Schizophrenia bulletin open最新文献

Background and hypothesis: Affective forecasting (AF), the ability to forecast emotional responses for future events, is critical for optimal decision-making and mental health. Most previous AF studies were conducted using laboratory-based tasks but overlooked the impacts of real-life situations and social interactions. This study used the experience sampling method to examine real-life AF in young healthy adults and individuals with high social anhedonia.

Study design: In Study 1, 109 young healthy adults reported anticipated and experienced emotions of personal events for 30 days on mobile phones. In Study 2, we examined real-life AF in 28 individuals with high social anhedonia (HSA) and 32 individuals with low social anhedonia (LSA).

Study results: In Study 1 (totaling 8031 real-life events), participants anticipated and experienced social events as more positive and more arousing than non-social events, but also with larger AF discrepancy. In Study 2 (totaling 2066 real-life events), compared with the LSA group, the HSA group anticipated less pleasure and displayed a larger valence discrepancy especially for social but not for non-social events. However, the HSA group reported less experienced pleasure for both social and non-social events.

Conclusions: Using an ecological method for assessing real-life AF, we extended the previous laboratory-based findings to real-life situations. These findings demonstrate the effects of sociality on real-life AF and elucidate the deficit in anticipating social pleasure among HSA individuals, which reflects liability to schizophrenia-spectrum disorders. Altered AF may be a potential intervention target in people with schizophrenia spectrum disorder.

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.

Background and hypothesis: The relationship between Klotho and cognitive dysfunction in schizophrenia has been scarcely explored, with a few paradoxical findings. Hence, we aimed to enhance our understanding by testing associations between the functional KL-VS gene variant and circulating protein levels.

Research design: This case-control study included 239 healthy controls and 241 patients with schizophrenia, who were comprehensively characterized by neurocognitive tests and further subtyped into cognitive clusters; cognitively deficient (CD) and cognitively spared (CS), using K-means cluster analysis. Linear regression models were run to assess the main and iinteraction effects of the KL-VS heterozygosity (KL-VS^Het+)/KL levels with confounding variables (disease status and age) on cognitive scores.

Results: There was no main effect of KL-VS^Het+ on the cognitive domains, but the CD cluster exhibited strong negative interactions between disease status and Klotho for executive function at the gene level, KL-VS^Het+ × disease status, β = -.61, P = .043, with comparatively higher effect observed for KL levels, KL levels × disease status, β = -.91, P = .028. There was an opposing positive interaction for response inhibition, KL-VS^Het+ × disease status, limited again to the CD cluster, β = .35, P = .046, with a higher effect at protein levels, KL levels × disease status, β = .72, <.004, though without CD cluster effect.

Conclusions: Overall, these dissociable patterns of association across cognitive domains indicate the need to exert caution over accepting any generalised direction of effect of Klotho at gene or protein level on cognition in schizophrenia.

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.