Background: Brain-derived neurotrophic factor (BDNF) is known to prevent methamphetamine (METH)-induced neurotoxicity and plays a role in various stages of METH addiction. However, there is a lack of research with longitudinal design on changes in plasma BDNF levels in active METH-dependent individuals.
Aims: The aim of the study was to investigate changes in BDNF levels during METH self-administration in monkeys.
Methods: This study measured plasma BDNF levels in three male rhesus monkeys with continuous METH exposure and four male control rhesus monkeys without METH exposure. Changes in plasma BDNF levels were then assessed longitudinally during 40 sessions of METH self-administration in the three monkeys.
Results: Repeated METH exposure decreased plasma BDNF levels. Additionally, plasma BDNF decreased with long-term rather than short-term accumulation of METH during METH self-administration.
Conclusions: These findings may indicate that the changes in peripheral BDNF may reflect the quantity of accumulative METH intake during a frequent drug use period.
Background: Case-finding is a recommended approach for dementia early detection in the community.
Aims: To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community.
Methods: The two-phase study was conducted in the community from 2009 to 2015 in Singapore. A total of 3780 participants (age ≥60 years) completed phase I (a brief cognitive screening); 918 completed phase II and were included in the final analysis. In phase I, all participants were administered the Abbreviated Mental Test (AMT) and the Progressive Forgetfulness Question (PFQ). Those who screened positive on either test were invited to phase II, whereby the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery were administered, followed by the research diagnosis of no cognitive impairment, cognitive impairment no dementia (CIND)-Mild (≤2 impaired cognitive domains), CIND-Moderate (>2 impaired domains) or dementia. Receiver operating characteristic curve analyses were conducted for the different cognitive instruments. All discriminant indices were calculated, including sensitivity, specificity, positive and negative predictive values (NPV) and accuracy. Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios, ie, with or without preselection by the PFQ.
Results: The stepwise case-finding approach (preselection by the PFQ, then MMSE or MoCA or AMT) showed an excellent NPV (>99%) and accuracy (>86%) for excluding dementia-free cases. Without preselection by the PFQ, screening time for the three cognitive tools were 317.5, 317.5 and 254 hours, with 159, 302 and 175 screen-positive older adults involved in further evaluation. By adopting the stepwise case-finding approach, total screening time were 156.5, 156.5 and 126.2 hours, which decreased by 50.7%, 50.7% and 50.3% as compared with those without preselection. Furthermore, after preselection, only 98, 167 and 145 screen-positive older adults required further evaluation, corresponding to a reduction of 38.4%, 44.7% and 17.1% in the numbers compared with those without preselection.
Conclusions: A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.
Incentivised by breakthroughs and data generated by the high-throughput sequencing technology, this paper proposes a distance-based framework to fulfil the emerging needs in elucidating insights from the high-dimensional microbiome data in psychiatric studies. By shifting focus from traditional methods that focus on the observations from each subject to the between-subject attributes that aggregate two or more subjects' entire feature vectors, the described approach revolutionises the conventional prescription for high-dimensional observations via microbiome diversity. To this end, we enrich the classical generalised linear models to articulate the multivariable regression relationship between distance-based variables. We also discuss a robust and computationally feasible semiparametric inference technique. Benefitting from the latest advances in the semiparametric efficiency theory for such attributes, the proposed estimators enjoy robustness and good asymptotic properties that guarantee sensitivity in detecting signals between clinical outcomes and microbiome diversity. It offers a readily implementable and easily interpretable solution for deciphering the gut-brain axis in mental health research.
Depression is a major contributor to poor global health and disability, with a recently increasing incidence. Although drug therapy is commonly used to treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates and severe adverse effects. Therefore, developing effective therapies for depression remains challenging. Although various aetiological theories of depression exist, the underlying mechanisms of depression are complex, and further research is crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis. Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders, and investigation of the mediators involved in these processes has emerged as a prominent and active research direction. One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression, and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosis in vivo, suggesting an important role of ferroptosis in the pathogenesis of depression. Hence, our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved, specifically concerning ferroptosis and OS in the context of depression, along with promising prospects for using molecular mediators to target ferroptosis. We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression, most notably reactive oxygen species and iron overload. Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders, delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.
Background: Youth suicide has been a pressing public mental health concern in China, yet there is a lack of gatekeeper intervention programmes developed locally to prevent suicide among Chinese adolescents.
Aims: The current Delphi study was the first step in the systematic development of the Life Gatekeeper programme, the first gatekeeper programme to be developed locally in China that aims to equip teachers and parents with the knowledge, skills and ability to identify and intervene with students at high risk of suicide.
Methods: The Delphi method was used to elicit a consensus of experts who were invited to evaluate the importance of training content, the feasibility of the training delivery method, the possibility of achieving the training goals and, finally, the appropriateness of the training materials. Two Delphi rounds were conducted among local experts with diversified professional backgrounds in suicide research and practice. Statements were accepted for inclusion in the adjusted training programme if they were endorsed by at least 80% of the panel.
Results: Consensus was achieved on 201 out of 207 statements for inclusion into the adapted guidelines for the gatekeeper programme, with 151 from the original questionnaire and 50 generated from comments of the panel members. These endorsed statements were synthesised to develop the content of the Life Gatekeeper training programme.
Conclusions: This Delphi study provided an evidence base for developing the first gatekeeper training programme systematically and locally in China. We hope that the current study can pave the way for more evidence-based suicide prevention programmes in China. Further study is warranted to evaluate the effectiveness of the Life Gatekeeper training programme.
Background: Avoidant paruresis is a common clinical condition in urology and psychosomatic medicine. However, it has limited treatment options that are safe and effective with few side effects.
Aims: Our study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural therapy (CBT) for avoidant paruresis.
Methods: Sixty-eight patients with avoidant paruresis were divided into a treatment group (33 patients) and a control group (35 patients). The control group was assigned 10 weeks of CBT and systematic desensitisation. In addition to CBT and systematic desensitisation, the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study. The Shy Bladder Syndrome Scale (SBS) and the Self-rating Anxiety Scale (SAS) were administered before and after treatment to measure any change.
Results: The overall efficacy in the treatment group (n=30) was 80.0% vs 62.5% in the control group (n=33). Comparing pretreatment and post-treatment measures, both groups showed improvement in SBS scores and SAS scores (treatment group: t(SBS) =8.397, p(SBS) <0.001, t(SAS) =8.216, p(SAS)<0.001; control group: t(SBS) =6.802, p(SBS) <0.001, t(SAS)=5.171, p(SAS) <0.001). Moreover, both groups' SBS and SAS scores changed significantly over time (SBS scores: Ftime =118.299, p<0.001; SAS scores: Ftime =92.114, p<0.001). However, the treatment group performed better than the control group (SBS scores: Ftime*group =5.709, p=0.020; SAS scores: Ftime*group =7.235, p=0.009).
Conclusions: The Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural psychotherapy positively affects the treatment of avoidant paruresis without significant adverse effects.