| 1. |
- Backlund, Lena, et al.
(författare)
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Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
- 2011
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 13:5-6, s. 500-8
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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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| 2. |
- Licht, Rasmus W., et al.
(författare)
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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
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Ingår i: Bipolar Disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 12:5, s. 483-493
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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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| 3. |
- Hales, Susie A., et al.
(författare)
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Cognitions in bipolar affective disorder and unipolar depression : imagining suicide
- 2011
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Ingår i: Bipolar Disorders. - : WILEY-BLACKWELL. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 651-661
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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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| 4. |
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| 5. |
- Ceulemans, Shana, et al.
(författare)
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Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population
- 2011
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Ingår i: Bipolar Disorders. - Malden, USA : John Wiley & Sons. - 1398-5647 .- 1399-5618. ; 13:7-8, s. 614-623
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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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| 6. |
- Miklowitz, David J., et al.
(författare)
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Facilitated Integrated Mood Management for adults with bipolar disorder
- 2012
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Ingår i: Bipolar Disorders. - : WILEY. - 1398-5647 .- 1399-5618. ; 14:2, s. 185-197
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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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| 7. |
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| 8. |
- Olsson, Sara K, et al.
(författare)
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Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder.
- 2012
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 14:7, s. 719-26
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Tidskriftsartikel (refereegranskat)abstract
- Olsson SK, Sellgren C, Engberg G, Landén M, Erhardt S. Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder. Bipolar Disord 2012: 14: 719-726. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Kynurenic acid (KYNA), an end metabolite of tryptophan degradation, antagonizes glutamatergic and cholinergic receptors in the brain. Recently, we reported elevated levels of cerebrospinal fluid (CSF) KYNA in male patients with bipolar disorder. Here, we investigate the relationship between symptomatology and the concentration of CSF KYNA in patients with bipolar I disorder. Methods: CSF KYNA levels from euthymic male {n=21; mean age: 41years [standard deviation (SD)=14]} and female [n=34; mean age: 37years (SD=14)] patients diagnosed with bipolar I disorder were analyzed using high-performance liquid chromatography (HPLC). Results: Euthymic bipolar I disorder patients with a lifetime occurrence of psychotic features had higher CSF levels of KYNA {2.0nm [standard error of the mean (SEM)=0.2]; n=43} compared to patients without any history of psychotic features [1.3nm (SEM=0.2); n=12] (p=0.01). Logistic regression, with age as covariate, similarly showed an association between a history of psychotic features and CSF KYNA levels [n=55; odds ratio (OR)=4.9, p=0.03]. Further, having had a recent manic episode (within the previous year) was also associated with CSF KYNA adjusted for age (n=34; OR=4.4, p=0.03), and the association remained significant when adjusting for a lifetime history of psychotic features (OR=4.1, p=0.05). Conclusions: Although the causality needs to be determined, the ability of KYNA to influence dopamine transmission and behavior, along with previous reports showing increased brain levels of the compound in patients with schizophrenia and bipolar disorder, may indicate a possible pathophysiological role of KYNA in the development of manic or psychotic symptoms.
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