当前期刊: Schizophrenia Bulletin Go to current issue    加入关注   
显示样式:        排序: 导出
我的关注
我的收藏
您暂时未登录!
登录
  • Emotion–Action–Fusion, Intrusive Thoughts, and Psychosis
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-16

    Corrigendum to “Emotion–Action–Fusion, Intrusive Thoughts, and Psychosis” by Anonymous. Schizophr Bull. 2019; doi:10.1093/schbul/sbz084.In the original publication of this article, the author’s name and contact details were made public, and have since been removed by the publisher. The author has requested that their authorship of this article be made anonymous.

    更新日期:2020-01-16
  • Research Domain Criteria: Controversial Paradigm
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-14
    Carpenter W, Jr.

    Schizophrenia Bulletin is very glad for the initiation of a cascade journal and welcome Schizophrenia Bulletin Open. Silvana Galderisi and Steve Marder represent the best of our field and will assure a critical role for communication. Responding to an invitation from the editors, the following is my first opportunity to contribute to SBOpen.

    更新日期:2020-01-14
  • Corrigendum to: Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies-PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-12

    Corrigendum to “Towards Precision Medicine in Psychosis: Benefits and Challenges of Multimodal Multicenter Studies—PSYSCAN: Translating Neuroimaging Findings From Research into Clinical Practice” by Tognin et al. Schizophr Bull. 2019; doi: 10.1093/schbul/sbz067.

    更新日期:2020-01-13
  • Assessing the Causal Effects of Human Serum Metabolites on 5 Major Psychiatric Disorders
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-10
    Yang J, Yan B, Zhao B, et al.

    Psychiatric disorders are the leading cause of disability worldwide while the pathogenesis remains unclear. Genome-wide association studies (GWASs) have made great achievements in detecting disease-related genetic variants. However, functional information on the underlying biological processes is often lacking. Current reports propose the use of metabolic traits as functional intermediate phenotypes (the so-called genetically determined metabotypes or GDMs) to reveal the biological mechanisms of genetics in human diseases. Here we conducted a two-sample Mendelian randomization analysis that uses GDMs to assess the causal effects of 486 human serum metabolites on 5 major psychiatric disorders, which respectively were schizophrenia (SCZ), major depression (MDD), bipolar disorder (BIP), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). Using genetic variants as proxies, our study has identified 137 metabolites linked to the risk of psychiatric disorders, including 2-methoxyacetaminophen sulfate, which affects SCZ (P= 1.7 × 10–5) and 1-docosahexaenoylglycerophosphocholine, which affects ADHD (P = 5.6 × 10–5). Fourteen significant metabolic pathways involved in the 5 psychiatric disorders assessed were also detected, such as glycine, serine, and threonine metabolism for SCZ (P = .0238), Aminoacyl-tRNA biosynthesis for both MDD (P =.0144) and ADHD (P =.0029). Our study provided novel insights into integrating metabolomics with genomics in order to understand the mechanisms underlying the pathogenesis of human diseases.

    更新日期:2020-01-10
  • Elevated Extracellular Free-Water in a Multicentric First-Episode Psychosis Sample, Decrease During the First 2 Years of Illness
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-09
    Bergé D, Mané A, Lesh T, et al.

    Recent diffusion imaging studies using free-water (FW) elimination have shown increased FW in gray matter (GM) and white matter (WM) in first-episode psychosis (FEP) and lower corrected fractional anisotropy (FAt) in WM in chronic schizophrenia. However, little is known about the longitudinal stability and clinical significance of these findings.To determine tissue-specific FW and FAt abnormalities in FEP, as part of a multicenter Spanish study, 132 FEP and 108 healthy controls (HC) were clinically characterized and underwent structural and diffusion-weighted MRI scanning. FEP subjects were classified as schizophrenia spectrum disorder (SSD) or non-SSD. Of these subjects, 45 FEP and 41 HC were longitudinally assessed and rescanned after 2 years. FA and FW tissue-specific measurements were cross-sectional and longitudinally compared between groups using voxel-wise analyses in the skeletonized WM and vertex-wise analyses in the GM surface.SSD and non-SSD subjects showed (a) higher baseline FW in temporal regions and in whole GM average (P.adj(SSD vs HC) = .003, P.adj(Non-SSD vs HC) = .040) and (b) lower baseline FAt in several WM tracts. SSD, but not non-SSD, showed (a) higher FW in several WM tracts and in whole WM (P.adj(SSD vs HC)= .049) and (b) a significant FW decrease over time in temporal cortical regions and in whole GM average (P.adj =.011). Increased extracellular FW in the brain is a reliable finding in FEP, and in SSD appears to decrease over the early course of the illness. FAt abnormalities are stable during the first years of psychosis.

    更新日期:2020-01-09
  • One-Year Stability of Frontoparietal Cognitive Control Network Connectivity in Recent Onset Schizophrenia: A Task-Related 3T fMRI Study
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-05
    Smucny J, Lesh T, Zarubin V, et al.

    Kraepelinian theory posits that schizophrenia (SZ) is a degenerative disorder that worsens throughout the lifespan. Behavioral studies of cognition have since challenged that viewpoint, particularly in the early phases of illness. Nonetheless, the extent to which cognition remains functionally stable during the early course of illness is unclear, particularly with regard to task-associated connectivity in cognition-related brain networks. In this study, we examined the 1-year stability of the frontoparietal control network during the AX-Continuous Performance Task (AX-CPT) from a new baseline sample of 153 participants scanned at 3T, of which 29 recent onset individuals with SZ and 42 healthy control (HC) participants had follow-up data available for analysis. Among individuals that had both baseline and follow-up data, reduced functional connectivity in SZ was observed between the dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex (SPC) during the high control (B cue) condition. Furthermore, this deficit was stable over time, as no significant time × diagnosis interaction or effects of time were observed and intraclass correlation coefficients were greater than 0.6 in HCs and SZ. Previous 1.5T findings showing stable deficits with no evidence of degeneration in performance or DLPFC activation in an independent SZ sample were replicated. Overall, these results suggest that the neuronal circuitry supporting cognitive control is stably impaired during the early course of illness in SZ across multiple levels of analysis with no evidence of functional decline.

    更新日期:2020-01-07
  • Suppression of Parvalbumin Interneuron Activity in the Prefrontal Cortex Recapitulates Features of Impaired Excitatory/Inhibitory Balance and Sensory Processing in Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-05
    Toader O, von Heimendahl M, Schuelert N, et al.

    Accumulating evidence supports parvalbumin expressing inhibitory interneuron (PV IN) dysfunction in the prefrontal cortex as a cause for cognitive impairment associated with schizophrenia (CIAS). PV IN decreased activity is suggested to be the culprit for many of the EEG deficits measured in patients, which correlate with deficits in working memory (WM), cognitive flexibility and attention. In the last few decades, CIAS has been recognized as a heavy burden on the quality of life of patients with schizophrenia, but little progress has been made in finding new treatment options. An important limiting factor in this process is the lack of adequate preclinical models and an incomplete understanding of the circuits engaged in cognition. In this study, we back-translated an auditory stimulation protocol regularly used in human EEG studies into mice and combined it with optogenetics to investigate the role of prefrontal cortex PV INs in excitatory/inhibitory balance and cortical processing. We also assessed spatial WM and reversal learning (RL) during inhibition of prefrontal cortex PV INs. We found significant impairments in trial-to-trial reliability, increased basal network activity and increased oscillation power at 20–60 Hz, and a decreased signal-to-noise ratio, but no significant impairments in behavior. These changes reflect some but not all neurophysiological deficits seen in patients with schizophrenia, suggesting that other neuronal populations and possibly brain regions are involved as well. Our work supports and expands previous findings and highlights the versatility of an approach that combines innovative technologies with back-translated tools used in humans.

    更新日期:2020-01-07
  • Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-07
    Moon A, Brydges N, Wilkinson L, et al.

    CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c+/−) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c+/− rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c+/− rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c+/− rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis.

    更新日期:2020-01-07
  • Morphological Profiling of Schizophrenia: Cluster Analysis of MRI-Based Cortical Thickness Data
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-04
    Pan Y, Pu W, Chen X, et al.

    The diagnosis of schizophrenia is thought to embrace several distinct subgroups. The manifold entities in a single clinical patient group increase the variance of biological measures, deflate the group-level estimates of causal factors, and mask the presence of treatment effects. However, reliable neurobiological boundaries to differentiate these subgroups remain elusive. Since cortical thinning is a well-established feature in schizophrenia, we investigated if individuals (patients and healthy controls) with similar patterns of regional cortical thickness form naturally occurring morphological subtypes. K-means algorithm clustering was applied to regional cortical thickness values obtained from 256 structural MRI scans (179 patients with schizophrenia and 77 healthy controls [HCs]). GAP statistics revealed three clusters with distinct regional thickness patterns. The specific patterns of cortical thinning, clinical characteristics, and cognitive function of each clustered subgroup were assessed. The three clusters based on thickness patterns comprised of a morphologically impoverished subgroup (25% patients, 1% HCs), an intermediate subgroup (47% patients, 46% HCs), and an intact subgroup (28% patients, 53% HCs). The differences of clinical features among three clusters pertained to age-of-onset, N-back performance, duration exposure to treatment, total burden of positive symptoms, and severity of delusions. Particularly, the morphologically impoverished group had deficits in N-back performance and less severe positive symptom burden. The data-driven neuroimaging approach illustrates the occurrence of morphologically separable subgroups in schizophrenia, with distinct clinical characteristics. We infer that the anatomical heterogeneity of schizophrenia arises from both pathological deviance and physiological variance. We advocate using MRI-guided stratification for clinical trials as well as case–control investigations in schizophrenia.

    更新日期:2020-01-06
  • Differences in Functional Connectivity Networks Related to the Midbrain Dopaminergic System-Related Area in Various Psychiatric Disorders
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-05
    Nakamura Y, Okada N, Koshiyama D, et al.

    ObjectiveDisruptions in the dopamine system have been observed in psychiatric disorders. Since dopamine is mainly produced in the ventral tegmental area (VTA), elucidating the differences in the VTA neural network across psychiatric disorders would facilitate a greater understanding of the pathophysiological mechanisms underlying these disorders. However, no study has compared VTA-seed-based functional connectivity across psychiatric disorders. Therefore, we conducted a resting-state functional magnetic resonance imaging (rs-fMRI) study to perform a seed-based fMRI analysis, using the VTA as a seed. MethodsWe included participants with major depressive disorder (MDD; n = 45), schizophrenia (n = 32), and bipolar disorder (BPD; n = 30), along with healthy control participants (n = 46) who were matched for age, gender, and handedness. ResultsThe results showed that patients with MDD and BPD had altered VTA-related connectivity in the superior frontal gyrus, frontal pole regions, hippocampus, cerebellum, and posterior cingulate cortex. Some of these differences in connectivity were also found between affective disorders and schizophrenia; however, there were no differences between the schizophrenia and control groups. Connectivity between the VTA and the hippocampus was correlated with positive symptoms in the schizophrenia group. The connectivity was not associated with medication dose, and the results remained significant after controlling for dose. ConclusionsThe results suggest that altered brain functional connectivity related to VTA networks could be associated with the distinctive pathophysiologies of psychiatric disorders, especially affective disorders.

    更新日期:2020-01-06
  • Involuntary Detention and Treatment: Are We Edging Toward a “Paradigm Shift”?
    Schizophr. Bull. (IF 7.289) Pub Date : 2020-01-05
    Szmukler G.

    Recent challenges to conventional mental health laws concerning involuntary detention and treatment of persons with a mental disorder have led to proposals, or indeed an insistence, that fundamental reform is necessary. A key theme has been the need to eliminate unfair discrimination against people with a mental disorder because their human rights are not respected on an equal basis with other people. Some proposals depart radically from conventional assumptions concerning the justification of involuntary detention and treatment. One is a “fusion law,” a generic law applying to all persons lacking the ability to make a treatment decision, whether resulting from a “mental” or “physical” illness. An authoritative interpretation of the UN Convention on the Rights of Persons with Disabilities (2006) goes so far as to maintain that involuntary interventions are a violation of the Convention.

    更新日期:2020-01-06
  • Resolving Repression
    Schizophr. Bull. (IF 7.289) Pub Date : 2018-07-03
    .

    One of the most difficult parts about having schizophrenia are the physiological effects it has had on my body. The illness caused me to become paranoid and stressed to the point where I could only sleep 2 to 3 hours per night. I had psychosis and neurosis and I had lost all my friends and I was out of touch with my family. The combination of stress and sleeplessness caused the male parts of my body to become dysfunctional. As a natural de-stressing mechanism I began having unbridled erections. It was extremely embarrassing and difficult to deal with. On top of this, it was during my first episode of schizophrenia. I was too much inside my own mind and I developed a number of misconceptions regarding the reasons I had all these erections.

    更新日期:2020-01-04
  • Using Machine Learning and Structural Neuroimaging to Detect First Episode Psychosis: Reconsidering the Evidence
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-02-27
    Vieira S, Gong Q, Pinaya W, et al.

    Despite the high level of interest in the use of machine learning (ML) and neuroimaging to detect psychosis at the individual level, the reliability of the findings is unclear due to potential methodological issues that may have inflated the existing literature. This study aimed to elucidate the extent to which the application of ML to neuroanatomical data allows detection of first episode psychosis (FEP), while putting in place methodological precautions to avoid overoptimistic results. We tested both traditional ML and an emerging approach known as deep learning (DL) using 3 feature sets of interest: (1) surface-based regional volumes and cortical thickness, (2) voxel-based gray matter volume (GMV) and (3) voxel-based cortical thickness (VBCT). To assess the reliability of the findings, we repeated all analyses in 5 independent datasets, totaling 956 participants (514 FEP and 444 within-site matched controls). The performance was assessed via nested cross-validation (CV) and cross-site CV. Accuracies ranged from 50% to 70% for surfaced-based features; from 50% to 63% for GMV; and from 51% to 68% for VBCT. The best accuracies (70%) were achieved when DL was applied to surface-based features; however, these models generalized poorly to other sites. Findings from this study suggest that, when methodological precautions are adopted to avoid overoptimistic results, detection of individuals in the early stages of psychosis is more challenging than originally thought. In light of this, we argue that the current evidence for the diagnostic value of ML and structural neuroimaging should be reconsidered toward a more cautious interpretation.

    更新日期:2020-01-04
  • Latent Profiles of Cognitive Control, Episodic Memory, and Visual Perception Across Psychiatric Disorders Reveal a Dimensional Structure
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-04-07
    Smucny J, Iosif A, Eaton N, et al.

    Although meta-analyses suggest that schizophrenia (SZ) is associated with a more severe neurocognitive phenotype than mood disorders such as bipolar disorder, considerable between-subject heterogeneity exists in the phenotypic presentation of these deficits across mental illnesses. Indeed, it is unclear whether the processes that underlie cognitive dysfunction in these disorders are unique to each disease or represent a common neurobiological process that varies in severity. Here we used latent profile analysis (LPA) across 3 distinct cognitive domains (cognitive control, episodic memory, and visual integration; using data from the CNTRACS consortium) to identify distinct profiles of patients across psychotic illnesses. LPA was performed on a sample of 223 psychosis patients (59 with Type I bipolar disorder, 88 with SZ, and 76 with schizoaffective disorder). Seventy-three healthy control participants were included for comparison but were not included in sample LPA. Three latent profiles (“Low,” “Moderate,” and “High” ability) were identified as the underlying covariance across the 3 domains. The 3-profile solution provided highly similar fit to a single continuous factor extracted by confirmatory factor analysis, supporting a unidimensional structure. Diagnostic ratios did not significantly differ between profiles, suggesting that these profiles cross diagnostic boundaries (an exception being the Low ability profile, which had only one bipolar patient). Profile membership predicted Brief Psychiatric Rating Scale and Young Mania Rating Scale symptom severity as well as everyday communication skills independent of diagnosis. Biological, clinical and methodological implications of these findings are discussed.

    更新日期:2020-01-04
  • Impaired Subcortical Detection of Auditory Changes in Schizophrenia but Not in Major Depression
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-04-11
    Gaebler A, Zweerings J, Koten J, Jr, et al.

    The mismatch negativity is a cortical response to auditory changes and its reduction is a consistent finding in schizophrenia. Recent evidence revealed that the human brain detects auditory changes already at subcortical stages of the auditory pathway. This finding, however, raises the question where in the auditory hierarchy the schizophrenic deficit first evolves and whether the well-known cortical deficit may be a consequence of dysfunction at lower hierarchical levels. Finally, it should be resolved whether mismatch profiles differ between schizophrenia and affective disorders which exhibit auditory processing deficits as well. We used functional magnetic resonance imaging to assess auditory mismatch processing in 29 patients with schizophrenia, 27 patients with major depression, and 31 healthy control subjects. Analysis included whole-brain activation, region of interest, path and connectivity analysis. In schizophrenia, mismatch deficits emerged at all stages of the auditory pathway including the inferior colliculus, thalamus, auditory, and prefrontal cortex. In depression, deficits were observed in the prefrontal cortex only. Path analysis revealed that activation deficits propagated from subcortical to cortical nodes in a feed-forward mechanism. Finally, both patient groups exhibited reduced connectivity along this processing stream. Auditory mismatch impairments in schizophrenia already manifest at the subcortical level. Moreover, subcortical deficits contribute to the well-known cortical deficits and show specificity for schizophrenia. In contrast, depression is associated with cortical dysfunction only. Hence, schizophrenia and major depression exhibit different neural profiles of sensory processing deficits. Our findings add to a converging body of evidence for brainstem and thalamic dysfunction as a hallmark of schizophrenia.

    更新日期:2020-01-04
  • The Impact of Childhood Adversity on Cognitive Development in Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-03
    Wells R, Jacomb I, Swaminathan V, et al.

    Childhood adversity, such as physical, sexual, and verbal abuse, as well as neglect and family conflict, is a risk factor for schizophrenia. Such adversity can lead to disruptions of cognitive function during development, undermining intellectual capabilities and academic achievement. Schizophrenia is a neurodevelopmental disorder that is associated with cognitive impairments that may become evident during childhood. The Australian Schizophrenia Research Bank database comprises a large community cohort (N = 1169) in which we previously identified 3 distinct cognitive groups among people with schizophrenia: (1) Compromised, current, and estimated premorbid cognitive impairment; (2) Deteriorated, substantial decline from estimated premorbid function; and (3) Preserved, performing in the normal cognitive range without decline. The compromised group displayed the worst functional and symptom outcomes. Here, we extend our previous work by assessing the relationship among these categories of cognitive abilities and reported childhood adversity in 836 patients and healthy controls. Exploratory factor analysis of the Childhood Adversity Questionnaire revealed 3 factors (lack of parental involvement; overt abuse; family breakdown and hardship). People with schizophrenia reported significantly more childhood adversity than healthy controls on all items and factors. People with schizophrenia in the compromised group reported significantly more lack of parental involvement and family breakdown and hardship and lower socioeconomic status than those in the deteriorated group. The cognitive groups were not related to family history of psychosis. These findings identify specific social and family factors that impact cognition, highlighting the important role of these factors in the development of cognitive and functional abilities in schizophrenia.

    更新日期:2020-01-04
  • Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder: A Clinical Study
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-03
    Nilsson M, Arnfred S, Carlsson J, et al.

    ObjectiveThere are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum. MethodsAll participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN). ResultsA total of 51 participants (As/ASD, n = 22; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups. ConclusionOur results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.

    更新日期:2020-01-04
  • Effectiveness of Family Intervention for Preventing Relapse in First-Episode Psychosis Until 24 Months of Follow-up: A Systematic Review With Meta-analysis of Randomized Controlled Trials
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-03
    Camacho-Gomez M, Castellvi P.

    BackgroundRelapse risk during the early years of first-episode psychosis (FEP) considerably increases the risk of chronicity. The effectiveness of family intervention for psychosis (FIp) for preventing relapse after FEP remains unknown. We assessed the effectiveness of FIp until 24 months of follow-up for preventing relapse and other relapse-related outcomes in patients following FEP. MethodsWe searched the Cochrane, PubMed, PsycINFO, and ProQuest databases in June 2018. A systematic review with meta-analysis of randomized controlled trials (RCTs), sensitivity analyses, and publication bias were performed, comparing to treatment as usual (TAU) or TAU plus other psychosocial interventions. Outcomes assessed were relapse rates, duration of hospitalization, psychotic symptoms, and functionality. Risk ratios (RRs) and (standardized) mean differences (SMD; MD) were calculated. ResultsOf the 2109 records retrieved, 14 (11 RCTs) were included. Pooled results showed that FIp was effective for preventing relapse (RR = 0.42; 95% CI = 0.29 to 0.61) compared to TAU and/or other psychosocial interventions. It also proved effective when compared to TAU alone (RR = 0.36) and TAU plus other psychosocial interventions (RR = 0.48). FIp showed benefits in reducing duration of hospitalization (TAU, MD = −3.31; other interventions, MD = −4.57) and psychotic symptoms (TAU, SMD = −0.68), and increased functionality (TAU, SMD = 1.36; other interventions, SMD = 1.41). ConclusionsThese findings suggest that FIp is effective for reducing relapse rates, duration of hospitalization, and psychotic symptoms, and for increasing functionality in FEP patients up to 24 months. The study’s main limitations were the inclusion of published research only; authors were not contacted for missing/additional data; and high heterogeneity regarding relapse definition was observed.

    更新日期:2020-01-04
  • Functional Brain Networks Underlying Evidence Integration and Delusions in Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-03
    Lavigne K, Menon M, Woodward T.

    Integrating evidence that contradicts a belief is a fundamental aspect of belief revision and is closely linked to delusions in schizophrenia. In a previous functional magnetic resonance imaging (fMRI) study on healthy individuals, we identified functional brain networks underlying evidence integration as visual attention network (VsAN; dorsal anterior cingulate cortex, insula, occipital regions), default-mode network (DMN), and cognitive evaluation network (CEN; orbitofrontal cortex, inferior frontal gyrus, parietal cortex). In the current clinical fMRI study, we compared network-based activity during evidence integration between healthy controls (n = 41), nondelusional (n = 37), and delusional (n = 33) patients with schizophrenia, and related this activity to cognitive processing involved in evidence integration measured outside the scanner. Task-induced coordinated activation was measured using group-constrained principal component analysis for fMRI. Increased VsAN activation, reduced DMN deactivation, and reduced CEN activation were observed for schizophrenia, with this pattern being most pronounced for the delusional group. Importantly, poor evidence integration comprehensively measured outside the scanner was significantly associated with increased VsAN activation and reduced DMN deactivation when processing confirmatory evidence, and with reduced CEN activation when processing disconfirmatory evidence. This is the first comprehensive study of the functional brain networks associated with evidence integration in schizophrenia and highlights how an imbalance of functional brain networks responding to confirmatory and disconfirmatory evidence may underlie delusions in schizophrenia.

    更新日期:2020-01-04
  • Exacerbation of Psychosis During the Perimenstrual Phase of the Menstrual Cycle: Systematic Review and Meta-analysis
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-09
    Reilly T, Sagnay de la Bastida V, Joyce D, et al.

    Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders in relation to the menstrual cycle. We extracted exacerbation measure, definition of menstrual cycle phase, and measurement of menstrual cycle phase. Standard incidence ratios were calculated for the perimenstrual phase based on the observed admissions during this phase divided by the expected number of admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Nineteen studies, comprising 1193 participants were eligible for inclusion. Eleven studies examined psychiatric admission rates, 5 examined symptoms scores, 2 examined self-reported exacerbation, and 1 examined both admission rates and symptom scores. A random effects model demonstrated the rate of admissions during the perimenstrual phase was 1.48 times higher than expected (95% CI: 1.31–1.67), with no significant heterogeneity detected. Four of six symptom score studies reported perimenstrual worsening, but lack of consistency in timepoints precluded meta-analysis. Two studies examining self-reported menstrual exacerbations reported prevalences ranging from 20% to 32.4%. Psychiatric admission rates are significantly higher than expected during the perimenstrual phase. There is some evidence that a worsening of psychotic symptoms also occurs during this phase, but further research with more precise measurement of the menstrual cycle and symptomatology is required.

    更新日期:2020-01-04
  • Abnormal Functional Relationship of Sensorimotor Network With Neurotransmitter-Related Nuclei via Subcortical-Cortical Loops in Manic and Depressive Phases of Bipolar Disorder
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-31
    Martino M, Magioncalda P, Conio B, et al.

    ObjectiveManic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. MethodIn this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. Results(1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. ConclusionsThese findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations.

    更新日期:2020-01-04
  • A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-21
    Lizano P, Bannai D, Lutz O, et al.

    BackgroundSchizophrenia (SZ) and bipolar disorder (BD) are characterized by reductions in gray matter and white matter. Limitations in brain imaging have led researchers to use optical coherence tomography (OCT) to explore retinal imaging biomarkers of brain pathology. We examine the retinal layers that may be associated with SZ or BD. MethodsArticles identified using PubMed, Web of Science, Cochrane Database. Twelve studies met inclusion for acutely/chronically ill patients. We used fixed or random effects meta-analysis for probands (SZ and BD), SZ or BD eyes vs healthy control (HC) eyes. We adjusted for sources of bias, cross-validated results, and report standardized mean differences (SMD). Statistical analysis performed using meta package in R. ResultsData from 820 proband eyes (SZ = 541, BD = 279) and 904 HC eyes were suitable for meta-analysis. The peripapillary retinal nerve fiber layer (RNFL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 12, SMD = −0.74, −0.51, −1.06, respectively). RNFL thinning was greatest in the nasal, temporal, and superior regions. The combined peripapillary ganglion cell layer and inner plexiform layer (GCL-IPL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 4, SMD = −0.39, −0.44, −0.28, respectively). No statistically significant differences were identified in other retinal or choroidal regions. Clinical variables were unrelated to the RNFL or GCL-IPL thickness by meta-regression. ConclusionThe observed retinal layer thinning is consistent with the classic gray- and white-matter atrophy observed on neuroimaging in SZ and BD patients. OCT may be a useful biomarker tool in studying the neurobiology of psychosis.

    更新日期:2020-01-04
  • Intrinsic Connectivity of the Globus Pallidus: An Uncharted Marker of Functional Prognosis in People With First-Episode Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-31
    Tarcijonas G, Foran W, Haas G, et al.

    There is growing evidence suggesting that abnormalities in cortical-basal ganglia circuitry may play a significant role in determining outcomes in schizophrenia. The globus pallidus (GP), a critical structure within this circuitry, unique in its role as a mediator of competing inputs through the striatum, has not been well characterized in schizophrenia. The following study examined functional interactions of the GP in individuals with first-episode schizophrenia (FES). To probe the large-scale intrinsic connectivity of the GP, resting-state fMRI scans were obtained from patients with FES and sex and age-matched healthy controls. Participants with FES were also evaluated after 6 months via the Strauss–Carpenter Outcomes Scale to assess overall functional trajectory. The GP was parcellated to generate seeds within its substructures, and connectivity maps were generated. Our FES cohort showed significantly lower functional connectivity between the left GP interna and a network of regions including the dorsolateral prefrontal cortex, caudate, and cerebellum at baseline. In addition, FES participants with lower overall scores of functioning at 6 months showed significantly decreased connectivity between the GP interna and the dorsal anterior cingulate and bilateral insula, all regions important for motivational salience. These results provide novel evidence for unique abnormalities in functional interactions of the GP with key prefrontal cortical regions in FES. Our findings also suggest that reduced prefrontal-pallidal connectivity may serve as a predictor of early functional outcome.

    更新日期:2020-01-04
  • Assessing Reality Testing in Mice Through Dopamine-Dependent Associatively Evoked Processing of Absent Gustatory Stimuli
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-05-31
    Fry B, Russell N, Gifford R, et al.

    Impairments in reality testing are core features of numerous neuropsychiatric conditions. However, relatively few animal models have been developed to assess this critical facet of neuropsychiatric illness, thus impeding our understanding of the underlying central systems and circuits. Using mice in which dominant-negative Disrupted-in-Schizophrenia-1 is expressed throughout central nervous system circuitry (DN-DISC1-PrP), the capacity for an auditory conditioned stimulus (CS) to evoke perceptual processing of an absent sucrose solution was examined. At test, during CS presentations, DN-DISC1-PrP mice consumed more water and displayed a licking profile that is more typically revealed while ingesting a sweet-tasting solution. DN-DISC1-PrP mice also displayed greater c-fos expression in the insular (gustatory) cortex when consuming water in the presence of the CS. This capacity for the CS to more readily substitute for the taste features of the absent sucrose solution in DN-DISC1-PrP mice was attenuated following systemic treatment with the antipsychotic haloperidol. Conversely, social isolation during adolescence promoted the manifestation of these effects. These results provide strong validation for using associative learning procedures to examine dopamine-mediated reality testing associated with insular cortex activation.

    更新日期:2020-01-04
  • Multimodal Magnetic Resonance Imaging Data Fusion Reveals Distinct Patterns of Abnormal Brain Structure and Function in Catatonia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-06-08
    Hirjak D, Rashidi M, Kubera K, et al.

    Catatonia is a nosologically unspecific syndrome, which subsumes a plethora of mostly complex affective, motor, and behavioral phenomena. Although catatonia frequently occurs in schizophrenia spectrum disorders (SSD), specific patterns of abnormal brain structure and function underlying catatonia are unclear at present. Here, we used a multivariate data fusion technique for multimodal magnetic resonance imaging (MRI) data to investigate patterns of aberrant intrinsic neural activity (INA) and gray matter volume (GMV) in SSD patients with and without catatonia. Resting-state functional MRI and structural MRI data were collected from 87 right-handed SSD patients. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). A multivariate analysis approach was used to examine co-altered patterns of INA and GMV. Following a categorical approach, we found predominantly frontothalamic and corticostriatal abnormalities in SSD patients with catatonia (NCRS total score ≥ 3; n = 24) when compared to SSD patients without catatonia (NCRS total score = 0; n = 22) matched for age, gender, education, and medication. Corticostriatal network was associated with NCRS affective scores. Following a dimensional approach, 33 SSD patients with catatonia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision were identified. NCRS behavioral scores were associated with a joint structural and functional system that predominantly included cerebellar and prefrontal/cortical motor regions. NCRS affective scores were associated with frontoparietal INA. This study provides novel neuromechanistic insights into catatonia in SSD suggesting co-altered structure/function-interactions in neural systems subserving coordinated visuospatial functions and motor behavior.

    更新日期:2020-01-04
  • Societal Costs of Schizophrenia in Denmark: A Nationwide Matched Controlled Study of Patients and Spouses Before and After Initial Diagnosis
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-06-12
    Hastrup L, Simonsen E, Ibsen R, et al.

    BackgroundInformation on welfare cost of patients with schizophrenia and spouses is limited. AimThe main aim of this study to investigate factual societal mean annual costs per individual during 5 years before and after the initial diagnosis of schizophrenia. MethodA register-based cohort study of 12 227 patients with incident schizophrenia (International Classification of Diseases, Tenth Revision F20-F20.99) with spouses and 48 907 matched controls in Denmark during 2002–2016. ResultsThe total annual costs of health care and lost productivity were Euro 43 561 higher for patients with schizophrenia and health care costs and costs of lost productivity were increased during 5 years before the initial diagnosis. The total annual direct health care and indirect costs of lost productivity were Euro 21 888 higher for spouses to patients with schizophrenia than spouses of individuals with no diagnosis of schizophrenia. Also before initial diagnosis, health care costs and lost productivity were increased among spouses of patients with schizophrenia. ConclusionPatients with schizophrenia differed from the general population with respect to all included costs. The study documented a significant burden on spouses. The excess health care costs of schizophrenia are further increased by psychiatric and somatic comorbidity, and the societal costs are 4–10 times higher than chronic neurological disorders such as epilepsy and multiple sclerosis. Early onset of schizophrenia implies that patients are affected before finishing school and before entrance to labor market. Cost savings could be achieved by investments in preventive interventions reaching young people’s needs; in initiatives to reduce hospital admissions caused by medication side effects, substance misuse, and lifestyle factors; and in occupational training.

    更新日期:2020-01-04
  • Morbidity and Mortality in the Children and Young Adult Offspring of Parents With Schizophrenia or Affective Disorders—A Nationwide Register-Based Cohort Study in 2 Million Individuals
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-06-08
    Ranning A, Benros M, Thorup A, et al.

    BackgroundThe offspring of parents with severe mental illness (SMI) are at higher risk of mortality and of developing certain somatic diseases. However, across the full spectrum of somatic illness, there remains a gap in knowledge regarding morbidity. MethodsWe conducted a register-based nationwide cohort study of all 2 000 694 individuals born in Denmark between 1982 and 2012. Maximum age of offspring at follow-up was 30 years. Information on parents’ psychiatric diagnoses of schizophrenia, bipolar disorder, and unipolar depression was retrieved from the Psychiatric Central Register. We estimated incidence rate ratio (IRR), cumulative incidence percentage and mortality rate ratio of first hospital contact for a broad spectrum of somatic illnesses according to the International Statistical Classification of Diseases and Related Health Problems. Analyses were adjusted for important confounders. ResultsOffspring of individuals with SMI had higher risk of somatic hospital contacts IRR: 1.17 (95% CI: 1.16–1.18) with maternal depression being associated with the highest IRR (1.22, 95% CI: 1.20–1.24). Offspring of parents with SMI had higher risk within most broad diagnostic categories with highest IRRs for unclassified somatic diagnoses, infections and endocrine diseases ranging from 1.27 (95% CI: 1.25–1.28) to 1.26 (95% CI: 1.23–1.29) (all P < .0001). Morbidity was particularly increased in children aged 0–7 years. The mortality rate ratio associated with parental SMI was 1.31 (95% CI: 1.21–1.41) with excess mortality mainly due to unnatural causes. ConclusionOur findings indicate that offspring of parents with SMI experienced increased mortality and somatic morbidity warranting heightened vigilance and support for this population.

    更新日期:2020-01-04
  • Data From the World Health Organization’s Pharmacovigilance Database Supports the Prominent Role of Pneumonia in Mortality Associated With Clozapine Adverse Drug Reactions
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-09-18
    De Leon J, Sanz E, De las Cuevas C.

    agranulocytosis/constipationcomplicationssudden deathcardiac/drug labeling/infection/mortalitydrug effects/myocarditischemically induced/seizures/syncope

    更新日期:2020-01-04
  • Retinal Changes in Schizophrenia: A Systematic Review and Meta-analysis Based on Individual Participant Data
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-10-18
    Kazakos C, Karageorgiou V.

    BackgroundRetinal assessment has indicated the presence of neuronal loss in neurodegenerative disorders, but its role in schizophrenia remains unclear. We sought to synthesize the available evidence considering 3 noninvasive modalities: optical coherence tomography, electroretinography, and fundus photography, and examine their diagnostic accuracy based on unpublished individual participant data, when provided by the primary study authors. MethodsWe searched MEDLINE, SCOPUS, clinicaltrials.gov, PSYNDEX, Cochrane Controlled Register of Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and Google Scholar, up to October 30, 2018. Authors were contacted and invited to share anonymized participant-level data. Aggregate data were pooled using random effects models. Diagnostic accuracy meta-analysis was based on multiple cutoffs logistic generalized linear mixed modeling. This study was registered with PROSPERO, number CRD42018109344. ResultsPooled mean differences of peripapillary retinal nerve fiber layer thickness in micrometer between 694 eyes of 432 schizophrenia patients and 609 eyes of 358 controls, from 11 case-control studies, with corresponding 95% confidence intervals (CIs) by quadrant were the following: −4.55, 95% CI: −8.28, −0.82 (superior); −6.25, 95% CI: −9.46, −3.04 (inferior); −3.18, 95% CI: −5.04, −1.31 (nasal); and −2.7, 95% CI: −4.35, −1.04 (temporal). Diagnostic accuracy, based on 4 studies, was fair to poor, unaffected by age and sex; macular area measurements performed slightly better. ConclusionThe notion of structural and functional changes in retinal integrity of patients with schizophrenia is supported with current evidence, but diagnostic accuracy is limited. The potential prognostic, theranostic, and preventive role of retinal evaluation remains to be examined.

    更新日期:2020-01-04
  • Map2k7 Haploinsufficiency Induces Brain Imaging Endophenotypes and Behavioral Phenotypes Relevant to Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-06-20
    Openshaw R, Thomson D, Thompson R, et al.

    c-Jun N-terminal kinase (JNK) signaling contributes to functional plasticity in the brain and cognition. Accumulating evidence implicates a role for MAP kinase kinase 7 (MAP2K7), a JNK activator encoded by the Map2k7 gene, and other JNK pathway components in schizophrenia (ScZ). Mice haploinsufficient for Map2k7 (Map2k7+/− mice) display ScZ-relevant cognitive deficits, although the mechanisms are unclear. Here we show that Map2k7+/− mice display translationally relevant alterations in brain function, including hippocampal and mesolimbic system hypermetabolism with a contrasting prefrontal cortex (PFC) hypometabolism, reminiscent of patients with ScZ. In addition Map2k7+/− mice show alterations in functional brain network connectivity paralleling those reported in early ScZ, including PFC and hippocampal hyperconnectivity and compromised mesolimbic system functional connectivity. We also show that although the cerebral metabolic response to ketamine is preserved, the response to dextroamphetamine (d-amphetamine) is significantly attenuated in Map2k7+/− mice, supporting monoamine neurotransmitter system dysfunction but not glutamate/NMDA receptor (NMDA-R) dysfunction as a consequence of Map2k7 haploinsufficiency. These effects are mirrored behaviorally with an attenuated impact of d-amphetamine on sensorimotor gating and locomotion, whereas similar deficits produced by ketamine are preserved, in Map2k7+/− mice. In addition, Map2k7+/− mice show a basal hyperactivity and sensorimotor gating deficit. Overall, these data suggest that Map2k7 modifies brain and monoamine neurotransmitter system function in a manner relevant to the positive and cognitive symptoms of ScZ.

    更新日期:2020-01-04
  • Service Use Following First-Episode Schizophrenia Among Commercially Insured Youth
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-07-11
    Gilmer T, van der Ven E, Susser E, et al.

    ObjectiveTo investigate patterns of mental health service and antipsychotic use following a first-episode schizophrenia (FES) and to examine the role of the treatment setting in which individuals are first diagnosed. MethodAnalysis of de-identified administrative claims data from the OptumLabs Data Warehouse was used to identify 1450 privately insured youth and young adults aged 14 through 30 with FES from January 1, 2011 through December 31, 2015. Regression analysis was used to estimate the use of mental health services during the year following FES, by type of service and by site of index diagnosis. ResultsIn the year following FES, 79.7% of youth received outpatient mental health services and 35.8% filled a prescription for antipsychotic medication. Among service users, mean outpatient visits were 15.9 and mean antipsychotic fills were 8.3. Youth who received an index diagnosis of FES in an inpatient setting were more likely to fill an antipsychotic medication than youth with FES in other settings. Youth who received an index diagnosis of FES during a specialty mental health outpatient visit had greater use of outpatient mental health than youth who received their diagnosis during a primary care visit. ConclusionsDespite evidence-based guidelines supporting outpatient psychosocial care and antipsychotic treatment for FES, one-fifth of this cohort did not use outpatient services and the majority did not fill any prescriptions for antipsychotic medications during the year following FES. Our findings provide renewed urgency to ongoing efforts to accelerate early identification and care coordination for youth with FES.

    更新日期:2020-01-04
  • What Causes the Onset of Psychosis in Individuals at Clinical High Risk? A Meta-analysis of Risk and Protective Factors
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-06-20
    Oliver D, Reilly T, Baccaredda Boy O, et al.

    Twenty percent of individuals at clinical high risk for psychosis (CHR-P) develop the disorder within 2 years. Extensive research has explored the factors that differentiate those who develop psychosis and those who do not, but the results are conflicting.The current systematic review and meta-analysis comprehensively addresses the consistency and magnitude of evidence for non-purely genetic risk and protective factors associated with the risk of developing psychosis in CHR-P individuals. Random effects meta-analyses, standardized mean difference (SMD) and odds ratio (OR) were used, in combination with an established stratification of evidence that assesses the association of each factor and the onset of psychotic disorders (from class I, convincing evidence to class IV weak evidence), while controlling for several types of biases.A total of 128 original controlled studies relating to 26 factors were retrieved. No factors showed class I-convincing evidence. Two further factors were associated with class II-highly suggestive evidence: attenuated positive psychotic symptoms (SMD = 0.348, 95% CI: 0.280, 0.415) and global functioning (SMD = −0.291, 95% CI: −0.370, −0.211). There was class III-suggestive evidence for negative psychotic symptoms (SMD = 0.393, 95% CI: 0.317, 0.469). There was either class IV-weak or no evidence for all other factors.Our findings suggest that despite the large number of putative risk factors investigated in the literature, only attenuated positive psychotic symptoms, global functioning, and negative psychotic symptoms show suggestive evidence or greater for association with transition to psychosis. The current findings may inform the refinement of clinical prediction models and precision medicine in this field.

    更新日期:2020-01-04
  • Issues in the Aggregation of Data on Retinal Structure and Function in Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-20
    Silverstein S.

    It may seem to some readers that the retina is far removed from what is important about schizophrenia. However, the retina is part of the central nervous system (CNS), and published reports continue to indicate that schizophrenia is associated with thinning of retinal layers (using optical coherence tomography; OCT), reduced retinal cell responses (using electroretinography; ERG), and, in some cases, widened retinal venules as measured with fundus photography.1,2 These data may both contribute to a better understanding of the multiple forms of subjective and laboratory-based visual processing changes observed in people with schizophrenia,3 and serve as a window into brain function in the syndrome. Kazakos and Karageorgiou4 have provided a valuable contribution to this growing field by providing an up-to-date meta-analysis of this literature, and the first meta-analysis based on individual participant data.

    更新日期:2020-01-04
  • Using Machine Learning in Psychiatry: The Need to Establish a Framework That Nurtures Trustworthiness
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-01
    Chandler C, Foltz P, Elvevåg B.

    The rapid embracing of artificial intelligence in psychiatry has a flavor of being the current “wild west”; a multidisciplinary approach that is very technical and complex, yet seems to produce findings that resonate. These studies are hard to review as the methods are often opaque and it is tricky to find the suitable combination of reviewers. This issue will only get more complex in the absence of a rigorous framework to evaluate such studies and thus nurture trustworthiness. Therefore, our paper discusses the urgency of the field to develop a framework with which to evaluate the complex methodology such that the process is done honestly, fairly, scientifically, and accurately. However, evaluation is a complicated process and so we focus on three issues, namely explainability, transparency, and generalizability, that are critical for establishing the viability of using artificial intelligence in psychiatry. We discuss how defining these three issues helps towards building a framework to ensure trustworthiness, but show how difficult definition can be, as the terms have different meanings in medicine, computer science, and law. We conclude that it is important to start the discussion such that there can be a call for policy on this and that the community takes extra care when reviewing clinical applications of such models..

    更新日期:2020-01-04
  • From Social Cognition to Negative Symptoms in Schizophrenia: How Do We Get There From Here?
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-28
    Green M.

    Somewhere in the vast landscape of clinical and neuroscientific issues confronting the study of schizophrenia resides a humble question regarding the interface between social cognition and negative symptoms. A focus on this particular linkage sounds narrow, a little wonkish, and far removed from the high visibility concerns of other areas of schizophrenia research. However, any mechanistic attempt to understand how the brain connects to disability in schizophrenia will need to travel through this intersection between social cognition and negative symptoms. Thus, it is valuable and instructive that Pelletier-Baldelli and Holt have written a piece that focuses on these constructs and this particular association.1 Their article raises several fundamental questions, a few of which I will discuss here.

    更新日期:2019-11-30
  • My 49-Year Recovery From Mental Illness
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-28
    Goulet L.

    Although I was a very insecure girl and young woman, I always managed to function until March of 1970—when I suffered a postpartum breakdown. It occurred about a year after my son, Matthew, was born. Before my breakdown, my pent up feelings made my brain feel like a worn-out machine—struggling to do its job. At my illness’s onset, I was hallucinating, thinking that the TV was sending me messages. I remember the fear I felt because our family was living way out in the countryside in such isolation. I felt devastated when I could not function well enough to take care of my baby.

    更新日期:2019-11-30
  • Abnormal Space Experiences in Persons With Schizophrenia: An Empirical Qualitative Study
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-30
    Stanghellini G, Fernandez A, Ballerini M, et al.

    Abnormal space experience (ASE) is a common feature of schizophrenia, despite its absence from current diagnostic manuals. Phenomenological psychopathologists have investigated this experiential disturbance, but these studies were typically based on anecdotal evidence from limited clinical interactions. To better understand the nature of ASE in schizophrenia and attempt to validate previous phenomenological accounts, we conducted a qualitative study of 301 people with schizophrenia. Clinical files were analyzed by means of Consensual Qualitative Research, an inductive method for analyzing descriptions of lived experience. Our main findings can be summed up as follows: (1) ASEs are a relevant feature in schizophrenia (70.1% of patients reported at least 1 ASE). (2) ASE in schizophrenia are characterized by 5 main categories of phenomena (listed from more represented to less represented): (a) experiences of strangeness and unfamiliarity (eg “Everything appeared weird. Face distorted, world looks terrible, nasty”); (b) experiences of centrality/invasion of peripersonal space (eg “Handkerchief on scaffolding: message telling him something”); (c) alteration of the quality of things (eg “Buildings leaning down”); (d) alteration of the quality of the environment (eg “Person sitting six feet away seemed to be at an infinite distance”); and (e) itemization and perceptive salience (eg “All patients [in ward] have bright eyes”). (3) ASEs are much more frequent in acute (91.9%) than in chronic (28.15%) schizophrenia patients. Moreover, our findings further empirical support for phenomenological accounts of schizophrenia, including those developed by Jaspers, Binswanger, Minkowski, and Conrad, among others and provide the background for translational research.

    更新日期:2019-11-30
  • Neurological Soft Signs and Brain Network Abnormalities in Schizophrenia
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-27
    Kong L, Herold C, Cheung E, et al.

    Neurological soft signs (NSS) are often found in patients with schizophrenia. A wealth of neuroimaging studies have reported that NSS are related to disturbed cortical-subcortical-cerebellar circuitry in schizophrenia. However, the association between NSS and brain network abnormalities in patients with schizophrenia remains unclear. In this study, the graph theoretical approach was used to analyze brain network characteristics based on structural magnetic resonance imaging (MRI) data. NSS were assessed using the Heidelberg scale. We found that there was no significant difference in global network properties between individuals with high and low levels of NSS. Regional network analysis showed that NSS were associated with betweenness centrality involving the inferior orbital frontal cortex, the middle temporal cortex, the hippocampus, the supramarginal cortex, the amygdala, and the cerebellum. Global network analysis also demonstrated that NSS were associated with the distribution of network hubs involving the superior medial frontal cortex, the superior and middle temporal cortices, the postcentral cortex, the amygdala, and the cerebellum. Our findings suggest that NSS are associated with alterations in topological attributes of brain networks corresponding to the cortical-subcortical-cerebellum circuit in patients with schizophrenia, which may provide a new perspective for elucidating the neural basis of NSS in schizophrenia.

    更新日期:2019-11-28
  • Brain Structural Correlates of Metacognition in First-Episode Psychosis
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-28
    Alkan E, Davies G, Greenwood K, et al.

    Metacognition is impaired in schizophrenia and is an important predictor of functional outcome, but the underlying neuropathology is not clear. Studies have implicated frontal regions and there is also some evidence that the hippocampus might play a pivotal role, but findings are inconsistent. We set out to more comprehensively investigate the neural underpinnings of insight in first-episode psychosis (FEP) using 2 metacognitive measures (the Beck Cognitive Insight Scale [BCIS]) and a perceptual metacognitive accuracy task alongside structural magnetic resonance imaging (MRI). We measured cortical thickness in insula and frontal regions, hippocampal (including subfield) volumes, hippocampal microstructure (using neurite orientation dispersion and density imaging [NODDI]), and fractional anisotropy in fornix. Relative to controls, FEP showed poorer metacognitive accuracy, thinner cortex in frontal regions and lower fornix integrity. In healthy controls (but not FEP), metacognitive accuracy correlated with cortical thickness in frontal cortex and insula. Conversely, in FEP (but not controls), metacognitive accuracy correlated with hippocampal volume and microstructural indices. Subicular hippocampal subregions were particularly implicated. No structural correlates of BCIS were found. These findings suggest that the neural bases of metacognition might differ in FEP: hippocampal (rather than frontal) integrity seems to be critical. Further, the use of objectively measured metacognitive indices seems to be a more powerful method for understanding the neurocircuitry of metacognition in FEP, which has the potential to inform therapeutic strategies and improve outcome in these patients.

    更新日期:2019-11-28
  • Erratum to: At Issue: Are Negative Symptoms Merely the “Real World” Consequences of Deficits in Social Cognition?
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-23

    In the original publication of “At Issue: Are Negative Symptoms Merely the “Real World” Consequences of Deficits in Social Cognition?” by Andrea Pelletier-Baldelli and Daphne J. Holt, the Key Words were incorrectly listed as: schizophrenia/negative, symptoms/social cognition/remove, mechanisms/social context. The Key Words have since been corrected to: schizophrenia/negative, symptoms/social cognition. The publisher regrets this error.

    更新日期:2019-11-26
  • Dopamine-Induced Dysconnectivity Between Salience Network and Auditory Cortex in Subjects With Psychotic-like Experiences: A Randomized Double-Blind Placebo-Controlled Study
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-21
    Rössler J, Rössler W, Seifritz E, et al.

    Dopamine is involved in the pathophysiology of schizophrenia. Disrupted salience processing by the salience network (SN) may be a central link between dysregulated dopamine function and psychotic symptoms. However, dopaminergic influence on the SN and its presumed influence on psychotic and subpsychotic symptoms or psychotic-like experiences in healthy individuals remain unclear. Therefore, we investigated dopamine-induced changes in functional connectivity of the right anterior insula (rAI), a central SN hub, and their association with psychotic-like experiences. We enrolled 54 healthy, right-handed male subjects in a randomized, double-blind, cross-sectional placebo-controlled experiment. Psychotic-like experiences were assessed using the revised Exceptional Experiences Questionnaire (PAGE-R). They then received either placebo (n = 32) or 200 mg L-DOPA (n = 33), a dopamine precursor, orally and underwent resting-state functional magnetic resonance imaging. In a seed-to-voxel approach, we analyzed dopamine-induced changes in functional connectivity of the rAI and assessed the relationship between functional connectivity changes and PAGE-R score. L-DOPA reduced functional connectivity between the rAI and the left auditory cortex planum polare. In the placebo group, we found a strong negative correlation between PAGE-R score and rAI to planum polare functional connectivity; in the L-DOPA group, there was a strong positive correlation between PAGE-R score and functional connectivity between rAI and planum polare. The PAGE-R score explained about 30% of the functional connectivity variation between rAI and planum polare in the two groups. Our findings suggest that psychotic-like experiences are associated with dopamine-induced disruption of auditory input to the SN, which may lead to aberrant attribution of salience.

    更新日期:2019-11-22
  • Transdiagnostic Dysfunctions in Brain Modules Across Patients with Schizophrenia, Bipolar Disorder, and Major Depressive Disorder: A Connectome-Based Study
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-22
    Ma Q, Tang Y, Wang F, et al.

    Psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), share clinical and neurobiological features. Because previous investigations of functional dysconnectivity have mainly focused on single disorders, the transdiagnostic alterations in the functional connectome architecture of the brain remain poorly understood. We collected resting-state functional magnetic resonance imaging data from 512 participants, including 121 with SCZ, 100 with BD, 108 with MDD, and 183 healthy controls. Individual functional brain connectomes were constructed in a voxelwise manner, and the modular architectures were examined at different scales, including (1) global modularity, (2) module-specific segregation and intra- and intermodular connections, and (3) nodal participation coefficients. The correlation of these modular measures with clinical scores was also examined. We reliably identify common alterations in modular organization in patients compared to controls, including (1) lower global modularity; (2) lower modular segregation in the frontoparietal, subcortical, visual, and sensorimotor modules driven by more intermodular connections; and (3) higher participation coefficients in several network connectors (the dorsolateral prefrontal cortex and angular gyrus) and the thalamus. Furthermore, the alterations in the SCZ group are more widespread than those of the BD and MDD groups and involve more intermodular connections, lower modular segregation and higher connector integrity. These alterations in modular organization significantly correlate with clinical scores in patients. This study demonstrates common hyper-integrated modular architectures of functional brain networks among patients with SCZ, BD, and MDD. These findings reveal a transdiagnostic mechanism of network dysfunction across psychiatric disorders from a connectomic perspective.

    更新日期:2019-11-22
  • Normalizing the Abnormal: Do Antipsychotic Drugs Push the Cortex Into an Unsustainable Metabolic Envelope?
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-22
    Turkheimer F, Selvaggi P, Mehta M, et al.

    The use of antipsychotic medication to manage psychosis, principally in those with a diagnosis of schizophrenia or bipolar disorder, is well established. Antipsychotics are effective in normalizing positive symptoms of psychosis in the short term (delusions, hallucinations and disordered thought). Their long-term use is, however, associated with side effects, including several types of movement (extrapyramidal syndrome, dyskinesia, akathisia), metabolic and cardiac disorders. Furthermore, higher lifetime antipsychotic dose-years may be associated with poorer cognitive performance and blunted affect, although the mechanisms driving the latter associations are not well understood. In this article, we propose a novel model of the long-term effects of antipsychotic administration focusing on the changes in brain metabolic homeostasis induced by the medication. We propose here that the brain metabolic normalization, that occurs in parallel to the normalization of psychotic symptoms following antipsychotic treatment, may not ultimately be sustainable by the cerebral tissue of some patients; these patients may be characterized by already reduced oxidative metabolic capacity and this may push the brain into an unsustainable metabolic envelope resulting in tissue remodeling. To support this perspective, we will review the existing data on the brain metabolic trajectories of patients with a diagnosis of schizophrenia as indexed using available neuroimaging tools before and after use of medication. We will also consider data from pre-clinical studies to provide mechanistic support for our model.

    更新日期:2019-11-22
  • A Network Analysis of Epigenetic and Transcriptional Regulation in a Neurodevelopmental Rat Model of Schizophrenia With Implications for Translational Research
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-18
    Du Y, Li X, Chen L, et al.

    Prenatal administration of mitotoxin methylazoxymethanol acetate (MAM) in rats produces behavioral, pharmacological, and anatomical abnormalities once offspring reach adulthood, thus establishing a widely used neurodevelopmental model of schizophrenia. However, the molecular aspects underlying this disease model are not well understood. Therefore, this study examines epigenetic and transcriptional dysregulation in the prefrontal cortex and hippocampus of MAM rats as these are brain regions closely associated with schizophrenia pathogenesis. Upon sequencing messenger and microRNA (mRNA and miRNA, respectively), differential expression was revealed in the prefrontal cortex and hippocampus between MAM- and saline-treated rats; sequencing data were validated by qualitative real-time polymerase chain reaction. Bioinformatic analyses demonstrated that the differentially expressed (DE) genes were strongly enriched in interactive pathways related to schizophrenia, including chemical synaptic transmission, cognition, and inflammatory responses; also, the potential target genes of the DE miRNAs were enriched in pathways related to synapses and inflammation. The blood of schizophrenia patients and healthy controls was further analyzed for several top DE mRNAs: DOPA decarboxylase, ret proto-oncogene, Fc receptor-like 2, interferon lambda receptor 1, and myxovirus (influenza virus) resistance 2. The results demonstrated that the expression of these genes was dysregulated in patients with schizophrenia; combining these mRNAs sufficiently differentiated schizophrenia patients from controls. Taken together, this study suggests that the MAM model has the potential to reproduce hippocampus and prefrontal cortex abnormalities, relevant to schizophrenia, at the epigenetic and transcriptional levels. These data also provide novel targets for schizophrenia diagnoses and treatments.

    更新日期:2019-11-18
  • The Development of Kraepelin’s Mature Diagnostic Concept of Catatonic Dementia Praecox: A Close Reading of Relevant Texts
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-02
    Kendler K.

    Through a close reading of texts, this essay traces the development of catatonia from its origination in Kahlbaum’s 1874 monograph to Kraepelin’s catatonic subtype of his new category of Dementia Praecox (DP) in 1899. In addition to Kraepelin’s second to sixth textbook editions, I examine the six articles referenced by Kraepelin: Kahlbaum 1874, Brosius 1877, Neisser 1887, Behr 1891, Schüle 1897, and Aschaffenburg 1897 (Behr and Aschaffenburg worked under Kraepelin). While Brosius and Neisser confirmed Kahlbaum’s descriptions, Behr, Schüle, and Aschaffenburg concluded that his catatonic syndrome was nonspecific and only more narrowly defined forms, especially those with deteriorating course, might be diagnostically valid. Catatonia is first described by Kraepelin as a subform of Verrücktheit (chronic nonaffective delusional insanity) in his second to fourth editions. In his third edition, he adds a catatonic form of Wahnsinn (acute delusional-affective insanity). His fourth and fifth editions contain, respectively, catatonic forms of his two proto-DP concepts: Psychischen Entartungsprocesse and Die Verblödungsprocesse. Kahlbaum’s catatonia required a sequential phasic course. Positive psychotic symptoms were rarely noted, and outcome was frequently good. While agreeing on the importance of key catatonic signs (stupor, muteness, posturing, verbigeration, and excitement), Kraepelin narrowed Kahlbaum’s concept, dropping the phasic course, emphasizing positive psychotic symptoms and poor outcome. In his fourth to sixth editions, as he tried to integrate his three DP subtypes, he stressed, as suggested by Aschaffenburg and Schüle, the close clinical relationship between catatonia and hebephrenia and emphasized the bizarre and passivity delusions seen in catatonia, typical of paranoid DP.

    更新日期:2019-11-04
  • Global and Specific Cortical Volume Asymmetries in Individuals With Psychosis Risk Syndrome and Schizophrenia: A Mixed Cross-sectional and Longitudinal Perspective.
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-11-05
    Katherine S F Damme,Teresa Vargas,Vince Calhoun,Jessica Turner,Vijay A Mittal

    Cortical volumetric asymmetry (CVA) has been widely observed in individuals with psychosis, and is associated with etiological risk factors (e.g., genetics, neuromaturation) and treatment response. However, it is unclear whether CVA abnormalities emerge before psychotic illness onset. Understanding whether CVA manifests in clinical high-risk (CHR)-compared with healthy controls and schizophrenia patients (SCZ)-over time may inform our understanding of pathogenic factors. A total of 233 individuals: 73 CHR, 112 healthy controls, and 48 SCZ underwent an MRI and clinical interviews. Ninety-four individuals including healthy volunteers (HV) (n = 49) and CHR (n = 45), completed another scan at 12-months. CVA was compared by lobe in a repeated-measure design across groups, then nested by time in a longitudinal model. CHR and SCZ groups showed reduced global CVA compared with the healthy control groups but the CHR and SCZ group did not differ from each other. A group by lobe interaction indicated the presence of lobe specific reductions in frontal and cingulate CVA. Cingulate CVA was reduced in CHR and SCZ groups compared to HC groups but did not differ from each other. Frontal CVA was reduced in the older healthy controls compared with younger-HC and CHR, but did not differ from the similarly aged SZ group. CVA is similarly impacted in SCZ and CHR groups, potentially reflecting pathogenic processes. Longitudinal analyses provided further support for the neurodevelopmental hypothesis as CHR exhibited longitudinal changes in opposite directions from normative neuromaturation in HV, which was related to increasing risk for psychosis in the CHR.

    更新日期:2019-11-01
  • Cognitive Behavioral Therapy Plus Standard Care Versus Standard Care Plus Other Psychosocial Treatments for People With Schizophrenia.
    Schizophr. Bull. (IF 7.289) Pub Date : 2019-03-08
    Christopher Jones,David Hacker,Irene Cormac,Alan Meaden,Claire B Irving,Jun Xia,Sai Zhao,Chunhu Shi,Jue Chen

    更新日期:2019-11-01
  • Reduced Neural Sensitivity to Social vs Nonsocial Reward in Schizophrenia.
    Schizophr. Bull. (IF 7.289) Pub Date : 2018-09-07
    Junghee Lee,Amy M Jimenez,Eric A Reavis,William P Horan,Jonathan K Wynn,Michael F Green

    BACKGROUND Human beings find social stimuli rewarding, which is thought to facilitate efficient social functioning. Although reward processing has been extensively studied in schizophrenia, a few studies have examined neural processes specifically involved in social reward processing. This study examined neural sensitivity to social and nonsocial rewards in schizophrenia. METHODS Twenty-seven patients with schizophrenia and 25 community controls completed a One-Armed Bandit Task, an implicit reinforcement learning task, in the scanner. There were 2 conditions with an identical trial structure, one with social rewards and the other with nonsocial rewards. The data were analyzed using a region of interest (ROI) approach, focusing on the ventral striatum, ventromedial prefrontal cortex, and anterior cingulate cortex. RESULTS Across all 3 ROIs, patients showed reduced activation for social rewards compared to controls. However, the 2 groups showed comparable levels of activation for nonsocial rewards. Within the patient group, levels of neural activation in these ROIs during the social reward condition were associated with better performance. CONCLUSIONS This study found reduced neural sensitivity in patients with schizophrenia in key reward-processing regions for social but not for nonsocial rewards. These findings suggest a relatively specific social reward-processing deficit in schizophrenia during an implicit reinforcement learning task.

    更新日期:2019-11-01
  • Motor Impairment and Developmental Psychotic Risk: Connecting the Dots and Narrowing the Pathophysiological Gap.
    Schizophr. Bull. (IF 7.289) Pub Date : 2018-07-15
    Michele Poletti,Eva Gebhardt,Marianne N Kvande,Judith Ford,Andrea Raballo

    The motor system in its manifold articulations is receiving increasing clinical and research attention. This is because motor impairments constitute a central, expressive component of the mental state examination and a key transdiagnostic feature indexing disease severity. Furthermore, within the schizophrenia spectrum, the integration of neurophysiological, developmental, and phenomenological perspectives suggests that motor impairment is not simply a generic, extrinsic proxy of an altered neurodevelopment, but might be more intimately related to psychotic risk. Therefore, an increased understanding, conceptualization, and knowledge of such motor system and its anomalies could empower contemporary risk prediction and diagnostic procedures.

    更新日期:2019-11-01
  • Relationship of Cognition to Clinical Response in First-Episode Schizophrenia Spectrum Disorders.
    Schizophr. Bull. (IF 7.289) Pub Date : 2015-09-27
    Joey W Trampush,Todd Lencz,Pamela DeRosse,Majnu John,Juan A Gallego,Georgios Petrides,Youssef Hassoun,Jian-Ping Zhang,Jean Addington,Charles H Kellner,Mauricio Tohen,Katherine E Burdick,Terry E Goldberg,John M Kane,Delbert G Robinson,Anil K Malhotra

    First-episode schizophrenia (FES) spectrum disorders are associated with pronounced cognitive dysfunction across all domains. However, less is known about the course of cognitive functioning, following the first presentation of psychosis, and the relationship of cognition to clinical course during initial treatment. The present longitudinal study examined the magnitude of neurocognitive impairment, using the MATRICS Consensus Cognitive Battery, in patients experiencing their first episode of psychosis at baseline and after 12 weeks of randomized antipsychotic treatment with either aripiprazole or risperidone. At baseline, FES patients evidenced marked impairments in cognitive functioning. Notably, performance on the mazes task of planning and reasoning significantly predicted the likelihood of meeting stringent criteria for positive symptom remission during the first 12 weeks of the trial. Performance on indices of general cognitive function, working memory, and verbal learning improved over time, but these improvements were mediated by improvements in both positive and negative symptoms. We did not detect any differential effects of antipsychotic medication assignment (aripiprazole vs risperidone) on cognitive functioning. Our results suggest that a brief paper-and-pencil measure reflecting planning/reasoning abilities may index responsivity to antipsychotic medication. However, improvements in cognitive functioning over time were related to clinical symptom improvement, reflecting "pseudospecificity."

    更新日期:2019-11-01
  • Mortality in schizophrenia and other psychoses: a 10-year follow-up of the ӔSOP first-episode cohort.
    Schizophr. Bull. (IF 7.289) Pub Date : 2014-09-30
    Ulrich Reininghaus,Rina Dutta,Paola Dazzan,Gillian A Doody,Paul Fearon,Julia Lappin,Margaret Heslin,Adanna Onyejiaka,Kim Donoghue,Ben Lomas,James B Kirkbride,Robin M Murray,Tim Croudace,Craig Morgan,Peter B Jones

    The excess mortality in people with psychotic disorders is a major public health concern, but little is known about the clinical and social risk factors which may predict this health inequality and help inform preventative strategies. We aimed to investigate mortality in a large epidemiologically characterized cohort of individuals with first-episode psychosis compared with the general population and to determine clinical and social risk factors for premature death. All 557 individuals with first-episode psychosis initially identified in 2 areas (Southeast London and Nottinghamshire, United Kingdom) were traced over a 10-year period in the ӔSOP-10 study. Compared with the general population, all-cause (standardized mortality ratio [SMR] 3.6, 95% confidence interval [CI] 2.6-4.9), natural-cause (SMR 1.7, 95% CI 1.0-2.7) and unnatural-cause (SMR 13.3, 95% CI 8.7-20.4) mortality was very high. Illicit drug use was associated with an increased risk of all-cause mortality (adj. rate ratio [RR] 2.31, 95% CI 1.06-5.03). Risk of natural-cause mortality increased with a longer time to first remission (adj. RR 6.61, 95% CI 1.33-32.77). Family involvement at first contact strongly reduced risk of unnatural-cause mortality (adj. RR 0.09, 95% CI 0.01-0.69). Our findings suggest that the mortality gap in people with psychotic disorders remains huge and may be wider for unnatural-cause mortality than previously reported. Efforts should now focus on further understanding and targeting these tractable clinical and social risk factors of excess mortality. Early intervention and dual diagnosis services may play a key role in achieving more rapid remission and carer involvement and addressing substance use problems to reduce excess mortality in psychosis.

    更新日期:2019-11-01
  • The effect of clozapine on premature mortality: an assessment of clinical monitoring and other potential confounders.
    Schizophr. Bull. (IF 7.289) Pub Date : 2014-08-27
    Richard D Hayes,Johnny Downs,Chin-Kuo Chang,Richard G Jackson,Hitesh Shetty,Matthew Broadbent,Matthew Hotopf,Robert Stewart

    Clozapine can cause severe adverse effects yet it is associated with reduced mortality risk. We test the hypothesis this association is due to increased clinical monitoring and investigate risk of premature mortality from natural causes. We identified 14 754 individuals (879 deaths) with serious mental illness (SMI) including schizophrenia, schizoaffective and bipolar disorders aged ≥ 15 years in a large specialist mental healthcare case register linked to national mortality tracing. In this cohort study we modeled the effect of clozapine on mortality over a 5-year period (2007-2011) using Cox regression. Individuals prescribed clozapine had more severe psychopathology and poorer functional status. Many of the exposures associated with clozapine use were themselves risk factors for increased mortality. However, we identified a strong association between being prescribed clozapine and lower mortality which persisted after controlling for a broad range of potential confounders including clinical monitoring and markers of disease severity (adjusted hazard ratio 0.4; 95% CI 0.2-0.7; p = .001). This association remained after restricting the sample to those with a diagnosis of schizophrenia or those taking antipsychotics and after using propensity scores to reduce the impact of confounding by indication. Among individuals with SMI, those prescribed clozapine had a reduced risk of mortality due to both natural and unnatural causes. We found no evidence to indicate that lower mortality associated with clozapine in SMI was due to increased clinical monitoring or confounding factors. This is the first study to report an association between clozapine and reduced risk of mortality from natural causes.

    更新日期:2019-11-01
  • Adolescent self-control predicts midlife hallucinatory experiences: 40-year follow-up of a national birth cohort.
    Schizophr. Bull. (IF 7.289) Pub Date : 2014-04-10
    Atsushi Nishida,Kate Man Xu,Tim Croudace,Peter B Jones,Jenifer Barnett,Marcus Richards

    BACKGROUND Associations between self-control in adolescence and adult mental health are unclear in the general population; to our knowledge, no study has investigated self-control in relation to psychotic-like symptoms. AIMS To investigate the relationship between adolescent self-control and the midlife mental health outcomes of anxiety and depression symptoms and psychotic-like experiences (PLEs), controlling for the effect of adolescent conduct and emotional problems and for parental occupational social class and childhood cognition. METHODS A population-based sample, the MRC National Survey of Health and Development (the British 1946 birth cohort) was contacted 23 times between ages 6 weeks and 53 years. Teachers completed rating scales to assess emotional adjustment and behaviors, from which factors measuring self-control, behavioral, and emotional problems were extracted. At age 53 years, PLEs were self-reported by 2918 participants using 4 items from the Psychosis Screening Questionnaire; symptoms of anxiety and depression were assessed using the scaled version of the General Health Questionnaire (GHQ-28). RESULTS After adjustment for the above covariates, poor adolescent self-control was associated with the presence of PLEs in adulthood, specifically hallucinatory experiences at age 53 years, even after adjustment for GHQ-28 scores. CONCLUSIONS Lower self-control in adolescence is a risk factor for hallucinatory experiences in adulthood.

    更新日期:2019-11-01
  • Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.
    Schizophr. Bull. (IF 7.289) Pub Date : 2013-12-19
    Marta Di Forti,Hannah Sallis,Fabio Allegri,Antonella Trotta,Laura Ferraro,Simona A Stilo,Arianna Marconi,Caterina La Cascia,Tiago Reis Marques,Carmine Pariante,Paola Dazzan,Valeria Mondelli,Alessandra Paparelli,Anna Kolliakou,Diana Prata,Fiona Gaughran,Anthony S David,Craig Morgan,Daniel Stahl,Mizanur Khondoker,James H MacCabe,Robin M Murray

    UNLABELLED Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. METHODS We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. RESULTS Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16-1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11-1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06-1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. CONCLUSIONS Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.

    更新日期:2019-11-01
  • Risk of adult schizophrenia and its relationship to childhood IQ in the 1958 British birth cohort.
    Schizophr. Bull. (IF 7.289) Pub Date : 2013-01-02
    Joerg Schulz,Josefin Sundin,Stuart Leask,D John Done

    BACKGROUND An inverse relationship between risk of schizophrenia and premorbid IQ is a robust empirical finding. Cognitive impairment may be a core feature of schizophrenia in addition to the clinical symptoms that have historically defined the disorder. AIMS To evaluate whether risk of schizophrenia increases linearly or nonlinearly with the lowering of premorbid IQ after adjustment for a range of confounding factors. METHODS IQ data from the 1958 National Child Development Study, a prospective national birth cohort (n = 17 419), were linked with psychiatric admissions in England and Wales over a 20-year period. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnoses were derived from case notes. RESULTS A clear nonlinear inverse relationship between general intelligence at ages 7 and 11 and risk of adult psychosis was found even after adjustment for potential social, behavioral, or demographic confounding factors. No such relationship was found for affective disorders. CONCLUSIONS The nonlinear relationship suggests an excess risk of schizophrenia in children with premorbid IQ in the learning disabilities range. Previous reports of a linear relationship are likely to be a result of less sensitive statistical methods for detecting nonlinearity.

    更新日期:2019-11-01
  • Social disadvantage: cause or consequence of impending psychosis?
    Schizophr. Bull. (IF 7.289) Pub Date : 2012-10-24
    Simona A Stilo,Marta Di Forti,Valeria Mondelli,Aurora M Falcone,Manuela Russo,Jennifer O'Connor,Emma Palmer,Alessandra Paparelli,Anna Kolliakou,Miriam Sirianni,Heather Taylor,Rowena Handley,Paola Dazzan,Carmine Pariante,Tiago R Marques,Rocco Zoccali,Anthony David,Robin M Murray,Craig Morgan

    BACKGROUND An association between social disadvantage and established psychosis is well documented in the literature, but there remains a lack of data on the social circumstances of patients before they became ill. We investigated whether social disadvantage at, and prior to, first contact with psychiatric services, is associated with psychosis. METHOD We collected information on social disadvantage in childhood and adulthood from 278 cases presenting with their first episode of psychosis to the South London and Maudsley National Health Service Foundation Trust and from 226 controls recruited from the local population. Three markers of childhood social disadvantage and 3 markers of disadvantage in adulthood were analyzed. RESULTS Long term separation from, and death of, a parent before the age of 17 years were both strongly associated with a 2- to 3-fold-increased odds of psychosis. Cases were also significantly more likely to report 2 or more markers of adult social disadvantage than healthy controls (OR = 9.03) at the time of the first presentation with psychosis, independent of a number of confounders. When we repeated these analyses for long-standing adult social disadvantage, we found that the strength of the association decreased but still remained significant for 1 year (OR = 5.67) and 5 years (OR = 2.57) prior to the first contact. CONCLUSIONS Social disadvantage indexes exposure to factors operating prior to onset that increase the risk of psychosis, both during childhood and adulthood.

    更新日期:2019-11-01
  • Pathways between childhood victimization and psychosis-like symptoms in the ALSPAC birth cohort.
    Schizophr. Bull. (IF 7.289) Pub Date : 2012-09-04
    Helen L Fisher,Andrea Schreier,Stanley Zammit,Barbara Maughan,Marcus R Munafò,Glyn Lewis,Dieter Wolke

    BACKGROUND Several large population-based studies have demonstrated associations between adverse childhood experiences and later development of psychotic symptoms. However, little attention has been paid to the mechanisms involved in this pathway and the few existing studies have relied on cross-sectional assessments. METHODS Prospective data on 6692 children from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) were used to address this issue. Mothers reported on children's exposure to harsh parenting and domestic violence in early childhood, and children self-reported on bullying victimization prior to 8.5 years. Presence of children's anxiety at 10 years and their depressive symptoms at 9 and 11 years were ascertained from mothers, and children completed assessments of self-esteem and locus of control at 8.5 years. Children were interviewed regarding psychotic symptoms at a mean age of 12.9 years. Multiple mediation analysis was performed to examine direct and indirect effects of each childhood adversity on psychotic symptoms. RESULTS The association between harsh parenting and psychotic symptoms was fully mediated by anxiety, depressive symptoms, external locus of control, and low self-esteem. Bullying victimization and exposure to domestic violence had their associations with psychotic symptoms partially mediated by anxiety, depression, locus of control, and self-esteem. Similar results were obtained following adjustment for a range of confounders and when analyses were conducted for boys and girls separately. CONCLUSIONS These findings tentatively suggest that specific cognitive and affective difficulties in childhood could be targeted to minimize the likelihood of adolescents exposed to early trauma from developing psychotic symptoms.

    更新日期:2019-11-01
  • Striatal dopamine transporter availability in drug-naive patients with schizophrenia: a case-control SPECT study with [(99m)Tc]-TRODAT-1 and a meta-analysis.
    Schizophr. Bull. (IF 7.289) Pub Date : 2011-12-14
    Kao Chin Chen,Yen Kuang Yang,Oliver Howes,I Hui Lee,Sabine Landau,Tzung Lieh Yeh,Nan Tsing Chiu,Po See Chen,Ru Band Lu,Anthony S David,Elvira Bramon

    Central dopaminergic hyperactivity has been one of the main hypotheses of the pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA) neurotransmission in the striatum is hypothesized to alter the processing of information and result in psychotic symptoms in schizophrenia. Single photon emission computerized tomography (SPECT) provides in vivo indices of DA neurotransmission. Our study aimed to compare dopamine transporter (DAT) availability between drug-naive patients with schizophrenia and controls using SPECT. DAT availability through [(99m)Tc]-TRODAT-1 SPECT was compared between 47 drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We also conducted a random-effects meta-analysis of the available literature synthesizing the results of 6 comparable published articles as well as our current data. The mean specific striatal binding showed a statistical trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI -0.01, 0.15; P = .08). There was an effect of gender, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohen's d) of -0.07 (95% CI -0.31, 0.18; P = .60) for the patient vs control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. Our findings suggest that striatal DAT levels are not altered in the early stages of schizophrenia before medication is introduced. We identified gender differences and aging effects that could have significance for future studies.

    更新日期:2019-11-01
  • High vs low frequency neural oscillations in schizophrenia.
    Schizophr. Bull. (IF 7.289) Pub Date : 2011-06-10
    Lauren V Moran,L Elliot Hong

    There is growing recognition that neural oscillations are important in a wide range of perceptual and cognitive functions. One of the key issues in electrophysiological studies of schizophrenia is whether high or low frequency oscillations, or both, are related to schizophrenia because many brain functions are modulated with frequency specificities. Many recent electrophysiological studies of schizophrenia have focused on high frequency oscillations at gamma band and in general support gamma band dysfunction in schizophrenia. We discuss the concept that gamma oscillation abnormalities in schizophrenia often occur in the background of oscillation abnormalities of lower frequencies. The review discusses the basic neurobiology for the emergence of oscillations of all frequency bands in association with networks of inhibitory interneurons and the convergence and divergence of such mechanisms in generating high vs low frequency oscillations. We then review the literature of oscillatory frequency abnormalities identified in each frequency band in schizophrenia. By describing some of the key functional roles exerted by gamma, low frequencies, and their cross-frequency coupling, we conceptualize that even isolated alterations in gamma or low frequency oscillations may impact the interactions of high and low frequency bands that are involved in key cognitive functions. The review concludes that studying the full spectrum and the interaction of gamma and low frequency oscillations may be critical for deciphering the complex electrophysiological abnormalities observed in schizophrenia patients.

    更新日期:2019-11-01
  • Abnormal relationship between medial temporal lobe and subcortical dopamine function in people with an ultra high risk for psychosis.
    Schizophr. Bull. (IF 7.289) Pub Date : 2011-05-04
    Paul Allen,Christopher A Chaddock,Oliver D Howes,Alice Egerton,Marc L Seal,Paolo Fusar-Poli,Isabel Valli,Fern Day,Philip K McGuire

    BACKGROUND Neuroimaging studies in humans have implicated both dysfunction of the medial temporal lobe (MTL) and the dopamine system in psychosis, but the relationship between them is unclear. We addressed this issue by measuring MTL activation and striatal dopaminergic function in individuals with an At Risk Mental State (ARMS) for psychosis, using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), respectively. METHODS Thirty-four subjects (20 ARMS and 14 Controls), matched for age, gender, digit span performance, and premorbid IQ, were scanned using fMRI, while performing a verbal encoding and recognition task, and using 18F-DOPA PET. All participants were naïve to antipsychotic medication. RESULTS ARMS subjects showed reduced MTL activation when encoding words and made more false alarm responses for Novel words than controls. The relationship between striatal dopamine function and MTL activation during both verbal encoding and verbal recognition was significantly different in ARMS subjects compared with controls. CONCLUSION An altered relationship between MTL function and dopamine storage/synthesis capacity exists in the ARMS and may be related to psychosis vulnerability.

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
导出
全部期刊列表>>
2020新春特辑
限时免费阅读临床医学内容
ACS材料视界
科学报告最新纳米科学与技术研究
清华大学化学系段昊泓
自然科研论文编辑服务
中国科学院大学楚甲祥
上海纽约大学William Glover
中国科学院化学研究所
课题组网站
X-MOL
北京大学分子工程苏南研究院
华东师范大学分子机器及功能材料
中山大学化学工程与技术学院
试剂库存
天合科研
down
wechat
bug