Medication and suicide risk in schizophrenia: A nested case-control study

Introduction: Patients with schizophrenia are at increased risk of suicide, but data from controlled studies of pharmacotherapy in relation to suicide risk is limited. Aim: To explore suicide risk in schizophrenia in relation to medication with antipsychotics, antidepressants, and lithium. Methods: Of all patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide within five years from diagnosis were defined as cases (n=84; 54% male). Individually matched controls were identified from the same population. Information on prescribed medication was retrieved from psychiatric records in a blinded way. Adjusted odds ratios [OR] of the association between medication and suicide were calculated by conditional logistic regression. Results: Lower suicide risk was found in patients who had been prescribed a second generation antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and 20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23 (95% CI 0.06-0.89). No significant association was observed between suicide and prescription of any antipsychotic, depot injection antipsychotics, antidepressants, SSRI, or lithium. Conclusions: Lower suicide risk for patients who had been prescribed second generation antipsychotics may be related to a pharmacological effect of these drugs, to differences in adherence, or to differences in other patient characteristics associated with lower suicide risk. © 2013 Elsevier B.V

Mortality trends in external causes of death in people with mental health disorders in Sweden, 1987-2010

AIM: We investigated mortality from external causes in Swedish people who had been hospitalised with a severe mental disorder.METHODS: Hospitalisations in people aged 15 years or older admitted to hospital with a main diagnosis of schizophrenia, bipolar mood disorder or unipolar mood disorder between 1987 and 2010 were linked to their causes of death.RESULTS: The mortality rate from all external causes was 20-fold higher in those with unipolar mood disorder, 15-fold higher in those with bipolar disorder and 12-fold higher in those with schizophrenia than in the general population. Over the study periods, the mortality rate declined more for people with unipolar mood disorder (-35%) and schizophrenia (-29%) than the total population (-25%) and those with bipolar mood disorder (-15%). The suicide rate declined most for those with unipolar mood disorder and schizophrenia (-42% for both) and less for the general population (-37%) and those with bipolar mood disorder (-21%). For external causes other than suicide, the mortality rate declined in the general population (-17%) but increased in people with schizophrenia (14%), bipolar mood disorder (30%) and unipolar mood disorder (52%).CONCLUSIONS: People with mental disorders have high but declining excess mortality from suicide. Mortality from other external causes has increased, as has the gap in mortality rates between psychiatric patients and the general population.</div

Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)

Background: Life expectancy is reduced by 19 years in men and 17 in women with psychosis in Sweden, largely due to cardiovascular disease. Aim: Assess whether a psychosocial health promotion intervention improves cardiometabolic risk factors, quality of life, and severity of illness in patients with psychotic disorders more than treatment as usual. Methods: A pragmatic intervention trial testing a manual-based multi-component health promotion intervention targeting patients with psychosis. The Swedish intervention was adapted from IMPaCT therapy, a health-promotion program based on motivational interviewing and cognitive behavioral therapy, designed to be incorporated into routine care. The intervention group consisted of 119 patients and a control group of 570 patients from specialized psychosis departments. Outcome variables were assessed 6 months before intervention during the run-in period, again at the start of intervention, and 12 months after the intervention began. The control group received treatment as usual. Results: The intervention had no significant effect on any of the outcome variables. However, BMI, waist circumference, systolic BP, heart rate, HbA1c, general health, and Clinical Global Impressions Scale score improved significantly during the run-in period before the start of the active intervention (observer effect). The multi-component design meant that treatment effects could only be calculated for the intervention as a whole. Conclusion: The results of the intervention are similar to those of the U.K. IMPaCT study, in which the modular health-promotion intervention had little effect on cardiovascular risk indicators. However, in the current study, the run-in period had a positive effect on cardiometabolic risk factors

Cardiorespiratory fitness in outpatients with bipolar disorder versus matched controls: An exploratory study

AbstractBackground Patients with bipolar disorder (BD) are approximately twice as likely to die prematurely due cardiovascular diseases (CVD) than the general population. Cardiorespiratory fitness (CRF) is an important health outcome measure, predictive for CVD and premature mortality. Aims The aim of the current study was to compare the CRF of outpatients with BD versus age-, gender-, and body mass index (BMI)-matched healthy controls (HC). A secondary aim was to assess potential correlates of CRF. Methods All participants underwent a maximal incremental exercise test to measure the maximum oxygen uptake (VO2max, the golden standard assessment of cardiorespiratory fitness), wore a Body Sensewear Armband for 5 subsequent days to assess their physical activity behavior and completed the Positive-and-Negative-Affect-Schedule (PANAS). Results Outpatients with BD (n=20; 47.8±7.6years) had a significantly lower VO2max compared with HC (n=20; 47.8±7.6years) (26.0±7.3 versus 30.4±6.5 ml/min/kg, P=0.047). A higher VO2max was correlated with younger age, higher active energy expenditure, higher PANAS positive and lower PANAS negative affect scores and a lower antipsychotic medication dose. Limitations The limited sample and cross-sectional design preclude definitive conclusions. Conclusions Compared with HC, outpatients with BD have reduced CRF levels of approximately 4.4 ml/min/kg. In the general population such reductions are associated with a 20% increased premature mortality risk. Interventions targeting CRF in BD are required. Although more research is needed, clinicians should consider the utility of objective assessments of CRF for risk stratification in outpatient settings

Physical health behaviours and health locus of control in people with schizophrenia-spectrum disorder and bipolar disorder: a cross-sectional comparative study with people with non-psychotic mental illness

<p>Abstract</p> <p>Background</p> <p>People with mental illness experience high levels of morbidity and mortality from physical disease compared to the general population. Our primary aim was to compare how people with severe mental illness (SMI; i.e. schizophrenia-spectrum disorders and bipolar disorder) and non-psychotic mental illness perceive their: (i) global physical health, (ii) barriers to improving physical health, (iii) physical health with respect to important aspects of life and (iv) motivation to change modifiable high-risk behaviours associated with coronary heart disease. A secondary aim was to determine health locus of control in these two groups of participants.</p> <p>Methods</p> <p>People with SMI and non-psychotic mental illness were recruited from an out-patient adult mental health service in London. Cross-sectional comparison between the two groups was conducted by means of a self-completed questionnaire.</p> <p>Results</p> <p>A total of 146 people participated in the study, 52 with SMI and 94 with non-psychotic mental illness. There was no statistical difference between the two groups with respect to the perception of global physical health. However, physical health was considered to be a less important priority in life by people with SMI (OR 0.5, 95% CI 0.2-0.9, <it>p </it>= 0.029). There was no difference between the two groups in their desire to change high risk behaviours. People with SMI are more likely to have a health locus of control determined by powerful others (<it>p </it>< 0.001) and chance (<it>p </it>= 0.006).</p> <p>Conclusions</p> <p>People with SMI appear to give less priority to their physical health needs. Health promotion for people with SMI should aim to raise awareness of modifiable high-risk lifestyle factors. Findings related to locus of control may provide a theoretical focus for clinical intervention in order to promote a much needed behavioural change in this marginalised group of people.</p

CRY2 Is Associated with Rapid Cycling in Bipolar Disorder Patients

Bipolar disorder patients often display abnormalities in circadian rhythm, and they are sensitive to irregular diurnal rhythms. CRY2 participates in the core clock that generates circadian rhythms. CRY2 mRNA expression in blood mononuclear cells was recently shown to display a marked diurnal variation and to respond to total sleep deprivation in healthy human volunteers. It was also shown that bipolar patients in a depressive state had lower CRY2 mRNA levels, nonresponsive to total sleep deprivation, compared to healthy controls, and that CRY2 gene variation was associated with winter depression in both Swedish and Finnish cohorts.Four CRY2 SNPs spanning from intron 2 to downstream 3'UTR were analyzed for association to bipolar disorder type 1 (n = 497), bipolar disorder type 2 (n = 60) and bipolar disorder with the feature rapid cycling (n = 155) versus blood donors (n = 1044) in Sweden. Also, the rapid cycling cases were compared with bipolar disorder cases without rapid cycling (n = 422). The haplotype GGAC was underrepresented among rapid cycling cases versus controls and versus bipolar disorder cases without rapid cycling (OR = 0.7, P = 0.006-0.02), whereas overrepresentation among rapid cycling cases was seen for AAAC (OR = 1.3-1.4, P = 0.03-0.04) and AGGA (OR = 1.5, P = 0.05). The risk and protective CRY2 haplotypes and their effect sizes were similar to those recently suggested to be associated with winter depression in Swedes.We propose that the circadian gene CRY2 is associated with rapid cycling in bipolar disorder. This is the first time a clock gene is implicated in rapid cycling, and one of few findings showing a molecular discrimination between rapid cycling and other forms of bipolar disorder

Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder

Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case–control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 × 10−8). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

The Lancet Psychiatry Commission : a blueprint for protecting physical health in people with mental illness

No abstract available