Search

Background The subgenual anterior cingulate cortex (sgACC) appears to play a central role in the pathophysiology of major depressive disorder (MDD). To wit, its functional interactive profile with the left dorsal lateral prefrontal cortex (DLPFC) has been shown to be related to treatment outcomes with transcranial magnetic stimulation (TMS) treatment outcomes. Nevertheless, previous research on sgACC functional connectivity (FC) in MDD has yielded inconsistent results, partly due to small sample sizes and limited statistical power of prior work.Methods Here, leveraging a large multi-site sample (1660 MDD patients vs. 1341 healthy controls) from Phase II of the Depression Imaging REsearch ConsorTium (DIRECT), we systematically delineated case-control difference maps of sgACC FC and examined their clinical relevance to previously identified TMS targets. We also investigated case-control FC difference maps of left DLPFC sub-fields.Results In MDD patients we found significantly increased FC between sgACC and thalamus and reduced FC to a broad array of brain regions, including somatosensory area, occipital lobe, medial and lateral temporal lobe, and insular cortex, when global signal regression (GSR) was not implemented. Intriguingly, we found enhanced left DLPFC-sgACC FC in MDD patients when GSR was performed. We leveraged an prior independent sample to explore the possible relationship between the case-control differences regarding sgACC’s FC profiles and the treatment out comes of TMS. In sites in which open TMS treatment was administered, case-control differences in sgACC FC, with GSR, were related to clinical improvement. Next we tested whether the position of peak of the FC maps (previously identified TMS target) could be altered in MDD patients as compred with healthy controls (HC)s. We found the optimized TMS target differed in MDD patients. Several DLPFC sub-fields yielded case-control differences in whole-brain FC maps.Conclusion In summary, we reliably delineated MDD-related abnormalities of sgACC FC profiles in a large sample. GSR was essential in applying case-control difference maps to identify optimized TMS targets. Our results highlight the functional heterogeneity of the left DLPFC and of precise TMS targets therein.

Major depressive disorder (MDD) is associated with functional disturbances in subcortical regions. However, little is known about how the subcortical functional network relates to depressive symptom profile and treatment outcome. In this study, we aimed to investigate associations among subcortical connectivity, clinical symptoms and antidepressant response in MDD using multivariate methods. Data for the present study were derived from the Towards Neurobiology-based Diagnosis and Treatment of Affective Disorders (TNDTAD), which is a naturalistic prospective study of mood disorders (NCT03294525). Medication-free participants with MDD (n = 135) underwent a functional magnetic resonance imaging scan at baseline and completed posttreatment clinical assessment after 8 weeks of antidepressant monotherapy. We used partial least squares (PLS) analysis to explore associations between subcortical connectivity and symptom profile. Replication was undertaken in an independent sample (n = 74). We also investigated the association between the observed subcortical connectivity pattern and treatment outcome in the discovery sample. A distinctive subcortical connectivity pattern, critically involving dorsal striatum and thalamus, was associated with negative affect. This association was partly replicated in the independent sample. Lower composite functional connectivity score (reflecting the connectivity pattern) at baseline predicted greater symptom improvement after 8 weeks of antidepressant treatment. The emphasis here on the role of dorsal striatum and thalamus consolidates prior work of subcortical connectivity in MDD. The findings provide insight into the pathogenesis of MDD, linking subcortical functional connectivity with negative affect. However, while connectivity pattern significantly predicted treatment outcome, the low odds ratio suggests that finding predictive biomarkers for depression remains an aspiration.

Prospective memory (PM) could be impaired in the non-psychotic first-degree relatives of patients with schizophrenia. This meta-analysis systematically examined the PM of non-psychotic first-degree relatives of patients with schizophrenia. Both Chinese and English databases were systematically searched for articles from the inception of the databases through November 13, 2018. Case-control studies of PM in non-psychotic first-degree relatives of patients with schizophrenia were included in the analyses. Confidence intervals (CIs) and standardized mean differences (SMDs) were calculated utilizing the random effects model. Four studies (n=268) that compared PM performance between non-psychotic first-degree relatives of patients with schizophrenia (n=136) and healthy controls (n=132) were included. Three studies were rated as "high quality", while the quality of evidence of the three outcomes included in this meta-analysis was moderate. Compared with the healthy controls, the non-psychotic first-degree relatives of patients with schizophrenia showed impairments in overall PM (two studies, n=127; SMD: -0.46; 95% CI=-0.82, -0.11, P=0.01; I=0%), event-based PM (EBPM) (four studies, n=268; SMD: -0.56; 95% CI=-0.80, -0.31, P

Previous neuroimaging studies have revealed abnormal functional connectivity of brain networks in patients with major depressive disorder (MDD), but findings have been inconsistent. A recent big‐data study found abnormal intrinsic functional connectivity within the default mode network in patients with recurrent MDD but not in first‐episode drug‐naïve patients with MDD. This study also provided evidence for reduced default mode network functional connectivity in medicated MDD patients, raising the question of whether previously observed abnormalities may be attributable to antidepressant effects. The present study (ClinicalTrials.gov identifier: NCT03294525) aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Forty‐one first‐episode drug‐naïve MDD patients were administrated antidepressant medication (escitalopram or duloxetine) for 8 weeks, with resting‐state functional connectivity compared between posttreatment and baseline. To assess the replicability of the big‐data finding, we also conducted a cross‐sectional comparison of resting‐state functional connectivity between the MDD patients and 92 matched healthy controls. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, indicating considerable antidepressant effects. Neither Network‐Based Statistic analyses nor large‐scale network analyses detected significant functional connectivity differences between treatment‐naïve patients and healthy controls. In short, antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD., The present study aimed to disentangle the effects of antidepressant treatment from the pathophysiology of MDD and test the medication normalization hypothesis. Both Network‐Based Statistic analyses and large‐scale network analyses revealed intrinsic functional connectivity decreases in extensive brain networks after treatment, while no significant functional connectivity differences were found between treatment‐naïve patients and healthy controls. These results indicate that antidepressant effects are widespread across most brain networks and need to be accounted for when considering functional connectivity abnormalities in MDD.

Bipolar disorder (BD) is a major and highly heritable mental illness with severe psychosocial impairment, but its etiology and pathogenesis remains unclear. This study aimed to identify the essential pathways and genes involved in BD using weighted gene coexpression network analysis (WGCNA), a bioinformatic method studying the relationships between genes and phenotypes. Using two available BD gene expression datasets (GSE5388, GSE5389), we constructed a gene coexpression network and identified modules related to BD. The analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were performed to explore functional enrichment of the candidate modules. A protein-protein interaction (PPI) network was further constructed to identify the potential hub genes. Ten coexpression modules were identified from the top 5,000 genes in 77 samples and three modules were significantly associated with BD, which were involved in several biological processes (e.g., the actin filament-based process) and pathways (e.g., MAPK signaling). Four genes (NOTCH1, POMC, NGF, and DRD2) were identified as candidate hub genes by PPI analysis and CytoHubba. Finally, we carried out validation analyses in a separate dataset, GSE12649, and verified NOTCH1 as a hub gene and the involvement of several biological processes such as actin filament-based process and axon development. Taken together, our findings revealed several candidate pathways and genes (NOTCH1) in the pathogenesis of BD and call for further investigation for their potential research values in BD diagnosis and treatment.

Crohn disease (CD) with complications such as penetrating, stricturing, and perianal disease is called complicated CD. The aim of this study is to test the efficiency with which the CD8+CD28+/CD8+CD28– cell balance can predict a subsequent active stage in patients with newly diagnosed complicated CD. Seventeen patients with complicated CD and 48 CD patients with no complications were enrolled. Blood CD8+ T cells were tested from all of the 65 newly diagnosed CD patients upon enrollment. The potential risk factors were compared between the 2 groups. A 30-week follow-up was performed, and the efficiency of the CD8+ cell balance at predicting active CD was analyzed using receiver-operating characteristic curves. The cumulative remission lasting rates (CRLRs) were analyzed using the Kaplan–Meier method. Compared with the control CD group, patients with complicated CD were predominantly male and younger in age; they also had lower body mass indices (BMIs), higher Crohn disease activity indices (CDAIs), higher immunosuppressant and steroid prescription rates, and significantly higher surgical rates. The CD8+CD28+/CD8+CD28– balance was associated with BMI, CDAI, steroids, and surgery. The CD8+CD28+/CD8+CD28– ratios were significantly lower at week 0 and on the 6th, 22nd, and 30th week during follow-up with a shorter lasting time of remission for the complicated CD patients. The CD8+CD28+/CD8+CD28– ratio could accurately predict the active stage for the patients with complicated CD, and the highest sensitivity (89.2%) and specificity (85.3%) were found when the ratio was 1.03. Treatment with steroids and surgery, along with a significantly lower CD8+CD28+/CD8+CD28– ratio and lower CRLRs, was closely related to a worse outcome for the patients with complicated CD. Patients requiring steroids and surgery experience more severe disease activity and thus a disequilibrated immunological balance, which could be the main reason for a decreased CD8+CD28+/CD8+CD28– ratio. This ratio can sensitively predict the active stage for patients with complicated CD, and more care should be taken when this ratio is