First-episode Schizophrenia Group Research Articles

Aberrant cerebro-cerebellar functional connectivity and minimal self-disturbance in individuals at ultra-high risk for psychosis and with first-episode schizophrenia

BackgroundIn the tradition of phenomenology, minimal selfdisturbance has been suggested as a manifestation of the core pathogenesis of schizophrenia; however, the underlying neural mechanism remains unclear. Here, in line with the concept of “cognitive dysmetria,” we investigated the cerebro-cerebellar default mode network (DMN) connectivity and its association with pre-reflective minimal selfdisturbance in individuals at ultra-high risk (UHR) for psychosis and patients with first-episode schizophrenia (FES). MethodsThirty-three UHR individuals, 18 FES patients, and 56 healthy controls (HCs) underwent functional magnetic resonance imaging during rest at baseline. Seed-based functional connectivity (FC) analysis was performed using the cerebellar DMN seeds from the bilateral Crus I, followed by between-group comparisons. Correlation analysis was conducted to examine the relationship between the cerebro-cerebellar FC and the self-reported severity of minimal self-disturbance in the UHR and FES groups, respectively. ResultsFES participants showed significantly reduced cerebellar FC with the left presupplementary motor area (preSMA), right anterior prefrontal cortex (aPFC), and precuneus compared to HCs, while UHR participants showed an intermediate decrease between the other two groups, particularly in the left preSMA and right aPFC. Minimal self-disturbance, which appeared at similar levels in both UHR and FES groups, was significantly associated with cerebro-cerebellar FC, although each group presented different patterns of associations. ConclusionsAberrant cerebro-cerebellar FC, which may be closely related to minimal self-disturbance, may be able to provide meaningful insights into the real gestalt of schizophrenia and contribute to further research to predict future psychosis in UHR individuals.

Abnormalities of regional homogeneity and its correlation with clinical symptoms in Naïve patients with first-episode schizophrenia.

Several resting-state neuroimaging studies have indicated abnormal regional homogeneity (ReHo) in chronic schizophrenia; however, little work has been conducted to investigate naïve patients with first-episode schizophrenia (FES). Even less investigated is the association between ReHo measures and clinical symptom severity in naïve patients with FES. The current study evaluated ReHo alterations in whole brain, and assessed the correlations between ReHo measures and clinical variables in naïve patients with FES. Forty-four naïve patients with FES and 26 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Group-level analysis was utilized to analyze the ReHo differences between FES and HC in a voxel-by-voxel manner. Severity of symptoms was evaluated using a five-factor model of the Positive and Negative Syndrome Scale (PANSS). The correlation between the severity of symptoms and ReHo map was examined in patients using voxel-wise correlation analyses within brain areas that showed a significant ReHo alteration in patients compared with controls. Compared with the healthy control group, the FES group showed a significant decrease in ReHo values in the left medial frontal gyrus (MFG), right precentral gyrus, left superior temporal gyrus (STG), left left middle temporal gyrus (MTG), left thalamus, and significant increase in ReHo values in the left MFG, left inferior parietal lobule (IPL), left precuneus, and right lentiform nucleus (LN). In addition, the correlation analysis showed the PANSS total score negatively correlated with ReHo in the right precentral gyrus and positively correlated with ReHo in the left thalamus, the positive factor positively correlated with ReHo in the right thalamus, the disorganized/concrete factor positively correlated with ReHo in left posterior cingulate gyrus (PCG), the excited factor positively correlated with ReHo in the left precuneus, and the depressed factor negatively correlated with ReHo in the right postcentral gyrus and positively correlated with ReHo in the right thalamus. Our results indicate that widespread ReHo abnormalities occurred in an early stage of schizophrenic onset, suggesting a potential neural basis for the pathogenesis and symptomatology of schizophrenia.

Abnormal auditory-evoked gamma band oscillations in first-episode schizophrenia during both eye open and eye close states

Abnormal auditory steady state response (ASSR) is a typical finding among schizophrenia patients, which is thought to directly reflect deficient gamma band oscillations in the brain. However, whether these ASSR alterations are state dependent, e.g. during eye-open or eye-closed conditions, has not yet been carefully elucidated in schizophrenia. Our study aimed to explore whether the abnormality of ASSR in patients with first-episode schizophrenia (FEP) is altered under eye-open (EO) and eye-closed (EC) states. ASSR was elicited using 40 Hz click trains under EO and EC states. Twenty-eight healthy control subjects (HC) and thirty-three FEP individuals, 17 of whom were medication-naïve, were recruited. The event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 40 Hz click sounds were quantified. Compared to HC group, FEP group showed a lower ITC and ERSP during EO state, as well as a decreased ITC during EC state. Our results suggest that abnormalities in gamma band oscillations among first-episode schizophrenia patients are present under both eye open and eye close states. Although differences in gamma band oscillations between EO and EC states within the FEP group were not observed, exploratory results suggest that state-sensitivity may be contingent on medication use.

Abnormalities in thalamo-cortical connections in patients with first-episode schizophrenia: a two-tensor tractography study.

The "cognitive dysmetria" hypothesis suggests that impairments in cognition and behavior in patients with schizophrenia can be explained by disruptions in the cortico-cerebellar-thalamic-cortical circuit. In this study we examine thalamo-cortical connections in patients with first-episode schizophrenia (FESZ). White matter pathways are investigated that connect the thalamus with three frontal cortex regions including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), and lateral oribitofrontal cortex (LOFC). We use a novel method of two-tensor tractography in 26 patients with FESZ compared to 31 healthy controls (HC), who did not differ on age, sex, or education. Dependent measures were fractional anisotropy (FA), Axial Diffusivity (AD), and Radial Diffusivity (RD). Subjects were also assessed using clinical functioning measures including the Global Assessment of Functioning (GAF) Scale, the Global Social Functioning Scale (GF: Social), and the Global Role Functioning Scale (GF: Role). FESZ patients showed decreased FA in the right thalamus-right ACC and right-thalamus-right LOFC pathways compared to healthy controls (HCs). In the right thalamus-right VLPFC tract, we found decreased FA and increased RD in the FESZ group compared to HCs. After correcting for multiple comparisons, reductions in FA in the right thalamus- right ACC and the right thalamus- right VLPC tracts remained significant. Moreover, reductions in FA were significantly associated with lower global functioning scores as well as lower social and role functioning scores. We report the first diffusion tensor imaging study of white matter pathways connecting the thalamus to three frontal regions. Findings of white matter alterations and clinical associations in the thalamic-cortical component of the cortico-cerebellar-thalamic-cortical circuit in patients with FESZ support the cognitive dysmetria hypothesis and further suggest the possible involvement of myelin sheath pathology and axonal membrane disruption in the pathogenesis of the disorder.

Structural and functional brain abnormalities in schizophrenia: A cross-sectional study at different stages of the disease

Structural and functional deficits associated with schizophrenia are observed prior to the onset of psychosis and differ according to the stage of illness. However, most previous studies concentrated on a limited period during the illness, and it remains uncertain how these abnormalities develop throughout the entire disease course. In the current study, we investigated the gray matter (GM) and regional neural activity alterations in subjects at 4 different stages of schizophrenia. The subjects comprised 53 genetic high risk (HR) individuals, 26 ultra-high risk (UHR) individuals, 58 patients with first-episode schizophrenia (FES), 41 patients with chronic schizophrenia (ChSz) and 39 healthy controls (HC), all of whom underwent structural and resting-state functional MRI scanning. Gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) values were compared voxelwise among the five groups using voxel-based morphometry (VBM) and the software REST. Correlations among structural, functional abnormalities and PANSS scores in the FES group were evaluated by partial correlation analysis and multiple stepwise regression. Pronounced GMV decline was observed in the bilateral occipital lobe, left orbital frontal cortex, bilateral superior parietal lobule (SPL), right middle temporal gyrus (MTG), gyrus rectus and medial superior frontal gyrus (SFG) in the FES group and in the bilateral occipital lobe in the HR group. The FES patients also showed increased ALFF in the caudate and decreased ReHo in the bilateral inferior parietal lobule (IPL) and precuneus. The ChSz patients displayed increased ALFF in the right hippocampus. The GMV of the right MTG and SPL and the ReHo of the precuneus were negatively correlated with the general psychopathology scale, while the GMV of the right MTG was negatively correlated with the total score on the Positive and Negative Syndrome Scale (PANSS). The GMV of the right occipital cortex and SPL were associated with the ALFF of the caudate, the GMV of the right SPL was associated with the ReHo of the bilateral IPL and precuneus. GM deficits and regional dysfunction are evident prior to the onset of psychotic symptoms and are more prominent during the onset of illness than during any other phase. The right MTG and SPL, the striatum and the DMN may play important roles in the pathological changes underlying schizophrenia.

Details of attention and learning change in first-episode schizophrenia

Impaired attention and learning functions are common in schizophrenia. The details of this impairment, and how these change across time, are not well known. We aimed to compare the parameters of well-known attention and learning neuropsychological tests in first-episode schizophrenia (FES) patients and healthy controls in a 2-year follow-up period. The performance of 28-25 FES patients and pairwise matched healthy controls on the Continuous Performance Test-Identical Pairs, the revised Hopkins Verbal Learning Test, and the revised Brief Visuospatial Memory Test was compared at baseline and 2 years later. The attention dysfunction of the FES group was driven by slow reaction time and a comparative failure to identify correct hits. The reaction time was reduced somewhat across time in the patient group. Regarding the learning tasks, both groups increased their number of correct answers across trials. However, at each trial, the patient group exhibited lower scores, with a trend towards better visual learning performance across time. In summary, the FES patients were impaired in most of the parameters of the attention and learning tasks. Across time, modest improvements in reaction time and visual learning were displayed in the FES group. However, this group never caught up with the control group.

Functional dysconnectivity of the limbic loop of frontostriatal circuits in first-episode, treatment-naive schizophrenia.

Frontostriatal circuits dysfunction has been implicated in the etiology and psychopathology of patients with schizophrenia (SZ). However, few studies have investigated SZ-related functional connectivity (FC) alterations in discrete frontostriatal circuits and their relationship with pathopsychology in first-episode schizophrenia (FESZ). The goal of this study was to identify dysfunctions in discrete frontostriatal circuits that are associated with key features of FESZ. To this end, a case-control, cross-sectional study was conducted, wherein resting-state (RS) functional magnetic resonance (fMRI) data were collected from 37 treatment-naïve FESZ patients and 29 healthy control (HC) subjects. Seed-based FC analyses were performed by placing six bilateral pairs of seeds within a priori defined subdivisions of the striatum. We observed significantly decreased FC for the FESZ group relative to the HC group [p < .05, family-wise error (FWE)-corrected] in the limbic loop, but not in the sensorimotor or associative loops, of frontostriatal circuitry. Moreover, bilaterally decreased inferior ventral striatum/nucleus accumbens (VSi)-dorsal anterior cingulate cortex (dACC) FC within the limbic loop correlated inversely with overall FESZ symptom severity and the disorganization factor score of PANSS. These findings provide new insight into the role of frontostriatal limbic loop hypoconnectivity in early-stage schizophrenia pathology and suggest potential novel therapeutic targets.

Prefrontal dysconnectivity links to working memory deficit in first-episode schizophrenia.

Working memory (WM) deficit is a core feature of schizophrenia and is characterized by abnormal functional integration in the prefrontal cortex, including the dorsolateral prefrontal cortex (dLPFC), dorsal anterior cingulate cortex (dACC), and ventrolateral prefrontal cortex (vLPFC). However, the specific mechanism by which the abnormal neuronal circuits that involve these brain regions contribute to this deficit is still unclear. Therefore, this study focused on these regions and sought to answer which abnormal causal relationships in these regions can be linked to impaired WM in schizophrenia. We used spectral dynamic causal modeling to estimate directed (effective) connectivity between these regions based on resting-state functional magnetic resonance imaging data from healthy control (HC) subjects and patients with first-episode schizophrenia (FES). By comparing these effective connections in the controls and patients, we found that the effective connectivity from the dACC to the dLPFC and from the right dLPFC to the left vLPFC was weaker in the FES group than in the HC group. Furthermore, these effective connections displayed a positive correlation with WM performance in the HCs. However, in the FES patients, the effective connectivity from the dACC to the dLPFC was not correlated with WM performance, and the effective connectivity from the right dLPFC to the left vLPFC was negatively correlated with WM performance. These results could be explained by an aberrant top-down mechanism of WM processing and provide new evidence for the dysconnectivity hypothesis of schizophrenia.

Longitudinal changes in prospective memory and their clinical correlates at 1-year follow-up in first-episode schizophrenia.

This study aimed to investigate prospective memory (PM) and the association with clinical factors at 1-year follow-up in first-episode schizophrenia (FES). Thirty-two FES patients recruited from a university-affiliated psychiatric hospital in Beijing and 17 healthy community controls (HCs) were included. Time- and event-based PM (TBPM and EBPM) performances were measured with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) at baseline and at one-year follow-up. A number of other neurocognitive tests were also administered. Remission was determined at the endpoint according to the PANSS score ≤ 3 for selected items. Repeated measures analysis of variance revealed a significant interaction between time (baseline vs. endpoint) and group (FES vs. HCs) for EBPM (F(1, 44) = 8.8, p = 0.005) and for all neurocognitive components. Paired samples t-tests showed significant improvement in EBPM in FES (13.1±3.7 vs. 10.3±4.8; t = 3.065, p = 0.004), compared to HCs (15.7±3.6 vs. 16.5±2.3; t = -1.248, p = 0.230). A remission rate of 59.4% was found in the FES group. Analysis of covariance revealed that remitters performed significantly better on EBPM (14.9±2.6 vs. 10.4±3.6; F(1, 25) = 12.2, p = 0.002) than non-remitters at study endpoint. The association between EBPM and 12-month clinical improvement in FES suggests that EBPM may be a potential neurocognitive marker for the effectiveness of standard pharmacotherapy. Furthermore, the findings also imply that PM may not be strictly a trait-related endophenotype as indicated in previous studies.

Altered effective brain connectivity at early response of antipsychotics in first-episode schizophrenia with auditory hallucinations.

This study aimed to examine the alterations of cortical connectivity in first-episode schizophrenia (FES) with auditory hallucinations at early response of antipsychotics. This was a nonexperimental control of medication study. We measured the cortical activity of 20 medicated patients with FES (medicated group), 19 nonmedicated patients with FES (nonmedicated group), and 22 healthy controls using electroencephalogram during eye-open resting state. Source reconstruction analysis was performed to determine the brain regions that showed significant group difference. A dynamic causal modelling (DCM) analysis was used to estimate the effective connectivity between sources. Both FES groups expressed increased activity in the right middle frontal gyrus (RMFG) and left/right superior temporal gyrus (L/RSTG) relative to that in the controls (p<0.05), and the nonmedicated group presented even higher activity than the medicated group (p<0.05). The effective connectivity from RMFG to LSTG was weaker in the nonmedicated group relative to that in the medicated group (p<0.01), although patients in the medicated group showed no difference with healthy controls in RMFG to L/RSTG connections. The Bayesian model selection analysis found modulatory lateralization in the nonmedicated group. The patients with FES showed frontotemporal hyperactivity and disconnectivity. The effective connections accompanied with modulation were improved when hallucination diminished at early response of routine medication. This study provided the first evidence of early drug response-related alterations in effective brain connectivity.

White Matter Integrity in Genetic High-Risk Individuals and First-Episode Schizophrenia Patients: Similarities and Disassociations.

White matter (WM) neuroimaging studies have shown varied findings at different stages of schizophrenia (SZ). Understanding these variations may elucidate distinct markers of genetic vulnerability and conversion to psychosis. To examine the similarities and differences in WM connectivity between those at-risk for and in early stages of SZ, a cross-sectional diffusion tensor imaging study of 48 individuals diagnosed with first-episode SZ (FE-SZ), 37 nonpsychotic individuals at a high genetic risk of SZ (GHR-SZ), and 67 healthy controls (HC) was conducted. Decreased fractional anisotropy (FA) in the corpus callosum (CC), anterior cingulum (AC), and uncinate fasciculus (UF) was observed in both the GHR-SZ and FE-SZ groups, while decreased FAs in the superior longitudinal fasciculus (SLF) and the fornix were only seen in the FE-SZ participants. Additionally, both GHR-SZ and FE-SZ showed worse executive performance than HC. The left SLF III FA was significantly positively correlated with hallucinations, and right SLF II was positively correlated with thought disorder. The presence of shared WM deficits in both FE-SZ and GHR-SZ individuals may reflect the genetic liability to SZ, while the disparate FA changes in the FE-SZ group may represent symptom-generating circuitry that mediates perceptual and cognitive disturbances of SZ and ultimately culminates in the onset of psychotic episodes.

Decreased white matter FA values in the left inferior frontal gyrus is a possible intermediate phenotype of schizophrenia: evidences from a novel group strategy.

Intermediate phenotype could be used to investigate genetic susceptibility. However, genetic and environmental heterogeneity may interfere with identification of intermediate phenotypes. In this study, we minimized these interferences by using a novel group strategy. A total of 22 drug-naive and first-episode schizophrenia (FES) patients, along with 22 of their kin healthy siblings (HS), 22 non-kin healthy siblings (nHS) of other schizophrenia patients and 22 healthy controls (HC), were recruited. Brain imaging was acquired from the participants. Voxel-based analysis was used to investigate differences in white matter integrity derived from diffusion tensor imaging among the four groups. Two cognitive tests related to our findings were selected to confirm the related phenotypic changes. All of the FES, HS, and nHS groups showed decreased fractional anisotropy (FA) values in the left inferior frontal gyrus (IFG) compared with the HC group (p<0.05, FDR corrected). The scores of Hopkins Verbal learning Test-Revised and Animal Naming in FES patients were significantly lower than in participants belonging to the other three groups (p<0.05). Significant correlation between Animal Naming scores and FA values in the left IFG was found in FES patients (r=0.53, p=0.01). Moreover, FES patients also showed decreased FA values in the left medial frontal gyrus, left inferior temporal gyrus, left parahippocampal gyrus, left posterior cingulate, and right middle temporal gyrus compared with HC (p<0.05, FDR corrected). Decreased FA values in the left IFG is a possible intermediate phenotype of schizophrenia, and this finding supports the hypothesis that disrupted connectivity of white matter may be the key substrate of schizophrenia.

New evidence in support of staging approaches in schizophrenia: Differences in clinical profiles between first episode, early stage, and late stage

Few studies have examined the progression of symptom dimensions in schizophrenia patients over the course of the illness. The objective of this study was to investigate whether clinical and psychopathological differences exist between first-episode schizophrenia (FES) and multiple-episode patients in an inpatient setting. Patients (N=203) were evaluated using the Positive and Negative Syndrome Scale (PANSS) over time. Five different generalized estimating equations were built for the PANSS factors using the following as covariates: sex, patient's age, assessment time point (i.e., moment of patient's evaluation, with a minimum of two and a maximum of four assessments throughout the study timeframe). The FES group was used as the reference to which the groups with up to five years of illness and more than five years of illness were compared. Remission rates and treatment resistance (TRS) rates were also compared. Generalized estimating equations were used to allow for different numbers of assessments over the study period. Patients with FES showed significantly milder severity in positive, disorganized, and hostility factors. Also, FES patients were more likely to achieve remission (P=0.002) and had lower rates of TRS (P=0.001). First-episode schizophrenia seems to be the critical period to improve outcome, as multiple-episode patients were similar in clinical characteristics regardless of illness duration.

Prognosis of Brief Psychotic Episodes: A Meta-analysis.

The prognostic significance of competing constructs and operationalizations for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent psychotic symptoms [BLIPS]) is unknown. To provide a meta-analytical prognosis of the risk of psychotic recurrence in patients with remitted first-episode ATPD, BPD, BIPS, and BLIPS and in a benchmark group of patients with remitted first-episode schizophrenia (FES). We hypothesized a differential risk: FES > ATPD > BPD > BIPS > BLIPS. The Web of Knowledge and Scopus databases were searched up to May 18, 2015; the articles identified were reviewed as well as citations of previous publications and results of a manual search of the reference lists of retrieved articles. We included original articles that reported the risk of psychotic recurrence at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES. Independent extraction by multiple observers. Random-effects meta-analysis was performed, and moderators were tested with meta-regression analyses, Bonferroni corrected. Heterogeneity was assessed with the I2 index. Sensitivity analyses tested the robustness of the results. Publication bias was assessed with funnel plots and the Egger test. Proportion of patients with baseline ATPD, BPD, BLIPS, and BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up. Eighty-two independent studies comprising up to 11,133 patients were included. There was no prognostic difference in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS at any follow-up (P > .03). In the long-term analysis, risk of psychotic recurrence (reported as mean [95% CI]) was significantly higher in the FES group (0.78 [0.58-0.93] at 24 months and 0.84 [0.70-0.94] at ≥ 36 months; P < .02 and P < .001, respectively) compared with the other 4 groups (0.39 [0.32-0.47] at 24 months and 0.51 [0.41-0.61] at ≥ 36 months). There were no publication biases. Sex and exposure to antipsychotic medication modulated the meta-analytical estimates (.002 < P < .03). There are no prognostic differences in risk of psychotic recurrence between ATPD, BPD, BLIPS, and BIPS constructs of brief psychotic episodes. Conversely, there is consistent meta-analytical evidence for better long-term prognosis of brief psychotic episodes compared with remitted first-episode schizophrenia. These findings should influence the diagnostic practice and clinical services in the management of early psychosis.

Association between impaired brain activity and volume at the sub-region of Broca's area in ultra-high risk and first-episode schizophrenia: A multi-modal neuroimaging study

Recent studies have suggested that functional abnormalities in Broca's area, which is important in language production (speech and thoughts before speech), play an important role in the pathophysiology of schizophrenia. While multi-modal approaches have proved useful in revealing the specific pathophysiology of psychosis, the association of functional abnormalities with gray matter volume (GMV) here in subjects with an ultra-high risk (UHR) of schizophrenia, those with first-episode schizophrenia (FES), and healthy controls has yet to be clarified. Therefore, the relationship between cortical activity measured using functional near-infrared spectroscopy (fNIRS) during a verbal fluency task, and GMV in the Broca's area assessed using a manual tracing in magnetic resonance imaging (MRI), which considers individual structural variation, was examined for 57 subjects (23 UHR/18 FES/16 controls). The UHR and FES group showed significantly reduced brain activity compared to control group in the left pars triangularis (PT) (P=.036, .003, respectively). Furthermore in the FES group, the reduced brain activity significantly positively correlated with the volume in the left PT (B=0.29, P=.027), while significant negative association was evident for all subjects (B=−0.18, P=.010). This correlation remained significant after adjusting for antipsychotics dosage, and voxel-wise analysis could not detect any significant correlation between impaired cortical activity and volume. The significant relationship between neural activity and GMV in the left PT may reflect a specific pathophysiology related to the onset of schizophrenia.

Three-year follow up of event-related potentials PPI, P50 and Color map of N400 during the rehabilitation of first episode schizophrenia patients

To investigate the relationship between the variations of event-related potentials (ERP) and clinical symptoms and treatment in first episode schizophrenia patients. The ERP (P50, color map of N400 and prepulse inhibition of the startle reflex (PPI) ) were tested in 85 first episode schizophrenia (FES) patients and 78 normal controls (NC), and followed-up at 1, 2 and 3 years after treatment in FES. Positive and negative symptom scale (PANSS) was used to evaluate the psychotic symptoms of patients. (1) Compared with NC, FES showed decreased PPI% (41% ± 37% vs 68% ± 42%, P < 0.001), increased P50 S2/S1(87 ± 41 vs 51 ± 47, P < 0.001), prolonged N400 latency and decreased N400 amplitudes (P < 0.05 - 0.01 ). ( 2) Significant correlations were found between variations of color map of N400 latencies and general scores of PANSS (r = 0.321, P = 0.042), N400 amplitude and positive symptom scores (r = -0.437, P = 0.008) and total scores of PANSS (r = -0.392, P = 0.023), but the variations of PPI and P50 latencies and amplitudes did not show significant correlation with the positive symptom scores and total scores of PANSS. (3) The color map of N400 latencies and amplitudes in FES group showed significant difference (P < 0.05) but the major indexes of PPI and P50 did not show significant difference (P > 0.05) among the 1, 2 and 3 years' follow-up after treatment. This follow-up study suggests that the variations of PPI and P50 is probably a trait marker of FES, and the variations of color map of N400 might be a status marker of FES.

Duration of Untreated Psychosis and Brain Function during Verbal Fluency Testing in First-Episode Schizophrenia: A Near-Infrared Spectroscopy Study.

A longer duration of untreated psychosis (DUP) has been associated with poor clinical outcomes in patients with schizophrenia (SZ); however, it remains unclear whether this is due to neurotoxic effects of psychosis. The purpose of this study was to use near-infrared spectroscopy (NIRS) to investigate the influence of DUP on brain function using two verbal fluency tests (VFTs) in patients with first-episode SZ (FES). A total of 28 FES patients and 29 healthy controls (HC) underwent NIRS during VFTs. Group comparisons of cortical activity were made using two-tailed t-tests and the false discovery rate method. We then examined the associations between DUP and hemodynamic changes in each channel to identify any effects of DUP on brain cortical activity. During the letter VFT, the HC group exhibited significantly greater cortical activations over bilateral frontotemporal regions compared to FES patients. However, this distinction was not observed while performing a category version of the VFT. In addition, no associations between DUP and brain cortical activity were observed in the FES group during either VFT. In conclusion, we did not find an association between DUP and frontotemporal cortical activities. This might be because neurodevelopmental disturbances result in neurocognitive deficits long before psychotic symptoms onset.

Neurocognitive impairments in individuals at ultra-high risk for psychosis: Who will really convert?

Impairments in neurocognitive function are considered as core features of schizophrenia. Individuals at ultra-high risk (UHR) for psychosis, the 'putative' prodrome of schizophrenia, generally show levels of impairments intermediate between schizophrenia patients and healthy controls. We investigated the neurocognitive performance of individuals at UHR for psychosis, comparing them with patients with first-episode schizophrenia (FES) and healthy controls (HC), and explored the predictivity of baseline neurocognitive function in the UHR group for transition to overt psychosis. Individuals at UHR for psychosis (n = 60), patients with FES (n = 39), and HC subjects (n = 94) participated in the present study. All participants performed a comprehensive neurocognitive battery, consisting of tests for five separate neurocognitive domains (executive function, attention/working memory, processing speed, verbal memory, and spatial memory). UHR subjects were assessed for transition every month during 24 months of follow-up. Neurocognitive performance in the UHR group was largely at intermediate levels. Attention/working memory and verbal memory were significantly different from both the FES and HC groups. In the UHR group, processing speed was decreased to the level of the FES group, while executive function and spatial memory were relatively preserved. In the Cox regression model, spatial memory significantly predicted the transition to overt psychosis in the UHR group. The present study showed that neurocognitive impairments were evident in UHR individuals prior to the onset of overt psychosis. Our findings generally support the neurodevelopmental model of schizophrenia and suggest that there could be different developmental trajectories between converters and non-converters.

Prospective memory performance in non-psychotic first-degree relatives of patients with schizophrenia: a controlled study.

ObjectiveWe aimed at investigating prospective memory and its socio-demographic and neurocognitive correlates in non-psychotic, first-degree relatives (FDRs) of patients with schizophrenia compared to patients with first episode schizophrenia (FES), and healthy controls (HCs).MethodsForty-seven FES patients, 50 non-psychotic FDRs (23 offspring and 27 siblings) of patients with chronic schizophrenia (unrelated to the FES group) and 51 HCs were studied. The Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) was used to measure time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance. Other cognitive functions (involving respective memory and executive functions) were evaluated with standardized tests.ResultsAfter controlling for basic demographic characteristics including age, gender and educational level, there was a significant difference between FDRs, FES and HCs with respect to both TBPM (F(2,142) = 10.4, p<0.001) and EBPM (F(2,142) = 10.8, p<0.001). Multiple linear regression analyses revealed that lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the STROOP Word-Color Test (SWCT) contributed to TBPM impairment, while lower educational level and higher scores of the Color Trails Test-2 (CTT-2) contributed to EBPM deficit in FDRs.ConclusionsFDRs share similar but attenuated prospective memory impairments with schizophrenia patients, suggesting that prospective memory deficits may represent an endophenotype of schizophrenia.

Differences in P50 and prepulse inhibition of the startle reflex between male smokers and non-smokers with first episode schizophrenia without medical treatment

Backgorund Nicotine may improve schizophrenia patient’s cognitive deficit symptoms. This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES). Methods The event-related potentials (ERP) recording and analysis instrument made by Brain Products, Germany, was used to detect PPI and P50 in 49 male FES patients (FES group, n=21 for smokers and n=28 for non-smokers) and 43 normal male controls (control group, n=19 for smokers and n=24 for non-smokers). Results Compared with normal controls, the FES group had prolonged PPI latency when elicited by single stronger stimulus (P &lt;0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P &lt;0.05, 0.01) when elicited by weak and strong stimuli. The FES group had lower PPI inhibition rate than normal controls (P &lt;0.05). Compared with normal controls, the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P &lt;0.05). In the control group, the smokers had a tendency of increase in P50-S2 amplitude (P &gt;0.05) and shorter P50-S2 latency (P &lt;0.05) than the non-smokers. The smokers had higher PPI amplitude than the non-smokers (P &lt;0.05). In the FES group, the smokers had higher P50-S1 amplitude, shorter P50-S2 latency, and higher amplitude ratio S2/S1 than the non-smokers (P &lt;0.05, 0.01). The smokers had higher PPI amplitude than the non-smokers (P &lt;0.05). Conclusions There is obvious PPI and P50 deficits in schizophrenic patients. However, these deficits are relatively preserved in the smokers compared with the non-smokers, which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients. Whether this conclusion can be deduced to female patients requires further follow-ups.