NPJ Schizophrenia最新文献

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions.

Plasma 24S-hydroxycholesterol mostly originates in brain tissue and likely reflects the turnover of cholesterol in the central nervous system. As cholesterol is disproportionally enriched in many key brain structures, 24S-hydroxycholesterol is a promising biomarker for psychiatric and neurologic disorders that impact brain structure. We hypothesized that, as schizophrenia patients have widely reported gray and white matter deficits, they would have abnormal levels of plasma 24S-hydroxycholesterol, and that plasma levels of 24S-hydroxycholesterol would be associated with brain structural and functional biomarkers for schizophrenia. Plasma levels of 24S-hydroxycholesterol were measured in 226 individuals with schizophrenia and 204 healthy controls. The results showed that levels of 24S-hydroxycholesterol were not significantly different between patients and controls. Age was significantly and negatively correlated with 24S-hydroxycholesterol in both groups, and in both groups, females had significantly higher levels of 24S-hydroxycholesterol compared to males. Levels of 24S-hydroxycholesterol were not related to average fractional anisotropy of white matter or cortical thickness, or to cognitive deficits in schizophrenia. Based on these results from a large sample and using multiple brain biomarkers, we conclude there is little to no value of plasma 24S-hydroxycholesterol as a brain metabolite biomarker for schizophrenia.

Extensive research has been carried out on the comparative effectiveness of antipsychotic medications. Most studies, however, have been performed in Western countries. The purpose of this study was to compare the effectiveness, indicated by time to any-cause discontinuation, of antipsychotic drugs in a large number of patients with schizophrenia in South Korea. We identified 1458 patients with schizophrenia or schizophreniform disorder who were treated with antipsychotic medications using a clinical data warehouse at the Seoul National University Hospital between March 2005 and February 2014. Kaplan-Meier survival analyses were used to estimate the time to discontinuation of antipsychotic drugs. We compared the survival curves of different antipsychotics using log-rank tests. Overall, the median time to discontinuation for any cause was 133 days (95% CI, 126-147). The longest time to discontinuation was observed for clozapine, followed by aripiprazole, paliperidone, olanzapine, amisulpride, risperidone, quetiapine, ziprasidone, and haloperidol. Specifically, clozapine was significantly different from all other antipsychotic drugs (all p < 0.001). Aripiprazole also had a significantly longer time to discontinuation than amisulpride (p = 0.001), risperidone (p < 0.001), quetiapine (p < 0.001), ziprasidone (p < 0.001), and haloperidol (p < 0.001). In Asian patients with schizophrenia, clozapine was the most effective antipsychotic in terms of time to discontinuation, followed by aripiprazole. This study extends the findings of previous effectiveness studies from Western populations and suggests the need to develop guidelines for the pharmacotherapy of schizophrenia tailored to Asian individuals.

There is a scarcity of evidence on subjectively reported cognitive difficulties in individuals at ultra-high risk (UHR) for psychosis and whether these self-perceived cognitive difficulties may relate to objective cognitive deficits, psychopathology, functioning, and adherence to cognitive remediation (CR). Secondary, exploratory analyses to a randomized, clinical trial were conducted with 52 UHR individuals receiving a CR intervention. Participants completed the Measure of Insight into Cognition-Self Report (MIC-SR), a measure of daily life cognitive difficulties within the domains of attention, memory, and executive functions along with measures of neuropsychological test performance, psychopathology, functioning, and quality of life. Our study found participants with and without objectively defined cognitive deficits reported self-perceived cognitive deficits of the same magnitude. No significant relationship was revealed between self-perceived and objectively measured neurocognitive deficits. Self-perceived cognitive deficits associated with attenuated psychotic symptoms, overall functioning, and quality of life, but not with adherence to, or neurocognitive benefits from, a CR intervention. Our findings indicate that UHR individuals may overestimate their cognitive difficulties, and higher levels of self-perceived cognitive deficits may relate to poor functioning. If replicated, this warrants a need for both subjective and objective cognitive assessment in at-risk populations as this may guide psychoeducational approaches and pro-functional interventions. Self-perceived cognitive impairments do not seem to directly influence CR adherence and outcome in UHR states. Further studies are needed on potential mediator between self-perceived cognitive deficits and functioning and quality of life.

Suicide is a major cause of death in patients with schizophrenia, particularly among those with recent disease onset. Although brain imaging studies have identified the neuroanatomical correlates of suicidal behavior, functional brain activity correlates particularly in patients with recent-onset schizophrenia (ROSZ) remain unknown. Using near-infrared spectroscopy (NIRS) recording with a high-density coverage of the prefrontal area, we investigated whether prefrontal activity is altered in patients with ROSZ having a history of suicide attempts. A 52-channel NIRS system was used to examine hemodynamic changes in patients with ROSZ that had a history of suicide attempts (n = 24) or that lacked such a history (n = 62), and age- and sex-matched healthy controls (n = 119), during a block-design letter fluency task (LFT). Patients with a history of suicide attempts exhibited decreased activation in the right dorsolateral prefrontal cortex compared with those without such a history. Our findings indicate that specific regions of the prefrontal cortex may be associated with suicidal attempts, which may have implications for early intervention for psychosis.

Over the past 20 years there has been a great deal of research into those considered to be at risk for developing psychosis. Much has been learned and studies have been encouraging. The aim of this paper is to offer an update of the current status of research on risk for psychosis, and what the next steps might be in examining the progression from CHR to psychosis. Advances have been made in accurate prediction, yet there are some methodological issues in ascertainment, diagnosis, the use of data-driven selection methods and lack of external validation. Although there have been several high-quality treatment trials the heterogeneity of this clinical high-risk population has to be addressed so that their treatment needs can be properly met. Recommendations for the future include more collaborative research programmes, and ensuring they are accessible and harmonized with respect to criteria and outcomes so that the field can continue to move forward with the development of large collaborative consortiums as well as increased funding for multisite projects.

Deficits in social functioning are especially severe amongst schizophrenia individuals with the prevalent comorbidity of social anxiety disorder (SZ&SAD). Yet, the mechanisms underlying the recognition of facial expression of emotions-a hallmark of social cognition-are practically unexplored in SZ&SAD. Here, we aim to reveal the visual representations SZ&SAD (n = 16) and controls (n = 14) rely on for facial expression recognition. We ran a total of 30,000 trials of a facial expression categorization task with Bubbles, a data-driven technique. Results showed that SZ&SAD's ability to categorize facial expression was impared compared to controls. More severe negative symptoms (flat affect, apathy, reduced social drive) was associated with more impaired emotion recognition ability, and with more biases in attributing neutral affect to faces. Higher social anxiety symptoms, on the other hand, was found to enhance the reaction speed to neutral and angry faces. Most importantly, Bubbles showed that these abnormalities could be explained by inefficient visual representations of emotions: compared to controls, SZ&SAD subjects relied less on fine facial cues (high spatial frequencies) and more on coarse facial cues (low spatial frequencies). SZ&SAD participants also never relied on the eye regions (only on the mouth) to categorize facial expressions. We discuss how possible interactions between early (low sensitivity to coarse information) and late stages of the visual system (overreliance on these coarse features) might disrupt SZ&SAD's recognition of facial expressions. Our findings offer perceptual mechanisms through which comorbid SZ&SAD impairs crucial aspects of social cognition, as well as functional psychopathology.

Negative symptoms are a transdiagnostic feature of serious mental illness (SMI) that can be potentially "digitally phenotyped" using objective vocal analysis. In prior studies, vocal measures show low convergence with clinical ratings, potentially because analysis has used small, constrained acoustic feature sets. We sought to evaluate (1) whether clinically rated blunted vocal affect (BvA)/alogia could be accurately modelled using machine learning (ML) with a large feature set from two separate tasks (i.e., a 20-s "picture" and a 60-s "free-recall" task), (2) whether "Predicted" BvA/alogia (computed from the ML model) are associated with demographics, diagnosis, psychiatric symptoms, and cognitive/social functioning, and (3) which key vocal features are central to BvA/Alogia ratings. Accuracy was high (>90%) and was improved when computed separately by speaking task. ML scores were associated with poor cognitive performance and social functioning and were higher in patients with schizophrenia versus depression or mania diagnoses. However, the features identified as most predictive of BvA/Alogia were generally not considered critical to their operational definitions. Implications for validating and implementing digital phenotyping to reduce SMI burden are discussed.

Treatment of schizophrenia has had limited success in treating core cognitive symptoms. The evidence of multi-gene involvement suggests that multi-target therapy may be needed. Meanwhile, the complexity of schizophrenia pathophysiology and psychopathology, coupled with the species-specificity of much of the symptomatology, places limits on analysis via animal models, in vitro assays, and patient assessment. Multiscale computer modeling complements these traditional modes of study. Using a hippocampal CA3 computer model with 1200 neurons, we examined the effects of alterations in NMDAR, HCN (I_h current), and GABA_AR on information flow (measured with normalized transfer entropy), and in gamma activity in local field potential (LFP). We found that altering NMDARs, GABA_AR, I_h, individually or in combination, modified information flow in an inverted-U shape manner, with information flow reduced at low and high levels of these parameters. Theta-gamma phase-amplitude coupling also had an inverted-U shape relationship with NMDAR augmentation. The strong information flow was associated with an intermediate level of synchrony, seen as an intermediate level of gamma activity in the LFP, and an intermediate level of pyramidal cell excitability. Our results are consistent with the idea that overly low or high gamma power is associated with pathological information flow and information processing. These data suggest the need for careful titration of schizophrenia pharmacotherapy to avoid extremes that alter information flow in different ways. These results also identify gamma power as a potential biomarker for monitoring pathology and multi-target pharmacotherapy.

We combined magnetoencephalography (MEG), 7 T proton magnetic resonance spectroscopy (MRS), and 7 T fMRI during performance of a task in a group of 23 first episode psychosis (FEP) patients and 26 matched healthy controls (HC). We recorded both the auditory evoked response to 40 Hz tone clicks and the resting state in MEG. Neurometabolite levels were obtained from the anterior cingulate cortex (ACC). The fMRI BOLD response was obtained during the Stroop inhibitory control task. FEP showed a significant increase in resting state low frequency theta activity (p < 0.05; Cohen d = 0.69), but no significant difference in the 40 Hz auditory evoked response compared to HC. An across-groups whole brain analysis of the fMRI BOLD response identified eight regions that were significantly activated during task performance (p < 0.01, FDR-corrected); the mean signal extracted from those regions was significantly different between the groups (p = 0.0006; d = 1.19). In the combined FEP and HC group, there was a significant correlation between the BOLD signal during task performance and MEG resting state low frequency activity (p < 0.05). In FEP, we report significant alteration in resting state low frequency MEG activity, but no alterations in auditory evoked gamma band response, suggesting that the former is a more robust biomarker of early psychosis. There were no correlations between gamma oscillations and GABA levels in either HC or FEP. Finally, in this study, each of the three imaging modalities differentiated FEP from HC; fMRI with good and MEG and MRS with moderate effect size.