Schizophrenia (Heidelberg, Germany)最新文献

To explore the potential role of circular RNAs (circRNAs) in children developing very early-onset schizophrenia (VEOS). Total RNA was extracted from the plasma samples of 10 VEOS patients and eight healthy controls. Expression profiles of circRNAs, micro RNAs (miRNAs), and messenger RNAs (mRNAs) were analyzed using RNA-seq. The interaction networks between miRNAs and targets were predicted using the miRanda tool. A differentially expressed circRNA-miRNA-mRNA (ceRNA) network was further constructed. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the target mRNAs in the ceRNA network were performed to predict the potential functions of their host genes. The patient group and the control group were also compared on the regulatory patterns of circRNAs on mRNAs. 1934 circRNAs were identified from the samples and reported for the first time in schizophrenia. The circRNA expression levels were lower in the VEOS group than in the healthy control group, and 1889 circRNAs were expressed only in the control group. Differential expression analysis (i.e., log₂fold change > 1.5, p 0.05) identified 235 circRNAs (1 up-regulated, 234 down-regulated), 11 miRNAs (7 up-regulated, 4 down-regulated), and 2,308 mRNAs (1906 up-regulated, 402 down-regulated) respectively. In VEOS, a ceRNA network with 10 down-regulated circRNA targets, 6 up-regulated miRNAs, and 47 down-regulated mRNAs was constructed. The target genes were involved in the membrane, the signal transduction, and the cytoskeleton and transport pathways. Finally, different expression correlation patterns of circRNA and mRNA in the network were observed between the patient group and the control group. The current research is the first to reveal the differentially expressed circRNAs in the plasma of VEOS patients. A circRNA-miRNA-mRNA network was also conducted in this study. It may be implied that the circRNAs in this network are potential diagnostic biomarkers for VEOS and they play an important role in the onset and development of VEOS symptoms.

One of the most robust neurochemical abnormalities reported in patients with schizophrenia is an increase in dopamine (DA) synthesis and release, restricted to the dorsal striatum (DS). This hyper functionality is strongly associated with psychotic symptoms and progresses in those who later transition to schizophrenia. To understand the implications of this progressive neurobiology on brain function, we have developed a model in rats which we refer to as EDiPs (Enhanced Dopamine in Prodromal schizophrenia). The EDiPs model features a virally mediated increase in dorsal striatal (DS) DA synthesis capacity across puberty and into adulthood. This protocol leads to progressive changes in behaviour and neurochemistry. Our aim in this study was to explore if increased DA synthesis capacity alters the physiology of DA release and DS connectivity. Using fast scan cyclic voltammetry to assess DA release we show that evoked/phasic DA release is increased in the DS of EDiPs rats, whereas tonic/background levels of DA remain unaffected. Using quantitative immunohistochemistry methods to quantify DS synaptic architecture we show a presynaptic marker for DA release sites (Bassoon) was elevated within TH axons specifically within the DS, consistent with the increased phasic DA release in this region. Alongside changes in DA systems, we also show increased density of vesicular glutamate transporter 1 (VGluT1) synapses in the EDiPs DS suggesting changes in cortical connectivity. Our data may prove relevant in understanding the long-term implications for DS function in response to the robust and prolonged increases in DA synthesis uptake and release reported in schizophrenia.

Neuroinflammation contributes to the pathophysiology of various mental illnesses including schizophrenia. We investigated peripheral inflammatory cytokines as a biomarker for predicting symptomatic remission in patients with first-episode schizophrenia. The study included 224 patients aged 15-60 years who fulfilled the criteria for schizophrenia spectrum disorder with a treatment duration ≤6 months. Serum levels of tumor necrosis factor (TNF) -α, interferon-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, and IL-12 were measured. Psychotic symptoms, depressive symptoms, and general functioning were assessed using the Positive and Negative Syndrome Scale, Beck Depression Inventory (BDI), Calgary Depression Scale for Schizophrenia, and Personal and Social Performance scale, respectively. Duration of untreated psychosis (DUP) was also recorded. We investigated the factors associated with remission for each sex in logistic regression analysis. In total, 174 patients achieved remission at the 6-month follow-up (females, 83.5%; males, 70.9%). Remission was associated with older age and lower BDI scores in male patients and with lower TNF-α levels and shorter DUP in female patients. Our findings suggest that peripheral inflammatory cytokines may impede early symptomatic remission in female patients with schizophrenia. In addition, depressive symptoms in males and long DUP in females may be poor prognostic factors for early remission in patients with first-episode psychosis.

Cognitive Remediation (CR) improves cognition and functioning but is implemented in a variety of ways (independent, group and one-to-one). There is no information on whether service users find these implementation methods acceptable or if their satisfaction influences CR outcomes. We used mixed participatory methods, including focus groups, to co-develop a CR satisfaction scale. This was refined using three psychometric criteria (Cronbach's alpha, item discrimination, test-retest agreement) to select items. Factor analysis explored potential substructures. The refined measure was used in structural equation joint modelling to evaluate whether satisfaction with CR is affected by implementation method and treatment engagement or influences recovery outcome, using data from a randomised controlled trial. Four themes (therapy hours, therapist, treatment effects, computer use) generated a 31-item Cognitive Remediation Satisfaction scale (CRS) that reduced to 18 Likert items, 2 binary and 2 open-ended questions following psychometric assessment. CRS had good internal consistency (Alpha = 0.814), test-retest reliability (r= 0.763), and concurrent validity using the Working Alliance Inventory (r = 0.56). A 2-factor solution divided items into therapy engagement and therapy effects. Satisfaction was not related to implementation method but was significantly associated with CR engagement. Therapy hours were significantly associated with recovery, but there was no direct effect of satisfaction on outcome. Although satisfaction is important to therapy engagement, it has no direct effect on outcome. CR therapy hours directly affect outcome irrespective of which implementation model is used, so measuring satisfaction early might help to identify those who are likely to disengage. The study has mixed methods design.

Schizophrenia patients make more errors and have longer reaction times (RTs) than healthy controls in most cognitive tasks. Deficits are also observed in subclinical participants having high scores on the schizotypal personality questionnaire (SPQ). They are accompanied by smaller amplitudes of the event-related brain potentials (ERPs) that index attention and semantic- and working-memory. These functions are thus thought to be impaired in individuals having various schizophrenia attributes (SzAs). Nevertheless, normal RTs were recently found in SzAs during a particular self-referential task where half of the stimuli were names of extraordinary social roles (e.g., genius). Each name (ordinary or extraordinary) was presented individually, and participants were asked to decide whether or not they would consider themselves performing the role at any moment of their lives. To further test an absence of cognitive deficits in this task, the ERPs elicited by names of social roles were also examined in 175 healthy participants. The absence of longer RTs in high- than in low-SPQs was replicated. Moreover, the ERPs of high SPQs had larger occipital N1s, larger P2s and larger occipital N400s than those of low SPQs while late positive potentials (LPPs) were of similar amplitudes. Such results are consistent with clinical observations of greater attention and faster processing of stimuli related to extraordinary/delusional beliefs. Further studies should test whether the cognitive deficits found in SzAs are due to the use of tasks and stimuli that are less within their focus of interest than within that of healthy controls.

This systematic review aimed to review neuroimaging studies comparing clozapine-resistant schizophrenia patients with clozapine-responding patients, and with first-line antipsychotic responding (FLR) patients. A total of 19 studies including 6 longitudinal studies were identified. Imaging techniques comprised computerized tomography (CT, n = 3), structural magnetic resonance imaging (MRI, n = 7), magnetic resonance spectroscopy (MRS, n = 5), functional MRI (n = 1), single-photon emission computerized tomography (SPECT, n = 3) and diffusion tensor imaging (DTI, n = 1). The most consistent finding was hypo-frontality in the clozapine-resistant group compared with the clozapine-responding group with possible differences in frontal-striatal-basal ganglia circuitry as well as the GABA level between the two treatment-resistant groups. Additional statistically significant findings were reported when comparing clozapine-resistant patients with the FLR group, including lower cortical thickness and brain volume of multiple brain regions as well as lower Glx/Cr level in the dorsolateral prefrontal cortex. Both treatment-resistant groups were found to have extensive differences in neurobiological features in comparison with the FLR group. Overall results suggested treatment-resistant schizophrenia is likely to be a neurobiological distinct type of the illness. Clozapine-resistant and clozapine-responding schizophrenia are likely to have both shared and distinct neurobiological features. However, conclusions from existing studies are limited, and future multi-center collaborative studies are required with a consensus clinical definition of patient samples, multimodal imaging tools, and longitudinal study designs.

This study evaluated the relationship between negative symptoms, daily time use (productive/non-productive activities, PA/NPA), and negative emotions in schizophrenia-spectrum disorders (SSDs): 618 individuals with SSDs (311 residential care patients [RCPs], 307 outpatients) were surveyed about socio-demographic, clinical (BPRS, BNSS) and daily time use (paper-and-pencil Time Use Survey completed twice/week) characteristics. Among them 57 RCPs and 46 outpatients, matched to 112 healthy controls, also underwent ecological monitoring of emotions (8 times/day for a week) through Experience Sampling Method (ESM). RCPs spent significantly less time in PA than outpatients. Patients with more negative symptomatology spent more time in NPA and less in PA compared to patients with milder symptoms. Higher time spent in NPA was associated with negative emotions (p < 0.001 during workdays) even when correcting for BNSS total and antipsychotic polypharmacy (p = 0.002 for workdays, p = 0.006 for Sundays). Future studies are needed to explore in more detail the relationship between negative emotions, negative symptoms, time use, and functioning in individuals with SSDs, providing opportunities for more informed and personalised clinical treatment planning and research into interactions between different motivational, saliency and behavioural aspects in individuals with SSDs.

Ganzfeld conditions induce alterations in brain function and pseudo-hallucinatory experiences, particularly in people with high positive schizotypy. The current study uses graph-based parameters to investigate and classify brain networks under Ganzfeld conditions as a function of positive schizotypy. Participants from the general population (14 high schizotypy (HS), 29 low schizotypy (LS)) had an electroencephalography assessment during Ganzfeld conditions, with varying visual activation (8 frequencies of random light flicker) and soundscape-induced mood (neutral, serenity, and anxiety). Weighted functional networks were computed in six frequency sub-bands (delta, theta, alpha-low, alpha-high, beta, and gamma) as a function of light-flicker frequency and mood. The brain network was analyzed using graph theory parameters, including clustering coefficient (CC), strength, and global efficiency (GE). It was found that the LS groups had higher CC and strength than the HS groups, especially in bilateral temporal and frontotemporal brain regions. Moreover, some decreases in CC and strength measures were found in LS groups among occipital and parieto-occipital brain regions. LS groups also had significantly higher GE in all Ganzfeld conditions compared to the HS groups. The random under-sampling boosting (RUSBoost) algorithm achieved the best classification performance with an accuracy of 95.34%, specificity of 96.55%, and sensitivity of 92.85% during an anxiety-induction Ganzfeld condition. This is the first exploration of the relationship between brain functional state changes under Ganzfeld conditions in individuals who vary in positive schizotypy. The accuracy of graph-based parameters in classifying brain states as a function of schizotypy is shown, particularly for brain activity during anxiety induction, and should be investigated in psychosis.

Family caregiving of people living with schizophrenia (PLS) can be burdensome, and some family caregivers may perpetrate abusive behavior that could be harmful to PLS. This study aims to examine the association of family caregivers' abusive behavior with internalized stigma of PLS and draw attention to this problem. PLS were recruited from four cities across China and completed measures of abusive behavior and internalized stigma. Linear regression analyses were used to determine the association between family caregivers' abusive behavior and internalized stigma of PLS. A total of 693 PLS were include in this study. 22.7% of the participants had experienced one or more of the abusive behaviors perpetrated by family caregivers. The most common type of abusive behavior towards PLS was verbal abuse and 4.2% of the participants reported physical abuse. 44.6 % of participants reported a high level of internalized stigma. PLS who experienced any abusive behavior by family caregivers had significantly higher levels of internalized stigma. Family caregivers' abusive behavior is positively associated with alienation and social withdrawal but not with stereotype endorsement and discrimination of PLS. To end all forms of stigma and discrimination against PLS, more attention needs to be paid to the families of PLS.