Schizophrenia Research最新文献

Background

Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization.

Methods

A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models.

Results

There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (−3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable.

Conclusion

COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

In people with schizophrenia (PwS), inflammation and metabolic issues significantly increase morbidity and mortality. However, our ability to understand inflammatory-metabolic mechanisms in this population has been limited to cross-sectional studies. This study involved 169 PwS and 156 non-psychiatric comparisons (NCs), aged 25–65, observed between 2012 and 2022 with 0 to 5 follow-ups post-baseline. High-sensitivity C-reactive protein (hs-CRP), a marker of inflammation, was measured via a particle-enhanced immuno-turbidimetric assay. Body mass index (BMI) was used as a proxy for metabolic function. The measurement intervals for hs-CRP and BMI ranged between 6 and 48 months. Linear mixed models (LMM) results revealed that at all time points, PwS has a higher hs-CRP (t (316) = 4.73, p < .001) and BMI (t (315) = 4.13, p < .001) than NCs; however, for BMI, this difference decreased over time (t (524) = −5.15, p < .001). To study interrelationships between hs-CRP and BMI, continuous time structural equational modeling (CTSEM) was used, accounting for uneven measurement intervals. CTSEM results showed that both hs-CRP predicted future BMI (Est. = 12.91, 95 % CI [7.70; 17.88]) and BMI predicted future hs-CRP (Est. = 1.54, 95 % CI [1.00; 2.04]), indicating a bidirectional relationship between inflammation and metabolic function. Notably, the influence of hs-CRP on future BMI was more robust than the other lagged relationship (p = .015), especially in PwS (Est. = 2.43, 95 % CI [0.39; 0.97]). Our study highlights the important role of inflammation in metabolic function and offers insights into potential interventions targeting inflammation in PwS.

Introduction

Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender differences from the time of entry in an early intervention program for psychosis, up to three years follow-up.

Methods

We conducted a prospective study including a cohort of 474 patients treated at the Treatment and Early Intervention in Psychosis (TIPP) program, 319 men and 155 women, having presented a first episode of psychosis (FEP). Data regarding premorbid and baseline sociodemographic, psychopathological and patient functioning, were collected. These data were reassessed longitudinally after 2, 6, 12, 18, 24, 30 and 36 months after entry in TIPP.

Results

Regarding premorbid and baseline characteristics, woman developed threshold symptoms of a FEP 1 year later than men on average. Women were more likely to be married, men were more likely to live in pension or care home facility or to be homeless. Women displayed a higher rate of history of suicide attempts and exposure to childhood trauma, while men were more likely to have a forensic history, a history of abuse of alcohol and cannabis as well as a dependency to cannabis at the time of entry in TIPP. Regarding evolution, men were more prone to violent acts and were less likely to decrease their usage of substances. The longitudinal analysis highlighted that men displayed greater negative symptoms over the entire treatment period, lower functioning after 6 months and on all assessment points after. Both genders displayed similar rate of improvement in these 3 dimensions over time.

Conclusion

Our study confirms that there are some gender differences in the early phase of psychosis that may require differentiation of assessment and treatment to improve recovery.

Background

The complement component C4 gene has been identified as a strong marker for schizophrenia (SCZ) risk. The C4 gene has a complex genetic structure consisting of variable structural elements (C4A, C4B, C4L, and C4S) and compound structural forms (C4AL, C4BL, C4AS and C4BS). In addition, the variations in C4 structural forms may have a direct or indirect effect on the brain expression level of C4A and C4B proteins. Previous studies have associated C4AL with higher brain C4A expression and sex-dimorphism of C4 between males and females was observed.

Study design

A total of 613 patients with DSM-IV SCZ or schizoaffective disorder (SCZ-AFF) were recruited to investigate the relationship between C4 gene variants and clinical characteristics of SCZ (age of onset, symptom severity, and global assessment of functioning (GAF)). This study also explored the effect of sex on the association of C4 with SCZ. 434 patients were included in the final analyses after genetic quality control.

Results

We observed associations between C4 and clinical characteristics of SCZ (age of onset, symptom severity, GAF) and found significant differences when males and females were examined separately.

Conclusion

Overall, our preliminary findings encourage future investigations of C4 in SCZ-related phenotypes, including antipsychotic response and side effects. The study sample was of moderate size; therefore, further studies in larger samples are needed to extend and validate these results.

Background

Neurocognitive deficits have been widely reported in clinical high-risk for psychosis (CHR) populations. Additionally, rates of cannabis use are high among CHR youth and are associated with greater symptom severity. Cannabis use has been sometimes shown to be associated with better neurocognition in more progressed psychosis cohorts, therefore in this study we aimed to determine whether a similar pattern was present in CHR.

Methods

CHR participants ages 12–30 from the North American Prodromal Longitudinal Study (NAPLS-3) (N = 698) were grouped according to: “minimal to no cannabis use” (n = 406), “occasional use” (n = 127), or “frequent use” (n = 165). At baseline, cannabis use groups were compared on neurocognitive tests, clinical, and functional measures. Follow-up analyses were used to model relationships between cannabis use frequency, neurocognition, premorbid, and social functioning.

Results

Occasional cannabis users performed significantly better than other use-groups on measures of IQ, with similar trend-level patterns observed across neurocognitive domains. Occasional cannabis users demonstrated better social, global, and premorbid functioning compared to the other use-groups and less severe symptoms compared to the frequent use group. Follow-up structural equation modeling/path analyses found significant positive associations between premorbid functioning, social functioning, and IQ, which in turn was associated with occasional cannabis use frequency.

Discussion

Better premorbid functioning positively predicts both better social functioning and higher IQ which in turn is associated with a moderate cannabis use pattern in CHR, similar to reports in first-episode and chronic psychosis samples. Better premorbid functioning likely represents a protective factor in the CHR population and predicts a better functional outcome.

Background

There is a well-established, although complex, association between aggression and psychosis, particularly in the early stages of illness. Some persons display aggressive behaviors even prior to psychosis onset. However, factors associated with aggressive behaviors prior to and at first-episode psychosis (FEP) onset remain underdocumented.

Aims

The objective is two-fold: 1) to describe the prevalence of verbal and physical aggression occurring during the premorbid phase and at FEP onset; 2) distinguish the factors associated with aggressive behaviors during these two periods.

Method

Data on aggressive behaviors and factors potentially associated therewith were collected through research interviews and chart reviews among 567 persons with FEP admitted to two early intervention services in Montreal, Canada. Logistic regression analyses were conducted to identify factors associated with aggressive behaviors in both periods.

Results

In the premorbid phase, 46.1 % (n = 257/558) of patients presented aggression (verbal: 35.9 %; towards objects: 24.2 %; against others: 27.9 %). At FEP, 18.1 % (n = 101/558) presented aggressive behaviors (verbal: 12.9 %; towards objects: 6.1 %; against others: 8.8 %). In the premorbid phase, lower education, prior justice involvement, cluster B personality traits/disorder and poorer functioning were associated with aggressive behaviors, while, at FEP, only prior homelessness was associated with aggression.

Conclusions

Aggressive behaviors are frequent in patients with FEP, prior onset and at FEP. Premorbid aggressive behaviors seem to be associated with premorbid difficulties. Early detection of youth with psychosis and those at high risk of psychosis, particularly homeless youth, is necessary to provide access to early specialized interventions and possibly prevent aggressive behaviors and their consequences.

Background

Thalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits.

Methods

75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments.

Results

No significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group.

Conclusions

Our findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease.

Trial registration

ClinicalTrials.gov NCT03965598; https://clinicaltrials.gov/ct2/show/NCT03965598.

Schizophrenia is a neurodevelopmental disorder associated with deficits in cognitive development and childhood psychopathology. Previous studies have focused on older children and the few studies of early childhood have yielded inconsistent findings. We studied cognitive development and psychopathology in children at familial high risk (FHR) of schizophrenia and matched controls from 1 to 6 years and hypothesized that FHR children would show consistent deficits across cognitive and behavioral measures in early childhood.

Study design

Cognitive development in children at high familial risk for schizophrenia or schizoaffective disorder (n = 33) and matched healthy controls (n = 66) was assessed at 1 and 2 years with the Mullen Scales of Early Learning, and at 4 and 6 years with the Stanford Binet Intelligence Scales, BRIEF-P/BRIEF and CANTAB. Psychopathology was assessed at 4 and 6 years with the BASC-2. General linear models were used to examine differences on outcome scores, and chi-square analyses were used to explore differences in the proportion of “at risk” or “below average” score profiles.

Study results

FHR children scored significantly lower than controls on Mullen Composite at age 2, and demonstrated broad deficits in IQ, executive function and working memory and 4 and 6 years. FHR children were also rated as significantly worse on most items of the BASC-2 at ages 4 and 6.

Conclusions

Children at FHR for schizophrenia demonstrate abnormal cognitive development and psychopathology at younger ages than previously detected, suggesting that early detection and intervention needs to be targeted to very early childhood.

Background

The ability to value rewards is crucial for adaptive behavior and is influenced by the time and effort required to obtain them. Impairments in these computations have been observed in patients with schizophrenia and may be present in individuals with subclinical psychotic symptoms (PS).

Methods

In this study, we employed delay and effort-discounting tasks with food rewards in thirty-nine participants divided into high and low levels of PS. We investigated the underlying mechanisms of effort-discounting through computational modelling of dopamine prefrontal and subcortical circuits and the electrophysiological biomarker of both delay and effort-discounting alterations through resting-state frontal alpha asymmetry (FAA).

Results

Results revealed greater delay discounting in the High PS group compared to the Low PS group but no differences in the effort discounting task. However, in this task, the same levels of estimated dopamine release were associated with a lower willingness to exert effort for high-calorie food rewards in High PS participants compared to Low PS participants. Although there were no significant differences in FAA between the High PS and Low PS groups, FAA was significantly associated with the severity of participants' negative symptoms.

Conclusions

Our study suggests that the dysfunction in temporal and effort cost computations, seen in patients with schizophrenia, may be present in individuals with subclinical PS. These findings provide valuable insight into the early vulnerability markers (behavioral, computational, and electrophysiological) for psychosis, which may aid in the development of preventive interventions. These findings are preliminary and warrant further investigation.