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Major depressive disorder (MDD) is a highly prevalent mood disorder, characterized by depressed mood, reduced capabilities to concentrate, impaired cognition, as well as a high risk of relapse. Unaffected siblings who have high risks for MDD development and yet without clinical symptoms may be helpful for understanding the neural mechanisms of MDD traits.We investigated both regional fluctuation and inter-regional synchronization in 31 fully remitted MDD patients, 29 unaffected siblings and 43 age, gender, and educational level matched helathy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). The 17-item HAMD and neurocognitive scales were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) strength were investigated.Compared with healthy control group, patients with remitted MDD and unaffected siblings showed increased fALFF in the left dorsomedial prefrontal cortex (dmPFC) and increased FC between the left dmPFC and the right ventromedial prefrontal cortex (vmPFC). In addition, a negative correlation was observed between the fALFF value in the left dmPFC and the speed of Trail Making Test in the remitted MDD patients. Higher vmPFC-dmPFC FC was positively correlated with Wisconsin Card Sorting Test (WCST) total correct, and negatively correlated with WCST random errors.In the absence of clinical symptoms, individuals with remitted MDD and unaffected siblings showed increased fALFF in left dmPFC as well as the vmPFC-dmPFC connectivity. These results suggest a specific trait abnormality in the default mode network associated with vulnerability to MDD, which may have implications for developing effective therapies using this network as a target.

Background The Low Resistance Thought Induction Psychotherapy (TIP) is a comprehensive psychological treatment which could improve the clinical symptoms of major depressive disorder (MDD). However, the neural mechanisms for TIP treating MDD still remain unclear. This study aimed to investigate the topology of intrinsic connectivity network and the therapeutic effects of TIP in MDD on these topological properties. Methods Longitudinal study was conducted in 20 first-episode, treatment-naive MDD patients at baseline and after 6 weeks (12 sessions) of TIP treatment based on resting-state functional magnetic resonance image (rsfMRI) in conjunction with graph theoretical analysis. We constructed functional connectivity matrices and extracted the attribute features of the small-world networks in both MDD and age-, education level-, and gender-matched healthy controls (HCs). The global and local small-world network properties were explored and compared between MDD at baseline and HCs. The therapeutic effect of TIP was examined by comparing alterations in global and local network properties between MDD at baseline and after treatment. Results At baseline, MDD showed altered small-worldness and aberrant nodal properties in the frontolimbic circuit particularly in the orbital frontal gyrus, insula, precuneus and middle cingulate gyrus as compared with HCs. Following 6 weeks treatment, the abnormalities in the small-worldness and the nodal metrics were modulated, which were accompanied by a significant improvement in the clinical symptoms. Conclusions Our findings contributed to the understanding of the abnormal topological patterns in the frontolimbic systems in MDD and implicated that these disruptions may be modified by TIP treatment.

Background The amygdala is a key region in emotion processing, and studies have suggested that amygdala-frontal functional connectivity deficits could be modulated by antidepressants in major depressive disorder (MDD). Transcutaneous vagus nerve stimulation (tVNS), a non-invasive, peripheral neuromodulation method at the ear, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism underlying tVNS treatment of depression has not been fully investigated. In this study, we investigated how tVNS can modulate the amygdala-lateral prefrontal network resting state functional connectivity (rsFC) in mild or moderate major depressive disorder (MDD) patients. Methods Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments for four weeks. Resting state fMRI scans were applied before and after treatments. Results After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) scores were reduced significantly in the tVNS group as compared with the sham tVNS group. The rsFC in the tVNS group between the right amygdala and left dorsolateral prefrontal cortex was increased compared with sham tVNS. All the rsFC increases were also associated with HAMD reduction as well as reductions in the anxiety and retardation HAMD subscales. Conclusions tVNS can significantly modulate the amygdala-lateral prefrontal rsFC of MDD patients; our results provide insights into the brain mechanism of tVNS treatment for MDD patients.

Background Patients with major depressive disorder (MDD) can frequently develop new depressive episodes after remission. However, the neural mechanisms underlying the increased risk for depressive relapse remain unclear. Herein, we aimed to explore whether the specific changes to regional and inter-regional spontaneous brain activities within DMN are associated with the course of episodes in pooled MDD patients. Methods Resting-state functional magnetic resonance imaging was performed on patients with single-episode MDD (SEMDD, n = 30) and multiple-episode MDD (MEMDD, n = 54), and 71 age-, gender-, and educational level-matched healthy controls (HCs). We then accessed the differences in both the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity by using the right precuneus as the seed among different groups. Results Compared to the MEMDD and HC groups, the SEMDD group exhibited increased fALFF values in the right subgenual anterior cingulate cortex and right middle temporal gyrus. Decreased fALFF values in the right thalamus in the MEMDD group were also identified relative to the SEMDD and HC group. The peak values of fALFF in the right precuneus showed a negative correlation with the number of depressive episodes across the entire pool of MDD patients. No correlation was identified between functional connectivity using the right precuneus as the seed and the number of depressive episodes for the pooled MDD patients. Limitations Medication, a relatively small sample size, and hypothesis driven study. Conclusions Our neuroimaging results identified depression relapse-associated neural signatures and also indicated the role of reduced emotional appraisals in the thalamus. It is now possible to believe that the regional activity not inter-regional connectivity within the DMN may be involved in the pathology of depression relapse.

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.