A multicenter, randomized controlled study on the efficacy of agomelatine in ameliorating anhedonia, reduced motivation, and circadian rhythm disruptions in patients with major depressive disorder (MDD).

OBJECTIVE: To evaluate the clinical efficacy and safety of Agomelatine in improving symptoms in patients with major depressive disorder (MDD), providing more scientific evidence for the treatment of depression, and offering more effective therapeutic options for patients. METHODS: A total of 180 MDD patients in acute phase from 10 psychiatric hospitals of Grade three in Zhejiang Province were enrolled in this 12-week study with the competitive and consecutive pattern, and they were randomized into two different groups treated with flexible-dosage antidepressants of selective serotonin reuptake inhibitors (SSRI) or agomelatine, respectively. The subjects were evaluated with psychological scales of HAMD-17, HAMA, SHAPS for anhedonia, MFI-20 for fatigue, PQSI for sleep quality and MEQ for disturbances in chronobiologic rhythms at baseline, 2, 4, 8 and 12-weekend points, and TESS was used for side-effect. The results were analyzed with repeated measurement analysis of variance. RESULTS: The two groups each had 90 participants, and there were no significant differences at baseline. The scores of various assessment scales showed statistically significant time main effects during the visits (P < 0.01). The Agomelatine group demonstrated faster efficacy within 2 weeks, with better improvement in SHAPS, MEQ, and PSQI compared to the SSRIs group. However, the remission rate at 12 weeks was lower in the Agomelatine group than in the SSRIs group (63.3% and 72.2%), but the difference between the groups was not statistically significant. The Agomelatine group had fewer adverse reactions (14.4% and 16.7%), but there was a slightly higher incidence of liver function impairment (6.7% and 4.4%), with no statistically significant difference between the groups. CONCLUSION: Agomelatine, as a novel antidepressant, shows certain advantages in improving depression and anxiety symptoms and is comparable to SSRIs in terms of safety. However, its long-term efficacy and safety on MDD or other depressive subtypes still require further observation and research.

Transcutaneous electrical acupoint stimulation for post-traumatic stress disorder: Assessor-blinded, randomized controlled study.

AIM: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. CONCLUSIONS: Additional TEAS augments the anti-PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255).

Psychological trauma, posttraumatic stress disorder and trauma-related depression: A mini-review.

There are various types of traumatic stimuli, such as catastrophic events like wars, natural calamities like earthquakes, and personal trauma from physical and psychological neglect or abuse and sexual abuse. Traumatic events can be divided into type I and type II trauma, and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals' self-evaluation of the traumatic events. Individual stress reactions to trauma include posttraumatic stress disorder (PTSD), complex PTSD and trauma-related depression. Trauma-related depression is a reactive depression with unclear pathology, and depression occurring due to trauma in the childhood has gained increasing attention, because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy, which is similar to the pattern observed for PTSD. Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse, it is necessary to explore its pathogenesis and therapeutic strategy.

[Effects of apolipoprotein E genetic polymorphism on susceptibility of depression and efficacy of antidepressants].

OBJECTIVE: To assess the effects of apolipoprotein E (APOE) polymorphism on the susceptibility of depression and the efficacy of antidepressants. METHODS: A total of 275 patients with depression, who met the diagnostic criteria of both CCMD-3 and DSM-4, were randomly assigned into venlafaxine group (n=136)and paroxetine group(n=139). Another 202 healthy subjects were enrolled as the control group. Hamilton Rating Scale for Depression (HAMD)-17 was adopted as the primary rating instrument to evaluate the severity of depression on the baseline and the end of the 1st, 2nd, 4th, 6th week after treatment, respectively. HAMD scores ≤7 was defined as remission, and the reduction of HAMD scores ≥50% was defined as response while <50% was defined as invalid. PCR-restriction fragment length polymorphisms (PCR-RFLP) was applied to detect the genetic polymorphism of the APOE in the case groups and control group. RESULTS: In the venlafaxine group, the remission rate was 52.9%(n=72), the response rate was 26.5%(n=36), and the invalid rate was 20.6%(n=28), whereas the corresponding data in the paroxetine group wee 42.4%(n=59), 31.7%(n=44), and 25.9% (n=36), respectively. There were no significant differences in the efficacy between the two groups(p>0.05). In the venlafaxine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 between the remitters, nonremitters, and healthy controls at the end of the 6th week(p>0.05), but there was significant differences in the allele distribution frequency between the nonremitters and healthy controls(p=0.02). In paroxetine group, there were no significant differences in the genotypes and the allele distribution frequency of APOEΕ2/Ε3/Ε4 among the remitters, nonremitters and healthy controls at the end of the 6th week(p>0.05), but there were significant differences in the allele distribution frequency between the nonremitters and healthy controls (p=0.04); in addition, there were also significant differences in Ε2/Ε3 and Ε4 allele between the two groups (p=0.014). CONCLUSIONS: The APOE gene may not play a major role in the pathogenesis of major depression. The efficacy of venlafaxine is same as paroxetine after treatment for six weeks. The APOE (Ε2+Ε3) allele may be an indicator of the bad efficacy of paroxetine treatment.

[Dynamic level observation of brain-derived neurotrophic factor in patients with first-episode generalized anxiety disorder].

OBJECTIVE: To examine the changing pattern of brain-derived neurotrophic factor (BDNF) in the patients with first-episode generalized anxiety disorder (GAD). METHODS: The levels of plasma BDNF and the Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores were measured in 34 patients with first-episode GAD recruited from our hospital between January and December 2007. At baseline and Week 6, they were treated by paroxetine and compared with 31 healthy participants in the control group. RESULTS: The baseline level of BDNF [(80 ± 51) ng/L] in the patients with first-episode GAD was higher than that in the control group and had no significant correlation with HAMA and HAMD scores. But at Week 6, the level of BDNF [(70 ± 49) ng/L] had significant correlations with HAMA and HAMD scores (r = 0.4, P = 0 and r = 0.4, P = 0 respectively). At Week 6, the levels of BDNF in the response group (including remission group) and ineffective group were (60 ± 42) ng/L and (83 ± 55) ng/L respectively. And there was significant difference in the levels of BDNF between the ineffective and control groups. The levels of BDNF in the remission and non-remission groups were (59 ± 52) ng/L and (73 ± 49) ng/L respectively. And there was significant difference in the levels of BDNF between the non-remission and control groups. CONCLUSION: The pre-treatment levels of plasma BDNF in the patients with first-episode GAD are higher than those of healthy counterparts. But normal levels may be restored if the patients are cured.

[A comparative study on mental health among students and adults in the earthquake-hit areas].

OBJECTIVE: To understand mental health status of the students and adults in the earthquake disaster areas, as to providing guidance on intervention for post-disaster psychological crisis. METHODS: The Self-Reporting Questionnaire (SRQ-20), an appendix of The Ministry of Health of "emergency psychological crisis intervention guiding principles", was used among 1222 victims in Wenchuan earthquake, Sichuan province. This questionnaire survey was conducted in 729 students and 493 adult victims in a randomized method. Of the 734 questionnaires distributed and received in students, 729 were validly responded with efficiency rate of 99.32%; while for adults, 496 questionnaires distributed, 496 received, 493 were valid with efficiency rate of 99.39%. RESULTS: (1) In students victims, 65% responded that they did feel "uneasy, nervous or worried", followed by "easy to be scared", "feel unhappy", "easy fatigue" and "hard to make a decision". For adult victims, 80.5% replied that they felt "uneasy, nervous or worried", followed by "feel unhappy", "easy fatigue", "difficult sleeping", "easy to be scared". (2) The average of the SRQ score of student victims was 6.58 +/- 3.99, and 6.07 +/- 4.02 for males, 7.03 +/- 3.91 for females. The average of the SRQ score of student victims was 7.36 +/- 3.98, male 6.68 +/- 3.82, female 7.99 +/- 4.03. The significant differences (t(women) = 2.985, P < 0.01; t(total) = 3.332, P < 0.01) was observed in women and the total group of students and adults. (3) The SRQ positive screening rate of students group was 46.50%, the adult group was 52.33%, SRQ >or= 7 points and SRQ < 7 sub-group of students and adults of the total score there were significant differences (t(1) = 39.771, P < 0.01; t(2) = 31.961, P < 0.01). SRQ >or= 7 sub-group of students and adult women in between there was a significant difference (t = 23.641, P < 0.01), SRQ < 7 sub-group of students and adults in general and women there were significant differences (t(1) = 3.092, P < 0.01; t(2) = 2.911, P < 0.01). (4) SRQ scores with gender and age had had a positive relation (r(SRQ total-sex) = 0.118, P = 0.000; r(SRQ total-age) = 0.103, P = 0.000). CONCLUSION: The emotional suffering symptoms of students victims and adult victims should be "nervous, unhappy, vulnerable on issues such as fatigue", the adult group had a higher symptom rate than the group of students, the mental health was more serious than that of students, as influenced by some factors including age and gender. Students, being a special population group should be paid more attention to focusing a designated behavior intervention, as a planned manner of intervention.

Caspase-8 Mediates Amyloid-ß-induced Apoptosis in Differentiated PC12 Cells.

The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-ß 1-40 (Aß1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aß-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aß1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aß1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aß1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aß1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.