blood pressure drops.

Highlights • We investigated whole-brain measures of integration, hierarchy, and metastability. • Depressive symptoms in a non-clinical sample revealed more static configurations. • Constrained spatiotemporal dynamics correlated with increased depressive symptoms. • Reduced global integration was associated with increased depressive symptoms., Depressive symptoms following a stressful life event, such as a relationship breakup, are common, and constitute a potent risk factor for the onset of a major depressive episode. Resting-state neuroimaging studies have increasingly identified abnormal whole-brain communication in patients with depression, but it is currently unclear whether depressive symptoms in individuals without a clinical diagnosis have reliable neural underpinnings. We investigated to what extent the severity of depressive symptoms in a non-clinical sample was associated with imbalances in the complex dynamics of the brain during rest. To this end, a novel intrinsic ignition approach was applied to resting-state neuroimaging data from sixty-nine participants with varying degrees of depressive symptoms following a relationship breakup. Ignition-based measures of integration, hierarchy, and metastability were calculated for each participant, revealing a negative correlation between these measures and depressive ratings. We found that the severity of depressive symptoms was associated with deficits in the brain’s capacity to globally integrate and process information over time. Furthermore, we found that increased depressive symptoms were associated with reduced spatial diversity (i.e., hierarchy) and reduced temporal variability (i.e., metastability) in the functional organization of the brain. These findings suggest the merit of investigating constrained dynamical complexity as it is sensitive to the level of depressive symptoms even in a non-clinical sample.

BACKGROUND: Research on environmental and individual risk-factors in patients with a psychotic disorder and co-occurring obsessive-compulsive symptoms (OCS) is limited. OBJECTIVE: This study aimed to examine the role of childhood trauma and coping on the occurrence of OCS in patients with a psychotic disorder and on a subclinical level in siblings. PARTICIPANTS AND SETTING: 626 patients and 638 siblings from the Genetic Risk and Outcome of Psychosis (GROUP) study were included in the current study. METHODS: Differences between patients and siblings with and without OCS were analyzed with between-group comparisons. Mediation analyses investigated the effect of coping on the association between trauma and OCS severity. RESULTS: Patients and siblings with OCS reported more childhood traumatic events, particularly sexual (OR = 1.62 / 3.26) and emotional (OR = 1.47 / 2.04) abuse compared to those without OCS. Both patients (d = 0.69) and siblings (d = 0.49) with co-occurring OCS showed a higher tendency for dysfunctional passive coping strategies compared to the group without OCS. The tendency for passive coping mediated the association between sexual and emotional abuse and OCS severity in patients. CONCLUSIONS: Results imply that childhood trauma is associated with the presence of co-occurring OCS. Enhancing active coping strategies might have a beneficial effect in the prevention and treatment of co-occurring OCS in patients with psychotic disorders. ispartof: Child Abuse & Neglect vol:99 pages:104243-104243 ispartof: location:England status: published

The primary afferent neurons are responsible for the fast and reliable encoding of sound over a wide range of frequencies and intensities. Populations of afferent neurons with heterogenous response properties are required to perform this remarkable incredible feat. This chapter reviews the anatomical, physiological, and genetic mechanisms that define subpopulations of auditory spiral ganglion neurons and afferents that contribute to the encoding of sound. Importantly, these mechanisms also contribute to the susceptibility of the auditory system to acoustic overexposure and aging.

Little is known about the brain's functional organization during resting-state in children with Tourette syndrome (TS). We aimed to investigate this with a specific focus on the role of comorbid attention-deficit/hyperactivity disorder (ADHD). We applied graph theoretical analysis to resting-state functional magnetic resonance imaging data of 109 8-to-12-year-old children with TS (n = 46), ADHD without tics (n = 23), and healthy controls (n = 40). First, we compared these three groups, and in a second comparison four groups, distinguishing TS with (TS + ADHD, n = 19) and without comorbid ADHD (TS−ADHD, n = 27). Weighted brain graphs were constructed for both comparisons to investigate global efficiency, local efficiency, and clustering coefficient per acquired network. Local efficiency and clustering coefficient were significantly lower in children with TS−ADHD in the default mode network compared with healthy controls, and in the frontoparietal network compared with ADHD; we also found associations with higher tic severity. Our study supports a different functional brain network organization in children with TS−ADHD, compared with healthy controls and children with ADHD.

BACKGROUND: Disentangling psychopathological heterogeneity in schizophrenia is challenging, and previous results remain inconclusive. We employed advanced machine learning to identify a stable and generalizable factorization of the Positive and Negative Syndrome Scale and used it to identify psychopathological subtypes as well as their neurobiological differentiations. METHODS: Positive and Negative Syndrome Scale data from the Pharmacotherapy Monitoring and Outcome Survey cohort (1545 patients; 586 followed up after 1.35 +/- 0.70 years) were used for learning the factor structure by an orthonormal projective non-negative factorization. An international sample, pooled from 9 medical centers across Europe, the United States, and Asia (490 patients), was used for validation. Patients were clustered into psychopathological subtypes based on the identified factor structure, and the neurobiological divergence between the subtypes was assessed by classification analysis on functional magnetic resonance imaging connectivity patterns. RESULTS: A 4-factor structure representing negative, positive, affective, and cognitive symptoms was identified as the most stable and generalizable representation of psychopathology. It showed higher internal consistency than the original Positive and Negative Syndrome Scale subscales and previously proposed factor models. Based on this representation, the positive-negative dichotomy was confirmed as the (only) robust psychopathological subtypes, and these subtypes were longitudinally stable in about 80% of the repeatedly assessed patients. Finally, the individual subtype could be predicted with good accuracy from functional connectivity profiles of the ventromedial frontal cortex, temporoparietal junction, and precuneus. CONCLUSIONS: Machine learning applied to multisite data with cross-validation yielded a factorization generalizable across populations and medical systems. Together with subtyping and the demonstrated ability to predict subtype membership from neuroimaging data, this work further disentangles the heterogeneity in schizophrenia.

BackgroundDisturbances in emotion regulation (ER) are characteristic of both patients with bipolar disorder (BD) and schizophrenia (SZ). We investigated the temporal dynamics of brain activation during cognitive ER in BD and SZ to understand the contribution of temporal characteristics of disturbed ER to their unique and shared symptomatology.MethodForty-six participants performed an ER-task (BD,n= 15; SZ,n= 16; controls,n= 15) during functional magnetic resonance imaging, in which they were instructed to use cognitive reappraisal techniques to regulate their emotional responses. Finite impulse response modeling was applied to estimate the temporal dynamics of brain responses during cognitive reappraisal (v.passive attending) of negative pictures. Group, time, and group × time effects were tested using multivariate modeling.ResultsWe observed a group × time interaction during ER in the ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) and inferior occipital gyrus. Patients with SZ demonstrated initial hyper-activation of the VLPFC and SMA activation that was not sustained in later regulatory phases. Response profiles in the inferior occipital gyrus in SZ showed abnormal activation in the later phases of regulation. BD-patients showed general blunted responsivity in these regions.ConclusionsThese results suggest that ER-disturbances in SZ are characterized by an inefficient initialization and failure to sustain regulatory control, whereas in BD, a failure to recruit regulatory resources may represent initial deficits in formulating adequate representations of the regulatory needs. This may help to further understand how ER-disturbances give rise to symptomatology of BD and SZ.

For almost 40 years, thinking about reasoning has been dominated by dual process theories. This model, consisting of two distinct types of human reasoning, one fast and effortless, the other slow and deliberate, has also been applied to medical diagnosis. Medical experts are trained to diagnose patients based on their symptoms. When symptoms are prototypical for a certain diagnosis, practitioners may rely on fast, recognition-based reasoning. However, if they are confronted with ambiguous clinical information slower, analytical reasoning is required. To examine the neural underpinnings of these two hypothesized forms of reasoning, sixteen highly experienced clinical neurologists were asked to diagnose two types of medical cases, straightforward and ambiguous cases, while functional magnetic resonance imaging was being recorded. Compared to reading control sentences, diagnosing cases resulted in increased activation in brain areas typically found to be active during reasoning such as the caudate nucleus, and frontal and parietal cortical regions. In addition, we found vast increased activity in the cerebellum. Regarding the activation differences between the two types of reasoning, no pronounced differences were observed in terms of regional activation. Notable differences were observed, though, in functional connectivity: cases containing ambiguous information showed stronger connectivity between specific regions in the frontal, parietal, and temporal cortex in addition to the cerebellum. Based on these results we propose that the higher demands in terms of controlled cognitive processing during analytical medical reasoning may be subserved by stronger communication between key regions for detecting and resolving uncertainty.

The alternative mechanical theory of glaucoma, in which an increased pressure difference across the lamina cribrosa (difference between intraocular and intracranial pressure; IOP and ICP), rather than solely an elevated IOP, leads to structural and functional vision loss, is still controversial. If the theory is true, a drug that simultaneously lowers both the IOP and ICP may be ineffective. The aim of this study was to determine how acetazolamide (AAZ; a drug prescribed in glaucoma that aims to lower the IOP) affects both IOP and ICP in glaucoma patients and to compare the magnitude and time course of the induced pressure changes with those of healthy subjects not taking AAZ. IOP and noninvasive ICP (measured through emissions from the ear) were measured in 20 glaucoma patients taking 125 mg of AAZ twice daily. Measurements were taken for 30 minutes before taking the drug and for 2 hours post-ingestion. Comparisons were made with 13 age-similar controls. After 12 hours with no anti-glaucoma medication, AAZ did not further reduce IOP in glaucoma patients compared to controls (P = 0.58) but did reduce ICP compared to controls (P = 0.035), by approximately 4 mmHg. Our findings suggest that there are periods during the day when the pressure difference across the lamina cribrosa is larger in case of AAZ use. Future studies should focus on improving the noninvasive ICP testing, different doses and dosing schedules of AAZ, and the time course of IOP in glaucoma patients not taking AAZ.

Introduction Magnetic resonance (MR) imaging is often used in diagnostic evaluation of tinnitus patients. Incidental findings like a neurovascular conflict (NVC) in the cerebellopontine angle are often found; however, the diagnostic value of this finding remains unclear. The aim of this study is to investigate whether the type or degree of compression of the vestibulocochlear nerve is of diagnostic value in patients with a NVC. Methods A retrospective study was performed in 111 tinnitus patients with available MR imaging between 2013 and 2015. Clinical and audiometric variables were gathered and MR imaging was reevaluated by two neuroradiologists. NVCs were analyzed using a grading system based on previous research by Sirikci et al. RESULTS:: In total, 220 ears were available for assessment. In patients with unilateral tinnitus a loop compression and an indentation of the cochleovestibular nerve were more frequent than in patients with bilateral tinnitus. However, there was no significant difference in distribution of the type of compression between tinnitus and nontinnitus ears. Patient with unilateral tinnitus had a significantly higher degree of hearing loss in the symptomatic ear, compared with the asymptomatic ear and with the bilateral tinnitus group. Also, it was found that the degree of hearing loss did not differ between the various types of compression. Conclusion This study did not find a diagnostic value of specific types of compression in patients with a NVC. Although the distribution of NVC classification was different in patients with unilateral and bilateral tinnitus, there was no definite relation between the type of NVC and the presence of ipsilateral tinnitus. Also, the degree of hearing loss was not related to specific types of NVC.

Highlights • We found a visual restitution training effect modulated by attention in hemianopia. • When at rest, Precuneus and Occipital Pole Network are functionally connected. • The strength of this connection prior to training was positively related to training effect. • Precuneus may play a role in visual field improvements by modulating attention. • Our finding may help identifying patients most likely to benefit from training., Visual field defects in chronic hemianopia can improve through visual restitution training, yet not all patients benefit equally from this long and exhaustive procedure. Here, we asked if resting-state functional connectivity prior to visual restitution could predict training success. In two training sessions of eight weeks each, 20 patients with chronic hemianopia performed a visual discrimination task by directing spatial selective attention towards stimuli presented in either hemifield, while suppressing eye movements. We examined two effects: a sensitivity change in the attended (trained) minus the unattended (control) hemifield (i.e., a training-specific improvement), and an overall improvement (i.e., a total change in sensitivity after both sessions). We then identified five visual resting-state networks and evaluated their functional connectivity in relation to both training effects. We found that the functional connectivity strength between the anterior Precuneus and the Occipital Pole Network was positively related to the attention modulated (i.e., training-specific) improvement. No such relationship was found for the overall improvement or for the other visual networks of interest. Our finding suggests that the anterior Precuneus plays a role in attention-modulated visual field improvements. The resting-state functional connectivity between the anterior Precuneus and the Occipital Pole Network may thus serve as an imaging-based biomarker that quantifies a patient's potential capacity to direct spatial attention. This may help to identify hemianopia patients that are most likely to benefit from visual restitution training.

Objective: Auditory verbal hallucinations (AVHs) are a common feature in youth and mostly transient. Nevertheless, while present, AVH can cause considerable distress. Children and adolescents seeking help for distressing AVH represent a heterogeneous group in terms of underlying factors, yet they consistently suffer from their AVH. Until now, a youth-specific psychotherapeutic intervention for AVH was lacking. Experts in the field of treating AVH in both adults and youngsters collaborated with service users to develop the cognitive behavioral therapy (CBT) “Stronger Than Your Voices” (STYV). We investigated feasibility and clinical outcomes of the STYV therapy. Methods: Patients were derived from children and adolescents seeking help for AVH at the UMC Utrecht outpatient clinic with an indication for STYV therapy. Therapists preferably originated from referring health care facilities and were required to have sufficient general knowledge and experience with CBT. They received a short individual training to apply STYV. After, patients and their therapists could participate this naturalistic pilot study, assessing feasibility, tolerability, and clinical change when applying the STYV therapy. Results: Six participants (10–16 years old), all suffering from comorbid psychopathology, provided pre and post measures, all completing STYV therapy without experiencing an aggravation of symptoms. AVH total impact decreased 40% with Cohen’s d within-group effect size (1.28) also suggesting clinically meaningful change. Therapists were positive about STYV therapy and manual. Conclusion: The STYV therapy is feasible for youth with distressing AVH. First results indicate that STYV may be clinically effective. A trial to further test effectiveness in a larger sample is needed.

Humans can learn simple new tasks very quickly. This ability suggests that people can reuse previously learned procedural knowledge when it applies to a new context. We have proposed a modeling approach based on this idea and used it to create a model of the attentional blink (AB). The main idea of the skill-based approach is that models are not created from scratch but, instead, built up from reusable pieces of procedural knowledge (skills). This approach not only provides an explanation for the fast learning of simple tasks but also shows much promise to improve certain aspects of cognitive modeling (e.g., robustness and generalizability). We performed two experiments, in order to collect empirical support for the model’s prediction that the AB will disappear when the two targets are consolidated as a single chunk. Firstly, we performed an unsuccessful replication of a study reporting that the AB disappears when participants are instructed to remember the targets as a syllable. However, a subsequent experiment using easily combinable stimuli supported the model’s prediction and showed a strongly reduced AB in a large group of participants. This result suggests that it is possible to avoid the AB with the right consolidation strategy. The skill-based approach allowed relating this finding to a general cognitive process, thereby demonstrating that incorporating this approach can be very helpful to generalize the findings of cognitive models, which otherwise tends to be rather difficult.

The recurrent nature of Major Depressive Disorder (MDD) necessitates a better understanding of mechanisms facilitating relapse. MDD has often been associated with abnormal emotion regulation, underpinned by aberrant interactions between the prefrontal cortex and subcortical areas. We assessed whether neural regulation abnormalities remain after remission and relate to emotion regulation problems in daily life. At the baseline measurement of a randomized controlled trial, an emotion regulation task was performed during fMRI scanning by 46 remitted recurrent (rrMDD) patients and 24 healthy controls. We assessed both fMRI peak activity and the temporal dynamics of the neural response during passive attendance and explicit regulation of positive and negative emotions. Furthermore, we assessed regulation strategy use in daily life using questionnaires, and attentional biases using a modified attentional dot-probe task. RrMDD patients showed lower activation and different temporal dynamics in occipital, parietal, and prefrontal brain regions during passive attendance of emotional material compared to healthy controls. During explicit downregulation of negative emotions, no group differences were found. However, during explicit upregulation of positive emotions, rrMDD patients showed a different neural response over time in the insula. Behaviourally, rrMDD patients were characterized by dysfunctional regulation strategies in daily life. Within rrMDD patients, rumination was associated with activation within a limbic- prefrontal network. After remission, immediate emotional processing seems unaffected, but regulatory abnormalities remain, especially uninstructed and in daily life. Abnormal insula activation during positive upregulation suggests decreased monitoring of positive emotions. The relation between inadequate rumination and brain activity during emotion regulation suggests that regulation of both positive and negative affect is important in understanding neurocognitive underpinnings of resilience.

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment-resistant\ud depression; disorder severity and unfavorable treatment outcomes are shown to be influenced\ud by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment\ud and response/nonresponse are associated with an increased genetic burden for major\ud depression (MD) using polygenic risk score (PRS), which summarize the contribution of diseaserelated\ud common risk variants. Fifty-one psychiatric inpatients suffering from a major depressive\ud episode underwent ECT. MD-PRS were calculated for these inpatients and a separate\ud population-based sample (n = 3,547 healthy; n = 426 self-reported depression) based on summary\ud statistics from the Psychiatric Genomics Consortium MDD-working group (Cases:\ud n = 59,851; Controls: n = 113,154). MD-PRS explained a significant proportion of disease status\ud between ECT patients and healthy controls (p = .022, R2 = 1.173%); patients showed higher\ud MD-PRS. MD-PRS in population-based depression self-reporters were intermediate between\ud ECT patients and controls (n.s.). Significant associations between MD-PRS and ECT response\ud (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate\ud that ECT cohorts show an increased genetic burden for MD and are consistent with the\ud hypothesis that treatment-resistant MD patients represent a subgroup with an increased genetic\ud risk for MD. Larger samples are needed to better substantiate these findings.

Objective: This article describes the development and testing of the Functional Recovery tool (FR tool), a short instrument for assessing functional recovery during routine outcome monitoring of people living with serious mental illnesses. Methods: To assess functional recovery, mental health professionals conducted semistructured interviews with people living with serious mental illnesses on three areas of social functioning: daily living and self-care, work and study, and social contacts. Functioning in each of these areas over the past 6 months was rated on a 3-point scale: 0 (independent), 1 (partially independent), and 2 (dependent). The dichotomous overall outcome of the tool is defined as independent functioning in all areas. We analyzed interrater and test–retest reliability, sensitivity to change, and correlations with constructs that are assumed to be similar to the FR tool (quality of life in daily living, work, and social contacts) or divergent from it (symptomatic functioning). Results: The FR tool was administered to 840 individuals with serious mental illnesses in Dutch mental health care services, 523 of whom were followed up for 1 year (response rate 62%). The tool was easy to complete and was appropriate for policy evaluation and practice. However, when it was combined with more elaborate instruments, it added little extra clinical information. Interrater and test–retest reliability, convergent and discriminant validity, and sensitivity to change were rated sufficient to good. Conclusions and Implications for Practice: The FR tool could be a useful measure of functional recovery in addition to current measures of symptomatic remission and personal recovery in routine outcome monitoring. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Although it is often assumed that valence processing in the prefrontal cortex (PFC) is similar for stimuli originating from different sensory modalities, evidence supporting this view is lacking. To address this, we recruited 20 male participants and used a delayed-response fMRI design to test whether perceived pleasantness of flavors and images is similarly processed in the PFC. As predicted, significant correlations were observed between image and flavor pleasantness ratings, and PFC response to these stimuli; however, these responses were spatially different, with flavor pleasantness reflected in more ventrally located PFC regions than image pleasantness. These results indicate that, contrary to the general assumption of a singular circuit representing pleasantness, distinct PFC circuits are recruited depending upon stimulus modality. We argue that the ventral-dorsal distinction may be attributed to a difference in proximal versus distal stimulus representations.

Background: Higher liability to psychosis is associated with low self-esteem and increased sensitivity to social stress. Recently, we reported a positive relation between liability to psychosis and affective and psychotic responses to social stress. This study investigated how self-esteem moderates paranoia, peak subjective distress and stress reactivity of people with different psychosis liability in response to social stressors in virtual reality.Methods: Ninety-four individuals with lower (41 siblings and 53 controls) and 75 persons with higher psychosis liability (55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis) explored five times a virtual cafe with various social stressors (crowdedness, ethnic minority status, and hostility). They rated momentary paranoia (State Social Paranoia Scale) after each experiment and subjective distress on a visual analogue scale before and after the experiments. Positive and negative self-esteem were assessed with the Self-Esteem Rating Scale.Results: Momentary paranoia, peak subjective distress, and reactivity to social stressors were associated with negative self-esteem, but not positive self-esteem. Effects of both positive and negative self-esteem on psychotic and affective stress responses, but not stress reactivity, became significantly stronger when individuals were exposed to more stressful environments. Effects of self-esteem on momentary paranoia and peak subjective distress did not differ between the high liability and low liability group. Persons with lower psychosis liability had a stronger effect of negative self-esteem on stress reactivity than persons with higher liability.Conclusions: Positive and negative self-esteem may play an important role in affective and psychotic responses to social stress. (C) 2018 Elsevier B.V. All rights reserved.

Previously we developed a mathematical model for describing the retinal nerve fiber bundle (RNFB) trajectories in the human retina. The model was based on Caucasian eyes that were not selected regarding refraction. The aim of this study was to determine the characteristics of the RNFB trajectories in Chinese myopic eyes. We collected high quality red free fundus images from 80 eyes of 80 Chinese myopic subjects (median [interquartile range/range] refraction - 3.9 [-6.0 to - 2.5/-10 to -1] D). We traced all visible RNFBs (n = 1460) and evaluated their trajectories using the previously published mathematical model. In the superior-temporal region, the RNFB trajectories of the Chinese myopic eyes were similar to that of the Caucasian eyes (86% of trajectories within the 95% central range of the Caucasian model). In the inferior-temporal region, the trajectories of the Chinese low to moderate myopic eyes were also similar to that of the Caucasian eyes (85%); trajectories of the high myopic eyes (spherical equivalent beyond -6.00 D) were clearly less curved (75%). Associations between individual deviations from the model and axial length, retinal vessel course, and optic disc anatomy were studied with multiple linear regression analysis. In the superior-temporal region, the trajectories were associated with retinal vessel course (P = 0.008) and optic disc size (P = 0.016). In the inferior-temporal region, there was a significant association with axial length (P

Suicidal behavior is highly prevalent in major depressive disorder (MDD), though not present in all patients. It is unclear whether the tendency for suicidal behavior is associated with a unique functional neuroanatomical signature identifiable through neuroimaging. In this study, we investigated brain activation in suicidal and non-suicidal patients with MDD during facial emotion processing and executive control. Functional magnetic resonance imaging (fMRI) data from the NESDA-fMRI study (MDD patients N = 103, healthy controls N = 26, HC) were analyzed. Patients were divided in a group of suicide attempters (N = 18, SA), suicide ideators (N = 31, SI) and a patient-control group (N = 73, PC). A gender discrimination task with emotional faces and the Tower of London executive planning task were investigated. An ANOVA was performed to compare brain activation among suicidal patients (SA + SI), PC and HC first and then among SI, SA, PC and HC. Significance was determined as meeting p

OBJECTIVE: This study aimed to assess the heterogeneity and stability of cognition in patients with a non-affective psychotic disorder and their unaffected siblings. In addition, we aimed to predict the cognitive subtypes of siblings by their probands. METHOD: Assessments were conducted at baseline, 3 and 6 years in 1119 patients, 1059 siblings and 586 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study. Group-based trajectory modeling was applied to identify trajectories and clustered multinomial logistic regression analysis was used for prediction modeling. A composite score of eight neurocognitive tests was used to measure cognitive performance. RESULTS: Five stable cognitive trajectories ranging from severely altered to high cognitive performance were identified in patients. Likewise, four stable trajectories ranging from moderately altered to high performance were found in siblings. Siblings had a higher risk of cognitive alteration when patients' alteration was mild (OR = 2.21), moderate (OR = 5.70), and severe (OR = 10.07) compared with patients with intact cognitive function. The familial correlation coefficient between pairs of index patients and their siblings was 0.27 (P = 0.003). CONCLUSIONS: The cognitive profiles identified in the current study might be suitable as endophenotypes and could be used in future genetic studies and predicting functional and clinical outcomes. ispartof: Acta Psychiatrica Scandinavica vol:138 issue:6 pages:591-604 ispartof: location:United States status: published

Large studies investigating the psychosocial effects of lifestyle interventions in patients with a severe mental illness (SMI) are scarce, especially in residential patients. This large, randomized controlled, multicentre pragmatic trial assessed the psychosocial effects of a combined diet-and-exercise lifestyle intervention targeting the obesogenic environment of SMI residential patients. Twenty-nine sheltered and clinical care teams were randomized into intervention (n = 15) or control (n = 14) arm. Team tailored diet-and-exercise lifestyle plans were set up to change the obesogenic environment into a healthier setting, and team members were trained in supporting patients to make healthier choices. The control group received care-as-usual. The Calgary Depression Scale for Schizophrenia (CDSS), Positive and Negative Syndrome Scale (PANSS), Health of the Nation Outcome Scales (HoNOS) and the Manchester Short Assessment of Quality of Life (MANSA) were assessed at baseline and after three and twelve months. Data were available for 384 intervention and 386 control patients (48.6 +/- 12.5 years old, 62.7% males, 73.7% psychotic disorder). Linear mixed model analysis showed no psychosocial improvements in the intervention group compared to care-as-usual; the intervention group showed a slightly reduced quality of life (overall) and a small increase in depressive symptoms (clinical care facilities) and psychotic symptoms (sheltered facilities). This may be due to difficulties with implementation, the intervention not being specifically designed for improvements in mental well-being, or the small change approach, which may take longer to reach an effect. Further research might elucidate what type of lifestyle intervention under what circumstances positively affects psychosocial outcomes in this population. (c) 2018 Elsevier B.V. All rights reserved.

BackgroundCortical glutamatergic dysfunction is thought to be fundamental for psychosis development, and may lead to structural degeneration through excitotoxicity. Glutamate levels have been related to gray matter volume (GMV) alterations in people at ultra-high risk of psychosis, and we previously reported GMV changes in individuals with high schizotypy (HS), which refers to the expression of schizophrenia-like characteristics in healthy people. This study sought to examine whether GMV changes in HS subjects are related to glutamate levels.MethodsWe selected 22 healthy subjects with HS and 23 healthy subjects with low schizotypy (LS) based on their rating on a self-report questionnaire for psychotic-like experiences. Glutamate levels were measured in the bilateral anterior cingulate cortex (ACC) using proton magnetic resonance spectroscopy, and GMV was assessed using voxel-based morphometry.ResultsSubjects with HS showed GMV decreases in the rolandic operculum/superior temporal gyrus (pFWE = 0.045). Significant increases in GMV were also detected in HS, in the precuneus (pFWE = 0.043), thereby replicating our previous finding in a separate cohort, as well as in the ACC (pFWE = 0.041). While the HS and LS groups did not differ in ACC glutamate levels, in HS subjects ACC glutamate was negatively correlated with ACC GMV (pFWE = 0.026). Such association was absent in LS.ConclusionsOur study shows that GMV findings in schizotypy are related to glutamate levels, supporting the hypothesis that glutamatergic function may lead to structural changes associated with the expression of psychotic-like experiences.

Background: Patients with psychotic disorders are at risk of developing mental health and social problems, and physical disorders. To monitor and treat these problems when indicated, an annual routine outcome monitoring program, Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS), was developed. This paper presents the background and content of PHAMOUS, implementation of PHAMOUS, characteristics of the patients screened in 2015, and the outcome of patients with three annual screenings between 2011 and 2015.Methods: PHAMOUS was implemented in four mental health institutions in the Northern Netherlands in 2006. During the PHAMOUS screening, patients are assessed on socio- demographics, psychiatric symptoms, medication, physical parameters, lifestyle, (psycho) social functioning and quality of life, using internationally validated instruments.Results: In 2015, 1955 patients with psychotic disorders were enrolled in the PHAMOUS screening. The majority (72%) was receiving mental healthcare for ten years or longer. A small group was hospitalized (10%) in the past year. Half of the patients were in symptomatic remission. Less than 10% had a paid job. More than half of the patients fulfilled the criteria for metabolic syndrome (54%). The subsamplewith three annual screenings from2011 to 2015 (N= 1230) was stable, except the increasing prevalence of high glucose levels and satisfaction with social relationships (Cochran's Q= 16.33, p=. 001 resp. Q= 14.79, p =.001).Conclusion: The annual PHAMOUS screening enables to follow themental, physical and social health problems of patients, which offers a good basis for shared- decision making with regard to updating the annual treatment plan, next to a wealth of data for scientific research. (C) 2018 Elsevier B. V. All rights reserved.

PURPOSE. To determine whether the De Vries-Rose, Weber's, and Ferry-Porter's law, which describe visual performance as a function of luminance, also hold in patients with glaucoma.METHODS. A case-control study with 19 glaucoma patients and 45 controls, all with normal visual acuity. We measured foveal and peripheral contrast sensitivity (CS) using static perimetry and foveal and peripheral critical fusion frequency (CFF; stimulus diameter 1 degrees) as a function of luminance (0.02 to 200 cd/m(2)). ANOVA was used to analyze the effect of glaucoma and luminance on CS and CFF; analyses were adjusted for age and sex.RESULTS. Foveally, logCS was proportional to log luminance at lower luminances (de Vries-Rose) and saturated at higher luminances (Weber); glaucoma patients had a 0.4 log unit lower logCS than controls (P CONCLUSIONS. Even in apparently intact areas of the visual field, visual performance is worse in glaucoma patients than in healthy subjects for a wide range of luminances, without a clear luminance dependency that is consistent across the various experiments. This indicates impaired signal processing downstream in the retina and beyond, rather than an impaired light adaptation in the strictest sense.

Introduction: Cognitive biases are associated with psychosis liability and paranoid ideation. This study investigated the moderating relationship between pre-existing self-reported cognitive biases and the occurrence of paranoid ideation in response to different levels of social stress in a virtual reality environment.Methods: This study included 170 participants with different levels of psychosis liability (55 recent onset psychosis, 20 ultrahigh risk for psychosis, 42 siblings of psychotic patients, and 53 controls). All participants were exposed to virtual environments with different levels of social stress. The level of experienced paranoia in the virtual environments was measured with the State Social Paranoia Scale. Cognitive biases were assessed with a self-report continuous measure. Also, cumulative number of cognitive biases was calculated using dichotomous measures of the separate biases, based on general population norm scores.Results: Higher belief inflexibility bias (Z = 2.83, P < .001), attention to threat bias (Z = 3.40, P < .001), external attribution bias (Z = 2.60, P < .001), and data-gathering bias (Z = 2.07, P < .05) were all positively associated with reported paranoid ideation in the social virtual environments. Level of paranoid response increased with number of cognitive biases present (B = 1.73, P < .001). The effect of environmental stressors on paranoid ideation was moderated by attention to threat bias (Z = 2.78, P < .01) and external attribution bias (Z = 2.75, P < .01), whereas data-gathering bias and belief inflexibility did not moderate the relationship.Conclusion: There is an additive effect of separate cognitive biases on paranoid response to social stress. The effect of social environmental stressors on paranoid ideation is further enhanced by attention to threat bias and external attribution bias.

Does the real or imagined presence of friends invariantly drive consumers to engage in disinhibited behavior, and give in to the "urge to splurge" in the face of consumption temptations? Or might there be situations in which being with friends or even merely thinking of friends or the friendships we have with them can actually improve self-control?In five studies, using a unique combination of controlled experiments examining overt consumer behavior and functional magnetic resonance imaging (fMRI), we propose and show that the extent to which consumers identify a goal conflict between giving in to buying temptations on the one hand and the perceived consequences for maintaining satisfactory relationships with close friends on the other is a critical mediator of whether friendship reminders decrease or increase self-control. We further show that such a goal conflict is most likely for consumers with a chronic, compulsive tendency for uncontrolled, disinhibited acquisition and consumption-for consumers classified as compulsive buyers. For their non-compulsive counterparts, in contrast, acts of acquisition and consumption, even incidental disinhibited ones, are perceived to be less problematic in light of their friendships and hence do not induce a goal conflict to the same extent. Our findings provide insights into social influences on self-control and identify the concept of friendship reminders as a way to reduce a common type of dysfunctional consumer behavior. In addition to enhancing consumer well-being, reducing compulsive buying will substantially reduce handling costs for organizations. Hence, the findings are of academic, societal and managerial relevance. (C) 2017 Elsevier B.V. All rights reserved.

The vocal tract length (VTL) of a speaker is an important voice cue that aids speech intelligibility in multi-talker situations. However, cochlear implant (CI) users demonstrate poor VTL sensitivity. This may be partially caused by the mismatch between frequencies received by the implant and those corresponding to places of stimulation along the cochlea. This mismatch can distort formant spacing, where VTL cues are encoded. In this study, the effects of frequency mismatch and band partitioning on VTL sensitivity were investigated in normal hearing listeners with vocoder simula- tions of CI processing. The hypotheses were that VTL sensitivity may be reduced by increased fre- quency mismatch and insufficient spectral resolution in how the frequency range is partitioned, specifically where formants lie. Moreover, optimal band partitioning might mitigate the detrimen- tal effects of frequency mismatch on VTL sensitivity. Results showed that VTL sensitivity decreased with increased frequency mismatch and reduced spectral resolution near the low fre- quencies of the band partitioning map. Band partitioning was independent of mismatch, indicating that if a given partitioning is suboptimal, a better partitioning might improve VTL sensitivity despite the degree of mismatch. These findings suggest that customizing the frequency partitioning map may enhance VTL perception in individual CI users.

People with psychotic disorders have an increased metabolic riskand their mean life expectancy is reduced with circa 28 years (Olfsonet al., 2015).Predictors of this increased metabolic risk are genetic predisposition (Liu et al., 2013), lifestyle factors such as unhealthy diet,physical inactivity and smoking (Bobes et al., 2010), and the side effectsof antipsychotic medication (Werner and Coveñas, 2014;Chadda et al.,2013). Low vitamin D status might also contribute to an increased metabolicrisk (Ginde et al., 2009;Kendrick et al., 2009;Kilkkinen et al.,2009;Ford et al., 2009) and all-cause mortality by promoting atherosclerosis,hypertension, inflammation and activation of the renin-angiotensinsystem (Wang et al., 2012;Garland et al., 2014;Lee et al., 2008). Also,one review demonstrated cardiovascular mortality rates in the generalpopulation were higher during winter than in summer (Zittermann etal., 2005).Vitamin D interacts with dopaminergic, cholinergic and noradrenergicneurotransmitter systems, which have all been implicated inSchizophrenia Research 195 (2018) 513–518⁎ Corresponding author at: University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research center, P.O. Box 30.001 (CC72), 9700 RB Groningen, The Netherlands.E-mail addresses: j.bruins@lentis.nl (J. Bruins), f.jorg@umcg.nl (F. Jörg),e.r.v.d.heuvel@tue.nl (E.R. van den Heuvel), a.a.bartels@umcg.nl (A.A. Bartels-Velthuis),e.corpeleijn@umcg.nl (E. Corpeleijn), f.a.j.muskiet@umcg.nl (F.A.J. Muskiet),g.h.m.pijnenborg@rug.nl (G.H.M. Pijnenborg), r.bruggeman@umcg.nl (R. Bruggeman).experiencing psychotic symptoms (Eyles et al., 2013). When vitaminD is low, dopamine signalling in the brain appears to decrease (Eyleset al., 2013;Cui et al., 2015;Cui et al., 2013;Groves et al., 2014), whichin its turn could lead to more severe negative symptoms of psychosis(Buchanan et al., 2007). Indeed, several studies found that vitamin D insufficiencywas strongly associated with negative symptoms of psychosis(Graham et al., 2015;Yüksel et al., 2014;Cieslak et al., 2014;OttesenBerg et al., 2010).Vitamin D is thus associated with both metabolic risk and negativesymptom severity. Negative symptoms have also been shown to interferewith patients' ability to be physically active and make healthy lifestylechoices, which can increase their metabolic risk (Bergqvist et al.,2013). Negative symptom severity may therefore mediate the associationbetween low vitamin D and increased metabolic risk in peoplewith a psychotic disorder.Vitamin D is mostly produced in the skin by exposure to ultravioletBradiation in sunlight (Brown et al., 1999;Holick, 2007). Absorption ofvitamin D and levels of circulation differ among individuals and can beinfluenced by determinants such as latitude, season, time of day, skincolor (Holick et al., 2011), bodyweight, age, calcium intake(Zittermann et al., 2014), diet and genetics (Mazahery and von Hurst,2015).Vitamin D shows a natural fluctuation throughout the year, with vitaminD insufficiency more likely to occur during winter than in summer(Rosecrans and Dohnal, 2014). A recent study suggestsseasonality may also affect clinical symptoms of schizophrenia, althoughthe underlying mechanism is unknown (Byrne et al., 2015).In this study we aim to investigate whether vitamin D levels are associatedwith metabolic risk in people with psychotic disorders andwhether this effect was mediated by negative symptoms. We hypothesizethat vitamin D levels may influence the severity of metabolic disturbancesand negative symptoms. As vitamin D levels naturally fluctuatethroughout the seasons (Rosecrans and Dohnal, 2014), we examinewhether metabolic risk and negative symptom severity follow a similarseasonal fluctuation pattern. Furthermore, we investigate whether thehttp://dx.doi.org/10.1016/j.schres.2017.08.0590920-9964/© 2017 Elsevier B.V. All rights reserved.Contents lists available at ScienceDirectSchizophrenia Researchjournal homepage: www.elsevier.com/locate/schresseverity of metabolic risk and negative symptoms differ between patientsusing and patients not using vitamin D supplementation. In thiscross-sectional study, seasonal patterns and differences with regard tosupplementation may indicate an interdependent and potentially causalconnection between vitamin D, metabolic risk and negative symptomseverity

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened\ud risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified\ud 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and\ud implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved\ud in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression\ud with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were\ud putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry\ud lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression\ud and imply that a continuous measure of risk underlies the clinical phenotype.

Item does not contain fulltext OBJECTIVE: To answer the dilemma clinician's face when deciding between cochlear implant (CI) and auditory brainstem implant (ABI) treatment options in patients with cochlear nerve deficiency (CND). STUDY DESIGN: Case study supplemented with literature review and meta-analysis. SETTING: Tertiary referral center. PATIENT(S): Child with CHARGE syndrome and congenital deafness. INTERVENTION(S): ABI as there was no benefit after bilateral cochlear implantation. MAIN OUTCOME MEASURES: Speech and language development, quality of life. RESULTS: In one ear the cochleovestibular nerve was present on magnetic resonance imaging (MRI) without preoperative ABR responses. In the contra lateral ear the nerve could not be identified, despite present ABR responses. Nevertheless, there was no positive outcome with CI. The patient had improved speech and language and quality of life with ABI. Of the 108 patients with CND and CI identified in the literature review, 25% attained open-set speech perception, 34% attained closed-set speech perception, and 41% detected sounds or less. The appearance of the cochlear nerve on MRI was a useful predictor of success, with cochlear nerve aplasia on MRI associated with a smaller chance of a positive outcome post cochlear implantation compared with patients with cochlear nerve hypoplasia. CONCLUSION: Although patients with (apparent) cochlear nerve aplasia are less likely to benefit from CI, CI before ABI is supported as some patients attain closed or open-set levels of speech perception after cochlear implantation.

In discriminating speakers' voices, normal-hearing individuals effectively use two vocal characteristics, vocal pitch (related to fundamental frequency, F0) and vocal-tract length (VTL, related to speaker size). Typical cochlear-implant users show poor perception of these cues. However, in implant users with low-frequency residual acoustic hearing, this bimodal electro-acoustic stimulation may provide additional voice-related cues, such as low-numbered harmonics and formants, which could improve F0/VTL perception. In acoustic noise-vocoder simulations, where added low-pass filtered speech simulated residual hearing, a strong bimodal benefit was observed for F0 perception. No bimodal benefit was observed for VTL, which seems to mainly rely on vocoder spectral resolution.

AIM: The primary aim was to examine differences in baseline symptom expression, neurocognition, social cognition and psychosocial functioning between Dutch, first-generation immigrants and second-generation immigrants with a first-episode psychosis (FEP). The secondary aim was to examine functional and symptomatic change and between-group differences at 12-months follow-up. Associations between migration, baseline characteristics and outcome were explored.METHODS: Forty-six Dutch, 56 second-generation- and 60 first-generation immigrant patients completed baseline measures for 6 symptom dimensions (positive symptoms, negative symptoms, neurocognitive functioning, social cognitive functioning, excitement and emotional distress) and 5 domains of psychosocial functioning (general functioning, work and study, relationships, self-care and disturbing behaviour). Functioning and psychotic symptoms were assessed at baseline and 12-months follow-up. ANCOVA and t tests were used to assess between-group differences. General linear models were used to explore within-group differences. Backward-regression was used to explore predictors of outcome.RESULTS: Levels of positive symptoms, excitement and emotional distress did not differ between groups at baseline or follow-up. Dutch patients had lower levels of negative symptoms than both immigrant groups at follow-up. On neurocognition and social cognition, Dutch performed better than second-generation immigrants, who in turn performed better than first-generation immigrants. Psychosocial functioning across all domains at baseline and at 12-months follow-up was similar across groups. Baseline levels of general psychosocial functioning and income were the strongest predictors of outcome at follow-up.CONCLUSIONS: Psychosocial functioning and symptom profiles are comparable between Dutch, first-generation immigrant and second-generation immigrant FEP patients, excluding neurocognitive and social cognitive deficits. A range of baseline characteristics predicted outcome.