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Schizophrenia Bulletin Current Issue





Published: Wed, 15 Feb 2017 00:00:00 GMT

Last Build Date: Wed, 15 Feb 2017 11:45:02 GMT

 



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2017-02-15




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2017-02-15




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2017-02-15




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2017-02-15




Modeling the Interplay Between Psychological Processes and Adverse, Stressful Contexts and Experiences in Pathways to Psychosis: An Experience Sampling Study

2017-02-15

Abstract
Several integrated models of psychosis have implicated adverse, stressful contexts and experiences, and affective and cognitive processes in the onset of psychosis. In these models, the effects of stress are posited to contribute to the development of psychotic experiences via pathways through affective disturbance, cognitive biases, and anomalous experiences. However, attempts to systematically test comprehensive models of these pathways remain sparse. Using the Experience Sampling Method in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls, we investigated how stress, enhanced threat anticipation, and experiences of aberrant salience combine to increase the intensity of psychotic experiences. We fitted multilevel moderated mediation models to investigate indirect effects across these groups. We found that the effects of stress on psychotic experiences were mediated via pathways through affective disturbance in all 3 groups. The effect of stress on psychotic experiences was mediated by threat anticipation in FEP individuals and controls but not in ARMS individuals. There was only weak evidence of mediation via aberrant salience. However, aberrant salience retained a substantial direct effect on psychotic experiences, independently of stress, in all 3 groups. Our findings provide novel insights on the role of affective disturbance and threat anticipation in pathways through which stress impacts on the formation of psychotic experiences across different stages of early psychosis in daily life.



Evidence That the Urban Environment Moderates the Level of Familial Clustering of Positive Psychotic Symptoms

2017-02-11

Abstract
If the shared familial risk factors that predispose to psychotic disorder interact with early-life exposures in the urban environment, familial correlations of psychosis proneness measures should be higher in the exposed environment. We tested the hypothesis that in sib-pairs with one member affected by psychotic disorder, the familial correlation of psychotic experiences, but not depression, negative symptoms, or intelligence quotient (IQ), would be higher if the nonaffected sibling was raised in an urban environment until age 15 years. The sample analyzed consisted of 959 sib-pairs of whom one was affected with psychotic disorder. Lifetime self-reported psychotic and depressive experiences were measured using the self-reported “Community Assessment of Psychic Experiences” (CAPE). In the unadjusted model of the sibling-patient association in CAPE positive symptoms, there was a significant interaction by urban environment (B interaction = 0.079, 95% CI: 0.021 to 0.137, P = .007, n = 828). Stratified analyses revealed a strong sib-pair association in the urban environment (B = 0.077, 95% CI: 0.037 to 0.117, P < .001) and absence of association in the rural environment (B = −0.002, 95% CI: −0.044 to 0.039, P = .920). Associations were not affected after taking into account confounders and outliers, and there was no evidence that sibling associations in IQ, depression, or negative symptoms were moderated by the urban environment. The results agree with previous work indicating that the effects of the genetic and environmental factors that occasion familial clustering of psychotic disorder depend on whether or not an individual spends his early life in an urban environment.



Fifty Years: Do Over or Move Forward

2017-02-08

The following text reflects remarks presented at the 2016 SIRS meeting where four of us from the durable goods department were asked to comment on what we would do if starting our careers today. For reasons best understood in the framework of ego psychology I opted to indicate how I would change what I have done before speculating on beginning a career now envisioning the next 50 years.



Studying Delusions Within Research Domain Criteria: The Challenge of Configural Traits When Building a Mechanistic Foundation for Abnormal Beliefs

2017-02-08

Abstract
Our understanding of belief formation, maintenance, and change is in its infancy, yet it is absolutely essential to make progress in understanding these processes to parse the puzzle of psychotic delusions. In this companion to Bebbington and Freeman, I consider a number of Research Domain Criteria constructs that may be helpful for exploring these processes but ultimately conclude (following Risen) that delusions are likely the result of several systems failing. I close with 4 recommendations for making progress: (1) prepare to study a variable space defined by several relevant constructs, (2) include the study of “unsanctioned” constructs, (3) examine the relationships between brain regions, rather than the local abnormalities, and (4) develop rigorous computational models of delusions.



Explaining Delusions: Reducing Uncertainty Through Basic and Computational Neuroscience

2017-02-08

Abstract
Delusions, the fixed false beliefs characteristic of psychotic illness, have long defied understanding despite their response to pharmacological treatments (e.g., D2 receptor antagonists). However, it can be challenging to discern what makes beliefs delusional compared with other unusual or erroneous beliefs. We suggest mapping the putative biology to clinical phenomenology with a cognitive psychology of belief, culminating in a teleological approach to beliefs and brain function supported by animal and computational models. We argue that organisms strive to minimize uncertainty about their future states by forming and maintaining a set of beliefs (about the organism and the world) that are robust, but flexible. If uncertainty is generated endogenously, beliefs begin to depart from consensual reality and can manifest into delusions. Central to this scheme is the notion that formal associative learning theory can provide an explanation for the development and persistence of delusions. Beliefs, in animals and humans, may be associations between representations (e.g., of cause and effect) that are formed by minimizing uncertainty via new learning and attentional allocation. Animal research has equipped us with a deep mechanistic basis of these processes, which is now being applied to delusions. This work offers the exciting possibility of completing revolutions of translation, from the bedside to the bench and back again. The more we learn about animal beliefs, the more we may be able to apply to human beliefs and their aberrations, enabling a deeper mechanistic understanding.



Evidence That the Impact of Childhood Trauma on IQ Is Substantial in Controls, Moderate in Siblings, and Absent in Patients With Psychotic Disorder

2017-02-08

Abstract
Research suggests that childhood trauma is associated with cognitive alterations, but it is not known whether the cognitive alterations observed in patients with psychotic disorder, and their relatives, is trauma-related. Patients with a schizophrenia-spectrum diagnosis (n = 1119), siblings of patients (n = 1059) and healthy comparison subjects (HCS; n = 586) were interviewed 3 times over a period of 6 years. Repeated measures of IQ were analyzed as a function of childhood trauma and group, controlling for confounders. There were significant differences in the impact of childhood trauma on IQ across the 3 groups. Exposure in HCS was associated with a nearly 5-point reduction in IQ (−4.85; 95% confidence interval [CI]: −7.98 to −1.73, P = .002), a lesser reduction in siblings (−2.58; 95% CI: −4.69 to −0.46, P = .017) and no significant reduction in patients (−0.84; 95% CI: −2.78 to 1.10, P = .398). One-fourth of the sibling-control difference in IQ was reducible to childhood trauma, whereas for patients this was only 5%. Over the 6-year follow-up, those with trauma exposure showed significantly less learning effects with repeated cognitive assessments (b = 1.36, 95% CI: 0.80‒1.92, P < .001) than the nonexposed (b = 2.31, 95% CI: 1.92‒2.71, P < .001; P interaction = .001). Although childhood trauma impacts cognitive ability and learning in non-ill people at low and high genetic risk, its effect on the observed cognitive alterations in psychotic disorder may be minor. Twin and family studies on cognitive alterations in psychotic disorder need to take into account the differential impact of trauma on cognition across ill and non-ill, at risk groups.



Why We Need Positive Psychiatry for Schizophrenia and Other Psychotic Disorders

2017-01-20

The traditional and still common perspective of schizophrenia is that this is an intractable illness with a dismal prognosis. Kraepelin proposed dementia praecox as a disease with poor prognosis as a cardinal feature. Schizophrenia has been likened to a cancer of the mind. That negative view persisted well into the late 20th century despite growing empirical evidence, especially from Europe, that this syndrome was associated with heterogeneity in course, including a favorable outcome in many persons. The bias was so ingrained that in the International Pilot Study of Schizophrenia, initiated in 1968, only the Washington center used developmental, prognostic, and follow-up outcome scales with multiple dimensions to capture the heterogeneity of course of illness; it demonstrated that the outcome was mainly predicted by developmental factors rather than by psychotic symptoms. A 1988 issue of Schizophrenia Bulletin (14:4) that contained reviews of several long-term follow-up investigations from Europe and North America, illustrated a wide range of courses including good outcomes. In a study in Vermont, Harding and colleagues2 followed a longitudinal cohort of individuals with schizophrenia for decades after initial hospitalization and found that one-half to two-thirds of them had substantial improvement. Our own studies have confirmed a long-term trend for improvement in psychosocial functioning, with reduced psychotic symptoms and fewer psychotic relapses that required hospitalization. Despite accelerated physical aging, with high rates of medical comorbidity and premature mortality, a sizable proportion of people with schizophrenia experience extended periods of psychosocial remission associated with resilience, optimism, and social support. Healthy survivor bias is not the primary explanation. In a recent qualitative study, 20 occupationally high-achieving individuals with schizophrenia identified eight categories of coping strategies that they found useful for managing symptoms and supporting recovery: utilizing supportive others, taking medications, enacting cognitive strategies, using avoidance behaviors, controlling the environment, engaging spirituality, focusing on well-being, and being employed or continuing education.3



SIRS 5th Biennial Schizophrenia International Research Meeting—Florence, April 2016 Possibilities and Pitfalls—Reflections on 42 Years in Academic Psychiatry and Lessons for a Suggested Repeat Performance

2017-01-20

Circumstances vary from place to place and change a great deal over time so that I am not sure that my experiences and opinions will be very relevant for other people nowadays, but I hope they may be of some interest.



Transdiagnostic Extension of Delusions: Schizophrenia and Beyond

2017-01-20

Abstract
Delusion is central to the conceptualization, definition, and identification of schizophrenia. However, in current classifications, the presence of delusions is neither necessary nor sufficient for the diagnosis of schizophrenia, nor is it sufficient to exclude the diagnosis of some other psychiatric conditions. Partly as a consequence of these classification rules, it is possible for delusions to exist transdiagnostically. In this article, we evaluate the extent to which this happens, and in what ways the characteristics of delusions vary according to diagnostic context. We were able to examine their presence and form in delusional disorder, affective disorder, obsessive-compulsive disorder, borderline personality disorder, and dementia, in all of which they have an appreciable presence. There is some evidence that the mechanisms of delusion formation are, at least to an extent, shared across these disorders. This transdiagnostic extension of delusions is an argument for targeting them therapeutically in their own right. However there is a dearth of research to enable the rational transdiagnostic deployment of either pharmacological or psychological treatments.



Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

2017-01-05

Abstract
Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function.



Biological Mechanisms Whereby Social Exclusion May Contribute to the Etiology of Psychosis: A Narrative Review

2017-01-04

Abstract
The purpose of this review is to examine whether a contribution of social exclusion to the pathogenesis of psychosis is compatible with the dopamine hypothesis and/or the neurodevelopmental hypothesis. Humans experience social exclusion as defeating. An animal model for defeat is the resident-intruder paradigm. The defeated animal shows evidence of an increased sensitivity to amphetamine, increased dopamine release in the nucleus accumbens and prefrontal cortex, and increased firing of dopaminergic neurons in the ventral tegmental area. As for humans, one study showed that amphetamine-induced striatal dopamine release was significantly greater among nonpsychotic young adults with severe hearing impairment than among normal hearing controls. Two other studies reported an association between childhood trauma and increased dopamine function in striatal subregions. Several studies have suggested that the perigenual anterior cingulate cortex (pgACC) may play a role in the processing of social stress. Importantly, the pgACC regulates the activity of the ventral striatum through bidirectional interconnections. We are not aware of studies in humans that examined whether (proxies for) social exclusion contributes to the structural brain changes present at psychosis onset. Animal studies, however, reported that long-term isolation may lead to reductions in volume of the total brain, hippocampus, or medial prefrontal cortex. Other animal studies reported that social defeat can reduce neurogenesis. In conclusion, the answer to the question as to whether there are plausible mechanisms whereby social exclusion can contribute to the pathogenesis of psychosis is cautiously affirmative.



Psychosis as a Barrier to the Expression of Sexuality and Intimacy: An Environmental Risk?

2017-01-03

Abstract
People diagnosed with schizophrenia and related psychotic disorders often have unmet needs around sexuality and intimacy issues. This can impact negatively upon a person’s recovery and the need to lead a fulfilling and satisfying life. The aim of the current review was to explore the available qualitative literature that addressed sexuality and intimacy issues published between the years 2006 and 2016. Records were screened for eligibility. Finally, 56 studies that addressed the aims were included in the review. The main themes that emerged are briefly discussed. The implications for clinical practice and future research are presented.



The Search for Environmental Mechanisms Underlying the Expression of Psychosis: Introduction

2016-12-30

Abstract
In this themed issue, a number of articles are presented that investigate environmental mechanisms in psychotic disorder. Below, we describe some of the challenges associated with this research, in terms of phenotypic definition, the nature of environmental impact and associated design and measurement issues.



Mistakes I Have Made in My Research Career

2016-12-21

schizophreniamistakesimagingepidemiology



The Clinical Features of Paranoia in the 20th Century and Their Representation in Diagnostic Criteria From DSM-III Through DSM-5

2016-12-21

Abstract
This review traces, through psychiatric textbooks, the history of the Kraepelinian concept of paranoia in the 20th century and then relates the common reported symptoms and signs to the diagnostic criteria for paranoia/delusional disorder in DSM-III through DSM-5. Clinical descriptions of paranoia appearing in 10 textbooks, published 1899 to 1970, revealed 11 prominent symptoms and signs reported by 5 or more authors. Three symptoms (systematized delusions, minimal hallucinations, and prominent ideas of reference) and 2 signs (chronic course and minimal affective deterioration) were reported by 8 or 9 of the authors. Four textbook authors rejected the Kraepelinian concept of paranoia. A weak relationship was seen between the frequency with which the clinical features were reported and the likelihood of their inclusion in modern DSM manuals. Indeed, the diagnostic criteria for paranoia/delusional disorder shifted substantially from DSM-III to DSM-5. The modern operationalized criteria for paranoia/delusional disorder do not well reflect the symptoms and signs frequently reported by historical experts. In contrast to results of similar reviews for depression, schizophrenia and mania, the clinical construct of paranoia/delusional disorder has been somewhat unstable in Western Psychiatry since the turn of the 20th century as reflected in both textbooks and the DSM editions.



Improving Prognostic Accuracy in Subjects at Clinical High Risk for Psychosis: Systematic Review of Predictive Models and Meta-analytical Sequential Testing Simulation

2016-08-17

Abstract
Discriminating subjects at clinical high risk (CHR) for psychosis who will develop psychosis from those who will not is a prerequisite for preventive treatments. However, it is not yet possible to make any personalized prediction of psychosis onset relying only on the initial clinical baseline assessment. Here, we first present a systematic review of prognostic accuracy parameters of predictive modeling studies using clinical, biological, neurocognitive, environmental, and combinations of predictors. In a second step, we performed statistical simulations to test different probabilistic sequential 3-stage testing strategies aimed at improving prognostic accuracy on top of the clinical baseline assessment. The systematic review revealed that the best environmental predictive model yielded a modest positive predictive value (PPV) (63%). Conversely, the best predictive models in other domains (clinical, biological, neurocognitive, and combined models) yielded PPVs of above 82%. Using only data from validated models, 3-stage simulations showed that the highest PPV was achieved by sequentially using a combined (clinical + electroencephalography), then structural magnetic resonance imaging and then a blood markers model. Specifically, PPV was estimated to be 98% (number needed to treat, NNT = 2) for an individual with 3 positive sequential tests, 71%–82% (NNT = 3) with 2 positive tests, 12%–21% (NNT = 11–18) with 1 positive test, and 1% (NNT = 219) for an individual with no positive tests. This work suggests that sequentially testing CHR subjects with predictive models across multiple domains may substantially improve psychosis prediction following the initial CHR assessment. Multistage sequential testing may allow individual risk stratification of CHR individuals and optimize the prediction of psychosis.



White Matter Disruptions in Schizophrenia Are Spatially Widespread and Topologically Converge on Brain Network Hubs

2016-08-17

Abstract
White matter abnormalities associated with schizophrenia have been widely reported, although the consistency of findings across studies is moderate. In this study, neuroimaging was used to investigate white matter pathology and its impact on whole-brain white matter connectivity in one of the largest samples of patients with schizophrenia. Fractional anisotropy (FA) and mean diffusivity (MD) were compared between patients with schizophrenia or schizoaffective disorder (n = 326) and age-matched healthy controls (n = 197). Between-group differences in FA and MD were assessed using voxel-based analysis and permutation testing. Automated whole-brain white matter fiber tracking and the network-based statistic were used to characterize the impact of white matter pathology on the connectome and its rich club. Significant reductions in FA associated with schizophrenia were widespread, encompassing more than 40% (234ml) of cerebral white matter by volume and involving all cerebral lobes. Significant increases in MD were also widespread and distributed similarly. The corpus callosum, cingulum, and thalamic radiations exhibited the most extensive pathology according to effect size. More than 50% of cortico-cortical and cortico-subcortical white matter fiber bundles comprising the connectome were disrupted in schizophrenia. Connections between hub regions comprising the rich club were disproportionately affected. Pathology did not differ between patients with schizophrenia and schizoaffective disorder and was not mediated by medication. In conclusion, although connectivity between cerebral hubs is most extensively disturbed in schizophrenia, white matter pathology is widespread, affecting all cerebral lobes and the cerebellum, leading to disruptions in the majority of the brain’s fiber bundles.



Schizophrenia and Infections: The Eyes Have It

2016-08-09

Abstract
The visual tract is prominently involved in schizophrenia, as evidenced by perceptual distortions and a type of nystagmus found in many individuals affected. Genetic explanations for these abnormalities have been suggested. This study proposes an alternate explanation based on infection. Several infectious agents thought to be associated with some cases of schizophrenia are known to cause both infection of the fetus and abnormalities of the eye. Toxoplasma gondii is examined in detail, and rubella, cytomegalovirus, varicella-zoster virus, and herpes simplex virus more briefly. Careful ophthalmic assessments, including funduscopy and direct examination of tissues for infectious agents, will clarify the role of such agents in ocular aspects of schizophrenia.



SZDB: A Database for Schizophrenia Genetic Research

2016-07-22

Abstract
Schizophrenia (SZ) is a debilitating brain disorder with a complex genetic architecture. Genetic studies, especially recent genome-wide association studies (GWAS), have identified multiple variants (loci) conferring risk to SZ. However, how to efficiently extract meaningful biological information from bulk genetic findings of SZ remains a major challenge. There is a pressing need to integrate multiple layers of data from various sources, eg, genetic findings from GWAS, copy number variations (CNVs), association and linkage studies, gene expression, protein–protein interaction (PPI), co-expression, expression quantitative trait loci (eQTL), and Encyclopedia of DNA Elements (ENCODE) data, to provide a comprehensive resource to facilitate the translation of genetic findings into SZ molecular diagnosis and mechanism study. Here we developed the SZDB database (http://www.szdb.org/), a comprehensive resource for SZ research. SZ genetic data, gene expression data, network-based data, brain eQTL data, and SNP function annotation information were systematically extracted, curated and deposited in SZDB. In-depth analyses and systematic integration were performed to identify top prioritized SZ genes and enriched pathways. Multiple types of data from various layers of SZ research were systematically integrated and deposited in SZDB. In-depth data analyses and integration identified top prioritized SZ genes and enriched pathways. We further showed that genes implicated in SZ are highly co-expressed in human brain and proteins encoded by the prioritized SZ risk genes are significantly interacted. The user-friendly SZDB provides high-confidence candidate variants and genes for further functional characterization. More important, SZDB provides convenient online tools for data search and browse, data integration, and customized data analyses.



Brain-Wide Analysis of Functional Connectivity in First-Episode and Chronic Stages of Schizophrenia

2016-07-21

Abstract
Published reports of functional abnormalities in schizophrenia remain divergent due to lack of staging point-of-view and whole-brain analysis. To identify key functional-connectivity differences of first-episode (FE) and chronic patients from controls using resting-state functional MRI, and determine changes that are specifically associated with disease onset, a clinical staging model is adopted. We analyze functional-connectivity differences in prodromal, FE (mostly drug naïve), and chronic patients from their matched controls from 6 independent datasets involving a total of 789 participants (343 patients). Brain-wide functional-connectivity analysis was performed in different datasets and the results from the datasets of the same stage were then integrated by meta-analysis, with Bonferroni correction for multiple comparisons. Prodromal patients differed from controls in their pattern of functional-connectivity involving the inferior frontal gyri (Broca’s area). In FE patients, 90% of the functional-connectivity changes involved the frontal lobes, mostly the inferior frontal gyrus including Broca’s area, and these changes were correlated with delusions/blunted affect. For chronic patients, functional-connectivity differences extended to wider areas of the brain, including reduced thalamo-frontal connectivity, and increased thalamo-temporal and thalamo-sensorimoter connectivity that were correlated with the positive, negative, and general symptoms, respectively. Thalamic changes became prominent at the chronic stage. These results provide evidence for distinct patterns of functional-dysconnectivity across FE and chronic stages of schizophrenia. Importantly, abnormalities in the frontal language networks appear early, at the time of disease onset. The identification of stage-specific pathological processes may help to understand the disease course of schizophrenia and identify neurobiological markers crucial for early diagnosis.



Depression and Schizophrenia: Cause, Consequence, or Trans-diagnostic Issue?

2016-07-15

Abstract
The presence of depression in schizophrenia has been a challenge to the Kraepelinian dichotomy, with various attempts to save the fundamental distinction including evoking and refining diagnoses such as schizoaffective disorder. But the tectonic plates are shifting. Here we put forward a summary of recent evidence regarding the prevalence, importance, possible aetiological pathways and treatment challenges that recognizing depression in schizophrenia bring. Taken together we propose that depression is more than comorbidity and that increased effective therapeutic attention to mood symptoms will be needed to improve outcomes and to support prevention.



Modality-Dependent Impact of Hallucinations on Low-Frequency Fluctuations in Schizophrenia

2016-07-15

Abstract
Prior resting-state functional magnetic resonance imaging (fMRI) analyses have identified patterns of functional connectivity associated with hallucinations in schizophrenia (Sz). In this study, we performed an analysis of the mean amplitude of low-frequency fluctuations (ALFF) to compare resting state spontaneous low-frequency fluctuations in patients with Sz who report experiencing hallucinations impacting different sensory modalities. By exploring dynamics across 2 low-frequency passbands (slow-4 and slow-5), we assessed the impact of hallucination modality and frequency range on spatial ALFF variation. Drawing from a sample of Sz and healthy controls studied as part of the Functional Imaging Biomedical Informatics Research Network (FBIRN), we replicated prior findings showing that patients with Sz have decreased ALFF in the posterior brain in comparison to controls. Remarkably, we found that patients that endorsed visual hallucinations did not show this pattern of reduced ALFF in the back of the brain. These patients also had elevated ALFF in the left hippocampus in comparison to patients that endorsed auditory (but not visual) hallucinations. Moreover, left hippocampal ALFF across all the cases was related to reported hallucination severity in both the auditory and visual domains, and not overall positive symptoms. This supports the hypothesis that dynamic changes in the ALFF in the hippocampus underlie severity of hallucinations that impact different sensory modalities.



Aberrant Force Processing in Schizophrenia

2016-07-06

Abstract
Initially considered as mere side effects of antipsychotic medication, there is now evidence that motor and somatosensory disturbances precede the onset of the illness and can be found in drug-naive patients. However, research on the topic is scarce. Here, we were interested in assessing the accuracy of the neural signal in detecting parametric variations of force linked to a voluntary motor act and a received tactile sensation, either self-generated or externally generated. Patients with a diagnosis of schizophrenia and healthy controls underwent functional magnetic resonance imaging while asked to press, or abstain from pressing, a lever in order to match a visual target force. Forces, exerted and received, varied on 10 levels from 0.5 N to 5 N in 0.5 N increments. Healthy participants revealed a positive correlation between force and activity in contralateral primary somatosensory area (S1) when performing a movement as well as when receiving a tactile sensation but only when this was externally, and not self-, generated. Patients showed evidence of altered force signaling in both motor and tactile conditions, as well as increased correlation with force when tactile sensation was self-generated. Findings are interpreted in line with accounts of predictive and sensory integration mechanisms and point toward alterations in the encoding of parametric forces in the motor and somatosensory domain in patients affected by schizophrenia.



The Relationship of Intellectual Functioning and Cognitive Performance to Brain Structure in Schizophrenia

2016-07-01

Abstract
Background:
Schizophrenia (SZ) is often characterized by cognitive and intellectual impairment. However, there is much heterogeneity across individuals, suggesting different trajectories of the illness. Recent findings have shown brain volume differences across subgroups of individuals with psychosis (SZ and bipolar disorder), such that those with intellectual and cognitive impairments presented evidence of early cerebral disruption, while those with cognitive but not intellectual impairments showed evidence of progressive brain abnormalities. Our aim was to investigate the relations of cognition and intellectual functioning with brain structure abnormalities in a sample of SZ compared to unaffected individuals.
Methods:
92 individuals with SZ and 94 healthy controls part of the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) underwent neuropsychological assessment and structural magnetic resonance imaging (MRI). Individuals with SZ were divided into subgroups according their estimated premorbid crystallized intellectual (ePMC-IQ) and cognitive performance. Brain volumes differences were investigated across groups.
Results:
SZ with ePMC-IQ and cognitive impairments had reduced total brain volume (TBV), intracranial volume (ICV), TBV corrected for ICV, and cortical gray matter volume, as well as reduced cortical thickness, and insula volumes. SZ with cognitive impairment but intact ePMC-IQ showed only reduced cortical gray matter volume and cortical thickness.
Conclusions:
These data provide additional evidence for heterogeneity in SZ. Impairments in cognition associated with reduced ePMC-IQ were related to evidence of broad brain structural alterations, including suggestion of early cerebral disruption. In contrast, impaired cognitive functioning in the context of more intact intellectual functioning was associated with cortical alterations that may reflect neurodegeneration.



Neuroanatomical Predictors of Functional Outcome in Individuals at Ultra-High Risk for Psychosis

2016-07-01

Abstract
Most individuals at ultra-high risk (UHR) for psychosis do not transition to frank illness. Nevertheless, many have poor clinical outcomes and impaired psychosocial functioning. This study used voxel-based morphometry to investigate if baseline grey and white matter brain densities at identification as UHR were associated with functional outcome at medium- to long-term follow-up. Participants were help-seeking UHR individuals (n = 109, 54M:55F) who underwent magnetic resonance imaging at baseline; functional outcome was assessed an average of 9.2 years later. Primary analysis showed that lower baseline grey matter density, but not white matter density, in bilateral frontal and limbic areas, and left cerebellar declive were associated with poorer functional outcome (Social and Occupational Functioning Assessment Scale [SOFAS]). These findings were independent of transition to psychosis or persistence of the at-risk mental state. Similar regions were significantly associated with lower self-reported levels of social functioning and increased negative symptoms at follow-up. Exploratory analyses showed that lower baseline grey matter densities in middle and inferior frontal gyri were significantly associated with decline in Global Assessment of Functioning (GAF) score over follow-up. There was no association between baseline grey matter density and IQ or positive symptoms at follow-up. The current findings provide novel evidence that those with the poorest functional outcomes have the lowest grey matter densities at identification as UHR, regardless of transition status or persistence of the at-risk mental state. Replication and validation of these findings may allow for early identification of poor functional outcome and targeted interventions.



Four-Year Cost-effectiveness of Cognitive Behavior Therapy for Preventing First-episode Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial

2016-06-15

Abstract
Background.
This study aims to evaluate the long-term cost-effectiveness of add-on cognitive behavior therapy (CBT) for the prevention of psychosis for individuals at ultrahigh risk (UHR) of psychosis.
Method.
The Dutch Early Detection and Intervention randomized controlled trial was used, comparing routine care (RC; n = 101) with routine care plus CBT for UHR (here called CBTuhr; n = 95). A cost-effectiveness analysis was conducted with treatment response (defined as proportion of averted transitions to psychosis) as an outcome and a cost-utility analysis with quality-adjusted life years (QALYs) gained as a secondary outcome.
Results.
The proportion of averted transitions to psychosis was significantly higher in the CBTuhr condition (with a risk difference of 0.122; b = 1.324, SEb = 0.017, z = 7.99, P < 0.001). CBTuhr showed an 83% probability of being more effective and less costly than RC by −US$ 5777 (savings) per participant. In addition, over the 4-year follow-up period, cumulative QALY health gains were marginally (but not significantly) higher in CBTuhr than for RC (2.63 vs. 2.46) and the CBTuhr intervention had a 75% probability of being the superior treatment (more QALY gains at lower costs) and a 92% probability of being cost-effective compared with RC at the Dutch threshold value (US$ 24 560; €20 000 per QALY).
Conclusions.
Add-on preventive CBTuhr had a high likelihood (83%) of resulting in more averted transitions to psychosis and lower costs as compared with RC. In addition, the intervention had a high likelihood (75%) of resulting in more QALY gains and lower costs as compared to RC.



Impaired Context Processing is Attributable to Global Neuropsychological Impairment in Schizophrenia and Psychotic Bipolar Disorder

2016-06-15

Abstract
Background:
Context processing may reflect a specific cognitive impairment in schizophrenia. Whether impaired context processing is observed across psychotic disorders or among relatives of affected individuals, and whether it is a deficit that is independent from the generalized neuropsychological deficits seen in psychotic disorders, are less established.
Methods:
Schizophrenia, schizoaffective, and psychotic bipolar probands (n = 660), their first-degree relatives (n = 741), and healthy individuals (n = 308) studied by the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium performed an expectancy task requiring use of contextual information to overcome a pre-potent response. Sensitivity for target detection and false alarm rates on trials requiring inhibition or goal maintenance were measured.
Results:
Proband groups and relatives with psychosis spectrum personality traits demonstrated reduced target sensitivity and elevated false alarm rates. False alarm rate was higher under inhibition vs goal maintenance conditions although this difference was attenuated in schizophrenia and schizoaffective proband groups. After accounting for global neuropsychological impairment, as reflected by the composite score from the Brief Assessment of Cognition in Schizophrenia neuropsychological battery, deficits in schizophrenia and bipolar proband groups were no longer significant. Performance measures were moderately familial.
Conclusion:
Reduced target detection, but not a specific deficit in context processing, is observed across psychotic disorders. Impairments in both goal maintenance and response inhibition appear to contribute comparably to deficits in schizophrenia and schizoaffective disorder, whereas greater difficulty with response inhibition underlies deficits in bipolar disorder. Yet, these deficits are not independent from the generalized neurocognitive impairment observed in schizophrenia and psychotic bipolar disorder.



Pitch and Duration Mismatch Negativity and Premorbid Intellect in the First Hospitalized Schizophrenia Spectrum

2016-05-26

Abstract
Mismatch negativity (MMN) is a robustly abnormal brainwave in chronically ill schizophrenia that has generated interest as a disease presence biomarker. Reports of MMN reduction in first-episode schizophrenia have been equivocal, raising uncertainty about its reduction at first psychotic break. Here we tested 29 schizophrenia-spectrum participants under 1 year from their first hospitalization for psychosis and 40 age-, gender-, parental socioeconomic status-, and Wechsler Adult Intelligence Scales III Information-matched healthy controls on both pitch and duration MMN. Participants performed a visual checkerboard tracking task while standard (1kHz, 50ms, 80%), pitch-deviant (1.2kHz, 50ms, 10%) and duration-deviant (1kHz, 100ms, 10%) tones were presented over headphones (75 dB) and EEG was recorded. Independent component analysis was used to remove eye movements and visual stimulus processing activity. Groups did not differ in pitch MMN or duration MMN amplitudes. Smaller pitch and duration MMN amplitudes were associated with lower estimates of premorbid intellect in all participants and independently with greater positive symptoms in first hospitalized schizophrenia. Overall MMN reduction was not present in these relatively high functioning individuals at the first episode of schizophrenia, and therefore is not a good disease presence biomarker for this sample. Future research is warranted to determine the degree of MMN reduction at the first episode of psychosis across a greater range of cognitive impairment, the utility of MMN as an indicator of risk or diagnosis, and its role for understanding pathophysiological mechanisms in emerging psychosis.



Association of the Jumping to Conclusions and Evidence Integration Biases With Delusions in Psychosis: A Detailed Meta-analysis

2016-05-11

Abstract
We completed a meta-analysis to investigate the relationship between delusions in psychosis and 4 cognitive biases: “jumping to conclusions” (JTC), the “bias against disconfirmatory evidence” (BADE), the “bias against confirmatory evidence” (BACE), and “liberal acceptance” (LA). Building on recent meta-analyses we compared more narrowly defined groups. We identified 35 JTC, 8 BADE, 7 BACE, and 6 LA studies for inclusion. Groups with schizophrenia who were currently experiencing delusions demonstrated greater JTC, BADE, BACE, and LA than groups with schizophrenia who were not currently experiencing delusions, who in turn demonstrated no more JTC than healthy control groups. Hence JTC, BADE, BACE, and LA co-vary with delusions in cross-sectional samples of people with schizophrenia. Groups who were experiencing delusions due to other psychiatric illnesses also demonstrated greater JTC than healthy controls, and equivalent JTC to groups with schizophrenia currently experiencing delusions. Hence JTC is associated with delusions across a range of diagnoses. Groups with other, non-delusional psychiatric illnesses demonstrated less JTC, BADE, BACE, and LA than groups with schizophrenia currently experiencing delusions, less JTC than groups experiencing delusions due to other diagnoses, and no more JTC, BADE, BACE, or LA than healthy control groups. Hence JTC, BADE, BACE, and LA were not associated with psychiatric illnesses in general. Our results indicate all 4 biases are associated with delusions specifically rather than merely with a diagnosis of schizophrenia or with being psychiatrically ill, consistent with the possibility that they contribute to delusional severity.



Early Intervention in First Episode Psychosis: A Service User’s Experience

2016-01-12

I had my first severe psychotic episode in early 2010. Two years prior to this my thoughts had began slowing down. Normally, thinking about doing an action and then moving the required body part happened simultaneously. Now there was a gap. I was a radiotherapy student and since operating X-ray machinery requires a smooth flow of decision making and intricate movement. These slow thoughts made me a hazard. Once I gave up my degree, I had no-where to go during the day and would lie in bed. My general practitioner thought I was depressed and gave me antidepressants. We know now that I wasn’t and I had prodromal psychosis. Eventually the slow thoughts took over my mind and I began hearing voices that were frightening.



Living With Schizophrenia

2015-05-25

I wonder why the almighty is upset with me



Resisting Voices Through Finding Our Own Compassionate Voice

2014-03-14

I am a mental health service user with 15 years experience of hearing voices and having delusions. I have been having compassionate focused therapy at my local mental hospital, as developed by Professor Paul Gilbert. My psychologist, Angela Kennedy, has an interest in voice dialogue approaches and has adapted compassion focused therapy to include talking to my voices. During this therapy, I discovered an inner voice, realized it was compassionate, and that it could help my therapeutic outcomes. I first want to outline this in terms of what I have been enlightened by theoretically and then provide examples to illustrate how this all works in practice.