NPJ Schizophrenia最新文献

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.

Schizophrenia is a neurocognitive illness of synaptic and brain network-level dysconnectivity that often reaches a persistent chronic stage in many patients. Subtle language deficits are a core feature even in the early stages of schizophrenia. However, the primacy of language network dysconnectivity and language-related genetic variants in the observed phenotype in early stages of illness remains unclear. This study used two independent schizophrenia dataset consisting of 138 and 53 drug-naïve first-episode schizophrenia (FES) patients, and 112 and 56 healthy controls, respectively. A brain-wide voxel-level functional connectivity analysis was conducted to investigate functional dysconnectivity and its relationship with illness duration. We also explored the association between critical language-related genetic (such as FOXP2) mutations and the altered functional connectivity in patients. We found elevated functional connectivity involving Broca's area, thalamus and temporal cortex that were replicated in two FES datasets. In particular, Broca's area - anterior cingulate cortex dysconnectivity was more pronounced for patients with shorter illness duration, while thalamic dysconnectivity was predominant in those with longer illness duration. Polygenic risk scores obtained from FOXP2-related genes were strongly associated with functional dysconnectivity identified in patients with shorter illness duration. Our results highlight the criticality of language network dysconnectivity, involving the Broca's area in early stages of schizophrenia, and the role of language-related genes in this aberration, providing both imaging and genetic evidence for the association between schizophrenia and the determinants of language.

Functional impairment remains one of the most challenging issues for treatment in schizophrenia. However, previous studies have mainly focused on the negative impact of symptoms excluding variables that could positively impact functional outcome, such as creativity, which is considered an adaptive capacity for real-life problem-solving. This study analyzed the predictive role of creativity on functional outcome in 96 patients with schizophrenia through a mediational model, including sociodemographic, clinical, neurocognitive, and social cognitive variables. Path analysis revealed that creativity significantly mediated the relationship between neurocognition and functional outcome, and that creativity mediated between negative symptoms and functional outcome. Additionally, neurocognition was directly associated with functional outcome and social functioning was associated with creativity. The involvement of creativity in functional outcome could have relevant implications for the development of new interventions. These findings open up a new field of research on additional personal resources as possible factors of functional outcome in schizophrenia and other diseases.

Negative symptoms have long been considered a core component of schizophrenia. Modern conceptualizations of the structure of negative symptoms posit that there are at least two broad dimensions (motivation and pleasure and diminished expression) or perhaps five separable domains (avolition, anhedonia, asociality, blunted affect, alogia). The current review synthesizes a body of emerging research indicating that avolition may have a special place among these dimensions, as it is generally associated with poorer outcomes and may have distinct neurobiological mechanisms. Network analytic findings also indicate that avolition is highly central and interconnected with the other negative symptom domains in schizophrenia, and successfully remediating avolition results in global improvement in the entire constellation of negative symptoms. Avolition may therefore reflect the most critical treatment target within the negative symptom construct. Implications for targeted treatment development and clinical trial design are discussed.

Patients with schizophrenia (SCZ) have a core impairment in the communicative-pragmatic domain, characterized by severe difficulties in correctly inferring the speaker's communicative intentions. While several studies have investigated pragmatic performance of patients with SCZ, little research has analyzed the errors committed in the comprehension of different communicative acts. The present research investigated error patterns in 24 patients with SCZ and 24 healthy controls (HC) during a task assessing the comprehension of different communicative acts, i.e., sincere, deceitful and ironic, and their relationship with the clinical features of SCZ. We used signal detection analysis to quantify participants' ability to correctly detect the speakers' communicative intention, i.e., sensitivity, and their tendency to wrongly perceive a communicative intention when not present, i.e., response bias. Further, we investigated the relationship between sensitivity and response bias, and the clinical features of the disorder, namely symptom severity, pharmacotherapy, and personal and social functioning. The results showed that the ability to infer the speaker's communicative intention is impaired in SCZ, as patients exhibited lower sensitivity, compared to HC, for all the pragmatic phenomena evaluated, i.e., sincere, deceitful, and ironic communicative acts. Further, we found that the sensitivity measure for irony was related to disorganized/concrete symptoms. Moreover, patients with SCZ showed a stronger response bias for deceitful communicative acts compared to HC: when committing errors, they tended to misattribute deceitful intentions more often than sincere and ironic ones. This tendency to misattribute deceitful communicative intentions may be related to the attributional bias characterizing the disorder.

One aspect of goal-directed behavior, which is known to be impaired in patients with schizophrenia (SZ), is balancing between exploiting a familiar choice with known reward value and exploring a lesser known, but potentially more rewarding option. Despite its relevance to several symptom domains of SZ, this has received little attention in SZ research. In addition, while there is increasing evidence that SZ is associated with chronic low-grade inflammation, few studies have investigated how this relates to specific behaviors, such as balancing exploration and exploitation. We therefore assessed behaviors underlying the exploration-exploitation trade-off using a three-armed bandit task in 45 patients with SZ and 19 healthy controls (HC). This task allowed us to dissociate goal-unrelated (random) from goal-related (directed) exploration and correlate them with psychopathological symptoms. Moreover, we assessed a broad range of inflammatory proteins in the blood and related them to bandit task behavior. We found that, compared to HC, patients with SZ showed reduced task performance. This impairment was due to a shift from exploitation to random exploration, which was associated with symptoms of disorganization. Relative to HC, patients with SZ showed a pro-inflammatory blood profile. Furthermore, high-sensitivity C-reactive protein (hsCRP) positively correlated with random exploration, but not with directed exploration or exploitation. In conclusion, we show that low-grade inflammation in patients with SZ is associated with random exploration, which can be considered a behavioral marker for disorganization. hsCRP may constitute a marker for severity of, and a potential treatment target for maladaptive exploratory behaviors.

Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD. However, no studies have investigated whole-brain functional correlates of CD in psychosis. We sought to investigate brain regions explaining the severity of CD in patients with first-episode psychosis (FEPs) compared with healthy controls (HCs). We computed whole-brain binarized degree centrality maps of 31 FEPs, 25 HCs, and characterized the patterns of network connectivity in the 2 groups. In FEPs, we related these findings to the severity of CD. We also studied the effect of positive and negative symptoms on altered network connectivity. Compared to HCs, reduced centrality of a right superior temporal gyrus (rSTG) cluster was observed in the FEPs. In patients exhibiting high CD, increased centrality of a medial superior parietal (mSPL) cluster was observed, compared to patients exhibiting low CD. This cluster was strongly correlated with CD scores but not with other symptom scores. Our observations are congruent with previous findings of reduced but not increased centrality. We observed increased centrality of mSPL suggesting that cortical reorganization occurs to provide alternate routes for information transfer. These findings provide insight into the underlying neural processes mediating the presentation of symptoms in untreated FEP. Longitudinal tracking of the symptom course will be useful to assess the mechanisms underlying these compensatory changes.

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.