Towards a youth mental health paradigm: a perspective and roadmap.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy.

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Patient Functioning, Life Engagement, and Treatment Goals in Schizophrenia.

Unmet needs in the treatment of schizophrenia include nonadherence to treatment, symptom relapse, incomplete functional recovery, and poor quality of life. Incorporating the patient's perspective into the treatment plan and measuring treatment outcomes that are meaningful to patients is an important part of addressing these issues. Goal setting is associated with greater improvements in motivation and role functioning, but clinicians should keep in mind that their goals for treatment may not align with those of their patients. Patients tend to think about their lives more holistically than clinicians, with equal weight given to social and clinical needs, and improved functioning and engagement with life are likely to emerge as priorities, beyond the need for symptom control. In a recent roundtable meeting, a panel of 5 experts discussed life engagement and its relationship to symptoms and functioning in patients with major depressive disorder (MDD) and schizophrenia. This Academic Highlights, part 2 in a series, summarizes the experts' discussion of how life engagement can inform goal-setting and treatment selection in patients with schizophrenia.

Brain stimulation and other biological non-pharmacological interventions in mental disorders: An umbrella review.

BACKGROUND: The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS: We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS: We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION: Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING: None.

Early detection of bipolar disorders and treatment recommendations for help-seeking adolescents and young adults: Findings of the Early Detection and Intervention Center Dresden.

BACKGROUND: Early identification and intervention of individuals with risk factors for or subtle prodromal symptoms of bipolar disorders (BD) may improve the illness course and prevent adverse long-term consequences. METHODS: We examined sociodemographic, clinical and psychopathological characteristics of help-seeking adolescents and young adults who consulted the Early Detection and Intervention Center Dresden at the University of Dresden (Germany) and presented with or without pre-defined at-risk criteria for BD. The standardized diagnostic procedure for all help-seeking youth included a comprehensive psychiatric history and a structured clinical interview. When BD at-risk state was suspected, early detection instruments (EPIbipolar, BPSS-FP) were applied. Treatment recommendations were formulated in multi-professional case conferences. RESULTS: Out of 890 help-seeking persons between 05/2009 and 04/2018, 582 (65%) completed the diagnostic process. Of these, 24 (4%) had manifest BD and 125 (21%) fulfilled at-risk BD criteria (age = 23.9 ± 0.6 years, female = 62%). Of the pre-defined main risk factors, family history for BD was reported in 22% of the at-risk persons, (hypo-)mania risk state in 44%, and increasing cyclothymic mood swings with increased activity in 48%. The most common secondary risk factors were decreased psychosocial functioning (78%), lifetime diagnosis of depressive disorder (67%) and specific sleep/circadian rhythm disturbances (59%). Substance use was very common in subjects at-risk for BD (cannabis = 50%, alcohol = 33%) and highest in patients with BD (cannabis = 75%, alcohol = 40%). Psychiatric treatment history, including psychopharmacological therapy, was similar between the groups, while treatment recommendations differed, with more advice for psychotherapy and antidepressants in the at-risk group with a lifetime diagnosis of depression and more advice for specialized BD treatment including mood stabilizers in patients with BD. CONCLUSION: This analysis on the phenomenology of different BD at-risk stages suggests that early detection of individuals presenting with suggested risk factors for the development of BD is feasible in help-seeking young people. Future research should further develop/test stage-specific prevention and early targeted intervention approaches that were described in a naturalistic setting.

The need for holistic, longitudinal and comparable, real-time assessment of the emotional, behavioral and societal impact of the COVID-19 pandemic across nations.

As of the end of 2020, the COVID-19 pandemic has led to over 82 million verified infections and almost 1.8 million COVID-19-related deaths worldwide,1 resulting to an unprecedented public health response around the globe. The COVID-19 pandemic, together with the applied multi-level restrictive measures, has generated a unique combination of an unpredictable and stressful biomedical and socioeconomic environment (i.e., syndemic),2 introducing real-life threat, involuntary and drastic every-day life-style changes with uncertain financial and future prospects, alongside with minimized coping and stress management possibilities.3 This combination of so many different and vital stressors may lead to acute as well as long-term, direct, indirect and even transgenerational unfavourable effects on physical and mental health and functioning, which might even represent the most precarious and still unpredictable public-health-related part of the pandemic.4 Thereby, specific population groups could be at particular risk of poor health outcomes in relation to applied public health measures.4, 5 However, not every individual will experience the same level of negative impact on health and well-being during the pandemic, as several additional national, socioeconomic, environmental, behavioural, emotional and cognitive factors can moderate individual resilience and coping.6 Pandemic-related research should, thus, assess as many multidimensional risk and protective factors as possible in a longitudinal, large-scale and multi-national manner, enabling a profound and comprehensive understanding of the complex health and societal impact of the pandemic worldwide.7 Nevertheless, to date, most research findings are cross-sectional, report on small and non- representative samples from individual countries, or on specific population groups (e.g., health care workers, students, clinical populations) and usually assess only a very restricted set of outcomes and time-points. Thereby, only few studies assess coping strategies, medical history or detailed socioeconomic, demographic and environmental data. In addition, most studies leave behind linguistic differences, being available in one or at best two different languages. Such investigations of small outcome subsets within a narrow framework preclude a broader and clear understanding of the multifaceted pandemic impact on the general population and specific subgroups. Acknowledging these gaps in the existing literature, large- scale, collaborative research prospectively collecting and monitoring a broad range of real- time, multi-dimensional health-related, societal and behavioural outcome data from countries across the globe is currently explicitly needed. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH- FIT) envisions to fill this gap. Based on an easy-to-access webpage (www.coh-fit.com), COH- FIT is the currently largest-scale known international collaborative study of over 200 researchers around the globe, prospectively collecting the biggest set of multi-dimensional and multi-disciplinary data from 150 high, middle, and low-income countries in over 30 languages and in three different age groups (adults, adolescents, children) of the general population, focusing also on relevant at-risk subgroups. Albeit being a cross-sectional anonymous survey on an individual level, it is a longitudinal study on a population level, as data are collected continuously since April 2020 and until the WHO declares the end of the pandemic. In addition to snowball recruitment, this project also collects information from nationally representative samples. Furthermore, COH-FIT is the first study of this scale investigating pandemic effects on health and functioning measures between family members, while it also specifically assesses a large list of behavioral and coping factors (e.g., screen time, social media usage, physical activity, social interaction, religious practices, etc.) on outcomes of interest. COH-FIT also monitors changes in public health restrictive measures to enhance data harmonization across nations and time, and to better investigate their impact on physical and mental health, while it also collects information on changes in healthcare systems functioning. The COH-FIT project was worldwide first initiated in Greece after the ethics committee approval of the School of Medicine of the Aristotle University of Thessaloniki and is officially supported by the Hellenic Psychiatric Association, European Psychiatric Association, World Association of Social Psychiatry, ECNP Network on the Prevention of Mental Disorders and Mental Health Promotion, among many other national and international scientific associations. To date, COH-FIT has already collected >115,000 participations worldwide (>8,000 in Greece), but more participants are still needed, both during the second and third wave of the pandemic, as in the future, after the pandemic has ended. Currently, the COH-FIT survey actively collects the largest sample on multifactorial data on the impact of the COVD-19 pandemic on health and functioning not only in Greece, but around the globe. The elaborated design of COH-FIT and similar studies may allow a better identification of key parameters and population groups at increased risk during the pandemic, as well as potential targets for acute and long-term prevention or intervention strategies in the current as in possible future pandemics. A profound understanding of the health and societal impact of the pandemic could facilitate an optimized governmental, social and individual health preparedness during infection times8 and the bridging of individuals', societal and systemic needs and actions through multi-level guideline development with the aim to improve mental health outcomes globally.

Long-Acting Injectable Antipsychotic Treatment in Schizophrenia and Co-occurring Substance Use Disorders: A Systematic Review.

Objectives: Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased symptom severity, worsened illness trajectory and high rates of treatment non-adherence. Recent evidence suggests that the use of long-acting injectable (LAI) antipsychotics may provide an effective treatment option for individuals with this dual-diagnosis. Methods: A systematic review of the literature was conducted using the databases PubMed, PsychInfo and Google Scholar for English-language studies, investigating the use of LAIs in co-occurring schizophrenia and substance use disorders (SCZ-SUDs). Results: Eight reports [one case study (n = 1), one case series (n = 8), three open-label retrospective studies (n = 75), and three randomized controlled trials (n = 273)] investigated the use of LAI antipsychotics in 357 participants with SCZ-SUDs [alcohol use disorder: 5 studies, n = 282; cocaine use disorder: 5 studies, n = 85; amphetamine use disorder: 1 study, n = 1; cannabis use disorder: 3 studies, n = 160; opioid use disorder: 3 studies, n = 19; methylenedioxymethamphetamine (MDMA) use disorder: 2 studies, n = 9; ketamine use disorder: 1 study, n = 4] and were included in this systematic review. Findings indicate significant improvements in substance use related outcomes across 7 of 8 studies, while in 6 of 8 studies, significant improvements in psychopathology-related outcomes were reported. Conclusions: LAI antipsychotics may be an efficacious intervention option for the treatment of SCZ-SUDs. However, varying methodological rigor, generally small sample sizes and heterogeneity of samples, settings, substances of abuse, tested LAIs and comparators, as well as psychosocial cotreatments and level of reported detail across studies requires that these findings be considered preliminary and interpreted with caution. Further research is required to better understand the effects of LAIs among individuals with SCZ-SUDs.

Outcomes of an Accelerated Inpatient Refeeding Protocol in 103 Extremely Underweight Adults with Anorexia Nervosa at a Specialized Clinic in Prien, Germany.

BACKGROUND: In mildly to moderately malnourished adolescent patients with anorexia nervosa (AN), accelerated refeeding protocols using higher initial calory supply coupled with phosphate supplements were not associated with a higher incidence of refeeding syndrome (RS). It is unclear whether this is also a feasible approach for extremely malnourished, adult AN patients. METHODS: Outcomes of a clinical refeeding protocol involving a targeted initial intake of ≥2000 kcal/day, routine supplementation of phosphate and thiamine as well as close medical monitoring, were evaluated. A retrospective chart review including AN patients with a body mass index (BMI) <13 kg/m² was conducted, to describe changes in weight, BMI, and laboratory parameters (phosphate, creatine kinase, hematocrit, sodium, liver enzymes, and blood count) over four weeks. RESULTS: In 103 female patients (age, mean ± standard deviation (SD) = 23.8 ± 5.3 years), BMI between admission and follow-up increased from 11.5 ± 0.9 to 13.1 ± 1.1 kg/m² and total weight gain within the first four weeks was 4.2 ± 2.0 kg (mean, SD). Laboratory parameter monitoring indicated no case of RS, but continuous normalization of blood parameters. CONCLUSIONS: Combined with close medical monitoring and electrolyte supplementation, accelerated refeeding may also be applied to achieve medical stabilization in extremely underweight adults with AN without increasing the risk of RS.

Predictors of psychosis breakthrough during 24 months of long-acting antipsychotic maintenance treatment in first episode schizophrenia.

BACKGROUND: Some patients develop breakthrough psychotic symptoms on antipsychotic maintenance medication (BAMM), despite receiving therapeutic antipsychotic doses to which they previously responded. METHODS: We examined the occurrence of BAMM in previously minimally treated first-episode patients with schizophrenia-spectrum disorders who were treated according to a standard protocol with a long-acting injectable antipsychotic and regularly assessed over 24 months. RESULTS: Of 99 patients (age = 24.1 ± 6.5 years, male = 73.7%) who received treatment for ≥6 months (mean follow-up = 20.0 ± 6.5 months) and had responded well to treatment, 21 (21.2%) developed BAMM using operationally defined criteria, after a mean of 17.4 ± 6.1 months. Baseline risk factors for BAMM included lower baseline Positive and Negative Syndrome Scale positive symptoms, poorer quality of life in social relationships and higher blood - high-density lipoprotein-cholesterol. Regarding intra-treatment-factors, BAMM was independently predicted by an increase in low-density lipoprotein-cholesterol and current cannabis use. We did not find a relationship between BAMM and cumulative antipsychotic exposure or dose escalation. While symptoms of the BAMM episode were less severe than during the first episode, the post-BAMM treatment response was poorer than that for the first psychotic episode, suggesting a relationship between BAMM and emergent treatment refractoriness. CONCLUSIONS: About one in five patients with first-episode schizophrenia developed BAMM during the first two years of treatment, despite assured antipsychotic LAI treatment, indicating that this phenomenon is not restricted to the chronic stages of illness. The role of cannabis use and a possible link between BAMM and blood lipids should be further explored.

Impact of comprehensive treatment for first episode psychosis on substance use outcomes: A randomized controlled trial.

Lifetime co-occurring substance use disorders are common at the time of presentation for treatment of a first episode of primary psychosis and persistent substance use disorder (SUD) leads to poorer outcomes. We assessed whether the NAVIGATE program, a coordinated specialty care service that includes optional substance abuse content reduced substance use compared to usual care in 404 individuals in the Recovery After Initial Schizophrenia Episode-Early Treatment Program (RAISE-ETP) study. Participants were randomized to two years of NAVIGATE (n = 223) or usual care (n = 181) and assessed monthly for substance use. At baseline, over one-half (51.7%) of the participants met criteria for a lifetime SUD, including over one-third with alcohol use disorder (36.4%) and with cannabis use disorder (34.7%). Contrary to our hypothesis, there was no treatment group by time interaction effect on days of self-reported substance use over the two-year follow-up. Participant exposure to the substance abuse component of the NAVIGATE program was low, suggesting that modifications to the program and training method for clinicians may be needed. Further research is needed to determine the most effective strategies for addressing substance use disorders in persons recovering from a first episode of psychosis.

Early detection and integrated care for adolescents and young adults with severe psychotic disorders: rationales and design of the Integrated Care in Early Psychosis Study (ACCESS III).

AIM: The Integrated Care in Early Psychosis (ACCESS III) Study examined the efficacy and cost-effectiveness of a combined intervention consisting of strategies to improve early detection and quality of care (integrated care including therapeutic assertive community treatment) in adolescents and young adults in the early phase of a severe psychotic disorder from 2011 to 2014. METHODS: This is a prospective, single-centre, 1-year cohort study comparing an intervention condition (early detection plus integrated care, n = 120) to the historical control condition (standard care, SC, n = 105) for adolescents and young adults aged 12-29 years suffering from a severe, early-phase psychotic disorder (i.e. within 2 years of treatment). RESULTS: Primary outcome is the rate of combined symptomatic (i.e. Positive and Negative Syndrome Scale (PANSS) criteria) and functional (i.e. Global Assessment of Functioning scale (GAF) ≥ 60 points criterion) remission over at least 6 months at study endpoint. Secondary outcome comprises the comparison of the reduction in the duration of untreated psychosis within the 4-year study duration between integrated care and SC, course of psychopathology, functioning, quality of life, satisfaction with care, cost and quality-adjusted life years (QALYs) in comparison to a historical control group. CONCLUSION: To the authors' knowledge, this is the first study assessing the efficacy and cost-effectiveness of a combined intervention consisting of early detection strategies and strategies to improve quality of care in both adolescents and young adults with early-phase psychosis. The results will be published in 2016.

Cost-Effectiveness of Comprehensive, Integrated Care for First Episode Psychosis in the NIMH RAISE Early Treatment Program.

This study compares the cost-effectiveness of Navigate (NAV), a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis (FEP) and usual Community Care (CC) in a cluster randomization trial. Patients at 34 community treatment clinics were randomly assigned to either NAV (N = 223) or CC (N = 181) for 2 years. Effectiveness was measured as a one standard deviation change on the Quality of Life Scale (QLS-SD). Incremental cost effectiveness ratios were evaluated with bootstrap distributions. The Net Health Benefits Approach was used to evaluate the probability that the value of NAV benefits exceeded its costs relative to CC from the perspective of the health care system. The NAV group improved significantly more on the QLS and had higher outpatient mental health and antipsychotic medication costs. The incremental cost-effectiveness ratio was $12 081/QLS-SD, with a .94 probability that NAV was more cost-effective than CC at $40 000/QLS-SD. When converted to monetized Quality Adjusted Life Years, NAV benefits exceeded costs, especially at future generic drug prices.

Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis.

OBJECTIVE: To investigate the role of oxidative stress and antioxidants in depression. DATA SOURCES: We searched the literature without language restrictions through MEDLINE/PubMed, Cochrane Library, Fisterra, and Galenicom from database inception until December 31, 2013, supplemented by a hand search of relevant articles. Search terms included (1) oxidative stress, antioxidant*, nitrosative stress, nitrative stress, nitro-oxidative stress, free radical*, and names of individual oxidative stress markers/antioxidants and (2) depression and related disorders and antidepressant. STUDY SELECTION: Included were studies in patients with depression comparing antioxidant or oxidative stress markers with those in healthy controls before and after antidepressant treatment. DATA EXTRACTION: Two authors independently extracted the data for antioxidant or oxidative stress markers. Standardized mean differences (SMDs) ± 95% confidence intervals (CIs) for results from ≥ 3 studies were calculated. DATA SYNTHESIS: Altogether, 29 studies (N = 3,961; patients with depression = 2,477, healthy controls = 1,484) reported on the oxidative stress marker malondialdehyde (MDA) and total nitrites, the antioxidants uric acid and zinc, or the antioxidant-enhancing enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). When patients with depression were compared with healthy controls, depression was associated with higher oxidative stress MDA levels (8 studies; n = 916; SMD = 1.34; 95% CI, 0.57 to 2.11; P < .001), lower antioxidant uric acid (4 studies; n = 512; SMD = -0.64; 95% CI, -1.22 to -0.06; P = .030) and zinc levels (13 studies; n = 2,002; SMD = -0.66; 95% CI, -0.98 to -0.34; P < .0001), and higher antioxidant-enhancing enzyme SOD levels (11 studies; n = 902; SMD = 0.62; 95% CI, 0.07 to 1.17; P = .028), while differences in total nitrites and CAT and GPX were nonsignificant. Antidepressant treatment, which significantly reduced Hamilton Depression Rating Scale scores (24.6 ± 0.7 to 16.2 ± 1.6; SMD = 2.65; 95% CI, 1.13 to 4.15; P = .00065), reduced MDA (4 studies; n = 194; SMD = -1.45; 95% CI, -2.43 to -0.47; P = .004) and increased uric acid (3 studies; n = 212; SMD = 0.76; 95% CI, 0.03 to 1.49; P = .040) and zinc levels (3 studies; n = 65; SMD = 1.22; 95% CI, 0.40 to 2.04, P = .004), without differences in MDA (P = .60), uric acid (P = .10), and zinc (P = .163) levels compared to healthy controls. CONCLUSIONS: Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.

Vitamin D status in anorexia nervosa: A meta-analysis.

OBJECTIVE: In anorexia nervosa (AN), osteoporosis and osteopenia are common, which have been associated with low circulating levels of vitamin D (VitD) in other settings. We aimed to meta-analyze cross-sectional studies reporting on VitD parameters in patients with AN and healthy controls (HCs). METHOD: Electronic PubMed search from database inception until December 31, 2013 and meta-analysis of cross-sectional studies comparing serum levels of 25-hydroxyvitamin D (25OH-D), 1,25-dihydroxyvitamin D (1,25OH-D) and dietary VitD between patients with AN and HCs, before or after VitD supplementation. We calculated random effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as effect size measures. RESULTS: Out of 1,739 initial hits, 15 studies with a total of 927 participants (AN = 408 and HCs = 519) were meta-analyzed. In the unsupplemented state, both serum 25OH-D (studies = 4; n = 168; SMD = -0.43; 95%CI: -0.83 to -0.03; p = .03) and 1,25OH-D levels (studies = 4; n = 113; SMD = -1.06; 95%CI: -1.47 to -0.66; p < .00001) were significantly lower in AN than HCs. In AN patients treated with cholecalciferol supplementation, serum 25OH-D levels were significantly higher than in HCs (studies = 5; n = 449; SMD = 0.66; 95%CI: 0.01-1.31; p = .05). Paradoxically, despite lower 25OH-D and 1,25OH-D levels, AN patients reported similar intake of VitD compared to HCs (studies = 6; n = 314; SMD = 0.33; 95%CI: -0.16, 0.81; p = .19). DISCUSSION: Although AN patients reported similar dietary VitD intake compared to HCs, AN patients had significantly lower 25OH-D and 1,25OH-D levels without supplementation. Conversely, supplementation with cholecalciferol fully normalized VitD serum levels. Future studies are needed to clarify the role of VitD supplementation in AN for improving bone health.

Adherence to guidelines for glucose assessment in starting second-generation antipsychotics.

OBJECTIVES: In 2003, the US Food and Drug Administration issued warnings about hyperglycemia and diabetes with second-generation antipsychotics (SGAs); guidelines have recommended metabolic screening since 2004. However, little is known of contemporary practices of glucose screening among youth initiating SGAs. Our objective was to evaluate baseline glucose assessment among youth in the Mini-Sentinel Distributed Database starting an SGA. METHODS: The cohort included youth ages 2 through 18 newly initiating SGAs January 1, 2006, through December 31, 2011, across 10 sites. Baseline glucose was defined as fasting/random glucose or hemoglobin A1c (GLU) measurement occurring relative to first SGA dispensing. Differences in GLU assessment were evaluated with χ(2) tests and logistic regression. RESULTS: The cohort included 16,304 youth; 60% boys; mean age 12.8 years. Risperidone was most commonly started (43%). Eleven percent (n = 1858) had GLU assessed between 90 days before and 3 days after first dispensing. Assessment varied across SGAs (olanzapine highest), sites (integrated health care systems higher), ages (16-18 highest), years (2007 highest), and gender (female higher; all P < .001). GLU assessment among those starting olanzapine was more likely than among those starting quetiapine (odds ratio [OR]: 1.72 [95% confidence interval (CI): 1.37-2.18]), aripiprazole (OR: 1.49 [95% CI: 1.18-1.87]), or risperidone (OR: 1.61 [95% CI: 1.28-2.03]). CONCLUSIONS: Few children and adolescents starting SGA have baseline glucose assessed. This is concerning because those at high diabetes risk may not be identified. Further, lack of screening impedes determining the contribution of SGAs to hyperglycemia development.

Early specific cognitive-behavioural psychotherapy in subjects at high risk for bipolar disorders: study protocol for a randomised controlled trial.

BACKGROUND: Bipolar disorders (BD) are among the most severe mental disorders with first clinical signs and symptoms frequently appearing in adolescence and early adulthood. The long latency in clinical diagnosis (and subsequent adequate treatment) adversely affects the course of disease, effectiveness of interventions and health-related quality of life, and increases the economic burden of BD. Despite uncertainties about risk constellations and symptomatology in the early stages of potentially developing BD, many adolescents and young adults seek help, and most of them suffer substantially from symptoms already leading to impairments in psychosocial functioning in school, training, at work and in their social relationships. We aimed to identify subjects at risk of developing BD and investigate the efficacy and safety of early specific cognitive-behavioural psychotherapy (CBT) in this subpopulation. METHODS/DESIGN: EarlyCBT is a randomised controlled multi-centre clinical trial to evaluate the efficacy and safety of early specific CBT, including stress management and problem solving strategies, with elements of mindfulness-based therapy (MBT) versus unstructured group meetings for 14 weeks each and follow-up until week 78. Participants are recruited at seven university hospitals throughout Germany, which provide in- and outpatient care (including early recognition centres) for psychiatric patients. Subjects at high risk must be 15 to 30 years old and meet the combination of specified affective symptomatology, reduction of psychosocial functioning, and family history for (schizo)affective disorders. Primary efficacy endpoints are differences in psychosocial functioning and defined affective symptomatology at 14 weeks between groups. Secondary endpoints include the above mentioned endpoints at 7, 24, 52 and 78 weeks and the change within groups compared to baseline; perception of, reaction to and coping with stress; and conversion to full BD. DISCUSSION: To our knowledge, this is the first study to evaluate early specific CBT in subjects at high risk for BD. Structured diagnostic interviews are used to map the risk status and development of disease. With our study, the level of evidence for the treatment of those young patients will be significantly raised. TRIAL REGISTRATION: WHO International Clinical Trials Platform (ICTRP), identifier: DRKS00000444, date of registration: 16 June 2010.

The relationship between acoustic startle response measures and cognitive functions in Japanese patients with schizophrenia.

Recently, schizophrenia endophenotypes have been actively investigated to better understand the pathophysiology of schizophrenia. Past studies have shown that cognitive functions, including working memory and executive function, correlate with acoustic startle responses, such as prepulse inhibition (PPI), in patients with schizophrenia. The aim of this study was to investigate the relationship between cognitive functions and acoustic startle response in Japanese patients with schizophrenia. In 100 patients with schizophrenia, we evaluated cognitive function, using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J), and acoustic startle responses, including acoustic startle reflex, habituation, and PPI (three different intensities: 82, 86, and 90 dB SPL, equivalent to signal-to-noise ratios of +12, +16, and +20 dB, respectively). Using multiple regression analysis, we examined the relationship between acoustic startle responses and BACS-J primary measures or composite score. Level of attention was associated with magnitude of habituation in schizophrenia (P = 0.0009, ß = -0.357). None of the other domains of cognitive function were significantly associated with any measure of acoustic startle response. This included attention regarding ASR (P = 0.513), PPI (P = 0.521-0.842), verbal memory (P = 0.423-0.981), working memory (P = 0.312-0.966), motor speed (P = 0.323-0.955), verbal fluency (P = 0.125-0.920), executive function (P = 0.118-0.470), and the BACS-J composite score (P = 0.230-0.912). In this first investigation of the relationship between cognitive functions and acoustic startle responses in Japanese patients with schizophrenia, attentional deficits correlated highly with the level of habituation. However, a replication study using other population samples is required to further investigate this relationship.