Interventions for co-occurring addictive and other mental disorders (AMDs)

While research on the management of co-occurring addictive and mental disorders (AMDs) has grown substantially in recent years, we still have little guidance on specific strategies. Consideration of epidemiological research and ethical principles can supplement existing clinical trials in providing a way forward. High frequencies of co-occurring disorders, equity of access for affected individuals and potential clashes between services in priorities and procedures, suggest that a stepped model of care by a single service may often be required. Typically, problems are multiple rather than dual, with potential for mutual influence, suggesting a need for interventions that are sensitive to and encompass complex co-occurring problems. Motivational problems are endemic, initial gains are often partial and unstable, and relapses potentially have serious consequences, suggesting a need for long-term, assertive follow-up. Principles such as these provide a solid framework for designing both services and interventions. However, there is a continuing need for controlled trials that unpack effective components of interventions, and increase their impact.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Screening in early childhood for risk of later mental health problems : a longitudinal study

Depression in childhood or adolescence is associated with increased rates of depression in adulthood. Does this justify efforts to detect (and treat) those with symptoms of depression in early childhood or adolescence? The aim of this study was to determine how well symptoms of anxiety/depression (A-D) in early childhood and adolescence predict adult mental health. The study sample is taken from a population-based prospective birth cohort study. Of the 8556 mothers initially approached to participate 8458 agreed, of whom 7223 mothers gave birth to a live singleton baby. Children were screened using modified Child Behaviour Checklist (CBCL) scales for internalizing and total problems (T-P) at age 5 and the CBCL and Youth Self Report (YSR) A-D subscale and T-P scale at age 14. At age 21, a sub-sample of 2563 young adults in this cohort were administered the CIDI-Auto. Results indicated that screening at age 5 would detect few later cases of significant mental ill-health. Using a cut-point of 20% for internalizing at child age 5 years the CBCL had sensitivities of only 25% and 18% for major depression and anxiety disorders at 21 years, respectively. At age 14, the YSR generally performed a little better than the CBCL as a screening instrument, but neither performed at a satisfactory level. Of the children who were categorised as having YSR A-D at 14 years 30% and 37% met DSM-IV criteria for major depression and anxiety disorders, respectively, at age 21. Our findings challenge an existing movement encouraging the detection and treatment of those with symptoms of mental illness in early childhood.

Validating a screening tool for mental health and substance use risk in an Indigenous prison population

Introduction and Aims: The Indigenous Risk Impact Screen (IRIS) is a validated culturally appropriate and widely used tool in the community for assessing substance use and mental disorder. This research aimed to assess the utility of this tool in an Indigenous prison population. Design and Methods: The study used data collected from a cross-sectional study of mental health among indigenous inmates in Queensland custodial centres (n=395, 84% male). Participants were administered a modified version of the IRIS, and ICD-10 diagnoses of substance use, depressive and anxiety disorders obtained using the Composite International Diagnostic Interview (CIDI). The concurrent validity of the modified IRIS was assessed against those of the CIDI. Results: 312 people screened as high risk for a substance use disorder and 179 were high risk for mental problems. 73% of males and 88% of females were diagnosed with a mental disorder. The IRIS was an effective screener for substance use disorders, with high sensitivity (Se) of 94% and low specificity (Sp) of 33%. The screener was less effective in identifying depression (Se 82%, Sp 59%) and anxiety (Se 68%, Sp 60%). Discussion: The IRIS is the first culturally appropriate screening instrument to be validated for the risk of drug and alcohol and mental disorder among Indigenous adults in custody. Conclusions: This study demonstrated that the IRIS is a valid tool for screening of alcohol and drug use risk among an incarcerated Indigenous population. The IRIS could offer an opportunity to improve the identification, treatment and health outcomes for incarcerated Indigenous adults.

Progress towards understanding the genetics of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a complex syndrome that occurs following exposure to a potentially life threatening traumatic event. This review summarises the literature on the genetics of PTSD including gene–environment interactions (GxE), epigenetics and genetics of treatment response. Numerous genes have been shown to be associated with PTSD using candidate gene approaches. Genome-wide association studies have been limited due to the large sample size required to reach statistical power. Studies have shown that GxE interactions are important for PTSD susceptibility. Epigenetics plays an important role in PTSD susceptibility and some of the most promising studies show stress and child abuse trigger epigenetic changes. Much of the molecular genetics of PTSD remains to be elucidated. However, it is clear that identifying genetic markers and environmental triggers has the potential to advance early PTSD diagnosis and therapeutic interventions and ultimately ease the personal and financial burden of this debilitating disorder.

Substance use disorders

Substance use disorders involve alcohol and a range of other legal and illicit drugs, and are characterised by a preoccupation with or craving for the substance, a greater priority to substance use than other goals, and/or a difficulty controlling consumption. Use of the substance may continue despite negative impacts on other activities, roles, relationships, and physical and mental health. Increased physical tolerance to the substance and withdrawal symptoms may also occur. Broad impacts on social and cognitive functioning and on physical and mental health emerge with increasing problem severity. Diffuse cognitive impairment may persist for up to 12 months post-detoxification in alcohol dependence. Psychological comorbidity is common, particularly mood and anxiety disorders. A quarter of all Australians will have a substance use disorder in their lifetime. One in five will consume alcohol at a level that puts them at risk of harm from an alcohol-related disease or injury over their lifetime. Australians aged 18 to 29 years are at higher risk than other age groups.

Validation of the Edinburgh Postnatal Depression Scale for men, and comparison of item endorsement with their partners

BACKGROUND: The Edinburgh Postnatal Depression Scale (EPDS) has been validated and used extensively in screening for depression in new mothers, both in English speaking and non-English speaking communities. While some studies have reported the use of the EPDS with fathers, none have validated it for this group, and thus the appropriate cut-off score for screening for depression or anxiety caseness for this population is not known. METHODS: Couples were recruited antenatally and interviewed at six weeks postpartum. EPDS scores and distress caseness (depression or anxiety disorders) for 208 fathers and 230 mothers were determined using the Diagnostic Interview Schedule. RESULTS: Analyses of the EPDS for fathers using distress caseness (depression or anxiety disorders) as the criterion shows that a cut-off of 5/6 has optimum receiver operating characteristics. Furthermore acceptable reliability (split-half and internal consistency) and validity (concurrent) coefficients were obtained. For mothers the optimum cut-off screening value to detect distress caseness was 7/8. Item analysis revealed that fathers endorsed seven of the ten items at lower rates to mothers, with the most significant being that referring to crying. CONCLUSIONS: The EPDS is a reliable and valid measure of mood in fathers. Screening for depression or anxiety disorders in fathers requires a two point lower cut-off than screening for depression or anxiety in mothers, and we recommend this cut-off to be 5/6

A pilot study utilising cross-age peer tutoring as a method of intervention for anxious adolescents

Anxiety disorders are the most common psychopathology experienced by young people, with up to 18% of adolescents developing an anxiety disorder. The consequences of these disorders, if left untreated, include impaired peer relationships, school absenteeism and self-concept problems. In addition, anxiety disorders may play a causal role in the development of depression in young people, precede eating disorders and predispose adolescents to substance abuse disorders. While the school is often chosen as a place to provide early intervention for this debilitating disorder, the fact that excessive anxiety is often not recognised in school and that young people are reluctant to seek help, makes identifying these adolescents difficult. Even when these young people are identified, there are problems in providing sensitive programs which are not stigmatising to them within a school setting. One method which may engage this adolescent population could be cross-age peer tutoring. This paper reports on a small pilot study using the “Worrybusters” program and a cross-age peer tutoring method to engage the anxious adolescents. These anxious secondary school students planned activities for teacher-referred anxious primary school students for a term in the high school setting and then delivered those activities to the younger students weekly in the next term in the primary school. Although the secondary school students decreased their scores on anxiety self-report measures there were no significant differences for primary school students’ self-reports. However, the primary school parent reports indicated a significant decrease in their child’s anxiety.

Psychotropic drugs

19.1 Depression and Antidepressants 19.1.1 Depression 19.1.2 Neurochemistry of Depression and the Monoamine Theory 19.1.3 Antidepressant Indications and Drug Classes 19.1.4 General Considerations with the use of Antidepressants 19.1.5 Tricyclic Antidepressants 19.1.6 Monoamine Oxidase Inhibitors 19.1.7 Selective Serotonin Reuptake Inhibitors 19.1.8 Combined Serotonin and Noradrenaline Reuptake Inhibitors 19.1.9 Long Term Adaptive Changes with Antidepressants 19.2 Psychosis, Schizophrenia, and Antipsychotics 19.2.1 Psychosis and Schizophrenia 19.2.2 Neurochemistry of Psychosis and the Dopamine Theory 19.2.3 Antipsychotic Drug Indications and Drug Classes 19.2.4 Antipsychotic Mechanisms of Action 19.2.5 Typical Antipsychotics (First Generation) 19.2.6 Atypical Antipsychotics (Second Generation) 19.3 Anxiety and Anxiolytics 19.3.1 Fear, Anxiety and Anxiety Disorders 19.3.2 Neurochemistry of Anxiety 19.3.3 Anxiolytic Drug Indications and Drug Classes 19.3.4 Benzodiazepines 19.3.5 Antidepressants 19.3.6 Buspirone

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

PP39 Mental health outcomes of abortion for young women aged 18-23 years, findings from an Australian longitudinal birth cohort study

Background: Few longitudinal studies have examined the mental health outcomes of women after abortion and the results are controversial. Despite falling birth rates, teenage pregnancies remain high and over half (53%) of teenage and a third (36%) of young adult (20_24 years) pregnancies are aborted. Recent findings from a NewZealand longitudinal birth cohort linked abortion and subsequent psychiatric disorders in young women. Limited Australian data is available examining this association. Methods: Data were taken from the Mater-University Study of Pregnancy (MUSP). Running since 1981, this is a prospective birth cohort study of 7223 mothers and children. At the 21-year follow-up 3775 (52.3% of the original cohort) participants were surveyed, of these 1132 young women had complete data on pregnancy outcomes and psychiatric diagnoses from a structured interview. Binary logistic regression examined the association between five lifetime psychiatric disorders (nicotine, alcohol, cannabis, affective and anxiety disorders) and ever having an abortion or birth. Analyses adjusted for age, concurrent and maternal sociodemographic factors, and factors related to adolescent behaviour, previous mental health and family functioning. Results: A quarter of the young women (n_261) reported at least one pregnancy and 32.6% had an abortion. Abortion was significantly associated with age-adjusted OR for all the lifetime disorders. After full adjustment abortion remained significantly associated with nicotine (OR_2.1, 1.2_3.6) and alcohol disorders (OR_2.0, 1.3_3.3). Conclusion: The findings suggest that abortion in young women is independently associated with an increased risk of nicotine and alcohol disorders.

A meta-analytic clarification of the relationship between posttraumatic growth and symptoms of posttraumatic distress disorder

Traumatic experiences can have a powerful impact on individuals and communities but the relationship between perceptions of beneficial and pathological outcomes are not known. Therefore, this meta-analysis examined both the strength and the linearity of the relationship between symptoms of posttraumatic stress disorder (PTSD) and perceptions of posttraumatic growth (PTG) as well as identifying the potential moderating roles of trauma type and age. Literature searches of all languages were conducted using the ProQuest, Wiley Interscience, ScienceDirect, Informaworld and Web of Science databases. Linear and quadratic (curvilinear) rs as well as βs were analysed. Forty-two studies (N=11, 469) that examined both PTG and symptoms of PTSD were included in meta-analytic calculations. The combined studies yielded a significant linear relationship between PTG and PTSD symptoms (r=.315, CI = 0.299, 0.331), but also a significantly stronger (as tested by Fisher’s transformation) curvilinear relationship (r=.372, CI = 0.353, 0.391). The strength and linearity of these relationships differed according to trauma type and age. The results remind those working with traumatised people that positive and negative post-trauma outcomes can co-occur. A focus only on PTSD symptoms only may limit or slow recovery and mask the potential for growth.

Traits of fear resistance and susceptibility in an advanced intercross line

Genetic variability in the strength and precision of fear memory is hypothesised to contribute to the etiology of anxiety disorders, including post-traumatic stress disorder. We generated fear-susceptible (F-S) or fear-resistant (F-R) phenotypes from an F8 advanced intercross line (AIL) of C57BL/6J and DBA/2J inbred mice by selective breeding. We identified specific traits underlying individual variability in Pavlovian conditioned fear learning and memory. Offspring of selected lines differed in the acquisition of conditioned fear. Furthermore, F-S mice showed greater cued fear memory and generalised fear in response to a novel context than F-R mice. F-S mice showed greater basal corticosterone levels and hypothalamic corticotrophin-releasing hormone (CRH) mRNA levels than F-R mice, consistent with higher hypothalamic-pituitary-adrenal (HPA) axis drive. Hypothalamic mineralocorticoid receptor and CRH receptor 1 mRNA levels were decreased in F-S mice as compared with F-R mice. Manganese-enhanced magnetic resonance imaging (MEMRI) was used to investigate basal levels of brain activity. MEMRI identified a pattern of increased brain activity in F-S mice that was driven primarily by the hippocampus and amygdala, indicating excessive limbic circuit activity in F-S mice as compared with F-R mice. Thus, selection pressure applied to the AIL population leads to the accumulation of heritable trait-relevant characteristics within each line, whereas non-behaviorally relevant traits remain distributed. Selected lines therefore minimise false-positive associations between behavioral phenotypes and physiology. We demonstrate that intrinsic differences in HPA axis function and limbic excitability contribute to phenotypic differences in the acquisition and consolidation of associative fear memory. Identification of system-wide traits predisposing to variability in fear memory may help in the direction of more targeted and efficacious treatments for fear-related pathology. Through short-term selection in a B6D2 advanced intercross line we created mouse populations divergent for the retention of Pavlovian fear memory. Trait distinctions in HPA-axis drive and fear network circuitry could be made between naïve animals in the two lines. These data demonstrate underlying physiological and neurological differences between Fear-Susceptible and Fear-Resistant animals in a natural population. F-S and F-R mice may therefore be relevant to a spectrum of disorders including depression, anxiety disorders and PTSD for which altered fear processing occurs.

Expression pattern of the cannabinoid receptor genes in the frontal cortex of mood disorder patients and mice selectively bred for high and low fear

Although the endocannabinoid system (ECS) has been implicated in brain development and various psychiatric disorders, precise mechanisms of the ECS on mood and anxiety disorders remain unclear. Here, we have investigated developmental and disease-related expression pattern of the cannabinoid receptor 1 (CB1) and the cannabinoid receptor 2 (CB2) genes in the dorsolateral prefrontal cortex (PFC) of humans. Using mice selectively bred for high and low fear, we further investigated potential association between fear memory and the cannabinoid receptor expression in the brain. The CB1, not the CB2, mRNA levels in the PFC gradually decrease during postnatal development ranging in age from birth to 50 years (r 2 > 0.6 & adj. p < 0.05). The CB1 levels in the PFC of major depression patients were higher when compared to the age-matched controls (adj. p < 0.05). In mice, the CB1, not the CB2, levels in the PFC were positively correlated with freezing behavior in classical fear conditioning (p < 0.05). These results suggest that the CB1 in the PFC may play a significant role in regulating mood and anxiety symptoms. Our study demonstrates the advantage of utilizing data from postmortem brain tissue and a mouse model of fear to enhance our understanding of the role of the cannabinoid receptors in mood and anxiety disorders

Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics

Saliva as a biological fluid is gaining wider acceptance for diagnosing diseases. The growing interest in saliva as a biological fluid is due to its noninvasiveness, ease of use, cost-effectiveness, and multiple sample collection possibilities as well as minimal risk to health care professionals of contracting infectious organisms such as HIV and Hep B. However, the clinical translation of saliva is hampered by our lack of understanding of the biomolecular transportation from blood into saliva, the diurnal variations of biomolecules present in saliva, and relatively low levels of analytes (100th to a 1000th fold less than in blood). We provide information on the current status of salivary research, salivary diagnostics empowered by nanotechnology, and future prospects in this emerging field of saliva diagnostics.