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Objectives: Schizophrenia is a debilitating psychiatric illness associated with positive and negative symptoms as well as significant impairments in cognition. Current antipsychotic medications do not alleviate these cognitive deficits, and more effective therapeutic options are required. Increased oxidative stress and altered antioxidant levels, including glutathione (GSH) have been observed both in individuals with cognitive impairment and in people with schizophrenia. A GSH precursor, the antioxidant N -acetylcysteine (NAC) has been investigated as a novel treatment for the cognitive symptoms of schizophrenia, and recent research suggests that NAC may be a promising adjunctive treatment option. However, the current literature lacks integration as to why NAC may effectively improve cognition in schizophrenia. The present theoretical synthesis aimed to address this gap by examining the processes by which NAC may improve cognitive function in schizophrenia. Methods: The schizophrenia literature was reviewed in three key domains: cognitive impairment, the relationship between oxidative stress and cognition, and the efficacy of NAC as a novel treatment. This led to a theoretical analysis of the neurobiological processes by which NAC may improve cognition in schizophrenia. Results: This theoretical review concluded that improved cognition may result from a combination of factors, including decreased oxidative stress, neuroprotection of cognitive networks and an increase in glutamatergic modulation of the N -methyl-d-aspartate receptor system. Whilst a number of mechanisms by which NAC may improve cognition and symptoms in schizophrenia have been proposed, there is still limited understanding of the specific metabolic pathways involved and how they interrelate and modify specific symptomology. Discussion: Exploration of how NAC treatment may act to improve cognitive function could guide clinical trials by investigation of the specific neurotransmitter systems and processes involved, allowing for targeted neurological outcome measures. Future research would benefit from the investigation of both in vivo cortical GSH concentration and peripheral plasma GSH in a population of individuals with chronic schizophrenia.

Cognitive deficits present from the first onset of schizophrenia are thought to arise from a core problem in neural synchrony. This is the first study to characterize the profile of gamma (30-100 Hz) synchrony (rather than power) and behavioral performance during higher-order cognitive processing in schizophrenia. Gamma synchrony was acquired from the EEG, and elicited by a Continuous Performance Test (CPT). We quantitated synchrony for regions associated with the fronto-parietal attention and visual networks for 59 young people with First Onset Schizophrenia (FOS) and 59 matched controls, facilitated by the BRAINnet.net data sharing initiative. We compared groups on gamma synchrony for intrinsic (pre-stimulus), task-evoked change (relative to baseline) and absolute (not relative to baseline) measures. Relationships between synchrony and CPT accuracy, symptoms and functioning were also assessed. FOS showed a reduced ability to modulate task-evoked changes in gamma synchrony, in the context of generally higher intrinsic and absolute synchrony, particularly in frontal regions. These gamma synchrony abnormalities in FOS were associated with performance on the CPT, but not with symptoms or functioning. Task-relevant changes in synchrony may be constrained by an overall excess of intrinsic background synchrony that is unrelated to specific task demands and this relates to cognitive performance. Results are in line with theoretical accounts of gamma synchrony as a core abnormality in schizophrenia, affecting functional connectivity in central executive circuits and causing cognitive symptoms. This study is the first to demonstrate that these gamma synchrony abnormalities are not limited to perceptual or lower-order cognitive processing., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Impaired ability to make inferences about what another person might think or feel (i.e., social cognition impairment) is recognised as a core feature of schizophrenia and a key determinant of the poor social functioning that characterizes this illness. The development of treatments to target social cognitive impairments as a causal factor of impaired functioning in schizophrenia is of high priority. In this study, we investigated the acceptability, feasibility, and limited efficacy of 2 programs targeted at specific domains of social cognition in schizophrenia: "SoCog" Mental-State Reasoning Training (SoCog-MSRT) and "SoCog" Emotion Recognition Training (SoCog-ERT)., Method: Thirty-one participants with schizophrenia or schizoaffective disorder were allocated to either SoCog-MSRT (n = 19) or SoCog-ERT (n = 12). Treatment comprised 12 twice-weekly sessions for 6 weeks. Participants underwent assessments of social cognition, neurocognition and symptoms at baseline, post-training and 3-months after completing training., Results: Attendance at training sessions was high with an average of 89.29 % attendance in the SoCog-MSRT groups and 85.42 % in the SoCog-ERT groups. Participants also reported the 2 programs as enjoyable and beneficial. Both SoCog-MSRT and SoCog-ERT groups showed increased scores on a false belief reasoning task and the Reading the Mind in the Eyes test. The SoCog-MSRT group also showed reduced personalising attributional biases in a small number of participants, while the SoCog-ERT group showed improved emotion recognition., Conclusions: The results are promising and support the feasibility and acceptability of the 2 SoCog programs as well as limited efficacy to improve social cognitive abilities in schizophrenia. There is also some evidence that skills for the recognition of basic facial expressions need specific training., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12613000978763 . Retrospectively registered 3/09/2013.

Schizophrenia is a debilitating disorder of unknown cause. There is increasing momentum to consider functional dysconnectivity as an endophenotype of schizophrenia, and in particular, how it relates to cognition as a core feature of the disorder. Here, the authors review the conceptual models of functional dysconnectivity in schizophrenia to date, the evidence they are based on and some of the limitations of these models. The authors then propose 'neural synchrony' as a potential mechanism for functional dysconnectivity and review the current state of evidence for a link between neural synchrony and cognition in schizophrenia across behavioral, physiological, brain imaging, neurochemical and neurogenetic units of enquiry. The authors conclude by outlining the unmet needs in this field and give an outlook on how to fill these gaps.

Objective: This study aims to describe the clinical course of psychotic disorders, including the premorbid history, symptoms and level of functioning in a group of children and adolescents treated by paediatric mental health services, mainly as inpatients., Method: A sample of 45 children and adolescents with a psychotic disorder (mean age 13.2 years) was assessed using questionnaires, semi-structured interviews, parent interviews and file audit. The symptoms of those with a schizophrenia spectrum disorder (SSD) were compared to those with a mood disorder (MD)., Results: This population showed a high level of premorbid impairment, including previous treatment for other psychiatric disorders. As well as hallucinations and delusions, high levels of self-harm, aggression, anxiety and depression were reported. The SSD and MD groups differed mainly in their levels of premorbid functioning., Conclusions: While it is well known that childhood-onset schizophrenia is a severe disorder with a poor outcome, this study found that young people diagnosed with other psychotic disorders also have significant impairment and are likely to require high levels of care to maximize their functional recovery.

Objective: Schizophrenia is characterized by a deficit in context processing, with physiological correlates of hypofrontality and reduced amplitude P3b event-related potentials. We hypothesized an additional physiological correlate: differences in the spatio-temporal dynamics of cortical activity along the anterior-posterior axis of the scalp., Methods: This study assessed latency topographies of spatio-temporal waves under task conditions that elicit the P3b. EEG was recorded during separate auditory and visual tasks. Event-related spatio-temporal waves were quantified from scalp EEG of subjects with first episode schizophrenia (FES) and matched controls., Results: The P3b-related task conditions elicited a peak in spatio-temporal waves in the delta band at a similar latency to the P3b event-related potential. Subjects with FES had fewer episodes of anterior to posterior waves in the 2-4 Hz band compared to controls. Within the FES group, a tendency for fewer episodes of anterior to posterior waves was associated with high Psychomotor Poverty symptom factor scores., Conclusions: Subjects with FES had altered global EEG dynamics along the anterior-posterior axis during task conditions involving context update., Significance: The directional nature of this finding and its association with Psychomotor Poverty suggest this result is related to findings of hypofrontality in schizophrenia.

Background: Schizophrenia may be understood as a disorder of neural synchrony. There is also increasing evidence that emotional and social cognitive impairments are central to this disorder. In patients with first-episode schizophrenia, we examined whether emotion perception is associated with disruptions to high-frequency (40 Hz) gamma synchrony and whether these disruptions predict self-regulatory adaptive compensations reflected in social cognitive behaviours., Methods: We obtained electroencephalography recordings from 28 patients with first-episode schizophrenia and matched healthy controls during perception of facial emotion under both conscious and nonconscious conditions. We extracted gamma-band synchrony from the electroencephalogram. We also used behavioural measures of emotion identification, emotional intelligence, negativity bias and social function, along with ratings of first-episode schizophrenia symptoms. We analyzed group differences and predicted social cognition to assess the potential contribution of medication., Results: Within 200 ms poststimulus, patients with first-episode schizophrenia showed alterations in gamma synchrony during both conscious and nonconscious emotion perception. Stimulus-locked synchrony was reduced in patients, particularly over the temporal cortex, whereas complementary enhancements in absolute gamma synchrony (independent of stimuli) were more distributed over temporal and left parieto-occipital regions. This pattern of altered synchrony predicted poor performance on each measure of social cognition among these patients. Medication dosage did not correlate significantly with either gamma synchrony or behavioural measures in this group., Limitations: Limitations to our study include the lack of comparison between medicated and unmedicated patients or between types of medication., Conclusion: These findings suggest that disruptions in integrative processing of motivationally important stimuli show promise as a potential biological marker of social cognitive impairments, present from the first episode of schizophrenia, and their outcomes.

Of the few studies that have directly investigated the neuroanatomical correlates of delusions in patients with recent-onset schizophrenia, a number have paradoxically reported a positive correlation between delusion severity and regional grey matter volume. In order to explore this relationship, 31 patients with first-episode schizophrenia (FES) underwent a clinical interview and a T1-weighted structural MRI scan. Patients' scores on the Delusions subscale of the Positive and Negative Syndrome Scale were correlated with the volume of every voxel in their grey matter images in SPM99. Patients' delusion scores were found to correlate with the volume of a cluster of voxels located in the dorso-medial frontal cortex, centred on the medial frontal gyrus. Post-hoc analysis revealed that this 'region-of-correlation' was volumetrically reduced in the FES patients relative to a group of 21 matched healthy controls. The results of this study support the hypothesis that while a certain level of structural brain atrophy is necessary for delusion formation in patients with FES, excessive structural atrophy may in fact preclude the formation of highly systematized delusions.

A disturbance in the interactions between distributed cortical regions may underlie the cognitive and perceptual dysfunction associated with schizophrenia. In this article, nonlinear measures of cortical interactions and graph-theoretical metrics of network topography are combined to investigate this schizophrenia "disconnection hypothesis." This is achieved by analyzing the spatiotemporal structure of resting state scalp EEG data previously acquired from 40 young subjects with a recent first episode of schizophrenia and 40 healthy matched controls. In each subject, a method of mapping the topography of nonlinear interactions between cortical regions was applied to a widely distributed array of these data. The resulting nonlinear correlation matrices were converted to weighted graphs. The path length (a measure of large-scale network integration), clustering coefficient (a measure of "cliquishness"), and hub structure of these graphs were used as metrics of the underlying brain network activity. The graphs of both groups exhibited high levels of local clustering combined with comparatively short path lengths--features consistent with a "small-world" topology--as well as the presence of strong, central hubs. The graphs in the schizophrenia group displayed lower clustering and shorter path lengths in comparison to the healthy group. Whilst still "small-world," these effects are consistent with a subtle randomization in the underlying network architecture--likely associated with a greater number of links connecting disparate clusters. This randomization may underlie the cognitive disturbances characteristic of schizophrenia.

Background: Although schizophrenia has been characterized by disruptions to neural synchrony, it remains unknown whether these disturbances are related to symptoms and loss of grey matter. We examined relations between 40 Hz Gamma band synchrony and grey matter in patients with schizophrenia at first episode and after 2.5 years., Methods: From an initial recruitment of 35 medicated patients with a first episode of schizophrenia, 25 patients completed clinical and oddball task-elicited Gamma synchrony within 3 months of health service contact and again after 2.5 years, 23 completed magnetic resonance imaging (MRI) at these time points, and 13 completed all sessions. We compared patients with 35 matched healthy controls. We identified early (0-150 ms) and late (250-500 ms) peaks in Gamma synchrony locked to oddball targets, and we analyzed MRI data using voxel-based morphometry. We evaluated group and test-retest differences using repeated-measures analyses of variance., Results: Compared with controls, at first contact, patients with a first episode of schizophrenia showed a disruption to the laterality of early Gamma synchrony and global reduction in late Gamma synchrony, with a corresponding loss of fronto-temporal-parietal grey matter. Gamma synchrony was increased at follow-up among patients with a first episode of schizophrenia. It related negatively to further loss of grey matter, but positively to improvement in reality distortion symptoms. These relations could not be explained by medication dose., Limitations: Our study did not include unmedicated patients or normative follow-up testing., Conclusion: Gamma synchrony may track the progression of schizophrenia from first episode. An increase in Gamma synchrony over time might reflect an attempt to adapt to a progressive loss of cortical grey matter and associated changes in cognitive and emotional function.

Objective: This study explored the concurrent courses of the neuroanatomical and neuropsychological changes that occurred over the first 2-3 years of illness in patients with first-episode schizophrenia (FES)., Methods: Fifty-two patients with FES underwent neuropsychological testing and a structural magnetic resonance imaging (sMRI) scan within three months of their first presentation to mental health services with psychotic symptoms (time1). Patients' cognitive performance was evaluated via an extensive neuropsychological test battery, which assessed 9 cognitive domains. Of the 52 patients at time1, 32 returned 2-3 years later (time2) for follow-up neuropsychological testing, and 20 of these also underwent follow-up sMRI. MR images were preprocessed in SPM99. Grey matter volumes of patients' whole-brain, frontal lobes and temporal lobes were calculated by convolving the preprocessed images with manually-drawn binary masks., Results: Patients exhibited longitudinal improvements in full-scale IQ, performance IQ and visual memory. In contrast, concurrent reductions in grey matter were observed for the whole-brain (3% reduction) and the frontal lobe (3.65% reduction). Furthermore, the extent of patients' whole-brain and frontal-lobe grey matter changes were positively correlated with longitudinal changes in verbal learning and memory., Discussion: The results of this study suggest that while the early stages of schizophrenia are associated with a mild improvement in patients' overall cognitive functioning, they are also associated with progressive grey matter atrophy.

Objective: It is increasingly recognized that cognitive assessments, unlike symptom ratings, provide a reliable predictor of functional outcome in schizophrenia. This study evaluated the utility of the 'IntegNeuro' computerized test battery for assessing cognition in first episode schizophrenia. We determined the presence of separable factors of general and social cognition, their equivalence to the consensus domains identified by the NIMH MATRICS project, and their effectiveness in predicting real world functional outcomes., Method: Fifty six first episode schizophrenia (FES) patients and 112 matched healthy controls were assessed on the touchscreen-based 'IntegNeuro' cognitive test battery and FES patients for social functioning (SOFAS) and quality of life (WHOQOL-BREF)., Results: Principal components analysis identified i) six factors corresponding to MATRICS domains of general cognition ('Information Processing Speed', 'Verbal Recall', 'Working Memory Capacity', 'Sustained Attention/Vigilance', 'Verbal Processing', 'Executive Function'), ii) an 'Emotional Intelligence' factor corresponding to the MATRICS social cognition domain, and iii) an additional 'Sensori-Motor Function' factor of general cognition and 'Negativity' factor of social cognition. Patients showed impairments relative to controls across all factors, but especially for Working Memory Capacity, followed by Verbal Memory, Sustained Attention/Vigilance and Negativity. These factors strongly predicted poorer social functioning in FES, along with poorer quality of life in psychological, social, and health satisfaction facets., Conclusion: The IntegNeuro battery has utility for assessing separable domains of general and social cognition in FES, which are predictive of real world outcomes. Thus, it may be appropriate for clinical application, including in multi-center trials targeting new treatments for cognition in schizophrenia.

Objective: While schizophrenia has long been considered a disorder of brain connectivity, few studies have investigated white matter abnormalities in patients with first-episode schizophrenia, and even fewer studies have investigated whether there is progressive white matter pathology in the disease., Method: The authors obtained a T1-weighted structural magnetic resonance imaging (MRI) scan on 41 patients with first-episode schizophrenia. These first-episode schizophrenia patients were analyzed relative to 47 age- and sex-matched healthy comparison subjects who also underwent an MRI scan. Of the baseline participants, 25 first-episode schizophrenia patients and 26 comparison subjects returned 2 to 3 years later for a follow-up scan. To identify regional volumetric white matter differences between the two groups at baseline, voxel-based morphometry in statistical parametric mapping-2 (SPM2) was used, while tensor-based morphometry was used to identify the longitudinal changes over the follow-up interval., Results: The first-episode schizophrenia patients exhibited volumetric deficits in the white matter of the frontal and temporal lobes at baseline, as well as volumetric increases in the white matter of the frontoparietal junction bilaterally. Furthermore, these first-episode schizophrenia patients lost considerably more white matter over the follow-up interval relative to comparison subjects in the middle and inferior temporal cortex bilaterally., Conclusions: These results indicate that patients with schizophrenia exhibit white matter abnormalities at the time of their first presentation of psychotic symptoms to mental health services and that these abnormalities degenerate further over the initial years of illness. Given the role that white matter plays in neural communication, the authors suggest that these white matter abnormalities may be a cause of the dysfunctional neural connectivity that has been proposed to underlie the symptoms of schizophrenia.

Schizophrenia patients show a disconnection in amygdala-medial prefrontal cortex and autonomic arousal systems for processing fear. Concurrent functional magnetic resonance imaging [fMRI] and skin conductance recording were used to determine whether these disturbances are specific to fear, or present in response to other signals of danger. We also examined whether these disturbances distinguish a specific symptom profile. During scanning, 27 schizophrenia (13 paranoid, 14 nonparanoid) and 22 matched healthy control subjects viewed standardized facial expressions of fear, anger and disgust (versus neutral). Skin conductance responses [SCRs]were acquired simultaneously to assess phasic increases in arousal. 'With-arousal' versus 'without-arousal' responses were analysed using non-parametric methods. For controls, 'with-arousal' responses were associated with emotion-specific activity for fear (amygdala), disgust (insula) and anger (anterior cingulate), together with common medial prefrontal cortex [MPFC] engagement, as predicted. Schizophrenia patients displayed abnormally increased phasic arousal, with concomitant reductions in emotion-specific regions and MPFC. These findings may reflect a general disconnection between central and autonomic systems for processing signals of danger. This disjunction was most apparent in patients with a profile of paranoia, coupled with poor social function and insight. Heightened autonomic sensitivity to signals of fear, threat or contamination, without effective neural mechanisms for appraisal, may underlie paranoid delusions which concern threat and contamination, and associated social and interpersonal difficulties.

Although there is substantial evidence indicating that patients with first-episode schizophrenia exhibit both anatomical and electrophysiological abnormalities, there has been little research investigating the relationship between these two indices. We acquired structural magnetic resonance images and resting electroencephalographic recordings from 19 patients with schizophrenia, both at the time of their first presentation to mental health services and 2-3 years subsequently. Patients' grey matter images were parcellated into four brain lobes, and slow-wave, alpha- and beta-electroencephalographic power was calculated in four corresponding cortical regions. Although grey matter volume decreased longitudinally, particularly fronto-parietally, electroencephalographic power increased in the slow-wave and beta-frequency bands. These results suggest that first-episode schizophrenia may be associated with abnormally elevated levels of neural synchrony.

Background: Schizophrenia patients show reduced neural activity, relative to controls, in the amygdala and its projection to the medial prefrontal cortex (MPFC) in response to fear perception. In this study we tested the hypothesis that schizophrenia is characterized by abnormal functional connectivity in the amygdala network underlying fear perception., Methods: Functional MRI images were acquired from 14 schizophrenia patients and 14 matched healthy control subjects during an emotion perception task, in which fearful and neutral facial expression stimuli were presented pseudorandomly under nonconscious (using masking) and conscious conditions. Both subtraction and functional connectivity analyses were undertaken using a region of interest approach., Results: In response to fearful facial expressions, schizophrenia patients displayed reduced amygdala activity, compared to controls, in both the conscious and nonconscious conditions. The amygdala displayed a reversal of the normal pattern of connectivity with the brainstem, visual cortex, and also with the dorsal and ventral divisions of the MPFC in the schizophrenia patients., Conclusions: The presence of functional disconnections in amygdala pathways suggests that schizophrenia patients have a failure in coordinating their automatic orienting to salient signals and the associated prefrontal monitoring of these signals.

Background: This paper examines the potential impact of recruitment source differences in schizophrenia research by comparing the neuropsychological performance of volunteers from the NISAD Schizophrenia Research Register with recently published schizophrenia normative data for the Repeatable Battery for Neuropsychological Status (RBANS)., Methods: The Register sample comprised 285 volunteers with schizophrenia or schizoaffective disorder. Their RBANS performance was compared with US data from 575 predominantly outpatient-recruited schizophrenia patients., Results: The Register sample displayed impairments in immediate and delayed memory, but near-normal language, attention and visuospatial-constructional performance (mean RBANS total score=88.72, SD=16.35). By contrast, health service-recruited schizophrenia patients displayed impairments on all RBANS scales (mean RBANS total score=70.54, SD=14.80). Within the Register sample, volunteers with low levels of current functioning had immediate and delayed memory performance comparable to the US schizophrenia sample. Gender and school completion status were also associated with different RBANS profiles., Conclusions: These findings reinforce the notion that a severity/functioning gradient exists across schizophrenia recruitment sources, which has important implications for research design and generalizability. Memory impairments have emerged as a central feature of schizophrenia.

Little is known about the structural brain changes that occur over the first few years of schizophrenia, or how these changes differ from those associated with healthy brain development in adolescence and early adulthood. In this study, we aimed to identify regional differences in grey matter (GM) volume between patients with first-episode schizophrenia (FES) and matched healthy controls, both at the time of the patients' first psychotic episode (baseline condition) and 2-3 years subsequently (follow-up condition). Forty-one patients with FES and 47 matched healthy controls underwent a T1-weighted structural MRI scan. Of these participants, 25 FES patients and 26 controls returned 2-3 years later for a follow-up scan. Voxel-based morphometry in SPM2 was used to identify the regions of GM difference between the groups in the baseline condition, while tensor-based morphometry was used to identify the longitudinal change within subject over the follow-up interval. The FES patients exhibited widespread GM reductions in the frontal, parietal, and temporal cortices and cerebellum in the baseline condition, as well as more circumscribed regions of GM increase, particularly in the occipital lobe. Furthermore, the FES subjects were observed to lose considerably more GM over the follow-up interval than the controls, especially in the parietal and temporal cortices. We argue that the progressive GM atrophy we have found to be associated with the onset of schizophrenia arises from a dysfunction in the dramatic period of healthy brain development typically associated with adolescence.

Background: We examined gray- and white-matter brain volumes in first episode psychosis (FEP) at initial presentation and at two-year follow-up. We predicted that FEP subjects would show longitudinal reductions in fronto-temporal gray- and white-matter volumes compared with controls. Furthermore, we expected groups to be differentiated by diagnosis-related reductions., Methods: Twenty-five schizophrenia and 8 bipolar disorder FEP patients underwent a structural MRI scan at first presentation and 2 years later. Matched healthy subjects (n = 22) underwent a single identical scan., Results: At initial presentation FEP subjects had significantly less gray- and white-matter than healthy subjects. Diagnostic dissociations were revealed both at first presentation and at follow-up. In schizophrenia patients, gray-matter deficits were observed in lateral and medial frontal regions and in bilateral posterior temporal lobe regions, with additional extensive losses over time in lateral fronto-temporal regions and left anterior cingulate gyrus. By contrast, gray matter deficit in bipolar patients was localized to bilateral inferior temporal gyri with additional loss over time observed only in the anterior cingulate cortex., Conclusions: The results are consistent with a dual process model of psychosis, in which the diagnosis-related gray matter loss is determined by neurodevelopmental gray-matter volumetric differences which predate symptom onset, and diagnosis-related neurodegenerative gray-matter loss over time.

Several studies have investigated grey matter reductions in first episode schizophrenia (FES), but few have examined the relationship between grey matter reduction and clinical profile. A group of 31 patients with strictly defined FES and 30 healthy controls underwent T1-weighted magnetic resonance imaging (MRI) scan. Voxel-based morphometry in SPM99 was used to identify four distinct regions of grey matter reduction in the FES subjects. The regions of interest (ROIs) were in the left ventral prefrontal cortex (ROI 1), left parietal and temporal cortices (ROI 2), right cerebellum (ROI 3), and right frontal and parietal cortices (ROI 4). These regions of reduction were transformed into binary masks, which were convolved with patients' pre-processed grey matter images. Patients' grey matter volumes in these regions were correlated with their composite scores on the following three symptom dimensions: Psychomotor Poverty, Disorganization and Reality Distortion. The volumes of ROIs 1, 2 and 4 were found to be significantly correlated with the Reality Distortion syndrome score. Our findings indicate that distinct, widespread grey matter reductions are present very early in the course of schizophrenia. The results also suggest a possible structural underpinning for the abnormal brain activity typically associated with symptoms of Reality Distortion.

Objective: There has been a convergence of models describing schizophrenia as a disconnection syndrome, with a focus on the temporal connectivity of neural activity. Synchronous gamma-band (40-Hz) activity has been implicated as a candidate mechanism for the binding of distributed neural activity. To the authors' knowledge, this is the first study to investigate "gamma synchrony" in first-episode schizophrenia., Method: Forty medicated first-episode schizophrenia patients and 40 age- and sex-matched healthy comparison subjects participated in a conventional auditory oddball paradigm. Gamma synchrony, time-locked to target stimuli, was extracted from an ongoing EEG. The magnitude and latency of both early (gamma 1: -150 msec to 150 msec poststimulus) and late (gamma 2: 200 to 550 msec poststimulus) synchrony were analyzed with multiple analysis of variance., Results: First-episode schizophrenia patients showed a decreased magnitude and delayed latency for global gamma 1 synchrony in relation to healthy comparison subjects. By contrast, there were no group differences in gamma 2 synchrony., Conclusions: These findings suggest that first-episode schizophrenia patients have a global decrease and delay of temporal connectivity of neural activity in early sensory response to task-relevant stimuli. This is consistent with cognitive evidence of perceptual integration deficits in this disorder and raises the possibility that a breakdown in the early synchrony of distributed neural networks is a marker for the onset of schizophrenia.

A recently developed quantitative model of cortical activity is used that permits data comparison with experiment using a quantitative and standardized means. The model incorporates properties of neurophysiology including axonal transmission delays, synaptodendritic rates, range-dependent connectivities, excitatory and inhibitory neural populations, and intrathalamic, intracortical, corticocortical and corticothalamic pathways. This study tests the ability of the model to determine unique physiological properties in a number of different data sets varying in mean age and pathology. The model is used to fit individual electroencephalographic (EEG) spectra from post-traumatic stress disorder (PTSD), schizophrenia, first episode schizophrenia (FESz), attention deficit hyperactivity disorder (ADHD), and their age/sex matched controls. The results demonstrate that the model is able to distinguish each group in terms of a unique cluster of abnormal parameter deviations. The abnormal physiology inferred from these parameters is also consistent with known theoretical and experimental findings from each disorder. The model is also found to be sensitive to the effects of medication in the schizophrenia and FESz group, further supporting the validity of the model.

Objective: There has been consistent evidence for a lower incidence and milder course of schizophrenia in women, yet there have been very few investigations of sex differences in brain function in this disorder. This study used a new high-temporal-resolution measure of functional brain connectivity to test the prediction that female patients would show relatively greater inter- and intrahemispheric connectivity than male patients, particularly in the early stage of schizophrenia., Method: Forty patients with chronic schizophrenia (20 women and 20 men) and 24 patients with first-episode schizophrenia (12 women and 12 men) and their respective matched comparison groups completed a conventional auditory oddball task. Phase synchronous gamma (40 Hz) activity was extracted from EEG recording during the task and time-locked to the oddball (target) stimuli., Results: Chronic schizophrenia subjects showed a reduction in global functional connectivity (lower gamma phase synchrony) relative to their matched healthy subjects. Unexpectedly, this reduction was most apparent in female patients. By contrast, while first-episode patients showed a general reduction in the speed of frontal connectivity, the speed of global connectivity was relatively faster in female patients., Conclusions: This is the first study to investigate sex differences in schizophrenia that used the functional connectivity measure of gamma phase synchrony. The results suggest that in female patients with schizophrenia, additional breakdowns in brain network connectivity may develop with illness chronicity.

Previous research demonstrates that people with schizophrenia have abnormally 'restricted' visual scanpaths to face and facial expression stimuli, which appear to be diagnostically specific to schizophrenia [Schizophr. Res. 55 (2002) 159; Biol. Psychiatry 52 (2002) 338]. This study examined the familial transmission of 'restricted' scanpaths in first-degree relatives of schizophrenia subjects. We recorded visual scanpaths for 65 schizophrenia subjects, 37 biological first-degree relatives and 61 nonrelated 'healthy' control subjects in two experiments: 'face recognition' and 'facial affect recognition'. Concurrent behavioral tasks were face matching and expression matching, each under two multiple-choice conditions (seven or three options). As predicted, first-degree relatives generally showed an attenuated form of the markedly 'restricted' scanpaths of schizophrenia subjects across all face stimuli. The notable exception to this pattern was the relatives' extreme avoidance of facial features (compared to both schizophrenia and healthy control groups). Our results offer the first evidence that some components of visual scanpath dysfunction may represent a trait marker in the familial transmission of schizophrenia, but that first-degree relatives may have additional disturbances in social cognition associated with the perception of facial features.

The aim of this study was to investigate the relationship between the five-factor model of psychopathology and depression in schizophrenia. Symptoms were rated using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS) in 105 chronic patients with schizophrenia. Principal-component analysis (PCA) produced a five-factor solution for the PANSS (psychomotor poverty, disorganisation, reality distortion, excitement, and depression), and a two-factor solution for the MADRS (psychological and behavioural depression). The PANSS depression factor was highly associated with the MADRS psychological depression factor but not with MADRS behavioural depression. By contrast, the PANSS excitement factor showed a strong positive correlation with the behavioural depression factor but not with psychological depression. These MADRS factors were not associated significantly with the core PANSS factors, including psychomotor poverty. It is suggested that depression exists as an independent domain, differentiated from negative symptoms, in the structure of schizophrenia symptomatology., (Copyright 2003 S. Karger AG, Basel)

We used a psychophysiological marker of visual attention (the visual scanpath) to investigate the effects of atypical (risperidone) vs. typical (haloperidol) antipsychotic medication on facial emotion perception in schizophrenia (n=28) and healthy control (n=28) groups. Of the schizophrenia subjects, 15 were prescribed risperidone. Visual scanpaths to 'happy', 'sad' and 'neutral' faces were recorded using video-oculography, and concurrent emotion-recognition accuracy was assessed using multiple-option tasks. Compared to control subjects, both schizophrenia subgroups showed a restriction in visual scanning (reduced total fixation number and decreased scanpath length). Haloperidol-treated schizophrenia subjects exhibited an additional and consistent pattern of reduced attention (fixation) to salient features for neutral and happy. By contrast, risperidone-treated subjects showed a relatively greater attention to salient features for these expressions, in which they did not differ from controls. Recognition accuracy for happy and neutral showed a similar lack of impairment. These findings suggest that risperidone may play a specific role in schizophrenia in the ability to attend to salient features, and to integrate this information into an accurate percept for neutral and positive expressions in particular.

Background: Traditional averaging of late component Event Related Potentials (ERPs) might obscure important psychophysiological subprocesses underlying schizophrenia disturbances in cognitive functioning. One such subprocess could be the active orientation of attention to significant or novel stimuli. In this study, we used skin conductance responses (SCRs) to index orienting responses (ORs). ERP activity was examined in relation to concomitant ORs in a schizophrenia and nonpsychiatric control group. Schizophrenia responses were considered with respect to the Reality Distortion, Disorganisation and Psychomotor Poverty syndromes., Method: Forty schizophrenia and 40 age and sex matched control subjects were tested. The three schizophrenia syndromes were derived from a principal component analysis of Positive and Negative Syndrome Scale (PANSS) ratings. Auditory ERPs (N100, N200, P200, P300) were elicited using a conventional auditory oddball paradigm, and electrodermal SCR data were acquired simultaneously., Results: ERP data were sub-averaged according to the presence/absence of an OR. For both 'with-' and 'without-OR' ERPs, schizophrenia subjects as a group showed reduced N100 (associated with vigilance level) and N200 (associated with response selection) amplitude, and for with-OR responses, they showed an additional reduction in P300 (context processing). Concerning schizophrenia syndromes, Reality Distortion was related primarily to frontal disturbances (earlier N100/N200 latency and decreased P200/P300 amplitude), and Psychomotor Poverty to a generally delayed P300 latency. Similarly delayed P300 in Disorganisation was explained by medication effects. There were no associations with syndromes for without-OR ERPs., Conclusion: These results suggest that schizophrenia syndromes are dissociated with regard to both the direction and nature of speed of information processing disturbances, in relation to task-relevant information that produces active orientation., (Copyright 2002 Elsevier Science B.V.)

Introduction: Cognitive impairments are a common and significant issue for young people with a severe mental illness. Young people with schizophrenia, bipolar disorder and major depression all experience significant cognitive problems that impede their ability to return to work or study. These neurocognitive problems are frequently exacerbated by social cognitive deficits that interfere with their ability to integrate into the community and understand the social and emotional nuances about them. This study aimed to assess if the addition of a social cognitive remediation treatment to a neurocognitive remediation therapy improved functional outcome. Methods: Five youth mental health services were trained in both the Neuropsychological Educational Approach to Remediation (NEAR) and the Social Cognition and Interaction Training (SCIT) treatments. Participants were randomised between receiving either NEAR + SCIT or NEAR + treatment as usual (TAU) over a 20-week period, with all participants receiving the NEAR treatment first. Symptoms, neurocognition, social cognition and functioning were examined at baseline, end of treatment and at 3 months follow-up and compared between the two arms of the study. The primary outcome was function. Results: Thirty-nine participants were randomised to treatment (Schizophrenia spectrum = 28, Bipolar disorder = 7, Major Depression = 2). The trial was curtailed by Covid-related service restrictions. There was an overall significant improvement in function over time with a trend towards a greater improvement in the NEAR + SCIT arm. No changes in symptoms, neurocognitive or social cognitive measures were seen. While 74% completed treatment only 49% agreed to follow up at 3 months affecting our ability to interpret the findings. Attrition did not differ by arm. Conclusions: In a pragmatic, service-based research project, treatment aimed at improving cognition enhanced functional outcome in young people with a range of severe mental illnesses. There was a trend towards improved function in young people who had a combined NEAR + SCIT approach. Clinical Trial Registration: Identifier: ACTRN12622000192785. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy, safety, and impact on hospitalizations of long-acting injectable paliperidone palmitate (PP) treatment, in patients with recent-onset schizophrenia who had not responded satisfactorily to oral antipsychotics. Methods: In this 18-month, open-label, Phase-IIIb study from Asia-Pacific region, patients (18-50 years) with recent-onset (⩽5 years) schizophrenia unsatisfactorily treated with previous oral antipsychotics were initiated on PP 150 mg eq on day 1, 100 mg eq on day 8, followed by flexible once monthly maintenance doses of 50-150 mg eq. The number and duration of hospitalizations were compared using a mirror analysis method between two periods: retrospective (12 months before PP initiation) and prospective (12 and 18 months after PP treatment) periods. Results: A total of 303 out of 521 (58%) patients (mean age, 28.7 years; 65.5% men, 92.5% Asian) completed the study. Positive and Negative Syndrome Scale (PANSS) total score improved significantly from baseline to month 18 (mean [standard deviation, SD] change: -11.3 [21.38], P<0.0001, primary endpoint). Subgroup analysis revealed greater improvements among patients with worse disease severity at baseline: PANSS ⩾70 versus <70 (mean [SD] change: -23.1 [24.62] vs -4.7 [15.98], P<0.0001 each). Secondary efficacy endpoints such as Clinical Global Impression of Schizophrenia (CGI-SCH), Medication Satisfaction Questionnaire (MSQ) scores showed significant improvements (P<0.0001) from baseline; 33.3% patients achieved symptom remission. In mirror analyses set (N=474), PP significantly (P<0.0001) reduced mean number of hospitalization days/person/year (12-month: 74.3 vs 19.7; 18-month: 74.3 vs 18.9) as well as percentage of patients requiring hospitalization in past 12 months (12-month: 39.7% vs 24.6%; 18-month: 39.7% vs 25%), and PP treatment increased the proportion of patients not requiring hospitalization (12-month: 60.3% vs 75.4%; 18-month: 60.3% vs 75%) from retrospective to prospective period. Adverse events (⩾15%) were extrapyramidal symptoms-related (31.3%), injection-site pain (18.6%), and insomnia (15.2%). Conclusion: PP was efficacious and generally tolerable with significant reductions observed in both number of hospitalizations and days spent in hospital. [ABSTRACT FROM AUTHOR]

Schizophrenia is characterized by deficits in face and facial emotion processing. This is the first study using event-related potentials (ERPs) to investigate the corresponding neural activation in first onset psychosis. ERPs for 108 first onset psychosis participants and 108 matched healthy controls were recorded while they viewed facial expressions. Group differences on general (neutral) face processing and emotional valence were examined under both unmasked (conscious) and backward-masked (nonconscious implicit) conditions over frontal and temporo-occipital regions. Clinical significance was assessed by comparing diagnoses and correlating ERPs with symptoms. During general face processing, patients showed reduced activation within 70 ms and exaggerated later processing from 160 ms over the frontal region, with a negative shift in voltage over left temporal and occipital regions across the time course. In addition, from 70 ms onwards, patients showed a positive shift in voltage for disgust whereas controls showed a negative shift in voltage for fear and anger (both compared to happy) over temporo-occipital regions. Effects were related to disorganization and depression symptoms and (preliminarily) were apparent across psychotic diagnoses. These results suggest that first onset psychosis is characterized by general as well as emotion-specific face processing impairments from the earliest, automatic processing period. [ABSTRACT FROM AUTHOR]

Modelos diferentes convergen cuando describen la esquizofrenia como un síndrome de escisión que afecta, preferentemente, a la conectividad temporal de la actividad neural. La actividad sincrónica de la banda gamma (40 Hz) se ha considerado un posible mecanismo de unión de una actividad neural diseminada. Los autores creen que se trata del primer estudio que investiga la "sincronía gamma" en el primer episodio de esquizofrenia. Método: Cuarenta pacientes medicados por un primer episodio de esquizofrenia y 40 individuos sanos de control equiparados en edad y sexo participaron en un paradigma auditivo estándar "oddball. " La sincronía gamma, bloqueada temporalmente a los estímulos objeto de estudio, se extrajo de un EEG en curso. Se analizaron el alcance y la latencia de la sincronía inicial (gamma 1:-150 mseg a 150 mseg después del estímulo) y tardía (gamma2: 200-550 mseg después del estímulo) con un análisis de la varianza múltiple. Resultados: Los pacientes con un primer episodio de esquizofrenia mostraron una menor magnitud y una latencia retardada de la sincronía total gamma 1 en comparación con los individuos sanos de control. Por otro lado, no se observaron diferencias de grupo en la sincronía gamma 2. Conclusiones: Estos resultados indican que los pacientes con un primer episodio de esquizofrenia presentan una disminución general y una demora de la conectividad temporal de la actividad neural en la respuesta sensorial inicial a los estímulos que revisten interés para la prueba. Esto concuerda con las pruebas cognitivas que revelan la existencia de alteraciones de la integración perceptiva en este trastorno, sugiriendo la posibilidad de que la interrupción de la sincronía inicial entre las redes neurales diseminadas constituya un marcador del inicio de la esquizofrenia. [ABSTRACT FROM PUBLISHER]