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Insomnia is one of the most common health complaints, with a high prevalence of 30~50% in the general population. In particular, neuroimaging research has revealed that widespread dysfunctions in brain regions involved in hyperarousal are strongly correlated with insomnia. However, whether the topology of the intrinsic connectivity is aberrant in insomnia remains largely unknown. In this study, resting-state functional magnetic resonance imaging (rsfMRI) in conjunction with graph theoretical analysis, was used to construct functional connectivity matrices and to extract the attribute features of the small-world networks in insomnia. We examined the alterations in global and local small-world network properties of the distributed brain regions that are predominantly implicated in the frontostriatal network between 30 healthy subjects with insomnia symptoms (IS) and 62 healthy subjects without insomnia symptoms (NIS). Correlations between the small-world properties and clinical measurements were also generated to identify the differences between the two groups. Both the IS group and the NIS group exhibited a small-worldness topology. Meanwhile, the global topological properties didn't show significant difference between the two groups. By contrast, participants in the IS group showed decreased regional degree and efficiency in the left inferior frontal gyrus (IFG) compared with subjects in the NIS group. More specifically, significantly decreased nodal efficiency in the IFG was found to be negatively associated with insomnia scores, whereas the abnormal changes in nodal betweenness centrality of the right putamen were positively correlated with insomnia scores. Our findings suggested that the aberrant topology of the salience network and frontostriatal connectivity is linked to insomnia, which can serve as an important biomarker for insomnia.

Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia.

We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal-limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

In the present study, we investigated differences in resting-state brain activity in patients with bipolar depression (BD) and unipolar depression (UD) by measuring the amplitude of low-frequency fluctuation (ALFF) of functional magnetic resonance imaging (fMRI) signals. Twenty-one BD and 21 gender-, age-, and education-matched UD patients participated in the fMRI analysis. We compared the differences in the ALFF between the two groups and investigated the correlation between clinical measurements and ALFF in the regions displaying significant group differences. BD subjects displayed significantly decreased ALFF in the left superior parietal lobule and the left posterior insula (l-PI). They also displayed increased ALFF in the right dorsal anterior insula (r-dAI) when compared to the UD group. Moderate negative correlations were found between the Hamilton Depression Rating Scale score (HAMD) and the ALFF in the l-PI for the BD ( r = −0.44, P = 0.02) and UD ( r = −0.45, P = 0.02) groups. Our results support the notion that insular subregions may contribute to the precise differentiation between BD and UD.

OBJECTIVE: This study aimed to investigate the single nucleotide polymorphisms (SNPs) of neuropeptide Y (NPY) and major depressive disorder (MDD) in Chinese Han population. DESIGN: Prospective and randomized studies were carried out. PATIENTS: A total of 700 patients (324 male and 376 female; mean age = 40±14.9 years) with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls (313 male and 360 female; mean age = 41.9±17.2 years) were used to investigate the relationship between SNPs of NPY and the pathogenesis of MDD. A total of 417 patients (195 male and 202 female; mean age = 36±14.2 years) diagnosed with MDD and 314 healthy controls (153 male and 161 female; mean age = 37.9±14.2 years) from Chinese Han population were used to verify the relationship between SNPs of NPY and the pathogenesis of MDD. INTERVENTION AND OUTCOME: Ligase detection reactions were performed to detect the SNP sites of NPY. A series of statistical methods was carried out to investigate the correlation between the NPY gene SNP and MDD. RESULTS: Statistical analysis showed a significant correlation between the SNP sites rs16139 in NPY and the morbidity of depression. Patients with MDD have a lower frequency of A-allele in rs16139 in replicate samples from Chinese Han population. However, the frequency varied between male and female patients. CONCLUSION: The gene polymorphism loci rs16139 was closely related to MDD in Chinese Han population.

Objective: Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression CUD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Methods: Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. Results: We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right middle frontal gyrus, the right dorsal anterior insular, the right cerebellum posterior gyrus, and the right posterior cingulate cortex showed abnormality specific to the UD group. Conclusions: We found brain regions showing resting state ReHo differences and examined their sensitivity and specificity, suggesting a potential neuroimaging biomarker to distinguish between BD-dep and UD patients. We further clarified the pathophysiological abnormality of these regions for each of the two patient populations. (C) 2012 Elsevier Inc. All rights reserved.

Background Major depressive disorder (MDD) is a highly heritable psychiatric disease, and the existing literature is not robust enough to allow us to evaluate whether MDD-associated biomarkers are state-independent heritable endophenotypes or state markers related to depression per se. Methods Twenty two patients diagnosed with MDD, 22 siblings, as well as 26 gender-, age-, and education-matched healthy subjects, participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the differences in the fractional amplitude of low-frequency fluctuation (fALFF) among the three groups and investigated the correlation between clinical measurements and fALFF in the regions displaying significant group differences. Results Both the MDD and siblings groups showed an increased fALFF in the left middle frontal gyrus (l-MFG, Brodmann Area, BA 10) compared to the healthy controls. The MDD groups demonstrated an increased fALFF in the right dorsal medial frontal gyrus (r-DMFG, BA 9) and a decreased fALFF in the bilateral lingual gyrus relative to siblings and healthy controls. Limitations Medication effects, an inability to control subjects' thoughts during imaging. Conclusions Our results suggest that the dysfunction in the l-MFG may represent an imaging endophenotype which may indicate a risk for MDD. The r-DMFG may play a critical role in depressive symptomatology and may reveal therapeutic target for MDD.

Objective This study aimed to investigate the association of galanin (GAL) gene and the development of depression in the Chinese Han population. Methods A total of 700 patients with depression who met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 673 healthy controls were used in this study. Ligase detection reactions were performed on 10 selected single nucleotide polymorphism (SNP) sites in the GAL gene. A series of statistical methods were carried out to investigate the correlation between the GAL gene SNP and the patient susceptibility to depression. Results The SNPs of rs694066 in the GAL gene showed a positive correlation with MDD. Compared with the healthy controls, lower frequency of G/G genotype and higher frequency of A/G genotype were observed in rs694066 in MDD patients, a lower frequency of G-allele and higher frequency of A-allele were observed in rs694066. These correlations were more pronounced in the 376 female patients and 360 female control subjects than in the 324 male patients and 313 healthy male subjects. Conclusions This study investigated the relationship between the GAL gene SNP and the susceptibility to depression in the Chinese Han population. The findings clearly indicate that the GAL gene polymorphism is closely correlated to the incidence of depression in the Chinese Han female patients.