Impaired attentional processing of negative facial expressions is prominent in schizophrenia and has been shown to be associated with patients' social dysfunctions. However, little is known about when and which specific attention deficits influence social functions. Given the dynamic feature of attention, it is necessary to investigate the attention deficits in negative emotional processing unfolding in time. The current study used event-related potentials (ERPs) to investigate the temporal dynamics of attention deficits in emotion perception and their potential relationship with emotional/social impairments in neuroleptic naive schizophrenic patients. Two specific attention deficits were identified and were found to be associated with emotional/social impairments. More specifically, the deficit in orienting attention (evidenced with the reduced P1 amplitude) was correlated with expressive deficits, while the deficit in executive control of attention (evidenced with the reduced P3 amplitude) was correlated with avolition/asociality. Together, these findings may provide novel insights into the core pathophysiological processes and offer objective biomarkers for specific emotional/social impairments in schizophrenia. It is also hoped that this study helps to bridge the gap between basic cognitive deficits and relative high-level social dysfunctions in schizophrenic patients.

Emotional prosody (EP) has been increasingly recognized as an important area of schizophrenic patients' dysfunctions in their language use and social communication. The present review aims to provide an updated synopsis on emotional prosody processing (EPP) in schizophrenic disorders, with a specific focus on performance characteristics, the influential factors and underlying neural mechanisms. A literature search up to 2018 was conducted with online databases, and final selections were limited to empirical studies which investigated the prosodic processing of at least one of the six basic emotions in patients with a clear diagnosis of schizophrenia without co-morbid diseases. A narrative synthesis was performed, covering the range of research topics, task paradigms, stimulus presentation, study populations and statistical power with a quantitative meta-analytic approach in Comprehensive Meta-Analysis Version 2.0. Study outcomes indicated that schizophrenic patients' EPP deficits were consistently observed across studies (d = -0.92, 95% CI = -1.06 < δ < -0.78), with identification tasks (d = -0.95, 95% CI = -1.11 < δ < -0.80) being more difficult to process than discrimination tasks (d = -0.74, 95% CI = -1.03 < δ < -0.44) and emotional stimuli being more difficult than neutral stimuli. Patients' performance was influenced by both participant- and experiment-related factors. Their social cognitive deficits in EP could be further explained by right-lateralized impairments and abnormalities in primary auditory cortex, medial prefrontal cortex and auditory-insula connectivity. The data pointed to impaired pre-attentive and attentive processes, both of which played important roles in the abnormal EPP in the schizophrenic population. The current selective review and meta-analysis support the clinical advocacy of including EP in early diagnosis and rehabilitation in the general framework of social cognition and neurocognition deficits in schizophrenic disorders. Future cross-sectional and longitudinal studies are further suggested to investigate schizophrenic patients' perception and production of EP in different languages and cultures, modality forms and neuro-cognitive domains.

Medication adherence of schizophrenic patients is a growing public health problem. We conducted a meta-analysis on the influencing factors of medication compliance in schizophrenic patients. We searched PubMed, Embase, Cochrane Library, and Web Of Science for relevant articles published up to December 22, 2022. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess influencing factors. Egger's test, funnel plot, the trim and fill method, and meta-regression analysis were used to assess publication bias. A total of 20 articles were included in the analysis. Twenty influencing factors were divided into seven categories: drug factors (OR = 1.96, 95% CI: 1.48-2.59), problem behavior (OR = 1.77, 95% CI: 1.43-2.19), income and quality of life (OR = 1.23, 95% CI: 1.08-1.39), personal characteristics (OR = 1.21, 95% CI: 1.14-1.30), disease factors (OR = 1.14, 95% CI: 1.98-1.21), support level (OR = 0.54, 95% CI: 0.42-0.70), and positive attitude and behavior (OR = 0.52, 95% CI: 0.45-0.62). This meta-analysis found that drug factors, disease factors, problem behavior, low income and quality of life, and factors related to personal characteristics appear to be risk factors for medication adherence in people with schizophrenia. And support level, positive attitude and behavior appear to be protective factors.

Neural adhesion proteins are crucial in the development and maintenance of functional neural connectivity. Growing evidence suggests that the IgLON family of neural adhesion molecules LSAMP, NTM, NEGR1, and OPCML are important candidates in forming the susceptibility to schizophrenia (SCZ). IgLON proteins have been shown to be involved in neurite outgrowth, synaptic plasticity and neuronal connectivity, all of which have been shown to be altered in the brains of patients with the diagnosis of schizophrenia. Here we optimized custom 5'-isoform-specific TaqMan gene-expression analysis for the transcripts of human IgLON genes to study the expression of IgLONs in the dorsolateral prefrontal cortex (DLPFC) of schizophrenic patients (n = 36) and control subjects (n = 36). Uniform 5'-region and a single promoter was confirmed for the human NEGR1 gene by in silico analysis. IgLON5, a recently described family member, was also included in the study. We detected significantly elevated levels of the NEGR1 transcript (1.33-fold increase) and the NTM 1b isoform transcript (1.47-fold increase) in the DLPFC of schizophrenia patients compared to healthy controls. Consequent protein analysis performed in male subjects confirmed the increase in NEGR1 protein content both in patients with the paranoid subtype and in patients with other subtypes. In-group analysis of patients revealed that lower expression of certain IgLON transcripts, mostly LSAMP 1a and 1b, could be related with concurrent depressive endophenotype in schizophrenic patients. Additionally, our study cohort provides further evidence that cannabis use may be a relevant risk factor associated with suicidal behaviors in psychotic patients. In conclusion, we provide clinical evidence of increased expression levels of particular IgLON family members in the DLPFC of schizophrenic patients. We propose that alterations in the expression profile of IgLON neural adhesion molecules are associated with brain circuit disorganization in neuropsychiatric disorders, such as schizophrenia. In the light of previously published data, we suggest that increased level of NEGR1 in the frontal cortex may serve as molecular marker for a wider spectrum of psychiatric conditions.

An accurate representation of task-set information is needed for successful goal directed behavior. Recent studies point to disturbances in the early processing stages as plausible causes for task-switching deficits in schizophrenia. A task-cueing protocol was administered to a group of schizophrenic patients and compared with a sample of age-matched healthy controls. Patients responded slower and less accurate compared with controls in all conditions. The concurrent recording of event-related brain potentials to contextual cues and target events revealed abnormalities in the early processing of both cue-locked and target-locked N1 potentials. Abnormally enhanced target-locked P2 amplitudes were observed in schizophrenic patients for task-switch trials only, suggesting disrupted stimulus evaluation and memory retrieval processes. The endogenous P3 potentials discriminated between task conditions but without further differences between groups. These results suggest that the observed impairments in task-switching behavior were not specifically related to anticipatory set-shifting, but derived from a deficit in the implementation of task-set representations at target onset in the presence of irrelevant and conflicting information.

Schizophrenia and bipolar disorder have been linked to alterations in the functional activity and grey matter volume of some brain areas, reflected in impaired regional homogeneity and aberrant voxel-based morphometry. However, because of variable findings and methods used across studies, identifying patterns of brain alteration in schizophrenia and bipolar disorder has been difficult.

Recent research shows ambivalent results regarding the relationship between mental imagery and schizophrenia. The role of voluntary visual imagery in schizophrenic hallucinations remains unclear. The aim of the study was to investigate the association between visual imagery, schizophrenia, and the occurrence of schizophrenic hallucinations using an objective visual imagery task.

Schizophrenic subject is thought as a self-disorder patient related with abnormal brain functional network. It has been hypothesized that self-disorder is associated with the deficient functional integration of multisensory body signals in schizophrenic subjects. To further verify this assumption, 53 chronic schizophrenic subjects and 67 healthy subjects were included in this study and underwent resting-state functional magnetic resonance imaging. The data-driven methods, whole-brain temporal variability of fractional amplitude of low-frequency fluctuations and regional homogeneity (ReHo), were used to investigate dynamic local functional connectivity and dynamic local functional activity changes in schizophrenic subjects. Patients with schizophrenia exhibited increased temporal variability ReHo and fractional amplitude of low-frequency fluctuations across time windows within sensory and perception network (such as occipital gyrus, precentral and postcentral gyri, superior temporal gyrus, and thalamus). Critically, the increased dynamic ReHo of thalamus is significantly correlated with positive and total symptom of schizophrenic subjects. Our findings revealed that deficit in sensory and perception functional networks might contribute to neural physiopathology of self-disorder in schizophrenic subjects.

Although some recent research has indicated reduced performance monitoring in patients with schizophrenia, the literature on this topic shows some remarkable inconsistencies. While most studies suggest diminished error signals following error responses, some studies reported normal post-error slowing, while others reported reduced post-error slowing. Here we review these studies and highlight the most important discrepancies. Furthermore, we argue that overall error rates are a mostly neglected issue that can at least partly explain these discrepancies. It has been reported previously that post-error slowing depends on the error rates. Participants or patients that make more errors are likely to show decreased post-error slowing. Therefore, when a group of patients is compared to a group of controls, it is extremely important to match error rates. For this purpose, we developed a procedure where we matched individuals' error rates. In a task where subjects had to press a response key corresponding to one of four colors we manipulated the difficulty on an individual basis by varying the discriminability between the colors. Schizophrenic patients and a group of controls were tested with this procedure showing that differences in accuracy disappear. Interestingly, we can see that in patients, the color values that were needed to reach similar levels of accuracy correlate with the Positive and Negative Syndrome Scale (PANSS) scale, with higher PANSS requiring more color. Most important, we found that schizophrenic patients have increased rather than decreased post-error slowing when the inter-trial interval (ITI) is short. This result can be interpreted within the framework of the orienting account, as it has been demonstrated previously that schizophrenic patients show increased distractibility.

Deficits in pragmatic abilities have frequently been observed in patients with schizophrenia. The objective of the study was to investigate the relationship between pragmatic deficits, ToM deficits and executive dysfunctions in schizophrenia. A group of 42 schizophrenic patients and 42 healthy controls were assessed on irony task (one type of pragmatic language), two subcomponents of ToM (cognitive and affective), and three subcomponents of EF (inhibition, updating, and switching). The clinical symptoms in schizophrenia were assessed using the positive and negative symptoms of schizophrenia. The schizophrenia group exhibited significant impairments in all above tasks compared to the control group. Correlation results found that irony scores were correlated with the two subcomponents of ToM and two of the three subcomponents of EF (inhibition and updating). The regression analysis revealed that the cognitive ToM and inhibition predicted 9.2% and 29.9% of the variance of irony comprehension in the patient group, and inhibition was the best predictor for performance on irony task. Irony understanding was related to positive symptoms, but not to negative symptoms. The results suggest that the ability to interpret pragmatic language depends on schizophrenic patients' ability to infer mental states and the ability of inhibition. It provides empirical evidence for a particular target of inhibition for rehabilitation and intervention programs developed for schizophrenic patients.

Studies comparing gray matter (GM) volume of schizophrenic patients with or without auditory verbal hallucinations (AVHs) to that of normal controls remain controversial. This project aims to investigate changes of GM volumes of drug-naïve schizophrenic patients with and without AVHs. Eighteen first episode schizophrenic (FES) patients with AVHs, 18 FES patients without AVHs, and 18 healthy controls were scanned using structural MRI. Voxel-based morphometry (VBM) analysis was conducted to investigate changes of GM volume among the three groups. Patients with and without AVHs exhibited reduced GM volumes relative to normal controls in the left superior temporal gyrus, frontal regions, cerebellum and caudate. Further analysis of the GM of subcortical structures found that patients with AVHs had reduced thalamic volume than healthy controls. No significant difference was found between patients with and without AVHs. Significant correlation was found between the total scores of the Positive and Negative Syndrome Scale and bilateral thalamic volume. ROC analysis of thalamic volumes of the patients with AVHs and normal controls showed that the area under the curve was 0.698 (P = 0.043). The decreased thalamic volumes might serve as a biomarker for discriminating FES AVHs patients from normals.

Irony is a type of figurative language in which the literal meaning of the expression is the opposite of what the speaker intends to communicate. Even though schizophrenic patients are known as typically impaired in irony comprehension and in the underlying neural functions, to date no one has explored the neural correlates of figurative language comprehension in first-degree relatives of schizophrenic patients. In the present study, we examined the neural correlates of irony understanding in schizophrenic patients and in unaffected first-degree relatives of patients compared to healthy adults with functional MRI. Our aim was to investigate if possible alterations of the neural circuits supporting irony comprehension in first-degree relatives of patients with schizophrenia would fulfill the familiality criterion of an endophenotype. We examined 12 schizophrenic patients, 12 first-degree relatives of schizophrenia patients and 12 healthy controls with functional MRI while they were performing irony and control tasks. Different phases of irony processing were examined, such as context processing and ironic statement comprehension. Patients had significantly more difficulty understanding irony than controls or relatives. Patients also showed markedly different neural activation pattern compared to controls in both stages of irony processing. Although no significant differences were found in the performance of the irony tasks between the control group and the relative group, during the fMRI analysis, the relatives showed stronger brain activity in the left dorsolateral prefrontal cortex during the context processing phase of irony tasks than the control group. However, the controls demonstrated higher activations in the left dorsomedial prefrontal cortex and in the right inferior frontal gyrus during the ironic statement phase of the irony tasks than the relative group. Our results show that despite good task performance, first-degree relatives of schizophrenia patients had alterations in the neural circuits during irony processing. Thus, we suggest that neural alteration of irony comprehension could be a potential endophenotypic marker of schizophrenia.

Sleep disorders are often not regarded as an important health problem, despite their impact on heath. Insomnia is the most frequent sleep disorder in mental health. The aim is to quantify the prevalence of insomnia in a population with schizophrenic disorder and assess its influence on quality of life. This is a descriptive, analytical and cross-sectional study conducted in a sample of 267 schizophrenic patients over 18 years of age using consecutive non-probabilistic sampling. The variables of interest were collected by means of the "Cuestionario Oviedo de Sueño," "Insomnia Severity Index" and EuqoQol-5D. The estimation of insomnia in our schizophrenic population according to the International Classification of Disease (ICD-10) criteria was 23.2%. The likelihood of insomnia when there are problems in the quality of life is significant in all its dimensions: mobility OR: 3.54 (95% CI 1.88- 6.65), self-care OR: 2.69 (95% CI 1.36-5.32), usual activities OR: 3.56 (95% CI 1.97-6.44), pain/discomfort OR: 4.29 (95% CI 2.37-7.74) and anxiety/depression OR: 3.01 (95% CI 1.61-5.65). The prevalence of insomnia fluctuates depending on the diagnostic criteria; however, the schizophrenic population shows high prevalence in some clinical characteristics. People with insomnia have a lower quality of life.

Three types of orbitofrontal cortex (OFC) sulcogyral patterns that have been identified in the population, and the distribution of these three types in clinically diagnosed schizophrenic patients has been found to be distinct from the normal population. Schizophrenia is associated with increased levels of social and physical anhedonia. In this study, we asked whether variation in anhedonia in a neurologically normal population is associated with altered sulcogyral pattern frequency. OFC sulcogyral type was classified and anhedonia was measured in 58 normal young adults, and the relationship between OFC sulcogyral type and anhedonia was explored. In line with other studies conducted in chronic schizophrenia, individuals with higher levels of physical anhedonia demonstrated atypical sulcogyral patterns. Individuals with higher physical anhedonia showed a reduced incidence of Type I OFC and an increased incidence of Type II OFC in the left hemisphere compared to individuals with lower physical anhedonia. These findings support the notion that Type I OFC sulcogyral pattern is protective of anhedonia compared to Type II, even in individuals that are not schizophrenic. Overall, these results support the view that symptoms and neural indices typically associated with neuropsychiatric disorders actually reflect quantitative traits that are continuously distributed throughout the general population. Hum Brain Mapp 37:3873-3881, 2016. © 2016 Wiley Periodicals, Inc.

Recently, the novel SNP rs12704290 in GRM3 was identified in a genome-wide association study on schizophrenia susceptibility. Our study was to investigate the association of 29 selected SNPs (including rs12704290) with schizophrenia and to evaluate any possible relationship between them and cognition related to schizophrenia. The SNPs were analyzed in 1115 unrelated schizophrenic patients and 2289 healthy controls. The results showed significant associations between these SNPs and schizophrenia as well as with changes in cognition.

Although cocaine abuse is up to three times more frequent among schizophrenic patients, it remains unclear why this should be the case and whether sex influences this relationship. Using a maternal immune activation model of schizophrenia, we tested whether animals at higher risk of developing a schizophrenia-like state are more prone to acquire cocaine self-administration behavior, and whether they show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction. Pregnant rats were injected with lipopolysaccharide on gestational day 15 and 16, and the offspring (both male and female) were tested in working memory (T-maze), social interaction and sensorimotor gating (prepulse inhibition of the acoustic startle response) paradigms. After performing these tests, the rats were subjected to cocaine self-administration regimes (0.5mg/kg), assessing their dose-response and extinction. Male rats born to dams administered lipopolysaccharide showed impaired working memory but no alterations to their social interactions, and both male and female rats showed prepulse inhibition deficits. Moreover, similar patterns of cocaine self-administration acquisition, responsiveness to dose shifts and extinction curves were observed in both control and experimental rats. These results suggest that the higher prevalence of cocaine abuse among schizophrenic individuals is not due to a biological vulnerability directly associated to the disease and that other factors (social, educational, economic, familial, etc.) should be considered given the multifactorial nature of this illness.

A major caveat with investigations on schizophrenic patients is the difficulty to control for medication usage across samples as disease-related neural differences may be confounded by medication usage. Following a thorough literature search (632 records identified), we included 37 studies with a total of 740 medicated schizophrenia patients and 367 unmedicated schizophrenia patients. Here, we perform several meta-analyses to assess the neurofunctional differences between medicated and unmedicated schizophrenic patients across fMRI studies to determine systematic regions associated with medication usage. Several clusters identified by the meta-analysis on the medicated group include three right lateralized frontal clusters and a left lateralized parietal cluster, whereas the unmedicated group yielded concordant activity among right lateralized frontal-parietal regions. We further explored the prevalence of activity within these regions across illness duration and task type. These findings suggest a neural compensatory mechanism across these regions both spatially and chronically, offering new insight into the spatial and temporal dynamic neural differences among medicated and unmedicated schizophrenia patients.

Introduction: Alterations of the "pre-reflective" sense of first-person perspective (e.g., of the "basic self") are characteristic features of schizophrenic spectrum disorders and are significantly present in the prodromal phase of psychosis and in subjects at ultra-high risk for psychosis (UHR). Studies in healthy controls suggest that neurobiological substrate of the basic self involves cortical midline structures, such as the anterior and posterior cingulate cortices. Neuroimaging studies have identified neuroanatomical cortical midline structure abnormalities in schizophrenic spectrum disorders. Objectives: i) To compare basic self-disturbances levels in UHR subjects and controls and ii) to assess the relationship between basic self-disturbances and alterations in cortical midline structures volume in UHR subjects. Methods: Thirty-one UHR subjects (27 antipsychotic-naïve) and 16 healthy controls were assessed using the 57-item semistructured Examination of Anomalous Self-Experiences (EASE) interview. All subjects were scanned using magnetic resonance imaging (MRI) at 3 T, and gray matter volume was measured in a priori defined regions of interest (ROIs) in the cortical midline structures. Results: EASE scores were much higher in UHR subjects than controls (p < 0.001). The UHR group had smaller anterior cingulate volume than controls (p = 0.037). There were no structural brain imaging alterations between UHR individuals with or without self-disturbances. Within the UHR sample, the subgroup with higher EASE scores had smaller anterior cingulate volumes than UHR subjects with lower EASE scores and controls (p = 0.018). In the total sample, anterior cingulate volume was inversely correlated with the EASE score (R = 0.52, p < 0.016). Conclusions: Basic self-disturbances in UHR subjects appear to be related to reductions in anterior cingulate volume.

The neurodegenerative and neurodevelopmental hypotheses represent the basic etiological framework for the origin of schizophrenia. Additionally, the dopamine hypothesis, adopted more than two decades ago, has repeatedly asserted the position of dopamine as a pathobiochemical substrate through the action of psychostimulants and neuroleptics on the mesolimbic and mesocortical systems, giving insight into the origin of positive and negative schizophrenic symptoms. Meanwhile, cognitive impairments in schizophrenia remain incompletely understood but are thought to be present during all stages of the disease, as well as in the prodromal, interictal and residual phases. On the other hand, observations on the effects of NMDA antagonists, such as ketamine and phencyclidine, reveal that hypoglutamatergic neurotransmission causes not only positive and negative but also cognitive schizophrenic symptoms. This review aims to summarize the different hypotheses about the origin of psychoses and to identify the optimal neuroimaging method that can serve to unite them in an integral etiological framework. We systematically searched Google scholar (with no concern to the date published) to identify studies investigating the etiology of schizophrenia, with a focus on impaired central neurotransmission. The complex interaction between the dopamine and glutamate neurotransmitter systems provides the long-needed etiological concept, which combines the neurodegenerative hypothesis with the hypothesis of impaired neurodevelopment in schizophrenia. Pharmaco-magnetic resonance imaging is a neuroimaging method that can provide a translation of scientific knowledge about the neural networks and the disruptions in and between different brain regions, into clinically applicable and effective therapeutic results in the management of severe psychotic disorders.

Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors) rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC) performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors) reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM-encoding and maintenance-are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.