Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed ...exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning.
Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups.
Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested.
Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
There is an ongoing debate concerning the risk benefit ratio of psychopharmacologic compounds. With respect to the benefit, recent reports and meta-analyses note only small effect sizes with ...comparably high placebo response rates in the psychiatric field. These reports together with others lead to a wider, general critique on psychotropic drugs in the scientific community and in the lay press. In a recently published article, Leucht and his colleagues compare the efficacy of psychotropic drugs with the efficacy of common general medicine drugs in different indications according to results from reviewed meta-analyses. The authors conclude that, overall, the psychiatric drugs were generally not less effective than most other medical drugs. This article will highlight some of the results of this systematic review and discuss the limitations and the impact of this important approach on the above mentioned debate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Randomized, double-blind, placebo-controlled trials constitute the gold standard in clinical research when testing the efficacy of new psychopharmacological interventions in the treatment of major ...depression. However, the blinded use of placebo has been found to influence clinical trial outcomes and may bias patient selection.
To improve clinical trial design in major depression so as to reflect clinical practice more closely we propose to present patients with a balanced view of the benefits of study participation irrespective of their assignment to placebo or active treatment. In addition every participant should be given the option to finally receive the active medication. A research agenda is outlined to evaluate the impact of the proposed changes on the efficacy of the drug to be evaluated and on the demographic and clinical characteristics of the enrollment fraction with regard to its representativeness of the eligible population.
We propose a list of measures to be taken to improve the external validity of double-blind, placebo-controlled trials in major depression. The recommended changes to clinical trial design may also be relevant for other psychiatric as well as medical disorders in which expectations regarding treatment outcome may affect the outcome itself.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives: In clinical practice patients with severe mania (agitation, insomnia and aggressive behaviour) still receive effective, but often not well tolerated typical antipsychotics. The aim of ...this study was to test the first‐generation atypical antipsychotic zotepine regarding its antimanic efficacy, tolerability and to find an adequate dosage for a loading strategy.
Method: Twelve patients (seven male) with an acute and severe manic episode, according to DSM‐IV, received zotepine loading in individual dosages (up to 600 mg/day) over a maximum period of 3 weeks. Clinical efficacy was measured using the Young‐Mania Rating Scale (Y‐MRS) total score. Response was defined as a 50% reduction in the Y‐MRS score. Safety was assessed by systematic collection of data on side effects and weight; Hamilton Rating Scale for Depression (HAM‐D) scores were used to detect a switch into depression.
Results: Two patients dropped out of the study after 2 days. Nine of ten patients (baseline mean Y‐MRS: 45 ± 7) were classified as responders, with five of them responding within 4 days. One patient did not respond sufficiently. No switch into a depressive episode occurred.
Conclusions: This open pilot study suggests that zotepine with a median daily dosage of 250 mg/day is effective with a rapid therapeutic effect in severely manic patients. In general, patients tolerated the drug well; dose‐dependent extrapyramidal side effects, an increase in weight and autonomic side effects occurred to a lesser degree. This is the first study assessing zotepine monotherapy in manic patients. Controlled studies are warranted.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Objectives: Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an ...independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients.
Methods: A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3rd edition (WAIS‐III) subtest Letter–Number Sequencing Test (LNST) and the HAWIE‐R (German version of the WAIS‐R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at −80°C. Total Hcy concentration was measured using high‐performance liquid chromatography.
Results: In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE‐R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 ± 3.2 μm/L in the patient group and 7.8 ± 2.1 μm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels.
Conclusions: Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract Background While studies demonstrated that bipolar patients (BP) display cognitive deficits during mood episodes and remission, little is known about the clinical influences underlying these ...deficits. The aim of this study was to compare the performance of euthymic and depressed BPs and non-affective/psychotic disorder controls at several cognitive tasks, exploring which clinical variables influenced the performance of these subtests. It is hypothesized that the cognitive deficits in rank order are: depressed BPs > euthymic BPs > controls. Methods Sixty-five bipolar-I outpatients and thirty-four controls were assessed by the Brazilian version of the Wechsler Adult Intelligence Scale, Third Edition (WAIS-III). BPs were divided into depressed and euthymics, and these two groups were then compared to non-affective/psychotic disorder controls. Results For 12 of 14 subtest scores, comparisons yielded statistically significant ( p < 0.05) between-group differences, including three subtests of attention and working memory (Digit Span and its two subtests) with both depressed and euthymic BPs, compared to controls, displaying significantly worse performance, and six subtests of visual and working memory with depressed (but not euthymic) BPs performing worse than controls. For all subtests, comparisons of depressed and euthymic patients’ scores were non-significant. Performance on several subtests was negatively predicted by the severity of the disorder in both patient groups. Limitations The cross-sectional design of the study, as well as confounding effects of medications and co-morbidities. Conclusions The fact that the impairment of cognitive performance of both groups of patients is influenced by the severity of the illness is consistent with the literature.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
There is a possible association between infectious agents and psychiatric disorders. Previous studies in the US provided evidence for cognitive impairment correlated with Herpes simplex virus type 1 ...(HSV-1) infection. For a replication study in Europe we chosed individuals diagnosed with bipolar disorder to analyse the correlation with HSV-1 infection. Antibody prevalence was analyzed by using solid phase immunoassay techniques. Cognitive functioning was tested with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Form A, the Trail Making Test A&B, and two subtests from the WAIS III: the Letter Number Sequencing Task and the subtest on information. History and psychopathology was assessed using structured interviews and validated rating scales (SCID, HRSD-21, YMRS, PANSS). Additionally, we investigated social functioning and quality of life using self-assessment-scales (SAS, LQLP). Prevalence rates of antibodies against diverse infectious agents did not differ significantly between patients and controls. We found a significant correlation between cognitive impairment in patients with bipolar disorder and the prevalence of antibodies directed against HSV-1. Cognitive functions were significantly impaired including language, attention, and immediate memory.
The results of this study confirm previous findings suggesting that HSV-1 affects cognitive functions in patients with bipolar disorder. This may also result in more impaired functioning, less quality of life and difficulties in social adjustment.
► Seropositive HSV-1 status was associated with cognitive impairment in bipolar disorder. ► European sample could replicate US study. ► Social functioning and quality of life were impaired and correlated with cognitive impairment. ► Psychosocial stressors could provide exacerbation when pre-existing. ► Impairment could be stress-induced or directly triggered by infectious genes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The German school system has been changed considerably during the past years. Traditional half-day schooling was supplemented nationwide by fulltime alternatives. The establishment of all-day ...schooling modifies the German welfare state in a double model which has--according to Esping-Andersen--been rated a conservative type: Firstly, the traditionally separated relation between education and social policy is getting closer. Secondly, the welfare state's support of the traditional family model is supplemented by the perspective of reconciliation of family and working life. This article shows how this change from traditional half-day schooling to the development of all-day schools in Germany was possible.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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