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The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Attention deficit hyperactivity disorder (ADHD) is the commonest disorder presenting to Child and Adolescent Mental Health Services in Ireland. This article considers the impact of the Covid-19 pandemic on the provision of mental health services for young people with ADHD with specific reference to the difficulties that have been experienced in ADMiRE, a specialist ADHD service in Dublin, since the outbreak of Covid-19 in Ireland. Current guidelines and alternative ways of ensuring adequate service provision are discussed. Restrictions to mitigate the spread of Covid-19 are likely to continue for many months, and child and adolescent mental health services need to find new ways to provide a sustainable service to young people in Ireland. There is a growing evidence base for the use of telepsychiatry in the assessment and management of ADHD. Factors that should be considered when developing a telepsychiatry service for children and adolescents with ADHD are highlighted.
Environmental factors such as sunshine hours, temperature and UV radiation (UVR) are known to influence seasonal fluctuations in vitamin D concentrations. However, currently there is poor understanding regarding the environmental factors or individual characteristics that best predict neonatal 25-hydroxyvitamin D (25(OH)D) concentrations. The aims of this study were to (1) identify environmental and individual determinants of 25(OH)D concentrations in newborns and (2) investigate whether environmental factors and individual characteristics could be used as proxy measures for neonatal 25(OH)D concentrations. 25-Hydroxyvitamin D3 (25(OH)D3) was measured from neonatal dried blood spots (DBS) of 1182 individuals born between 1993 and 2002. Monthly aggregated data on daily number of sunshine hours, temperature and UVR, available from 1993, were retrieved from the Danish Meteorological Institute. The individual predictors were obtained from the Danish National Birth register, and Statistics Denmark. The optimal model to predict 25(OH)D3 concentrations from neonatal DBS was the one including the following variables: UVR, temperature, maternal education, maternal smoking during pregnancy, gestational age at birth and parity. This model explained 30 % of the variation of 25(OH)D3 in the neonatal DBS. Ambient UVR in the month before the birth month was the best single-item predictor of neonatal 25(OH)D3, accounting for 24 % of its variance. Although this prediction model cannot substitute for actual blood measurements, it might prove useful in cohort studies ranking individuals in groups according to 25(OH)D3 status.
Studies have suggested that vitamin D status at birth may be associated with a range of neonatal outcomes. The aim of this study was to assess the association between neonatal 25-hydroxyvitamin D3 (25(OH)D3) concentration and gestational age, birth weight, Ponderal Index and size for gestational age. Neonatal capillary blood stored as dried blood spots was used to assess 25(OH)D3 concentrations among 2686 subjects selected from a random population sub-sample of individuals, born in Denmark from 1 May 1981 to 31 December 2002. There was an inverse association between 25(OH)D3 concentration and gestational age at birth of −0·006 (95 % CI −0·009, −0·003, P<0·001) weeks of gestation per 1 nmol/l increase in 25(OH)D3 concentration. An inverted U-shaped association between 25(OH)D3 and birth weight and Ponderal Index (P=0·04) was found, but no association with size for gestational age was shown. This study suggests that neonatal 25(OH)D3 concentration is associated with anthropometric measures at birth known to be correlated with many subsequent health outcomes such as obesity and type 2 diabetes.
Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders.
In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments.
After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1–1.5] to 1.9 (95% CI 1.4–2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2–1.9) to 1.7 (95% CI 1.2–2.4).
PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.
There is growing interest in linking vitamin D deficiency with autism spectrum disorders (ASDs). The association between vitamin D deficiency during gestation, a critical period in neurodevelopment, and ASD is not well understood.
To determine the association between gestational vitamin D status and ASD.
Based on a birth cohort (n=4334), we examined the association between 25-hydroxyvitamin D (25OHD), assessed from both maternal mid-gestation sera and neonatal sera, and ASD (defined by clinical records; n=68 cases).
Individuals in the 25OHD-deficient group at mid-gestation had more than twofold increased risk of ASD (odds ratio (OR)=2.42, 95% confidence interval (CI) 1.09 to 5.07, P=0.03) compared with the sufficient group. The findings persisted in analyses including children of European ethnicity only.
Mid-gestational vitamin D deficiency was associated with an increased risk of ASD. Because gestational vitamin D deficiency is readily preventable with safe, inexpensive and readily available supplementation, this risk factor warrants closer scrutiny.
Traumatic events are associated with increased risk of psychotic experiences, but it is unclear whether this association is explained by mental disorders prior to psychotic experience onset.
To investigate the associations between traumatic events and subsequent psychotic experience onset after adjusting for post-traumatic stress disorder and other mental disorders.
We assessed 29 traumatic event types and psychotic experiences from the World Mental Health surveys and examined the associations of traumatic events with subsequent psychotic experience onset with and without adjustments for mental disorders.
Respondents with any traumatic events had three times the odds of other respondents of subsequently developing psychotic experiences (OR=3.1, 95% CI 2.7–3.7), with variability in strength of association across traumatic event types. These associations persisted after adjustment for mental disorders.
Exposure to traumatic events predicts subsequent onset of psychotic experiences even after adjusting for comorbid mental disorders.
Measuring cortisol in hair is a promising method to assess long-term alterations of the biological stress response system, and hair cortisol concentrations (HCC) may be altered in psychiatric disorders and in subjects suffering from chronic stress. However, the pattern of associations between HCC, chronic stress and mental health require clarification. Our exploratory study: (1) assessed the association between HCC and perceived stress, symptoms of depression and neuroticism, and the trait extraversion (as a control variable); and (2) made use of the twin design to estimate the genetic and environmental covariance between the variables of interest. Hair samples from 109 (74 female) subjects (age range 12–21 years, mean 15.1) including 8 monozygotic (MZ) and 21 dizygotic (DZ) twin pairs were analyzed. Perceived stress was measured with the Perceived Stress Scale and/or the Daily Life and Stressors Scale, neuroticism, and extraversion with the NEO-Five Factor Inventory or the Junior Eysenck Personality Questionnaire, and depressive symptoms with the Somatic and Psychological Health Report. We found a modest positive association between HCC and the three risk factors — perceived stress, symptoms of depression, and neuroticism (r = 0.22–0.33) — but no correlation with extraversion (-0.06). A median split revealed that the associations between HCC and risk factors were stronger (0.47–0.60) in those subjects with HCC >11.36 pg/mg. Furthermore, our results suggest that the genetic effects underlying HCC are largely shared with those that influence perceived stress, depressive symptoms, and neuroticism. These results of our proof of principle study warrant replication in a bigger sample but raise the interesting question of the direction of causation between these variables.
Federal agencies perform many important tasks, from guarding against terrorist plots to mailing social security checks. A key question is whether Congress can effectively manage such a large and influential bureaucracy. We argue that Congress, in using oversight to ensure agency responsiveness to legislative preferences, risks harming agency morale, which could have negative long-run effects on performance and the implementation of public policy. More specifically, we argue that oversight’s effects on agency morale are conditional on whether oversight is adversarial or friendly. We assess our claims using a novel data set of the frequency and tone of hearings in which federal agencies are called to testify before Congress from 1999 to 2011 and merge it with data on agency autonomy and job satisfaction. Our findings suggest that agency morale is sensitive to congressional oversight attention, and thus speak to questions regarding democratic accountability, congressional policymaking and the implementation of public policy.
Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
Dialectical behavior therapy (DBT) is a form of cognitive behavior therapy (CBT) for mood disorders. There are three categories of core strategies employed in DBT: change strategies, acceptance and validation strategies, and dialectical strategies. Change strategies in DBT, for the most part, are based on learning principles. One rationale for using DBT to treat mood disorders is the significant co-morbidity between borderline personality disorder (BPD) and mood disorders. Adapting DBT is different from adopting DBT. In the latter, DBT, e.g. the modes of treatment delivery, may be changed to meet the needs of the setting or target population. Programs which adopt comprehensive DBT benefit from the existing evidence base. DBT is an efficacious treatment proven to reduce suicidal behavior and nonsuicidal self-injury. DBT has been adapted for both bipolar adolescents and geriatric patients with treatment-resistant depression or depression co-morbid with BPD.
This chapter deals with brain imaging techniques. MRI and computer tomography (CT) scans have been used to identify changes in brain morphology in major depressive disorder (MDD). Functional MRI (fMRI), positron emission tomography (PET), and single photon emission computer tomography (SPECT) have all been utilized to identify regions of the brain that are differentially activated in MDD when compared to healthy control subjects. Altered correlation of activity between the frontal lobe and the amygdale has been reported during fMRI studies of patients with MDD. Both bipolar disorder and MDD are likely heterogeneous conditions with different molecular, cellular, genetic, or environmental causes that produce the same clinical phenotype of the disorder. Technical advances in neuroimaging techniques may allow for new questions to be asked into the biological underpinnings of mood disorders and may be used to predict responses to treatments.
There has been considerable controversy over the correct diagnosis for patients with mood disorder associated with the lifetime occurrence of hypomanic symptoms which are sub-threshold for the diagnosis of bipolar disorder. Extrapolating from the accelerating accumulation of knowledge of the biology of psychiatric disorders over the last several decades, it is easy to anticipate that this trend will continue and that such knowledge will define the molecular pathways whereby genes and environment affect the risk for mood disorders. There are early efforts to apply proteomic methods to mood disorders. Electrophysiology, primarily in the form of electroencephalographic recording, has shown significant promise in application to mood disorder therapeutics. An important intellectual trend is that the rapidly advancing technologies of quantitative neuroscience and molecular genetics appear to be making enormous progress toward demonstrating a neurobiological substrate of mood disorder.