Chronic Schizophrenia Group Research Articles

Common Hematological Disorders in Patients with Schizophrenia: In-Patient Case — Control Study

INTRODUCTION: Although common hematological abnormalities (CHA) such as anemia, macrocytosis, and platelet dysfunction are often present in patients with schizophrenia, empirical data are limited. Thus far, such deviations have been mentioned either in reports or in a series of clinical cases.
 AIM: To study the incidence of CHA in patients with schizophrenia.
 MATERIALS AND METHODS: This study involved 791 patients with schizophrenia [including those who did not receive medical drugs (n = 115) and patients with chronic schizophrenia (n = 376)] and 504 healthy volunteers. From each participant, blood samples were taken and analyzed for CHA using an automatic Coulter counter. In the three groups, 2 tests and analysis of variance (ANOVA) were conducted to compare the variables.
 RESULTS: The incidence of macrocytosis was nearly the same in the schizophrenia group (patients not receiving medications, 10.5%; patients with chronic schizophrenia, 10.6%) and was significantly higher than that in the control group (4.2%). The platelet count was considerably higher in the chronic schizophrenia group ([282.5 87.9] 103/L) than in the group not receiving medical drugs ([277.0 92.8] 103/L) and control group ([249.6 85.2] 103/L), whereas the differences in the concentration of hemoglobin and leukocytes in the blood were insignificant.
 CONCLUSION: Patients with schizophrenia have a higher proportion of macrocytosis in combination with increased platelet count, which shows that the underlying diseases should be diagnosed and treated as early as possible. Moreover, prospective studies with a larger sample size are necessary to determine the etiology of these conditions in patients with schizophrenia.

Pineal morphology of the clinical high-risk state for psychosis and different psychotic disorders

BackgroundPineal volume reductions have been reported in schizophrenia and clinical high-risk states for the development of psychosis, supporting the role of melatonin dysregulation in the pathophysiology of psychosis. However, it remains unclear whether pineal volume is associated with the later onset of psychosis in individuals at clinical high-risk (CHR) of psychosis or if pineal atrophy is specific to schizophrenia among different psychotic disorders. MethodsThis magnetic resonance imaging study examined the volume of and cyst prevalence in the pineal gland in 135 individuals at CHR of psychosis [52 (38.5%) subsequently developed psychosis], 162 with first-episode psychosis (FEP), 89 with chronic schizophrenia, and 87 healthy controls. The potential contribution of the pineal morphology to clinical characteristics was also examined in the CHR and FEP groups. ResultsPineal volumes did not differ significantly between the CHR, FEP, and chronic schizophrenia groups, but were significantly smaller than that in healthy controls. However, pineal volumes were not associated with the later onset of psychosis in the CHR group or FEP sub-diagnosis (i.e., schizophrenia, schizophreniform disorder, affective psychosis, and other psychoses). No significant differences were observed in the prevalence of pineal cysts between the groups, and it also did not correlate with clinical characteristics in the CHR and FEP groups. ConclusionThese results suggest that pineal atrophy is a general vulnerability marker of psychosis, while pineal cysts do not appear to contribute to the pathophysiology of psychosis.

Relationship between White Matter Alterations and Pathophysiological Symptoms in Patients with Ultra-High Risk of Psychosis, First-Episode, and Chronic Schizophrenia.

Some symptoms of schizophrenia might be present before full-blown psychosis, so white matter changes must be studied both in individuals with emerging psychosis and chronic schizophrenia. A total of 86 patients—12 ultra-high risk of psychosis (UHR), 20 first episode psychosis (FEP), 54 chronic schizophrenia (CS), and 33 healthy controls (HC)—underwent psychiatric examination and diffusion tensor imaging (DTI) in a 3-Tesla MRI scanner. We assessed fractional anisotropy (FA) and mean diffusivity (MD) of the superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILS). We found that CS patients had lower FA than FEP patients (p = 0.025) and HC (p = 0.088), and higher MD than HC (p = 0.037) in the right SLF. In the CS group, we found positive correlations of MD in both right ILF (rho = 0.39, p < 0.05) and SLF (rho = 0.43, p < 0.01) with disorganization symptoms, as well as negative correlation of FA in the right ILF with disorganization symptoms (rho = −0.43, p < 0.05). Among UHR individuals, we found significant negative correlations between MD in the left ILF and negative (r = −0.74, p < 0.05) and general symptoms (r = −0.77, p < 0.05). However promising, these findings should be treated as preliminary, and further research must verify whether they can be treated as potential biomarkers of psychosis.

Regional Homogeneity Brain Alterations in Schizophrenia: An Activation Likelihood Estimation Meta-Analysis.

ObjectiveResting state functional magnetic resonance imaging (rsfMRI) provides a lot of evidence for local abnormal brain activity in schizophrenia, but the results are not consistent. Our aim is to find out the consistent abnormal brain regions of the patients with schizophrenia by using regional homogeneity (ReHo), and indirectly understand the degree of brain damage of the patients with drug-naive first episode schizophrenia (Dn-FES) and chronic schizophrenia. MethodsWe performed the experiment by activation likelihood estimation (ALE) software to analysis the differences between people with schizophrenia group (all schizophrenia group and chronic schizophrenia group) and healthy controls. ResultsThirteen functional imaging studies were included in quantitative meta-analysis. All schizophrenia group showed decreased ReHo in bilateral precentral gyrus (PreCG) and left middle occipital gyrus (MOG), and increased ReHo in bilateral superior frontal gyrus (SFG) and right insula. Chronic schizophrenia group showed decreased ReHo in bilateral MOG, right fusiform gyrus, left PreCG, left cerebellum, right precuneus, left medial frontal gyrus and left anterior cingulate cortex (ACC). No significant increased brain areas were found in patients with chronic schizophrenia. ConclusionOur findings suggest that patients with chronic schizophrenia have more extensive brain damage than FES, which may contribute to our understanding of the progressive pathophysiology of schizophrenia.

M46. THE STUDY OF HEART RATE VARIABILITY AND EMOTIONAL RESPONSE TO POSITIVE AND NEGATIVE AUDIOVISUAL STIMULATION IN PATIENTS WITH SCHIZOPHRENIA

BackgroundThis study was to investigate the Heart Rate Variability (HRV) and emotional response to positive and negative audiovisual stimulation in patients with chronic schizophrenia and healthy control group.MethodsAmong 253 chronic schizophrenic patients, 104 patients were informed about this research and consented. 35 healthy control consisted of peoples that did not have past and present history of mental and physical illness. Positive and negative affect and HRV were compared between chronic schizophrenia and healthy control groups, and positive and negative affect and HRV to positive and negative audiovisual stimulation were measured. Positive and negative audiovisual stimulation was defined by an art therapy professionalist and a psychiatrist as 10 positive and negative pictures. 3 positive and negative musics were shown to two groups for 4 minutes simulta¬neously. Positive and negative audiovisual stimulation were shown to two groups during 1-week intermission. HRV was measured with Ubpulse H3, an equipment for autonomic nervous system test made by Laxtha company and also analyzed by frequency domain analysis. Emotional Empathy Scale(EES) and Positive Affect and Negative Affect Schedule (PANAS) of two groups were measured at baseline and after positive and negative audiovisual stimulation. Global Assessment of Functioning Scale(GAF) and Positive and Negative Syndrome Scale(PANSS) of chronic schizophrenia group were measured by a psychiatrist.ResultsPositive affect of patients group were significantly lower than control group, negative affect of patients group were significantly higher than control group. Low Frequency (LF), High Frequency (HF), and Total Power (TP) of HRV in patients group were significantly lowered than control group at baseline. 7 subscales of emotional empathy scale were lowered in patients group compared to control group. Positive affect of patients group was significantly less increased compared to the control group after positive audiovisual stimulation, negative affect of patients group was significantly less decreased to the control group after positive audiovisual stimulation. Positive affect of patients group was increased after negative audiovisual stimulation, but positive affect of control group was significantly decreased compared to the patients group after negative audiovisual stimulation. There was no significant difference in negative affect between two groups after audiovisual stimulation. LF of patients group was significantly higher than control group after positive audiovisual stimulation, HF and TP of patients group were significantly lowered than control group after positive audiovisual stimulation. LF of patients group was significantly higher than control group after negative audiovisual stimulation, HF and PT of patients were significantly lowered than control group after negative audiovisual stimulation.DiscussionAudiovisual stimulation in integrative arts therapy program for schizophrenia might have avoid overactive sympathetic stimulation and recommend activate parasympathetic stimulation. Integrative art therapy for schizophrenia must be sufficiently relaxed, empathetic, and promote positive affect during therapeutic process.

Plasma Apelin, Visfatin and Resistin Levels in Patients with First Episode Psychosis and Chronic Schizophrenia.

ObjectiveThis study aims to investigate the possible relationship between plasma concentrations of apelin, visfatin and resistin levels of first episode psychosis patients and chronic schizophrenia patients.MethodsA total number of 29 untreated patients with first episode psychosis, 30 chronic schizophrenia and 29 randomly selected weight- and body mass index-matched healthy volunteers were included. The Diagnostic and Statistical Manual of Mental Disorders 4th edition, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale were applied to the patient groups. The enzyme-linked immunosorbent assay method was used to measure plasma apelin, visfatin and resistin levels.ResultsThere was no difference in age, marital status, occupation, and BMI between the groups. Plasma apelin levels were significantly higher in first episode psychosis group than chronic schizophrenia and control group. There was no statistically significant difference in plasma visfatin levels between the groups: first episode psychosis group, chronic schizophrenia and control group. Plasma resistin levels were higher in both first episode psychosis group and chronic schizophrenia group than the control group. There was no statistically significant correlation between plasma apelin and resistin levels and total PANSS scores in the group of patients.ConclusionTo our knowledge, this study is the first which investigates the plasma apelin, visfatin and resistin levels in patients with first episode psychosis and chronic schizophrenia. Based on the results of this study, apelin and resistin may be related with some central nervous system pathologies, including the severity of a psychiatric disorder.

Plasma monoamines change under dopamine supersensitivity psychosis in patients with schizophrenia: A comparison with first-episode psychosis.

Patients with first-episode psychosis respond well to initial antipsychotic treatment, but among patients experiencing a relapse of psychosis, the response rate falls to approximately 30%. The mechanism of this discrepancy has not been clarified, but the development of dopamine supersensitivity psychosis with the underlying up-regulation of post-synaptic dopamine D2 receptors could be involved in this lesser response. It is uncertain whether elevated dopamine synthesis and release occurs in patients with dopamine supersensitivity psychosis, in contrast to those with first-episode psychosis. We examined a first-episode psychosis group (n=6) and a chronic schizophrenia group, i.e. patients experiencing relapse (n=23) including those who relapsed due to dopamine supersensitivity psychosis (n=18). Following the initiation of treatment, we measured the patients' blood concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol at two weeks and four weeks after the baseline measurements. The first-episode psychosis group tended to show decreased homovanillic acid, accompanied by an improvement of symptoms. The chronic schizophrenia group showed no alteration of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol over the treatment period. These results were the same in the dopamine supersensitivity psychosis patients alone. Our findings suggest that unlike first-episode psychosis, the release of dopamine from presynaptic neurons did not increase in relapse episodes in the patients with dopamine supersensitivity psychosis. This indirectly indicates that the development of supersensitivity of post-synapse dopamine D2 receptor is involved in relapse in dopamine supersensitivity psychosis patients.

Striato-nigro-striatal tract dispersion abnormalities in patients with chronic schizophrenia

The white matter connections between the midbrain dopamine neurons and the striatum are part of a neural system involved in reward-based learning, a process that is impaired in patients with schizophrenia. The striato-nigro-striatal (SNS) tract, which participates in this process, has not as yet been explored. The present study aimed to use diffusion MRI (dMRI) to delineate the SNS tract, and to compare the application of two dMRI measures, Tract Dispersion (TD), an index of white matter morphology, and Fractional Anisotropy (FA), an index of white matter integrity, to detect group differences between patients with chronic schizophrenia (CSZ) and healthy controls (HC). dMRI scans were acquired in 22 male patients with CSZ and 23 age-matched HC. Two-tensor tractography was used in addition to manually-delineated regions of interest to extract the SNS tract. A mixed-model analysis of variance was used to investigate differences in TD and FA between CSZ patients and HC. The associations between TD and behavioral measures were also explored. Patients and controls differed significantly in TD (P = 0.04), but not in FA (P = 0.69). The group differences in TD were driven by a higher TD in the right hemisphere in the CSZ group. Higher TD correlated significantly with poorer performance in the Iowa Gambling Task (IGT) when combining the scores of both groups. The findings suggest that dysconnectiviy of the SNS tract which is associated with schizophrenia, could arise from abnormalities in white matter morphology. These abnormalities may potentially reflect irregularities in brain development.

O6.8. GLUTAMATERGIC DYSFUCTION AND TREATMENT RESPONSE IN MINIMALLY TREATED AND CHRONIC SCHIZOPHRENIA PATIENTS

BackgroundGlutamatergic dysfunction as a result of NMDA receptor hypofunction has been implicated in antipsychotic treatment-resistant schizophrenia, however its nature in very early stages and chronic stages of the disease is still unknown. Data on glutamate and treatment response are currently limited in two separate studies, one in first-episode patients (Egerton et al., 2012) and one in chronic patients (Mouchlianitis et al., 2016). Here we acquired proton magnetic resonance spectroscopy measures from a large sample of minimally treated first episode and chronic schizophrenia patients, and a group of matched healthy controls. Both first-episode and chronic schizophrenia groups were further stratified by treatment response. This allowed us to investigate glutamatergic dysfunction in both early and later stages of the diseases in relation to treatment-response.MethodsWe acquired proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla from bilateral anterior cingulate cortex (ACC) from 170 participants. 137 participants with a diagnosis of schizophrenia (according to ICD-10 criteria) and 33 healthy controls matched for age, sex, and socioeconomic background consented to participate in this study. The patient sample included 95 minimally treated first-episode patients, with illness duration less than 36 months, of which 65 has shown good response and 26 have shown persistent psychotic symptoms; and a group of 42 chronically-ill patients with illness duration over 3 years. The chronic group was classified into 21 antipsychotic treatment-resistant patients and 21 antipsychotic treatment-responsive patients. 1H-MRS data were analyzed using a standard basis function within LC-Model. Our primary measure was glutamate to creatine ratio (Glu/Cre) and its correlation to N-Acetylaspartic acid to creatine ratio (NAA/Cre).ResultsThe main new finding is that first-episode patients with persistent psychotic symptoms show significantly higher Glu/Cr and NAA/Cr correlation R(23)=0.76, P<0.001.compared to first-episode patients in remission R(65)=0.43, P<0.00, Fisher’s r-to-z, Z=1.97, P<0.05, effect size d=0.48. Compared to healthy controls (who did not show any Glu/Cr to and NAA/Cr correlation R(33)=0.24, P=0.33) the FEP-resistant group showed a significant difference, Z=2.6, P<0.005, representing a large effect size of d=0.87 but not the FEP-responsive group, Z=0.97, P=0.17. Remarkably, when we examined first-episode patients with antipsychotic exposure of less than 6 months, we found an extremely high correlation in the non-responsive group R(5)=0.95, P=0.01, compared to the responsive-group,R(20)=0.44, P<0.05, which reflected a large effect size of d=0.99. Chronically-ill resistant patients showed a significant correlation R(21)=0.48, P<0.05 and responsive trend-level correlation R(21)=0.41, P=0.07, but neither group differed from healthy controls.DiscussionOur study provides the first 1H-MRS evidence for acute metabolic perturbations in glutamatergic neurotransmission in minimally treated schizophrenia patients with persistent psychotic symptoms. These are absent in later stages of the disease for both treatment-resistant and treatment-responsive patients. It is likely that neurodegenerative processes resulting from excitotoxity due glutamatergic dysfuntion are most impactful within the first few months from illness onset. Our data point to the urgent need to identify reliable biomarkers for the prediction of antipsychotic treatment-response and the development of novel interventions to address glutamatergic perturbations at the beginning of their illness.

F223. COMPARATIVE STUDY OF HEART RATE VARIABILITY AND EMOTIONAL RESPONSE TO POSITIVE AND NEGATIVE AUDIOVISUAL STIMULATION IN PATIENTS WITH CHRONIC SCHIZOPHRENIA AND HEALTHY CONTROL

BackgroundThis study was to investigate the Heart Rate Variability(HRV) and emotional response to positive and negative audiovisual stimulation in patients with chronic schizophrenia and healthy control groupMethodsAmong 253 chronic schizophrenic patients admitted in 00 Hospital in 00 city by psychiatrist, 104 patients were informed about this research and consented. Those who met this study criteria were randomly selected. 35 healthy control consisted of peoples that did not have past and present history of mental and physical illness. Positive and negative affect and HRV were compared between chronic schizophrenia and healthy control groups, and positive and negative affect and HRV to positive and negative audiovisual stimulation were measured according to planed research process. Positive and negative audiovisual stimulation was defined by an art therapy professionalist and a psychiatrist as 10 positive and negative pictures. 3 positive and negative musics were shown to two groups for 4 minutes simultaneously. Positive and negative audiovisual stimulation were shown to two groups during 1-week intermission. HRV was measured with Ubpulse H3, an equipment for autonomic nervous system test made by Laxtha company and also analyzed by frequency domain analysis. Emotional Empathy Scale(EES) and Positive Affect and Negative Affect Schedule (PANAS) of two groups were measured at baseline and after positive and negative audiovisual stimulation. Global Assessment of Functioning Scale(GAF) and Positive and Negative Syndrome Scale(PANSS) of chronic schizophrenia group were measured by a psychiatrist.Results1) Positive affect of patients group were significantly lower than control group, negative affect of patients group were significantly higher than control group. Low Frequency(LF), High Frequency(HF), and Total Power(TP) of HRV in patients group were significantly lowered than control group at baseline.2) 7 subscales of emotional empathy scale were lowered in patients group compared to control group.3) Positive affect of patients group was significantly less increased compared to the control group after positive audiovisual stimulation, negative affect of patients group was significantly less decreased to the control group after positive audiovisual stimulation.4) Positive affect of patients group was increased after negative audiovisual stimulation, but positive affect of control group was significantly decreased compared to the patients group after negative audiovisual stimulation. There was no significant difference in negative affect between two groups after audiovisual stimulation.5) LF of patients group was significantly higher than control group after positive audiovisual stimulation, HF and TP of patients group were significantly lowered than control group after positive audiovisual stimulation.6) LF of patients group was significantly higher than control group after negative audiovisual stimulation, HF and PT of patients were significantly lowered than control group after negative audiovisaul stimulation.DiscussionPatients with schizophrenia showed lower positive affect, higher negative affect, and lowered HRV parameters compared to the control group. They also showed lower empathy ability and inappropriate and non-contexual response. Schizophrenic patients represented hypersensitive sympathetic nervous system activity and lowered parasympathetic nervous system activity to the audiovisual stimulation. These results suggested that schizophrenic patients would show higher negative affect, less adaptive autonomic nervous system and hypersensitive or sharp to audiovisual stimulation, and decreased relaxation ability after stimulation. Audiovisual stimulation in integrative arts therapy program for schizophrenia might have avoid overactive sympathetic stimulation and recommend activate parasympathetic stimulation. Integrative art therapy for schizophrenia must be sufficiently relaxed, empathetic, and promote positive affect during therapeutic process.

Correlation of DRD2 mRNA expression levels with deficit syndrome severity in chronic schizophrenia patients receiving clozapine treatment.

Schizophrenia is a complex, severe, chronic psychiatric disorder, and the associated deficit syndrome is widely regarded as an important clinical aspect of schizophrenia. This study analyzed the relationship of deficit syndrome severity with the mRNA levels of members of signaling pathways that associate with the pathophysiology of schizophrenia, including the dopamine D2 receptor (DRD2), protein kinase B (AKT1), and phosphoinositide-3 kinase (PI3KCB), in peripheral blood leukocytes (PBLs) of 20 healthy controls and 19 chronic schizophrenia patients with long-term clozapine treatment. The DRD2 expression levels in chronic schizophrenia group were statistically higher than those in controls (t=2.168, p=0.037). Moreover, in chronic schizophrenia group, correlations were observed between the expression levels of DRD2 and PI3KCB (r=0.771, p<0.001), DRD2 and AKT1 (r=0.592, p=0.008), and PI3KCB and AKT1 (r=0.562, p=0.012) and between the DRD2 mRNA levels and the Proxy for the Deficit Syndrome score (r=0.511, p=0.025). In control group, the correlation between PI3KCB expression levels and DRD2 expression levels was only observed (r=0.782, p<0.001). In conclusion, a correlation was observed between increased deficit syndrome severity and elevated expression levels of DRD2 in PBLs of chronic schizophrenia patients receiving long-term clozapine treatment.

Characterizing white matter changes in chronic schizophrenia: A free-water imaging multi-site study

Diffusion tensor imaging (DTI) studies in chronic schizophrenia have found widespread but often inconsistent patterns of white matter abnormalities. These studies have typically used the conventional measure of fractional anisotropy, which can be contaminated by extracellular free-water. A recent free-water imaging study reported reduced free-water corrected fractional anisotropy (FAT) in chronic schizophrenia across several brain regions, but limited changes in the extracellular volume. The present study set out to validate these findings in a substantially larger sample. Tract-based spatial statistics (TBSS) was performed in 188 healthy controls and 281 chronic schizophrenia patients. Forty-two regions of interest (ROIs), as well as average whole-brain FAT and FW were extracted from free-water corrected diffusion tensor maps. Compared to healthy controls, reduced FAT was found in the chronic schizophrenia group in the anterior limb of the internal capsule bilaterally, the posterior thalamic radiation bilaterally, as well as the genu and body of the corpus callosum. While a significant main effect of group was observed for FW, none of the follow-up contrasts survived correction for multiple comparisons. The observed FAT reductions in the absence of extracellular FW changes, in a large, multi-site sample of chronic schizophrenia patients, validate the pattern of findings reported by a previous, smaller free-water imaging study of a similar sample. The limited number of regions in which FAT was reduced in the schizophrenia group suggests that actual white matter tissue degeneration in chronic schizophrenia, independent of extracellular FW, might be more localized than suggested previously.

Serum levels of brain-derived neurotrophic factor (BDNF), proBDNF and plasma 3-methoxy-4-hydroxyphenylglycol levels in chronic schizophrenia.

BackgroundWe investigated the serum levels of brain-derived neurotrophic factor (BDNF), proBDNF and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with chronic schizophrenia.MethodsSixty-eight patients who met the DSM-IV-TR criteria and had a chronic schizophrenia (CS) duration of ≥ 5 years were enrolled. Their serum brain-derived BDNF and proBDNF levels were measured by enzyme-linked immunosorbent assays, and their plasma MHPG levels were analyzed by high-performance liquid chromatography with electrochemical detection.ResultsThe plasma MHPG levels were significantly lower in the CS group (3.9 ± 1.8 ng/ml) compared to those in the group of 32 age- and sex-matched healthy controls (5.1 ± 2.4 ng/ml). The serum BDNF levels were significantly lower in the CS group (8.9 ± 4.8 ng/ml) compared to the control group (12.2.1 ± 6.8 ng/ml). No correlation was observed between plasma MHPG and BDNF in the CS group.ConclusionThese results suggest that hypo-activity of noradrenergic neurons and decreased BDNF secretion exist in chronic schizophrenic patients.

Inflammatory Markers in Recent Onset Psychosis and Chronic Schizophrenia.

Immune markers have been associated with schizophrenia, but few studies have examined multiple markers in both recent onset and chronic schizophrenia patients. The sample of 588 individuals included 79 with recent onset psychosis, 249 with chronic schizophrenia, and 260 controls. A combined inflammation score was calculated by principal components factor analysis of the levels of C-reactive protein, Pentraxin 3, and IgG antibodies to gliadin, casein, and Saccharomyces cerevisiae measured in blood samples. Inflammation scores among groups were compared by multivariate analyses. The chronic schizophrenia group showed significant elevations in the combined inflammation score compared with controls. The recent onset group surprisingly showed a reduction in the combined inflammation score. Consistent with these findings, the chronic schizophrenia group had significantly increased odds of a combined inflammation score greater than the 75th and the 90th percentile of that of the controls. The recent onset group had significantly increased odds of a combined inflammation score less than the 10th and the 25th percentile level of the controls. The recent onset of psychosis may be associated with inherent deficits in innate immunity. Individuals later in the course of disease may have increased levels of innate immunity. The reasons for these changes are not known with certainty but may be related to compensatory increases as the disease progresses. Longitudinal studies are needed to determine the course of immune abnormalities in schizophrenia and their role in the clinical manifestations of the disorder.

Verbal fluency in chronic schizophrenia and severity of psychotic symptoms: consideration of their relationship with errors in the tasks

There are many associations between psychotic symptoms and performance in Verbal Fluency (VF) tasks. However, most of these are found are with negative symptoms. In this study we examined the relationship between the performance in four VF tasks and the severity of both positive and negative symptoms. Methods: To compare performance in different VF tasks, two groups of participants were matched for age, sex and educational level, a Healthy Control Group (N = 83) and a Chronic Schizophrenia Group (N = 83). We examined the correlation between cognitive performance in these verbal tests and the severity of psychotic symptoms in the group of patients. Results: The results show that the performance of patients with chronic schizophrenia in VF tests is significantly lower than for healthy individuals. The analysis of correlations between tasks showed a significant correlation between the severity of negative symptoms and poor performance in VF tasks. Another interesting result was the association between the severity of formal thought disorder and poor performance in semantic VF. A particularly striking result was the correlation between the severity of positive symptoms and the number of errors in VF tasks in the patient group. Conclusions: These results have provided evidence for some of the proposed hypotheses and are in accordance with previous investigations. The correlations between the positive symptoms and the number of errors in the different VF tasks have not been previously reported. It is important to note that most of these correlations are between the severity of positive symptoms and intrusion errors.

Different hemodynamic response patterns in the prefrontal cortical sub-regions according to the clinical stages of psychosis

BackgroundSymptomatic and functional outcomes in schizophrenia are associated with the duration of untreated psychosis. However, no candidate biomarkers have been adopted in clinical settings. Multichannel near-infrared spectroscopy (NIRS), which can easily and noninvasively measure hemodynamics over the prefrontal cortex, is a candidate instrument for clinical use. AimsWe intended to explore prefrontal dysfunction among individuals at different clinical stages, including ultra-high-risk (UHR), first-episode psychosis (FEP), and chronic schizophrenia (ChSZ), compared to healthy subjects. MethodTwenty-two UHR subjects, 27 patients with FEP, 38 patients with ChSZ, and 30 healthy subjects participated. We measured hemodynamic changes during a block-designed letter fluency task using multichannel NIRS instruments. ResultsWe found that the activations of the bilateral ventrolateral prefrontal cortex, and the fronto-polar and anterior parts of the temporal cortical regions in the UHR group were lower than those of the controls, but similar to those of the FEP and ChSZ groups. However, the activations in the bilateral dorsolateral prefrontal cortex regions decrease with advancing clinical stage. ConclusionsTo the best of our knowledge, this is the first study directly comparing differences in hemodynamic changes with respect to the 3 clinical stages of psychosis. Furthermore, this study also demonstrates different patterns of impairment according to the progression of clinical stages using NIRS instruments. NIRS measurements for UHR and FEP individuals may be candidate biomarkers for the early detection of the clinical stages of psychosis.

P.1.036 Neurophysiological markers of cognitive disorders and 1H-magnetic resonance spectroscopy in dorsolateral prefrontal cortex of first-episode patients

Objectives: Event-related potential (ERP) abnormalities to target stimuli are reliably found in schizophrenia. However, as people with schizophrenia are thought to have difficulty discerning the relevance of incoming sensory stimuli it is also important to examine ERPs to non-targets. To differentiate between potential trait markers of the disease and deficits that might be associated with the consequence of illness chronicity, this study investigated ERPs to both target and non-target stimuli in groups of people with either first episode or chronic schizophrenia (CSz).Methods: Using an auditory oddball paradigm, ERPs to target, non-target before target (Nt before) and non-target after target (Nt after) stimuli were analysed for 40 patients with CSz, 40 patients with first episode schizophrenia (FESz) and two groups of normal controls matched for age and sex with their patient counterparts.Results: The FESz group showed the same pattern of amplitude disturbance as the CSz group to both targets (reduced N100, N200, P300 and increased P200) and non-targets (reduced N100) compared to controls. Both CSz and FESz groups also failed to show the changes to the P200–N200 component between targets and non-target stimuli that was exhibited by controls (smaller earlier P200 to targets vs. increased delayed P200 to non-targets) or the reduction in N100 amplitude of ERPs to the Nt after stimuli compared with ERPs to the Nt before stimuli. Previous literature has focussed on the sensitivity of P300 deficits in classifying persons into schizophrenia and non-schizophrenia groups. This study demonstrated improved accuracy in the classification of patients with schizophrenia from controls using discriminant analysis of target and non-target N100 and P200 components.Conclusions: The results suggest that ERP disturbances are evident at the time of first referral to mental health services and may be a potential trait (rather than secondary effect) of the illness. It is important to include both target and non-target stimuli processing, and their interrelationship in future research.

Stabilization of the Internal Structure of Persistent Auditory Verbal Hallucinations in Schizophrenia

Numerous studies have been conducted to investigate the phenomenological characteristics of auditory verbal hallucinations in schizophrenia. Difficulties in understanding the clinical significance of auditory verbal hallucinations may be attributed to the changes in symptom structure over the long-term course of the illness. The purpose of the present study was therefore to investigate the longitudinal changes in the phenomenological dimensions of auditory verbal hallucinations in patients with schizophrenia. Using the Psychotic Symptom Rating Scales-Auditory Hallucination Subscale, 40 patients meeting DSM-IV criteria for schizophrenia (drug-naive first-episode schizophrenia, n=21; and drug-free chronic schizophrenia, n=19) who reported persistent auditory verbal hallucinations were assessed before the initiation of antipsychotic treatment and after 6 months of treatment. To detect the changes in underlying clusters of phenomenological variables, hierarchical clustering and multidimensional analysis were performed. The phenomenological variables of auditory verbal hallucinations formed two main clusters with 6 month treatment: emotional and cognitive. Physical characteristics failed to indicate a stable cluster. Psychosocial disruption, which initially formed a cluster with cognitive variables, congregated with emotional variables at 6 months. Subgroup analysis indicated that the cluster structure of the first-episode group showed more dynamic changes than did that of the chronic schizophrenia group. Phenomenological variables characterizing persistent auditory verbal hallucinations can be differentiated into emotional and cognitive clusters with achievement of symptom stabilization, and the changes in physical characteristics may not be the sole sign of clinical improvement.

Morphology of the corpus callosum at different stages of schizophrenia: Cross-sectional study in first-episode and chronic illness

The shape of the corpus callosum may differ in schizophrenia, although no study has compared first-episode with established illness. To investigate the size and shape of the corpus callosum in a large sample of people with first-episode and established schizophrenia. Callosal size and shape were determined using high-resolution magnetic resonance imaging on 76 patients with first-episode schizophrenia-spectrum disorders, 86 patients with established schizophrenia and 55 healthy participants. There were no significant differences in total area across groups. Reductions in callosal width were seen in the region of the anterior genu in first-episode disorder (P<0.005). Similar reductions were seen in the chronic schizophrenia group in the anterior genu, but also in the posterior genu and isthmus (P=0.0005). Reductions in anterior callosal regions connecting frontal cortex are present at the onset of schizophrenia, and in established illness are accompanied by changes in other regions of the callosum connecting cingulate, temporal and parietal cortices.

Visual form perception: A comparison of individuals at high risk for psychosis, recent onset schizophrenia and chronic schizophrenia

Schizophrenia has been associated with deficits in visual perception and processing, but there is little information about their temporal development and stability. We assessed visual form perception using the Rorschach Comprehensive System (RCS) in 23 individuals at clinical high risk for psychosis, 15 individuals with recent onset schizophrenia (≤ 2 years since onset), and 34 with chronic schizophrenia (≥ 3 years since onset). All three groups demonstrated reduced conventional form perception (X+%), as compared with published norms, but did not differ significantly from one another. In contrast, the high-risk group had significantly better performance on an index of clarity of conceptual thinking (WSUM6) compared to the chronic schizophrenia patients, with the recent onset group scoring intermediate to the high-risk and chronic schizophrenia groups. The results suggest that individuals at clinical high risk for psychosis display substantial deficits in visual form perception prior to the onset of psychosis and that these deficits are comparable in severity to those observed in individuals with schizophrenia. Therefore, visual form perception deficits may constitute a trait-like risk factor for psychosis in high-risk individuals and may potentially serve as an endophenotype of risk for development of psychosis. Clarity of conceptual thinking was relatively preserved among high-risk patients, consistent with a relationship to disease expression, not risk. These deficits are discussed in the context of the putative neurobiological underpinnings of visual deficits and the developmental pathophysiology of psychosis in schizophrenia.