| 1. |
- Joas, Erik, et al.
(författare)
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Effect of CYP2C19 polymorphisms on antidepressant prescription patterns and treatment emergent mania in bipolar disorder.
- 2023
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Ingår i: The pharmacogenomics journal. - : Springer Science and Business Media LLC. - 1473-1150 .- 1470-269X. ; 23:1, s. 28-35
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Tidskriftsartikel (refereegranskat)abstract
- Antidepressant medication is used extensively to treat bipolar depression despite uncertain efficacy. The cytochrome P450 (CYP) 2C19 enzyme metabolize several antidepressants, and polymorphisms in the corresponding gene CYP2C19 influence plasma concentration and hence treatment outcomes in major depressive disorder. Here, we investigate if CYP2C19 polymorphisms are associated with antidepressant treatment patterns and the risk of mania when antidepressants are used in bipolar disorder. Two single nucleotide polymorphisms (rs4244285 and rs12248560) were used to classify 5019 bipolar disorder patients into CYP2C19 metabolic phenotypes ranging from poor to ultra-rapid metabolizers. We used Swedish national registry data 2005-2017 on dispensed medications and inpatient care to estimate risks for early-treatment persistence, treatment discontinuation, switching to a new antidepressant medication, and mania within 3 months of treatment initiation in patients treated with citalopram, escitalopram, sertraline, amitriptyline, and clomipramine. Metabolic phenotypes of CYP2C19 were not robustly associated with the investigated treatment outcomes based on dispense patterns. Slower metabolism was associated with an increased risk of treatment emergent mania for sertraline (hazard ratio [HR] = 1.3, 95% CI = 1.04-1.62, p = 0.02) and the tricyclic antidepressants amitriptyline and clomipramine (HR = 1.46, 95% CI = 1.05-2.02, p = 0.024). In a large study of the impact of CYP2C19 metabolic phenotypes on antidepressant treatment of bipolar depression, we found an association between slower CYP2C19 metabolism and higher risk of treatment emergent mania, which is a step towards personalized risk assessments. There were, however, no clear associations with early treatment persistence, treatment discontinuation, and switching to a new antidepressant.
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| 2. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 3. |
- Göteson, Andreas, 1991, et al.
(författare)
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Alterations in the Serum Proteome Following Electroconvulsive Therapy for a Major Depressive Episode: A Longitudinal Multicenter Study
- 2023
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Ingår i: Biological Psychiatry: Global Open Science. - : Elsevier BV. - 2667-1743. ; 3:4, s. 884-892
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but the biological changes induced by ECT remain poorly understood.METHODS: This study investigated alterations in blood serum proteins in 309 patients receiving ECT for a major depressive episode. We analyzed 201 proteins in samples collected at 3 time points (T): just before the first ECT treatment session (T0), within 30 minutes after the first ECT session (T1), and just before the sixth ECT session (T2).RESULTS: Using statistical models to account for repeated sampling, we identified 152 and 70 significantly (,5% false discovery rate) altered proteins at T1 and T2, respectively. The most pronounced alterations at T1 were tran-siently increased levels of prolactin, myoglobin, and kallikrein-6. However, most proteins had decreased levels at T1, with the largest effects observed for pro-epidermal growth factor, proto-oncogene tyrosine-protein kinase Src, tumor necrosis factor ligand superfamily member 14, sulfotransferase 1A1, early activation antigen CD69, and CD40 ligand. The change of several acutely altered proteins correlated with electric current and pulse frequency in a dose-response-like manner. Over a 5-session course of ECT, some acutely altered levels were sustained while others increased, e.g., serine protease 8 and chitinase-3-like protein 1. None of the studied protein biomarkers were associated with clinical response to ECT.CONCLUSIONS: We report experimental data on alterations in the circulating proteome triggered by ECT in a clinical setting. The findings implicate hormonal signaling, immune response, apoptotic processes, and more. None of the findings were associated with clinical response to ECT.
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| 4. |
- Göteson, Andreas, 1991, et al.
(författare)
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Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 7446-53
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Tidskriftsartikel (refereegranskat)abstract
- The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.
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| 5. |
- Hansson, Caroline, 1981, et al.
(författare)
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Risk factors for suicide in bipolar disorder: a cohort study of 12 850 patients
- 2018
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 138:5, s. 456-463
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveMethodBipolar disorder carries a high risk of suicide. Identification of risk factors is important. The aim of this study was to study risk factors for suicide in a large cohort of men and women with bipolar disorder. A prospective cohort study using clinical data from the Swedish National Quality Register for Bipolar Affective Disorder (BipolaR). The outcome variable was suicide captured in the Cause of Death Register between 2004 and 2014. Hazard ratios (HR) were calculated using Cox proportional hazards models. ResultsConclusionsOf 12 850 persons (4844 men and 8006 women) with bipolar disorder, 90 (55 men and 35 women) died by suicide during the follow-up period (between 1 and 10 years). Male sex (HR 2.56), living alone (HR 2.45), previous suicide attempts (HR 4.10), comorbid psychiatric disorder (HR 2.64), recent affective episodes (HR 2.39), criminal conviction (HR 4.43), psychiatric inpatient care (HR 2.79), and involuntary commitment (HR 3.50) were significant risk factors for suicide. Several of the statistically significant risk factors for suicide in bipolar disorder differed between men and women. Risk factors for suicide in bipolar disorder include factors associated with suicide in general, but also diagnosis-specific factors.
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| 6. |
- Joas, Erik, 1983, et al.
(författare)
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Psychoeducation for bipolar disorder and risk of recurrence and hospitalization - a within-individual analysis using registry data.
- 2020
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Ingår i: Psychological medicine. - 1469-8978. ; 50:6, s. 1043-1049
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy of psychoeducation for bipolar disorder has been demonstrated in clinical trials, but it is not known if the results translate into effectiveness in routine clinical practice. The aim was to determine the effectiveness of psychoeducation for bipolar disorder in a routine clinical setting.We identified 2819 patients with at least three registrations in the Swedish Quality Assurance Register for Bipolar Disorder. Among those, 402 had not been exposed to psychoeducation at the first visit, but received psychoeducation during any of the following registrations. Using within-individual analyses, the risk of recurrence after having received psychoeducation was compared with the risk prior to psychoeducation.In adjusted within-individuals comparisons, periods after psychoeducation was associated with decreased risks of any recurrence [odds ratio (OR) 0.57, 95% CI 0.42-0.78], (hypo-)manic or mixed episodes (OR 0.54, 95% CI 0.39-0.76), depressive episodes (OR 0.63, 95% CI 0.47-0.86), and inpatient care (OR 0.54, 95% CI 0.33-0.86) relative to periods prior to psychoeducation. There was no association with rates of involuntary sectioning or suicide attempts.The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice.
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| 7. |
- Karanti, Alina (Aikaterini), et al.
(författare)
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Characteristics of bipolar I and II disorder: A study of 8766 individuals.
- 2020
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 22:4, s. 392-400
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Tidskriftsartikel (refereegranskat)abstract
- Large-scale studies on phenotypic differences between bipolar disorder type I (BDI) and type II (BDII) are scarce.Individuals with BDI (N = 4806) and BDII (N = 3960) were compared with respect to clinical features, illness course, comorbid conditions, suicidality, and socioeconomic factors using data from the Swedish national quality assurance register for bipolar disorders (BipoläR).BDII had higher rate of depressive episodes and more frequent suicide attempts than BDI. Furthermore, the BDII group were younger at first sign of mental illness and showed higher prevalence of psychiatric comorbidity but were more likely to have completed higher education and to be self-sustaining than the BDI group. BDII more frequently received psychotherapy, antidepressants, and lamotrigine. BDI patients had higher rate of hospitalizations and elated episodes, higher BMI, and higher rate of endocrine, nutritional, and metabolic diseases. BDI were more likely to receive mood stabilizers, antipsychotic drugs, electroconvulsive therapy, and psychoeducation.These results demonstrate clear differences between BDI and II and counter the notion that BDII is a milder form of BDI, but rather a more complex condition with regard to clinical course and comorbidity.
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| 8. |
- Najar, Hemen, et al.
(författare)
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Recent Secular Trends of Body Mass Index in Individuals With Bipolar Disorders and in the General Population.
- 2024
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Ingår i: The American journal of psychiatry. - 1535-7228. ; 181:1, s. 39-46
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to investigate secular trends and distribution of body mass index (BMI) among individuals with bipolar disorders and the general population between 2008 and 2019.Data were from the Swedish National Quality Register for Bipolar Disorder, where 24,423 adults with bipolar disorders were identified, and from the national Swedish Living Conditions Surveys, where 77,485 adults from the general population were identified. Quantile regression was used to compare the 15th, 50th, and 85th percentiles of BMI across age and study years.The study sample included 22,127 individuals with bipolar disorders (mean age, 48 years; 63% women) and 71,894 individuals from the general population (mean age, 52 years; 51% women). BMI percentiles were higher among individuals with bipolar disorders. At the 50th percentile, the BMI group differences were 1.1 (95% CI=0.8-1.14) for men and 1.8 (95% CI=1.5-2.1) for women. The gap was widest at the 85th BMI percentile: men, 2.3 (95% CI=1.8-2.8); women, 4.1 (95% CI=3.7-4.6). BMI increased over time in both study groups, but more in the group with bipolar disorders. The changes per decade in mean BMI were 0.4 (95% CI=0.3-0.5) among men in the general population, 1.1 (95% CI=0.7-1.4) among men with bipolar disorders, 0.6 (95% CI=0.5-0.7) among women in the general population, and 1.4 (95% CI=1.1-1.7) among women with bipolar disorders. Women with bipolar disorders had the highest prevalence and the greatest rate of increase of obesity. In 2019, the obesity prevalence was 33% among women and 29% among men with bipolar disorders, compared with 13% and 15%, respectively, among women and men in the general population.Adults with bipolar disorders had a higher BMI and a higher prevalence of obesity than the general population, indicating a higher cardiometabolic risk. Annually, BMI increased more in the group with bipolar disorders than in the general population, particularly among women and among those with high BMI.
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| 9. |
- Najar, Hemen, 1979, et al.
(författare)
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Time effect on cardiometabolic risk indicators in patients with bipolar disorder: a longitudinal case-control study
- 2023
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - : Springer Science and Business Media LLC. - 0940-1334 .- 1433-8491. ; 273:5, s. 1191-1200
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with bipolar disorder are at increased risk for cardiovascular diseases. Most studies have described increases in cardiometabolic risk indicators (CMRIs) using clinical cut-off values. Further, there are no longitudinal studies on CMRIs. We aimed to investigate continuous measures of CMRIs in individuals with bipolar disorder and controls using both cross-sectional and longitudinal data. We used data from the Swedish St. Goran Bipolar project. Study individuals were examined at baseline and after a median of 6 and 7 years for the control and patient group, respectively. Data were collected December 2005-December 2020. The cohort included 281 individuals with bipolar disorder (mean age 39 years, 59% women) and 114 controls (mean age 38 years, 55% women). Of those, 155 patients and 74 controls also provided follow-up data. At baseline, individuals with bipolar disorder had significantly higher mean values of waist-to-hip ratio (WHR) (beta = 0.142, p = 0.001), body mass index (beta = 0.150, p = 0.006), plasma triacylglycerol (TAG) (beta = 0.218, p < 0.001), total/plasma high-density lipoprotein-cholesterol (TChol/HDL-C) ratio (beta = 0.103, p = 0.03), TAG/HDL-C ratio (beta = 0.151, p = 0.006), and non-HDL-C (beta = 0.168, p = 0.001) than controls. Most CMRIs remained higher in the patient group at follow-up. The difference between patients and controls increased over time for WHR (0.005 unit/year, p < 0.001), and systolic (1.1 mm Hg/year, p = 0.002) and diastolic (0.8 mm Hg/year, p < 0.001) blood pressure. Individuals with bipolar disorder displayed persistently higher levels of nearly all included CMRIs. Over time, a subset of CMRIs worsened in patients relative to controls. This suggests that active measures to counter cardiovascular risk in persons with bipolar disorder should be considered.
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| 10. |
- Najar, Hemen, 1979, et al.
(författare)
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Weight gain with add-on second-generation antipsychotics in bipolar disorder: a naturalistic study
- 2017
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 135:6, s. 606-611
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveOur aim was to investigate the prevalence and magnitude of weight gain in-patients with bipolar disorder when treated with a second-generation antipsychotic as an add-on treatment to a mood stabilizer in routine clinical practice. MethodsData were derived from the quality register for bipolar disorder in Sweden (BipolaR). Patients with bipolar disorder who started add-on treatment with a SGA (n=575) were compared at next yearly follow-up with age and sex matched patients who were only treated with a mood stabilizer (n=566). The primary outcome measure was change in body weight and body mass index (BMI). We also assessed the prevalence of clinically significant weight gain defined as 7% gain in body weight. ResultsThe group that received add-on treatment with antipsychotics neither gained more weight nor were at higher risk for a clinically significant weight gain than the reference group. Instead, factors associated with clinically significant weight gain were female sex, young age, low-baseline BMI, and occurrence of manic/hypomanic episodes. ConclusionWe found no evidence of an overall increased risk of weight gain for patients with bipolar disorder after receiving add-on SGA to a mood stabilizer in a routine clinical setting.
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