Sometimes It's Good to be Short: The Serotonin Transporter Gene, Positive Parenting, and Adolescent Depression.

In threatening environments, the short (S) allele of 5-HTTLPR is proposed to augment risk for depression. However, it is unknown whether 5-HTTLPR variation increases risk for depression in environments of deprivation, lacking positive or nurturant features. Two independent longitudinal studies (n = 681 and 176, respectively) examined whether 5-HTTLPR moderated associations between low levels of positive parenting at 11-13 years and subsequent depression at 17-19 years. In both studies only LL homozygous adolescents were at greater risk for depression with decreasing levels of positive parenting. Thus, while the S allele has previously been identified as a susceptible genotype, these findings suggest that the L allele may also confer sensitivity to depression in the face of specific environmental challenges.

Health-Related Quality of Life in People Living with Psychotic Illness and Factors Associated with Its Variation.

OBJECTIVES: To establish whether the four-dimensional Assessment of Quality of Life (AQoL-4D) produces robust utility values in adults with psychotic illness, and identify health inequalities compared with the general population. METHODS: The AQoL-4D was completed by 1613 individuals with an International Classification of Diseases, Tenth Revision, psychotic illness in the 2010 Australian National Survey of Psychosis. Utilities were assessed for this sample and 20 subgroups, and were compared with general population norms. Modified Cohen d was used as an index of effect size. Utilities were collapsed into 10 health-related quality-of-life (HRQOL) bands or decades. RESULTS: HRQOL in people with psychotic illness was half of the maximum achievable utility (half-"full health") with a mean utility of 0.49 (95% confidence interval [CI] 0.48-0.51), and showing substantial variability across subgroups. Participants with essentially normal functioning had the highest mean utility (0.72; 95% CI 0.68-0.77), and those with very poor perceived mental health had the lowest (0.22; 95% CI 0.18-0.26). These subgroups showed the most variability. Negative symptoms also gave rise to substantial variation. Among diagnostic categories, only depressive psychosis had a large effect relative to delusional disorders. The distribution of utilities in people with psychotic illness differed markedly from that in the general population, with 6.8% versus 47.2% having values in the highest decade (>0.90-1.00). Utilities were lower in every age group in people with psychosis. CONCLUSIONS: Profound HRQOL impacts are revealed by the AQoL-4D in people with psychotic illness, and marked variations in utilities were observed for key subjective and objective measures. We provide a suite of utility values for economic modeling studies and recommend the AQoL-4D for assessing HRQOL in people with psychotic illness.

Counting up the risks: How common are risk factors for morbidity and mortality in young people with psychosis?

BACKGROUND: This study examined the prevalence of risk factors for cardiovascular (CV)-related morbidity and mortality in young people with psychosis aged 18 to 24 years. METHODS: The study included 132 people aged 18 to 24 years who participated in the 2010 second Australian national survey of people living with psychosis. The 2009 World Health Organisation (WHO) Global Health Risks report was used as a framework to determine which specific risk factors were present in each in these young people. The risk factors assessed in this study were smoking, alcohol use, hypertension, overweight/obesity, physical inactivity, high blood glucose, high cholesterol and poor diet. Each risk factor was defined according to WHO criteria. A count of the total number of risk factors present for each participant was determined. Data for male and female participants were compared. RESULTS: Young men had an average of 2.9 (SD 1.2) risk factors. Young women had an average of 2.4 (SD 1.2) risk factors. The most common risk factors were low fruit and vegetable intake (77.9%), cigarette smoking (67.7%), overweight/obesity (55%) and physical inactivity (39.8%). There were no significant differences between men and women in the number of risk factors present, or the prevalence of individual risk factors. CONCLUSION: This study demonstrated that many of the risk factors that ultimately contribute to disability and premature death are present at an early age in people with psychosis. Preventive measures need to be an integral component of early intervention services for this client population to avert progression to serious CV morbidity and early mortality.

Comorbid Diabetes and Depression in a National Sample of Adults With Psychosis.

Objective: People with psychosis have an elevated risk of depression and diabetes but no large-scale study has characterized their relationship. We aimed to assess this association and to evaluate possible explanatory factors. Methods: Analysis of cross-sectional data from a national sample of 1155 people with psychosis who gave a fasting blood sample and could be tested for diabetes mellitus. The association between current diabetes mellitus and current depression was estimated using logistic regression, adjusted for age, sex and current psychotropic medication. Results: A diagnosis of depression was significantly associated with diabetes (OR = 2.16, P = .048) and diabetes medication (OR = 2.50, P = .050) in people with schizophrenia but no other psychosis subtype. Adjustment for cognitive processing speed and current residence (especially psychiatric hospitalization) attenuated that association to nonsignificance. Diabetes and diabetes medication were not significantly associated with antidepressant or mood stabilizer medication. Conclusions: Clinicians should be aware that people with schizophrenia and diabetes have twice the rate of current depression, and that comorbid diabetes and depression is associated with cognitive impairment and hospitalization. Efforts to disentangle the causal pathways between diabetes, depression, and cognition in people with schizophrenia may be complicated by multiple indications in people with psychosis for the prescription of depression medication, and their lack of association with diabetes mellitus.

The role of arterial elasticity and cardiovascular peripheral resistance as clinically relevant indices of health status in people with psychosis.

OBJECTIVE: Hypertension is one of the most important risk factors for cardiovascular disease (CVD). Systolic and diastolic blood pressure (BP) are higher in people with psychosis compared to the general population, but there is little research into measures of the elasticity of the arterial wall (pulse pressure; PP) and peripheral resistance (mean arterial pressure; MAP). PP and MAP can provide an additional perspective on the functioning of the circulatory system. This study investigated PP and MAP in people with psychosis, using factors known to be related to PP and MAP in the general population. METHOD: Participants included 1421 people aged 18-64years, from the second Australian national survey of psychosis, untreated with antihypertensive medication. We tested the interaction and main effects between age and gender on PP, MAP, systolic BP and diastolic BP. Odds ratios were calculated in people exceeding the at-risk thresholds for PP and MAP. Multiple linear regression was used to test whether factors associated with at-risk PP and MAP in the general population were similarly associated in the psychosis population. RESULTS: The interaction effect between age and gender on PP, MAP, systolic BP and diastolic BP was not statistically significant. Variables that retained significance in the regression model in explaining higher PP and MAP were: male gender, higher age, and having a family history of hypertension. CONCLUSION: Clinicians monitoring and treating CV risk in this population need to ensure that they have recorded whether there is a family history of hypertension, and should be especially, more vigilant in men and in older patients.

Responding to challenges for people with psychotic illness: Updated evidence from the Survey of High Impact Psychosis.

OBJECTIVE: The objective is to summarise recent findings from the 2010 Australian Survey of High Impact Psychosis (SHIP) and examine their implications for future policy and planning to improve mental health, physical health and other circumstances of people with a psychotic disorder. METHODS: Survey of High Impact Psychosis collected nationally representative data on 1825 people with psychotic illness. Over 60 papers have been published covering key challenges reported by participants: financial problems, loneliness and social isolation, unemployment, poor physical health, uncontrolled symptoms of mental illness, and lack of stable, suitable housing. Findings are summarised under the rubric of participant-ranked top challenges. RESULTS: The main income source for the majority (85%) of participants was a government benefit. Only one-third was employed, and the most appropriate employment services for this group were under-utilised. High rates of loneliness and social isolation impacted mental and physical health. The rate of cardiometabolic disease was well above the general population rate, and associated risk factors were present from a very young age. Childhood abuse (30.6%), adult violent victimisation (16.4%) and alcohol and substance abuse/dependence (lifetime rates of 50.5% and 54.5%, respectively) complicated the clinical profile. Treatment with medication was suboptimal, with physical health conditions undertreated, a high rate of psychotropic polypharmacy and underutilisation of clozapine in chronic persistent psychotic illness. Only 38.6% received evidence-based psychosocial therapies. In the previous year, 27.4% had changed housing and 12.8% had been homeless, on average for 155 days. CONCLUSION: Money, social engagement and employment are the most important challenges for people with psychotic illness, as well as good physical and mental health. An integrated approach to recovery is needed to optimise service delivery and augment evidence-based clinical practice with measures to improve physical health and social circumstances. Meeting these challenges has the potential to reduce costs to government and society, as well as promote recovery.

The value of counting WHO-defined cardiovascular risk factors for death and disability in a national sample of adults with psychosis.

OBJECTIVE: This study explored the prevalence and associations of eight WHO-defined CVD risk factors for death and disability in people with psychosis. METHOD: The study included 1156 people aged 18-64years, diagnosed with psychosis. The 2009 World Health Organisation (WHO) Global Health Risks Report was used as a framework to determine the prevalence and number of eight key risk factors for cardiovascular disease (CVD) in men and women with psychosis. Differences in the number and type of risk factors by age and gender were investigated. Multi-predictor analysis was performed to identify associations between demographic factors, psychiatric diagnosis and accumulative CVD risk factors. RESULTS: Women had fewer CVD risk factors than men. The number of risk factors significantly decreased in association with single marital status, current employment and significantly increased with earning a higher income. People aged 35-49years and 50-64years had an average of 4 risk factors (SD 1.38 and 1.30); people aged 18-34years had an average of 3 risk factors (SD 1.30). Mean risk factors were higher in the middle age and older age groups (35-49years and 50-64years) compared with the younger age group (18-34years) (p<0.0001). Overweight/obesity, hypertension, high blood glucose/diabetes and high cholesterol were significantly more prevalent in older men and women. CONCLUSION: People with psychosis have a high prevalence of individual and aggregate CVD risks. These were more common in men and rose with age, implying the necessity of close clinical monitoring. The most common risk factors should be targeted by lifestyle interventions.

Risk Factors for Obstructive Sleep Apnea Are Prevalent in People with Psychosis and Correlate with Impaired Social Functioning and Poor Physical Health.

BACKGROUND: Obstructive sleep apnea (OSA) in the general community is associated with obesity, smoking, alcohol, and sedative medication use and contributes to depressed mood, daytime sedation, and sudden cardiovascular deaths. Poor cardiovascular health, impaired social functioning, and negative and cognitive symptoms are also among the common clinical features of psychotic disorders. People with psychosis have higher rates of sleep disturbance; however, OSA has not been extensively investigated in this population. AIMS: This study aimed to determine the prevalence of OSA and general sleep disruption symptoms in a representative Australian sample of people with psychosis. We investigated the prevalence of potential risk factors for OSA, including obesity, psychotropic medications, and substance abuse in this population. Finally, we evaluated associations between symptoms of OSA, symptoms of general sleep disruption, and various clinical features in people with psychosis. METHODS: Participants took part in the Second National Australian Survey of Psychosis, a population-based survey of Australians with a psychotic disorder aged 18-64 years. Symptoms associated with OSA (snoring and breathing pauses during sleep) in the past year were assessed using questions from the University of Maryland Medical Centre Questionnaire and symptoms associated with general sleep disruption in the past week using the Assessment of Quality of Life Questionnaire. Data collected included psychiatric diagnosis and symptoms, education, employment, medications, smoking status, physical activity, drug and alcohol use, and cognitive function. Physical health measures included body mass index, waist circumference, blood pressure, fasting blood glucose, and lipids. RESULTS: Snoring was reported by 41.9%; 7% stating they frequently stopped breathing (pauses) during sleep. Univariate logistic regressions show OSA symptoms (pauses and snoring) were associated with older age, female gender, lower levels of social participation or employment, cardiovascular risk factors, sedentary lifestyle, and poorer quality of life, while symptoms of general sleep disruption were more likely in people with depressive symptoms. CONCLUSION: Australians with psychosis have high levels of sleep disturbance, including OSA. OSA symptoms were associated with cardiovascular disease risk factors, reduced social participation and employment, and poorer quality of life. Whether correction of OSA can improve these factors in people with psychosis remains to be determined.

Awareness of Pre-diabetes or Diabetes and Associated Factors in People With Psychosis.

OBJECTIVE: To estimate awareness of pre-diabetes or type 2 diabetes and associated factors in people with psychosis, a known high-risk group. METHODS: Cross sectional analysis of a national sample with psychosis who were aged 18-64 years, gave a fasting blood sample (n = 1155), had pre-diabetes or diabetes based on testing (n = 359) and reported if they knew they had high blood sugar or diabetes at survey (n = 356). Logistic regression was used to identify factors associated with awareness of pre-diabetes or diabetes prior to testing. RESULTS: The prevalence of pre-diabetes (19.0% 219/1153) or type 2 diabetes (12.1%, 140/1153) was 31.1% (359/1153); 45% (160/356) were known prior to testing. Factors associated with detection were higher fasting blood glucose, older age, a perception of poor health, severe obesity, dyslipidaemia or treatment with a lipid regulating drug, a family history of diabetes, Aboriginal or Torres Strait Islander descent, decreased cognitive functioning, regional economic disadvantage, treatment with an antihypertensive drug, and an elevated 5-year risk for cardiovascular disease. The prevalence of undiagnosed pre-diabetes/diabetes was highest in those aged 25-34 years at 34.2%. CONCLUSIONS: Clinical detection of pre-diabetes or diabetes in people with psychosis was strongly dependent on established risk factors for type 2 diabetes in the population but not on current antipsychotic drug treatment or psychiatric case management which should ensure regular screening. Screening must become a clinical priority and should not wait until age 40.

Common familial risk factors for schizophrenia and diabetes mellitus.

OBJECTIVE: The co-occurrence of type 2 diabetes and psychosis is an important form of medical comorbidity within individuals, but no large-scale study has evaluated comorbidity within families. The aim of this study was to determine whether there is evidence for familial comorbidity between type 2 diabetes and psychosis. METHOD: Data were analysed from an observational study of a nationally representative sample of 1642 people with psychosis who were in contact with psychiatric services at the time of survey (The 2010 Australian National Survey of Psychosis). Participants were aged 18-64 years and met World Health Organization's International Classification of Diseases, 10th Revision diagnostic criteria for a psychotic disorder (857 with schizophrenia, 319 with bipolar disorder with psychotic features, 293 with schizoaffective disorder, 81 with depressive psychosis and 92 with delusional disorder or other non-organic psychoses). Logistic regression was used to estimate the association between a family history of diabetes and a family history of schizophrenia. RESULTS: A positive family history of diabetes was associated with a positive family history of schizophrenia in those with a psychotic disorder (odds ratio = 1.35, p = 0.01, adjusted for age and gender). The association was different in those with an affective versus non-affective psychosis (odds ratio = 0.613, p = 0.019, adjusted for age and gender) and was significant only in those with a non-affective psychosis, specifically schizophrenia (odds ratio = 1.58, p = 0.005, adjusted for age and sex). Adjustment for demographic factors in those with schizophrenia slightly strengthened the association (odds ratio = 1.74, p = 0.001, adjusted for age, gender, diagnosis, ethnicity, education, employment, income and marital status). CONCLUSION: Elevated risk for type 2 diabetes in people with schizophrenia is not simply a consequence of antipsychotic medication; type 2 diabetes and schizophrenia share familial risk factors.

Linking the serotonin transporter gene, family environments, hippocampal volume and depression onset: A prospective imaging gene × environment analysis.

A single imaging gene-environment (IGxE) framework that is able to simultaneously model genetic, neurobiological, and environmental influences on psychopathology outcomes is needed to improve understanding of how complex interrelationships between allelic variation, differences in neuroanatomy or neuroactivity, and environmental experience affect risk for psychiatric disorder. In a longitudinal study of adolescent development we demonstrate the utility of such an IGxE framework by testing whether variation in parental behavior at age 12 altered the strength of an imaging genetics pathway, involving an indirect association between allelic variation in the serotonin transporter gene to variation in hippocampal volume and consequent onset of major depressive disorder by age 18. Results were consistent with the presence of an indirect effect of the serotonin transporter S-allele on depression onset via smaller left and right hippocampal volumes that was significant only in family environments involving either higher levels of parental aggression or lower levels of positive parenting. The previously reported finding of S-allele carriers' increased risk of depression in adverse environments may, therefore, be partly because of the effects of these environments on a neurobiological pathway from the serotonin transporter gene to depression onset that proceeds through variation in hippocampal volume.

Effect of age, family history of diabetes, and antipsychotic drug treatment on risk of diabetes in people with psychosis: a population-based cross-sectional study.

BACKGROUND: Psychosis is associated with an increased risk of diabetes mellitus. A positive synergy between antipsychotic drug effects and a pre-existing liability to diabetes mellitus might explain the especially high relative risk of diabetes mellitus in young adults with psychosis. We aimed to assess the individual and joint effect of age, family history of diabetes mellitus, and currently prescribed antipsychotic drug treatment on risk for diabetes mellitus. METHODS: In this study, we used data from the 2010 Australian National Survey of Psychosis-an observational study done at seven sites in five Australian states. We included data from 1155 people with psychosis aged 18-64 years who were in contact with psychiatric services and who gave a fasting blood sample to test for current diabetes mellitus. Using logistic regression, we modelled the association of diabetes mellitus with age, family history of diabetes mellitus, and current antipsychotic drug treatment. We compared model fit with and without two-way and three-way interaction terms and used likelihood ratio tests to establish which terms to include in the final model. FINDINGS: After adjustment for older age, which was an independent risk factor, compared with not taking antipsychotic drugs, antipsychotic drug treatment was associated with diabetes mellitus only in those without a family history of diabetes mellitus (clozapine adjusted odds ratio [OR] 7·22, 95% CI 1·62-32·20, p=0·01; quetiapine 5·91, 1·33-26·30, p=0·02; aripiprazole 5·06, 0·86-29·64, p=0·07; risperidone 4·17, 0·90-19·24, p=0·07; and olanzapine 2·23, 0·45-11·06, p=0·32). Antipsychotic drug treatment was not associated with additional risk of diabetes mellitus in those with a family history (clozapine adjusted OR 1·51, 95% CI 0·64-3·54, p=0·34; quetiapine 1·09, 0·49-2·43, p=0·82; aripiprazole 0·43, 0·12-1·49, p=0·18; risperidone 1·12, 0·48-2·63, p=0·79; and olanzapine 0·67, 0·26-1·71, p=0·39). INTERPRETATION: People with psychosis are at increased risk of diabetes mellitus if they have a family history of diabetes mellitus or if they have no family history of diabetes mellitus but are taking antipsychotic drugs. Increasing age increases risk but independently of family history or antipsychotic drug treatment. Clinicians should not think the absence of a family history of diabetes mellitus protects their patients from the diabetic side-effects of antipsychotics. FUNDING: Australian Federal Government and Orygen.

Cardiovascular risk factor associations in adults with psychosis and adults in a national comparator sample.

OBJECTIVE: Antipsychotic drug treatment alters status on key risk factors for cardiovascular disease. The aim of this study was to test whether cardiovascular risk factor associations differ in adults with psychosis and adults from the general community. METHOD: Data were analysed for those aged 25-64 years from a nationally representative psychosis sample (n = 1,457) and a national comparator sample (n = 8,866). The Pearson correlation coefficient was used to estimate the association among tobacco use, body mass index, waist circumference, diastolic and systolic blood pressure and fasting total-, LDL- and HDL-cholesterol, triglycerides and plasma glucose. The robust Levene test was used to test for sample differences in variance. RESULTS: Correlations among cardiovascular risk indicators and between cardiovascular risk indicators and age were often significantly weaker in those with psychosis than in those from the national comparator sample. This was not due to a reduction in variance within the psychosis sample. CONCLUSIONS: Risk prediction that synthesizes multivariate risk indicator data needs to be connected to verified cardiovascular morbidity and mortality in those with psychosis to determine if standard risk calculators adequately discriminate those at high, medium and low future risk of cardiovascular morbidity and mortality. Until then the clinical implications of low or absent correlations among cardiovascular risk indicators and their low or absent association with increasing age is unclear but may indicate that risk equations commonly used in the general population may not be applicable for those with treated psychosis.

Inadequate fruit and vegetable intake in people with psychosis.

OBJECTIVE: The objective of this study was to identify factors associated with poor dietary intake (less than four servings of fruit and vegetables daily) in a large nationally representative sample of adults with psychotic disorders. METHODS: The sample comprised 1286 adults aged 18-64 years who took part in the second Australian national survey of psychosis. Dietary information was obtained using a standardised questionnaire; all participants provided fasting blood samples. Variables that may be related to diet and nutritional intake were investigated; these included demographics, physical health outcomes, physical activity, substance use, symptom severity and financial difficulty. Dietary status was explored by sex, age and body mass index using univariate analyses, while a multivariate analysis was performed to identify predictors of low nutritional intake. RESULTS: Approximately 74% of participants ate less than four servings of fruit and vegetables daily. This was associated with a lower body mass index (p<0.05), lower levels of physical activity (p<0.05), sedentary behaviour (p<0.05), substance use (p<0.001), more negative symptoms (p<0.05), eating less frequently (p<0.001), consuming whole fat milk compared to low fat milk (p<0.05), adding salt to food (p<0.05) and financial difficulty (p<0.05). Male sex and younger age (18-34 years) were also associated with lower fruit and vegetable intake (p<0.001). A multivariate regression analysis showed that current smoking (p<0.001) and alcohol (p<0.01) and cannabis abuse (p<0.05) were risk factors for lower fruit and vegetable intake. CONCLUSION: The findings suggest that poor diet in people with psychosis, as reflected by less than four servings of fruit and vegetables daily, is accompanied by other unhealthy behaviours, which has important implications for the development of effective interventions. Importantly, current smoking is a significant predictor of dietary inadequacy.

Predictors of type 2 diabetes in a nationally representative sample of adults with psychosis.

Antipsychotic drugs such as clozapine and olanzapine are associated with an increased risk for type 2 diabetes, but relatively little is known about the relationship between risk factors for type 2 diabetes established in the general population and type 2 diabetes in people with psychosis. We estimated the prevalence of established risk factors and their association with type 2 diabetes in a nationally representative sample of people with an ICD-10 psychosis (N=1642) who gave a fasting blood sample (N=1155). Logistic regression was used to summarize associations adjusted for age and sex. In this sample, whose mean duration of psychosis was 14.7 years, 12.1% (13.1% of women and 11.5% of men) had type 2 diabetes at age 18-64 years based on current fasting blood glucose levels or treatment with a hypoglycaemic drug. Risk was greatly increased in young adults compared with the general population and peaked in middle age. Risk factors in the general population were common in people with psychosis and strongly associated with type 2 diabetes in those people. Treatment with clozapine was associated with an increased risk and treatment with olanzapine with a decreased risk for type 2 diabetes. The development of diabetes or pre-diabetes may therefore influence the likelihood of treatment with olanzapine over time. The strongest predictors of type 2 diabetes in a multivariate model were a body mass index of at least 40 and treated hypercholesterolemia, followed by a body mass index between 35 and 39.9, a family history of diabetes and treated hypertension. There was minimal to no confounding of the association between type 2 diabetes and current clozapine or olanzapine treatment, but neither association remained significant after adjustment for other predictors. Longitudinal relationships among predictors are likely to be complex, and previous antipsychotic drug treatment may at least partly explain risks associated with severe obesity, dyslipidemia and hypertension. A focus on weight loss is warranted in people with psychosis, but prevention strategies for type 2 diabetes should be broadened to include those with emerging dyslipidemia, hypertension and a family history of diabetes.

Prevalence and heritability of obsessive-compulsive spectrum and anxiety disorder symptoms: A survey of the Australian Twin Registry.

While past twin studies indicate moderate levels of heritability of "obsessive-compulsive related" and anxiety disorder symptoms, no single study has reported such estimates in the same twin population nor examined potential genetic sex differences. We assessed symptoms of obsessive-compulsive disorder, body dysmorphic disorder, hoarding disorder, hypochondriasis, panic disorder, social phobia and generalized anxiety disorder in 2,495 adult twins (1,468 female). Prevalence estimates for the corresponding symptom measures were determined using empirically derived cut-off scores. Twin resemblance was assessed by Pearson correlations and biometrical model-fitting analyses, incorporating sex-specific effects, using OpenMx. Prevalence estimates ranged from 1.6% in the symptoms of generalized anxiety to 16.9% for social phobia. Female twins demonstrated significantly higher prevalence rates across all domains with the exception of obsessive-compulsive symptoms. Additive genetic factors accounted for a moderate proportion of the total liability to each symptom domain. Evidence suggesting qualitative genetic sex differences (i.e., distinct genetic influences between genders) was observed for body dysmorphic concern and panic symptoms, while quantitative differences were observed for hoarding and social phobia symptoms, indicating stronger heritability in females. Novel findings in this study include the observation of probable genetic sex differences in liability towards hoarding symptoms and dysmorphic concern, as well as the lack of such differences in hypochondriasis. The trend towards qualitative sex differences in panic symptoms has some intuitive appeal with regard to biological-experimental models of panic.

Cardiometabolic risk indicators that distinguish adults with psychosis from the general population, by age and gender.

Individuals with psychosis are more likely than the general community to develop obesity and to die prematurely from heart disease. Interventions to improve cardiovascular outcomes are best targeted at the earliest indicators of risk, at the age they first emerge. We investigated which cardiometabolic risk indicators distinguished those with psychosis from the general population, by age by gender, and whether obesity explained the pattern of observed differences. Data was analyzed from an epidemiologically representative sample of 1,642 Australians with psychosis aged 18-64 years and a national comparator sample of 8,866 controls aged 25-64 years from the general population. Cubic b-splines were used to compare cross sectional age trends by gender for mean waist circumference, body mass index [BMI], blood pressure, fasting blood glucose, triglycerides, LDL, HDL, and total cholesterol in our psychosis and control samples. At age 25 individuals with psychosis had a significantly higher mean BMI, waist circumference, triglycerides, glucose [women only], and diastolic blood pressure and significantly lower HDL-cholesterol than controls. With the exception of triglycerides at age 60+ in men, and glucose in women at various ages, these differences were present at every age. Differences in BMI and waist circumference between samples, although dramatic, could not explain all differences in diastolic blood pressure, HDL-cholesterol or triglycerides but did explain differences in glucose. Psychosis has the hallmarks of insulin resistance by at least age 25. The entire syndrome, not just weight, should be a focus of intervention to reduce mortality from cardiovascular disease.

Long-term follow-up of a group at ultra high risk ("prodromal") for psychosis: the PACE 400 study.

IMPORTANCE: The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known. OBJECTIVE: To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry. DESIGN: Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006. SETTING: The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia. PARTICIPANTS: Four hundred sixteen UHR patients previously seen at the PACE clinic. MAIN OUTCOMES AND MEASURES: Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records. RESULTS: During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content. CONCLUSIONS AND RELEVANCE: The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Australian Twin Registry: 30 years of progress.

The Australian Twin Registry (ATR) is a national volunteer resource of twin pairs and higher-order multiples willing to consider participating in health, medical, and scientific research. The vision of the ATR is 'to realize the full potential of research involving twins to improve the health and well-being of all Australians'. The ATR has been funded continuously by the National Health and Medical Council for more than 30 years. Its core functions entail the recruitment and retention of twin members, the maintenance of an up-to-date database containing members' contact details and baseline information, and the promotion and provision of open access to researchers from all institutes in Australia, and their collaborators, in a fair and equitable manner. The ATR is administered by The University of Melbourne, which acts as custodian. Since the late 1970s the ATR has enrolled more than 40,000 twin pairs of all zygosities and facilitated more than 500 studies that have produced at least 700 peer-reviewed publications from classical twin studies, co-twin control studies, within-pair comparisons, twin family studies, longitudinal twin studies, randomized controlled trials, and epigenetics studies, as well as studies of issues specific to twins. New initiatives include: a Health and Life Style Questionnaire; data collection, management, and archiving using a secure online software program (The Ark); and the International Network of Twin Registries. The ATR's expertise and 30 years of experience in providing services to national and international twin studies has made it an important resource for research across a broad range of disciplines.