Showing papers in "Schizophrenia Bulletin in 2012"
TL;DR: It is shown that childhood adversity is strongly associated with increased risk for psychosis and population attributable risk was 33% (16%–47%).
Abstract: Evidence suggests that adverse experiences in childhood are associated with psychosis. To examine the association between childhood adversity and trauma (sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death, and bullying) and psychosis outcome, MEDLINE, EMBASE, PsychINFO, and Web of Science were searched from January 1980 through November 2011. We included prospective cohort studies, large-scale cross-sectional studies investigating the association between childhood adversity and psychotic symptoms or illness, case-control studies comparing the prevalence of adverse events between psychotic patients and controls using dichotomous or continuous measures, and case-control studies comparing the prevalence of psychotic symptoms between exposed and nonexposed subjects using dichotomous or continuous measures of adversity and psychosis. The analysis included 18 case-control studies (n = 2048 psychotic patients and 1856 nonpsychiatric controls), 10 prospective and quasi-prospective studies (n = 41 803) and 8 population-based cross-sectional studies (n = 35 546). There were significant associations between adversity and psychosis across all research designs, with an overall effect of OR = 2.78 (95% CI = 2.34–3.31). The integration of the case-control studies indicated that patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls (95% CI = 1.90–3.88). The association between childhood adversity and psychosis was also significant in population-based cross-sectional studies (OR = 2.99 [95% CI = 2.12–4.20]) as well as in prospective and quasi-prospective studies (OR = 2.75 [95% CI = 2.17–3.47]). The estimated population attributable risk was 33% (16%–47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.
1,893 citations
TL;DR: It is concluded that while dysregulation of NMDARs may play an important role in the pathophysiology of schizophrenia, additional research is required to determine the particular cell type(s) that mediate dysfunctional N MDAR signaling in the illness.
Abstract: Gamma oscillations appear to be dependent on inhibitory neurotransmission from parvalbumin (PV)-containing gamma-amino butyric acid neurons. Thus, the abnormalities in PV neurons found in schizophrenia may underlie the deficits of gamma-band synchrony in the illness. Because gamma-band synchrony is thought to be crucial for cognition, cognitive deficits in schizophrenia may reflect PV neuron dysfunction in cortical neural circuits. Interestingly, it has been suggested that PV alterations in schizophrenia are the consequence of a hypofunction of signaling through N-methyl-D-aspartate (NMDA) receptors (NMDARs). Here, we review recent findings that address the question of how NMDAR hypofunction might produce deficits of PV neuron–mediated inhibition in schizophrenia. We conclude that while dysregulation of NMDARs may play an important role in the pathophysiology of schizophrenia, additional research is required to determine the particular cell type(s) that mediate dysfunctional NMDAR signaling in the illness.
401 citations
TL;DR: This study used quantitative methods of meta-analysis to assess the efficacy of behavioral training programs designed to improve social cognitive function and found that effects of social cognitive training programs on positive and negative symptoms of schizophrenia were nonsignificant.
Abstract: A wealth of evidence has revealed that deficits in social cognitive skills (including facial affect recognition (FAR), social cue perception, Theory of Mind (ToM), and attributional style) are evident in schizophrenia and are linked to a variety of domains of functional outcome. In light of these associations, a growing number of studies have attempted to ameliorate these deficits as a means of improving outcome in the disorder through the use of structured behavioral training. This study used quantitative methods of meta-analysis to assess the efficacy of behavioral training programs designed to improve social cognitive function. A total of 19 studies consisting of 692 clients were aggregated from relevant databases. Outcome measures were organized according to whether they were social cognitive tests proximal to the intervention or whether they represented measures of treatment generalization (symptoms, observer-rated community, and institutional function). With respect to social cognitive measures, weighted effect-size analysis revealed that there were moderate-large effects of social cognitive training procedures on FAR (identification, d = 0.71 and discrimination, d = 1.01) and small-moderate effects of training on ToM (d = 0.46), while effects on social cue perception and attributional style were not significant. For measures of generalization, weighted effect-size analysis revealed that there were moderate-large effect on total symptoms (d = 0.68) and observer-rated community and institutional function (d = 0.78). Effects of social cognitive training programs on positive and negative symptoms of schizophrenia were nonsignificant. Moderating variables and implications for future research and treatment development are discussed.
396 citations
TL;DR: The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications, and social cognitive performance was impaired across all domains of social cognition and in all clinical samples.
Abstract: Social cognitive impairments are consistently reported in schizophrenia and are associated with functional outcome. We currently know very little about whether these impairments are stable over the course of illness. In the current study, 3 different aspects of social cognition were assessed (emotion processing, Theory of Mind [ToM], and social relationship perception) at 3 distinct developmental phases of illness: prodromal, first episode, and chronic. In this cross-sectional study, participants included 50 individuals with the prodromal risk syndrome for psychosis and 34 demographically comparable controls, 81 first-episode schizophrenia patients and 46 demographically comparable controls, and 53 chronic schizophrenia patients and 47 demographically comparable controls. Outcome measures included total and subtest scores on 3 specialized measures of social cognition: (1) emotion processing assessed with the Mayer-Salovey-Caruso Emotional Intelligence Test, (2) ToM assessed with The Awareness of Social Inference Test, and (3) social relationship perception assessed the Relationships Across Domains Test. Social cognitive performance was impaired across all domains of social cognition and in all clinical samples. Group differences in performance were comparable across phase of illness, with no evidence of progression or improvement. Age had no significant effect on performance for either the clinical or the comparison groups. The findings suggest that social cognition in these 3 domains fits a stable pattern that has outcome and treatment implications. An accompanying article prospectively examines the longitudinal stability of social cognition and prediction of functional outcome in the first-episode sample.
392 citations
TL;DR: Results indicate that peer-delivered mental illness self-management training reduces psychiatric symptoms, enhances participants' hopefulness, and improves their QOL over time.
Abstract: The purpose of this study was to determine the efficacy of a peer-led illness self-management intervention called Wellness Recovery Action Planning (WRAP) by comparing it with usual care. The primary outcome was reduction of psychiatric symptoms, with secondary outcomes of increased hopefulness, and enhanced quality of life (QOL). A total of 519 adults with severe and persistent mental illness were recruited from outpatient community mental health settings in 6 Ohio communities and randomly assigned to the 8-week intervention or a wait-list control condition. Outcomes were assessed at end of treatment and at 6-month follow-up using an intent-to-treat mixedeffects random regression analysis. Compared to controls, at immediate postintervention and at 6-month follow-up, WRAP participants reported: (1) significantly greater reduction over time in Brief Symptom Inventory Global Symptom Severity and Positive Symptom Total, (2) significantly greater improvement over time in hopefulness as assessed by the Hope Scale total score and subscale for goal directed hopefulness, and (3) enhanced improvement over time in QOL as assessed by the World Health Organization Quality of Life-BREF environment subscale. These results indicate that peer-delivered mental illness self-management training reduces psychiatric symptoms, enhances participants’ hopefulness, and improves their QOL over time. This confirms the importance of peerled wellness management interventions, such as WRAP, as part of a group of evidence-based recovery-oriented services.
382 citations
TL;DR: A linear association was observed between the logarithm of the odds ofrisk for schizophrenia and urbanicity and the risk for schizophrenia at the most urban environment was estimated to be 2.37 times higher than in the most rural environment.
Abstract: The association between urbanicity and risk of schizophrenia is well established. The incidence of schizophrenia has been observed to increase in line with rising levels of urbanicity, as measured in terms of population size or density. This association is expressed as Incidence Rate Ratio (IRR), and the results are usually presented by comparing the most urban with the most rural environment. In this study, we undertook to express the effect of urbanicity on the risk of schizophrenia in a linear form and to perform a meta-analysis of all available evidence. We first employed a simple regression analysis of log (IRR) as given in each study on the urbanicity category, assuming a uniform distribution and a linear association. In order to obtain more accurate estimates, we developed a more sophisticated method that generates individual data points with simulation from the summary data presented in the original studies, and then fits a logistic regression model. The estimates from each study were combined with meta-analysis. Despite the challenges that arise from differences between studies as regards to the number and relative size of urbanicity levels, a linear association was observed between the logarithm of the odds of risk for schizophrenia and urbanicity. The risk for schizophrenia at the most urban environment was estimated to be 2.37 times higher than in the most rural environment. The same effect was found when studies measuring the risk for nonaffective psychosis were included.
367 citations
TL;DR: The associations between sexual trauma, physical abuse, bullying, and being brought up in institutional or local authority care and reports of auditory hallucinations and paranoid beliefs in the 2007 Adult Psychiatric Morbidity Survey are examined.
Abstract: Previous studies have reported associations between childhood adversities, eg, loss of a parent, being raised in institutional care, sexual and other kinds of abuse by adults and bullying by peers, and psychosis in adulthood. However, the mechanisms by which these adversities lead to psychotic experiences are poorly understood. From models of the psychological processes involved in positive symptoms, it was predicted that childhood sexual abuse would be specifically associated with auditory hallucinations in adulthood, and that disruption of early attachment relations and more chronic forms of victimization such as bullying would be specifically associated with paranoid ideation. We therefore examined the associations between sexual trauma, physical abuse, bullying, and being brought up in institutional or local authority care and reports of auditory hallucinations and paranoid beliefs in the 2007 Adult Psychiatric Morbidity Survey. All simple associations between childhood adversities and the two symptom types were significant. Childhood rape was associated only with hallucinations (OR 8.9, CI = 1.86–42.44) once co-occurring paranoia was controlled for. Being brought up in institutional care (OR = 11.08, CI = 3.26–37.62) was specifically associated with paranoia once comorbid hallucinations had been controlled for. For each symptom, dose-response relationships were observed between the number of childhood traumas and the risk of the symptom. The specific associations observed are consistent with current psychological theories about the origins of hallucinations and paranoia. Further research is required to study the psychological and biological mediators of these associations.
358 citations
TL;DR: Persistent blockade of NMDA receptors recreates in experimental animals the critical pathologic features of schizophrenia including downregulation of parvalbumin-positive cortical GABAergic neurons, pyramidal neuron dendritic dysgenesis, and reduced spine density.
Abstract: Although glutamate was first hypothesized to be involved in the pathophysiology of schizophrenia in the 1980s, it was the demonstration that N-methyl-D-aspartate (NMDA) receptor antagonists, the dissociative anesthetics, could replicate the full range of psychotic, negative, cognitive, and physiologic features of schizophrenia in normal subjects that placed the “NMDA receptor hypofunction hypothesis” on firm footing. Additional support came from the demonstration that a variety of agents that enhanced NMDA receptor function at the glycine modulatory site significantly reduced negative symptoms and variably improved cognition in patients with schizophrenia receiving antipsychotic drugs. Finally, persistent blockade of NMDA receptors recreates in experimental animals the critical pathologic features of schizophrenia including downregulation of parvalbumin-positive cortical GABAergic neurons, pyramidal neuron dendritic dysgenesis, and reduced spine density.
351 citations
TL;DR: It is suggested that AHs arise from an interaction between abnormal neural activation patterns that produce salient auditory signals and top-down mechanisms that include signal detection errors, executive and inhibition deficits, a tapestry of expectations and memories, and state characteristics that influence how these experiences are interpreted.
Abstract: While the majority of cognitive studies on auditory hallucinations (AHs) have been conducted in schizophrenia (SZ), an increasing number of researchers are turning their attention to different clinical and nonclinical populations, often using SZ findings as a model for research. Recent advances derived from SZ studies can therefore be utilized to make substantial progress on AH research in other groups. The objectives of this article were to (1) present an up-to-date review regarding the cognitive mechanisms of AHs in SZ, (2) review findings from cognitive research conducted in other clinical and nonclinical groups, and (3) integrate these recent findings into a cohesive framework. First, SZ studies show that the cognitive underpinnings of AHs include self-source-monitoring deficits and executive and inhibitory control dysfunctions as well as distortions in top-down mechanisms, perceptual and linguistic processes, and emotional factors. Second, consistent with SZ studies, findings in other population groups point to the role of top-down processing, abnormalities in executive inhibition, and negative emotions. Finally, we put forward an integrated model of AHs that incorporates the above findings. We suggest that AHs arise from an interaction between abnormal neural activation patterns that produce salient auditory signals and top-down mechanisms that include signal detection errors, executive and inhibition deficits, a tapestry of expectations and memories, and state characteristics that influence how these experiences are interpreted. Emotional factors play a particular prominent role at all levels of this hierarchy. Our model is distinctively powerful in explaining a range of phenomenological characteristics of AH across a spectrum of disorders.
344 citations
TL;DR: The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors, and antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia.
Abstract: The failure to find genes of major effect in schizophrenia has refocused attention on nongenetic, including infectious factors. In a previous study, antibodies to Toxoplasma gondii were found to be elevated in 23 studies of schizophrenia (OR 2.73; 95% CI 2.10–3.60). The current study replicates this finding with 15 additional studies (OR 2.71; 95% CI 1.93–3.80) and compares this with other identified schizophrenia risk factors. The highest risk factors are having an affected mother (relative risks [RR] 9.31; 95% CI 7.24–11.96), father (RR 7.20; 95% CI 5.10–10.16), or sibling (RR 6.99; 95% CI 5.38–9.08) or being the offspring of immigrants from selected countries (RR 4.5; 95% CI 1.5–13.1). Intermediate risk factors, in addition to infection with T. gondii, include being an immigrant from and to selected countries (RR 2.7; 95% CI 2.3–3.2), being born in (RR 2.24; 95% CI 1.92–2.61) or raised in (RR 2.75; 95% CI 2.31–3.28) an urban area, cannabis use (OR 2.10–2.93; 95% CI 1.08–6.13), having minor physical anomalies (OR 2.23; 95% CI 1.42–3.58), or having a father 55 or older (OR 2.21–5.92; 95% CI 1.46-17.02). Low-risk factors include a history of traumatic brain injury (OR 1.65; 95% CI 1.17–2.32), sex abuse in childhood (OR 1.46; 95% CI 0.84–2.52), obstetrical complications (OR 1.29–1.38; 95% CI 1.00–1.84), having a father 45 or older (OR 1.21–1.66; 95% CI 1.09–2.01), specific genetic polymorphisms (OR 1.09–1.24; 95% CI 1.06–1.45), birth seasonality (OR 1.07–1.95; 95% CI 1.05–2.91), maternal exposure to influenza (RR 1.05; 95% CI 0.98–1.12), or prenatal stress (RR 0.98–1.00; 95% CI 0.85–1.16).
342 citations
TL;DR: Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.
Abstract: BACKGROUND It is commonly assumed that there are clear lines of demarcation between anxiety and depressive disorders on the one hand and psychosis on the other. Recent evidence, however, suggests that this principle may be in need of updating. METHODS Depressive and/or anxiety disorders, with no previous history of psychotic disorder, were examined for the presence of psychotic symptoms in a representative community sample of adolescents and young adults (Early Developmental Stages of Psychopathology study; n = 3021). Associations and consequences of psychotic symptomatology in the course of these disorders were examined in terms of demographic distribution, illness severity, onset of service use, and risk factors. RESULTS Around 27% of those with disorders of anxiety and depression displayed one or more psychotic symptoms, vs 14% in those without these disorders (OR 2.23, 95% CI 1.89-2.66, P < .001). Presence as compared with nonpresence of psychotic symptomatology was associated with younger age (P < .0001), male sex (P < .0058), and poorer illness course (P < .0002). In addition, there was greater persistence of schizotypal (P < .0001) and negative symptoms (P < .0170), more observable illness behavior (P < .0001), greater likelihood of service use (P < .0069), as well as more evidence of familial liability for mental illness (P < .0100), exposure to trauma (P < .0150), recent and more distant life events (P < .0006-.0244), cannabis use (P < .0009), and any drug use (P < .0008). CONCLUSION Copresence of psychotic symptomatology in disorders of anxiety and depression is common and a functionally and etiologically highly relevant feature, reinforcing the view that psychopathology is represented by a network or overlapping and reciprocally impacting dimensional liabilities.
TL;DR: The prevalence of the presence of at least one psychotic symptom has a wide range worldwide varying as much as from 0.8% to 31.4% and is related to a significant poorer health status.
Abstract: OBJECTIVE: To identify the cross-national prevalence of psychotic symptoms in the general population and to analyze their impact on health status. METHOD: The sample was composed of 256,445 subjects (55.9% women), from nationally representative samples of 52 countries worldwide participating in the World Health Organization's World Health Survey. Standardized and weighted prevalence of psychotic symptoms were calculated in addition to the impact on health status as assessed by functioning in multiple domains. RESULTS: Overall prevalences for specific symptoms ranged from 4.80% (SE = 0.14) for delusions of control to 8.37% (SE = 0.20) for delusions of reference and persecution. Prevalence figures varied greatly across countries. All symptoms of psychosis produced a significant decline in health status after controlling for potential confounders. There was a clear change in health impact between subjects not reporting any symptom and those reporting at least one symptom (effect size of 0.55). CONCLUSIONS: The prevalence of the presence of at least one psychotic symptom has a wide range worldwide varying as much as from 0.8% to 31.4%. Psychotic symptoms signal a problem of potential public health concern, independent of the presence of a full diagnosis of psychosis, as they are common and are related to a significant decrement in health status. The presence of at least one psychotic symptom is related to a significant poorer health status, with a regular linear decrement in health depending on the number of symptoms.
TL;DR: The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk, the low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.
Abstract: In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were helpseeking for nonpsychotic disorders at the secondary mental health services in the Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.
TL;DR: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas and neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.
Abstract: Background: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Methods: Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and “signed differential mapping” voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Results: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Conclusions: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms.
TL;DR: It is demonstrated that low-intensity text-messaging interventions like MATS are feasible and effective interventions to improve several important outcomes, especially for higher functioning consumers with schizophrenia.
Abstract: Mobile Assessment and Treatment for Schizophrenia (MATS) employs ambulatory monitoring methods and cognitive behavioral therapy interventions to assess and improve outcomes in consumers with schizophrenia through mobile phone text messaging. Three MATS interventions were developed to target medication adherence, socialization, and auditory hallucinations. Participants received up to 840 text messages over a 12-week intervention period. Fifty-five consumers with schizophrenia or schizoaffective disorder were enrolled, but 13 consumers with more severe negative symptoms, lower functioning, and lower premorbid IQ did not complete the intervention, despite repeated prompting and training. For completers, the average valid response rate for 216 outcome assessment questions over the 12-week period was 86%, and 86% of phones were returned undamaged. Medication adherence improved significantly, but only for individuals who were living independently. Number of social interactions increased significantly and a significant reduction in severity of hallucinations was found. In addition, the probability of endorsing attitudes that could interfere with improvement in these outcomes was also significantly reduced in MATS. Lab-based assessments of more general symptoms and functioning did not change significantly. This pilot study demonstrated that low-intensity text-messaging interventions like MATS are feasible and effective interventions to improve several important outcomes, especially for higher functioning consumers with schizophrenia.
TL;DR: Developments in two key predictions of the glutamatergic models of schizophrenia are reviewed: first, that neurocognitive deficits in schizophrenia should follow the pattern of deficit predicted based on underlying NMDAR dysfunction and, second, that agents that stimulate N MDAR function should be therapeutically beneficial.
Abstract: Over the last 20 years, glutamatergic models of schizophrenia have become increasingly accepted as etiopathological models of schizophrenia, based on the observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews developments in two key predictions of the model: first, that neurocognitive deficits in schizophrenia should follow the pattern of deficit predicted based on underlying NMDAR dysfunction and, second, that agents that stimulate NMDAR function should be therapeutically beneficial. As opposed to dopamine receptors, NMDAR are widely distributed throughout the brain, including subcortical as well as cortical brain regions, and sensory as well as association cortex. Studies over the past 20 years have documented severe sensory dysfunction in schizophrenia using behavioral, neurophysiological, and functional brain imaging approaches, including impaired generation of key sensory-related potentials such as mismatch negativity and visual P1 potentials. Similar deficits are observed in humans following administration of NMDAR antagonists such as ketamine in either humans or animal models. Sensory dysfunction, in turn, predicts impairments in higher order cognitive functions such as auditory or visual emotion recognition. Treatment studies have been performed with compounds acting directly at the NMDAR glycine site, such as glycine, D-serine, or D-cycloserine, and, more recently, with high-affinity glycine transport inhibitors such as RG1678 (Roche). More limited studies have been performed with compounds targeting the redox site. Overall, these compounds have been found to induce significant beneficial effects on persistent symptoms, suggesting novel approaches for treatment and prevention of schizophrenia.
TL;DR: Findings extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures, to serve as useful vulnerability indicators and early clinical intervention targets.
Abstract: This study evaluated the longitudinal stability and functional correlates of social cognition during the early course of schizophrenia. Fifty-five first-episode schizophrenia patients completed baseline and 12-month follow-up assessments of 3 key domains of social cognition (emotional processing, theory of mind, and social/relationship perception), as well as clinical ratings of real-world functioning and symptoms. Scores on all 3 social cognitive tests demonstrated good longitudinal stability with test-retest correlations exceeding .70. Higher baseline and 12-month social cognition scores were both robustly associated with significantly better work functioning, independent living, and social functioning at the 12-month follow-up assessment. Furthermore, cross-lagged panel analyses were consistent with a causal model in which baseline social cognition drove later functional outcome in the domain of work, above and beyond the contribution of symptoms. Social cognitive impairments are relatively stable, functionally relevant features of early schizophrenia. These results extend findings from a companion study, which showed stable impairments across patients in prodromal, first-episode, and chronic phases of illness on the same measures. Social cognitive impairments may serve as useful vulnerability indicators and early clinical intervention targets.
TL;DR: Some of the most prominent descriptive features of AVHs in schizophrenia (SZ) are looked at and these are examined in clinical conditions including substance abuse, Parkinson's disease, epilepsy, dementia, late-onset SZ, mood disorders, borderline personality disorder, hearing impairment, and dissociative disorders.
Abstract: Despite a growing interest in auditory verbal hallucinations (AVHs) in different clinical and nonclinical groups, the phenomenological characteristics of such experiences have not yet been reviewed and contrasted, limiting our understanding of these phenomena on multiple empirical, theoretical, and clinical levels. We look at some of the most prominent descriptive features of AVHs in schizophrenia (SZ). These are then examined in clinical conditions including substance abuse, Parkinson's disease, epilepsy, dementia, late-onset SZ, mood disorders, borderline personality disorder, hearing impairment, and dissociative disorders. The phenomenological changes linked to AVHs in prepsychotic stages are also outlined, together with a review of AVHs in healthy persons. A discussion of key issues and future research directions concludes the review.
TL;DR: The results demonstrate increased levels of CSF KYN and KYNA in patients with schizophrenia and further support the hypothesis that KYNA is involved in the pathophysiology of schizophrenia.
Abstract: Background: The kynurenic acid (KYNA) hypothesis for schizophrenia is partly based on studies showing increased brain levels of KYNA in patients. KYNA is an endogenous metabolite of tryptophan (TRP ...
TL;DR: There are differences between the SGAs in their ability to induce EPS that clinicians consider warrant treatment with antimuscarinic drugs, and they might be important for individual patients and should be taken into account in drug choice.
Abstract: Objective: While all second-generation antipsychotics (SGAs) are promoted for having a low risk of extrapyramidal side effects (EPS), clinical observations suggest differences between the various agents. Nevertheless, this question has never been examined in a systematic review and meta-analysis of head-to-head comparisons. Methods: We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE (last search July 2009) for randomized, blinded studies comparing the following SGAs in the treatment of schizophrenia or related disorders: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, and zotepine. At least 3 reviewers extracted the data independently. The primary outcome was “use of antiparkinson medication.” The results were combined in a meta-analysis. Results: We included 54 studies with 116 arms. Risperidone was associated with more use of antiparkinson medication than clozapine, olanzapine, quetiapine, and ziprasidone. Ziprasidone showed more use of antiparkinson medication than olanzapine and quetiapine and zotepine more than clozapine. There was no significant difference between amisulpride and its comparators (olanzapine, risperidone, or ziprasidone). Quetiapine showed significantly less use of antiparkinson medication than the 3 other SGAs it was compared with (olanzapine, risperidone, and ziprasidone). Scale-derived data (Barnes Akathisia Scale and Simpson Angus Scale) were limited. Conclusions: Our meta-analysis demonstrates that there are differences between the SGAs in their ability to induce EPS that clinicians consider warrant treatment with antimuscarinic drugs. Even though the differences were relatively small, they might be important for individual patients and should be taken into account in drug choice.
TL;DR: The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further "closing in" on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders.
Abstract: Introduction Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an “ultra high risk” (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder.
Methods Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days.
Results Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases.
Discussion The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further “closing in” on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of “false positive” cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.
TL;DR: It is suggested that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients and this association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients.
Abstract: Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP - CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of "neurocognitively less impaired" patients, who only developed psychosis after a relatively early initiation into cannabis use.
North Shore-LIJ Health System1, University of Calgary2, Harvard University3, Beth Israel Deaconess Medical Center4, Emory University5, University of California, Los Angeles6, University of California, San Diego7, Yale University8, University of North Carolina at Chapel Hill9, National Institutes of Health10, Albert Einstein College of Medicine11
TL;DR: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.
Abstract: Objectives: Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Methods: Ageappropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. Results: At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Conclusions: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.
TL;DR: This report provides an update of neuroimaging studies of AH with a particular emphasis on more recent anatomical, physiological, and neurochemical imaging studies, and practical recommendations for future studies.
Abstract: Despite more than 2 decades of neuroimaging investigations, there is currently insufficient evidence to fully understand the neurobiological substrate of auditory hallucinations (AH). However, some progress has been made with imaging studies in patients with AH consistently reporting altered structure and function in speech and language, sensory, and nonsensory regions. This report provides an update of neuroimaging studies of AH with a particular emphasis on more recent anatomical, physiological, and neurochemical imaging studies. Specifically, we provide (1) a review of findings in schizophrenia and nonschizophrenia voice hearers, (2) a discussion regarding key issues that have interfered with progress, and (3) practical recommendations for future studies.
TL;DR: Collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance the understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia are described.
Abstract: Here, we describe our collaborative efforts to use N-methyl-d-aspartate (NMDA) receptor antagonists as a translational tool to advance our understanding of the pathophysiology of schizophrenia and identify potential new targets for treatment of schizophrenia. We began these efforts in the late 1980s with a keen sense that, in both human and animal studies, we needed to move beyond the dopamine hypothesis of schizophrenia; if the dopamine hypothesis were correct, the existing dopamine antagonists should have cured the disease but they have not. We used NMDA receptor antagonists, not to produce schizophrenia, but as a tool to provide insights into effects of disturbances in glutamate synaptic function in schizophrenia. Our work has provided insights into potential mechanisms that may contribute to disrupted cortical function in schizophrenia and has helped identify potential treatment targets for the disorder. The translational nature of this study made the clinical testing of the first of these targets feasible. Advances in systems neuroscience approaches in animals and humans make new types of translational research possible; however, our concern is that the current obstacles facing translational research funding and academia-industry collaborations threaten the future progress in this field.
TL;DR: The data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.
Abstract: Background: In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. Methods: DTI was performed in 78 healthy subjects aged 8–21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence. Results: In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age. Conclusions: These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.
TL;DR: People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia, suggesting the onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.
Abstract: Background: Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.
Methods: Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.
Results: At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to controls, first-episode patients showed widespread reductions in FA and increases in diffusivity. DTI indices in the UHR group were intermediate relative to those in the other 2 groups. Longitudinal analysis revealed a significant group by time interaction in the left frontal WM (P < .001). In this region, there was a progressive reduction in FA in UHR subjects who developed psychosis that was not evident in UHR subjects who did not make a transition.
Conclusions: People at UHR for psychosis show alterations in WM qualitatively similar to, but less severe than, those in patients with schizophrenia. The onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM.
TL;DR: A trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states are suggested and specific impairments in emotion recognition may be apparent in people at clinical high- risk for schizophrenia before the full expression of psychotic illness.
Abstract: Problems in the perception of emotional material, in particular deficits in the recognition of negative stimuli, have been demonstrated in schizophrenia including in first-episode samples. However, it is largely unknown if emotion recognition impairment is present in people with subthreshold psychotic symptoms. Here, we examined the capacity to recognize facially expressed emotion and affective prosody in 79 individuals at ultra high-risk for psychosis, 30 clinically stable individuals with first-episode schizophrenia assessed as outpatients during the early recovery phase of illness, and 30 unaffected healthy control subjects. We compared (1) scores for a combined fear-sadness aggregate index across face and voice modalities, (2) summary scores of specific emotions across modalities, and (3) scores for specific emotions for each sensory modality. Findings supported deficits in recognition of fear and sadness across both modalities for the clinical groups (the ultra high-risk and first-episode group) as compared with the healthy controls. Furthermore, planned contrasts indicated that compared with the healthy control subjects, both clinical groups had a significant deficit for fear and sadness recognition in faces and for anger recognition in voices. Specific impairments in emotion recognition may be apparent in people at clinical high-risk for schizophrenia before the full expression of psychotic illness. The results suggest a trait deficit and an involvement of the amygdala in the pathology of ultra high-risk states.
TL;DR: Evidence is provided for the role of negative cognition in the maintenance of paranoia, a role of central relevance, both to the design of psychological interventions and to the conceptualizations of psychosis.
Abstract: The role of negative cognition and effect in maintaining psychotic symptoms is increasingly recognized but has yet to be substantiated though longitudinal analysis. Based on an a priori theoretical model, we hypothesized that negative cognition and depressed mood play a direct causal role in maintaining paranoia in people with psychosis and that the effect of mood is mediated by negative cognition. We used data from the 301 patients in the Prevention of Relapse in Psychosis Trial of cognitive behavior therapy. They were recruited from consecutive Community Mental Health Team clients presenting with a recent relapse of psychosis. The teams were located in inner and outer London and the rural county of Norfolk, England. The study followed a longitudinal cohort design, with initial measures repeated at 3 and 12 months. Structural equation modeling was used to investigate the direction of effect between negative cognition, depressed mood, and paranoia. Overall fit was ambiguous in some analyses and confounding by unidentified variables cannot be ruled out. Nevertheless, the most plausible models were those incorporating pathways from negative cognition and depressed mood to paranoid symptoms: There was no evidence whatsoever for pathways in the reverse direction. The link between depressed mood and paranoia appeared to be mediated by negative cognition. Our hypotheses were thus corroborated. This study provides evidence for the role of negative cognition in the maintenance of paranoia, a role of central relevance, both to the design of psychological interventions and to the conceptualizations of psychosis.
TL;DR: In this paper, the authors explored the distribution of experiences at all levels of severity in populations and its genetic and nongenetic causes, and found that affective dysregulation, psychotic experiences, motivational impairments, and cognitive alterations have been shown to index risk for later onset of disorder, particularly if they tend to persist over time.
Abstract: In clinical practice, psychotic disorders naturally come as diagnosable ‘‘things,’’ categories, the carriers of which form a diagnostic boundary below which reside the healthy noncarriers who do not display the mental phenomena observed in patients. In research, however, the focus is on scientific exploration of the distribution of experiences at all levels of severity in populations and its genetic and nongenetic causes. Population research has shown high rates of psychotic experiences in people who are not readily diagnosable according to ICD/DSM/ RDC criteria—suggesting an ‘‘extended psychosis phenotype,’’ which shares demographic, etiological, familial, and psychopathological factors with clinical psychotic disorder. In fact, affective dysregulation, psychotic experiences, motivational impairments, and cognitive alterationsappeartobedistributed andcoexpressedtoadegree in nonill individuals and have been shown to index risk for later onset of disorder, particularly if they tend to persist over time. 1 (also, R. J. L & J. v. O., unpublished data,