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1.
  • Song, Jie, et al. (författare)
  • Bipolar disorder and its relation to major psychiatric disorders : a family-based study in the Swedish population
  • 2015
  • Ingår i: Bipolar Disorders. - Stockholm : Wiley-Blackwell. - 1398-5647 .- 1399-5618. ; 17:2, s. 184-193
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Bipolar disorder (BPD) shares genetic components with other psychiatric disorders; however, uncertainty remains about where in the psychiatric spectra BPD falls. To understand the etiology of BPD, we studied the familial aggregation of BPD and co-aggregation between BPD and schizophrenia, depression, anxiety disorders, attention-deficit hyperactivity disorder, drug abuse, personality disorders, and autism spectrum disorders.METHODS: A population-based cohort was created by linking several Swedish national registers. A total of 54,723 individuals with BPD were identified among 8,141,033 offspring from 4,149,748 nuclear families. The relative risk of BPD in relatives and the co-occurrence of other psychiatric disorders in patients with BPD and their relatives were compared to those of matched-population controls. Structural equation modeling was used to estimate the heritability and tetrachoric correlation.RESULTS: The familial risks for relatives of BPD probands were 5.8-7.9 in first-degree relatives, and decreased with genetic distance. Co-occurrence risks for other psychiatric disorders were 9.7-22.9 in individuals with BPD and 1.7-2.8 in full siblings of BPD probands. Heritability for BPD was estimated at 58%. The correlations between BPD and other psychiatric disorders were considerable (0.37-0.62) and primarily due to genetic effects. The correlation with depression was the highest (0.62), and was 0.44 for schizophrenia.CONCLUSIONS: The high familial risks provide evidence that genetic factors play an important role in the etiology of BPD, and the shared genetic determinants suggest pleiotropic effects across different psychiatric disorders. Results also indicate that BPD is in both the mood and psychotic spectra, but possibly more closely related to mood disorders.
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2.
  • Backlund, Lena, et al. (författare)
  • Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
  • 2011
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 13:5-6, s. 500-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.
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3.
  • Licht, Rasmus W., et al. (författare)
  • Lamotrigine versus lithium as maintenance treatment in bipolar I disorder: an open, randomized effectiveness study mimicking clinical practice. The 6th trial of the Danish University Antidepressant Group (DUAG-6)
  • 2010
  • Ingår i: Bipolar Disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 12:5, s. 483-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In industry-generated pivotal studies, lamotrigine has been found to be superior to placebo and comparable to lithium in the maintenance treatment of bipolar I disorder. Here, we directly compared lamotrigine to lithium under conditions similar to clinical routine conditions. Methods: Adult bipolar I disorder patients with at least two episodes within the last five years and an index episode requiring treatment were randomized to lithium (n = 78; doses adjusted to obtain serum levels of 0.5-1.0 mmol/L) or to lamotrigine (n = 77; up-titrated to 400 mg/day) as maintenance treatments. Randomization took place when clinically appropriate, and comedication was allowed within the first six months after randomization. The patients were enrolled from March 2001 to December 2005, and observations were censored December 2006, allowing a subgroup of patients to be followed for more than five years. The primary outcome measure was time to predefined endpoints indicating insufficient maintenance treatment, and the major secondary outcome measure was time to any study endpoint. Data were analyzed primarily by Cox proportional regression models. Results: For the primary outcome measure, the crude Hazard Rate Ratio (HRR) (lamotrigine relative to lithium) was 0.92 [95% confidence interval (CI): 0.60-1.40]. When the primary endpoints were broken down by polarity, the HRRs (lamotrigine relative to lithium) for mania and depression were, respectively, 1.91 (95% CI: 0.73-5.04) and 0.69 (95% CI: 0.41-1.22). There was no between-group difference in terms of staying in study [HRR: 0.85 (95% CI: 0.61-1.19)]. Most treatment failures occurred within the first 1.5 years of treatment, and, among patients followed for at least five years, practically no patients were maintained successfully on monotherapy with either of the drugs. The lithium-treated patients reported diarrhea, tremor, polyuria, and thirst more frequently. Two cases, probably lamotrigine-related, of benign rash occurred. Conclusions: No differences in maintenance effectiveness between lithium and lamotrigine could be demonstrated. Lamotrigine was better tolerated than lithium, but apparently this did not influence the outcome.
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4.
  • Hales, Susie A., et al. (författare)
  • Cognitions in bipolar affective disorder and unipolar depression : imagining suicide
  • 2011
  • Ingår i: Bipolar Disorders. - : WILEY-BLACKWELL. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 651-661
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Bipolar disorder has the highest rate of suicide of all the psychiatric disorders. In unipolar depression, individuals report vivid, affect-laden images of suicide or the aftermath of death (flashforwards to suicide) during suicidal ideation but this phenomenon has not been explored in bipolar disorder. Therefore the authors investigated and compared imagery and verbal thoughts related to past suicidality in individuals with bipolar disorder (n = 20) and unipolar depression (n = 20). Methods: The study used a quasi-experimental comparative design. The Structured Clinical Interview for DSM-IV was used to confirm diagnoses. Quantitative and qualitative data were gathered through questionnaire measures (e. g., mood and trait imagery use). Individual interviews assessed suicidal cognitions in the form of (i) mental images and (ii) verbal thoughts. Results: All participants reported imagining flashforwards to suicide. Both groups reported greater preoccupation with these suicide-related images than with verbal thoughts about suicide. However, compared to the unipolar group, the bipolar group were significantly more preoccupied with flashforward imagery, rated this imagery as more compelling, and were more than twice as likely to report that the images made them want to take action to complete suicide. In addition, the bipolar group reported a greater trait propensity to use mental imagery in general. Conclusions: Suicidal ideation needs to be better characterized, and mental imagery of suicide has been a neglected but potentially critical feature of suicidal ideation, particularly in bipolar disorder. Our findings suggest that flashforward imagery warrants further investigation for formal universal clinical assessment procedures.
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6.
  • Ceulemans, Shana, et al. (författare)
  • Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population
  • 2011
  • Ingår i: Bipolar Disorders. - Malden, USA : John Wiley & Sons. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 614-623
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most consistent findings in the pathophysiology of mood disorders. The potential role of genes related to HPA axis function has been investigated extensively in major depression. However, in bipolar disorder (BPD) such studies are scarce. We performed a systematic HapMap-based association study of six genes crucial for HPA axis function in relation to BPD. Methods: Haplotype tagging single nucleotide polymorphisms (htSNPs) were selected in order to identify all haplotypes with a frequency of more than 1% in the genes encoding the glucocorticoid receptor (GR), mineralocorticoid receptor (MR), corticotrophin releasing hormone receptor 1 (CRH-R1) and 2 (CRH-R2), CRH binding protein (CRH-BP), and FK binding protein 5 (FKBP5). This resulted in a total selection of 225 SNPs that were genotyped and analyzed in 309 BPD patients and 364 matched control individuals all originating from an isolated northern Swedish population. Results: Consistent evidence for an association with BPD was found for NR3C1, the gene encoding GR. Almost all SNPs in two adjacent haplotype blocks contributed to the positive signal, comprised of significant single marker, sliding window, and haplotype-specific p-values. All these results point to a moderately frequent (10–15%) susceptibility haplotype covering the entire coding region and 3? untranslated region (UTR) of NR3C1. Conclusions: This study contributes to the growing evidence for a role of the glucocorticoid receptor gene (NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. However, this association might be restricted to this specific population, as it is observed in a rather small sample from an isolated population without replication, and data from large meta-analyses for genome-wide association studies in BPD do not show the GR as a very strong candidate.
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7.
  • Engström, C, et al. (författare)
  • Bipolar disorder. II : Personality and age of onset
  • 2003
  • Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 5:5, s. 340-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this study was to examine whether personality i.e. temperament and character interacts with age of onset in bipolar disorder. Methods: Bipolar patients were recruited among in- and outpatients from lithium dispensaries of northern Sweden. Patients were diagnosed according to DSM-IV criteria for bipolar disorder type I and II. Temperament and Character Inventory (TCI) was used for measuring personality. TCI was administered to 100 lithium treated bipolar patients and 100 controls. Results: Treatment response was significantly lower (p = 0.005) in patients with early onset compared with late onset. Family history (p = 0.013) and suicide attempts (p = 0.001) were also significantly more common in patients with early onset. Further, patients with early onset were significantly higher (p = 0.045) in the temperament factor harm avoidance (HA) than patients with late onset, but the difference was weak. Patients with early onset had more fear of uncertainty (HA2, P = 0.022) and were more shy (HA3, p = 0.030). Bipolar I patients showed similar results as those in the total bipolar group (I and II), with significantly higher HA (p = 0.019, moderate difference), HA2 (p = 0.015) and HA3 (p = 0.043) in patients with early onset compared with late onset. Bipolar II patients showed no differences between early and late age of onset but the groups are small and the results are therefore uncertain. Conclusions: Early age of onset in bipolar disorder was correlated to an increase in severity, family history, poorer treatment response and poorer prognosis. Early onset was also correlated to personality.
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8.
  • Engström, Christer, et al. (författare)
  • Bipolar disorder. III : harm avoidance a risk factor for suicide attempts
  • 2004
  • Ingår i: Bipolar Disorders. - Copenhagen : Blackwell Munksgaard. - 1398-5647 .- 1399-5618. ; 6:2, s. 130-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of the study was to examine whether personality, i.e. temperament and character influence suicide attempts in bipolar patients.Methods: Bipolar patients were recruited from lithium dispensaries. Temperament and character inventory (TCI) was administered to 100 euthymic bipolar patients and 100 controls.Results: Age of onset was significantly lower in patients with suicide attempts in the total bipolar group (I and II) and bipolar I patients compared with patients without suicide attempts. Bipolar (I and II) and bipolar I patients with suicide attempts were significantly higher in harm avoidance (HA) and reward dependence compared with patients without suicide attempts. Patients (I and II) with suicide attempts had significantly more anticipatory worry, fatigability and asthenia than patients without suicide attempts. Bipolar I patients with suicide attempts had significantly more fatigability and asthenia and were more dependent than patients without suicide attempts. HA was lowest in patients with no suicide attempts and no family history of suicide, higher in patients with family history of suicide or patients with suicide attempts, and significantly highest in patients with suicide attempts and family history of suicide. Patients with suicide attempts and family history of suicide had more anticipatory worry, fatigability and asthenia. Bipolar disorder was significantly correlated to HA and suicide attempts to HA and PS. Family history of suicide and gender were significantly correlated to suicide attempts.Conclusions: Age of onset, HA, PS, gender and family history of suicide had a moderate to very strong effect on suicide attempts in bipolar patients.
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10.
  • Miklowitz, David J., et al. (författare)
  • Facilitated Integrated Mood Management for adults with bipolar disorder
  • 2012
  • Ingår i: Bipolar Disorders. - : WILEY. - 1398-5647 .- 1399-5618. ; 14:2, s. 185-197
  • Forskningsöversikt (refereegranskat)abstract
    • Objectives: We describe the development of a five-session psychoeducational treatment, Facilitated Integrated Mood Management (FIMM), which contains many of the core elements of longer evidencebased psychosocial treatments for bipolar disorder. FIMM incorporated a novel mood monitoring program based on mobile phone technology. Methods: Adult patients with bipolar I and II disorders (N = 19) received six sessions (Pilot I: n = 14) or five sessions (Pilot II: n = 5) of FIMM with pharmacotherapy. Treatment facilitators were novice counselors who were trained in a three-day workshop and supervised for six months. FIMM sessions focused on identifying early signs of recurrence, maintaining regular daily and nightly routines, rehearsing mood management strategies, maintaining adherence to medications, and education about substance abuse. Patients sent daily text messages or e-mails containing ratings of their mood and sleep, and weekly messages containing self-ratings on the Quick Inventory of Depressive Symptomatology (QIDS) and the Altman Self Rating Mania Scale (ASRM). Patients also completed a weekly mood management strategies questionnaire. Results: Of the 19 patients, 17 (89.5%) completed FIMM in an average of 9.2 +/- 3.4 weeks (Pilot I) and 7.6 +/- 0.9 weeks (Pilot II). Patients reported stable moods on the QIDS and ASRM over a 120-day period, and on average responded to 81% of the daily message prompts and 88% of the weekly QIDS and ASRM prompts. Facilitators maintained high levels of fidelity to the FIMM manual. Patients +/- knowledge of mood management strategies increased significantly between the first and last weeks of treatment. Conclusions: Patients with bipolar disorder can be engaged in a short program of facilitated mood management. The effects of FIMM on the course of bipolar disorder await evaluation in randomized trials. The program may be a useful adjunct to pharmacotherapy in community centers that cannot routinely administer full courses of psychosocial treatment.
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12.
  • Welander-Vatn, Audun S, et al. (författare)
  • No altered dorsal anterior cingulate activation in bipolar II disorder patients during a Go/No-go task : an fMRI study.
  • 2009
  • Ingår i: Bipolar Disorders. - 1398-5647 .- 1399-5618. ; 11:3, s. 270-279
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: It has been reported that one of the core features in patients with bipolar disorder II (BD II) is increased impulsivity. The aim of this study was to investigate whether patients with BD II showed decreased activation in the dorsal anterior cingulate cortex (dACC) as compared to healthy controls when performing a task sensitive to impulsivity.METHODS: Twenty-seven BD II patients and 28 healthy controls performed a Go/No-go task during a functional magnetic resonance imaging (fMRI) session. Eleven of the patients were unmedicated, and possible group differences between medicated and unmedicated patients were also assessed. Results: The groups did not differ in behavioral performance on the Go/No-go task. Both BD II subjects and healthy controls demonstrated dACC activity during the task, and analyses revealed no statistically significant group differences. Medicated and unmedicated patients also did not differ in the degree of fMRI activation.CONCLUSIONS: These findings do not support the hypothesis of abnormal dACC activity during a Go/No-go task in BD II patients.
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17.
  • Bosi, A., et al. (författare)
  • Quality of laboratory biomarker monitoring during treatment with lithium in patients with bipolar disorder
  • 2023
  • Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 25:6, s. 499-506
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundClinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden. MethodsThis is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007-2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid-stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out-migration, or to the end of 2018. ResultsWe identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9-7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium. ConclusionsIn a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels.
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19.
  • Di Simplicio, Martina, et al. (författare)
  • An investigation of mental imagery in bipolar disorder : Exploring "the mind's eye"
  • 2016
  • Ingår i: Bipolar Disorders. - : WILEY-BLACKWELL. - 1398-5647 .- 1399-5618. ; 18:8, s. 669-683
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non-clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders. Methods: Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non-clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non-emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery. Results: (i) Compared to non-clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and "real" negative images (prospective imagery task), and higher self-involvement (picture-word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained-across all groups, imagery differences were associated with affective lability and anxiety. Conclusions: Compared to non-clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD-rather, imagery may reflect a transdiagnostic marker of emotional psychopathology.
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20.
  • Jansåker, Filip, et al. (författare)
  • Association between neighborhood deprivation and mortality in patients with schizophrenia and bipolar disorder—A nationwide follow-up study
  • 2023
  • Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 25:6, s. 489-498
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim was to explore the association between neighborhood deprivation and all-cause mortality and cause-specific mortalities in patients with schizophrenia and bipolar disorder. A better understanding of this potential relationship may help to identify patients with schizophrenia and bipolar disorder with an increased mortality risk. Methods: This nationwide study included practically all adults (≥30 years) diagnosed with schizophrenia (n = 34,544) and bipolar disorder (n = 64,035) in Sweden (1997–2017). The association between neighborhood deprivation and mortality was explored using Cox regression. All models were conducted in both men and women and adjusted for individual-level sociodemographic factors and comorbidities. Results: There was an association between level of neighborhood deprivation and all-cause mortality in both groups. The adjusted hazard ratios for all-cause mortality associated with high compared to low neighborhood deprivation were 1.18 (95% confidence interval 1.11–1.25) in patients with schizophrenia and 1.33 (1.26–1.41) in patients with bipolar disorder. The two most common mortality causes in both groups were coronary heart disease and cancer. The mortality due to coronary heart disease increased when neighborhood deprivation increased and reached 1.37 (1.18–1.60) in patients with schizophrenia and 1.70 (1.44–2.01) in patients with bipolar disorder living in the most deprived neighborhoods. Conclusions: This study shows that neighborhood deprivation is an important risk factor for all-cause mortality and most cause-specific mortalities among patients with schizophrenia and bipolar disorder. These findings could serve as aid to policymakers when allocating healthcare resources and to clinicians who encounter patients with these conditions in deprived neighborhoods.
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21.
  • Kalman, Janos L, et al. (författare)
  • Investigating polygenic burden in age at disease onset in bipolar disorder: Findings from an international multicentric study.
  • 2019
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 21:1, s. 68-75
  • 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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22.
  • Karanti, Alina (Aikaterini), et al. (författare)
  • Characteristics of bipolar I and II disorder: A study of 8766 individuals.
  • 2020
  • Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 22:4, s. 392-400
  • 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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23.
  • Kohler-Forsberg, O., et al. (författare)
  • Pre-diagnostic and post-diagnostic psychopharmacological treatment of 16 288 patients with bipolar disorder
  • 2021
  • Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 23:4, s. 357-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The aim was to describe the pre-diagnostic and post-diagnostic psychopharmacological treatment of bipolar disorder over the past two decades. Methods We identified all 16 288 individuals aged >= 18 years, who received their first diagnosis of bipolar disorder at a psychiatric hospital in Denmark between 1997 and 2014. For each calendar year, we calculated the proportion of patients (with index date in the respective calendar years) who were prescribed psychopharmacological treatment in the 2 years preceding and the 2 years following the date of the first diagnosis of bipolar disorder. For patients diagnosed with bipolar disorder from 2007 to 2010 (n = 3949), we described the psychopharmacological treatment from 1995 to 2016, that is, from up to 16 years prior to and up to 10 years after the diagnosis. Results Concomitant use of >= 2 antidepressants in the 2 years preceding the bipolar disorder diagnosis increased over the study period. In the 2 years following the diagnosis, the use of lithium decreased, while use of atypical antipsychotics (particularly quetiapine), valproate, and lamotrigine increased over the study period. During the 10 years following the diagnosis, 53%-90% of the patients received any psychotropic drug while 12%-26% received treatment with an antidepressant without overlapping treatment with a mood-stabilizing drug. Conclusion The increased use of two or more antidepressants suggests more focus on bipolar disorder as a differential diagnosis to treatment-resistant unipolar depression. The decreased use of lithium (consistent with international trends) and the prevalent use of antidepressants without overlapping treatment with a drug with mood-stabilizing properties are concerning.
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24.
  • Lai, Foon Yin (författare)
  • A mood state-specific interaction between kynurenine metabolism and inflammation is present in bipolar disorder
  • 2020
  • Ingår i: Bipolar Disorders. - : Wiley. - 1398-5647 .- 1399-5618. ; 22, s. 59-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Cytokines are thought to contribute to the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) and studied their relation to kynurenine metabolites and mood. Methods Patients with BD suffering from an acute mood episode were assigned to the depressive (n = 35) or (hypo)manic (n = 32) subgroup. Plasma levels of inflammatory markers [cytokines, C-reactive protein] and kynurenine metabolites [tryptophan (TRP), kynurenine (KYN), 3-hydroxykynurenine (3-HK), quinolinic acid (QA), kynurenic acid (KYNA)] were measured on 6 time points during 8 months follow-up. Biological marker levels in patients were compared to controls (n = 35) and correlated to scores on mood scales. Spearman correlations and linear mixed models were used for statistical analysis. Results Twenty patients of the manic subgroup, 29 of the depressive subgroup, and 30 controls completed the study. The manic subgroup had a rapid remission of mood symptoms, but in the depressive subgroup subsyndromal symptoms persisted. No differences in inflammation were found between groups. A strong correlation between tumor necrosis factor-alpha and KYN, KYN/TRP, 3-HK and QA (rho > 0.60) was specific for the manic group, but only at baseline (during mania). The depressive subgroup had a lower neuroprotective ratio (KYNA/3-HK, P = .0004) and a strong association between interferon-y and kynurenine pathway activation (P < .0001). KYNA was low in both patient groups versus controls throughout the whole follow-up (P = .0008). Conclusions Mania and chronic depressive symptoms in BD are accompanied by a strong interaction between inflammation and a potentially neurotoxic kynurenine metabolism.
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