Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = −0.14; 95% confidence interval [CI]: −0.24 to −0.03; p value = 0.010) and MDD (β = −0.16; 95% CI: −0.27 to −0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34–1.93; p value = 2e−7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD

Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden

Objective To estimate the cardiovascular mortality among persons with bipolar disorder in Sweden compared to the general population. Design Population register-based cohort study with a 20-year follow-up. Setting Sweden. Participants The entire population of Sweden (n=10.6 million) of whom 17101 persons were diagnosed with bipolar disorder between 1987 and 2006. Main outcome measures Mortality rate ratios (MRR), excess mortality (excess deaths), cardiovascular disorder (CVD) and specifically cerebrovascular disease, coronary heart disease, acute myocardial infarction, sudden cardiac deaths and hospital admission rate ratio (ARR). Results Persons with bipolar disorder died of CVD approximately 10years earlier than the general population. One third (38%) of all deaths in persons with bipolar disorder were caused by CVD and almost half (44%) by other somatic diseases, whereas suicide and other external causes accounted for less than a fifth of all deaths (18%). Excess mortality of both CVD (n=824) and other somatic diseases (n=988) was higher than that of suicide and other external causes (n=675 deaths). MRRs for cerebrovascular disease, coronary heart disease and acute myocardial infarction were twice as high in persons with bipolar disorder compared to the general population. Despite the increased mortality of CVD, hospital admissions (ARR) for CVD treatment were only slightly increased in persons with bipolar disorder when compared to the general population. Conclusions The increased cardiovascular mortality in persons with bipolar disorder calls for renewed efforts to prevent and treat somatic diseases in this group. Specifically, our findings further imply that it would be critical to ensure that persons with bipolar disorder receive the same quality care for CVD as persons without bipolar disorder

High prevalence of diagnosis of diabetes, depression, anxiety, hypertension, asthma and COPD in the total population of Stockholm, Sweden : a challenge for public health

Background: There is limited knowledge on the prevalence of disease in total populations. Such studies have historically been difficult to conduct but the development of health data registers has facilitated large-scale studies on recorded diagnoses in entire regions. The aim of this study was to analyze the prevalence of diagnosis of six common diseases in the Swedish capital region. Methods: The study population included all living persons who resided in Stockholm County, Sweden, on December 31st 2011 (N = 2 093 717). Information on all consultations between 2007 and 2011 was obtained from primary health care, specialist outpatient care and inpatient care. Prevalence was defined as the proportion of individuals with a recorded diagnosis of diabetes, depression, anxiety disorders, hypertension, asthma and chronic obstructive pulmonary disease during the five year period, respectively. Analyses were done by age and gender. Results: Hypertension had the highest five-year prevalence (12.2%), followed by depression (6.6%), diabetes mellitus (6.2%), asthma (5.9%), anxiety disorders/phobia (4.8%), and COPD (1.8%). Diabetes was more common in men (5.3% of women and 7.1% of men) while depression (8.7% in women and 4.4% in men) and anxiety (6.3% in women and 3.4% in men) were considerably more common in women. Smaller gender differences were also found for hypertension (13.0% in women and 11.4% in men), asthma (6.4% in women and 5.4% in men) and COPD (2.1% in women and 1.6% in men). Diabetes, hypertension and COPD increased markedly with age, whereas anxiety, depression and asthma were fairly constant in individuals above 18 years. During one year of observation, more than half of all patients had only been diagnosed in primary health care, with hypertension being the diagnosis with the largest proportion of patients only identified in primary health care (70.6%). Conclusion: The prevalence of common diseases in the population can be estimated by combining data gathered during consecutive years from primary care, specialist outpatient care and inpatient care. However, accuracy of disease prevalence is highly dependent on the quality of the data. The high prevalence of the six diagnoses analysed in this study calls for preventive action to minimize suffering and costs to society

Health-related quality of life and metabolic risk in patients with psychosis

Improved Health-related quality of life (HRQoL) is an alternative treatment goal for individuals with psychosis, who have up to two times greater prevalence of type 2 diabetes, hypertension and obesity than the general population. Aim: to compare HRQoL in patients with psychosis, especially schizophrenia, with a reference sample and explore the relationship between HRQoL and metabolic risk factors in these patients. Methods: a prospective cohort study was carried out in specialized psychiatric outpatient departments in Sweden. The patients were invited consecutively. A prospective population-based study of public health in the south-east of Sweden served as reference group. Patients were assessed with psychiatric questionnaires that included Global Assessment of Functioning (GAF). Health-related quality of life was assessed using the questionnaire EQ5D, both for patients and the population, and several other health status outcomes were used. Results: At 73%, schizophrenia and schizoaffective disorder were the most common diagnoses in the patient group. The results in patients (n = 903) and population (n = 7238) showed significant differences in lower EQ5D among patients. According to the definition by the International Diabetes Federation (IDF), elevated blood pressure was the only metabolic risk associated with lower HRQoL in patients. Raised LDL-cholesterol levels were also significantly related to lower HRQoL. Conclusion: patients suffering from psychosis had significantly lower HRQoL regarding all components in EQ5D, except for the pain/discomfort component. Almost half of the patient group met the criteria for metabolic syndrome. According to the IDF criteria, elevated blood pressure was the only metabolic risk factor that had an impact on HRQoL

Swedish clinical guidelines-Prevention and management of metabolic risk in patients with severe psychiatric disorders

Individuals with severe psychiatric disorders are more likely than the population at large to develop metabolic derangements such as overweight and diabetes. Cardiovascular disease is also more frequently seen in this group. Contributing factors may include inappropriate diet or lack of physical activity, but antipsychotic medication may also play a role. Seven Swedish specialist medical societies have collaborated in formulating a set of concise clinically applicable guidelines-reproduced here in modified form-for the prevention and management of metabolic risk in this patient group. The importance of implementation is emphasized

Copyright: Elsevier

quality of life and metabolic ris

P2RX7: expression responds to sleep deprivation and associates with rapid cycling in bipolar disorder type 1.

Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatment-responsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling.To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients.Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients.Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044).P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10(-9)). The P2RX7 rs2230912 _A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45-0.49, p = 0.003-0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls.Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system