Miaoyu Yu

Functional and anatomical brain deficits in drug-naive major depressive disorder.

BACKGROUND Functional and anatomical deficits have been involved in the neurobiology of major depressive disorder (MDD). However, no study has ever been conducted to examine whether and how functional alterations are related to anatomical deficits in MDD. This study aimed to determine the association between brain functional and anatomical deficits in drug-naive MDD. METHODS Forty-four patients with MDD and 44 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. The voxel-based morphometry (VBM) and amplitude of low-frequency fluctuation (ALFF) methods were used to analyze the imaging data. RESULTS VBM analysis showed gray matter volume (GMV) reductions in the parietal-temporal regions (i.e., the right inferior temporal gyrus and the left angular gyrus). Functional alterations revealed by ALFF mainly occurred in the temporal regions (i.e., the left middle temporal gyrus and the right superior temporal gyrus) and the cerebellum (i.e., the culmen). There is no overlap between brain regions with functional alterations and anatomical deficits in the patients and their subgroups (first-episode depression and recurrent depression). The episode number and the illness duration were correlated with the mean GMV values of the left angular gyrus. CONCLUSIONS A dissociation pattern of brain functional and anatomical deficits is observed in MDD. Our findings suggest that brain functional and anatomical deficits contribute independently to the neurobiology of MDD.

Increased cerebellar-default-mode-network connectivity in drug-naive major depressive disorder at rest.

AbstractThe default-mode network (DMN) has been implicated in the neurobiology of major depressive disorder (MDD), and the cerebellum is suggested to be involved in high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN alterations remains equivocal. This study was conducted to examine the cerebellar-DMN connectivity in drug-naive MDD directly by using the cerebellum Crus I as seeds.Forty-four drug-naive MDD patients and 44 healthy controls participated in the resting-state scan. Functional connectivity (FC) was applied to analyze the images.Significantly increased FCs were observed between the right Crus I and the right inferior frontal cortex (orbital part)/superior temporal pole, bilateral MPFC (orbital part), and left middle temporal gyrus in the patients compared with the controls. There was a significantly positive correlation between the z values of the right Crus I–bilateral MPFC (orbital part) connectivity and the scores of Automatic Thoughts Questionnaire in the patients (r = 0.329, P = 0.029).The findings reveal that depressed patients have increased cerebellar-DMN connectivity with clinical significance, and thus highlight the contribution of the cerebellum to the DMN alterations in neurobiology of MDD.

Decreased insular connectivity in drug-naive major depressive disorder at rest.

BACKGROUND The insula has extensive links to the fronto-limbic circuit and associated regions, which is involved in the neurobiology of major depressive disorder (MDD). However, few studies are designed to examine the insular connectivity in MDD. This study was performed to examine the insular connectivity in drug-naive MDD directly by using the insular cortices as seeds. METHODS Functional magnetic resonance imaging data were obtained from 44 drug-naive MDD patients and 44 healthy controls at rest. The functional connectivity (FC) method was used to analyze the images. RESULTS Significantly decreased FCs were found between the right insula and the left middle frontal gyrus (MFG, orbital part), left superior temporal gyrus (STG), right putamen, and right middle occipital gyrus (MOG), and between the left insula and the left superior temporal pole and right MOG in the patients compared with the controls. There were significantly negative correlations between the z values of the left insula-left superior temporal pole connectivity and the current episode duration (r=-0.332, p=0.028), between the z values of the right insula-left STG connectivity and the episode number (r=-0.343, p=0.023), and between the z values of the right insula-left MFG (orbital part) connectivity and the Automatic Thoughts Questionnaire scores (r=-0.359, p=0.017) in the patients. CONCLUSIONS The findings reveal that depressed patients have decreased insular connectivity with the fronto-limbic circuit, hate circuit, and visual regions, and suggest that the insula may act as an integration center of emotional processing which is disrupted in the depressed patients.

Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder

Background: Evidence of brain structural and functional alterations have been implicated in patients with somatization disorder (SD). However, little is known about brain functional connectivity in SD. In the present study, resting-state functional magnetic resonance imaging (fMRI) and graph theory were used to obtain a comprehensive view of whole-brain functional connectivity and to investigate the changes of voxel-wise functional networks in patients with SD. Methods: Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex- and education-matched healthy controls (HCs) underwent resting-state fMRI. The graph theory approach was employed to analyze the data. Results: Compared to the HCs, patients with SD showed significantly increased functional connectivity strength in the right inferior temporal gyrus (ITG). There is a significant positive correlation between the z-values of the cluster in the right ITG and Hamilton Anxiety Scale scores. Conclusions: Our findings indicate that there is a disruption of the functional connectivity pattern in the right ITG in first-episode, treatment-naive patients with SD, which bears clinical significance.

Increased short-range and long-range functional connectivity in first-episode, medication-naive schizophrenia at rest

OBJECTIVE Schizophrenia is conceived as a disconnection syndrome and anatomical distance may affect functional connectivity (FC) in schizophrenia patients. However, whether and how anatomical distance affects FC remains unclear in first-episode, medication-naive schizophrenia at rest. METHODS Forty-nine schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scanning. Regional FC strength was computed for each voxel in the brain, which was further divided into short-range and long-range FC strength. RESULTS The patients exhibited increased short-range positive FC strength in the left superior medial frontal gyrus, and increased long-range positive FC strength in the right angular gyrus and bilateral posterior cingulate cortex (PCC)/precuneus compared with the controls. Further seed-based FC analysis showed that the left superior medial frontal gyrus had increased short-range FC with the right inferior frontal gyrus, while the right angular gyrus and bilateral PCC/precuneus had increased long-range FC with the prefrontal gyrus. No significant correlation was observed between abnormal FC strength and clinical variables in the patient group. CONCLUSIONS The findings reveal a pattern of increased anatomical distance affecting FC in the patients, with the results of increased short-range positive FC strength in the anterior default-mode network (DMN) and increased long-range positive FC strength in the posterior DMN in schizophrenia, and highlight the importance of the DMN in the neurobiology of schizophrenia.

Resting-state cerebellar-cerebral networks are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings

Dysconnectivity hypothesis posits that schizophrenia is a disorder with dysconnectivity of the cortico-cerebellar-thalamic-cortical circuit (CCTCC). However, it remains unclear to the changes of the cerebral connectivity with the cerebellum in schizophrenia patients and unaffected siblings. Forty-nine patients with first-episode, drug-naive schizophrenia patients, 46 unaffected siblings of schizophrenia patients and 46 healthy controls participated in the study. Seed-based resting-state functional connectivity approach was employed to analyze the data. Compared with the controls, the patients and the siblings share increased default-mode network (DMN) seed – right Crus II connectivity. The patients have decreased right dorsal attention network (DAN) seed – bilateral cerebellum 4,5 connectivity relative to the controls. By contrast, the siblings exhibit increased FC between the right DAN seed and the right cerebellum 6 and right cerebellum 4,5 compared to the controls. No other abnormal connectivities (executive control network and salience network) are observed in the patients/siblings relative to the controls. There are no correlations between abnormal cerebellar-cerebral connectivities and clinical variables. Cerebellar-cerebral connectivity of brain networks within the cerebellum are differently affected in first-episode, drug-naive schizophrenia patients and unaffected siblings. Increased DMN connectivity with the cerebellum may serve as potential endophenotype for schizophrenia.

Decreased regional activity and network homogeneity of the fronto-limbic network at rest in drug-naive major depressive disorder

Objective: The fronto-limbic network is implicated in the neurobiology of major depressive disorder. However, no studies are designed to assess directly the abnormalities of regional activity and network homogeneity of this network in major depressive disorder. Methods: A total of 44 drug-naive major depressive disorder patients and 44 healthy controls participated in the study, and resting-state functional magnetic resonance imaging data were obtained. The fractional amplitude of low-frequency fluctuations and network homogeneity methods were employed to analyze the data. Results: Compared with the controls, the patients exhibited reduced fractional amplitude of low-frequency fluctuations in the right middle frontal gyrus (orbital part) and decreased network homogeneity in the left middle frontal gyrus. There was no correlation between abnormal fractional amplitude of low-frequency fluctuations/network homogeneity and clinical variables. Conclusions: Our findings suggest that decreased regional activity and network homogeneity in the frontal cortex may be the key impairment of the fronto-limbic network in major depressive disorder, and thus highlight the importance of the fronto-limbic network in the neurobiology of major depressive disorder.

Dissociation of Regional Activity in Default Mode Network in Medication-Naive, First-Episode Somatization Disorder

Background Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest. Methods Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data. Results Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD. Conclusions Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.

Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients

OBJECTIVE Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. METHODS Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. RESULTS The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. CONCLUSIONS A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. SIGNIFICANCE Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients.

Unidirectionally affected causal connectivity of cortico-limbic-cerebellar circuit by structural deficits in drug-naive major depressive disorder.

BACKGROUND Structural deficits and resting-state functional connectivity (FC) alterations in the cortico-limbic-cerebellar circuit have been implicated in the neurobiology of major depressive disorder (MDD). This study was conducted to examine the causal connectivity biased by structural deficits in MDD patients. METHODS Resting-state functional magnetic resonance imaging data were acquired from 44 drug-naive MDD patients and 44 healthy controls. Granger causality analysis (GCA) was used to analyze the functional data. RESULTS We previously observed two brain regions, the left angular gyrus (AG) and the right inferior temporal gyrus (ITG), with reduced gray matter volume (GMV), which were selected as seeds. Compared with healthy controls, the patients showed inhibitory effect from the left AG to the left superior temporal gyrus (STG) and the left inferior frontal gyrus (IFG, opercular part), and from the right ITG to bilateral cerebellum 6. In contrast, the right ITG exhibited excitatory effect to the right insula. However, no abnormal feedback effect was observed in patients. There was no significant correlation between abnormal causal effect and clinical variables, such as HRSD scores, illness duration, and episode number. CONCLUSIONS Brain regions within the cortico-limbic-cerebellar circuit showed unidirectionally affected causal connectivities driven by structural deficits in MDD. The findings suggest that the causal topology of the cortico-limbic-cerebellar circuit may be disrupted unidirectionally by structural deficits in MDD.