Keep at bay! - Abnormal personal space regulation as marker of paranoia in schizophrenia.

BACKGROUND During threat, interpersonal distance is deliberately increased. Personal space regulation is related to amygdala function and altered in schizophrenia, but it remains unknown whether it is particularly associated with paranoid threat. METHODS We compared performance in two tests on personal space between 64 patients with schizophrenia spectrum disorders and 24 matched controls. Patients were stratified in those with paranoid threat, neutral affect or paranoid experience of power. In the stop-distance paradigm, participants indicated the minimum tolerable interpersonal distance. In the fixed-distance paradigm, they indicated the level of comfort at fixed interpersonal distances. RESULTS Paranoid threat increased interpersonal distance two-fold in the stop-distance paradigm, and reduced comfort ratings in the fixed-distance paradigm. In contrast, patients experiencing paranoid power had high comfort ratings at any distance. Patients with neutral affect did not differ from controls in the stop-distance paradigm. Differences between groups remained when controlling for gender and positive symptom severity. Among schizophrenia patients, the stop-distance paradigm detected paranoid threat with 93% sensitivity and 83% specificity. CONCLUSIONS Personal space regulation is not generally altered in schizophrenia. However, state paranoid experience has distinct contributions to personal space regulation. Subjects experiencing current paranoid threat share increased safety-seeking behavior.

Nonverbal synchrony in social interactions of patients with schizophrenia indicates socio-communicative deficits

Background Disordered interpersonal communication can be a serious problem in schizophrenia. Recent advances in computer-based measures allow reliable and objective quantification of nonverbal behavior. Research using these novel measures has shown that objective amounts of body and head movement in patients with schizophrenia during social interactions are closely related to the symptom profiles of these patients. In addition to and above mere amounts of movement, the degree of synchrony, or imitation, between patients and normal interactants may be indicative of core deficits underlying various problems in domains related to interpersonal communication, such as symptoms, social competence, and social functioning. Methods Nonverbal synchrony was assessed objectively using Motion Energy Analysis (MEA) in 378 brief, videotaped role-play scenes involving 27 stabilized outpatients diagnosed with paranoid-type schizophrenia. Results Low nonverbal synchrony was indicative of symptoms, low social competence, impaired social functioning, and low self-evaluation of competence. These relationships remained largely significant when correcting for the amounts of patients‘ movement. When patients showed reduced imitation of their interactants’ movements, negative symptoms were likely to be prominent. Conversely, positive symptoms were more prominent in patients when their interaction partners’ imitation of their movements was reduced. Conclusions Nonverbal synchrony can be an objective and sensitive indicator of the severity of patients’ problems. Furthermore, quantitative analysis of nonverbal synchrony may provide novel insights into specific relationships between symptoms, cognition, and core communicative problems in schizophrenia.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

15 Years of Microstate Research in Schizophrenia - Where Are We? A Meta-Analysis

Schizophrenia patients show abnormalities in a broad range of task demands. Therefore, an explanation common to all these abnormalities has to be sought independently of any particular task, ideally in the brain dynamics before a task takes place or during resting state. For the neurobiological investigation of such baseline states, EEG microstate analysis is particularly well suited, because it identifies subsecond global states of stable connectivity patterns directly related to the recruitment of different types of information processing modes (e.g., integration of top-down and bottom-up information). Meanwhile, there is an accumulation of evidence that particular microstate networks are selectively affected in schizophrenia. To obtain an overall estimate of the effect size of these microstate abnormalities, we present a systematic meta-analysis over all studies available to date relating EEG microstates to schizophrenia. Results showed medium size effects for two classes of microstates, namely, a class labeled C that was found to be more frequent in schizophrenia and a class labeled D that was found to be shortened. These abnormalities may correspond to core symptoms of schizophrenia, e.g., insufficient reality testing and self-monitoring as during auditory verbal hallucinations. As interventional studies have shown that these microstate features may be systematically affected using antipsychotic drugs or neurofeedback interventions, these findings may help introducing novel diagnostic and treatment options.

Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia

Patients with schizophrenia show abnormal dynamics and structure of temporally ­coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs – default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) – and three EEG bands – theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback ­targeting prestates could be beneficial as task performance relies on the preparatory state of the brain.

Internet-based self-help for schizophrenia – risks and chances

Purpose: Schizophrenia is a severe mental disorder which is accompanied by an enormous individual and societal burden. Despite established efficacy of cognitive behavioral therapy (CBT) for schizophrenia, its dissemination into routine mental health care remains poor. Internet-based cognitive behavioral therapy in a self-help format helps to narrow the treatment gap in many mental disorders. Are Internet-based self-help programs, which are based on the principles of CBT, also feasible and viable for patients with schizophrenia? Methods: Mental health professionals (target N=50) as well as individuals with schizophrenia spectrum disorders (target N=50) reported their opinion regarding potential chances and risks of Internet-based self-help for schizophrenia in an online survey. Results: The preliminary data analysis of n=30 health professionals revealed a general acceptance of Internet-based programs for schizophrenia (53% acceptable, 47% acceptable after empirical evaluation) and specific contraindications (e.g., severe psychotic symptoms; 73%). People with schizophrenia highlighted the attractiveness of self-help interventions due to a wish for empowerment and for opportunities to strengthen self-efficacy. Conclusions: Risks, limitations and chances of Internet-based programs for patients with schizophrenia will be discussed.

Structural brain correlates of defective gesture performance in schizophrenia

INTRODUCTION The neural correlates of impaired performance of gestures are currently unclear. Lesion studies showed variable involvement of the ventro-dorsal stream particularly left inferior frontal gyrus (IFG) in gesture performance on command. However, findings cannot be easily generalized as lesions may be biased by the architecture of vascular supply and involve brain areas beyond the critical region. The neuropsychiatric syndrome of schizophrenia shares apraxic-like errors and altered brain structure without macroanatomic lesions. Schizophrenia may therefore qualify as a model disorder to test neural correlates of gesture impairments. METHODS We included 45 schizophrenia patients and 44 healthy controls in the study to investigate the structural brain correlates of defective gesturing in schizophrenia using voxel based morphometry. Gestures were tested in two domains: meaningful gestures (transitive and intransitive) on verbal command and imitation of meaningless gestures. Cut-off scores were used to separate patients with deficits, patients without deficits and controls. Group differences in gray matter (GM) volume were explored in an ANCOVA. RESULTS Patients performed poorer than controls in each gesture category (p < .001). Patients with deficits in producing meaningful gestures on command had reduced GM predominantly in left IFG, with additional involvement of right insula and anterior cingulate cortex. Patients with deficits differed from patients without deficits in right insula, inferior parietal lobe (IPL) and superior temporal gyrus. CONCLUSIONS Impaired performance of meaningful gestures on command was linked to volume loss predominantly in the praxis network in schizophrenia. Thus, the behavioral similarities between apraxia and schizophrenia are paralleled by structural alterations. However, few associations between behavioral impairment and structural brain alterations appear specific to schizophrenia.

Dimensional approaches to schizophrenia: A comparison of the Bern Psychopathology scale and the five-factor model of the Positive and Negative Syndrome Scale

The aim was to examine to what extent the dimensions of the BPS map the five factors derived from the PANSS in order to explore the level of agreement of these alternative dimensional approaches in patients with schizophrenia. 149 inpatients with schizophrenia spectrum disorders were recruited. Psychopathological symptoms were assessed with the Bern Psychopathology Scale (BPS) and the Positive and Negative Syndrome Scale (PANSS). Linear regression analyses were conducted to explore the association between the factors and the items of the BPS. The robustness of patterns was evaluated. An understandable overlap of both approaches was found for positive and negative symptoms and excitement. The PANSS positive factor was associated with symptoms of the affect domain in terms of both inhibition and disinhibition, the PANSS negative factor with symptoms of all three domains of the BPS as an inhibition and the PANSS excitement factor with an inhibition of the affect domain and a disinhibition of the language and motor domains. The results show that here is only a partial overlap between the system-specific approach of the BPS and the five-factor PANSS model. A longitudinal assessment of psychopathological symptoms would therefore be of interest.

Cooperation & Competition Between Navigation Systems in the Rat Brain: The Role of the Hippocampus and Striatum During a Dissociative Maze Task

While many tend to think of memory systems in the brain as a single process, in reality several experiments have supported multiple dissociations of different forms of learning, such as spatial learning and response learning. In both humans and rats, the hippocampus has long been shown to be specialized in the storage of spatial and contextual memory whereas the striatum is associated with motor responses and habitual behaviors. Previous studies have examined how damage to hippocampus or striatum has affected the acquisition of either a spatial or response navigation task. However even in a very familiar environment organisms must continuously switch between place and response strategies depending upon circumstances. The current research investigates how these two brain systems interact under normal conditions to produce navigational behavior. Rats were tested using a task developed by Jacobson and colleagues (2006) in which the two types of navigation could be controlled and studied simultaneously. Rats were trained to solve a plus maze using both a spatial and a response strategy. A cue (flashing light) was employed to indicate the correct strategy on a given trial. When no light was present, the animals were rewarded for making a 90º right turn (motor response). When the light was on, the animals were rewarded for going to a specific goal location (place strategy). After learning the task, animals had a sham surgery or dorsal striatum or hippocampus damaged. In order to investigate the individual role of each brain system and evaluate whether these brain regions compete or cooperate for control over strategy, we utilized a within-animal comparisons. The configuration of the maze allowed for the comparison of behavior in individual animals before and after specific brain areas were damaged. Animals with hippocampal lesions showed selective deficits on place trials after surgery and learned the reversal of the motor response more rapidly than striatal lesioned or sham rats. Unlike previous findings regarding maze learning, animals with striatal lesions showed deficits in both place and response trials and had difficulty learning the reversal of motor response. Therefore, the effects of lesions on the ability to switch back and forth between strategies were more complex than previously suggested. This work may reveal important new insight on the integration of hippocampal and striatal learning systems, and facilitate a better understanding of the brain dynamics underlying similar navigational processes in humans.

Psychiatric Epidemiology and Neuroscience Unite in the Pursuit of Reformulated Schizophrenia Nosologies

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