Sample Of First-episode Schizophrenia Patients Research Articles

Do deficits in the magnocellular priming underlie visual derealization phenomena? Preliminary neurophysiological and self-report results in first-episode schizophrenia patients

BackgroundEarly visual impairments probably partially caused by impaired interactions between magnocellular (M) and parvocellular (P) pathways (M priming deficit), and disturbances of basic self-awareness or self-disorders (SDs) are core features of schizophrenia. The relationships between these features have not yet been studied. We hypothesized that the M priming was impaired in first-episode patients and that this deficit was associated with visual aspects of SDs. AimTo investigate early visual processing in a sample of first-episode schizophrenia patients and to explore the relationships between M and P functioning and visual aspects of SDs addressed by the Examination of Anomalous Self-Experience (EASE) interview. MethodNine stimulating conditions were used to investigate M and P pathways and their interaction in a pattern reversal visually evoked potential (VEP) paradigm. N80 at mixed M- and P-conditions was used to investigate magnocellular priming. Generators were analyzed using source localization (Brain Electrical Source Analysis software: BESA). VEPs of nineteen first-episode schizophrenia patients were compared to those of twenty matched healthy controls by a bootstrap resample procedure. Visual aspects of SDs were analyzed through a factor analysis to separate symptom clusters of derealization phenomena. Thereafter, the associations between the main factors and the N80 component were explored using linear mixed models. ResultsFactor analyses separated two EASE factors (“distance to the world”, and “intrusive world”). The N80 component was represented by a single dipole located in the occipital visual cortex. The bootstrap analysis yielded significant amplitude reductions and prolonged latencies in first-episode patients relative to controls in response to mixed M–P conditions, and normal amplitudes and latencies in response to isolated P- and M-biased stimulation. Exploratory analyses showed significant negative correlations between the N80 amplitude values at mixed M–P conditions and the EASE factor “distance to the world”, i.e. relatively higher amplitudes in the patient group were associated with higher subjective perceived derealization (“distance to the world”). ConclusionsThe early VEP component N80 evoked by mixed M–P conditions is assumed to be a correlate of M priming, and showed reduced amplitudes and longer latencies in first-episode patients. It probably reflects a hypoactivation of the M-pathway. The negative association between visual SDs (derealization phenomena characterized by visual experiences of being more distant to the world), and the M priming deficit was counterintuitive. It might indicate a dysregulated activity of the M-pathway in patients with SDs. Further research is needed to better understand this preliminary finding.

Schizophrenia: from risk genes to outcome and comorbidity

Springer-Verlag 2012 Dedicated to neurobiology, therapy and outcome of schizophrenia, this issue opens with the effects of the schizophrenia risk gene D-amino acid oxidase activator (DAOA) in healthy probands. During the last years, there is increasing evidence of the involvement of risk genes in the pathophysiology of severe psychiatric diseases, but neurobiological consequences of these gene variants are widely unknown. The DAOA polymorphism has been shown to be associated with a dysfunction of the glutamatergic NMDA receptor that in turn influences dopaminergic and serotonergic metabolism. Andreou et al. [1] investigated effects of DAOA SNPs on the major dopamine metabolite homovanillic acid (HVA), the serotonine metabolite 5-HIAA and the noradrenaline metabolite MHPG in cerebrospinal fluid of healthy probands. They found an association of two polymorphisms with HVA concentrations and one of them with 5-HIAA levels. This suggests DAOA gene variants to possibly affect dopamine turnover. Investigation of gene effects in healthy probands is recommended to avoid the influence of other disease factors and treatment, but as a next step neurobiological consequences should be assessed in schizophrenia patients. Ayesa-Arriola et al. [2] investigated the relationship between elevated plasma homocysteine levels and cognitive deficits in a large sample of first-episode schizophrenia patients and controls. However, despite very sophisticated neuropsychological testing, they found no evidence for a respective tie, which points to another neurobiological background than in neurological diseases. Since plasma

Cannabis use and cognitive functioning in first-episode schizophrenia patients

Cannabis is one of the most widely used illicit drugs in the world. In healthy individuals cannabis is associated with cognitive impairments. Research into the effect of cannabis use in schizophrenia has yielded contradictory findings. Our aim has been to explore the correlates of cannabis use in cognitive and psychopathological features, both cross-sectional and longitudinally, in early phases of schizophrenia. 104 patients with a first episode of non-affective psychosis and 37 healthy controls were studied. Patients were classified according to their use of cannabis prior to the onset of the illness (47 users vs. 57 non-users). They were cross-sectionally and longitudinally studied and compared on clinical and cognitive variables and also on their level of premorbid adjustment. Cannabis user patients had better attention and executive functions than non-cannabis user patients at baseline and after 1 year of treatment. Both groups showed similar improvement in their cognitive functioning during the 1-year follow-up period. We also found that users had a better social premorbid adjustment, particularly during the early periods of life. The amount of cannabis consumed and the length of time of consumption did not significantly relate to cognitive performance. The use of cannabis does not seem to be associated with a negative effect on cognition in a representative sample of first-episode schizophrenia patients. Cannabis user patients appear to comprise a subgroup of patients with a better premorbid adjustment and premorbid frontal cognitive functions.

MEG does not reveal impaired sensory gating in first-episode schizophrenia

Objective The inability to adequately suppress the second of two identical stimuli is called sensory gating deficit and can be studied by recording evoked potentials to auditory stimuli, e.g. the P50 and the N100. It has been considered the physiological correlate of schizophrenia patients' perception of being flooded by sensory impressions. According to the notion that the gating deficit constitutes a genetic trait, we expected to demonstrate the phenomenon in first-episode schizophrenia patients by using Magnetencephalography (MEG). Methods Eighteen inpatients in remission of their first psychotic episode and 24 healthy, age- and sex-matched control subjects participated in the study. Diagnoses, psychopathology, and handedness were assessed with established instruments. Stimulation was performed with the double click paradigm (ISI 500 ms, ITI 9–10 s). MEG recordings of 15 patients and 18 controls entered further analyses with the software BESA for spatio-temporal source analyses and statistical analyses with MATLAB. Results Neither P50 nor N100 responses differed statistically between the groups, which means that gating was not impaired in this sample of first-episode schizophrenia patients. Conclusions These results are not in line with the majority of studies on sensory gating in schizophrenia, however, studies on first-episode patients are scarce. The most likely reasons for not observing a gating deficit in our study are patients' first-episode status and atypical antipsychotic medication.

ATTRIBUTIONAL REASONING BIASES, PARANOIA AND DEPRESSION IN FIRST-EPISODE SCHIZOPHRENIA

Background: Evidence that paranoid people with schizophrenia show a 'self-serving' bias, whereby they externalize the blame for negative events, has prompted the development of 'attributional interventions' to augment cognitive behavioral therapies. However, longitudinal and first-episode research to validate these interventions is lacking. This study aimed to address this gap in the literature by examining attributional biases, paranoia and depression in a sample of first-episode schizophrenia patients. Methods: Twenty-four young people with schizophrenia-spectrum disorders (23 males and one female with a mean age of 20.9 years, SD=1.8) were recruited from two early psychosis intervention services in Sydney, Australia. Inclusion criteria included less than two years since the onset of psychosis, a minimum age of 18 years, English-speaking, and no current major co-morbidity. Nineteen healthy controls (19 males and two females with a mean age of 20.8 years, SD=1.7) also took part. Patient diagnosis was confirmed using the Diagnostic Interview for Psychosis (Castle et al., 2006) and symptom severity was rated using the SAPS, SANS and BPRS. All participants were assessed for levels of paranoia (Paranoia Scale; Fenigstein & Vanable, 1992), suspiciousness (BPRS), depression (Hamilton Depression Scale: HAM-D; Hamilton, 1967) and attributional biases (Internal, Personal and Situational Attributions Questionnaire: IPSAQ; Kinderman & Bentall, 1997). Results: Across patients and controls, levels of suspiciousness were associated with a standard measure of self-serving bias (SSB: proportion of positive events attributed to self minus proportion of negative events attributed to self); however, levels of SSBwere nomore extreme in the first-episode patients than the controls. First-episode patients did, however, show a greater 'self-promoting' bias to credit themselves with causing positive (but not negative) events. Whereas controls showed evidence of the commonly observed association between depression and a bias to blame one-self for negative events, levels of depression in the first-episode patientswere associated, instead, with a bias to credit one-self with causing both positive and negative events. Discussion: Findings are not indicative of a universal self-serving bias at early stages of schizophrenic illness and suggest, instead, a form of compensatory self-promoting bias which may be secondary to the onset of psychosis. The novel findings with regard to depression suggest that young people, who develop depression after the onset of psychosis, may experience a need to re-establish a sense of personal control over life events, whether positive or negative.

Additive effect of NRG1 and DISC1 genes on lateral ventricle enlargement in first episode schizophrenia

Neuregulin 1 (NRG1) and Disrupted-in-schizophrenia (DISC1) genes, which are candidate genes for schizophrenia, are implicated in brain development. We have previously reported an association between the T allele of the rs6994992 SNP within NRG1 gene and lateral ventricle (LV) enlargement in first-episode schizophrenia patients. Moreover, transgenic mice with mutant DISC1 have also been reported as showing LV enlargement. In this study, we examined the possible interactive effects of NRG1 and DISC1 on brain volumes in a sample of first-episode schizophrenia patients. Ninety-one patients experiencing their first episode of schizophrenia underwent genotyping of three SNPs within DISC1 and structural brain MRI. These results were combined with our previously reported genotypes on three SNPs within NRG1. The T/T genotype of rs2793092 SNP in DISC1 was significantly associated with increased LV volume. However, taking into account the rs6994992 SNP in the NRG1 gene, which was also associated with LV volume in a previous study, the DISC1 SNP only predicted LV enlargement among those patients carrying the T allele in the NRG1 SNP. Those patients with the “at risk” allelic combinations in both genes had LV volumes which were 48% greater than those with none of the allelic combinations. Our findings suggest that NRG1 and DISC1 genes may be associated with brain abnormalities in schizophrenia through their influence on related pathways of brain development.

Movement sequencing abilities and basal ganglia morphology in first-episode schizophrenia

Introduction. Studies of brain morphology suggest a link between movement sequencing ability and basal ganglia dysfunction. Unfortunately, relevant studies have provided inconsistent data, which may be the result of differences in the methods of brain morphology assessment, statistical analysis or heterogeneity of the populations studied. Aim. to test the hypothesis of a link between the dysfunction of movement sequencing and basal ganglia morphology in a homogenous sample of first-episode schizophrenia patients. Method. Thirty-seven first-episode schizophrenia patients underwent an assessment of movement sequencing abilities using the NES scale and basal ganglia morphology from MR images. The data were compared with a group of 19 age- and sex-matched healthy controls. Results. The group of first-episode patients had a higher concentration of gray matter than healthy controls in the putamen and pallidum in both hemispheres. Patients with abnormal sequencing of movements had lower gray matter concentration than patients without such abnormalities in the left putamen, and no differences were found between the symptomatic group and healthy controls. Summary and conclusion. Our study suggests the involvement of the left putamen in the movement sequencing abnormalities in schizophrenia. Because of the potential confounding effect of medication, the lack of support from external evidence and the low power to perform the whole-brain analysis the results should be considered as preliminary. Further studies, especially with antipsychotic-naive first-episode schizophrenia patients are needed to solve these issues.

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: An fMRI multi-center study

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal–parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Structural neural networks subserving oculomotor function in first-episode schizophrenia

Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia.