Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Association between T-182C, G1287A polymorphism in NET gene and suicidality in major depressive disorder in Chinese patients.

Objective: Previous studies have implicated norepinephrine transporter gene (NET) polymorphisms in the etiology of major depressive disorder (MDD). A functional NET T-182C polymorphism (rs2242446) in the promoter region and a synonymous polymorphisms G1287A in the exon 9 (rs5569) were associated with MDD in different populations. However, few studies have focused on the relationship between these polymorphisms and MDD patients with suicidality. The objective of the present study was to examine whether the two polymorphisms are associated with MDD patients with suicidality in the Han Chinese population. Methods: Two hundred and sixty-three suicidal depressed patients and 241 non-suicidal depressed patients who met DSM-IV criteria for MDD were recruited from our hospital. Three hundred and three unrelated, age- and sex-matched healthy control subjects participated in this case-control study. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton rating scale for depression (HAMD). Genotypes of T-182C polymorphism (rs2242446) and G1287A (rs5569) were screened by polymerase chain reaction. Results: No statistical significant differences between patients and controls were found for any of the analysed polymorphisms, either in the genotype or allele distribution. Conclusions: Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of MDD with suicidality. However, the results must be verified in larger samples and different ethnicities.

Planning skills moderate the intention-planning cognitions-behaviour relation: a longitudinal study on physical activity in Chinese adolescents.

Our objective is to examine the role of planning skills for translating intentions into physical activity via planning cognitions. A study with 534 adolescents was conducted. Over 4 weeks, intention, planning cognitions (prospective anticipation of when, where, and how to perform activities), planning skills (successful past planning experiences), and physical activity were assessed. The results were that skills correlated with intention, planning cognitions, and subsequent physical activity. Planning cognitions were found to mediate the intention-behavior relation, whereas skills moderated the mediating role of planning cognitions: If students reported high skills, they were more likely to translate their intentions into plans and behavior. We conclude that having more skills makes it more likely that adolescents successfully translate their intentions into plans. Promotion of physical activity should improve planning cognitions but also planning skills. Only with planning cognitions and skills might adolescents better be able to act in accordance with their intentions and perform physical activity.

Reduced nucleus accumbens functional connectivity in reward network and default mode network in patients with recurrent major depressive disorder.

The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

The DIRECT consortium and the REST-meta-MDD project: towards neuroimaging biomarkers of major depressive disorder.

Despite a growing neuroimaging literature on the pathophysiology of major depressive disorder (MDD), reproducible findings are lacking, probably reflecting mostly small sample sizes and heterogeneity in analytic approaches. To address these issues, the Depression Imaging REsearch ConsorTium (DIRECT) was launched. The REST-meta-MDD project, pooling 2428 functional brain images processed with a standardized pipeline across all participating sites, has been the first effort from DIRECT. In this review, we present an overview of the motivations, rationale, and principal findings of the studies so far from the REST-meta-MDD project. Findings from the first round of analyses of the pooled repository have included alterations in functional connectivity within the default mode network, in whole-brain topological properties, in dynamic features, and in functional lateralization. These well-powered exploratory observations have also provided the basis for future longitudinal hypothesis-driven research. Following these fruitful explorations, DIRECT has proceeded to its second stage of data sharing that seeks to examine ethnicity in brain alterations in MDD by extending the exclusive Chinese original sample to other ethnic groups through international collaborations. A state-of-the-art, surface-based preprocessing pipeline has also been introduced to improve sensitivity. Functional images from patients with bipolar disorder and schizophrenia will be included to identify shared and unique abnormalities across diagnosis boundaries. In addition, large-scale longitudinal studies targeting brain network alterations following antidepressant treatment, aggregation of diffusion tensor images, and the development of functional magnetic resonance imaging-guided neuromodulation approaches are underway. Through these endeavours, we hope to accelerate the translation of functional neuroimaging findings to clinical use, such as evaluating longitudinal effects of antidepressant medications and developing individualized neuromodulation targets, while building an open repository for the scientific community.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Biotypes of major depressive disorder: Neuroimaging evidence from resting-state default mode network patterns.

BACKGROUND: Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. METHODS: The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. RESULTS: Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. CONCLUSIONS: Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

No association of the rs9722 C >T in the S100B gene and susceptibility to major depression in a Chinese population.

OBJECTIVE: Astroglial-derived protein S100B is known to play important roles in axonal growth, neural plasticity, and energy regulation. Disturbance of these neurodevelopmental processes is proposed as one of the etiologies for mood disorder, and genetic polymorphisms of S100B have a possibility to be in susceptibility to major depressive disorder (MDD). METHOD: We first investigated the association of the rs9722 C > T polymorphism of the S100B gene and susceptibility to MDD by comparing 152 major depressive patients with 150 healthy individuals in a Chinese population. RESULTS: The genotype frequencies of the S100B rs9722 C > T polymorphism were 30% (C/C), 56% (C/T), and 14% (T/T) in depressed patients, 32% (C/C), 53% (C/T), and 15% (T/T) in healthy volunteers, respectively. The allele frequencies of the S100B rs9722 C > T polymorphism were 58% (C allele) and 42% (T allele) in depressed patients, and 59% (C allele) and 41% (T allele) in healthy volunteers, respectively. CONCLUSION: There were no significant differences in the genotype distribution and allele frequencies between major depressive patients and healthy individuals. S100B rs9722 C > T polymorphism appears not to be an important factor in susceptibility to MDD in a Chinese population.

White matter microstructural abnormalities and their association with anticipatory anhedonia in depression.

Anhedonia is associated with dysfunction of the neural circuitry of reward in patients with major depressive disorder (MDD). However, its neurobiological basis is not fully understood. The present study examined the association between anhedonia and white matter (WM) characteristics in patients with first-episode MDD. We recruited 30 patients with first-episode drug-naive MDD and 28 healthy controls (HC) to undergo diffusion weighted imaging. We examined specifically the correlation between WM characteristics and anhedonia measured with the Temporal Experience of Pleasure Scale (TEPS) in MDD patients. Using Track-Based Spatial Statistics (TBSS), we found that MDD patients exhibited reduced fractional anisotropy (FA) in the left cingulum and the forceps minor. These patients also exhibited increased radial diffusivity (RD) in several major tracts including the bilateral anterior thalamic radiation, the corticospinal tract, the superior longitudinal fasciculus and the uncinate fasciculus in the left hemisphere. Correlational analysis showed that increased RD was significantly correlated with anticipatory anhedonia in the MDD group, while reduced mean FA was correlated with consummatory anhedonia in HC. These preliminary findings suggest that left-sided WM tracts abnormalities may contribute to the development of anhedonia in MDD patients.

Anhedonia correlates with abnormal functional connectivity of the superior temporal gyrus and the caudate nucleus in patients with first-episode drug-naive major depressive disorder.

BACKGROUND: Recent empirical findings have suggested that imbalanced neural networks may underlie the pathophysiology of major depressive disorder (MDD). However, the contribution of the superior temporal gyrus (STG) and the caudate nucleus to its pathophysiology remains unclear. METHODS: Functional magnetic resonance imaging (MRI) date were acquired from 40 patients with first-episode drug-naive MDD and 36 matched healthy controls during wakeful rest. We used whole-brain voxel-wise statistical maps to quantify within-group resting state functional connectivity (RSFC) and between-group differences of bilateral caudate and STG seeds. RESULTS: Compared with healthy controls, first-episode MDD patients were found to have reduced connectivity between the ventral caudate and several brain regions including the superior frontal gyrus (SFG), the superior parietal lobule (SPL) and the middle temporal gyrus (MTG), as well as increased connectivity with the cuneus. We also found increased connectivity between the left STG and the precuneus, the angular gyrus and the cuneus. Moreover, we found that increased anhedonia severity was correlated with the magnitude of ventral caudate functional connectivity with the cuneus and the MTG in MDD patients. LIMITATIONS: Due to our small sample size, we did not correct the statistical threshold in the correlation analyses between clinical variables and connectivity abnormalities. CONCLUSIONS: The present study suggests that anhedonia is mainly associated with altered ventral caudate-cortical connectivity and highlights the importance of the ventral caudate in the neurobiology of MDD.

Neural substrates of the impaired effort expenditure decision making in schizophrenia.

OBJECTIVE: Unwillingness to expend more effort to pursue high value rewards has been associated with motivational anhedonia in schizophrenia (SCZ) and abnormal dopamine activity in the nucleus accumbens (NAcc). The authors hypothesized that dysfunction of the NAcc and the associated forebrain regions are involved in the impaired effort expenditure decision-making of SCZ. METHOD: A 2 (reward magnitude: low vs. high) × 3 (probability: 20% vs. 50% vs. 80%) event-related fMRI design in the effort-expenditure for reward task (EEfRT) was used to examine the neural response of 23 SCZ patients and 23 demographically matched control participants when the participants made effort expenditure decisions to pursue uncertain rewards. RESULTS: SCZ patients were significantly less likely to expend high level of effort in the medium (50%) and high (80%) probability conditions than healthy controls. The neural response in the NAcc, the posterior cingulate gyrus and the left medial frontal gyrus in SCZ patients were weaker than healthy controls and did not linearly increase with an increase in reward magnitude and probability. Moreover, NAcc activity was positively correlated with the willingness to expend high-level effort and concrete consummatory pleasure experience. CONCLUSION: NAcc and posterior cingulate dysfunctions in SCZ patients may be involved in their impaired effort expenditure decision-making. (PsycINFO Database Record

Diminished caudate and superior temporal gyrus responses to effort-based decision making in patients with first-episode major depressive disorder.

BACKGROUND: Anhedonia, the loss of interest or pleasure in reward processing, is a hallmark feature of major depressive disorder (MDD), but its underlying neurobiological mechanism is largely unknown. The present study aimed to examine the underlying neural mechanism of reward-related decision-making in patients with MDD. METHOD: We examined behavioral and neural responses to rewards in patients with first-episode MDD (N=25) and healthy controls (N=25) using the Effort-Expenditure for Rewards Task (EEfRT). The task involved choices about possible rewards of varying magnitude and probability. We tested the hypothesis that individuals with MDD would exhibit a reduced neural response in reward-related brain structures involved in cost-benefit decision-making. RESULTS: Compared with healthy controls, patients with MDD showed significantly weaker responses in the left caudate nucleus when contrasting the 'high reward'-'low reward' condition, and blunted responses in the left superior temporal gyrus and the right caudate nucleus when contrasting high and low probabilities. In addition, hard tasks chosen during high probability trials were negatively correlated with superior temporal gyrus activity in MDD patients, while the same choices were negatively correlated with caudate nucleus activity in healthy controls. CONCLUSIONS: These results indicate that reduced caudate nucleus and superior temporal gyrus activation may underpin abnormal cost-benefit decision-making in MDD.

Increased prefrontal and parietal cortical thickness does not correlate with anhedonia in patients with untreated first-episode major depressive disorders.

Cerebral morphological abnormalities in major depressive disorder (MDD) may be modulated by antidepressant treatment and course of illness in chronic medicated patients. The present study examined cortical thickness in patients with untreated first-episode MDD to elucidate the early pathophysiology of this illness. Here, we examined cortical thickness in patients with first-episode MDD (N=27) and healthy controls (N=27) using an automated surface-based method (in FreeSurfer). By assessing the correlation between caudate volume and cortical thickness at each vertex on the cortical surface, a caudate-cortical network was obtained for each group. Subsequent analysis was performed to assess the effect of anhedonia by the Temporal Experience of Pleasure Scale. We observed increased cortical thickness at the right orbital frontal cortex and the left inferior parietal gyrus in MDD patients compared with healthy controls. Furthermore, morphometric correlational analysis using cortical thickness measurement revealed increased caudate-cortical connectivity in the bilateral superior parietal gyrus in MDD patients. All changes were not related to anhedonia. These preliminary findings may reflect disorder manifestation close to illness onset and may provide insight into the early neurobiology of MDD.

Motivational deficits in effort-based decision making in individuals with subsyndromal depression, first-episode and remitted depression patients.

Anhedonia is a hallmark symptom of major depressive disorder (MDD). Preliminary findings suggest that anhedonia is characterized by reduced reward anticipation and motivation of obtaining reward. However, relatively little is known about reward-based decision-making in depression. We tested the hypothesis that anhedonia in MDD may reflect specific impairments in motivation on reward-based decision-making and the deficits might be associated with depressive symptoms severity. In study 1, individuals with and without depressive symptoms performed the modified version of the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of cost/benefit decision-making. In study 2, MDD patients, remitted MDD patients and healthy controls were recruited for the same procedures. We found evidence for decreased willingness to make effort for rewards among individuals with subsyndromal depression; the effect was amplified in MDD patients, but dissipated in patients with remitted depression. We also found that reduced anticipatory and consummatory pleasure predicted decreased willingness to expend efforts to obtain rewards in MDD patients. For individuals with subsyndromal depression, the impairments were correlated with anticipatory anhedonia but not consummatory anhedonia. These data offer novel evidence that motivational deficits in MDD are correlated with depression severity and predicted by self-reported anhedonia.

The relationship between single nucleotide polymorphisms in 5-HT2A signal transduction-related genes and the response efficacy to selective serotonin reuptake inhibitor treatments in Chinese patients with major depressive disorder.

OBJECTIVE: To explore the possible relationship between six single nucleotide polymorphisms (SNPs) (rs6311 and rs6305 of 5-HT2A, rs5443 of Gß3, rs2230739 of ACDY9, rs1549870 of PDE1A and rs255163 of CREB1, which are all related with 5-HT2A the signal transduction pathway) and the response efficacy to selective serotonin reuptake inhibitor (SSRI) treatments in major depressive disorder (MDD) Chinese. METHODS: This study included 194 depressed patients to investigate the influence of 6 polymorphisms in 5-HT2A signal transduction-related genes on the efficacy of SSRIs assessed over 1 year. The efficacies of SSRIs on 194 MDD patients were evaluated in an 8-week open-trial study. Over 1 year, a follow-up study was completed for 174 of them to observe the long-term efficacy of SSRIs. The optimal-scaling regression analysis was used for testing the relationship between the different genotypes of five SNPs and the efficacy in MDD. RESULTS: It showed that the patients with rs5443TT and rs2230739GG have a relatively good efficacy in response to short-term SSRIs. We also found that good efficacy appeared in depressed patients with rs2230739GG in response to long-term SSRIs. CONCLUSIONS: It suggested that different genotypes of rs5443 and rs2230739 might influence the signal transduction pathways of second message and affect therapeutic efficacy.

Association study of astrocyte-derived protein S100B gene polymorphisms with major depressive disorder in Chinese people.

OBJECTIVE: Astroglial-derived protein S100B is known to play important roles in axonal growth, neural plasticity, and energy regulation. Disturbance of these neurodevelopmental processes is proposed as one possible etiology for mood disorder. Therefore, we performed a genetic analysis of S100B in patients with major depressive disorder (MDD). METHOD: The polymorphisms of S100B were determined by polymerase chain reaction-restriction fragment length polymorphism in patients (n = 152) with MDD and healthy control subjects (n = 150). The genotypic and allelic distributions of 2 variants were analyzed in Chinese patients. RESULTS: Two single nucleotide polymorphisms did not display significant associations with MDD. However, there were significant differences in age of onset in 3 genotypes of S100B rs9722. Significant differences in the subgroup depression (first-episode and recurrent depression) were also shown in 3 genotypes of S100B rs9722 and rs11911834 in patients and control subjects (P < 0.05). CONCLUSIONS: Our findings did not suggest association of S100B gene polymorphisms in patients with MDD in China. We found there were differences in depressive episodes among different genotypes of S100B gene.

The effects of gender and numbers of depressive episodes on serum S100B levels in patients with major depression.

S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cell depending on its concentration. It has been reported that S100B played an important role as a potential marker in psychiatric disorders. Thus, we will explore the clinical implication of S100B in major depression, especially the effect of gender and numbers of depressive episodes on S100B. The levels of serum S100B were measured with enzyme-linked immunosorbent assay (ELISA) in 54 patients with major depression and 35 age-matched healthy controls. The S100B levels in major depressed patients were significantly higher than those in controls. The serum S100B levels in female patients were significantly higher than those in male patients. Patients with recurrent depressive episodes had significantly higher S100B levels than those in first-episode depression. Serum S100B levels were significantly positive related with the numbers of depressive episode, family history and cognitive disturbance scores. These findings confirmed an increase in serum S100B levels in major depressive patients and presence of a sexual dimorphism. Moreover, numbers of depressive episodes in depression seemed to have an additional increasing effect on S100B levels.