Zhening Liu

Altered resting-state functional connectivity and anatomical connectivity of hippocampus in schizophrenia

Hippocampus has been implicated in participating in the pathophysiology of schizophrenia. However, the functional and anatomical connectivities between hippocampus and other regions are rarely concurrently investigated in schizophrenia. In the present study, both functional magnetic resonance imaging (fMRI) during rest and diffusion tensor imaging (DTI) were performed on 17 patients with paranoid schizophrenia and 14 healthy subjects. Resting-state functional connectivities of the bilateral hippocampi were separately analyzed by selecting the anterior hippocampus as region of interest. The fornix body was reconstructed by diffusion tensor tractography, and the integrity of this tract was evaluated using fractional anisotropy (FA). In patients with schizophrenia, the bilateral hippocampi showed reduced functional connectivities to some regions which have been reported to be involved in episodic memory, such as posterior cingulate cortex, extrastriate cortex, medial prefrontal cortex, and parahippocampus gyrus. We speculated that these reduced connectivity may reflect the disconnectivity within a neural network related to the anterior hippocampus in schizophrenia. Meanwhile the mean FA of the fornix body was significantly reduced in patients, indicating the damage in the hippocampal anatomical connectivity in schizophrenia. The concurrence of the functional disconnectivity and damaged anatomical connectivity between the hippocampus and other regions in schizophrenia suggest that the functional-anatomical relationship need to be further investigated.

Functional dysconnectivity of the dorsolateral prefrontal cortex in first-episode schizophrenia using resting-state fMRI

The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in schizophrenia has given prominence to its importance in studies on the dysconnection associated with schizophrenia. Abnormal functional connectivities of the DLPFC have been found during various goal-directed tasks; however, the occurrence of the abnormality during rest in patients with schizophrenia has rarely been reported. In the present study, we selected bilateral Brodmanns area 46 as region of interest and analyzed the differences in the DLPFC functional connectivity pattern between 17 patients with first-episode schizophrenia (FES) and 17 matched controls using resting-state fMRI. We found that the bilateral DLPFC showed reduced functional connectivities to the parietal lobe, posterior cingulate cortex, thalamus and striatum in FES patients. We also found enhanced functional connectivity between the left DLPFC and the left mid-posterior temporal lobe and the paralimbic regions in FES patients. Our results suggest that functional dysconnectivity associated with the DLPFC exists in schizophrenia during rest. This may be partially related to disturbance in the intrinsic brain activity.

Depression uncouples brain hate circuit

It is increasingly recognized that we need a better understanding of how mental disorders such as depression alter the brains functional connections to improve both early diagnosis and therapy. A new holistic approach has been used to investigate functional connectivity changes in the brains of patients suffering from major depression using resting-state functional magnetic resonance imaging (fMRI) data. A canonical template of connectivity in 90 different brain regions was constructed from healthy control subjects and this identified a six-community structure with each network corresponding to a different functional system. This template was compared with functional networks derived from fMRI scans of both first-episode and longer-term, drug resistant, patients suffering from severe depression. The greatest change in both groups of depressed patients was uncoupling of the so-called ‘hate circuit’ involving the superior frontal gyrus, insula and putamen. Other major changes occurred in circuits related to risk and action responses, reward and emotion, attention and memory processing. A voxel-based morphometry analysis was also carried out but this revealed no evidence in the depressed patients for altered gray or white matter densities in the regions showing altered functional connectivity. This is the first evidence for the involvement of the ‘hate circuit’ in depression and suggests a potential reappraisal of the key neural circuitry involved. We have hypothesized that this may reflect reduced cognitive control over negative feelings toward both self and others.

Abnormal amplitude low-frequency oscillations in medication-naive, first-episode patients with major depressive disorder: A resting-state fMRI study

BACKGROUND Recent resting-state fMRI studies on major depressive disorder (MDD) have found altered temporal correlation between low-frequency oscillations (LFOs). However, changes on the amplitudes of these LFOs remain largely unknown. METHODS Twenty-two medication-naive, first-episode patients with MDD and 19 age-, sex-, education-matched healthy controls were recruited. Resting-state fMRI was obtained by using an echo-planar imaging sequence and the fractional amplitude of low-frequency fluctuations (fALFF) was calculated to investigate the amplitude of LFOs in the resting state. RESULTS Compared with control subjects, patients with MDD showed significantly decreased fALFF in right cerebellum posterior lobe, left parahippocampal gyrus and right middle frontal gyrus and increased fALFF in left superior occipital gyrus/cuneus (p<0.05, corrected for multiple comparisons). Further receiver operating characteristic curves (ROC) analyses suggested that the alterations of fALFF in these regions might be used as markers to classify patients with MDD from healthy controls. CONCLUSIONS These findings indicated LFOs abnormalities in MDD and the fALFF analysis might be a potential approach in further exploration of this disorder.

Abnormal neural activity in the patients with remitted geriatric depression: a resting-state functional magnetic resonance imaging study.

OBJECTIVE To investigate regional activity abnormalities of first-episode remitted geriatric depression (RGD) using a resting-state functional magnetic resonance imaging (fMRI) in closely matched patients and healthy controls, and to examine the relationship between performances on neuropsychological tests and regional activity abnormalities. METHOD A newly reported regional homogeneity approach was used to analyze blood oxygen level-dependent fMRI data on resting state in 18 patients with remitted geriatric depression and 14 well-matched healthy controls. All subjects were measured by neuropsychological tests. RESULTS Decreased regional homogeneity (ReHo) in remitted geriatric depression distributed over the frontal, temporal and parietal lobes. In addition, increased ReHo were found mainly in the putamen, frontal and parietal lobes. The RGD patients performed significantly worse in the delayed recall of Rey Auditory Verbal Learning Test (RAVLT) and Trail Making Test A and B (seconds) when compared with the control group. And there are significant negative correlations between ReHo values of right putamen, left superior frontal gyrus and Trail Making Test A (seconds) (r=-0.583, P=0.023; r=-0.598, P=0.018, respectively), Trail Making Test B (seconds) (r=-0.587, P=0.021; r=-0.545, P=0.036, respectively) in the patients with RGD. LIMITATIONS This study is cross-sectional, therefore it cannot determine whether abnormal brain activation is a state marker or trait marker of RGD in resting-state fMRI. CONCLUSION Our study reveals that RGD is associated with abnormal activity of certain brain regions, which are believed to be involved in the psychopathology and pathophysiology of executive function in remitted geriatric depression.

Schizophrenic Patients and Their Unaffected Siblings Share Increased Resting-State Connectivity in the Task-Negative Network but Not Its Anticorrelated Task-Positive Network

BACKGROUND Abnormal connectivity of the anticorrelated intrinsic networks, the task-negative network (TNN), and the task-positive network (TPN) is implicated in schizophrenia. Comparisons between schizophrenic patients and their unaffected siblings enable further understanding of illness susceptibility and pathophysiology. We examined the resting-state connectivity differences in the intrinsic networks between schizophrenic patients, their unaffected siblings, and healthy controls. METHODS Resting-state functional magnetic resonance images were obtained from 25 individuals in each subject group. The posterior cingulate cortex/precuneus and right dorsolateral prefrontal cortex were used as seed regions to identify the TNN and TPN through functional connectivity analysis. Interregional connectivity strengths were analyzed using overlapped intrinsic networks composed of regions common to all subject groups. RESULTS Schizophrenic patients and their unaffected siblings showed increased connectivity in the TNN between the bilateral inferior temporal gyri. By contrast, schizophrenic patients alone demonstrated increased connectivity between the posterior cingulate cortex/precuneus and left inferior temporal gyrus and between the ventral medial prefrontal cortex and right lateral parietal cortex in the TNN. Schizophrenic patients exhibited increased connectivity between the left dorsolateral prefrontal cortex and right inferior frontal gyrus in the TPN relative to their unaffected siblings, though this trend only approached statistical significance in comparison to healthy controls. CONCLUSION Resting-state hyperconnectivity of the intrinsic networks may disrupt network coordination and thereby contribute to the pathophysiology of schizophrenia. Similar, though milder, hyperconnectivity of the TNN in unaffected siblings of schizophrenic patients may contribute to the identification of schizophrenia endophenotypes and ultimately to the determination of schizophrenia risk genes.

Classification of Different Therapeutic Responses of Major Depressive Disorder with Multivariate Pattern Analysis Method Based on Structural MR Scans

Background Previous studies have found numerous brain changes in patients with major depressive disorder (MDD), but no neurological biomarker has been developed to diagnose depression or to predict responses to antidepressants. In the present study, we used multivariate pattern analysis (MVPA) to classify MDD patients with different therapeutic responses and healthy controls and to explore the diagnostic and prognostic value of structural neuroimaging data of MDD. Methodology/Principal Findings Eighteen patients with treatment-resistant depression (TRD), 17 patients with treatment-sensitive depression (TSD) and 17 matched healthy controls were scanned using structural MRI. Voxel-based morphometry, together with a modified MVPA technique which combined searchlight algorithm and principal component analysis (PCA), was used to classify the subjects with TRD, those with TSD and healthy controls. The results revealed that both gray matter (GM) and white matter (WM) of frontal, temporal, parietal and occipital brain regions as well as cerebellum structures had a high classification power in patients with MDD. The accuracy of the GM and WM that correctly discriminated TRD patients from TSD patients was both 82.9%. Meanwhile, the accuracy of the GM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 82.4%, respectively; and the WM that correctly discriminated TRD or TSD patients from healthy controls were 85.7% and 91.2%, respectively. Conclusions/Significance These results suggest that structural MRI with MVPA might be a useful and reliable method to study the neuroanatomical changes to differentiate patients with MDD from healthy controls and patients with TRD from those with TSD. This method might also be useful to study potential brain regions associated with treatment response in patients with MDD.

Schizophrenia patients and their healthy siblings share disruption of white matter integrity in the left prefrontal cortex and the hippocampus but not the anterior cingulate cortex

Healthy siblings of schizophrenia patients have an almost 9-fold higher risk for developing the illness than the general population. Disruption of white matter (WM) integrity as indicated by reduced fractional anisotropy (FA) derived from diffusion tensor imaging (DTI), is believed to be the key substrate of schizophrenia. However, it remains unclear whether schizophrenia patients and their healthy siblings share a specific pattern of disruption of WM integrity that may be related to the disease risk. The objective of this study is to determine whether a specific brain regional pattern of disruption of WM integrity is shared by schizophrenia patients and their healthy siblings. We investigated brain white matter abnormalities by voxel-based analysis of white matter FA data acquired from diffusion tensor imaging in 34 pairs of schizophrenia patients and their healthy siblings, as well as in 32 healthy controls. Both schizophrenia patients and their healthy siblings showed reduced white matter FA in the left prefrontal cortex and the hippocampus in comparison to healthy controls, without significant difference between patients and siblings. In marked contrast, only schizophrenia patients exhibited reduced white matter FA in the left anterior cingulate cortex in comparison to both siblings and controls, without significant difference between siblings and controls. Thus, schizophrenia patients and their healthy siblings share disruption of WM integrity in the left prefrontal cortex and the hippocampus that may be related to higher risk of healthy siblings to develop schizophrenia, which may be eventually attributed to additional disruption of WM integrity in the left anterior cingulate cortex.

Abnormal neural activities in first-episode, treatment-naïve, short-illness-duration, and treatment-response patients with major depressive disorder: A resting-state fMRI study

BACKGROUND Abnormality of limbic-cortical networks was postulated in depression. Using a regional homogeneity (ReHo) approach, we explored the regional homogeneity (ReHo) of the brain regions in patients with first-episode, treatment-naïve, short-illness-duration, and treatment-response depression in resting state to test the abnormality hypothesis of limbic-cortical networks in major depressive disorder (MDD). METHODS Seventeen patients with treatment-response MDD and 17 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. RESULTS CONCLUSIONS Our findings suggested the abnormality of limbic-cortical networks in first-episode, treatment-naïve, short-illness-duration, and treatment-response MDD patients, and added an expanding literature to the abnormality hypothesis of limbic-cortical networks in MDD.

Effect of Antipsychotic Medication Alone vs Combined With Psychosocial Intervention on Outcomes of Early-Stage Schizophrenia: A Randomized, 1-Year Study

CONTEXT Antipsychotic drugs are limited in their ability to improve the overall outcome of schizophrenia. Adding psychosocial treatment may produce greater improvement in functional outcome than does medication treatment alone. OBJECTIVE To evaluate the effectiveness of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia. DESIGN Randomized controlled trial. SETTING Ten clinical sites in China. PARTICIPANTS Clinical sample of 1268 patients with early-stage schizophrenia treated from January 1, 2005, through October 31, 2007. Intervention Patients were randomly assigned to receive antipsychotic medication treatment only or antipsychotic medication plus 12 months of psychosocial intervention consisting of psychoeducation, family intervention, skills training, and cognitive behavior therapy administered during 48 group sessions. MAIN OUTCOME MEASURES The rate of treatment discontinuation or change due to any cause, relapse or remission, and assessments of insight, treatment adherence, quality of life, and social functioning. RESULTS The rates of treatment discontinuation or change due to any cause were 32.8% in the combined treatment group and 46.8% in the medication-alone group. Comparisons with medication treatment alone showed lower risk of any-cause discontinuation with combined treatment (hazard ratio, 0.62; 95% confidence interval, 0.52-0.74; P < .001) and lower risk of relapse with combined treatment (0.57; 0.44-0.74; P < .001). The combined treatment group exhibited greater improvement in insight (P < .001), social functioning (P = .002), activities of daily living (P < .001), and 4 domains of quality of life as measured by the Medical Outcomes Study 36-Item Short Form Health Survey (all P < or = .02). Furthermore, a significantly higher proportion of patients receiving combined treatment obtained employment or accessed education (P = .001). CONCLUSION Compared with those receiving medication only, patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change, a lower risk of relapse, and improved insight, quality of life, and social functioning. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00654576.