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Preview: Schizophrenia Bulletin - current issue

Schizophrenia Bulletin Current Issue





Published: Sat, 13 Jan 2018 00:00:00 GMT

Last Build Date: Fri, 12 Jan 2018 18:47:46 GMT

 



Commentary on “The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis”

Sat, 13 Jan 2018 00:00:00 GMT

There is currently great interest in the therapeutic potential of cannabidiol (CBD) in psychosis. In this timely article, Hahn1 focuses on one possible application—its use in patients who have a psychotic disorder and are also regular cannabis users.



Employment and Schizophrenia: Three Innovative Research Approaches

Thu, 14 Dec 2017 00:00:00 GMT

In the era of deinstitutionalization, employment was an uncommon outcome for people with schizophrenia and other severe mental illnesses living in the community.1 Mental health and vocational rehabilitation professionals initially offered little help, perhaps because they believed that people with severe mental illnesses were unable or unlikely to work competitively. Instead, professionals referred people coming out of hospitals to sheltered settings, such as day programs and sheltered workshops, where they could be monitored closely and trained to work in a slow, step-wise fashion. Even the Program for Assertive Community Treatment2—a pioneer in community integration in the 1970s and 1980s—initially endorsed sheltered work.



Editorial Board Changes for 2018

Mon, 13 Nov 2017 00:00:00 GMT

Members of the editorial board at the Schizophrenia Bulletin are substantially involved in the journal’s peer review process, in the organization of our theme issues, and other activities that advance the mission of the journal. This work is time-consuming, and in an effort to limit the burden imposed and to recognize exceptional service as an ad hoc referee, it is our policy to revisit Editorial Board membership every 4 years. A considerable number of changes to the editorial board will become effective with the issuance of Volume 44 (January 2018). We express our deep appreciation for the exceptional service provided by the members who are rotating off of the Board. Your work ensured the success of the Bulletin, including the difficult transition to a broader scientific mission than that defined by schizophrenia alone.



Antipsychotic Combinations for Schizophrenia

Mon, 13 Nov 2017 00:00:00 GMT




Basic Neuroscience Illuminates Causal Relationship Between Sleep and Memory: Translating to Schizophrenia

Thu, 09 Nov 2017 00:00:00 GMT

Abstract
Patients with schizophrenia are often plagued by sleep disturbances that can exacerbate the illness, including potentiating psychosis and cognitive impairments. Cognitive dysfunction is a core feature of schizophrenia with learning and memory being particularly impaired. Sleep disruptions often accompanying the illness and may be key mechanism that contribute to these core dysfunctions. In this special translational neuroscience feature, we highlight the role of sleep in mediating cognitive function, with a special focus on learning and memory. By defining dysfunctional sleep architecture and rhythms in schizophrenia, we focus on the disarray of mechanisms critical to learning and memory and postulate an association between sleep disturbances and cognitive impairments in the disorder. Lastly, we review preclinical models of schizophrenia and highlight exciting translational research that may lead to new therapeutic approaches to alleviating sleep disturbances and effectively improving cognitive function in schizophrenia.



Economic, Labor, and Regulatory Moderators of the Effect of Individual Placement and Support Among People With Severe Mental Illness: A Systematic Review and Meta-analysis

Thu, 28 Sep 2017 00:00:00 GMT

Abstract
As Individual Placement and Support (IPS) has become the international standard for vocational rehabilitation of adults with serious mental illness, researchers must consider the relationship between IPS and local environments. This meta-analysis used mixed-effects meta-regressions to assess the impact of site-level moderators on the likelihood that IPS recipients, compared with recipients of alternative vocational services, achieved competitive employment. Potential moderators included change in gross domestic product (GDP), local unemployment and unionization rates, and indices describing employment protection regulations, level of disability benefits compensation, and efforts to integrate people with disabilities into the workforce. Regulatory moderators represent facilitators and barriers to employment that may reinforce or detract from the effectiveness of IPS. Across 30 sites drawn from 21 randomized controlled trials in 12 countries (33% in the United States), IPS recipients were 2.31 (95% CI 1.99–2.69) times more likely to find competitive employment than recipients of alternative vocational rehabilitation services. The significant competitive-employment rate advantage of IPS over control services increased in the presence of weaker employment protection legislation and integration efforts, and less generous disability benefits. Policy makers should recognize and account for the fact that labor and disability regulations can create an arrangement of incentives that reduces the relative efficacy of supported employment.



Learning to Live With Schizoaffective Disorder: A Transformative Journey Toward Recovery

Thu, 28 Sep 2017 00:00:00 GMT

I have endured auditory and visual hallucinations, paranoid thoughts, and depressive symptoms since the age of 6 (some 40 years ago), and was formally diagnosed with schizoaffective disorder, depressive type in young adulthood. I chose not to surrender to my illness, but instead to wage a war against my symptoms. And I felt that I was winning that war until I chose to leave a successful but stressful career (built over a period of 25 years) to restore my health and my quality of life.



Cognitive Predictors of Work Among Social Security Disability Insurance Beneficiaries With Psychiatric Disorders Enrolled in IPS Supported Employment

Thu, 31 Aug 2017 00:00:00 GMT

Abstract
Background: Impaired cognitive functioning is a significant predictor of work dysfunction in schizophrenia. Less is known, however about relationships of cognition and work in people with less severe disorders with relatively normal cognitive functioning. Methods: This secondary analysis evaluated cognitive predictors of work in Social Security Disability Insurance (SSDI) beneficiaries with a recent work history who were randomized to receive mental health services, supported employment, and freedom from work disincentives over a 2-year study period in the Mental Health Treatment Study. Of the 1045 participants randomized to the treatment package, 945 (90.4%) received a cognitive assessment at study entry. Competitive work activity was evaluated using a computer-assisted timeline follow-back calendar at baseline and quarterly for 24 months. Results: Mood disorders were the most common psychiatric diagnoses (64.9%), followed by schizophrenia or schizoaffective disorder (35.1%). Tobit regression analyses predicting the average number of hours worked per week, controlling for demographic characteristics, diagnosis, and work history indicated that the cognitive composite score (P < .01) and verbal learning subscale scores (P < .001) were associated with fewer hours of weekly work over the study period. Conclusions: Cognitive functioning predicted work over 2 years in SSDI beneficiaries with mood or schizophrenia-spectrum disorders who were receiving supported employment and mental health interventions, despite a relative absence of cognitive impairment in the study participants. The findings suggest cognitive functioning contributes to competitive work outcomes in persons with psychiatric disorders who have relatively unimpaired cognitive abilities, even under optimal conditions of treatment and vocational support.



The Potential of Cannabidiol Treatment for Cannabis Users With Recent-Onset Psychosis

Fri, 11 Aug 2017 00:00:00 GMT

Abstract
A major factor associated with poor prognostic outcome after a first psychotic break is cannabis misuse, which is prevalent in schizophrenia and particularly common in individuals with recent-onset psychosis. Behavioral interventions aimed at reducing cannabis use have been unsuccessful in this population. Cannabidiol (CBD) is a phytocannabinoid found in cannabis, although at low concentrations in modern-day strains. CBD has a broad pharmacological profile, but contrary to ∆9-tetrahydrocannabinol (THC), CBD does not activate CB1 or CB2 receptors and has at most subtle subjective effects. Growing evidence indicates that CBD acts as an antipsychotic and anxiolytic, and several reports suggest neuroprotective effects. Moreover, CBD attenuates THC’s detrimental effects, both acutely and chronically, including psychotogenic, anxiogenic, and deleterious cognitive effects. This suggests that CBD may improve the disease trajectory of individuals with early psychosis and comorbid cannabis misuse in particular—a population with currently poor prognostic outcome and no specialized effective intervention.



Improving Work Outcome in Supported Employment for Serious Mental Illness: Results From 2 Independent Studies of Errorless Learning

Wed, 26 Jul 2017 00:00:00 GMT

Abstract
Background
Heterogeneity in work outcomes is common among individuals with serious mental illness (SMI).
Objective
In 2 studies, we sought to examine the efficacy of adding errorless learning, a behavioral training intervention, to evidence-based supported employment to improve SMI work outcomes. Work behavior problems were targeted for intervention. We also explored associations between early work behavior and job tenure.
Methods
For both studies (VA: n = 71; community mental health center: n = 91), randomization occurred at the time of job obtainment with participants randomized (1:1) to either errorless learning plus ongoing supported employment or ongoing supported employment alone and then followed for 12 months. Dependent variables included job tenure, work behavior, and hours worked and wages earned per week. For the primary intent-to-treat analyses, data were combined across studies.
Results
Findings revealed that participants in the errorless learning plus supported employment group stayed on their jobs significantly longer than those in the supported employment alone group (32.8 vs 25.6 wk). In addition, differential treatment effects favoring errorless learning were found on targeted work behavior problems (50.5% vs 27.4% improvement from baseline to follow-up assessment). There were no other differential treatment effects. For the prediction analyses involving work behavior, social skills explained an additional 18.3% of the variance in job tenure beyond levels of cognition, symptom severity, and past work history.
Conclusions
These data support errorless learning as an adjunctive intervention to enhance supported employment outcomes and implicate the relevance of workplace social difficulties as a key impediment to prolonged job tenure.



Neurobiological Commonalities and Distinctions Among Three Major Psychiatric Diagnostic Categories: A Structural MRI Study

Tue, 13 Jun 2017 00:00:00 GMT

Abstract
Background: Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are distinct diagnostic categories in current psychiatric nosology, yet there is increasing evidence for shared clinical and biological features in these disorders. No previous studies have examined brain structural features concurrently in these 3 disorders. The aim of this study was to identify the extent of shared and distinct brain alterations in SZ, BD, and MDD. We examined gray matter (GM) volume and white matter (WM) integrity in a total of 485 individuals (135 with SZ, 86 with BD, 108 with MDD, and 156 healthy controls [HC]) who underwent high-resolution structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at a single site. Results: Significant 4-group (SZ, BD, MDD, and HC groups) differences (P < .05, corrected) in GM volumes were found primarily in the paralimbic and heteromodal corticies. Post hoc analyses showed that the SZ, BD, and MDD groups shared GM volume decreases in 87.9% of the total regional volume with significant 4-group differences. Significant 4-group differences in WM integrity (P < .05 corrected) were found in callosal, limbic-paralimbic-hetermodal, cortico-cortical, thalamocortical and cerebellar WM. Post hoc analyses revealed that the SZ and BD groups shared WM alterations in all regions, while WM alterations were not observed with MDD. Conclusions: Our findings of common alterations in SZ, BD, and MDD support the presence of core neurobiological disruptions in these disorders and suggest that neural structural distinctions between these disorders may be less prominent than initially postulated, particularly between SZ and BD.



Increased Striatal and Reduced Prefrontal Cerebral Blood Flow in Clinical High Risk for Psychosis

Tue, 30 May 2017 00:00:00 GMT

Abstract
Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.



Following Instructions in Patients With Schizophrenia: The Benefits of Actions at Encoding and Recall

Mon, 22 May 2017 00:00:00 GMT

Abstract
The ability to follow spoken instructions is important to everyday functioning but has seldom been studied in patients with schizophrenia (SZ). Recent evidence suggests that action-based processing may facilitate the ability to follow instructions, which relies largely on working memory. In this study, we tested the hypothesis that SZ patients may also benefit from action-based advantages in following instructions. Forty-eight clinically stable SZ patients and 48 demographic- and IQ-matched controls completed a following spoken instruction span task involving varied encoding and recall conditions. While SZ patients were impaired in the overall performance of following spoken instructions, this deficit could be attributed to working memory impairment. More importantly, SZ patients showed action-based advantages both at the encoding and retrieval stage to the same extent as healthy controls. Specifically, both healthy controls and SZ patients showed improved memory performance when they additionally performed the actions, or watched the experimenter carrying out the actions compared with simply listening to spoken instructions during the encoding stage. During the retrieval stage, memory was improved when they recalled the instructions by physical enactment compared with oral repetition. The present study provides the first empirical evidence for the impairment in the ability to follow instructions in SZ. We have shown that involving action-based processing in the encoding and retrieval stage facilitated memory of instructions, indicating that the enactment advantage in working memory also applies to SZ patients. These findings provide useful insights for clinical interventions and cognitive remediation for SZ patients.



Too Fast or Too Slow? Time and Neuronal Variability in Bipolar Disorder—A Combined Theoretical and Empirical Investigation

Fri, 19 May 2017 00:00:00 GMT

Abstract
Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article combines theoretical and empirical approaches to integrate phenomenological, psychological, and neuroscientific accounts of abnormal time perception in BP. Phenomenology distinguishes between perception of inner time, ie, self-time, and outer time, ie, world-time, that desynchronize or dissociate from each other in BP: inner time speed is abnormally slow (as in depression) or fast (as in mania) and, by taking on the role as default-mode function, impacts and modulates the perception of outer time speed in an opposite way, ie, as too fast in depression and too slow in mania. Complementing, psychological investigation show opposite results in time perception, ie, time estimation and reproduction, in manic and depressed BP. Neuronally, time speed can be indexed by neuronal variability, ie, SD. Our own empirical data show opposite changes in manic and depressed BP (and major depressive disorder [MDD]) with abnormal SD balance, ie, SD ratio, between somatomotor and sensory networks that can be associated with inner and outer time. Taken together, our combined theoretical-empirical approach demonstrates that desynchronization or dissociation between inner and outer time in BP can be traced to opposite neuronal variability patterns in somatomotor and sensory networks. This opens the door for individualized therapeutic “normalization” of neuronal variability pattern in somatomotor and sensory networks by stimulation with TMS and/or tDCS.



Sex and Diffusion Tensor Imaging of White Matter in Schizophrenia: A Systematic Review Plus Meta-analysis of the Corpus Callosum

Wed, 26 Apr 2017 00:00:00 GMT

Abstract
Sex is considered an understudied variable in health research. Schizophrenia is a brain disorder with known sex differences in epidemiology and clinical presentation. We systematically reviewed the literature for sex-based differences of diffusion properties of white matter tracts in schizophrenia. We then conducted a meta-analysis examining sex-based differences in the genu and splenium of the corpus callosum in schizophrenia. Medline and Embase were searched to identify relevant papers. Studies fulfilling the following criteria were included: (1) included individuals with a diagnosis of schizophrenia, (2) included a control group of healthy individuals, (3) included both sexes in the patient and the control groups, (4) used diffusion tensor imaging, and (5) involved analyzing metrics of white matter microstructural integrity. Fractional anisotropy (FA) was used as the measure of interest in the meta-analysis. Of 730 studies reviewed, 75 met the inclusion criteria. Most showed no effect of sex, however, those that did found either that females have lower FA than males, or that the effect of disease in females is larger than that in males. The findings of the meta-analysis in the corpus callosum supported this result. There is a recognized need for studies on schizophrenia with a sufficient sample of female patients. Lack of power undermines the ability to detect sex-based differences. Understanding the sex-specific impact of illness on neural circuits may help inform development of new treatments, and improvement of existing interventions.



Reduced Short-Latency Afferent Inhibition in Prefrontal but not Motor Cortex and Its Association With Executive Function in Schizophrenia: A Combined TMS-EEG Study

Sat, 01 Apr 2017 00:00:00 GMT

Abstract
Background: Cholinergic dysfunction is increasingly assumed to be involved in the pathophysiology of schizophrenia. Short-latency afferent inhibition (SAI) is a transcranial magnetic stimulation (TMS) paradigm that has been shown to assay central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia. We investigated SAI in M1 and DLPFC in schizophrenia. We hypothesized that modulation of N100 on TMS-evoked potentials (TEPs) from the DLPFC would be attenuated in patients with schizophrenia compared to healthy controls. Methods: SAI was examined in 12 patients, whose age was matched to controls, using TMS combined with electroencephalography (EEG). SAI was recorded with TMS applied to left M1 (M1-SAI) and DLPFC (DLPFC-SAI). For group comparison, we used the SAI data of healthy participants in our previous study. Results: In patients, N100 TEP was significantly attenuated with DLPFC-SAI, whereas P180 TEP was significantly increased with M1-SAI. Between patients and controls, there were significant differences in modulation of P180 TEP by M1-SAI (t22 = −2.748, P = .012; patients > controls) and N100 TEP by DLPFC-SAI (t22 = 5.456, P < .0001; patients < controls). Further, modulation of N100 TEP by DLPFC-SAI significantly correlated with executive function (r = −.740, P = .006, N = 12). Conclusion: Our findings suggest that DLPFC-SAI but not M1-SAI were reduced in patients with schizophrenia and this was linked to deficits in cognition. This may reflect prefrontal cholinergic deficits and represent a biomarker for cholinergic and executive dysfunction in patients with schizophrenia.



Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia: A Nation-Wide Register Study

Sat, 01 Apr 2017 00:00:00 GMT

Abstract
Objective: Negative symptoms and cognitive deficits are main features of schizophrenia but with limited treatment options. Earlier studies have suggested that central nervous system (CNS) stimulants have a small effect on these domains, but with inconclusive results. As the first study to date, we aimed to investigate whether CNS stimulants improve naturalistic outcomes (psychiatric admissions and antipsychotic use) in patients with schizophrenia. Methods: By using extensive health registers all patients with schizophrenia and their use of CNS stimulants in Denmark were identified. Two models were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. Results: CNS stimulants use was associated with a reduction in number of psychiatric admissions from 3.43 (95% CI = 2.86 to 4.01) to 2.62 (95% CI = 1.99 to 3.25) (P = .009), with a more pronounced reduction for women (mean difference: −1.37, 95% CI = −2.34 to −0.40, P = .006). Psychiatric bed-days were reduced by 40 (95% CI = 24.5 to 55.6, P < .001) for individuals with at least 1 admission before CNS stimulant use. In addition, the total amount of antipsychotic use (Defined Daily Dose [DDD]) was reduced (P = .001). The Hazard rate ratio in psychiatric admissions between women taking CNS stimulants compared to women not taking CNS stimulants was 0.77 (95% CI = 0.67 to 0.88). Conclusion: CNS stimulants may have clinical potentials for improving functional outcomes in patients with schizophrenia and randomized clinical studies evaluating this topic are warranted.



Loneliness in Psychosis: A Meta-analytical Review

Tue, 21 Mar 2017 00:00:00 GMT

Abstract
Loneliness may be related to psychotic symptoms but a comprehensive synthesis of the literature in this area is lacking. The primary aim of the current study is to provide a systematic review and meta-analysis of the association between loneliness and psychotic symptoms in people with psychosis. A search of electronic databases was conducted (PsychINFO, MEDLINE, EMBASE, and Web of Science). A random effects meta-analysis was used to compute a pooled estimate of the correlation between loneliness and psychotic symptoms. Study and outcome quality were assessed using adapted versions of the Agency for Healthcare Research and Quality (AHRQ) tool and GRADE approach, respectively. Thirteen studies were included, providing data from 15 647 participants. A moderate association between psychosis and loneliness was observed (k = 13, N = 15 647, r = .32, 95% CI 0.20, 0.44; I2 = 97.56%; moderate quality evidence). Whether loneliness was assessed by a single-item or a more comprehensive measure had no moderating effect on the estimate. Results indicate that there is a significant positive relationship between loneliness and psychosis. Further studies are needed to determine the causal status of this relationship, but this robust finding should be considered in clinical practice and treatment provision for those with psychotic disorders.



Attacking Heterogeneity in Schizophrenia by Deriving Clinical Subgroups From Widely Available Symptom Data

Mon, 20 Mar 2017 00:00:00 GMT

Abstract
Previous research has identified (1) a “deficit” subtype of schizophrenia characterized by enduring negative symptoms and diminished emotionality and (2) a “distress” subtype associated with high emotionality—including anxiety, depression, and stress sensitivity. Individuals in deficit and distress categories differ sharply in development, clinical course and behavior, and show distinct biological markers, perhaps signaling different etiologies. We tested whether deficit and distress subtypes would emerge from a simple but novel data-driven subgrouping analysis, based on Positive and Negative Syndrome Scale (PANSS) negative and distress symptom dimensions, and whether subgrouping was informative regarding other facets of behavior and brain function. PANSS data, and other assessments, were available for 549 people with schizophrenia diagnoses. Negative and distress symptom composite scores were used as indicators in 2-step cluster analyses, which divided the sample into low symptom (n = 301), distress (n = 121), and deficit (n = 127) subgroups. Relative to the low-symptom group, the deficit and distress subgroups had comparably higher total PANSS symptoms (Ps < .001) and were similarly functionally impaired (eg, global functioning [GAF] Ps < .001), but showed markedly different patterns on symptom, cognitive and personality variables, among others. Initial analyses of functional magnetic resonance imaging (fMRI) data from a 182-participant subset of the full sample also suggested distinct patterns of neural recruitment during working memory. The field seeks more neuroscience-based systems for classifying psychiatric conditions, but these are inescapably behavioral disorders. More effective parsing of clinical and behavioral traits could identify homogeneous target groups for further neural system and molecular studies, helping to integrate clinical and neuroscience approaches.



Meta-analysis of Cerebrospinal Fluid Cytokine and Tryptophan Catabolite Alterations in Psychiatric Patients: Comparisons Between Schizophrenia, Bipolar Disorder, and Depression

Fri, 17 Mar 2017 00:00:00 GMT

Abstract
Introduction: Schizophrenia, bipolar disorder, and major depressive disorder (MDD) have all been associated with immune system dysfunction, including aberrant cerebrospinal fluid (CSF) levels of cytokines and tryptophan catabolites; however, the pattern of alterations has not been compared across disorders. We performed a meta-analysis of CSF cytokine and tryptophan catabolites in patients with these major psychiatric disorders. Methods: Articles were identified by searching Pub Med, PsycInfo, and Web of Science, and the reference lists of these studies. Results: Twenty-eight studies met the inclusion criteria (16 schizophrenia, 4 bipolar disorder, and 9 MDD). CSF levels of IL-1β and kynurenic acid were significantly increased in patients with schizophrenia and bipolar disorder compared to healthy controls (P < .001). CSF levels of IL-6 and IL-8 were significantly increased in patients with schizophrenia and MDD compared to healthy controls (P ≤ .013). Discussion: There is preliminary evidence for similarities in the pattern of CSF cytokine and tryptophan catabolite alterations across major psychiatric disorders, although findings must be interpreted with caution in light of small numbers of studies/subjects. Many CSF alterations are also concordant with those in the peripheral blood, particularly for schizophrenia. Findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.



Dysfunction of Large-Scale Brain Networks in Schizophrenia: A Meta-analysis of Resting-State Functional Connectivity

Sat, 11 Mar 2017 00:00:00 GMT

Abstract
Schizophrenia is a complex mental disorder with disorganized communication among large-scale brain networks, as demonstrated by impaired resting-state functional connectivity (rsFC). Individual rsFC studies, however, vary greatly in their methods and findings. We searched for consistent patterns of network dysfunction in schizophrenia by using a coordinate-based meta-analysis. Fifty-six seed-based voxel-wise rsFC datasets from 52 publications (2115 patients and 2297 healthy controls) were included in this meta-analysis. Then, coordinates of seed regions of interest (ROI) and between-group effects were extracted and coded. Seed ROIs were categorized into seed networks by their location within an a priori template. Multilevel kernel density analysis was used to identify brain networks in which schizophrenia was linked to hyper-connectivity or hypo-connectivity with each a priori network. Our results showed that schizophrenia was characterized by hypo-connectivity within the default network (DN, self-related thought), affective network (AN, emotion processing), ventral attention network (VAN, processing of salience), thalamus network (TN, gating information) and somatosensory network (SS, involved in sensory and auditory perception). Additionally, hypo-connectivity between the VAN and TN, VAN and DN, VAN and frontoparietal network (FN, external goal-directed regulation), FN and TN, and FN and DN were found in schizophrenia. Finally, the only instance of hyper-connectivity in schizophrenia was observed between the AN and VAN. Our meta-analysis motivates an empirical foundation for a disconnected large-scale brain networks model of schizophrenia in which the salience processing network (VAN) plays the core role, and its imbalanced communication with other functional networks may underlie the core difficulty of patients to differentiate self-representation (inner world) and environmental salience processing (outside world).



Data-Gathering, Belief Flexibility, and Reasoning Across the Psychosis Continuum

Wed, 08 Mar 2017 00:00:00 GMT

Abstract
Background
There is evidence for a group of nonclinical individuals with full-blown, persistent psychotic experiences (PEs) but no need-for-care: they are of particular importance in identifying risk and protective factors for clinical psychosis. The aim of this study was to investigate whether reasoning biases are related to PEs or need-for-care.
Method
Two groups with persistent PEs (clinical; n = 74; nonclinical; n = 92) and a control group without PEs (n = 83) were compared on jumping-to-conclusions (JTC) and belief flexibility. A randomly selected subset of interviews (n = 104) was analyzed to examine differences in experiential and rational reasoning.
Results
As predicted JTC was more common in the clinical than the other 2 groups. Unexpectedly no group differences were observed between clinical and nonclinical groups on measures of belief flexibility. However, the clinical group was less likely to employ rational reasoning, while the nonclinical group was more likely to use experiential reasoning plus a combination of both types of reasoning processes, compared to the other 2 groups.
Conclusions
Reasoning biases differ in groups with PEs with and without need-for-care. JTC is associated with need-for-care rather than with PEs. The ability to invoke rational reasoning processes, together with an absence of JTC, may protect against pathological outcomes of persistent PEs. However, marked use of experiential reasoning is associated with the occurrence of PEs in both clinical and nonclinical groups. Implications for theory development, intervention and further research are discussed.



Telomere Length and CCL11 Levels are Associated With Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging

Wed, 22 Feb 2017 00:00:00 GMT

Abstract
Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL), and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume and episodic memory performance in individuals with SZ compared to healthy controls (HC). One hundred twelve participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Participants with SZ had decreased TL and GM volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and both biomarkers were related to reduced GM volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was associated with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except between memory and GM. Our results are consistent with the hypothesis of accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ.



Reducing Voices by Direct Dialogue

Tue, 20 Dec 2016 00:00:00 GMT

One central idea of the recovery movement is to work with voices to accept them somehow. I have often heard that voices are associated with life events, people we know and things that have happened to us. The fears from these experiences are being played back to us in the form of what we are hearing. The key to my partial recovery along these lines has been the power that the authority of the therapist has had in refuting what the influence of what voices were saying about or to me and how this suggests a new approach to dealing with them.



Comorbid Diabetes and Depression in a National Sample of Adults With Psychosis

Mon, 21 Nov 2016 00:00:00 GMT

Abstract
Objective
People with psychosis have an elevated risk of depression and diabetes but no large-scale study has characterized their relationship. We aimed to assess this association and to evaluate possible explanatory factors.
Methods
Analysis of cross-sectional data from a national sample of 1155 people with psychosis who gave a fasting blood sample and could be tested for diabetes mellitus. The association between current diabetes mellitus and current depression was estimated using logistic regression, adjusted for age, sex and current psychotropic medication.
Results
A diagnosis of depression was significantly associated with diabetes (OR = 2.16, P = .048) and diabetes medication (OR = 2.50, P = .050) in people with schizophrenia but no other psychosis subtype. Adjustment for cognitive processing speed and current residence (especially psychiatric hospitalization) attenuated that association to nonsignificance. Diabetes and diabetes medication were not significantly associated with antidepressant or mood stabilizer medication.
Conclusions
Clinicians should be aware that people with schizophrenia and diabetes have twice the rate of current depression, and that comorbid diabetes and depression is associated with cognitive impairment and hospitalization. Efforts to disentangle the causal pathways between diabetes, depression, and cognition in people with schizophrenia may be complicated by multiple indications in people with psychosis for the prescription of depression medication, and their lack of association with diabetes mellitus.



Ventral Striatal Dysfunction and Symptom Expression in Individuals With Schizotypal Personality Traits and Early Psychosis

Tue, 25 Oct 2016 00:00:00 GMT

Abstract
Striatal abnormalities play a crucial role in the pathophysiology of schizophrenia. Growing evidence suggests an association between aberrant striatal activity during reward anticipation and symptom dimensions in schizophrenia. However, it is not clear whether this holds across the psychosis continuum. The aim of the present study was to investigate alterations of ventral striatal activation during reward anticipation and its relationship to symptom expression in persons with schizotypal personality traits (SPT) and first-episode psychosis. Twenty-six individuals with high SPT, 26 patients with non-affective first-episode psychosis (including 13 with brief psychotic disorder (FEP-BPD) and 13 with first-episode schizophrenia [FEP-SZ]) and 25 healthy controls underwent event-related functional magnetic resonance imaging while performing a variant of the Monetary Incentive Delay task. Ventral striatal activation was positively correlated with total symptom severity, in particular with levels of positive symptoms. This association was observed across the psychosis continuum and within each subgroup. Patients with FEP-SZ showed the strongest elevation of striatal activation during reward anticipation, although symptom levels did not differ between groups in the psychosis continuum. While our results provide evidence that variance in striatal activation is mainly explained by dimensional symptom expression, patients with schizophrenia show an additional dysregulation of striatal activation. Trans-diagnostic approaches are promising in order to disentangle dimensional and categorical neural mechanisms in the psychosis continuum.