BMC Psychiatry

Onset of alcohol use by 14 relative to 21 years of age strongly predicts elevated risk for severe alcohol use problems, with 27% versus 4% of individuals exhibiting alcohol dependence within 10 years of onset. What remains unclear is whether this early alcohol use (i) is a marker for later problems, reflected as a pre-existing developmental predisposition, (ii) causes global neural atrophy or (iii) specifically disturbs neuro-maturational processes implicated in addiction, such as executive functions or reward processing. Since our group has demonstrated that a novel intervention program targeting personality traits associated with adolescent alcohol use can prevent the uptake of drinking and binge drinking by 40 to 60%, a crucial question is whether prevention of early onset alcohol misuse will protect adolescent neurodevelopment and which domains of neurodevelopment can be protected. A subsample of 120 youth at high risk for substance misuse and 30 low-risk youth will be recruited from the Co-Venture trial (Montreal, Canada) to take part in this 5-year follow-up neuroimaging study. The Co-Venture trial is a community-based cluster-randomised trial evaluating the effectiveness of school-based personality-targeted interventions on substance use and cognitive outcomes involving approximately 3800 Grade 7 youths. Half of the 120 high-risk participants will have received the preventative intervention program. Cognitive tasks and structural and functional neuroimaging scans will be conducted at baseline, and at 24- and 48-month follow-up. Two functional paradigms will be used: the Stop-Signal Task to measure motor inhibitory control and a modified version of the Monetary Incentive Delay Task to evaluate reward processing. The expected results should help identify biological vulnerability factors, and quantify the consequences of early alcohol abuse as well as the benefits of early intervention using brain metrics.

Rối loạn giấc ngủ, bao gồm mất ngủ, là phổ biến ở người lớn mắc Rối loạn Tăng động Giảm chú ý (ADHD). Phương pháp điều trị lựa chọn cho mất ngủ là liệu pháp hành vi nhận thức (CBT-i), nhưng chứng cứ về CBT-i ở bệnh nhân ADHD còn thiếu. Mục đích của nghiên cứu này là điều tra xem liệu bệnh nhân có triệu chứng mất ngủ và các vấn đề giấc ngủ khác, tại một phòng khám chuyên biệt cho ADHD, có được hưởng lợi từ việc điều trị hành vi nhóm dựa trên CBT-i hay không; liệu mức độ nghiêm trọng của mất ngủ có cải thiện sau điều trị này hay không. Nghiên cứu thí nghiệm trong nhóm này với thiết kế trước và sau điều trị và theo dõi ba tháng được thực hiện tại một phòng khám tâm thần ngoại trú chuyên biệt cho ADHD ở người lớn. Như một phần bổ sung cho chăm sóc thông thường tại phòng khám, một liệu pháp nhóm dựa trên CBT-i nhằm vào các vấn đề giấc ngủ phổ biến trong dân số ADHD đã được cung cấp dưới hình thức 10 buổi nhóm 90 phút hàng tuần và hỗ trợ qua điện thoại theo lịch. Tất cả các chỉ số kết quả đều được báo cáo chủ quan bởi các người tham gia. Dữ liệu được phân tích bằng các bài kiểm tra t phụ thuộc theo hướng điều trị dự kiến. Mười chín bệnh nhân (37 [SD 13.7] tuổi; 68% nữ) mắc ADHD và có các vấn đề giấc ngủ được báo cáo chủ quan đã cung cấp sự đồng ý tham gia và các chỉ số trước điều trị. Bệnh nhân đã phải chịu đựng các vấn đề giấc ngủ trong 15.3 [SD 13.4] năm, 42% đã sử dụng thuốc ngủ, 79% đã sử dụng thuốc kích thích. Sau điều trị, mức độ nghiêm trọng của mất ngủ (Chỉ số Mức độ Nghiêm trọng Của Mất Ngủ; khoảng điểm 0–28) đã cải thiện 4.5 điểm (95% CI, 2.06–6.99, p = .002), tại 3 tháng là 6.8 điểm (95% CI, 4.71–8.91, p < .0001) so với trước điều trị. CBT-i điều chỉnh cho ADHD hứa hẹn sẽ cải thiện mức độ nghiêm trọng của mất ngủ ở bệnh nhân trưởng thành tại các phòng khám tâm thần ngoại trú chuyên biệt, những người mắc ADHD và rối loạn giấc ngủ. Nghiên cứu đã được đăng ký với Hội đồng đánh giá đạo đức khu vực tại Stockholm, ngày 13 tháng 1 năm 2016, ID nghiên cứu: 2015/2078–31/1. Nghiên cứu đã được đăng ký hồi tố với Clinicaltrials.org, ngày 21 tháng 2 năm 2019, ID: NCT03852966.

The association between sleep-related disorders and inflammation has been demonstrated in previous studies. The systemic immune-inflammation index (SII) is a novel inflammatory index based on leukocytes, but its relationship with sleep-related disorder is unclear. We aimed to investigate the relationship between sleep-related disorder and SII in a nationally representative nonhospitalized sample. Data were obtained from the 2005–2008 National Health and Nutrition Examination Survey (NHANES). Exposure variables included self-reported sleep-related disorders, such as sleep duration, sleep problems, high risk of OSA, and daytime sleepiness. SII and other traditional markers of inflammation were considered as outcome variables, including platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). Multiple linear regression models were employed to examine the correlation between sleep-related disorders and inflammatory markers. Subgroup interactions were analyzed using likelihood ratio tests, and nonlinear relationships were explored by fitting restricted cubic splines. A total of 8,505 participants were enrolled in this study. Overall, sleep-related disorders were found to have a stronger association with SII compared to the PLR and NLR. The results of multiple linear regression analysis revealed that participants who experienced sleep problems (β: 21.421; 95% CI 1.484, 41.358), had symptoms of OSA (β: 23.088; 95% CI 0.441, 45.735), and reported daytime sleepiness (β: 30.320; 95% CI 5.851, 54.789) exhibited a positive association with higher SII. For the analysis of other inflammatory markers, we only found that daytime sleepiness was associated with increased NLR levels (β: 0.081; 95% CI 0.002, 0.159). Sleep problems, symptoms of OSA, and daytime sleepiness were found to have a positive association with the SII in US adults. However, further prospective studies are necessary to establish whether there is a causal relationship between these factors.

Many Canadian adolescents and young adults with mental health problems face delayed detection, long waiting lists, poorly accessible services, care of inconsistent quality and abrupt or absent inter-service transitions. To address these issues, ACCESS Open Minds, a multi-stakeholder network, is implementing and systematically evaluating a transformation of mental health services for youth aged 11 to 25 at 14 sites across Canada. The transformation plan has five key foci: early identification, rapid access, appropriate care, the elimination of age-based transitions between services, and the engagement of youth and families. The ACCESS Open Minds Research Protocol has multiple components including a minimum evaluation protocol and a stepped-wedge cluster randomized trial, that are detailed in this paper. Additional components include qualitative methods and cost-effectiveness analyses. The services transformation is being evaluated at all sites via a minimum evaluation protocol. Six sites are participating in the stepped-wedge trial whereby the intervention (a service transformation along the key foci) was rolled out in three waves, each commencing six months apart. Two sites, one high-population and one low-population, were randomly assigned to each of the three waves, i.e., randomization was stratified by population size. Our primary hypotheses pertain to increased referral numbers, and reduced wait times to initial assessment and to the commencement of appropriate care. Secondary hypotheses pertain to simplified pathways to care; improved clinical, functional and subjective outcomes; and increased satisfaction among youth and families. Quantitative measures addressing these hypotheses are being used to determine the effectiveness of the intervention. Data from our overall research strategy will help test the effectiveness of the ACCESS Open Minds transformation, refine it further, and inform its scale-up. The process by which our research strategy was developed has implications for the practice of research itself in that it highlights the need to actively engage all stakeholder groups and address unique considerations in designing evaluations of complex healthcare interventions in multiple, diverse contexts. Our approach will generate both concrete evidence and nuanced insights, including about the challenges of conducting research in real-world settings. More such innovative approaches are needed to advance youth mental health services research. Clinicaltrials.gov, ISRCTN23349893 (Retrospectively registered: 16/02/2017).

Theoretically, consumption of complex, multinutrient formulations of vitamins and minerals should be safe, as most preparations contain primarily the nutrients that have been in the human diet for millennia, and at safe levels as defined by the Dietary Reference Intakes. However, the safety profile of commercial formulae may differ from foods because of the amounts and combinations of nutrients they contain. As these complex formulae are being studied and used clinically with increasing frequency, there is a need for direct evaluation of safety and tolerability. All known safety and tolerability data collected on one complex nutrient formula was compiled and evaluated. Data were assembled from all the known published and unpublished studies for the complex formula with the largest amount of published research in mental health. Biological safety data from 144 children and adults were available from six sources: there were no occurrences of clinically meaningful negative outcomes/effects or abnormal blood tests that could be attributed to toxicity. Adverse event (AE) information from 157 children and adults was available from six studies employing the current version of this formula, and only minor, transitory reports of headache and nausea emerged. Only one of the studies permitted a direct comparison between micronutrient treatment and medication: none of the 88 pediatric and adult participants had any clinically meaningful abnormal laboratory values, but tolerability data in the group treated with micronutrients revealed significantly fewer AEs and less weight gain. This compilation of safety and tolerability data is reassuring with respect to the broad spectrum approach that employs complex nutrient formulae as a primary treatment.

Prenatal depression can negatively affect the physical and mental health of both mother and fetus. The aim of this study was to determine the effectiveness of yoga as an intervention in the management of prenatal depression. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching PubMed, Embase, the Cochrane Library and PsycINFO from all retrieved articles describing such trials up to July 2014. Six RCTs were identified in the systematic search. The sample consisted of 375 pregnant women, most of whom were between 20 and 40 years of age. The diagnoses of depression were determined by their scores on Structured Clinical Interview for DSM-IV and the Center for Epidemiological Studies Depression Scale. When compared with comparison groups (e.g., standard prenatal care, standard antenatal exercises, social support, etc.), the level of depression statistically significantly reduced in yoga groups (standardized mean difference [SMD], −0.59; 95% confidence interval [CI], −0.94 to −0.25; p = 0.0007). One subgroup analysis revealed that both the levels of depressive symptoms in prenatally depressed women (SMD, −0.46; CI, −0.90 to −0.03; p = 0.04) and non-depressed women (SMD, −0.87; CI, −1.22 to −0.52; p < 0.00001) were statistically significantly lower in yoga group than that in control group. There were two kinds of yoga: the physical-exercise-based yoga and integrated yoga, which, besides physical exercises, included pranayama, meditation or deep relaxation. Therefore, the other subgroup analysis was conducted to estimate effects of the two kinds of yoga on prenatal depression. The results showed that the level of depression was significantly decreased in the integrated yoga group (SMD, −0.79; CI, −1.07 to −0.51; p < 0.00001) but not significantly reduced in physical-exercise-based yoga group (SMD, −0.41; CI, −1.01 to −0.18; p = 0.17). Prenatal yoga intervention in pregnant women may be effective in partly reducing depressive symptoms.

Depression is a mental disease involving complex pathophysiological mechanisms, and there are many ways to establish depressive mouse models. The purpose of this study is to comprehensively compare the behavioral changes and its mechanism induced by two different models. This study established two depressive mouse models by maternal separation (MS) or lipopolysaccharide (LPS) administration, and added fluoxetine treatment group respectively for comparison. MS induced more apparent anxiety-like behavior while LPS induced more apparent depressive-like behavior. LPS increased peripheral inflammatory factors more apparent, which were mitigated by fluoxetine. MS inhibited the 5-HT system more obviously and was relieved by fluoxetine. LPS triggered stronger immune response in the hippocampus and prefrontal cortex (PFC). MS significantly reduced the expression of neurotrophic proteins and was alleviated by fluoxetine. Overall, LPS induced stronger system inflammation, while MS impaired the function of HPA axis and 5-HT system. Our results will contribute to a deeper understanding of the pathophysiology of different stress-induced depression and will also help researchers select appropriate models of depression for their own needs.

Use of the atypical antipsychotic sertindole was suspended for four years due to safety concerns. During the suspension, the regulatory authorities required further studies, including this one, to be conducted. The purpose of this study was to determine if a subset of patients with psychotic illness exists which particularly benefits from sertindole treatment after failure of other antipsychotic drugs, including atypical antipsychotics. This was a retrospective single-arm observational crossover study of 344 patients, who served as their own controls. Patients mainly from the Sertindole Safety Study who had shown good response to sertindole, and who had followed up to four alternating six month periods of treatment with sertindole and other antipsychotics, were included. (In Period 1 patients took non-sertindole treatment, in Period 2, sertindole was taken, in Period 3, patients reverted to non-sertindole treatment, and in Period 4, sertindole was taken again.) Patient records for each period of treatment were assessed for objective data: number and duration of hospitalizations due to worsening of psychotic symptoms; the amount of self-harming behaviour; indicators of social status. Retrospective evaluation of changes in clinical symptoms from the patients' records was also conducted. Dates and reasons for stopping and/or switching medication were also recorded. There was improvement in all objective measured parameters during the periods of sertindole treatment. In particular, the average number of hospitalizations per year due to worsening of psychotic symptoms was reduced in the following way in the group studied over four treatment periods: Period 1 (non-sertindole treatment) 3.4; Period 2 (sertindole treatment) 1.0; Period 3 (non-sertindole treatment) 2.0; Period 4 (sertindole treatment) 1.8. The duration of hospitalizations also decreased significantly during the periods of sertindole treatment. Results showed that patients improved in objective social parameters when switched to sertindole treatment; assessment of the patients' affective lives showed a significant increase in the number of patients having a stable relationship during sertindole treatment; and assessment of the number of patients employed showed an increase after the first and second switch to sertindole treatment (from Period 1 to Period 2 and from Period 3 to Period 4, respectively). Adverse events and lack of efficacy were the main reasons for switching to sertindole. A group of patients benefited from sertindole after other antipsychotic treatments, including that with atypical antipsychotics, had failed. Further studies are needed to investigate if there is a specific patient profile that corresponds to these responders.

Individuals with major depressive disorder (MDD) have a high suicide risk. Some evidence suggests that uric acid (UA) may be involved in the pathophysiology of MDD. The purpose of this study was to evaluate whether serum UA levels were associated with suicide risk in MDD patients. One hundred four female patients with MDD (52 patients with suicide risk and 52 patients without suicide risk) and 52 healthy individuals were included in this study. The suicide risk was evaluated by Mini International Neuropsychiatric Interview (M.I.N.I.). Fasting serum levels of UA, as well as glucose, lipid and renal function indicators were measured. Serum UA levels in MDD patients with suicide risk (245.01 ± 55.44 μmol/L) were significantly lower than those in MDD patients without suicide risk (274.17 ± 72.65 μmol/L) (p = 0.017) and healthy controls (271.42 ± 55.25 μmol/L) (p = 0.030). There was no difference in serum UA levels between the MDD patients without suicide risk and healthy controls (p = 0.821). Binary logistic regression analysis revealed a significant relationship between suicide risk and decreased serum UA levels (OR = 0.989, p = 0.010) in MDD patients. Decreased serum UA levels were associated with suicide risk in MDD patients. Purinergic system dysfunction may be involved in the neurobiological basis of suicide risk in these patients.