NPJ Schizophrenia最新文献

Impairments in social cognition-including recognition of facial expressions-are increasingly recognised as a core deficit in schizophrenia. It remains unclear whether other aspects of face processing (such as identity recognition) are also impaired, and whether such deficits can be attributed to more general cognitive difficulties. Moreover, while the majority of past studies have used picture-based tasks to assess face recognition, literature suggests that video-based tasks elicit different neural activations and have greater ecological validity. This study aimed to characterise face processing using video-based stimuli in psychiatric inpatients with and without psychosis. Symptom correlates of face processing impairments were also examined. Eighty-six psychiatric inpatients and twenty healthy controls completed a series of tasks using video-based stimuli. These included two emotion recognition tasks, two non-emotional facial identity recognition tasks, and a non-face control task. Symptoms were assessed using the Positive and Negative Syndrome Scale. Schizophrenia and bipolar disorder groups were significantly impaired on the emotion-processing tasks and the non-face task compared to healthy controls and patients without psychosis. Patients with other forms of psychosis performed intermediately. Groups did not differ in non-emotional face processing. Positive symptoms of psychosis correlated directly with both emotion-processing performance and non-face discrimination across patients. We found that identity processing performance was inversely associated with cognition-related symptoms only. Findings suggest that deficits in emotion-processing reflect symptom pathology independent of diagnosis. Emotion-processing deficits in schizophrenia may be better accounted for by task-relevant factors-such as attention-that are not specific to emotion processing.

Early-onset schizophrenia (EOS) may have stronger familial aggregation and a more severe outcome than adult-onset schizophrenia (AOS). MicroRNA (miRNA) takes on dual roles as a genetic and epigenetic modulator, which may mediate the influence of genetic risk. Neurological soft signs (NSS) are neurological abnormalities that may be intermediate phenotypes or endophenotypes for schizophrenia. Our previous study found poorer performance on NSS tests from patients with EOS and their unaffected first-degree relatives. Thus, we aimed to identify a set of aberrant neurodevelopmental-related miRNAs that could serve as potential biomarkers for EOS or schizophrenia with NSS. This study included 215 schizophrenia patients (104 EOS and 111 AOS), 72 unaffected first-degree relatives, 31 patients with bipolar disorder, and 100 healthy controls. Differential expression analysis revealed that miR-137, miR-34b, and miR-34c were significantly up-regulated in patients with schizophrenia and their unaffected first-degree relatives compared to healthy controls. Receiver operating characteristic (ROC) analysis showed that the miR-137 expression signature could be used to discriminate between patients with EOS and healthy controls (AUC = 0.911). Additionally, miR-34b had the highest ability to discriminate between EOS and AOS (AUC = 0.810), which may indicate different aetiological pathways to disease onset. Moreover, miR-137 dysregulation was correlated with almost all NSS subscales (i.e., sensory integration, motor sequencing, etc.) and, when EOS patients with NSS, miR-137 expression discriminated these patients from healthy controls to a greater extent (AUC = 0.957). These findings support the potential for neurodevelopmental-related miRNAs to be used as indicators of vulnerability to EOS.

Schizophrenia and related disorders have heterogeneous outcomes. Individualized prediction of long-term outcomes may be helpful in improving treatment decisions. Utilizing extensive baseline data of 523 patients with a psychotic disorder and variable illness duration, we predicted symptomatic and global outcomes at 3-year and 6-year follow-ups. We classified outcomes as (1) symptomatic: in remission or not in remission, and (2) global outcome, using the Global Assessment of Functioning (GAF) scale, divided into good (GAF ≥ 65) and poor (GAF < 65). Aiming for a robust and interpretable prediction model, we employed a linear support vector machine and recursive feature elimination within a nested cross-validation design to obtain a lean set of predictors. Generalization to out-of-study samples was estimated using leave-one-site-out cross-validation. Prediction accuracies were above chance and ranged from 62.2% to 64.7% (symptomatic outcome), and 63.5-67.6% (global outcome). Leave-one-site-out cross-validation demonstrated the robustness of our models, with a minor drop in predictive accuracies of 2.3% on average. Important predictors included GAF scores, psychotic symptoms, quality of life, antipsychotics use, psychosocial needs, and depressive symptoms. These robust, albeit modestly accurate, long-term prognostic predictions based on lean predictor sets indicate the potential of machine learning models complementing clinical judgment and decision-making. Future model development may benefit from studies scoping patient's and clinicians' needs in prognostication.

Chronic cannabis use and schizophrenia are both thought to affect reward processing. While behavioural and neural effects on reward processing have been investigated in both conditions, their interaction has not been studied, although chronic cannabis use is common among these patients. In the present study eighty-nine participants divided into four groups (control chronic cannabis users and non-users; schizophrenia patient cannabis users and non-users) performed a two-choice decision task, preceded by monetary cues (high/low reward/punishment or neutral), while being scanned using functional magnetic resonance imaging. Reward and punishment anticipation resulted in activation of regions of interest including the thalamus, striatum, amygdala and insula. Chronic cannabis use and schizophrenia had opposing effects on reward anticipation sensitivity. More specifically control users and patient non-users showed faster behavioural responses and increased activity in anterior/posterior insula for high magnitude cues compared to control non-users and patient users. The same interaction pattern was observed in the activation of the right thalamus for reward versus punishment cues. This study provided evidence for interaction of chronic cannabis use and schizophrenia on reward processing and highlights the need for future research addressing the significance of this interaction for the pathophysiology of these conditions and its clinical consequences.

Age plays a crucial role in the performance of schizophrenia vs. controls (SZ-HC) neuroimaging-based machine learning (ML) models as the accuracy of identifying first-episode psychosis from controls is poor compared to chronic patients. Resolving whether this finding reflects longitudinal progression in a disorder-specific brain pattern or a systematic but non-disorder-specific deviation from a normal brain aging (BA) trajectory in schizophrenia would help the clinical translation of diagnostic ML models. We trained two ML models on structural MRI data: an SZ-HC model based on 70 schizophrenia patients and 74 controls and a BA model (based on 561 healthy individuals, age range = 66 years). We then investigated the two models' predictions in the naturalistic longitudinal Northern Finland Birth Cohort 1966 (NFBC1966) following 29 schizophrenia and 61 controls for nine years. The SZ-HC model's schizophrenia-specificity was further assessed by utilizing independent validation (62 schizophrenia, 95 controls) and depression samples (203 depression, 203 controls). We found better performance at the NFBC1966 follow-up (sensitivity = 75.9%, specificity = 83.6%) compared to the baseline (sensitivity = 58.6%, specificity = 86.9%). This finding resulted from progression in disorder-specific pattern expression in schizophrenia and was not explained by concomitant acceleration of brain aging. The disorder-specific pattern's progression reflected longitudinal changes in cognition, outcomes, and local brain changes, while BA captured treatment-related and global brain alterations. The SZ-HC model was also generalizable to independent schizophrenia validation samples but classified depression as control subjects. Our research underlines the importance of taking account of longitudinal progression in a disorder-specific pattern in schizophrenia when developing ML classifiers for different age groups.

Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions.

Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D₂ receptor (D₂R) partial agonists and D₂R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D₂R partial agonists with D₂R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D₂R partial agonist, and was not significantly different from pooled D₂R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D₂R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D₂R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole's efficacy did not differ substantially from D₂R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D₂R partial agonists with D₂R antagonists in early stages of schizophrenia.

An impairment in pragmatic communication is a core feature of schizophrenia, often associated with difficulties in social interactions. The pragmatic deficits regard various pragmatic phenomena, e.g., direct and indirect communicative acts, deceit, irony, and include not only the use of language but also other expressive means such as non-verbal/extralinguistic modalities, e.g., gestures and body movements, and paralinguistic cues, e.g., prosody and tone of voice. The present paper focuses on the identification of those pragmatic features, i.e., communicative phenomena and expressive modalities, that more reliably discriminate between individuals with schizophrenia and healthy controls. We performed a multimodal assessment of communicative-pragmatic ability, and applied a machine learning approach, specifically a Decision Tree model, with the aim of identifying the pragmatic features that best separate the data into the two groups, i.e., individuals with schizophrenia and healthy controls, and represent their configuration. The results indicated good overall performance of the Decision Tree model, with mean Accuracy of 82%, Sensitivity of 76%, and Precision of 91%. Linguistic irony emerged as the most relevant pragmatic phenomenon in distinguishing between the two groups, followed by violation of the Gricean maxims, and then extralinguistic deceitful and sincere communicative acts. The results are discussed in light of the pragmatic theoretical literature, and their clinical relevance in terms of content and design of both assessment and rehabilitative training.

Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR) <1.2), suggesting that more functional risk variants remain to be identified. Here, we employed region-based multi-marker analysis of genomic annotation (MAGMA) to identify additional risk loci containing variants with large OR value from Psychiatry Genomics Consortium (PGC2) schizophrenia GWAS data and then employed summary-data-based mendelian randomization (SMR) to prioritize schizophrenia susceptibility genes. The top-ranked susceptibility gene ATP5MD, encoding an ATP synthase membrane subunit, is observed to be downregulated in schizophrenia by the risk allele of CNNM2-rs1926032 in the schizophrenia-associated 10q24.32 locus. The Atp5md knockout (KO) in mice was associated with abnormal startle reflex and gait, and ATP5MD knockdown (KD) in human induced pluripotent stem cell-derived neurons disrupted the neural development and mitochondrial respiration and ATP production. Moreover, CNNM2-rs1926032 KO could induce downregulation of ATP5MD expression and disruptions of mitochondrial respiration and ATP production. This study constitutes an important mechanistic component that links schizophrenia-associated CNNM2 regions to disruption in energy adenosine system modulation and neuronal function by long-distance chromatin domain downregulation of ATP5MD. This pathogenic mechanism provides therapeutic implications for schizophrenia.

Identifying state-sensitive measures of perceptual and cognitive processes implicated in psychosis may allow for objective, earlier, and better monitoring of changes in mental status that are predictive of an impending psychotic episode, relative to traditional self-report-based clinical measures. To determine whether a measure of visual perception that has demonstrated sensitivity to the clinical state of schizophrenia in multiple prior studies is sensitive to features of the at-risk mental state, we examined differences between young people identified as being at clinical high risk for psychosis (CHR; n = 37) and non-psychiatric matched controls (n = 29) on the Mooney Faces Test (MFT). On each trial of the MFT, participants report whether they perceive a face in a degraded face image. The CHR group reported perceiving a greater number of faces in both upright and inverted MFT stimuli. Consistent with prior work, males reported more faces on the MFT than females in both conditions. However, the finding of greater reported face perception among CHR subjects was robustly observed in the female CHR group relative to the female control group. Among male CHR participants, greater reported face perception was related to increased perceptual abnormalities. These preliminary results are consistent with a small but growing literature suggesting that heightened perceptual sensitivity may characterize individuals at increased clinical risk for psychosis. Further studies are needed to determine the contributions of specific perceptual, cognitive, and motivational mechanisms to the findings.