Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.

Methamphetamine abuse is getting worse amongst the younger population. While there is methadone or buprenorphine harm-reduction treatment for heroin addicts, there is no drug treatment for addicts with methamphetamine use disorder (MUD). Recently, non-medication treatment, such as the cue-elicited craving method integrated with biofeedback, has been widely used. Further, virtual reality (VR) is proposed to simulate an immersive virtual environment for cue-elicited craving in therapy. In this study, we developed a VR system equipped with flavor simulation for the purpose of inducing cravings for MUD patients in therapy. The VR system was integrated with multi-model sensors, such as an electrocardiogram (ECG), galvanic skin response (GSR) and eye tracking to measure various physiological responses from MUD patients in the virtual environment. The goal of the study was to validate the effectiveness of the proposed VR system in inducing the craving of MUD patients via the physiological data. Clinical trials were performed with 20 MUD patients and 11 healthy subjects. VR stimulation was applied to each subject and the physiological data was measured at the time of pre-VR stimulation and post-VR stimulation. A variety of features were extracted from the raw data of heart rate variability (HRV), GSR and eye tracking. The results of statistical analysis found that quite a few features of HRV, GSR and eye tracking had significant differences between pre-VR stimulation and post-VR stimulation in MUD patients but not in healthy subjects. Also, the data of post-VR stimulation showed a significant difference between MUD patients and healthy subjects. Correlation analysis was made and several features between HRV and GSR were found to be correlated. Further, several machine learning methods were applied and showed that the classification accuracy between MUD and healthy subjects at post-VR stimulation attained to 89.8%. In conclusion, the proposed VR system was validated to effectively induce the drug craving in MUD patients.

Methamphetamine use disorder (MUD) is a brain disease that leads to altered regional neuronal activity. Virtual reality (VR) is used to induce the drug cue reactivity. Previous studies reported significant frequency-specific neuronal abnormalities in patients with MUD during VR induction of drug craving. However, whether those patients exhibit neuronal abnormalities after VR induction that could serve as the treatment target remains unclear. Here, we used an integrated VR system for inducing drug related changes and investigated the neuronal abnormalities after VR exposure in patients. Fifteen patients with MUD and ten healthy subjects were recruited and exposed to drug-related VR environments. Resting-state EEG were recorded for 5 minutes twice-before and after VR and transformed to obtain the frequency-specific data. Three self-reported scales for measurement of the anxiety levels and impulsivity of participants were obtained after VR task. Statistical tests and machine learning methods were employed to reveal the differences between patients and healthy subjects. The result showed that patients with MUD and healthy subjects significantly differed in Θ, α, and γ power changes after VR. These neuronal abnormalities in patients were associated with the self-reported behavioral scales, indicating impaired impulse control. Our findings of resting-state EEG abnormalities in patients with MUD after VR exposure have the translational value and can be used to develop the treatment strategies for methamphetamine use disorder.

Although previous animal studies have indicated that certain micro ribonucleic acids (microRNAs) play a part in the pathway of opioid addiction, whether such findings extend to human models is yet unknown. This study aims to investigate the important microRNA expressions in patients with opioid use disorder (OUD) on methadone maintenance treatment (MMT) compared to healthy controls and analyze the correlation between microRNAs and opioid characteristics among the patients. We recruited 50 patients and 25 controls, and both groups were matched regarding gender, age, and body mass index. Serum microRNAs (miR-133b, miR-23b, miR-190, miR-206, miR-210, and miR-21) were measured. The age of OUD onset, duration of MMT participation, and recent daily methadone dosage were considered the opioid characteristics. We adopted the t-test to compare the difference between patients and controls and Pearson’s correlation to evaluate the association between microRNAs and opioid profiles. Only the level of miR-133b in OUD patients on MMT was significantly lower than that in healthy controls. We did not detect differences of any other microRNA expressions between the two groups. Furthermore, we found no evidence to support the association between microRNAs and opioid characteristics. This study indicates that miR-133b values may be decreased in OUD patients on MMT.

The pathophysiology of alcohol use disorder (AUD) is not totally clear. The aim of this study was to investigate the serum levels of brain-derived neurotrophic factor (BDNF) and oxidative stress markers in AUD patients during alcohol detoxification. Evaluation of changes in BDNF, glutathione peroxidase (GPX), catalase, superoxide dismutase, thiobarbituric acid reactive substances, 8-hydroxy 2’-deoxyguanosine, PCC and S100B were carried out. 14 AUD inpatients and 20 healthy control subjects were recruited for this study. The serum BDNF, S100B and oxidative stress markers were measured with assay kits. Serum levels of catalase, GPX, PCC and 8-hydroxy 2’-deoxyguanosine were significantly higher in the AUD group subjects than in the controls (P < .05). However, BDNF levels were lower in the AUD group than in the controls (P < .05). After alcohol detoxification treatment, the GPX levels in the AUD group dropped (P < .05) and the BDNF levels rose (P < .05). The results suggest that serum BDNF and GPX levels might be state biomarkers for AUD patients undergoing alcohol detoxification.