Schizophrenia Bulletin最新文献

Background and hypothesis: People with psychotic disorders have a higher risk of mortality following cancer diagnosis, compared to people without psychosis. The extent to which this disparity is influenced by differences in cancer-related treatment is currently unknown. We hypothesized that, following a cancer diagnosis, people with psychotic disorders were less likely to receive treatment and were at higher risk of death than those without psychosis.

Study design: We constructed a retrospective cohort of cases of non-affective psychotic disorder (NAPD) and a general population comparison group, using Ontario Health (OH) administrative data. We identified cases of all cancers diagnosed between 1995 and 2019 and obtained information on cancer-related treatment and mortality. Cox proportional hazards models were used to compare the probability of having a consultation with an oncologist and receiving cancer-related treatment, adjusting for tumor site and stage. We also compared the rate of all-cause and cancer-related mortality between the two groups, adjusting for tumor site.

Study results: Our analytic sample included 24 944 people diagnosed with any cancer. People with NAPD were less likely to receive treatment than people without psychosis (HR = 0.87, 95% CI = 0.82, 0.91). In addition, people with NAPD had a greater risk of death from any cause (HR = 1.68, 95% CI = 1.60, 1.76), compared to people without NAPD.

Conclusions: The lower likelihood of receiving cancer treatment reflects disparities in accessing cancer care for people with psychotic disorders, which may partially explain the higher mortality risk following cancer diagnosis. Future research should explore mediating factors in this relationship to identify targets for reducing health disparities.

Background and hypothesis: Individuals with schizophrenia (SCZ) suffer from comorbidities that substantially reduce their life expectancy. Socioeconomic inequalities could contribute to many of the negative health outcomes associated with SCZ.

Study design: We investigated genome-wide datasets related to SCZ (52 017 cases and 75 889 controls) from the Psychiatric Genomics Consortium, household income (HI; N = 361 687) from UK Biobank, and 2202 medical endpoints assessed in up to 342 499 FinnGen participants. A phenome-wide genetic correlation analysis of SCZ and HI was performed, also assessing whether SCZ genetic correlations were influenced by the HI effect on SCZ. Additionally, SCZ and HI direct effects on medical endpoints were estimated using multivariable Mendelian randomization (MR).

Study results: SCZ and HI showed overlapping genetic correlations with 70 traits (P < 2.89 × 10-5), including mental health, substance use, gastrointestinal illnesses, reproductive outcomes, liver diseases, respiratory problems, and musculoskeletal phenotypes. SCZ genetic correlations with these traits were not affected by the HI effect on SCZ. Considering Bonferroni multiple testing correction (P < 7.14 × 10-4), MR analysis indicated that SCZ and HI may affect medical abortion (SCZ OR = 1.07; HI OR = 0.78), panic disorder (SCZ OR = 1.20; HI OR = 0.60), personality disorders (SCZ OR = 1.31; HI OR = 0.67), substance use (SCZ OR = 1.2; HI OR = 0.68), and adjustment disorders (SCZ OR = 1.18; HI OR = 0.78). Multivariable MR analysis confirmed that SCZ effects on these outcomes were independent of HI.

Conclusions: The effect of SCZ genetic liability on mental and physical health may not be strongly affected by socioeconomic differences. This suggests that SCZ-specific strategies are needed to reduce negative health outcomes affecting patients and high-risk individuals.

Background and hypothesis: There is mounting evidence that cardiac interoception, the perception of one's heartbeat, is central to affective experiences. It has been proposed that symptoms of psychosis could arise from interoceptive dysfunction. Here we hypothesized that people with psychotic disorders would have a specific impairment in cardiac interoception, over and above broader perceptual deficits.

Study design: 43 adults with a history of psychosis (31 schizophrenia, 12 schizoaffective disorder) and 41 matched control participants completed a heart rate discrimination task. Participants responded to whether they perceived a sequence of auditory tones to be faster or slower than their heart rate. By trialing a range of auditory tone rates, we estimated a threshold for each participant, the difference between perceived heart rate and actual heart rate. To test whether differences were specific to interoception, participants completed an exteroceptive control condition, testing their discrimination of the rate of 2 sets of audible sounds instead of heart rate.

Study results: Participants with a history of psychosis had greater absolute differences between perceived and actual heart rate, indicating over- or under-estimation of heart rate compared to healthy controls. This difference was specific to the interoceptive condition, and not explained by group differences in exteroceptive perception.

Conclusions: Psychotic disorders are associated with misestimation of heart rate. Further research may elucidate whether interoceptive abnormalities contribute to specific symptoms such as somatic delusions or affective features, and whether interoception could be a treatment target in psychotic disorders.

Background and hypothesis: Suicide is a leading cause of death in first-episode psychosis (FEP), with an elevated risk during the first year following illness onset. The association between negative symptoms and suicidality remains contentious. Some studies suggest that negative symptoms may be associated with lower suicidality, while others fail to find an association between the two. No previous studies have specifically investigated suicidality in Persistent Negative Symptoms (PNS) and its associated subgroups.

Study design: In a large cohort of FEP patients (n = 515) from an early intervention service, we investigated suicidality in those with PNS, secondary PNS (ie, sPNS; PNS with clinical-level positive, depressive, or extrapyramidal symptoms), and non-PNS (all other patients) over 24 months. Patients were categorized into PNS groups based on symptoms from month 6 to month 12, and suicidality was evaluated using the Brief Psychiatric Rating Scale (BPRS).

Study results: Covarying for age and sex, we found that sPNS had higher suicidality relative to PNS and non-PNS throughout the 24-month period, but PNS and non-PNS did not differ. These differences were maintained after adjusting for depressive symptoms.

Conclusion: We observed that PNS did not significantly differ from non-PNS. However, we identified sPNS as a group with elevated suicidality above and beyond depression, suggesting that sPNS would benefit from targeted intervention and that PNS categorization identifies a subgroup for whom negative symptoms are not associated with lower suicidality.

Background: Schizophrenia, a multifaceted psychiatric disorder characterized by functional dysconnectivity, poses significant challenges in clinical practice. This study explores the potential of functional connectivity (FC)-based searchlight multivariate pattern analysis (CBS-MVPA) to discriminate between schizophrenia patients and healthy controls while also predicting clinical variables.

Study design: We enrolled 112 schizophrenia patients and 119 demographically matched healthy controls. Resting-state functional magnetic resonance imaging data were collected, and whole-brain FC subnetworks were constructed. Additionally, clinical assessments and cognitive evaluations yielded a dataset comprising 36 clinical variables. Finally, CBS-MVPA was utilized to identify subnetworks capable of effectively distinguishing between the patient and control groups and predicting clinical scores.

Study results: The CBS-MVPA approach identified 63 brain subnetworks exhibiting significantly high classification accuracies, ranging from 62.2% to 75.6%, in distinguishing individuals with schizophrenia from healthy controls. Among them, 5 specific subnetworks centered on the dorsolateral superior frontal gyrus, orbital part of inferior frontal gyrus, superior occipital gyrus, hippocampus, and parahippocampal gyrus showed predictive capabilities for clinical variables within the schizophrenia cohort.

Conclusion: This study highlights the potential of CBS-MVPA as a valuable tool for localizing the information related to schizophrenia in terms of brain network abnormalities and capturing the relationship between these abnormalities and clinical variables, and thus, deepens our understanding of the neurological mechanisms of schizophrenia.

Background and hypothesis: Social cognitive impairments are central to psychosis, including lower severity psychosis-like experiences (PLEs). Nonetheless, progress has been hindered by social cognition's poorly defined factor structure, as well as limited work examining the specificity of social cognitive impairment to psychosis. The present study examined how PLEs relate to social cognition in the context of other psychopathology dimensions, using a hierarchical factors approach to social cognition.

Study design: Online community participants (N = 1026) completed psychosis, autism, and personality disorder questionnaires, as well as 3 social cognitive tasks that varied in methodology (vignette vs video) and construct (higher- vs lower-level social cognition). Exploratory (EFA) and confirmatory factor analyses (CFA) were used to model social cognition, with the best models being examined in association with PLEs and psychopathology dimensions.

Study results: EFA and CFA supported a hierarchical model of social cognition, with 2 higher-order factors emerging: verbal/vignette task methodology and a multimethod general social cognition factor. These higher-order factors accounted for task-level associations to psychopathology, with relations to positive symptoms (r = .23) and antagonism (r = .28). After controlling for other psychopathology, positive symptoms were most clearly related to tasks with verbal methodology (β = -0.34).

Conclusions: These results suggest that broad social cognitive processes and method effects may account for many previous findings in psychosis and psychopathology research. Additionally, accounting for broad social cognitive impairment may yield insights into more specific social cognitive processes as well.

Background and hypothesis: The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia.

Study design: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29).

Study results: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits.

Conclusions: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.

Background and hypothesis: Schizophrenia is associated with a decreased pursuit of risky rewards during uncertain-risk decision-making. However, putative mechanisms subserving this disadvantageous risky reward pursuit, such as contributions of cognition and relevant traits, remain poorly understood.

Study design: Participants (30 schizophrenia/schizoaffective disorder [SZ]; 30 comparison participants [CP]) completed the Balloon Analogue Risk Task (BART). Computational modeling captured subprocesses of uncertain-risk decision-making: Risk Propensity, Prior Belief of Success, Learning Rate, and Behavioral Consistency. IQ, self-reported risk-specific processes (ie, Perceived Risks and Expected Benefit of Risks), and non-risk-specific traits (ie, defeatist beliefs; hedonic tone) were examined for relationships with Risk Propensity to determine what contributed to differences in risky reward pursuit.

Study results: On the BART, the SZ group exhibited lower Risk Propensity, higher Prior Beliefs of Success, and comparable Learning Rates. Furthermore, Risk Propensity was positively associated with IQ across groups. Linear models predicting Risk Propensity revealed 2 interactions: 1 between group and Perceived Risk, and 1 between IQ and Perceived Risk. Specifically, in both the SZ group and individuals with below median IQ, lower Perceived Risks was related to lower Risk Propensity. Thus, lower perception of financial risks was associated with a less advantageous pursuit of uncertain-risk rewards.

Conclusions: Findings suggest consistently decreased risk-taking on the BART in SZ may reflect risk imperception, the failure to accurately perceive and leverage relevant information to guide the advantageous pursuit of risky rewards. Additionally, our results highlight the importance of cognition in uncertain-risk decision-making.

Background and hypothesis: Altered functional connectivity (FC) has been frequently reported in psychosis. Studying FC and its time-varying patterns in early-stage psychosis allows the investigation of the neural mechanisms of this disorder without the confounding effects of drug treatment or illness-related factors.

Study design: We employed resting-state functional magnetic resonance imaging (rs-fMRI) to explore FC in individuals with early psychosis (EP), who also underwent clinical and neuropsychological assessments. 96 EP and 56 demographically matched healthy controls (HC) from the Human Connectome Project for Early Psychosis database were included. Multivariate analyses using spatial group independent component analysis were used to compute static FC and dynamic functional network connectivity (dFNC). Partial correlations between FC measures and clinical and cognitive variables were performed to test brain-behavior associations.

Study results: Compared to HC, EP showed higher static FC in the striatum and temporal, frontal, and parietal cortex, as well as lower FC in the frontal, parietal, and occipital gyrus. We found a negative correlation in EP between cognitive function and FC in the right striatum FC (pFWE = 0.009). All dFNC parameters, including dynamism and fluidity measures, were altered in EP, and positive symptoms were negatively correlated with the meta-state changes and the total distance (pFWE = 0.040 and pFWE = 0.049).

Conclusions: Our findings support the view that psychosis is characterized from the early stages by complex alterations in intrinsic static and dynamic FC, that may ultimately result in positive symptoms and cognitive deficits.