Poonam Gardner-Sood

Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study

BACKGROUND The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. METHODS We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. FINDINGS Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. INTERPRETATION The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. FUNDING UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at Kings College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Communitys Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).

Vitamin D deficiency in first episode psychosis: A case–control study

BACKGROUND Vitamin D deficiency is seen in a high proportion of people with established psychotic disorders, but it is not known if this is present at onset of the illness. We set out to examine vitamin D levels in people with their first episode of psychosis (FEP). METHOD We conducted a matched case-control study to examine vitamin D levels and rates of vitamin D deficiency in sixty nine patients presenting with their FEP and sixty nine controls matched for age, sex and ethnicity. Differences between groups were tested using students-t tests, paired t-tests and odds ratios for further analysis. RESULTS Vitamin D levels were significantly lower in cases than in controls (p<0.001). The odds ratio of being vitamin D deficient was 2.99 in the FEP group relative to the control group. There was no correlation between vitamin D levels and length of hospitalisation in the patient group (r=-0.027, p=0.827). CONCLUSIONS We found higher rates of vitamin D deficiency in people with FEP compared to matched controls. Given that vitamin D is neuroprotective; that developmental vitamin D deficiency may be a risk factor for psychosis, and that incipient psychosis may affect lifestyle factors and diet, future studies are required to examine this association further. In the meantime, there is a need for more widespread testing of vitamin D levels in FEP and for the development of appropriate management strategies.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses: baseline data from the IMPaCT randomized controlled trial.

Background The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment. Method Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria. Results High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS. Conclusions In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.

Cardiovascular risk factors and metabolic syndrome in people with established psychotic illnesses

Background The aims of the study were to determine the prevalence of cardiometabolic risk factors and establish the proportion of people with psychosis meeting criteria for the metabolic syndrome (MetS). The study also aimed to identify the key lifestyle behaviours associated with increased risk of the MetS and to investigate whether the MetS is associated with illness severity and degree of functional impairment. Method Baseline data were collected as part of a large randomized controlled trial (IMPaCT RCT). The study took place within community mental health teams in five Mental Health NHS Trusts in urban and rural locations across England. A total of 450 randomly selected out-patients, aged 18–65 years, with an established psychotic illness were recruited. We ascertained the prevalence rates of cardiometabolic risk factors, illness severity and functional impairment and calculated rates of the MetS, using International Diabetes Federation (IDF) and National Cholesterol Education Program Third Adult Treatment Panel criteria. Results High rates of cardiometabolic risk factors were found. Nearly all women and most men had waist circumference exceeding the IDF threshold for central obesity. Half the sample was obese (body mass index ≥ 30 kg/m2) and a fifth met the criteria for type 2 diabetes mellitus. Females were more likely to be obese than males (61% v. 42%, p < 0.001). Of the 308 patients with complete laboratory measures, 57% (n = 175) met the IDF criteria for the MetS. Conclusions In the UK, the prevalence of cardiometabolic risk factors in individuals with psychotic illnesses is much higher than that observed in national general population studies as well as in most international studies of patients with psychosis.

An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis

BACKGROUND Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses. METHODS The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis. RESULTS PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10-6), but lower in individuals of African ancestry (R2 = 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2 = 9.2%, p = .002). CONCLUSIONS PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.

Sedentary behaviour is associated with elevated C-reactive protein levels in people with psychosis

Psychosis is associated with elevated inflammatory markers including C-reactive protein (CRP), a marker of cardiovascular disease (CVD) risk. Using a cross sectional design, 250 participants with established psychosis (48.2years (SD 10.2), 39.2% female) were classified as having normal (<5.0mg/μl, N=159) or high CRP levels (>5.0mg/μl, N=91). Regression analysis demonstrated that higher sedentary behaviour was associated with elevated CRP levels (β=.155, p=.01) after adjustment for confounding variables. Female gender (β=.229, p=.001), waist circumference (β=.205, p=.003) and non-white ethnicity (β=.181, p=.005) were also associated with elevated CRP. Sedentary behaviour is modifiable and increasing physical activity may reduce CRP levels.

Provision of health promotion programmes to people with serious mental illness: a mapping exercise of four South London boroughs

ACCESSIBLE SUMMARY BACKGROUND People with serious mental illness (SMI) are at increased risk of developing various physical health diseases, contributing to significantly reduced life expectancies compared with the general population. In light of this, the Department of Health have set the physical health of people with mental health problems as a priority for improvement. Additionally, the UK government encourages the NHS and local authorities to develop health promotion programmes (HPPs) for people with SMI. AIMS To document how many and what types of HPPs were available to people with SMI across four South London boroughs, UK. RESULTS We found 145 HPPs were available to people with SMI across the four boroughs, but with an inequitable distribution. We also found that certain HPPs set admission criteria that were likely to act as a barrier to improving health. CONCLUSIONS A more integrated approach of documenting and providing information regarding the provision of HPPs for or inclusive of people with SMI is needed. ABSTRACT People with serious mental illness (SMI) such as schizophrenia, schizoaffective disorders and bipolar disorder are at increased risk of developing diabetes, cardiovascular disease and respiratory disease, contributing to significantly reduced life expectancies. As a result, emphasis has been placed on developing Health Promotion Programmes (HPPs) to modify the risk of poor physical health in SMI. We examined how many and what types of HPPs are available for or inclusive of people with SMI across four borough in South London, UK. A cross-sectional mapping study was carried out to identify the number of HPPs available to people with SMI. We found 145 HPPs available to people with SMI existed across the four boroughs but with an inequitable distribution, which in some boroughs we anticipate may not meet need. In some cases, HPPs set admission conditions which were likely to further impede access. We recommend that accurate and readily available information on the provision of HPPs for or inclusive of people with SMI is needed.

Inflammation and metabolic changes in first episode psychosis: Preliminary results from a longitudinal study

Metabolic abnormalities are commonly observed in patients with psychosis, and may confer greater risk of developing cardiovascular disease later in life. Such abnormalities are associated with inflammation in the general population, and there is increasing evidence for elevated inflammation in patients with first episode psychosis (FEP). The aim of this preliminary study is to examine the effect of changes in inflammation, as measured by high-sensitivity C-reactive protein (hsCRP), on metabolic changes in a three-month longitudinal study in a FEP sample. Fifty-three FEP patients from in- and out-patient services in South London, England, were included in this longitudinal study. Social and clinical data were collected, and fasting blood samples and anthropometric measurements (weight, Body Mass Index (BMI), lipid profile and gluco-metabolic parameters) were obtained at baseline and at three-month follow-up. Correlation analyses showed that those with increases in hsCRP over the three-month period also had increases in triglyceride levels (r=0.49, p=0.02). No association was observed with other lipid profile, or gluco-metabolic parameters, across the whole sample. Increases in weight and BMI were also associated with increases in triglyceride levels (r=0.33, p=0.02; and r=0.31, p=0.03, respectively); however, a multiple linear regression analysis found that the effects of inflammation on triglycerides were independent from the effect of changes in weight, and from the baseline inflammatory state. Our preliminary findings suggest that those patients experiencing greater increases in inflammation early on in the course of their illness may be at greater risk of developing short-term metabolic abnormalities, in particular dyslipidaemia, independent of weight-gain. Future work should investigate the use of inflammatory markers to identify patients in greater need of physical health interventions.

Pain is independently associated with reduced health related quality of life in people with psychosis

The objective was to investigate the relationship between pain and health related quality of life (HRQOL) in people with psychosis. The study utilised a cross-sectional design including individuals with established psychosis from five Mental Health Trusts across England. Participants were classified as having pain or not and HRQOL was determined with the EQ-5D-3L. Covariates considered include the Positive and Negative Syndrome Scale (PANSS), the Montgomery Asberg Depression Rating Scale (MADRS) and Global Assessment of Functioning (GAF). Hierarchical multiple linear regression analyses were conducted. The final sample included 438 individuals with psychosis (47.5 years, SD 10.1, 193 females (42.9%)). 160 participants reported pain (36.5%) and compared to the non-pain group (N=278) they had significantly higher depressive symptoms (MADRS 14.91 vs 8.68), total (51.8 vs 47.9) and general PANSS scores (26.8 vs. 23.5) and lower overall HRQOL (54.7 vs 68.3). The final regression analysis (n=387) demonstrated that lower levels of pain were a predictor of better HRQOL (β=.173) after adjusting for the PANSS, MADRS and GAF. Depressive symptoms were the largest predictor of HRQOL (β=-.486). Only 1-2% of the sample were in receipt of analgesic medication suggesting pain is greatly overlooked despite its wider deleterious impact on HRQOL.

Hyperprolactinaemia in first episode psychosis - A longitudinal assessment

Little is known about hyperprolactinaemia (HPL) in first episode psychosis (FEP) patients. We investigated longitudinal changes in serum prolactin in FEP, and the relationship between HPL, and antipsychotic medication and stress. Serum prolactin was recorded in FEP patients at recruitment and again, 3 and 12months later. HPL was defined as a serum prolactin level >410mIU/L (~19.3ng/ml) for males, and a serum prolactin level >510mIU/L (~24.1ng/ml) for females. From a total of 174 people with serum prolactin measurements at study recruitment, 43% (n=74) had HPL, whilst 27% (n=21/78) and 27% (n=26/95) had HPL at 3 and 12months respectively. We observed higher serum prolactin levels in females versus males (p<0.001), and in antipsychotic treated (n=68) versus antipsychotic naïve patients (p<0.0001). Prolactin levels were consistently raised in FEP patients taking risperidone, amisulpride and FGAs compared to other antipsychotics. No significant relationship was observed between perceived stress scores (β=7.13, t=0.21, df=11, p=0.0.84 95% CI -72.91-87.16), or objective life stressors (β=-21.74, t=-0.31, df=8, p=0.77 95% CI -218.57-175.09) and serum prolactin. Our study found elevated rates of HPL over the course of the first 12months of illness. We found no evidence to support the notion that stress is related to elevated serum prolactin at the onset of psychosis.