Military psychiatry, a new subcategory of psychiatry, has become an invaluable, intangible effect of the war. In this review, we begin by examining related military research, summarizing the related epidemiological data, neuropathology, and the research achievements of diagnosis and treatment technology, and discussing its comorbidity and sequelae. To date, advances in neuroimaging and molecular biology have greatly boosted the studies on military traumatic brain injury (TBI). In particular, in terms of pathophysiological mechanisms, several preclinical studies have identified abnormal protein accumulation, blood–brain barrier damage, and brain metabolism abnormalities involved in the development of TBI. As an important concept in the field of psychiatry, TBI is based on organic injury, which is largely different from many other mental disorders. Therefore, military TBI is both neuropathic and psychopathic, and is an emerging challenge at the intersection of neurology and psychiatry.

Extracellular vesicles (EVs) are nanoscale particles with various physiological functions including mediating cellular communication in the central nervous system (CNS), which indicates a linkage between these particles and mental disorders such as schizophrenia, bipolar disorder, major depressive disorder, etc. To date, known characteristics of mental disorders are mainly neuroinflammation and dysfunctions of homeostasis in the CNS, and EVs are proven to be able to regulate these pathological processes. In addition, studies have found that some cargo of EVs, especially miRNAs, were significantly up- or down-regulated in patients with mental disorders. For many years, interest has been generated in exploring new diagnostic and therapeutic methods for mental disorders, but scale assessment and routine drug intervention are still the first-line applications so far. Therefore, underlying the downstream functions of EVs and their cargo may help uncover the pathogenetic mechanisms of mental disorders as well as provide novel biomarkers and therapeutic candidates. This review aims to address the connection between EVs and mental disorders, and discuss the current strategies that focus on EVs-related psychiatric detection and therapy.

Background: Most of the previous studies have demonstrated the potential antidepressive and anxiolytic role of prebiotic supplement in male subjects, yet few have females enrolled. Herein, we explored whether prebiotics administration during chronic stress prevented depression‐like and anxiety‐like behavior in a sex‐specific manner and the mechanism of behavioral differences caused by sex.Methods: Female and male C57 BL/J mice on normal diet were supplemented with or without a combination of fructo‐oligosaccharides (FOS) and galacto‐oligosaccharides (GOS) during 3‐ and 4‐week chronic restraint stress (CRS) treatment, respectively. C57 BL/J mice on normal diet without CRS were used as controls. Behavior consequences, gut microbiota, dysfunction of gut and brain–blood barriers, and inflammatory profiles were measured.Results: In the 3rd week, FOS + GOS administration attenuated stress‐induced anxiety‐like behavior in female, but not in male mice, and the anxiolytic effects in males were observed until the 4th week. However, protective effects of prebiotics on CRS‐induced depression were not observed. Changes in the gene expression of tight junction proteins in the distal colon and hippocampus, and decreased number of colon goblet cells following CRS were restored by prebiotics only in females. In both female and male mice, prebiotics alleviated stress‐induced BBB dysfunction and elevation in pro‐inflammatory cytokines levels, and modulated gut microbiota caused by stress. Furthermore, correlation analysis revealed that anxiety‐like behaviors were significantly correlated with levels of pro‐inflammatory cytokines and gene expression of tight junction proteins in the hippocampus of female mice, and the abundance of specific gut microbes was also correlated with anxiety‐like behaviors, pro‐inflammatory cytokines, and gene expression of tight junction proteins in the hippocampus of female mice.Conclusion: Female mice were more vulnerable to stress and prebiotics than males. The gut microbiota, gut and blood–brain barrier, and inflammatory response may mediate the protective effects of prebiotics on anxiety‐like behaviors in female mice.

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

The clinical efficacy of lurasidone and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, and metabolic profiles in children and adolescents with bipolar depression. We recruited young participants (aged 10–17 years old) with a DSM-5 diagnosis of bipolar disorder during a depressive episode, who were then randomly assigned to two groups and treated with flexible doses of lurasidone (60 to 120 mg/day) or quetiapine (300 to 600 mg/day) for consecutive 8 weeks, respectively. All the participants were clinically evaluated on cognitive function using the THINC-it instrument at baseline and week 8, and emotional status was assessed at baseline and the end of week 2, 4, and 8. Additionally, the changes in weight and serum metabolic profiles (triglyceride, cholesterol, and fasting blood glucose) during the trial were also analyzed. In results, a total of 71 patients were randomly assigned to the lurasidone group (n = 35) or the quetiapine group (n = 36), of which 31 patients completed the whole treatment course. After an 8-week follow-up, participants in the lurasidone group showed better performance in the Symbol Check Reaction and Accuracy Tests, when compared to those in the quetiapine group. No inter-group difference was observed in the depression scores, response rate, or remission rate throughout the trial. In addition, there was no significant difference in serum metabolic profiles between the lurasidone group and the quetiapine group, including triglyceride level, cholesterol level, and fasting blood glucose level. However, the quetiapine group presented a more apparent change in body weight than the lurasidone group. In conclusion, the present study provided preliminary evidence that quetiapine and lurasidone had an equivalent anti-depressive effect, and lurasidone appeared to be superior to quetiapine in improving the cognitive function of young patients with bipolar depression.