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Abstrac: Objectives: This study aimed to preliminarily and exploratorily examine the associations between childhood trauma (CT), its subtypes, and personality traits among unaffected first-degree relatives (FDR, children, or siblings) of patients with major depressive disorder (MDD). Methods: The study sample included three subgroups: MDD patients (N = 85), Patients' FDRs (N = 35), and healthy control individuals (HC, N = 89). The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma and the Eysenck Personality Questionnaire was used to assess personality traits. Results: Significant differences were found in a few personality traits (p < 0.05 for extraversion, neuroticism, and psychoticism) among MDD patients, FDR, and HC, and there were no significant differences between HC and FDR. In the FDR group, compared with those without CT, participants with CT scored significantly higher for neuroticism (N) (F = 3.246, p = 0.046). CT was significantly associated with N, psychoticism (P) and Lie (L), and the strongest association was between CT total score and N. Significantly positive correlations were found between N and sexual abuse (SA) (r = 0.344, p = 0.043), emotional neglect (EN) (r = 0.394, p = 0.019), physical neglect (PN) (r = 0.393, p = 0.019), and CTQ total score (r = 0.452, p = 0.006); between P and CTQ total score (r = 0.336, p = 0.049); and significant negative correlations were found between L and EN (r = -0.446, p = 0.007), CTQ total score (r = -0.375, p = 0.027). Conclusion: In unaffected FDRs, there were significant associations between childhood trauma and a few personality traits, including neuroticism, psychoticism, and lie, and emotional neglect was significantly associated with neuroticism. [ABSTRACT FROM AUTHOR]

Background: Insomnia is one of the main symptom correlates of major depressive disorder (MDD), but the neural mechanisms underlying the multifaceted interplay between insomnia and depression are not fully understood. Materials and methods: Patients with MDD and high insomnia (MDD-HI, n = 24), patients with MDD and low insomnia (MDD-LI, n = 37), and healthy controls (HCs, n = 51) were recruited to participate in the present study. The amplitude of low-frequency fluctuations (ALFF) during the resting state were compared among the three groups. results: We observed ALFF differences between the three groups in the right inferior frontal gyrus/anterior insula (IFG/AI), right middle temporal gyrus, left calcarine, and bilateral dorsolateral prefrontal cortex (dlPFC). Further region of interest (ROI) comparisons showed that the increases in the right IFG/AI reflected an abnormality specific to insomnia in MDD, while increases in the bilateral dlPFC reflected an abnormality specific to MDD generally. Increased ALFF in the right IFG/AI was also found to be correlated with sleep disturbance scores when regressing out the influence of the severity of anxiety and depression. conclusion: Our findings suggest that increased resting state ALLF in IFG/AI may be specifically related to hyperarousal state of insomnia in patients with MDD, independently of the effects of anxiety and depression. Background: Insomnia is one of the main symptom correlates of major depressive disorder (MDD), but the neural mechanisms underlying the multifaceted interplay between insomnia and depression are not fully understood. Materials and methods: Patients with MDD and high insomnia (MDD-HI, n = 24), patients with MDD and low insomnia (MDD-LI, n = 37), and healthy controls (HCs, n = 51) were recruited to participate in the present study. The amplitude of low-frequency fluctuations (ALFF) during the resting state were compared among the three groups. results: We observed ALFF differences between the three groups in the right inferior frontal gyrus/anterior insula (IFG/AI), right middle temporal gyrus, left calcarine, and bilateral dorsolateral prefrontal cortex (dlPFC). Further region of interest (ROI) comparisons showed that the increases in the right IFG/AI reflected an abnormality specific to insomnia in MDD, while increases in the bilateral dlPFC reflected an abnormality specific to MDD generally. Increased ALFF in the right IFG/AI was also found to be correlated with sleep disturbance scores when regressing out the influence of the severity of anxiety and depression. conclusion: Our findings suggest that increased resting state ALLF in IFG/AI may be specifically related to hyperarousal state of insomnia in patients with MDD, independently of the effects of anxiety and depression. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder (MDD). In a randomized, double-blind trial of 8 weeks active treatment, patients with non-psychotic MDD were randomized to duloxetine 60 mg ( n = 238) or paroxetine 20 mg ( n = 240) once daily. Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression (HAMD17) using a non-inferiority test with a margin of 2.2. Secondary efficacy measures included the HAMD17 subscales, Hamilton Rating Scale for Anxiety, Clinical Global Impressions–Severity, Patient Global Impressions–Improvement, Somatic Symptoms Inventory and Visual Analog Scales (VAS) for pain. Safety measures included treatment-emergent adverse events (TEAE), vital signs, weight, laboratory analyses and electrocardiograms. Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD17 change (0.71) was less than the non-inferiority margin. Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain, where the pooled mean was lower in the duloxetine group (17.1) compared with the paroxetine group (20.3, P = 0.048). No significant differences were observed in the number of early discontinuations and overall TEAE. However, significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations. No clinically relevant changes in laboratory values, vital signs, weight or electrocardiograms were observed with either treatment. The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample. [ABSTRACT FROM AUTHOR]

Objective Anxious depression is a distinct clinical subtype of major depressive disorder (MDD) characterized by palpitations, somatic complaints, altered interoceptive awareness, high risk of suicide, and poor response to pharmacotherapy. However, the neural mechanisms of anxious depression are still not well understood. In this study we investigated changes in neural oscillation during the resting-state of patients with anxious depression by measuring differences in the amplitude of low-frequency fluctuation (ALFF). Methods Resting-state functional magnetic resonance imaging was acquired in 31 patients with anxious depression, 18 patients with remitted depression, as well as 68 gender- and age-matched healthy participants. We compared the differences both in the ALFF and fractional ALFF (fALFF) among the three groups. We also examined the correlation between the ALFF/fALFF and the severity of anxiety as well as depression. Results Anxious depression patients showed increased ALFF/fALFF in the right dorsal anterior insular cortex and decreased ALFF/fALFF in the bilateral lingual gyrus relative to remitted depression patients and healthy controls. The increased ALFF in the dorsal anterior insula was also positively correlated with stronger anxiety in the anxious depression group. Anxious depression patients also displayed increased fALFF in the right ventral anterior cingulate cortex (ACC) compared to remitted depression patients and healthy controls. Conclusions Our results suggest that alterations of the cortico-limbic networks, including the right dorsal anterior insula and right ventral ACC, may play a critical role in the physiopathology of anxious depression. [ABSTRACT FROM AUTHOR]

Abstract: Medical intervention for major depressive disorder (MDD) can be more appropriately focused through the identification and characterization of neurobiological markers that are specific to the disorder, and this study aims to examine the abnormality in the fractional amplitude of low-frequency fluctuation (fALFF) and the amplitude of low-frequency fluctuation (ALFF) in currently depressed and remitted female MDD patients and to correlate these fluctuations with clinical markers of MDD. Nineteen currently depressed female patients, 19 remitted female patients, as well as 19 age- and education-matched healthy females participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the fALFF/ALFF maps among the three groups and investigated the correlation between clinical measurements and statistically significant differences in the fALFF/ALFF of various brain regions. Compared with healthy controls, both currently depressed and remitted patients showed increased fALFF/ALFF in the right putamen. Currently depressed MDD patients showed increased fALFF/ALFF in the right ventral median frontal gyrus relative to both the remitted MDD group and the healthy control group. The ALFF of the right precuneus was found to be positively correlated with the number of depressive episodes and the fALFF of the right precuneus to be positively correlated with the disease duration in currently depressed MDD patients. An abnormal fALFF/ALFF in the right ventral median frontal gyrus was found only in currently depressed patients, suggesting that such an anomaly may play a critical role in depressive symptomatology and may be a therapeutic target for MDD. An abnormal fALFF/ALFF in the right putamen is a potential candidate as a trait-related marker of vulnerability to major depression. [Copyright &y& Elsevier]

Abstract: 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 (UD), 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: Objective: This study aimed to determine the 12-month and lifetime prevalence of major depressive episode (MDE) and their socio-demographic correlates in both the urban and rural areas of Beijing, China. Methods: A total of 4767 adults were randomly selected and interviewed in Beijing using the Composite International Diagnostic Interview (CIDI 1.0). Basic socio-demographic and clinical data were collected during the interviews. Results: The overall 12-month prevalence of MDE was 3.2%; 2.8% and 3.8% for men and women, respectively. The overall lifetime prevalence of MDE was 5.3%; 4.4% and 6.3% for men and women, respectively. Being older than 25 years of age was independently associated with increased risk of MDE. Sixteen point three percent of the subjects with lifetime MDE attempted suicide while the rate of suicide attempts was only 0.2% in subjects without MDE. The percentage of subjects with MDE who received any type of treatment from medical practitioners was 33.1%; of them, only 5.4% sought help from mental health professionals. Conclusions: National epidemiologic surveys are needed to further explore the prevalence of MDE in China. The low percentage of subjects treated for MDE constitutes a major public health problem that should be urgently addressed. [Copyright &y& Elsevier]

Abstract: Schizophrenic outpatients (n =102) whose condition had stabilized with clozapine (CLZ) therapy and were being maintained on CLZ were followed for 1 year. Clinical status and concentrations of serum clozapine (CLZ) and its metabolite norclozapine (NCLZ) were evaluated periodically or when relapse occurred. Relapse was defined as a significant exacerbation of psychotic symptoms or hospitalization. Thirty-three patients relapsed and 69 did not. Relapse patients displayed significantly lower serum concentrations of CLZ and a sum of CLZ and NCLZ at endpoint than non-relapses (CLZ: 162 ng/ml vs. 237 ng/ml, p <0.001; CLZ+NCLZ: 225 ng/ml vs. 301 ng/ml, p <0.001). When all subjects were pooled together, a significant inverse correlation was observed between percent increase in the total score on the Brief Psychiatric Rating Scale (BPRS) from baseline and serum levels of CLZ alone (r=0.404, p <0.001) and the sum of CLZ and NCLZ (r=0.364, p <0.001). Relapses and non-relapses were well separated by a threshold CLZ serum concentration of 200 ng/ml with a sensitivity of 73% and a specificity of 80%. The threshold value represented about a 40% lower serum CLZ level than concentration achieved in acute treatment. Survival analysis showed a similarity of the relapse risk over time defined by the CLZ serum threshold and by symptomatic criteria. These results suggest that effective relapse prevention may require maintenance of patients at CLZ serum concentrations above 200 ng/ml and above 60% of the acute-phase level during long-term maintenance treatment of schizophrenia. [Copyright &y& Elsevier]