Linking individual variability in functional brain connectivity to polygenic risk in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disease, which brings great difficulties to clinical diagnosis and therapy. Its mechanism is still unknown. Prior neuroimaging studies mainly focused on mean differences between patients and healthy controls (HC), largely ignoring individual differences between patients. METHODS: This study included 112 MDD patients and 93 HC subjects. Resting-state functional MRI data were obtained to examine the patterns of individual variability of brain functional connectivity (IVFC). The genetic risk of pathways including dopamine, 5-hydroxytryptamine (5-HT), norepinephrine (NE), hypothalamic-pituitary-adrenal (HPA) axis, and synaptic plasticity was assessed by multilocus genetic profile scores (MGPS), respectively. RESULTS: The IVFC pattern of the MDD group was similar but higher than that in HCs. The inter-network functional connectivity in the default mode network contributed to altered IVFC in MDD. 5-HT, NE, and HPA pathway genes affected IVFC in MDD patients. The age of onset, duration, severity, and treatment response, were correlated with IVFC. IVFC in the left ventromedial prefrontal cortex had a mediating effect between MGPS of the 5-HT pathway and baseline depression severity. LIMITATIONS: Environmental factors and differences in locations of functional areas across individuals were not taken into account. CONCLUSIONS: This study found MDD patients had significantly different inter-individual functional connectivity variations than healthy people, and genetic risk might affect clinical manifestations through brain function heterogeneity.

Abnormal functional network of the thalamic subregions in adult patients with obsessive-compulsive disorder.

The thalamus plays an important role in pathological mechanisms underlying obsessive-compulsive disorder (OCD). As the thalamus is a heterogeneous brain region, functional connectivity (FC) between thalamic subregions and other brain regions is worth investigating in OCD. In addition, the relationship between abnormal FC and clinical symptoms is still unclear. In this study, we used resting-state functional magnetic resonance imaging to scan 45 OCD patients and 43 well-matched healthy controls (HCs). Thalamic subregions were defined according to the Human Brainnetome Atlas. The fractional amplitude of low-frequency fluctuations (fALFF) and FC seeding-based connectivity were compared using a two-sample t-test. Correlations between abnormal FC and clinical symptoms were analyzed in OCD patients. Compared with HCs, increased fALFF was found in the bilateral thalamus, and increased FC was observed between the right posterior parietal thalamus (PPtha) and left middle occipital gyrus (LMOG) and between the right occipital thalamus (Otha) and right middle occipital gyrus (RMOG) in OCD patients. In addition, OCD patients had reduced FC between the left sensory thalamus (Stha) and left orbital inferior frontal gyrus, right PPtha and left prefrontal cortex, and between the right Otha and left inferior parietal gyrus (LIPG), respectively. Within the OCD group, the FC between right PPtha-LMOG was correlated with severity of clinical symptoms. These results revealed that the FC between the thalamus and occipital lobe is related to obsessive-compulsive symptoms in OCD patients. This finding provides more accurate information about the involvement of the thalamus in the pathophysiology of OCD.

Antidepressant-like and anti-oxidative efficacy of Campsis grandiflora flower.

OBJECTIVES: Our study aimed to investigate the antidepressant-like effect of ethyl acetate extract of the flowers of Campsis grandiflora (EFCG) in a mice model of chronic unpredictable mild stress (CUMS). METHODS: HPLC-Q-TOF-MS was used to identify the chemical constituents of EFCG. The DPPH assay and ABTS radical-scavenging assay were performed to measure the antioxidant properties. The protective properties of EFCG against H2 O2 -induced oxidative damage were analysed in PC12 cells. The changes of behaviour profiles were investigated by using open-field test, sucrose preference test, forced swimming test (FST) and tail suspension test (TST). Brain tissue samples of mice were collected, and antioxidative measure levels were measured. KEY FINDINGS: The result showed that EFCG had the most active anti-oxidative effect and the protective effect against H2 O2 oxidative injury in PC12 cells. Treatment with the EFCG significantly reduced the depressant-like severity and immobility period as compared with untreated CUMS mice in FST and TST. Moreover, EFCG significantly elevated the contents of superoxide dismutase, Glutathione Peroxidase and decreased the contents of Malonaldehyde (MDA) in mice brain. CONCLUSIONS: Our study found first the antidepressant activity of the EFCG. The results suggested the therapeutic potential of EFCG for depressive disorder.