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Impairments in social cognition contribute significantly to disability in schizophrenia patients (SzP). Perception of facial expressions is critical for social cognition. Intact perception requires an individual to visually scan a complex dynamic social scene for transiently moving facial expressions that may be relevant for understanding the scene. The relationship of visual scanning for these facial expressions and social cognition remains unknown.
In 39 SzP and 27 healthy controls (HC), we used eye-tracking to examine the relationship between performance on The Awareness of Social Inference Test (TASIT), which tests social cognition using naturalistic video clips of social situations, and visual scanning, measuring each individual's relative to the mean of HC. We then examined the relationship of visual scanning to the specific visual features (motion, contrast, luminance, faces) within the video clips.
TASIT performance was significantly impaired in SzP for trials involving sarcasm (p < 10−5). Visual scanning was significantly more variable in SzP than HC (p < 10−6), and predicted TASIT performance in HC (p = 0.02) but not SzP (p = 0.91), differing significantly between groups (p = 0.04). During the visual scanning, SzP were less likely to be viewing faces (p = 0.0001) and less likely to saccade to facial motion in peripheral vision (p = 0.008).
SzP show highly significant deficits in the use of visual scanning of naturalistic social scenes to inform social cognition. Alterations in visual scanning patterns may originate from impaired processing of facial motion within peripheral vision. Overall, these results highlight the utility of naturalistic stimuli in the study of social cognition deficits in schizophrenia.
The rate of manifestation of depressive episodes can vary appreciably. The complete development of a depressive episode may be very rapid, taking less than one hour or be very slow, taking up to one month. Altough this clinical observation suggests different neurobiological pathomechanisms, the onset speed of depressive episodes in different affective disorders has not been investigated systematically up to now. The objective of this study was to establish the onset speed of depressive episodes in patients with a history of at least one depressive episode and to compare the onset speed in unipolar with that in bipolar affective disorders.
A group of 96 inpatients was investigated consecutively using the structured patient interview “Onset of Depression Inventory” (ODI). In 76 patients, there was a unipolar depressive disorder and 20 patients suffered from a bipolar depressive disorder.
The onset speed of the current depressive episode in patients with effective disorders correlated significantly with the onset speed of the previous depressive episodes (p < 0.001). Furthermore, there was a significant difference in the onset of the depressive episodes between unipolar and bipolar affective disorders (p < 0.001). In 55% of patients with a bipolar disorder, the depressive episode was manifested within one week whereas this was the case in only 22,37% of the patients with a unipolar affective disorder.
The rate of manifestation of depressive episodes differs between unipolar and bipolar disorders. The clinical observation reported here can support the diagnostic appraisal of depressive episodes.
The increasing evidence that bipolar and unipolar affective disorders have different biological etiologies and courses of illness has been associated with an intensifying interest in specific treatment regimens for both disorders during the last decade. In this context, the question arose whether antidepressants exert similar efficacy in the acute treatment of bipolar compared to unipolar depression. Although the clinical impression does not indicate substantial differences in the efficacy of antidepressants between these groups of patients, empirical databases concerning this topic are rare. The present study compared the efficacy of antidepressants in 50 unipolar and 50 bipolar depressed inpatients (ICD-9 criteria) under naturalistic treatment conditions. Both groups of patients were mahed for age, gender and duration of illness. Clinical assessments of status at the time of admission and at discharge were used to rate response to antidepressant treatment. Analyses of the data revealed that both groups of patients needed the same time for treatment response and did not show any significant differences in ouome measures at discharge. These findings do not concur with the hypothesis formulated by some experts in the field of affective disorders that antidepressants are less effective in the acute treatment of bipolar depressed patients compared to unipolar depressed patients.
In the context of the development of DSM-V and ICD-11 it appears to be useful to get further data on the validity of the diagnostic differentiation between schizophrenic and affective disorders. This study investigated the relevance of the main diagnostic groups schizophrenia, schizoaffective psychosis and affective disorder in the context of different diagnostic systems (ICD-9, ICD-10, DSM –IV), assessing their time stability, long-term courses, types and functional outcome.
A total of 323 first hospitalized inpatients of the Psychiatric Department of the University Munich were recruited at index time. The full follow-up evaluation including standardized assessment procedures could be performed in 197 patients.
The re-diagnosis of the patients’ disorders shows that with the transition from ICD-9 to ICD-10 or DSM-IV, the group of affective disorders increased numerically while the diagnostic groups of schizophrenia and schizoaffective disorders decreased in size. The structured clinical interview for DSM-IV (SCID) analysis showed that altogether ICD-10 and DSM-IV had a relatively high diagnostic stability. Of the patients with an ICD-10 diagnosis of schizophrenia, 57% had a chronic course; 61% of the patients with a DSM-IV diagnosis of schizophrenia. Patients with affective disorders, according either to ICD-10 or DSM-IV, had in more than 90% of the cases an episodic-remitting course. In terms of prediction of long-term outcome regarding the differentiation between chronic and non-chronic course, the ICD-10 diagnoses did give a slightly better predictive result than a dimensional approach based on the key psychopathological syndrome scores.
The differentiation between schizophrenic and affective disorders seems meaningful especially under predictive aspects. A dimensional syndromatological description does not exceed the predictive power of the investigated main diagnostic categories, but might increase the clinically relevant information.
To detect eating disorders and risky eating behaviour in early stages, screening tests are used. In order to examine as many adolescents as possible, these tests should be economic, i. e. as short as possible but at the same time they should fulfil the psychometric quality criteria. We compared the German version of the Eating Attitudes Test (EAT-26D) and the German version of the SCOFF test (which contains only five Yes-no questions) in a sample of 425 twelve year old girls and 382 boys from Thuringia, Germany. Although the EAT-26D reached higher psychometric properties, the SCOFF has been proved as a useful screening tool with a test-retest reliability of rtt = .73 and a maximum accuracy of 82% (area under the ROC curve). In reference to the EAT-26D (20 point cut-off) the sensitivity of the SCOFF was 78%, specificity 75%, positive predictive value 28%, and the negative predictive value, which is more relevant for screenings, was 96%. The construct validity reached r = .52.
The speed of onset of depressive episodes is a clinical aspect of affective disorders that has not been sufficiently investigated. Thus, we aimed to explore whether patients with fast onset of the full-blown depressive symptomatology (≤ 7 days) differ from those with slow onset (> 7 days) with regard to demographic and clinical aspects.
Subjects and methods:
Data were obtained within an observational study conducted in outpatients with major depression who were treated with duloxetine (30–120 mg/day). Onset of depression (without any preceding critical life event) was fast in 416 (less than one week) and slower in 2220 patients.
Compared to patients with slow onset, those with fast onset of depression had more suicide attempts in the previous 12 months (2.7% versus 1.3%, P = 0.046) and less somatic comorbidity (61.7% versus 74.1%, P < 0.0001). In addition, they were slightly younger at onset of depression (mean ± SD 40.2 ± 14.6 versus 42.8 ± 14.2 years, P < 0.001) and used analgesics at baseline significantly less frequently (22.8% versus 33.4%, P < 0.0001).
Discussion and conclusion:
The speed of onset of depression has to be regarded as a relevant clinical characteristic in patients with unipolar depression.
Schizophrenia (SZ) is typically preceded by a prodromal (i.e. pre-illness) period characterized by attenuated positive symptoms and declining functional outcome. Negative symptoms are prominent among individuals at clinical high-risk (CHR) for psychosis (i.e. those with prodromal syndromes) and highly predictive of conversion to illness. Mechanisms underlying negative symptoms in the CHR population are unclear. Two studies were conducted to evaluate whether abnormalities in a reward processing mechanism thought to be core to negative symptoms in SZ, value representation, also exist in CHR individuals and whether they are associated with negative symptoms transphasically.
Study 1 included 33 individuals in the chronic phase of illness who have been diagnosed with schizophrenia or schizoaffective disorder (SZ) and 40 healthy controls (CN). Study 2 included 37 CHR participants and 45 CN. In both studies, participants completed the delay discounting (DD) task as a measure of value representation and the Brief Negative Symptom Scale was rated to measure negative symptoms.
Results indicated that patients with SZ had steeper discounting rates than CN, indicating impairments in value representation. However, CHR participants were unimpaired on the DD task. In both studies, steeper discounting was associated with greater severity of negative symptoms.
These findings suggest that deficits in value representation are associated with negative symptoms transphasically.
Access to cognitive behaviour therapy for those with psychosis (CBTp) remains poor. The most frequently endorsed barrier to implementation is a lack of resources. To improve access to CBTp, we developed a brief form of CBTp that specifically targets voice-related distress. The results of our pilot trial of guided self-help CBT for voices (GiVE) suggest that the therapy is both acceptable and beneficial. The present study aims to explore the subjective patient experience of accessing GiVE in the context of a trial. We interviewed nine trial participants using the Change Interview and a mixed methods approach. Most participants reported at least one positive change that they attributed to GiVE. We extracted five themes: (1) changes that I have noticed; (2) I am not alone; (3) positive therapy experiences; (4) I want more therapy; and (5) helping myself. The themes indicate that participating in the GiVE trial was generally a positive experience. The main areas in which participants experienced changes were improved self-esteem, and the ability to cope with voices. Positive changes were facilitated by embracing and enacting ‘self-help’ and having support both in and out of the therapy sessions. The findings support the use of self-help materials with those distressed by hearing voices, but that support both within and outside the clinical setting can aid engagement and outcomes. Overall, the findings support the continued investigation of GiVE.
Key learning aims
(1) To explore participants’ experience of accessing GiVE as part of a trial.
(2) To identify what (if any) changes participants noticed over the course of the GiVE trial.
(3) To identify what participants attribute these changes to.
Abnormal effort-based decision-making represents a potential mechanism underlying motivational deficits (amotivation) in psychotic disorders. Previous research identified effort allocation impairment in chronic schizophrenia and focused mostly on physical effort modality. No study has investigated cognitive effort allocation in first-episode psychosis (FEP).
Cognitive effort allocation was examined in 40 FEP patients and 44 demographically-matched healthy controls, using Cognitive Effort-Discounting (COGED) paradigm which quantified participants’ willingness to expend cognitive effort in terms of explicit, continuous discounting of monetary rewards based on parametrically-varied cognitive demands (levels N of N-back task). Relationship between reward-discounting and amotivation was investigated. Group differences in reward-magnitude and effort-cost sensitivity, and differential associations of these sensitivity indices with amotivation were explored.
Patients displayed significantly greater reward-discounting than controls. In particular, such discounting was most pronounced in patients with high levels of amotivation even when N-back performance and reward base amount were taken into consideration. Moreover, patients exhibited reduced reward-benefit sensitivity and effort-cost sensitivity relative to controls, and that decreased sensitivity to reward-benefit but not effort-cost was correlated with diminished motivation. Reward-discounting and sensitivity indices were generally unrelated to other symptom dimensions, antipsychotic dose and cognitive deficits.
This study provides the first evidence of cognitive effort-based decision-making impairment in FEP, and indicates that decreased effort expenditure is associated with amotivation. Our findings further suggest that abnormal effort allocation and amotivation might primarily be related to blunted reward valuation. Prospective research is required to clarify the utility of effort-based measures in predicting amotivation and functional outcome in FEP.
Disturbances in trait emotions are a predominant feature in schizophrenia. However, less is known about (a) differences in trait emotion across phases of the illness such as the clinical high-risk (CHR) phase and (b) whether abnormalities in trait emotion that are associated with negative symptoms are driven by primary (i.e. idiopathic) or secondary (e.g. depression, anxiety) factors.
To examine profiles of trait affective disturbance and their clinical correlates in individuals with schizophrenia and individuals at CHR for psychosis.
In two studies (sample 1: 56 out-patients diagnosed with schizophrenia and 34 demographically matched individuals without schizophrenia (controls); sample 2: 50 individuals at CHR and 56 individuals not at CHR (controls)), participants completed self-report trait positive affect and negative affect questionnaires, clinical symptom interviews (positive, negative, disorganised, depression, anxiety) and community-based functional outcome measures.
Both clinical groups reported lower levels of positive affect (specific to joy among individuals with schizophrenia) and higher levels of negative affect compared with controls. For individuals with schizophrenia, links were found between positive affect and negative symptoms (which remained after controlling for secondary factors) and between negative affect and positive symptoms. For individuals at CHR, links were found between both affect dimensions and both types of symptom (which were largely accounted for by secondary factors).
Both clinical groups showed some evidence of reduced trait positive affect and elevated trait negative affect, suggesting that increasing trait positive affect and reducing trait negative affect is an important treatment goal across both populations. Clinical correlates of these emotional abnormalities were more integrally linked to clinical symptoms in individuals with schizophrenia and more closely linked to secondary influences such as depression and anxiety in individuals at CHR.
To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS.
We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents’ functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents’ cognitive status independently.
The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status.
A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.
Background: SMA is a neurodegenerative disease caused by biallelic deletion/mutation of SMN1. Copies of a similar gene (SMN2) modify disease severity. In a phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA patients with two SMN2 copies (2xSMN2) dosed ≤6 months. Because motor neuron loss can be insidious and disease progression is rapid, early intervention is critical. This study evaluates AVXS-101 in presymptomatic SMA newborns. Methods: SPR1NT is a multicenter, open-label, phase 3 study enrolling ≥27 SMA patients with 2–3xSMN2. Asymptomatic infants ≤6 weeks receive a one-time intravenous AVXS-101 infusion (1.1x1014 vg/kg). Safety and efficacy are assessed through study end (18 [2xSMN2] or 24 months [3xSMN2]). Primary outcomes: independent sitting for ≥30 seconds (18 months [2xSMN2]) or assisted standing (24 months [3xSMN2]). Results: From April–September 2018, 7 infants received AVXS-101 (4 female; 6 with 2xSMN2) at ages 8–37 days. Mean baseline CHOP-INTEND score was 41.7 (n=6), which increased by 6.8, 11.0, 18.0, and 22.5 points at day 14 (n=4), month 1 (n=3), 2 (n=3), and 3 (n=2). Updated data available at the time of the congress will be presented. Conclusions: Preliminary data from SPR1NT show rapid motor function improvements in presymptomatic SMA patients.
Adverse childhood experiences (ACE) exhibit long-lasting consequences on later life and are considered as a major public health problem. ACEs can be divided into household dysfunctions, which affect the child indirectly, and direct maltreatment. As a high correlation between ACEs in general is known, we assessed the risk for child maltreatment associated with the occurrence of household dysfunctions. To provide a better understanding for the mechanisms leading to the deleterious sequelae of ACEs, we furthermore assessed whether the long-term consequences of household dysfunction are mediated by child maltreatment and thereby might be targeted by effective child protection programs.
A representative sample of the German population above the age of 14 (N = 2531) was assessed in a cross-sectional observational population-based survey.
The data reveal that mental illness of a household member was associated with significantly increased risks for all child maltreatment subtypes (ORs 4.95–5.55), just as household substance abuse (ORs 5.32–6.98), violence against the mother (ORs 4.43–10.26), incarceration of a household member (ORs 6.11–14.93) and parental separation (OR 3.37–4.87). Child maltreatment partially mediated the association of household mental illness, substance abuse and parental separation with later depression, anxiety, life satisfaction and subjective general health status and completely mediated the associations of intimate partner violence (IPV) and incarceration of a household member with anxiety, depression and subjective health status in adulthood.
ACEs linked to household dysfunction are associated with an increased risk for all subtypes of child maltreatment. The assessed widespread consequences of household dysfunction are mediated by child maltreatment. This underlines the role of prevention of child maltreatment in families with household dysfunction and implies child protection as a priority in any interventions.
To extend evidence on the short-term variability of passive and active suicidal ideation (SI) and the association with suggested proximal risk factors such as interpersonal variables (perceived burdensomeness [PB], thwarted belongingness [TB], hopelessness, and depression) in real-time.
This is an observational study using a prospective design applying ecological momentary assessments (EMA). Eligible for study inclusion were inpatients with unipolar depression, current or lifetime suicidal ideation, and fluent German. Over six days, 74 participants rated their momentary level of passive and active SI, PB, TB, depressiveness, and hopelessness up to 10 times per day on smartphones. Data was collected from August 2015 to July 2017. Compliance was excellent (89.7%).
Mean squared successive differences supported temporal instability for all variables. According intra-class correlations, between 25% and 47% of variance was accounted for by within-person variability. Multilevel analysis demonstrated significant positive associations between hopelessness, depressiveness, PB, and TB with passive SI. Prospectively, hopelessness and PB remained predictors of passive SI. For active SI, hopelessness, depression, PB, and TB were significantly associated cross-sectionally. Prospectively, hopelessness, PB, and the interaction PBxTB predicted active SI. All models were controlled for previous level of SI.
This study provides further evidence on the short-term variability of SI in very short time frames implying the need of assessing SI repeatedly in clinical and research settings. The associations between interpersonal variables and passive and active SI were only partial in line with assumptions of the Interpersonal Theory of Suicide. Overall, the effects were small warranting further investigation.
This paper aims to situate the Late Formative urban center of Izapa, Chiapas, Mexico into the greater discussion of early Mesoamerican writing systems. The elites of Izapa produced elaborate carved stone monuments in an era that bore witness to the fluorescence of three great hieroglyphic programs—the Zapotec, the Epi-Olmec, and the Maya—and, yet, only a handful of glyphs appear in Izapa's monumental corpus. In a discussion that includes Izapan iconoglyphs, possible nominal phrases, and the calendrical inscriptions on Izapa Stela 27, Stela 9, and Miscellaneous Monument 60, this study juxtaposes Izapan visual culture with representational systems to the east and west, and ultimately explores the narrative domains of greatest salience to Izapa's elite: image and cyclical time.
Individuals with schizophrenia have deficits in social cognition that are associated with poor functional outcome. Unfortunately, current treatments result in only modest improvement in social cognition. Oxytocin, a neuropeptide with pro-social effects, has significant benefits for social cognition in the general population. However, studies examining the efficacy of oxytocin in schizophrenia have yielded inconsistent results. One reason for inconsistency may be that oxytocin has typically not been combined with psychosocial interventions. It may be necessary for individuals with schizophrenia to receive concurrent psychosocial treatment while taking oxytocin to have the context needed to make gains in social cognitive skills.
The current study tested this hypothesis in a 24-week (48 session) double-blind, placebo-controlled trial that combined oxytocin and Cognitive-Behavioral Social Skills Training (CBSST), which included elements from Social Cognition and Interaction Training (SCIT). Participants included 62 outpatients diagnosed with schizophrenia (placebo n = 31; oxytocin n = 31) who received 36 IU BID, with supervised administration 45 min prior to sessions on CBSST group therapy days. Participants completed a battery of measures administered at 0, 12, and 24 weeks that assessed social cognition.
CBSST generally failed to enhance social cognition from baseline to end of study, and there was no additive benefit of oxytocin beyond the effects of CBSST alone.
Findings suggest that combined CBSST and oxytocin had minimal benefit for social cognition, adding to the growing literature indicating null effects of oxytocin in multi-dose trials. Methodological and biological factors may contribute to inconsistent results across studies.
Cryo-electron microscopy (cryo-EM) is a powerful tool for macromolecular to near-atomic resolution structure determination in the biological sciences. The specimen is maintained in a near-native environment within a thin film of vitreous ice and imaged in a transmission electron microscope. The images can then be processed by a number of computational methods to produce three-dimensional information. Recent advances in sample preparation, imaging, and data processing have led to tremendous growth in the field of cryo-EM by providing higher resolution structures and the ability to investigate macromolecules within the context of the cell. Here, we review developments in sample preparation methods and substrates, detectors, phase plates, and cryo-correlative light and electron microscopy that have contributed to this expansion. We also have included specific biological applications.