Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS: After treatment for 24 weeks, the change in HbA1c was -0.93% (95% CI -1.03 to -0.83) (-10.2 mmol/mol [-11.3 to -9.1]) and -0.87% (-0.99 to -0.76) (-9.5 mmol/mol [-10.8 to -8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was -0.05% (95% CI -0.18 to 0.07) (-0.5 mmol/mol [-2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS: SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.

Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomized, double-blind, phase 3 trial (CMAS).

Chiglitazar (Carfloglitazar) is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes. In this randomized phase 3 trial, we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen. Eligible patients were randomized (1:1:1) to receive chiglitazar 32 mg (n = 245), chiglitazar 48 mg (n = 246), or sitagliptin 100 mg (n = 248) once daily for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin A1C (HbA1c) from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin. Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of -1.40%, -1.47%, and -1.39% for chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg, respectively. Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg, with mean differences of -0.04% (95% confidential interval (CI) -0.22 to 0.15) and -0.08% (95% CI -0.27 to 0.10), respectively. Compared with sitagliptin, greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar. Overall adverse event rates were similar between the groups. A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported. The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions, thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.

Role of surface charge on the interaction between carbon nanodots and human serum albumin.

Carbon nanodots (Cdots) have aroused widespread concerns in the field of biomedical applications. In order to achieve better implications of behavior of Cdots in the biological environment, an array of spectroscopic, electrochemical and calorimetric techniques were performed to study the interaction of Cdots possessing different charges with human serum albumin (HSA) in physiological condition. Two polymer, polyethylene glycol (PEG) and polyetherimide (PEI), were applied to passivate the bare Cdots to achieve the Cdots with different surface charge, namely negatively charged PEG Cdots and positively charged PEI Cdots. The fluorescence of HSA was obviously quenched by both Cdots in a charge-independent behavior through a dynamic collision mechanism. Moreover, the association affinity of PEG Cdots or PEI Cdots bound to HSA was very close to each other. In addition, PEG Cdots with diverse content exhibited little effects on the secondary structure of HSA while only high content of PEI Cdots induced obvious conformation perturbation of HSA. The electrostatic forces dominate the association between HSA and PEI Cdots while the association of PEG Cdots to HSA is initiated by hydrophobic and van der Waals forces. Furthermore, the results of isothermal titration calorimetry revealed that both the interaction was driven by favorable entropy and enthalpy, which confirmed that these association processes are thermodynamically spontaneous. Finally, the sites marker competitive experiment showed that the association sites of Cdots with HSA exhibit a charge dependent manner, namely PEG Cdots effectively occupy the site I of HSA while the association sites of PEI Cdots are mainly located in site II.

Decreased interhemispheric functional connectivity in insula and angular gyrus/supramarginal gyrus: Significant findings in first-episode, drug-naive somatization disorder.

Neuroimaging data have demonstrated brain functional alterations in patients with somatization disorder (SD). However, there is little information on interhemispheric resting-state functional connectivity (FC) in SD. In this study, resting-state functional magnetic resonance imaging (fMRI) and voxel-mirrored homotopic connectivity (VMHC) were applied to examine the changes of interhemispheric FC of the whole brain in patients with SD. A total of 25 first-episode, medication-naive SD patients and 28 age-, sex-, education-matched healthy controls (HC) underwent resting-state fMRI, and the data were analyzed by VMHC. Compared with HC, patients had lower VMHC in the angular gyrus/supramarginal gyrus (AG/SG) and insula. The reproducibility of the results was validated using the split-half and leave-one-out validations. No significant correlation was found between the VMHC in AG/SG or insula and clinical variables. Our findings indicate that the interhemispheric FC in the AG/SG and insula is decreased in first-episode, treatment-naive patients with SD, and thus provide new insight for disruption of interhemispheric FC in the pathophysiological mechanism of SD.

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.

Increased Causal Connectivity Related to Anatomical Alterations as Potential Endophenotypes for Schizophrenia.

Anatomical and functional abnormalities in the cortico-cerebellar-thalamo-cortical circuit have been observed in schizophrenia patients and their unaffected siblings. However, it remains unclear to the relationship between anatomical and functional abnormalities within this circuit in schizophrenia patients and their unaffected siblings, which may serve as potential endophenotypes for schizophrenia.Anatomical and resting-state functional magnetic resonance imaging data were acquired from 49 first-episode, drug-naive schizophrenia patients, 46 unaffected siblings, and 46 healthy controls. Data were analyzed by using voxel-based morphometry and Granger causality analysis.The patients and the siblings shared anatomical deficits in the left middle temporal gyrus (MTG) and increased left MTG-left angular gyrus (AG) connectivity. Moreover, the left MTG-left AG connectivity negatively correlates to the duration of untreated psychosis in the patients.The findings indicate that anatomical deficits in the left MTG and its increased causal connectivity with the left AG may serve as potential endophenotypes for schizophrenia with clinical implications.

Abnormal regional homogeneity and its correlations with personality in first-episode, treatment-naive somatization disorder.

BACKGROUND: Structural and functional abnormalities of the default mode network (DMN) and their correlations with personality have been found in somatization disorder (SD). However, no study is conducted to identify regional neural activity and its correlations with personality in SD. In this study, regional homogeneity (ReHo) was applied to explore whether abnormal regional neural activity is present in patients with SD and its correlations with personality measured by Eysenck Personality Questionnaire (EPQ). METHODS: Twenty-five first-episode, treatment-naive patients with SD and 28 sex-, age-, and education-matched healthy controls participated in the whole study. During the scanning, all subjects were instructed to lie still with their eyes closed and remain awake. A ReHo approach was employed to analyze the data. RESULTS: The SD group had a significantly increased ReHo in the left angular gyrus (AG) compared to healthy controls. The increased ReHo positively correlated to the neuroticism scores of EPQ (EPQ-N). No other correlations were detected between the ReHo values and other related factors, such as symptom severity and education level. CONCLUSIONS: Our results suggest that abnormal regional neural activity of the DMN may play a key role in SD with clinical implications and emphasize the importance of the DMN in the pathophysiological process of SD.

Alterations in white matter integrity in first-episode, treatment-naive patients with somatization disorder.

White matter (WM) abnormality in somatization disorder (SD) has not been reported yet. This study was designed to elucidate the alterations in WM integrity in SD. A total of 25 patients with SD and 28 healthy controls were enrolled in the study. WM integrity was analyzed using tract-based spatial statistics. No differences were found between the patients and the controls for fractional anisotropy (FA) values, mean diffusivity (MD), axial diffusivity, and radial diffusivity values at the corrected p<0.05 level. Patients with SD had significantly decreased FA values in the cingulum and inferior fronto-occipital fasciculus, and significantly increased MD values in the anterior thalamic radiation and corticospinal tract compared with the controls at the uncorrected p<0.005 level. Somatization severity was correlated with the FA values of the cingulum and inferior fronto-occipital fasciculus in the patients. The patients exhibit suggestive alterations in WM integrity in the cingulum, inferior fronto-occipital fasciculus, anterior thalamic radiation, and corticospinal tract.

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.

Increased Cerebellar Functional Connectivity With the Default-Mode Network in Unaffected Siblings of Schizophrenia Patients at Rest.

The default-mode network (DMN) is vital in the neurobiology of schizophrenia, and the cerebellum participates in the high-order cognitive network such as the DMN. However, the specific contribution of the cerebellum to the DMN abnormalities remains unclear in unaffected siblings of schizophrenia patients. Forty-six unaffected siblings of schizophrenia patients and 46 healthy controls were recruited for a resting-state scan. The images were analyzed using the functional connectivity (FC) method. The siblings showed significantly increased FCs between the left Crus I and the left superior medial prefrontal cortex (MPFC), as well as between the lobule IX and the bilateral MPFC (orbital part) and right superior MPFC compared with the controls. No significantly decreased FC was observed in the siblings relative to the controls. The analyses were replicated in 49 first-episode, drug-naive patients with schizophrenia, and the results showed that the siblings and the patients shared increased FCs between the left Crus I and the left superior MPFC, as well as between the lobule IX and the left MPFC (orbital part) compared with the controls. These findings suggest that increased cerebellar-DMN connectivities emerge earlier than illness onset, which highlight the contribution of the cerebellum to the DMN alterations in unaffected siblings. The shared increased cerebellar-DMN connectivities between the patients and the siblings may be used as candidate endophenotypes for schizophrenia.

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

The 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.

Dissociation of anatomical and functional alterations of the default-mode network in first-episode, drug-naive schizophrenia.

OBJECTIVE: Anatomical and functional alterations of the default-mode network (DMN) have been implicated in the pathophysiology of schizophrenia. However, no study is engaged to explore whether structural and functional abnormalities of the DMN overlap in schizophrenia. This study was undertaken to examine whether anatomical and functional abnormalities are present in similar or different brain regions of the DMN in first-episode, drug-naive schizophrenia. METHODS: Forty-nine first-episode, drug-naive schizophrenia patients and 50 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging (fMRI) scanning. The voxel-based morphometry (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) methods were used to analyze imaging data. RESULTS: The patients exhibited significantly decreased gray matter volume (GMV) in the left medial prefrontal cortex (orbital part) and increased fALFF in the left posterior cingulate cortex compared with the controls. No overlap of brain regions with anatomical and functional abnormalities was observed in the patient group. There was also no correlation between decreased GMV/increased fALFF and clinical variables in patients. CONCLUSIONS: A dissociation pattern of brain regions with anatomical and functional changes within the DMN is revealed in schizophrenia patients. SIGNIFICANCE: Our findings suggest that brain functional and anatomical abnormalities within the DMN might contribute independently to the pathophysiology of 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 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.

Abnormal causal connectivity by structural deficits in first-episode, drug-naive schizophrenia at rest.

Anatomical deficits and resting-state functional connectivity (FC) alterations in prefrontal-thalamic-cerebellar circuit have been implicated in the neurobiology of schizophrenia. However, the effect of structural deficits in schizophrenia on causal connectivity of this circuit remains unclear. This study was conducted to examine the causal connectivity biased by structural deficits in first-episode, drug-naive schizophrenia patients. Structural and resting-state functional magnetic resonance imaging (fMRI) data were obtained from 49 first-episode, drug-naive schizophrenia patients and 50 healthy controls. Data were analyzed by voxel-based morphometry and Granger causality analysis. The causal connectivity of the integrated prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit was partly affected by structural deficits in first-episode, drug-naive schizophrenia as follows: (1) unilateral prefrontal-sensorimotor connectivity abnormalities (increased driving effect from the left medial prefrontal cortex [MPFC] to the sensorimotor regions); (2) bilateral limbic-sensorimotor connectivity abnormalities (increased driving effect from the right anterior cingulate cortex [ACC] to the sensorimotor regions and decreased feedback from the sensorimotor regions to the right ACC); and (3) bilateral increased and decreased causal connectivities among the sensorimotor regions. Some correlations between the gray matter volume of the seeds, along with their causal effects and clinical variables (duration of untreated psychosis and symptom severity), were also observed in the patients. The findings indicated the partial effects of structural deficits in first-episode, drug-naive schizophrenia on the prefrontal-thalamic (limbic)-cerebellar (sensorimotor) circuit. Schizophrenia may reinforce the driving connectivities from the left MPFC or right ACC to the sensorimotor regions and may disrupt bilateral causal connectivities among the sensorimotor regions.

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.

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.

Decreased default-mode network homogeneity in unaffected siblings of schizophrenia patients at rest.

The dysconnectivity hypothesis proposes that abnormal resting state connectivity within the default-mode network (DMN) plays a key role in schizophrenia. Little is known, however, about alterations of the network homogeneity (NH) of the DMN in unaffected siblings of patients with schizophrenia. Unaffected siblings have unique advantages as subjects of neuroimaging studies independent of the clinical and treatment issues that complicate studies of the patients themselves. In the present study, we investigated NH of the DMN in unaffected siblings of schizophrenia. Participants comprised 46 unaffected siblings of schizophrenia patients and 50 age-, sex-, and education-matched healthy controls who underwent resting state functional magnetic resonance imaging (fMRI). Automated NH and group independent component analysis (ICA) approaches were used to analyze the data. Compared with healthy controls, the unaffected siblings of schizophrenia patients showed decreased DMN homogeneity in the left precuneus. No significantly increased DMN homogeneity was found in the sibling group relative to the control group. Our results suggest that there is decreased NH of the DMN in unaffected siblings of schizophrenia patients and indicate that the alternative perspective of examining the DMN NH in patients׳ siblings may improve understanding of the nature of 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.