The gut microbiota is a complex and dynamic ecosystem known as the ‘second brain’. Composing the microbiota‐gut‐brain axis, the gut microbiota and its metabolites regulate the central nervous system through neural, endocrine and immune pathways to ensure the normal functioning of the organism, tuning individuals’ health and disease status. Short‐chain fatty acids (SCFAs), the main bioactive metabolites of the gut microbiota, are involved in several neuropsychiatric disorders, including depression. SCFAs have essential effects on each component of the microbiota‐gut‐brain axis in depression. In the present review, the roles of major SCFAs (acetate, propionate and butyrate) in the pathophysiology of depression are summarised with respect to chronic cerebral hypoperfusion, neuroinflammation, host epigenome and neuroendocrine alterations. Concluding remarks on the biological mechanisms related to gut microbiota will hopefully address the clinical value of microbiota‐related treatments for depression.

Background The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation. Aims The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety. Methods 1501 adolescents aged 12–19 years were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale, and 716 adolescents who scored ≥5 on both scales were selected as participants. Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms. Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9. A comparison was made between the depression–anxiety symptom networks of the two groups. Results ‘Restlessness’, ‘sad mood’ and ‘trouble relaxing’ were the most prominent central symptoms in the depression–anxiety symptom network, and ‘restlessness’, ‘nervousness’ and ‘reduced movement’ were the bridge symptoms in this network. ‘Sad mood’ was found to be directly related to ‘suicide ideation’ with the highest variance. The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group, with ‘restlessness’ and ‘sad mood’ exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group. Conclusion Restlessness and sad mood could be targeted for the intervention of depression–anxiety symptoms among adolescents with suicide ideation.

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour.