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2.
Med J Aust ; 211 Suppl 9: S3-S46, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31679171

RESUMO

Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change. Consequently, the effects of adolescent-onset mood and psychotic syndromes can have long term consequences. A key clinical challenge for youth mental health is to develop and test new systems that align with current evidence for comorbid presentations and underlying neurobiology, and are useful for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. Our highly personalised and measurement-based care model includes three core concepts: ▶ A multidimensional assessment and outcomes framework that includes: social and occupational function; self-harm, suicidal thoughts and behaviour; alcohol or other substance misuse; physical health; and illness trajectory. ▶ Clinical stage. ▶ Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on proposed pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). The model explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within this highly personalised approach is the incorporation of other evidence-based processes, including real-time measurement-based care as well as utilisation of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality, mental health care for young people. CHAPTER 1: MULTIDIMENSIONAL OUTCOMES IN YOUTH MENTAL HEALTH CARE: WHAT MATTERS AND WHY?: Mood and psychotic syndromes present one of the most serious public health challenges that we face in the 21st century. Factors including prevalence, age of onset, and chronicity contribute to substantial burden and secondary risks such as alcohol or other substance misuse. Mood and psychotic syndromes most often emerge during adolescence and young adulthood, a period characterised by major physical and social change; thus, effects can have long term consequences. We propose five key domains which make up a multidimensional outcomes framework that aims to address the specific needs of young people presenting to health services with emerging mental illness. These include social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Impairment and concurrent morbidity are well established in young people by the time they present for mental health care. Despite this, services and health professionals tend to focus on only one aspect of the presentation - illness type, stage and trajectory - and are often at odds with the preferences of young people and their families. There is a need to address the disconnect between mental health, physical health and social services and interventions, to ensure that youth mental health care focuses on the outcomes that matter to young people. CHAPTER 2: COMBINING CLINICAL STAGE AND PATHOPHYSIOLOGICAL MECHANISMS TO UNDERSTAND ILLNESS TRAJECTORIES IN YOUNG PEOPLE WITH EMERGING MOOD AND PSYCHOTIC SYNDROMES: Traditional diagnostic classification systems for mental disorders map poorly onto the early stages of illness experienced by young people, and purport categorical distinctions that are not readily supported by research into genetic, environmental and neurobiological risk factors. Consequently, a key clinical challenge in youth mental health is to develop and test new classification systems that align with current evidence on comorbid presentations, are consistent with current understanding of underlying neurobiology, and provide utility for predicting outcomes and guiding decisions regarding the provision of appropriate and effective care. This chapter outlines a transdiagnostic framework for classifying common adolescent-onset mood and psychotic syndromes, combining two independent but complementary dimensions: clinical staging, and three proposed pathophysiological mechanisms. Clinical staging reflects the progression of mental disorders and is in line with the concept used in general medicine, where more advanced stages are associated with a poorer prognosis and a need for more intensive interventions with a higher risk-to-benefit ratio. The three proposed pathophysiological mechanisms are neurodevelopmental abnormalities, hyperarousal and circadian dysfunction, which, over time, have illness trajectories (or pathways) to psychosis, anxious depression and bipolar spectrum disorders, respectively. The transdiagnostic framework has been evaluated in young people presenting to youth mental health clinics of the University of Sydney's Brain and Mind Centre, alongside a range of clinical and objective measures. Our research to date provides support for this framework, and we are now exploring its application to the development of more personalised models of care. CHAPTER 3: A COMPREHENSIVE ASSESSMENT FRAMEWORK FOR YOUTH MENTAL HEALTH: GUIDING HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE USING MULTIDIMENSIONAL AND OBJECTIVE MEASURES: There is an urgent need for improved care for young people with mental health problems, in particular those with subthreshold mental disorders that are not sufficiently severe to meet traditional diagnostic criteria. New comprehensive assessment frameworks are needed to capture the biopsychosocial profile of a young person to drive highly personalised and measurement-based mental health care. We present a range of multidimensional measures involving five key domains: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness type, stage and trajectory. Objective measures include: neuropsychological function; sleep-wake behaviours and circadian rhythms; metabolic and immune markers; and brain structure and function. The recommended multidimensional measures facilitate the development of a comprehensive clinical picture. The objective measures help to further develop informative and novel insights into underlying pathophysiological mechanisms and illness trajectories to guide personalised care plans. A panel of specific multidimensional and objective measures are recommended as standard clinical practice, while others are recommended secondarily to provide deeper insights with the aim of revealing alternative clinical paths for targeted interventions and treatments matched to the clinical stage and proposed pathophysiological mechanisms of the young person. CHAPTER 4: PERSONALISING CARE OPTIONS IN YOUTH MENTAL HEALTH: USING MULTIDIMENSIONAL ASSESSMENT, CLINICAL STAGE, PATHOPHYSIOLOGICAL MECHANISMS, AND INDIVIDUAL ILLNESS TRAJECTORIES TO GUIDE TREATMENT SELECTION: New models of mental health care for young people require that interventions be matched to illness type, clinical stage, underlying pathophysiological mechanisms and individual illness trajectories. Narrow syndrome-focused classifications often direct clinical attention away from other key factors such as functional impairment, self-harm and suicidality, alcohol or other substance misuse, and poor physical health. By contrast, we outline a treatment selection guide for early intervention for adolescent-onset mood and psychotic syndromes (ie, active treatments and indicated and more specific secondary prevention strategies). This guide is based on experiences with the Brain and Mind Centre's highly personalised and measurement-based care model to manage youth mental health. The model incorporates three complementary core concepts: ▶A multidimensional assessment and outcomes framework including: social and occupational function; self-harm, suicidal thoughts and behaviours; alcohol or other substance misuse; physical health; and illness trajectory. ▶Clinical stage. ▶Three common illness subtypes (psychosis, anxious depression, bipolar spectrum) based on three underlying pathophysiological mechanisms (neurodevelopmental, hyperarousal, circadian). These core concepts are not mutually exclusive and together may facilitate improved outcomes through a clinical stage-appropriate and transdiagnostic framework that helps guide decisions regarding the provision of appropriate and effective care options. Given its emphasis on adolescent-onset mood and psychotic syndromes, the Brain and Mind Centre's model of care also respects a fundamental developmental perspective - categorising childhood problems (eg, anxiety and neurodevelopmental difficulties) as risk factors and respecting the fact that young people are in a period of major biological and social transition. Based on these factors, a range of social, psychological and pharmacological interventions are recommended, with an emphasis on balancing the personal benefit-to-cost ratio. CHAPTER 5: A SERVICE DELIVERY MODEL TO SUPPORT HIGHLY PERSONALISED AND MEASUREMENT-BASED CARE IN YOUTH MENTAL HEALTH: Over the past decade, we have seen a growing focus on creating mental health service delivery models that better meet the unique needs of young Australians. Recent policy directives from the Australian Government recommend the adoption of stepped-care services to improve the appropriateness of care, determined by severity of need. Here, we propose that a highly personalised approach enhances stepped-care models by incorporating clinical staging and a young person's current and multidimensional needs. It explicitly aims to prevent progression to more complex and severe forms of illness and is better aligned to contemporary models of the patterns of emergence of psychopathology. Inherent within a highly personalised approach is the incorporation of other evidence-based processes, includingreal-time measurement-based care and use of multidisciplinary teams of health professionals. Data-driven local system modelling and personalised health information technologies provide crucial infrastructure support to these processes for better access to, and higher quality of, mental health care for young people.

3.
Biol Psychiatry ; 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31690495

RESUMO

BACKGROUND: NEURAPRO was a multicenter, placebo-controlled trial of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) (fish oil) in 304 individuals at ultra-high risk for psychotic disorders. The study failed to show benefits of n-3 PUFAs over placebo. Although the randomized controlled trial design is placed at the top of the evidence hierarchy, this methodology has limitations in fish oil randomized controlled trials, as not only is the test agent present in the intervention group, but also n-3 fats are present in the diet and the body tissue of all participants. METHODS: Analysis of biomarker data (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], n-3 index, EPA+DHA) collected as part of NEURAPRO was conducted on 218 participants with longitudinal biomarker data to determine if n-3 PUFAs measured in erythrocytes at baseline and month 6 predicted clinical outcomes. RESULTS: Increases of the n-3 index, EPA, and DHA predicted less severe psychopathology and better functioning at both follow-up time points. Higher baseline levels and increases of n-3 index also predicted overall clinical improvement at month 6 (n-3 index baseline: adjusted odds ratio [95% confidence interval (CI)] = 1.79 [1.30-2.48]; n-3 PUFA increase: adjusted odds ratio [95% CI] = 1.43 [1.16-1.76]) and at month 12 (n-3 index baseline: adjusted odds ratio [95% CI] = 2.60 [1.71-3.97]; n-3 PUFA increase: adjusted odds ratio [95% CI] = 1.36 [1.06-1.74]). CONCLUSIONS: These data suggest that n-3 PUFAs can exert therapeutic effects in ultra-high-risk individuals. This finding has implications for early intervention and treatment guidelines, as n-3 PUFA supplementation can easily and safely be used in a wide variety of settings, from primary care to specialist services.

4.
Schizophr Res ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31606244

RESUMO

Omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) are necessary for optimum mental health, with recent studies showing low n-3 LCPUFA in people at ultra-high risk (UHR) of developing psychosis. Furthermore, people at UHR of psychosis had increased erythrocyte sphingomyelin (SM) and reduced phosphatidylethanolamine (PE) concentrations as well as 27 erythrocyte phospholipid species that differed when compared to erythrocytes from age matched people not at UHR of psychosis. The aim of this analysis was to evaluate the effect of n-3 supplementation on the different erythrocyte lipid species (including SM and PE concentrations) in people at UHR of psychosis. Participants were randomly assigned to fish oil (containing 840 mg EPA and 560 mg DHA per day) or placebo (paraffin oil) for 6 months. Fasted blood samples were taken at baseline and post intervention. Mass spectrometry was used to analyse the molecular phospholipids and fatty acid composition of erythrocytes for both groups. The n-3 index was significantly increased from 3.0% to 4.12% after 6 months of receiving n-3 capsules. Fish oil capsules increased the phospholipid molecular species containing n-3 LCPUFA, and concomitant decreases in n-6 LCPUFA species. SM species did not show any significant changes in n-3 LCPUFA group however, three SM species (SM 16:0, SM 18:0, SM 18:1) significantly increased after 6 months of supplementation with placebo. N-3 supplementation for 6 months led to higher n-3 incorporation into erythrocytes, at the expense of n-6 PUFA across all phospholipid classes analyzed and may have prevented the increase in SM seen in the placebo group.

7.
Med J Aust ; 211 Suppl 7: S3-S39, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31587276

RESUMO

Project Synergy aims to test the potential of new and emerging technologies to enhance the quality of mental health care provided by traditional face-to-face services. Specifically, it seeks to ensure that consumers get the right care, first time (delivery of effective mental health care early in the course of illness). Using co-design with affected individuals, Project Synergy has built, implemented and evaluated an online platform to assist the assessment, feedback, management and monitoring of people with mental disorders. It also promotes the maintenance of wellbeing by collating health and social information from consumers, their supportive others and health professionals. This information is reported back openly to consumers and their service providers to promote genuine collaborative care. The online platform does not provide stand-alone medical or health advice, risk assessment, clinical diagnosis or treatment; instead, it supports users to decide what may be suitable care options. Using an iterative cycle of research and development, the first four studies of Project Synergy (2014-2016) involved the development of different types of online prototypes for young people (i) attending university; (ii) in three disadvantaged communities in New South Wales; (iii) at risk of suicide; and (iv) attending five headspace centres. These contributed valuable information concerning the co-design, build, user testing and evaluation of prototypes, as well as staff experiences during development and service quality improvements following implementation. Through ongoing research and development (2017-2020), these prototypes underpin one online platform that aims to support better multidimensional mental health outcomes for consumers; more efficient, effective and appropriate use of health professional knowledge and clinical skills; and quality improvements in mental health service delivery.

8.
Med J Aust ; 211(7): 315-316, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31587293
9.
Psychiatry Res ; 281: 112604, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31627073

RESUMO

The Empathy Quotient (EQ) self-report questionnaire is used to measure empathy in individuals with clinical conditions that have been associated with social impairments. In this study, older teens and adults with autism spectrum disorder (ASD; N = 60), early psychosis (EP; N = 51) and social anxiety disorder (SAD; N = 71) and neurotypical controls (NT; N = 26) were compared on the cognitive empathy, emotional reactivity and social skills sub-scales of the Empathy Quotient (EQ) measure. All three clinical groups reported lower cognitive empathy than NT controls, and the ASD group reported lower cognitive empathy than EP and SAD groups. The ASD group reported lower emotional reactivity than the SAD group. All three clinical groups reported lower social skills that NT controls. The poor self-rated empathy for the ASD and EP groups generally reflects previous research that found individuals with these conditions perform relatively poorly on certain objective measures of empathy. However, the poor self-rated cognitive empathy and social skills for the SAD group conflicts with previous research that has found that SAD groups perform well on objective measures of empathy. This suggests that both EQ and objective measures should be used to fully assess empathy in clinical groups.

10.
Neurosci Biobehav Rev ; 107: 388-398, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31560922

RESUMO

Early life social experiences shape neural pathways in infants to develop lifelong social skills. This review presents the first unified circuit-based model of social learning that can be applied to early life social development, drawing together unique human developmental milestones, sensitive learning periods, and behavioral and neural scaffolds. Circuit domains for social learning are identified governing Activation, Integration, Discrimination, Response and Reward (AIDRR) to sculpt and drive human social learning. This unified model can be used to identify social delays earlier in development. We propose social impairments observed in Autism Spectrum Disorder are underpinned by early mistimed sensitive periods in brain development and alterations in amygdala development to disrupt the AIDRR circuits. This model directs how interventions can target neural circuits for social development and be applied early in life. To illustrate, the role of oxytocin and its use as an intervention is explored. The AIDRR model shifts focus away from delivering broad treatments based only on diagnostic classifications, to specifying and targeting the relevant circuits, at the right time of development, to optimize social learning.

11.
Mol Psychiatry ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471575

RESUMO

Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

12.
J Med Internet Res ; 21(8): e14127, 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376271

RESUMO

BACKGROUND: The Mental Health eClinic (MHeC) aims to deliver best-practice clinical services to young people experiencing mental health problems by making clinical care accessible, affordable, and available to young people whenever and wherever they need it most. The original MHeC consists of home page with a visible triage system for those requiring urgent help; a online physical and mental health self-report assessment; a results dashboard; a booking and videoconferencing system; and the generation of a personalized well-being plan. Populations who do not speak English and reside in English-speaking countries are less likely to receive mental health care. In Australia, international students have been identified as disadvantaged compared with their peers; have weaker social support networks; and have higher rates of psychological distress. This scenario is acquiring significant relevance as Spanish-speaking migration is rapidly growing in Australia, and the mental health services for culturally and linguistically diverse populations are limited. Having a Spanish version (MHeC-S) of the Mental Health eClinic would greatly benefit these students. OBJECTIVE: We used participatory design methodologies with users (young people aged 16-30 years, supportive others, and health professionals) to (1) conduct workshops with users to co-design and culturally adapt the MHeC; (2) inform the development of the MHeC-S alpha prototype; (3) test the usability of the MHeC-S alpha prototype; (4) translate, culturally adapt, and face-validate the MHeC-S self-report assessment; and (5) collect information to inform its beta prototype. METHODS: A research and development cycle included several participatory design phases: co-design workshops; knowledge translation; language translation and cultural adaptation; and rapid prototyping and user testing of the MHeC-S alpha prototype. RESULTS: We held 2 co-design workshops with 17 users (10 young people, 7 health professionals). A total of 15 participated in the one-on-one user testing sessions (7 young people, 5 health professionals, 3 supportive others). We collected 225 source documents, and thematic analysis resulted in 5 main themes (help-seeking barriers, technology platform, functionality, content, and user interface). A random sample of 106 source documents analyzed by 2 independent raters revealed almost perfect agreement for functionality (kappa=.86; P<.001) and content (kappa=.92; P<.001) and substantial agreement for the user interface (kappa=.785; P<.001). In this random sample, no annotations were coded for help-seeking barriers or the technology platform. Language was identified as the main barrier to getting medical or psychological services, and smartphones were the most-used device to access the internet. Acceptability was adequate for the prototype's 5 main elements: home page and triage system, self-report assessment, dashboard of results, booking and video visit system, and personalized well-being plan. The data also revealed gaps in the alpha prototype, such as the need for tailored assessment tools and a greater integration with Spanish-speaking services and communities. Spanish-language apps and e-tools, as well as online mental health information, were lacking. CONCLUSIONS: Through a research and development process, we co-designed and culturally adapted, developed and user tested, and evaluated the MHeC-S. By translating and culturally adapting the MHeC to Spanish, we aimed to increase accessibility and availability of e-mental health care in the developing world, and assist vulnerable populations that have migrated to English-speaking countries.

13.
JAMA Psychiatry ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31461129

RESUMO

Importance: The large contribution of psychiatric disorders to premature death and persistent disability among young people means that earlier identification and enhanced long-term care for those who are most at risk of developing life-threatening or chronic disorders is critical. Clinical staging as an adjunct to diagnosis to address emerging psychiatric disorders has been proposed for young people presenting for care; however, the longer-term utility of this system has not been established. Objectives: To determine the rates of transition from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders and to identify the demographic and clinical characteristics that are associated with the time course of these transitions. Design, Setting, and Participants: A longitudinal, observational study of 2254 persons aged 12 to 25 years who obtained mental health care at 2 early intervention mental health services in Sydney, Australia, and were recruited to a research register between June 18, 2008, and July 24, 2018 (the Brain and Mind Centre Optymise Cohort). Main Outcomes and Measures: The primary outcome of this study was transition from earlier to later clinical stages. A multistate Markov model was used to examine demographic (ie, age, sex, engagement in education, employment, or both) and clinical (ie, social and occupational function, clinical presentation, personal history of mental illness, physical health comorbidities, treatment use, self-harm, suicidal thoughts and behaviors) factors associated with these transitions. Results: Of the 2254 individuals included in the study, mean (SD) age at baseline was 18.18 (3.33) years and 1330 (59.0%) were female. Data on race/ethnicity were not available. Median (interquartile range) follow-up was 14 (5-33) months. Of 685 participants at stage 1a (nonspecific symptoms), 253 (36.9%) transitioned to stage 1b (attenuated syndromes). Transition was associated with lower social functioning (hazard ratio [HR], 0.77; 95% CI, 0.66-0.90), engagement with education, employment, or both (HR, 0.47; 95% CI, 0.25-0.91), manic-like experiences (HR, 2.12; 95% CI, 1.19-3.78), psychotic-like experiences (HR, 2.13; 95% CI, 1.38-3.28), self-harm (HR, 1.42; 95% CI, 1.01-1.99), and older age (HR, 1.27; 95% CI, 1.11-1.45). Of 1370 stage 1b participants, 176 (12.8%) transitioned to stage 2 (full-threshold) disorders. Transition was associated with psychotic-like experiences (HR, 2.31; 95% CI, 1.65-3.23), circadian disturbance (HR, 1.66; 95% CI, 1.17-2.35), psychiatric medication (HR, 1.43; 95% CI, 1.03-1.99), childhood psychiatric disorder (HR, 1.62; 95% CI, 1.03-2.54), and older age (HR, 1.24; 95% CI, 1.05-1.45). Conclusions and Relevance: Differential rates of progression from earlier to later stages of anxiety, mood, psychotic, or comorbid disorders were observed in young persons who presented for care at various stages. Understanding the rate and factors associated with transition assists planning of stage-specific clinical interventions and secondary prevention trials.

14.
Brain Behav Immun ; 82: 76-83, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376496

RESUMO

BACKGROUND: Substantial heterogeneity exists in both the severity of symptoms experienced as part of the sickness response to naturally-occurring infections, and the time taken for individuals to recover from these symptoms. Although contributing immunological and genetic factors have been previously been explored, less is known about the role of individual psychological and psychosocial factors, which may modulate the host immune response, or contribute independently, to symptom severity and duration. METHODS: Longitudinally-collected data from 484 Caucasian participants (mean age: 33.5 years; 51% women) experiencing a naturally-occurring acute infective illness enrolled in the prospective Dubbo Infection Outcome Study (DIOS) were analysed. At intake and subsequent follow-up assessments, self-report questionnaires were used to ascertain individual psychological and psychosocial characteristics and symptom information. Principal component analysis was applied to symptom data to derive endophenotype severity scores representing discrete symptom domains (fatigue, mood, pain, neurocognitive difficulties) and an overall index of severity. The contribution of individual psychological (trait neuroticism, locus of control, and illness behaviours) and psychosocial factors (relative socioeconomic advantage) to endophenotype severity at baseline were examined using multivariable linear regression models; interval-censored flexible parametric proportional hazards survival models were used to explore time to recovery (defined using within-sample negative threshold values). RESULTS: After controlling for time since symptom onset, greater levels of trait neuroticism consistently predicted greater symptom severity across all symptom domains (all p's < 0.015). Similarly, greater relative socioeconomic disadvantage was significantly associated with greater severity across all endophenotypes (p's < 0.025) except neurocognitive disturbance. Locus of control and illness behaviours contributed differentially across endophenotypes. Reduced likelihood of recovery was significantly predicted by greater initial symptom severity for all endophenotypes (all p's < 0.001), as well as higher levels of trait neuroticism. CONCLUSIONS: Individual psychological and psychosocial factors contribute to the initial severity and to the prolonged course of symptoms after naturally-occurring infective illnesses. These factors may play an independent role, represent a bias in symptom reporting, or reflect increased stress responsivity and a heightened inflammatory response. Objective metrics for severity and recovery are required to further elucidate their roles.

15.
Schizophr Res ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301881

RESUMO

People classified as ultra-high risk (UHR) of developing psychosis have reduced cellular membrane omega-3 and omega-6 polyunsaturated fatty acids (PUFA). We aimed to compare omega-3 index, fatty acids and molecular phospholipid species from erythrocytes of people with UHR (n = 285) with age-matched healthy controls (n = 120) assessed by mass spectrometry. Lower proportions of PUFA were observed in the UHR group compared to healthy controls; specifically, eicosapentaenoic acid (EPA) was 29.3% lower, docosahexaenoic acid (DHA) was 27.2% lower, arachidonic acid (AA) was 15.8% lower and the omega-3 index was 26.9% lower. The AA to EPA ratio was higher in the UHR group compared to the healthy group. Smoking status had no significant effect on PUFA levels in healthy or the UHR groups. BMI was associated with PUFA levels in the UHR group only and the statistical model only explains 2% of the variance of the PUFA levels. The proportion of nervonic acid was 64.4% higher in the UHR group compared to healthy controls. At a lipid class level, the UHR group had 16% higher concentrations of sphingomyelin (SM) and 46% lower concentrations phosphatidylethanolamine (PE) compared to healthy group. Of the 49 individual molecular phospholipids, twenty-seven phospholipid species were lower in the UHR group. In conclusion, there are clear differences in the proportions of erythrocyte fatty acids and phospholipids between UHR and healthy controls and UHR had higher concentrations of SM and lower concentrations of PE. These differences may represent a promising prodromal risk biomarker in the UHR population to aid clinical diagnosis.

16.
Am J Psychiatry ; : appiajp201918101144, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31352813

RESUMO

OBJECTIVE: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects. METHODS: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1. RESULTS: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset. CONCLUSIONS: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.

17.
Addiction ; 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31313399

RESUMO

BACKGROUND AND AIMS: The non-medical use of over-the-counter or prescribed analgesics (NMUA) is a significant public health problem. Little is known about the genetic and environmental etiology of NMUA and how these risks relate to other classes of substance use and misuse. Our aims were to estimate the heritability NMUA and sources of genetic and environmental covariance with cannabis and nicotine use, cannabis and alcohol use disorders and nicotine dependence in Australian twins. DESIGN: Biometrical genetic analyses or twin methods using structural equation univariate and multivariate modeling. SETTING: Australia. PARTICIPANTS: A total of 2007 young adult twins [66% female; µage  = 25.9, standard deviation (SD) = 3.6, range = 18-38] from the Brisbane Longitudinal Twin Study retrospectively assessed between 2009 and 2016. MEASUREMENTS: Self-reported NMUA (non-opioid or opioid-based), life-time nicotine, cannabis and opioid use, DSM-V cannabis and alcohol use disorders and the Fagerström Test for Nicotine Dependence. FINDINGS: Life-time NMUA was reported by 19.4% of the sample. Univariate heritability explained 46% [95% confidence interval (CI) = 0.29-0.57] of the risks in NMUA. Multivariate analyses revealed that NMUA is moderately associated genetically with cannabis (rg  = 0.41) and nicotine (rg  = 0.45) use and nicotine dependence (rg  = 0.34). In contrast, the genetic correlations with cannabis (rg  = 0.15) and alcohol (rg  = 0.07) use disorders are weak. CONCLUSIONS: In young male and female adults in Australia, the non-medical use of over-the-counter or prescribed analgesics appears to have moderate heritability. NMUA is moderately associated with cannabis and nicotine use and nicotine dependence. Its genetic etiology is largely distinct from that of cannabis and alcohol use disorders.

18.
Twin Res Hum Genet ; 22(3): 154-163, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31198126

RESUMO

The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20-39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range =  22-44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep-wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.

19.
J Psychiatr Res ; 116: 51-60, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195164

RESUMO

BACKGROUND: Impulsivity is considered a possible phenotype underlying the expression of self-harm and suicidal behaviors. Yet impulsivity is a not a unitary construct and there is evidence that different facets of impulsivity follow different neurodevelopmental trajectories and that some facets may be more strongly associated with such behaviors than others. Moreover, it is unclear whether impulsivity is a useful predictor of self-harm or suicidal behavior in young people, a population already considered to display heightened impulsive behavior. METHODS: A systematic review and meta-analysis of studies published in Medline, PubMed, PsychInfo or Embase between 1970 and 2017 that used a neurocognitive measure to assess the independent variable of impulsivity and the dependent variable of self-harm and/or suicidal behavior among young people (mean age < 30 years old). RESULTS: 6183 titles were identified, 141 full texts were reviewed, and 18 studies were included, with 902 young people with a self-harm or suicidal behavior and 1591 controls without a history of these behaviors. Deficits in inhibitory control (13 studies, SMD 0.21, p-value = 0.002, 95% confidence interval (CI) (0.08-0.34), prediction interval (PI) = 0.06-0.35) and impulsive decision-making (14 studies, SMD 0.17, p-value = 0.008, 95% CI (0.045-0.3), PI = 0.03-0.31) were associated with self-harm or suicidal behavior. There were no significant differences between measures of different facets of impulsivity (ie. delay discounting, risky decision-making, cognitive or response inhibition) and self-harm or suicidal behavior. CONCLUSION: Multiple facets of impulsivity are associated with suicidal behavior in young people. Future suicide research should be designed to capture impulsive states and investigate the impact on different subtypes of impulsivity.

20.
Psychiatry Res ; 276: 232-238, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31121529

RESUMO

Neuropsychological assessments have provided the field of psychiatry with important information about patients. As an assessment tool, a neuropsychological battery can be useful in a clinical setting; however, implementation as standard clinical care in an inpatient unit has not been extensively evaluated. A computerized cognitive battery was administered to 103 current young adult inpatients (19.2 ±â€¯3.1 years; 72% female) with affective disorder. Neurocognitive tasks included Verbal Recognition Memory (VRM), Attention Switching (AST), Paired Association Learning (PAL), and Rapid Visual Processing (RVP). Patients also completed a computerized self-report questionnaire evaluating subjective impressions of their cognition. Hierarchical cluster analysis determined three neurocognitive subgroups: cluster 1 (n = 17) showed a more impaired neurocognitive profile on three of the four variables compared to their peers in cluster 2 (n = 59), and cluster 3 (n = 27), who had the most impaired attentional shifting. Two of the four neurocognitive variables were significantly different between all three cluster groups (verbal learning and sustained attention). Overall group results showed an association between poorer sustained attention and increased suicidal ideation. These findings strengthen the idea that neurocognitive profiles may play an important role in better understanding the severity of illness in young inpatients with major psychiatric disorders.

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