Haojuan Tao

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

BACKGROUND Abnormalities in the corpus callosum have long been implicated in schizophrenia. Previous diffusion tensor imaging (DTI) studies in patients with different durations of schizophrenia yielded inconsistent results. By comparing patients with different durations of schizophrenia, we investigated if white matter abnormalities of the corpus callosum emerge at an early stage in the illness or result from pathological progression. METHODS We recruited patients with first-episode schizophrenia, patients with chronic schizophrenia and age-, sex- and handedness-matched healthy controls. We used 2 DTI techniques (voxel-based and fibre-tracking DTI) to investigate differences in corpus callosum integrity among the 3 groups. RESULTS With both DTI techniques, significantly decreased fractional anisotropy values were identified in the genu of corpus callosum in patients with chronic schizophrenia, but not first-episode schizophrenia, compared with healthy controls. LIMITATIONS This study was cross-sectional, and the sample size was relatively small. CONCLUSION Abnormalities in the genu of the corpus callosum might be a progressive process in schizophrenia, perhaps related to disease severity and prognosis.

Opposite Effective Connectivity in the Posterior Cingulate and Medial Prefrontal Cortex between First-Episode Schizophrenic Patients with Suicide Risk and Healthy Controls

Objective The schizophrenic patients with high suicide risk are characterized by depression, better cognitive function, and prominent positive symptoms. However, the neurobiological basis of suicide attempts in schizophrenia is not clear. The suicide in schizophrenia is implicated in the defects in emotional process and decision-making, which are associated with prefrontal-cingulate circuit. In order to explore the possible neurobiological basis of suicide in schizophrenia, we investigated the correlation of prefrontal-cingulate circuit with suicide risk in schizophrenia via dynamic casual modelling. Method Participants were 33 first-episode schizophrenic patients comprising of a high suicide risk group (N = 14) and a low suicide risk group (N = 19). A comparison group of healthy controls (N = 15) were matched for age, gender and education. N-back tasking functional magnetic resonance imaging data was collected. Results Compared with healthy controls group, the two patients groups showed decreased task-related suppression during 2-back task state versus baseline state in the left posterior cingulate and medial prefrontal cortex; the hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex existed in both schizophrenic patients groups, but hypo-connectivity in the opposite direction only existed in the schizophrenic patients group with high suicide risk. Conclusions The hyper-connectivity from the left posterior cingulate cortex to the left medial prefrontal cortex may suggest that the abnormal effective connectivity was associated with risk for schizophrenia. The hypo-connectivity in the opposite direction may represent a possible correlate of increased vulnerability to suicide attempt.

The diminished interhemispheric connectivity correlates with negative symptoms and cognitive impairment in first-episode schizophrenia

BACKGROUND Previous studies imply that interhemispheric disconnectivity plays a more important role on information processing in schizophrenia. However, the role of the aberrant interhemispheric connection in the pathophysiology of this disorder remains unclear. Recently, resting-state functional Magnetic Resonance Imaging (fMRI) has reported to have potentials of mapping functional interactions between pairs of brain hemispheres. METHODS Resting-state whole-brain functional connectivity analyses were performed on 41 schizophrenia patients and 33 healthy controls. RESULTS The first-episode schizophrenia patients showed significant aberrant interhemispheric connection in the globus pallidus, medial frontal gyrus and inferior temporal gyrus. The correlation of Wechsler Adult Intelligence Scale scores with odds ratio of the aberrant interhemispheric connections revealed positive correlation in the pallidum (rho=0.335, p=.003) and medial frontal gyrus (rho=0.260, p=.025). The connection in the pallidum was also positively correlated with duration of illness (rho=-0.407, p=.009). Whereas, the aberrant interhemispheric connection in the inferior temporal gyrus was positively correlated with scores of Scale for the Assessment of Negative Symptoms (rho=0.393, p=.012). CONCLUSION The present study provides fMRI evidence for the aberrant interhemispheric resting-state functional connectivity within resting-state networks in first-episode schizophrenia patients. These aberrant interhemispheric connections, in particular the pallidum, due to its anatomical and functional connectivities, may be the primary disturbance for cognitive impairment, negative symptoms and chronicity of schizophrenia.

Inefficient DMN Suppression in Schizophrenia Patients with Impaired Cognitive Function but not Patients with Preserved Cognitive Function

Previous studies have observed reduced suppression of the default mode network (DMN) during cognitive tasks in schizophrenia, suggesting inefficient DMN suppression is critical for the cognitive deficits of schizophrenia. Cognitive function in schizophrenia patients, however, varies from relatively intact to severely impaired. This study, which compared the DMN suppression patterns between first-episode schizophrenia patients with (SZ-Imp) and without (SZ-Pre) impaired cognitive function, may provide further insight into the role of DMN dysfunction in cognitive deficits of schizophrenia. Independent component analysis (ICA) was applied to resting-state fMRI data to identify the DMN in each subject, and then general linear modeling based on the task-fMRI data was used to examine the different DMN activation patterns between groups. We observed that the SZ-Imp group, but not the SZ-Pre group, showed reduced suppression in the medial prefrontal cortex and posterior cingulated cortex when compared to the healthy controls (HC) group. Moreover, less DMN suppression was associated with poorer task performance in both HC and patient groups. Our findings provide the first direct evidence that disrupted DMN activity only exists in schizophrenia patients with impaired cognitive function, supporting the specific neuro-pathological role of inefficient DMN suppression in cognitive deficits of first-episode schizophrenia.

Comparing the PANSS in Chinese and American inpatients: cross-cultural psychiatric analyses of instrument translation and implementation.

This article compares data from the Positive and Negative Syndrome Scale (PANSS) collected from Chinese and American inpatients diagnosed with schizophrenia to show how patterned differences in item ratings may reflect cultural attitudes of the raters. The Chinese sample (N=553) was based on consecutive admissions to four academic hospitals in Changsha, China. Only patients ill for 3 or more years were included in the analysis to match the chronically ill sample represented in the US CATIE sample. A total of 261 PANSS assessments were completed during a month when CATIE subjects had been hospitalized for 15 days or more to optimize equivalence of the US and Chinese samples. Controlling for age and gender, the total PANSS and the three sub-scores were all significantly lower in the Chinese than in the US CATIE sample by 5-8% (all p<.05). However, on 9 items, the Chinese sample scored 10-30% higher than the US sample (all p<.05) and on 5 items they scored over 20% higher (all p<.0001). These items rated increased hostility, poorer attention, lack of judgment and insight, disturbance of volition, and poorer impulse control. We ascribe these differences to cultural variations in the ways individuals relate to others in their social environment within Chinese and American societies.

Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings

BACKGROUND Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patients genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. METHODS 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. RESULTS We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. CONCLUSIONS This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia.

Grey matter morphological anomalies in the caudate head in first-episode psychosis patients with delusions of reference

Delusions of reference (DOR) are theoretically linked with aberrant salience and associative learning. Previous studies have shown that the caudate nucleus plays a critical role in the cognitive circuits of coding prediction errors and associative learning. The current study aimed at testing the hypothesis that abnormalities in the caudate nucleus may be involved in the neuroanatomical substrate of DOR. Structural magnetic resonance imaging of the brain was performed in 44 first-episode psychosis patients (with diagnoses of schizophrenia or schizophreniform disorder) and 25 healthy controls. Patients were divided into three groups according to symptoms: patients with DOR as prominent positive symptom; patients with prominent positive symptoms other than DOR; and patients with minimal positive symptoms. All groups were age-, gender-, and education-matched, and patient groups were matched for diagnosis, duration of illness, and antipsychotic treatment. Voxel-based morphometric analysis was performed to identify group differences in grey matter density. Relationships were explored between grey matter density and DOR. Patients with DOR were found to have reduced grey matter density in the caudate compared with patients without DOR and healthy controls. Grey matter density values of the left and right caudate head were negatively correlated with DOR severity. Decreased grey matter density in the caudate nucleus may underlie DOR in early psychosis.

The instability of functional connectivity in patients with schizophrenia and their siblings: A dynamic connectivity study

BACKGROUND The distributed connectivity among brain regions is in a constant state of flux, even when a subject is at rest. This instability (temporal variability), when optimal, may contribute to efficient cross-network communications. We investigate the role of this variability in the genetic diathesis and symptom expression of schizophrenia. METHODS Resting state functional MRI data acquired from 116 subjects (28 patients with schizophrenia, 28 siblings and 60 matched healthy controls). Using a sliding-window dynamic connectivity approach, we quantified the variability of whole-brain connectivity (dynamic functional connectivity or dFC) of each of the 90 brain regions obtained using a parcellation scheme that covered all contiguous brain regions of the cerebral cortex. RESULTS We noted a high degree of instability anchored on the precuneus in patients with schizophrenia compared to both healthy controls (t=3.60, p=0.0005) and unaffected siblings (t=3.61, p=0.001) indicating a role for dFC of precuneus in the clinical expression of schizophrenia. Compared to patients, siblings also showed an increase in medial orbitofrontal but reduced putaminal instability; these latter changes were not seen in patients when compared to controls, indicating a lack of specificity for diathesis or expression related effects. CONCLUSIONS Instability in the intrinsic connectivity of precuneus, a functional core hub with a major role in task-free self-processing, is likely to be a core substrate of the clinical expression of schizophrenia.

Psychotic-like experiences and correlation with childhood trauma and other socio-demographic factors: A cross-sectional survey in adolescence and early adulthood in China

Psychotic-like experiences (PLEs) in adolescence are found to be risk factors for later mental disorders. Previous research has also found that childhood trauma has a positive correlation with mental health problems. However, few studies have focused on the relationship between them, especially in adolescence and early adulthood. A total of 9122 students (age between 10 and 23.3) were surveyed and assessed with the positive and depressive subscales of the Community Assessment of Psychic Experiences and the Trauma History Questionnaire. A total of 20.7% students experienced frequent PLEs, 17.5% had frequent delusional experiences, and 7.6% had frequent hallucinatory experiences. Only a small portion of this sample experienced frequent PLEs, associated with more types of PLEs, more distress, and more depressive experiences. Several socio-demographic factors were associated with frequent PLEs in this sample, which could be further examined in future prevention studies. Students with frequent PLEs experienced significantly higher impact from trauma events, both at the time of the events and in the present, indicating a possible reciprocal effect between childhood trauma and PLEs. The impact of childhood trauma played an important role in the relationship between childhood trauma and PLEs.

T184. BRAIN-WIDE FUNCTIONAL DYSCONNECTIVITY IN SCHIZOPHRENIA: PARSING DIATHESIS, RESILIENCE AND THE EFFECTS OF CLINICAL EXPRESSION

Abstract Background The functional dysconnectivity observed from resting-state fMRI studies in schizophrenia is also seen in unaffected siblings indicating its association with the genetic diathesis of the illness. Nevertheless, when compared to patients, the extent of dysconnectivity appears to be limited both in spatial distribution and magnitude in siblings, suggesting that some of the abnormalities could be exclusively linked to the clinical expression or treatment effect rather than genetic diathesis. We investigated brain-wide functional connectivity using a graph theory approach to apportion resting-state dysconnectivity into components that represent genetic diathesis, clinical expression or treatment effect and resilience. Methods Resting state functional MRI data acquired from 116 subjects (28 patients with schizophrenia, 28 unaffected siblings and 60 matched healthy controls). Based on Dosenbach’s atlas applied to 6 minutes (180 time points with TR=2 s) of eyes-open resting fMRI scan, we extracted time series of 160 functional network nodes. After constructing a 160*160 functional network, we investigated between-group differences in strength and diversity of functional connectivity and topological properties of undirected graphs constructed from thresholded correlation matrices. We also used Support Vector Machine approach to estimate the ability of functional connectivity metrics to discriminate the three groups from each other. Results Using ANOVA [FDR corrected p<0.05], we found 88 out of 12720 pairs of functional links to be significantly different among the three groups. 48.8% of these 88 links included nodes from the Default Mode Network (DMN), with the largest portion of these involving Salience Network/DMN connectivity (14.8%). Post-hoc t tests revealed that 62.5% of these disconnected links were associated with genetic diathesis of schizophrenia (i.e. both patients and siblings showing same direction of significant post-hoc difference compared to HC) and 21.6% were associated with clinical expression or treatment effect (i.e. patients differed from siblings and healthy controls, but no difference between controls and siblings). Topologically, we observed increased degree, clustering coefficient and global efficiency but reduced local efficiency in the sibling group compared to both patients and controls, indicating a resilience (or compensation) effect. Support vector machine analysis revealed a high degree of accuracy when classifying the genetically predisposed (patients and siblings) vs. healthy controls (Area Under the Curve - AUC 0.97) or the patient groups vs. healthy controls (AUC 0.97) but not when discriminating patients vs. siblings (AUC 0.58) Discussion A large portion of the resting-state functional dysconnectivity seen in patients with schizophrenia represent a genetic diathesis effect. The most prominent network level disruption in this context is the dysconnectivity among nodes of the default-mode and salience networks. Despite their predisposition, unaffected siblings show a pattern of resilience in the emergent connectomic topology. Our findings could potentially help refine imaging genetics approaches currently used in the pursuit of the pathophysiology of schizophrenia.