Abnormal cortical-striatal-thalamic-cortical circuit centered on the thalamus in MDD patients with somatic symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: Somatic symptoms are common comorbidities of major depressive disorder (MDD), and negatively impact the course and severity of the disease. In order to enrich the understanding of the pathological mechanism and clarify the neurobiological basis of somatic symptoms in depression, we attempted to explore the changes of brain structure and function in a large sample between depression with and without somatic symptoms. METHODS: Structure magnetic resonance imaging (MRI) data were collected from 342 patients with somatic symptoms (SD), 208 patients without somatic symptoms (NSD), and 510 healthy controls (HCs) based on the REST-meta-MDD project. We analyzed the whole brain VBM maps of the three groups, and combined with weight degree centrality (DC) index, we investigated whether the brain regions with gray matter volume (GMV) and gray matter density (GMD) abnormalities in MDD patients with somatic symptoms had corresponding brain functional abnormalities. RESULTS: Between depression with and without somatic symptoms, we found that there are extensive GMV and GMD differences involving cortical regions such as the temporal lobe, occipital lobe, and insula, as well as subcortical brain regions such as thalamus and striatum. The comparison results of weight DC signals of GMV and GMD abnormal clusters between the SD and NSD groups were basically consistent with the GMV and GMD abnormal clusters. CONCLUSION: The results indicate that the structure and function of cortical-striatal-thalamic-cortical (CSTC) circuit centered on the thalamus were abnormal in MDD patients with somatic symptoms. This may be the neurobiological basis of somatic symptoms in MDD.

Neuroanatomical Correlates of Mild-to-Moderate Depression: Memory Ability Mediates the Association Between Gray Matter Volume and Antidepressant Treatment Outcome.

Mild-to-moderate depression (MMD) is frequently encountered in clinical practice. Investigating the brain mechanism and its relationship with symptoms in patients with MMD can help us understand the occurrence and development of depression, thus optimizing the prevention and treatment of depression. Shugan Jieyu capsule (SG), a traditional Chinese medicine, is commonly used to ameliorate emotional and cognitive symptoms induced by patients with MMD. Combining clinical assessments and magnetic resonance imaging (MRI), we obtained the emotional and cognitive status of MMD patients and also explored the structural and functional alterations in MMD patients after SG treatments. Structural MRI demonstrated that the gray matter volumes of the left thalamus, right thalamus, and right amygdala in MMD patients were significantly smaller than in healthy controls, and the right amygdala volume was negatively related to depression symptoms in MMD patients. Resting-state functional MRI data demonstrated that MMD patients exhibited decreased temporal coupling between the right amygdala and nucleus accumbens, which was further associated with the severity of depression. Furthermore, right amygdala volume at baseline served as a significant predictor to identify the treatment outcome after 8 weeks of SG treatment in the patients' group, and importantly, the memory ability mediated the relationship from right amygdala volume to the treatment outcome. These data revealed the structural and functional deficits in the right amygdala, which were highly correlated with the symptoms of depression and its cognitive ability, likely predicting treatment outcome. Therefore, this study strengthened our understanding of the pathogenesis of MMD, which is hoped that it will contribute to tailoring a personalized method for treating the patients.

Functional connectivity between the thalamus and the primary somatosensory cortex in major depressive disorder: a resting-state fMRI study.

BACKGROUND: Studies have confirmed that the thalamus and the primary somatosensory cortex (SI) are associated with cognitive function. These two brain regions are closely related in structure and function. The interactions between SI and the thalamus are of crucial significance for the cognitive process. Patients with major depressive disorder (MDD) have significant cognitive impairment. Based on these observations, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate whether there is an abnormality in the SI-thalamic functional connection in MDD. Furthermore, we explored the clinical symptoms related to this abnormality. METHODS: We included 31 patients with first-episode major depressive disorder and 28 age-, gender-, and education-matched healthy controls (HC). The SI-thalamic functional connectivity was compared between the MDD and HC groups. The correlation analyses were performed between areas with abnormal connectivity and clinical characteristics. RESULTS: Compared with healthy subjects, the MDD patients had enhanced functional connectivity between the thalamus and SI (p < 0.05, corrected). Brain areas with significantly different levels of connectivity had a negative correlation with the Assessment of Neuropsychological Status total score (r = - 0.383, p = 0.033), delayed memory score (r = - 0.376, p = 0.037) and two-digit continuous operation test score (r = - 0.369, p = 0.041) in MDD patients. CONCLUSIONS: These results demonstrate that SI-thalamic functional connectivity is abnormal and associated with the core clinical symptoms in MDD. The SI-thalamic functional connectivity functions as a neurobiological feature and potential biomarker for MDD.

Cerebralcare Granule® attenuates cognitive impairment in rats continuously overexpressing microRNA-30e.

Previous studies have demonstrated that dysregulation of micro (mi)RNAs is associated with the etiology of various neuropsychiatric disorders, including depression and schizophrenia. Cerebralcare Granule® (CG) is a Chinese herbal medicine, which has been reported to have an ameliorative effect on brain injury by attenuating blood­brain barrier disruption and improving hippocampal neural function. The present study aimed to evaluate the cognitive behavior of rats continuously overexpressing miRNA­30e (lenti­miRNA­30e), prior to and following the administration of CG. In addition, the mechanisms underlying the ameliorative effects of CG were investigated. The cognitive ability of the rats was assessed using an open­field test and a Morris water maze spatial reference/working memory test. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect neuronal apoptosis in the dentate gyrus of the hippocampus. Immunohistochemical analysis and western blotting were conducted to detect the expression levels of B­cell lymphoma 2 (BCL­2) and ubiquitin­conjugating enzyme 9 (UBC9), in order to examine neuronal apoptosis. The lenti­miRNA­30e rats exhibited increased signs of anxiety, depression, hyperactivity and schizophrenia, which resulted in a severe impairment in cognitive ability. Furthermore, in the dentate gyrus of these rats, the expression levels of BCL­2 and UBC9 were reduced and apoptosis was increased. The administration of CG alleviated cognitive impairment, enhanced the expression levels of BCL­2 and UBC9, and reduced apoptosis in the dentate gyrus in the lenti­miRNA­30e rats. No significant differences were detected in behavioral indicators between the lenti­miRNA­30e rats treated with CG and the normal controls. These findings suggested that CG exerts a potent therapeutic effect, conferred by its ability to enhance the expression levels of BCL­2 and UBC9, which inhibits the apoptotic process in neuronal cells. Therefore, CG may be considered a potential therapeutic strategy for the treatment of cognitive impairment in mental disorders.

A combined study of GSK3ß polymorphisms and brain network topological metrics in major depressive disorder.

GSK3ß genotypes may interact with major depressive disorder (MDD) and may have a role in determining regional gray matter volume differences from healthy comparison subjects. However, any associations of GSK3ß genotypes with MDD related to abnormal functional brain activity have yet to be elucidated. In the present study, resting state functional brain networks were constructed by thresholding partial correlation matrices of 90 regions. Differences in the network features of GSK3ß-rs6438552 genotypes were tested, and a 2×2 analysis of variance was performed to identify the main effects of genotypes, disease status, and their interactions in MDD. Compared with CC carriers, T+ carriers with MDD showed increased nodal centralities in many brain regions-mainly the limbic system, thalamus and parts of the parietal, temporal, occipital, and frontal regions. Decreased nodal centralities predominantly occurred in the sensorimotor area and parts of the frontal, occipital, and temporal lobes. Significant interactions between genotypes and disease status were found in the left thalamus, left superior occipital gyrus, and left inferior parietal lobe. Only altered nodal centrality in the left angular gyrus was negatively correlated with scores on the Hamilton Depression Rating Scale. Our results suggest the GSK3ß genotypic effect of rs6438552 and its interaction with disease status may contribute to the altered topological organization of resting state functional brain networks in MDD patients.