Maorong Hu

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 regional spontaneous neural activity in first-episode, treatment-naive patients with late-life depression: a resting-state fMRI study.

BACKGROUND The previous resting perfusion or task-based studies have provided evidence of functional changes in the brains of patients with late-life depression (LLD). Little is known, so far, about the changes in the spontaneous brain activity in LLD during the resting state. The aim of this study was to investigate the spontaneous neural activity in first-episode, treatment-naive patients with LLD by using resting-state functional magnetic resonance imaging (fMRI). METHODS A novel analytical method, coherence-based regional homogeneity (Cohe-ReHo), was used to assess regional spontaneous neural activity during the resting state in 15 first-episode, treatment-naive patients with LLD and 15 age- and gender-matched healthy controls. RESULTS Compared to the healthy controls, the LLD group showed significantly decreased Cohe-ReHo in left caudate nucleus, right anterior cingulate gyrus, left dorsolateral prefrontal cortex, right angular gyrus, bilateral medial prefrontal cortex, and right precuneus, while significantly increased Cohe-ReHo in left cerebellum posterior lobe, left superior temporal gyrus, bilateral supplementary motor area, and right postcentral gyrus (p<0.005, corrected for multiple comparisons). CONCLUSIONS These findings indicated abnormal spontaneous neural activity was distributed extensively in first-episode, treatment-naive patients with LLD during the resting state. Our results might supply a novel way to look into the underlying pathophysiology mechanisms of patients with LLD.

Decreased left middle temporal gyrus volume in antipsychotic drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings

BACKGROUND The shared neuropathological characteristics of patients with schizophrenia and their siblings might represent intermediate phenotypes that could be used to investigate genetic susceptibility to the illness. We sought to discover gray matter volume differences in patients with schizophrenia and their unaffected siblings with voxel-based morphometry (VBM). METHODS We recruited antipsychotic drug-naive, first-episode schizophrenia (FES) patients, their unaffected siblings and age-, sex- and handedness-matched healthy controls. We used VBM to investigate differences in gray matter volume among the 3 groups. RESULTS There were significant gray matter volumetric differences among the 3 groups in bilateral hippocampal and parahippocampal gyri, bilateral middle temporal gyri, and superior temporal gyri (FDR p<0.05). Patients had significant regional gray matter reduction in all regions listed above compared with healthy volunteers, and their gray matter volume in the right hippocampus and parahippocampus was also lower than the sibling group. The sibling group had significantly lower volumes compared to healthy individuals only in the left middle temporal gyrus, and volume of this region was not different between siblings and patients. CONCLUSIONS Our findings confirm and extend previous VBM analyses in schizophrenia and it indicate that schizophrenia may be characterized by an abnormal development of cerebral lateralization. Furthermore, these data argue that patients and their unaffected siblings might share decreases in the gray matter volume of the left middle temporal gyrus, and this regional reduction might be a potential endophenotype for schizophrenia.

Early and late onset, first-episode, treatment-naive depression: same clinical symptoms, different regional neural activities

BACKGROUND Patients with early onset depression (EOD) and late onset depression (LOD) have distinctive risk factors and clinical pictures. Using regional homogeneity (ReHo) approach, we were to test the hypothesis of the different abnormal neural activity between patients with EOD or LOD. METHODS Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS participated in the study. ReHo approach was employed to analyze the scans. RESULTS ANOVA analysis revealed widespread differences in ReHo values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ReHo in right precuneus (PCu) and bilateral superior frontal gyrus, and lower ReHo in left superior temporal gyrus. Compared to young HS, lower ReHo in left parahippocampal gyrus and higher ReHo in left fusiform gyrus and bilateral superior frontal gyrus were seen in EOD group; in contrast, in LOD group, lower ReHo in right PCu and higher ReHo in left superior temporal gyrus and left Crus I of the cerebellum were observed. Further ROC analysis suggested that the mean ReHo values in right PCu and bilateral superior frontal gyrus could serve as markers to identify patients with EOD from individuals with LOD. LIMITATION The large age gap may limit the translational value of our findings. CONCLUSIONS Patients with EOD and those with LOD have abnormal neural activities in different brain regions, although the two groups share the same symptoms.

Hippocampal and orbital inferior frontal gray matter volume abnormalities and cognitive deficit in treatment-naive, first-episode patients with schizophrenia

BACKGROUND Cognitive impairment is a core feature of schizophrenia. Some evidence suggests an association between cognition deficits and gray matter reductions. In this study, we investigated the relationship between cognitive performance and gray matter volumes in patients with treatment-naïve, first-episode schizophrenia. METHOD First-episode patients with treatment-naïve schizophrenia and healthy controls went through brain imaging scan using high resolution magnetic resonance imaging. A neuropsychological battery including 8 neurocognitive tests was used to assess cognitive function. Voxel-based methods were used for volumetric measure in the brain. RESULTS Fifty-one patients and 41 healthy controls were included in the analysis. Patients exhibited a poorer performance on all 7 cognitive function tests compared with healthy controls (ps<0.006). There were significant gray matter volume differences between the two groups in bilateral hippocampus gyri, right superior temporal gyrus, left fusiform gyrus and orbital inferior frontal gyri (FDR, ps<0.05). Within the schizophrenia group, multiple regression analysis demonstrated that poorer performance on the working memory, verbal learning and visual learning was associated with smaller hippocampal gray matter volume, and poorer executive function was associated with smaller left orbital inferior frontal gray matter volume after controlling for potential confounding variables (β ≥ 0.420, ps ≤ 0.010). CONCLUSIONS Our findings suggest that cognitive deficits are associated with hippocampal and orbital inferior frontal gray matter volume abnormalities in treatment-naïve, first-episode patients with schizophrenia.

Decreased gray matter volume in the left middle temporal gyrus as a candidate biomarker for schizophrenia: A study of drug naive, first-episode schizophrenia patients and unaffected siblings

BACKGROUND Studies have shown that patients with schizophrenia and their siblings share decreased gray matter (GM) volumes in certain brain regions, which may represent candidate endophenotypes of schizophrenia. However, the specificity and utility of these possible endophenotypes in relation to schizophrenia remain unclear. METHODS Twenty drug-naive, first-episode schizophrenia patients and 20 first-degree unaffected siblings from the same families as the patients (USS group), a separate group of 25 first-degree unaffected siblings of schizophrenia patients from other families (USO group), and 43 healthy controls were recruited. Voxel-based morphometry (VBM) was used to analyze structural imaging data. RESULTS The VBM analysis showed a significant difference in GM volume between the combined sibling group and the control group in the left middle temporal gyrus (MTG). Group comparison showed that the patients, the USS, and the USO had significantly decreased GM volume of the left MTG compared with the controls; such a difference did not exist among the patients and the two sibling groups. A receiver operating characteristic curve (ROC curve) analysis showed good predictive value of the mean cluster volume in the left MTG to distinguish patients, USS, and USO from healthy controls. There were no significant correlations between the mean cluster volume in the left MTG and clinical variables in the patients. CONCLUSIONS The GM volume decrease of the left MTG may be utilized as a candidate biomarker for schizophrenia. The novel design of including a USO group in our study enhances both the specificity and the heritability of the biomarker identified.

Regional white matter abnormalities in drug-naive, first-episode schizophrenia patients and their healthy unaffected siblings

Objective: Shared neuropathological features between schizophrenia patients and their siblings may represent intermediate phenotypes of schizophrenia and can be used to investigate genetic susceptibility to the illness. This study aimed to discover regional white matter abnormalities in first-episode schizophrenia (FES) patients and their unaffected siblings compared to healthy subjects in the Chinese Han population using optimized Voxel-Based Morphometry (VBM). Method: A total of 51 drug-naive, FES patients, 45 of their unaffected siblings and 59 healthy comparisons were studied with magnetic resonance imaging (MRI). Results: FES patients exhibited significant regional white matter deficits in the left inferior frontal gyrus and left joint of external capsule and internal capsule compared with healthy subjects (corrected FDR, p<0.005). The sibling group also showed significant white matter deficits in these two regions compared with the healthy comparison group (uncorrected, p<0.001). White matter deficits with a less stringent threshold for significance in the left cerebellum anterior lobe, left middle frontal gyrus, left hippocampus, right anterior cingulate and right internal capsule were observed in patients compared to their siblings. Conclusions: Our findings extend those from previous VBM analyses showing that FES patients and their unaffected siblings may share white matter deficits in the left inferior frontal gyrus and the left joint of external capsule and internal capsule. These regional white matter deficits may be related to genetic factors related to schizophrenia susceptibility.

No association of ZNF804A rs1344706 with white matter integrity in schizophrenia: a tract-based spatial statistics study.

Altered brain connectivity has been widely considered as a genetic risk mechanism for schizophrenia. Of the many susceptibility genes identified so far, ZNF804A (rs1344706) is the first common genetic variant associated with schizophrenia on a genome-wide level. Previous fMRI studies have found that carriers of rs1344706 exhibit altered functional connectivity. However, the relationship between ZNF804A and white matter structural connectivity in patients of schizophrenia remains unknown. In this study, 100 patients with schizophrenia and 69 healthy controls were genotyped at the single nucleotide polymorphism rs1344706. Diffusion tensor imaging (DTI) was conducted and analyzed with tract-based spatial statistics. Systematic statistical analysis was conducted on multiple diffusion indices, including fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity. Unpaired two-sample t-test revealed significant differences in fractional anisotropy and diffusivity between schizophrenia and control groups. A two-way ANOVA analysis was conducted to assess the main effects of and the interaction between schizophrenia and ZNF804A. Although significant main effects of the diagnosis of schizophrenia were found on radial diffusivity, no association between the ZNF804A (rs1344706) and white matter connectivity was found in the entire group of subjects or in a selected subgroup of age-matched subjects (n=72).

Neurocognitive effects of first- and second-generation antipsychotic drugs in early-stage schizophrenia: A naturalistic 12-month follow-up study

The study aimed to assess the cognitive effects of first- and second-generation antipsychotics on neurocognition under naturalistic treatment conditions. In a 12-month, open-label, multicenter study, 698 patients with early-stage schizophrenia (duration of illness ≤5 years) were prescribed chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole monotherapy. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was administered at baseline, 6- and 12-months. The primary outcome was change in a cognitive composite score after 12-months of treatment. At 12 months, treatment resulted in mild to moderate neurocognitive improvements of z=0.32 for chlorpromazine, 0.33 for sulpiride, 0.43 for clozapine, 0.51 for risperidone, 0.69 for olanzapine, 0.64 for quetiapine and 0.46 for aripiprazole. However, the olanzapine and quetiapine groups demonstrated greater improvement in the composite score and processing speed than did the chlorpromazine and sulpiride groups. Both first- and second-generation antipsychotics may improve cognitive function in patients with early-stage schizophrenia. Given that some neurocognitive improvement is attributable to a practice effect, any improvement is likely to be in the range of a small effect size.

Cognitive effects of atypical antipsychotic drugs in first-episode drug-naïve schizophrenic patients

Cognitive impairment is a core feature of schizophrenia. The present randomized open study enrolled antipsychotic-naïve patients who were experiencing their first episode of schizophrenia. After baseline neurocognitive tests and clinical assessment, subjects were randomly assigned to olanzapine, risperidone and aripiprazole treatment groups. A battery of neurocognitive tests showed that risperidone produced cognitive benefits in all five cognitive domains, including verbal learning and memory, visual learning and memory, working memory, processing speed, and selective attention; olanzapine improved processing speed and selective attention; and aripiprazole improved visual learning and memory, and working memory. However, the three atypical antipsychotic drugs failed to reveal any significant differences in the composite cognitive scores at the study endpoint. In addition, the three drugs all significantly improved clinical measures without significant differences between the drugs after 6 months. These results suggest that the atypical antipsychotics, olanzapine, risperidone and aripiprazole may improve specific cognitive domains with similar global clinical efficacy. In clinical practice, it may be feasible to choose corresponding atypical antipsychotics according to impaired cognitive domains.