Serotonin 2A receptor polymorphism rs3803189 mediated by dynamics of default mode network: a potential biomarker for antidepressant early response.

BACKGROUND: Serotonin 2A receptors (HTR2A) play a crucial role in the therapeutic response to antidepressant. The activity of serotonergic system could modulate the connectivity of the default mode network (DMN) in human brain. Our research investigated the influence of the single nucleotide polymorphism (SNP) of HTR2A on the early treatment response of antidepressant and their relation to dynamic changes of DMN for the first time. METHODS: A total of 134 major depressive disorder patients and 95 healthy controls from two independent datasets were enrolled. All subjects have genotyped candidate HTR2A polymorphisms, dynamic brain parameters flexibility and integration were calculated according to the resting-state functional magnetic resonance imaging (rs-fMRI) at baseline. Patients received selective serotonin reuptake inhibitors (SSRIs) treatment with conventional dose in the next two weeks. RESULTS: We found the correlation of the risk-associated variant belonged to HTR2A polymorphism rs3803189 with the achievements of antidepressant early response, and also with the stronger dynamic changes of DMN. Further mediation analysis indicated that the bond between rs3803189 and antidepressant early response was mediated by the integration between the right angular gyrus (AG.R) and the subcortical network (SCN), which were validated over both the main and replication datasets. LIMITATIONS: Except the AG.R-SCN circuit, other factors which influence the relationship between rs3803189 and antidepressant therapy deserve to be explored further. Besides, heterogeneity of samples limited the power of the current result. CONCLUSIONS: Our findings provided a potential biomarker for individual treatment sensitivity and produced positive effects on revealing the complicated gene-brain-disorder relationship.

Antidepressants normalize brain flexibility associated with multi-dimensional symptoms in major depressive patients.

BACKGROUND: The fundamental pathophysiology of major depressive disorder (MDD) could be characterized by functional brain networks which tightly and dynamically connect into groups as communities, making the flexible brain possible to external multifarious demands. We aim to scrutinize what brain dynamics go awry in MDD and antidepressants effects on multi-dimensional symptoms. METHODS: Thirty-five patients and thirty-five controls underwent resting-state functional magnetic resonance imaging (MRI). Patients were scanned before and after 8 or 12 weeks of pharmacotherapy. Group independent component analysis decomposed resting-state images to instinct networks and networks' integrated flexibility was calculated. Network flexibility between patients at baseline and after therapy were compared. RESULTS: All patients completed the clinical trial and MRI scans. Following antidepressants treatment, we found significant normalization of reduced network flexibility in default mode network (DMN) and cognitive control network (CCN) of MDD patients. Selectively significant correlations between network flexibility and multi-dimensional symptoms such as anxiety/somatization and hysteresis factor were also found. CONCLUSIONS: "Hypoflexible" CCN may involve in anxiety syndrome. Low flexibility in DMN may be indicative of hysteresis. These suggest an important pathophysiology of depressive manifestation of MDD. The antidepressant-induced normalization of the "hypoflexibility" suggests a selective pathway through which antidepressants may alleviate symptoms in depression.

Predicting escitalopram monotherapy response in depression: The role of anterior cingulate cortex.

Neuroimaging biomarkers of treatment efficacy can be used to guide personalized treatment in major depressive disorder (MDD). Escitalopram is recommended as first-line therapy for MDD and severe depression. An interesting hypothesis suggests that the reconfiguration of dynamic brain networks might provide important insights into antidepressant mechanisms. The present study assesses whether the spatiotemporal modulation across functional brain networks could serve as a predictor of effective antidepressant treatment with escitalopram. A total of 106 first-episode, drug-naïve patients and 109 healthy controls from three different multicenters underwent resting-state functional magnetic resonance imaging. Patients were considered as responders if they had a reduction of at least 50% in Hamilton Rating Scale for Depression scores at endpoint (>2 weeks). Multilayer modularity framework was applied on the whole brain to construct features in relation to network dynamic characters that were used for multivariate pattern analysis. Linear soft-threshold support vector machine models were used to separate responders from nonresponders. The permutation tests demonstrated the robustness of discrimination performances. The discriminative regions formed a spatially distributed pattern with anterior cingulate cortex (ACC) as the hub in the default mode subnetwork. Interestingly, a significantly larger module allegiance of ACC was also found in treatment responders compared to nonresponders, suggesting high interactivities of ACC to other regions may be beneficial for the recovery after treatment. Consistent results across multicenters confirmed that ACC could serve as a predictor of escitalopram monotherapy treatment outcome, implying strong likelihood of replication in the future.

Altered regional homogeneity in patients with somatic depression: A resting-state fMRI study.

BACKGROUND: Somatic symptoms are common among patients with major depressive disorder (MDD), and are known to negatively impact the course and severity of the disease. Although previous studies have attempted to explore the neuropathology of MDD, little is known regarding the neural basis of somatic symptoms in MDD. METHODS: Resting-state functional magnetic resonance images of 28 MDD patients with somatic symptoms (somatic depression, SD), 30 patients without somatic symptoms (non-somatic depression, NSD) and 30 healthy controls (HC) were obtained. We investigated the neural basis of MDD with somatic symptoms based on the measure of regional homogeneity (ReHo). We also investigated whether the altered regional homogeneity may be correlated to any clinical features of depression. These comparison were also carried out in female and male subjects respectively. RESULTS: The SD exhibited higher ReHo in the bilateral parahippocampus and left lingual gyrus than HC, as well as lower ReHo in the right frontal gyrus. Relative to NSD, the SD exhibited lower ReHo in the right middle frontal gyrus and left precentral gyrus. Furthermore, in the SD, ReHo in the left precentral gyrus was positively correlated with cognitive factor scores of the HAMD-17. In female subjects, SD exhibited increased ReHo in the right STG and decreased ReHo in the right MFG, relative to women of the NSD group. CONCLUSIONS: Our preliminary findings indicated that abnormal ReHo in the frontal and temporal regions may play an important role in the neural basis of somatic depression.