| 1. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 2. |
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| 3. |
- Hou, Liping, et al.
(författare)
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Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:15, s. 3383-94
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p=5.87×10(-9); odds ratio=1.12) and markers within ERBB2 (rs2517959, p=4.53×10(-9); odds ratio=1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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| 4. |
- Hukic, Dzana Sudic, et al.
(författare)
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Cognitive Manic Symptoms in Bipolar Disorder Associated with Polymorphisms in the DAOA and COMT Genes
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Bipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.Methodology:Focusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. Results: The finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. Conclusion:Identifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population. © 2013 Hukic et al.
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| 5. |
- Hukic, Dzana Sudic, et al.
(författare)
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Troponin T levels associated with genetic variants in NOTCH2 and MTNR1B in women with psychosis
- 2017
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 250, s. 217-220
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Tidskriftsartikel (refereegranskat)abstract
- Psychosis patients have increased prevalence of metabolic disorders, which increase the risk for cardiovascular disease. Elevated troponin T level is an early biomarker of cardiovascular damage. We tested for association between troponin T levels and genetic risk variants of elevated blood glucose level in psychosis. Glucose and troponin T levels correlated positively. MTNR1B rs10830963 and NOTCH2 rs10923931 associated with troponin T levels in women, adjusted for glucose levels. These findings may indicate metabolic genetic influences on troponin T levels among women with psychosis.
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| 6. |
- Kalman, Janos L, et al.
(författare)
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Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
- 2019
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- Bipolar disorder (BD) with early disease onset is associated with an unfavorable clinical outcome and constitutes a clinically and biologically homogenous subgroup within the heterogeneous BD spectrum. Previous studies have found an accumulation of early age at onset (AAO) in BD families and have therefore hypothesized that there is a larger genetic contribution to the early-onset cases than to late onset BD. To investigate the genetic background of this subphenotype, we evaluated whether an increased polygenic burden of BD- and schizophrenia (SCZ)-associated risk variants is associated with an earlier AAO in BD patients.A total of 1995 BD type 1 patients from the Consortium of Lithium Genetics (ConLiGen), PsyCourse and Bonn-Mannheim samples were genotyped and their BD and SCZ polygenic risk scores (PRSs) were calculated using the summary statistics of the Psychiatric Genomics Consortium as a training data set. AAO was either separated into onset groups of clinical interest (childhood and adolescence [≤18years] vs adulthood [>18years]) or considered as a continuous measure. The associations between BD- and SCZ-PRSs and AAO were evaluated with regression models.BD- and SCZ-PRSs were not significantly associated with age at disease onset. Results remained the same when analyses were stratified by site of recruitment.The current study is the largest conducted so far to investigate the association between the cumulative BD and SCZ polygenic risk and AAO in BD patients. The reported negative results suggest that such a polygenic influence, if there is any, is not large, and highlight the importance of conducting further, larger scale studies to obtain more information on the genetic architecture of this clinically relevant phenotype.
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| 7. |
- Laursen, Thomas Munk, et al.
(författare)
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Life expectancy and death by diseases of the circulatory system in patients with bipolar disorder or schizophrenia in the Nordic countries.
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Excess mortality from diseases and medical conditions (natural death) in persons with psychiatric disorders has been extensively reported. Even in the Nordic countries with well-developed welfare systems, register based studies find evidence of an excess mortality. In recent years, cardiac mortality and death by diseases of the circulatory system has seen a decline in all the Nordic countries, but a recent paper indicates that women and men in Denmark, Finland, and Sweden, who had been hospitalised for a psychotic disorder, had a two to three-fold increased risk of dying from a cardiovascular disease. The aim of this study was to compare the mortality by diseases of the circulatory system among patients with bipolar disorder or schizophrenia in the three Nordic countries Denmark, Sweden, and Finland. Furthermore, the aim was to examine and compare life expectancy among these patients. Cause specific Standardized Mortality Rates (SMRs) were calculated for each specific subgroup of mortality. Life expectancy was calculated using Wiesler's method.RESULTS: The SMR for bipolar disorder for diseases of the circulatory system was approximately 2 in all countries and both sexes. SMR was slightly higher for people with schizophrenia for both genders and in all countries, except for men in Denmark. Overall life expectancy was much lower among persons with bipolar disorder or schizophrenia, with life expectancy being from 11 to 20 years shorter.CONCLUSION: Our data show that persons in the Nordic countries with schizophrenia or bipolar disorder have a substantially reduced life expectancy. An evaluation of the reasons for these increased mortality rates should be prioritized when planning healthcare in the coming years.
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| 8. |
- Ludvigsson, Jonas F., et al.
(författare)
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Coeliac disease and risk of mood disorders : a general population-based cohort study
- 2007
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Ingår i: Journal of Affective Disorders. - Amsterdam : Elsevier Biomedical. - 0165-0327 .- 1573-2517. ; 99:1, s. 117-126
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundEarlier research has indicated a positive association between coeliac disease (CD) and some mental disorders. Studies on CD and depression have inconsistent findings and we know of no study of CD and the risk of bipolar disorder (BD).MethodsWe used Cox regression to investigate the risk of subsequent mood disorders (MD); depression and BD in 13,776 individuals with CD and 66,815 age- and sex-matched reference individuals in a general population-based cohort study in Sweden. We also studied the association between prior MD and CD through conditional logistic regression.ResultsCD was associated with an increased risk of subsequent depression (Hazard ratio (HR)=1.8; 95% CI=1.6–2.2; p<0.001, based on 181 positive events in individuals with CD and 529 positive events in reference individuals). CD was not associated with subsequent BD (HR=1.1; 95% CI=0.7–1.7; p=0.779, based on 22 and 99 positive events). Individuals with prior depression (OR=2.3; 95% CI=2.0–2.8; p<0.001) or prior BD (OR=1.7; 95% CI=1.2–2.3; p=0.001) were at increased risk of a subsequent diagnosis of CD.LimitationsStudy participants with CD and MD may have more severe disease than the average patient with these disorders since they were identified through a hospital-based register.ConclusionsCD is positively associated with subsequent depression. The risk increase for CD in individuals with prior depression and BD may be due to screening for CD among those with MD.
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| 9. |
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| 10. |
- Olsson, Eric, et al.
(författare)
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Diabetes and glucose disturbances in patients with psychosis in Sweden
- 2015
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Ingår i: BMJ Open Diabetes Research & Care. - : BMJ. - 2052-4897. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:The objectives of this study were to (1) analyze the prevalence of diabetes, prediabetes, and antidiabetic medication in patients with psychosis compared with control subjects and (2) determine what factors in patients with psychosis were associated with antidiabetic medication.METHOD:We studied 977 patients with psychosis recruited from outpatient clinics in Stockholm County, Sweden, and they were compared with 3908 non-psychotic control subjects for fasting plasma glucose levels; prevalence of diabetes, prediabetes, antidiabetic treatment, and tobacco use; and blood pressure, weight, height, and waist circumference. Group differences were evaluated with analysis of variance and χ(2) test, and factors associated with antidiabetic treatment were evaluated with logistic regression.RESULTS:Diabetes was observed in 94 (10%) patients with psychosis, 2.7 times the prevalence observed in control subjects. Among patients with psychosis, 87 (10%) had prediabetes (fasting glucose, 6.1-6.9 mmol/L) compared with 149 (3.8%) control subjects. Most patients with psychosis (77%) who had prediabetes fulfilled criteria for metabolic syndrome. In patients with psychosis, both lipid-lowering medication and fasting glucose were significantly associated with antidiabetic treatment. There was no significant relation between antidiabetic treatment and lifestyle factors such as smoking or degree of psychiatric illness.CONCLUSIONS:The high prevalence of impaired fasting glucose and metabolic syndrome in patients with psychosis warrants further clinical research in preventing or delaying the onset of diabetes in these patients by pharmacotherapy and/or lifestyle intervention.
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| 11. |
- Ragazan, Dragos C., et al.
(författare)
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Gender influence on the bipolar disorder inpatient length of stay in Sweden, 2005–2014 : A register-based study
- 2019
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 256, s. 183-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: The influence of gender on bipolar disorder is controversial and it is unclear if inpatient care differs between men and women. Here, we investigate for gender differences in the inpatient length of stay for Swedes admitted for bipolar disorder and explore other factors that could explain any observed association. Methods: Admission data were extracted from the Swedish National Patient Register and included all patients first admitted to a psychiatric inpatient unit with a bipolar disorder diagnosis, circa 2005–2014. Patients were then retrospectively followed for subsequent hospitalizations. Diagnostic subtypes were categorized by ICD-10 clusters: depressive, depressive with psychotic features, manic, manic with psychotic features, mixed, and other. Psychotropic therapies preceding the corresponding admissions were attained from the Prescribed Drug Register. Mixed-effects zero-truncated negative binomial regressions were employed to model the length of stay per admission. Results: Analysis included 39,653 admissions by 16,271 inpatients (60.0% women). Overall, when compared to men, women spent 7.5% (95% CI: 4.2–11.0%, p < 0.001) extra days hospitalized per admission. However, upon adjusting for candidate confounders, including the bipolar subtype, and selected comorbidities and psychotropics, the association weakened wherein women then spent 3.7% (95% CI: 0.1–6.9%, p = 0.028) extra days hospitalized per admission. Limitations: The integrity of register data can be variable and the adherence to outpatient dispensed psychotropics could not be validated. Conclusion: Although the influence of gender on the bipolar disorder inpatient length of stay is evident, other factors attenuate and better explain this crude observation.
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| 12. |
- Reutfors, Johan, et al.
(författare)
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Medication and suicide risk in schizophrenia : A nested case-control study
- 2013
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 150:2-3, s. 416-420
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Reutfors, J., et al.
(författare)
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Seasonality of suicide in Sweden : relationship with psychiatric disorder
- 2009
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 119:1-3, s. 59-65
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Tidskriftsartikel (refereegranskat)abstract
- Background: Little is known as to whether suicide seasonality is related to psychiatric disorders affecting suicide risk/incidence. The present study aims to assess suicide seasonality patterns with regard to the history of psychiatric morbidity among suicide victims. Methods: The history of psychiatric inpatient diagnoses in the five years prior to suicide was identified among all suicides in Sweden from 1992 to 2003. Suicide seasonality was estimated as the relative risk of suicide during the month of highest to that in the month of lowest suicide incidence. Analyses were performed with respect to sex, suicide method and history of inpatient treatment of psychiatric disorder. Results: Among both male (n = 9,902) and female (n = 4,128) suicide victims, there were peaks in suicide incidence in the spring/early summer. This seasonal variation was more evident in suicide victims with a psychiatric inpatient diagnosis than in those without such a diagnosis. A seasonal variation was found in most diagnostic groups, with significant peaks in males with a history of depression and in females with a history of a neurotic, stress-related, or somatoform disorder. Overall, suicide seasonality was more evident in violent than in non-violent suicide methods. Limitation: Only psychiatric disorders severe enough to require hospital admission were studied. Conclusion: A history of inpatient-treated psychiatric disorder appears to be associated with an increase in suicide seasonality, especially in violent suicide methods. This increase is found in several psychiatric disorders.
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| 14. |
- Reutfors, Johan, et al.
(författare)
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Suicide risk and antipsychotic side effects in schizophrenia : nested case-control study.
- 2016
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Ingår i: Human Psychopharmacology. - : Wiley. - 0885-6222 .- 1099-1077. ; 31:4, s. 341-345
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study explores suicide risk in schizophrenia in relation to side effects from antipsychotic medication.METHODS: Among patients with a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder in Stockholm County between 1984 and 2000 (n = 4000), those who died by suicide within 5 years from diagnosis were defined as cases (n = 84; 54% male). For each case, one individually matched control was identified from the same population. Information on antipsychotic side effects, including extrapyramidal symptoms (EPS) and akathisia, as well as prescriptions of anticholinergic medication, was retrieved from clinical records in a blinded fashion. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of the association between suicide and side effects as well as anticholinergic medication were estimated using conditional logistic regression.RESULTS: A lower suicide risk was found in patients with a history of EPS (aOR 0.33, 95% CI 0.12-0.94). There was no statistically significant association between akathisia or anticholinergic medication use and the suicide risk.CONCLUSIONS: A lower suicide risk identified among patients with EPS could potentially reflect higher antipsychotic adherence, exposure to higher dosage, or polypharmacy among these patients.
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| 15. |
- Westman, Jeanette, et al.
(författare)
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Outcome of a psychosocial health promotion intervention aimed at improving physical health and reducing alcohol use in patients with schizophrenia and psychotic disorders (MINT)
- 2019
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Ingår i: Schizophrenia Research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 208, s. 138-144
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Tidskriftsartikel (refereegranskat)abstract
- 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 the 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.
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| 16. |
- Ösby, Urban
(författare)
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Mortality in schizophrenia and affective disorder
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with psychiatric disorders such as schizophrenia, bipolar disorder and unipolar disorder have a considerably increased mortality compared to the population. To reduce this increased mortality is a major task for clinical psychiatry, and the aim of this study is to improve the knowledge about the increased mortality in order to reduce its effects for the patients. The studies in this thesis are based upon register linkages. Information about diagnosis and time of admission and discharge from the Patient register has been linked with information about cause and time of death from the Cause-of-death register, and information about first-degree relatives from the Second-generation register. First admissions with schizophrenia in Stockholm County during 1978 to 1994 were reduced by 1.3% yearly for males and 1.9% for females, while first admissions with either schizophrenia or paranoid psychosis were unchanged for both sexes, indicating that the reduction of first schizophrenia admissions may be an effect of diagnostic changes during the study period. For schizophrenics in Stockholm County followed-up from the first diagnosis, standardized mortality ratios (SMR:s) for all causes of death were increased to 2.8 for males and 2.4 for females. SMR was most increased in suicide, with 15.7 for males and 19.7 for females, and in unspecified violence, with 11.7 for males and 9.9 for females. SMR:s for suicide were particularly increased for young patients during the first year after the first admission. More excess deaths were caused by natural (somatic) than by unnatural causes of death, although the specific causes of death that caused most extra deaths were suicide in males and cardiovascular disease in females. Time trends in SMR for all causes of death during 1976 to 1995, for patients in Stockholm County diagnosed with schizophrenia for the first time, increased 1.7 times for males and 1.3 times for females. Cardiovascular death increased 4.7 times for males and 2.7 times for females, while all unnatural causes of death increased 1.8 times for males and suicide increased 1.9 times for females. The increase in mortality may be an effect of the concomitant reduction with 64% of days in hospital for schizophrenia. SMR:s for all patients with a hospital diagnosis of bipolar or unipolar disorder in Sweden for all causes of death were 2.5 for males and 2.7 for females in bipolar disorder, and 2.0 for both sexes in unipolar disorder. SMR:s for suicide in bipolar disorder were 15.0 for males and 22.4 for females, and in unipolar disorder 20.9 and 27.0 respectively. In bipolar disorder, most extra deaths were caused by natural causes, while in unipolar disorder, unnatural causes caused most extra deaths. Time trends for suicide mortality increased, both for bipolar and unipolar disorder. SMR:s for suicide for siblings to patients with schizophrenia, bipolar or unipolar disorder were not increased, unless the siblings had a psychiatric diagnosis of their own. Siblings with psychiatric diagnoses had as high suicide mortality as the probands. However, previous suicide in the family increased the suicide risk for patients with schizophrenia and bipolar disorder, but not unipolar disorder.
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