Cognitive alterations in patients with non-affective psychotic disorder and their unaffected siblings and parents

Meijer J, Simons CJP, Quee PJ, Verweij K, GROUP Investigators. Cognitive alterations in patients with non-affective psychotic disorder and their unaffected siblings and parents

Familial aggregation and heritability of schizophrenia and co-aggregation of psychiatric illnesses in affected families

Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55-46.92), 6.30 (6.09-6.53), 2.44 (1.91-3.12), and 1.88 (1.64-2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79-6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00-16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34-3.64) for mood disorders and 3.91 (3.35-4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia

The association between intelligence scores and family history of psychiatric disorder in schizophrenia patients, their siblings and healthy controls.

BACKGROUND:The degree of intellectual impairment in schizophrenia patients and their relatives has been suggested to be associated with the degree of familial loading for schizophrenia. Since other psychiatric disorders are also more present in relatives of schizophrenia patients, the definition of family history should be broadened. The association between family history for psychiatric disorder and intelligence scores was investigated in patients with non-affective psychosis, their unaffected siblings and controls. METHODS:A sample of 712 schizophrenia proband families (696 patients and 766 siblings) and 427 healthy control families (517 subjects) participated in this study. Family history of psychiatric disorder was determined while excluding the data of the participating schizophrenia patient. A dichotomous division was made between families with no first- or second degree relative with psychiatric disorder and families with one or more affected relatives. Total intelligence scores were estimated by admission of the short form of the Wechsler Adult Intelligence Scale III. RESULTS:A significant interaction was found between family history of psychiatric disorder and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family history of psychiatric disorder obtained higher intelligence scores compared to patients with no family history (mean IQ scores are 95.52 and 92.72) with an opposite effect in controls (mean IQ scores are 108.71 and 111.19). No significant difference was found between siblings of schizophrenia patients with or without a positive family history (mean IQ scores are 102.98 and 103.24). CONCLUSION:In patients with schizophrenia, a negative family history of psychiatric disorder was associated with relatively low IQ suggesting that the etiology in these patients may involve environmental or genetic factors which are unique to the patient and are not observed in other relatives. Possible factors include severe environmental stressors containing premature birth or brain injury and genetic factors (e.g de novo Copy Number Variants)

The heritability of delusional-like experiences

Objective: Delusional-like experiences (DLE) are common in the general community and are associated with a family history of mental illness. The aim of this study was to estimate the heritability of DLE. Method: The Peters Delusional Inventory (PDI) was administered to a population-based cohort of mothers (n = 2861, aged 3567 years) and their adult offspring (n = 3079, aged 1823 years). Heritability of DLE was estimated from the sum scores of the 21 item PDI under the assumption that the covariance between motheroffspring scores is attributable to shared additive genetic factors. Results: The means (medians and standard deviations) for the total PDI scores for the mothers and their offspring were 3.6 (3.0, 3.0) and 5.0 (4.0, 3.5), respectively. The Pearson correlation coefficient between mother and offspring PDI scores was 0.17 (P < 0.001). The heritability was estimated to be 0.35 (standard error 0.04). Conclusion: Heritable factors contribute to over a third of the variance of PDI scores in this population. In light of the association between a family history of a wide range of mental disorders and DLE, these experiences may represent a useful quantitative endophenotype for genetic studies of common mental disorders in population settings

Cognitive functioning and age at onset in non-affective psychotic disorder

van der Werf M, Köhler S, Verkaaik M, Verhey F, van Os J, GROUP Investigators. Cognitive functioning and age at onset in non-affective psychotic disorder. Objective:  Age at psychosis onset has been related to variability in cognitive functioning, but its effect may be mediated by demographic and clinical factors. The aim of the current study was to study the contribution of age at onset, as well as demographic and illness characteristics, to variation in cognitive functioning in patients with schizophrenia spectrum disorder. Method:  Patients (n = 1053) and healthy controls (n = 631) underwent comprehensive neuropsychological and clinical assessments. The effect of age at onset on age-standardized cognitive test scores was assessed with multiple linear regression analyses. Mediation by illness and demographic factors was tested using a multiple mediation Sobel test. Results:  A diagnosis of schizophrenia, higher antipsychotic dose, and more negative symptoms were associated with earlier onset of illness, while female sex and a more chronic course were associated with later illness onset. Furthermore, earlier onset was associated with worse performance on immediate recall and sustained attention. However, male sex, more negative symptoms, and higher antipsychotic dose mediated the effect of age at onset on memory, while negative symptoms explained its association with attention/vigilance. Conclusion:  Greater impairment in memory and attention in early-onset psychosis may be explained by features indicative of underlying neurodevelopmental vulnerabilit

A health promotion intervention to improve lifestyle choices and health outcomes in people with psychosis:a research programme including the IMPaCT RCT

Background: People with psychotic disorders have reduced life expectancy largely because of physical health problems, especially cardiovascular disease, that are complicated by the use of tobacco and cannabis. / Objectives: We set out to (1) chart lifestyle and substance use choices and the emergence of cardiometabolic risk from the earliest presentation with psychosis, (2) develop a pragmatic health promotion intervention integrated within the clinical teams to improve the lifestyle choices and health outcomes of people with psychosis and (3) evaluate the clinical effectiveness and cost-effectiveness of that health promotion intervention. / Design: We performed a longitudinal cohort study of people presenting with their first episode of psychosis in three mental health trusts and followed up participants for 1 year [work package 1, physical health and substance use measures in first episode of psychosis (PUMP)]. We used an iterative Delphi methodology to develop and refine a modular health promotion intervention, improving physical health and reducing substance use in psychosis (IMPaCT) therapy, which was to be delivered by the patient’s usual care co-ordinator and used motivational interviewing techniques and cognitive–behavioural therapy to improve health choices of people with psychosis (work package 2). We then conducted a multicentre, two-arm, parallel-cluster, randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of using the intervention with people with established psychosis (work package 3: IMPaCT randomised controlled trial) in five UK mental health trusts. The work took place between 2008 and 2014. / Participants: All people aged between 16 and 65 years within 6 months of their first presentation with a non-organic psychosis and who were proficient in English were eligible for inclusion in the PUMP study. Participants in the work package 2 training development were staff selected from a range of settings, working with psychosis. Participants in the phase 3 Delphi consensus and manual development comprised three expert groups of (1) therapists/researchers recruited from the local and national community, (2) clinicians and (3) service users, each of whom took part in two iterative review and feedback sessions. For work package 3, IMPaCT randomised controlled trial, care co-ordinators in participating community mental health teams who were permanently employed and had a minimum of four eligible patients (i.e. aged between 18 and 65 years with a diagnosis of a psychotic disorder) on their caseload were eligible to participate. In studies 1 and 3, patient participants were ineligible if they were pregnant or had a major illness that would have had an impact on their metabolic status or if they had a significant learning disability. All participants were included in the study only after giving written confirmed consent. / Main outcome measures: Cardiometabolic risk markers, including rates of obesity and central obesity, and levels of glycated haemoglobin (HbA1c) and lipids, were the main outcomes in work package 1 (PUMP), with descriptive data presented on substance use. Our primary outcome measure for the IMPaCT randomised controlled trial was the physical or mental health component Short Form questionnaire-36 items quality-of-life scores at 12 months. / Results: Obesity rates rose from 18% at first presentation with psychosis to 24% by 1 year, but cardiometabolic risk was not associated with baseline lifestyle and substance use choices. Patterns of increase in the levels of HbA1c over the year following first presentation showed variation by ethnic group. We recruited 104 care co-ordinators, of whom 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) were randomised to deliver treatment as usual, in keeping with our power calculations. Of these 406 participants with established psychosis, 318 (78%) and 301 (74%) participants, respectively, attended the 12- and 15-month follow-ups. We found no significant effect of IMPaCT therapy compared with treatment as usual on the physical or mental health component Short Form questionnaire-36 items scores at either time point in an intention-to-treat analysis [physical health score (‘d’) –0.17 at 12 months and –0.09 at 15 months; mental health score (‘d’) 0.03 at 12 months and –0.05 at 15 months] or on costs. Nor did we find an effect on other cardiovascular risk indicators, including diabetes, except in the case of high-density lipoprotein cholesterol, which showed a trend for greater benefit with IMPaCT therapy than with treatment as usual (treatment effect 0.085, 95% confidence interval 0.007 to 0.16; p = 0.034). / Limitations: Follow-up in work package 1 was challenging, with 127 out of 293 participants attending; however, there was no difference in cardiometabolic measures or demographic factors at baseline between those who attended for follow-up and those who did not. In work package 3, the IMPaCT randomised controlled trial, care co-ordinators struggled to provide additional time to their patients that was devoted to the health promotion intervention on top of their usual clinical care contact with them. / Conclusions: Cardiometabolic risk is prominent even soon after first presentation with psychosis and increases over time. Lifestyle choices and substance use habits at first presentation do not predict those who will be most cardiometabolically compromised 1 year later. Training and supervising care co-ordinators to deliver a health promotion intervention to their own patients on top of routine care is not effective in the NHS for improving quality of life or reducing cardiometabolic risk. / Future work: Further work is needed to develop and evaluate effective, cost-effective and affordable ways of preventing the emergence of and reversing existing cardiometabolic risk indicators in people with psychosis. / Trial registration: Current Controlled Trials ISRCTN58667926