Schizophrenia bulletin open最新文献

There is a pressing need for biomarkers of violent behavior risk in psychosis. Previous research indicates that electrophysiological measures of automatic defensive reactions may have potential. The purpose of this study was to investigate associations between violent behavior in individuals with and without psychosis and electromyography (EMG) and electroencephalography (EEG) responses to startling auditory stimuli. Electromyography and EEG were recorded during an auditory startle paradigm from healthy controls (HC, n = 211), individuals with psychosis and a history of violent behavior (violent-PSY, n = 18), individuals with psychosis without a history of violence (nonviolent-PSY, n = 32), and individuals with a history of violence without psychosis (violent non-PSY, n = 22). We estimated the auditory startle response (ASR) and prepulse inhibition (PPI) using EMG (ie, EMG_ASR and EMG_PPI) and the auditory-evoked potential (ie, AEP_ASR and AEP_PPI) of the EEG. There were no significant effects of group on the EMG_ASR (P = .10) or the 30-, 60-, and 120-ms prepulse + pulse EMG_PPI amplitudes (P = .11, P = .19, and P = .50, respectively). The N1 amplitude of the AEP_ASR was reduced in the violent-PSY group (P < .001) and the nonviolent-PSY group (P = .015) compared with HC. The P2 amplitude of the AEP_ASR was reduced in violent-PSY relative to nonviolent-PSY (P = .003), violent non-PSY (P = .016), and HC (P < .001). Together, these results show that EEG-based neural responses to startling auditory stimuli are promising biomarkers of violence risk in psychosis.

Cognitive impairment is a core feature of schizophrenia and a key determinant of functional outcome. Although conventional paper-and-pencil based cognitive assessments used in schizophrenia remained relatively static during most of the 20th century, this century has witnessed the emergence of innovative digital technologies that aim to enhance the ecological validity of performance-based assessments. This narrative review provides an overview of new technologies that show promise for enhancing the ecological validity of cognitive and functional assessments. We focus on 2 approaches that are particularly relevant for schizophrenia research: (1) digital functional capacity tasks, which use simulations to measure performance of important daily life activities (e.g., virtual shopping tasks), delivered both in-person and remotely, and (2) remote device-based assessments, which include self-administered cognitive tasks (e.g., processing speed test) or functionally-focused surveys regarding momentary activities and experiences (e.g., location, social context), as well as passive sensor-based metrics (e.g., actigraphy measures of activity), during daily life. For each approach, we describe the potential for enhancing ecological validity, provide examples of select measures that have been used in schizophrenia research, summarize available data on their feasibility and validity, and consider remaining challenges. Rapidly growing evidence indicates that digital technologies have the potential to enhance the ecological validity of cognitive and functional outcome assessments, and thereby advance research into the causes of, and treatments for, functional disability in schizophrenia.

Clinical high-risk for psychosis (CHR-P) individuals are typically recruited from clinical services but the clinical and functional outcomes of community-recruited CHR-P individuals remain largely unclear. The Youth Mental Health Risk and Resilience Study (YouR-Study) obtained a community sample of CHR-P individuals through an online-screening approach and followed-up these individuals for a period of up to 3 years to determine transition rates, persistence of attenuated psychotic symptoms (APS) and functional outcomes. Baseline data were obtained from n = 144 CHR-P participants, n = 51 participants who met online cutoff criteria but not CHR-P criteria (CHR-Ns), and n = 58 healthy controls. Baseline assessments included clinical measures for assessing CHR-P status, including the Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Schizophrenia Proneness Instrument, Adult version (SPI-A), as well as functioning and cognitive measures. CHR-P and CHR-N groups were followed-up. Results show that 12.1% of CHR-P individuals transitioned to psychosis over 3 years, with no transitions in the CHR-N group. Nearly 60% of CHR-P individuals experienced poor functional outcome (PFO) and over 40% experienced persistent APS. A combination of CAARMS/SPI-A criteria was associated with a higher likelihood of PFO, but not with transition to psychosis nor APS persistence. However, transition risk was generally higher among those meeting both CAARMS/SPI-A criteria (64.3%) vs CAARMS (28.6%) or SPI-A (7.1%) alone. In summary, community-recruited CHR-P individuals are characterized by similar clinical characteristics and longitudinal outcomes to those recruited from clinical services, emphasizing the need to widen the scope of early detection and intervention strategies.

Background: Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical, cognitive, social cognitive, and functional differences between youth at clinical high-risk (CHR) for psychosis with and without comorbid ADHD.

Method: Data were drawn from the North American Prodrome Longitudinal Studies (NAPLS2 and NAPLS3), which included 764 and 710 CHR individuals, respectively. After applying exclusion criteria, the sample consisted of 271 CHR participants with ADHD and 1118 without ADHD. All data were examined cross-sectionally.

Results: Compared with the non-ADHD group, the ADHD group was younger, had more difficulties with role functioning, premorbid functioning, and social cognition, were more likely to have a comorbid learning disorder, and reported less depression symptoms. There were no significant differences between the groups on positive or negative psychotic symptoms, transition rates, adverse events, or other comorbid disorders including substance use and depression.

Discussion: Comorbid ADHD is likely not a significant predictor of transition to psychosis among CHR youth; however, those CHR with ADHD may experience symptoms at a younger age than those without and present with a distinct clinical profile.

Background and hypothesis: Gut microbiota has been implicated in the pathogenesis of schizophrenia (SZ) and relevant changes in the brain, but the underlying mechanism remains elusive. This study aims to investigate the microbiota-gut-brain crosstalk centered on peripheral inflammation in SZ patients.

Study design: We recruited a cohort of 182 SZ patients and 120 healthy controls (HC). Multi-omics data, including fecal 16S rRNA, cytokine data, and neuroimaging data, were collected and synthesized for analysis. Multi-omics correlations and mediation analyses were utilized to determine the associations of gut microbiome with inflammatory cytokines and neuroimaging characteristics. Additionally, machine learning models for effective SZ diagnosis were separately generated based on gut microbial and neuroimaging data.

Study results: Gut microbial dysbiosis, characterized by a decrease in butyrate-producing bacteria and an increase in proinflammatory bacteria, has been identified in SZ patients. These key microbial taxa were associated with increased inflammatory cytokines, potentially through mediating lipid metabolic pathways such as steroid biosynthesis and linoleic acid metabolism. Further analysis revealed altered microbial genera to be correlated with disrupted gray matter volume and regional homogeneity in SZ patients. Importantly, certain inflammatory cytokines mediated the relationship between the SZ-enriched genus Succinivibrio and aberrant activity of anterior cingulate cortex and left inferior temporal gyrus in the SZ group. Moreover, the classification model based on gut microbial data showed comparable efficacy to the model based on brain functional signatures in SZ diagnosis.

Conclusions: This study presents evidence for the dysregulated microbiota-gut-brain axis in SZ and emphasizes the central role of peripheral inflammation.

Some but not other studies on oxytocin for schizophrenia, particularly those using a higher dose, indicate that oxytocin improves negative symptoms of schizophrenia. We performed an add-on randomized controlled trial to examine the effect of high-dose oxytocin, social skills training, and their combination in the treatment of negative symptoms and social dysfunction in schizophrenia. Fifty-one subjects with schizophrenia were randomized, employing a two-by-two design: intranasal oxytocin (24 IU X3/day) or placebo, and social skills training or supportive psychotherapy, for 3 weeks. The primary outcome was the difference in the total score from baseline to end-of-study of a semi-structured interview which assessed patients' social interactions in 3 scenarios: sharing a positive experience, sharing a conflict, and giving support when the experimenter shared a conflict. The interactions were scored using the Coding Interactive Behavior Manual (CIB), clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). No significant difference was found between groups in the total CIB or PANSS scores. The majority of comparisons in the different social interactions between oxytocin and placebo, and between social skills training vs supportive psychotherapy, were also nonsignificant. Social skills training reduced blunted affect and gaze. In post-hoc analyses of the support interaction, oxytocin improved synchrony and decreased tension, while in the positive interaction it improved positive affect and avoidance. None of these findings remained significant when controlling for multiple comparisons. In conclusion, oxytocin did not influence participants' social behavior, and was not effective in improving the symptoms of schizophrenia. Clinicaltrials.gov Identifier: NCT01598623.

There is a broad consensus that the commonly used clinician-administered rating scales for assessment of negative symptoms share significant limitations, including (1) reliance upon accurate self-report and recall from the patient and caregiver; (2) potential for sampling bias and thus being unrepresentative of daily-life experiences; (3) subjectivity of the symptom scoring process and limited sensitivity to change. These limitations led a work group from the International Society of CNS Clinical Trials and Methodology (ISCTM) to initiate the development of a multimodal negative symptom instrument. Experts from academia and industry reviewed the current methods of assessing the domains of negative symptoms including diminished (1) affect; (2) sociality; (3) verbal communication; (4) goal-directed behavior; and (5) Hedonic drives. For each domain, they documented the limitations of the current methods and recommended new approaches that could potentially be included in a multimodal instrument. The recommended methods for assessing negative symptoms included ecological momentary assessment (EMA), in which the patient self-reports their condition upon receipt of periodic prompts from a smartphone or other device during their daily routine; and direct inference of negative symptoms through detection and analysis of the patient's voice, appearance or activity from audio/visual or sensor-based (eg, global positioning systems, actigraphy) recordings captured by the patient's smartphone or other device. The process for developing an instrument could resemble the NIMH MATRICS process that was used to develop a battery for measuring cognition in schizophrenia. Although the EMA and other digital measures for negative symptoms are at relatively early stages of development/maturity and development of such an instrument faces substantial challenges, none of them are insurmountable.

Negative symptoms (NS) of schizophrenia spectrum disorders (SSD) are also prevalent in bipolar disorder I (BD-I) and show associations with impaired working memory (WM). However, empirical work on their relationship to other clinical factors across SSD and BD-I is sparse. Here, we characterized the associations of NS with key clinical variables and WM capacity across a combined sample of SSD and BD. We included 50 outpatients with SSD and 49 with BD-I and assessed NS domains using SANS global scores for avolition-apathy, anhedonia-asociality, alogia, and blunted affect. We assessed the transdiagnostic relationship between NS and other clinical variables, including positive symptoms, disorganization, depressive symptoms, and antipsychotic medication, using multiple regressions. The strength of these associations was further determined through dominance analyses. Finally, we used multiple regression to assess the relationship between NS domains and WM. To assess the generalizability of transdiagnostic associations, analyses were repeated in each diagnostic group separately. Across SSD and BD-I, disorganization was associated with avolition-apathy and anhedonia-asociality and depressive symptoms additionally predicted anhedonia-asociality. Antipsychotic dose was associated with blunted affect while group differences only predicted alogia. Higher avolition-apathy was related to impaired WM transdiagnostically, partially mediated by the severity of disorganization, whereas only in BD-I higher anhedonia-asociality was associated with better WM capacity. This study demonstrated transdiagnostic associations of both avolition-apathy and anhedonia-asociality with disorganization and identified avolition-apathy as a potential transdiagnostic predictor of WM impairments. Overall, our findings highlight the importance of understanding the relationship between NS domains and other clinical factors with cognitive function across SSD and BD.

Background and hypothesis: Problematic gaming (PG) is an emerging mental health condition associated with significant adverse outcomes. Even though PG has been linked to other psychiatric disorders, its association with psychotic experiences (PEs) remains poorly explored to date. The aim of our study was to examine the association between both conditions in a large Brazilian community sample. We hypothesized that adolescents with PG were more likely to report PE compared with those without the disorder.

Study design: Our investigation was based on a cross-sectional subsample of a large Brazilian cohort (n = 1616; 13- to 21-year age range). Using the 7-item version of the Game Addiction Scale, participants were classified according to their gaming status: no PG, PG, or gaming addiction (GA). The association between PG, GA, and PE was assessed through linear regression analyses, which were adjusted for the presence of significant covariates, including other psychiatric conditions.

Study results: 9.5% (n = 154) presented PG and 2.7% (n = 43) had GA. 28.0% received any Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis and the mean PE score was 9.39 (SD = 4.35). Participants presenting PG had greater levels of PE, compared with participants with no PG, even controlled by sociodemographic variables and the presence of any DSM-IV diagnosis (b = 0.96, 95% CI = 0.17-1.75, P = .017).

Conclusions: According to our results, PG was significantly associated with PE, even in the presence of other covariates. Although preliminary, these results suggest that PG and PE may have shared neurobiological and/or behavioral pathways.