Cerebrospinal fluid proteomic study of two bipolar disorder cohorts

The pathophysiology of bipolar disorder remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, we analyzed 201 proteins in cerebrospinal fluid (CSF) from mood stable bipolar disorder patients and control subjects sampled from two independent cohorts, amounting to a total of 204 patients and 144 controls. We used three Olink Multiplex panels, whereof one specifically targets immune biomarkers, to assess a broad set of CSF protein concentrations. After quality control and removal of proteins with a low detection rate, 105 proteins remained for analyses in relation to case-control status and clinical variables. Only case-control differences that replicated across cohorts were considered. Results adjusted for potential confounders showed that CSF concentrations of growth hormone were lower in bipolar disorder compared with controls in both cohorts. The effect size was larger when the analysis was restricted to bipolar disorder type 1 and controls. We found no indications of immune activation or other aberrations. Growth hormone exerts many effects in the central nervous system and our findings suggest that growth hormone might be implicated in the pathophysiology of bipolar disorder

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium

OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations

Treatments and outcomes in bipolar disorder

Bipolar disorder is defined by recurring mood episodes and patients have a markedly increased risk of suicide. Pharmacological and psychological treatments for bipolar disorder have proven efficacy in clinical trials yet the generalizability of current evidence to routine clinical practice is contested. This thesis presents studies on treatments and outcomes relevant to bipolar disorder patients using data from national registers. In study I, II, IV, we studied the effectiveness of different treatments using within-individual study designs to reduce the impact of confounding-by-indication. In study I, we showed that commonly used drugs, such as lithium, several anticonvulsants, and atypical antipsychotics, were associated with a reduced risk of psychiatric hospital admissions. The association between treatment and hospital admission was stronger for lithium compared to the atypical antipsychotics olanzapine and quetiapine. This differs from previous clinical trial evidence. In study II, we showed that lithium, but not valproate, was associated with a lower risk of suicide-related behaviour. In study III, we studied risk factors for completed suicide in the Swedish National Quality Register for Bipolar Disorder (BipoläR). We identified several risk factors for suicide, e.g., recent affective episodes and psychiatric comorbidity. In study IV, psychoeducation was associated with a reduced risk of recurrence and hospital admission in BipoläR. Finally, in study V, we studied the impact of CYP2C19 polymorphisms on antidepressant treatment patterns as well as the risk for treatment emergent mania using a large sample of patients with bipolar disorder. The mainly negative results suggest that information on CYP2C19 genotype has limited clinical value. These studies showcase the possibility of conducting psychiatric treatment research in national registers to fill important knowledge gaps. The studies can be used as supporting evidence when there is a lack of evidence on the effectiveness of different treatments in routine clinical care. We also underline the unique position of lithium in bipolar disorder treatment and extend current knowledge on risk factors for suicide

Attityder till arbetslösa -en studie av bakomliggande faktorer

Syfte och frågeställningar: Studien syftar till att undersöka vilka bakomliggande faktorer det finns för attityder till arbetslösa och hur dessa har förändrats under perioden 1986-2002. Utgångspunkten är att undersöka vilken inverkan politiska sympatier, erfarenhet/kontakt med arbetslöshet och reell arbetslöshet har på attityderna till arbetslösa. Den huvudsakliga frågeställningen är vilka samband man kan se mellan dessa tre variabler och attityder till arbetslöshet. Metod och material: Studien bygger på statistiska analyser av studierna Åsikter om den offentliga sektorn 1986 samt Åsikter om den offentliga sektorn och skatterna 1992, 1997 och 2002. Logistisk regression har varit den statistiska metoden som använts för analysen. Huvudresultat: Resultaten visar att erfarenhet och kontakt med arbetslöshet till viss del har samband med attityder till arbetslösa. Den viktigaste faktorn bakom attityderna är dock politiska sympatier. Respondenter med borgerliga partisympatier instämmer i mycket högre grad till att arbetslösa skulle vara arbetsovilliga i jämförelse med respondenter ur vänsterblocket och respondenter utan partipolitiska sympatier. Under tidperioden som studerats har negativa attityder till arbetslösa gått ned när arbetslösheten varit hög. Innehållsförteckning 1. Inledning, syfte och problemformuleri

Personality traits in bipolar disorder and influence on outcome

Abstract Background The aim was to investigate the personality profile of bipolar disorder I and II, and healthy controls, and to study whether personality influences the course of bipolar disorder. Methods One hundred ten patients with bipolar disorder I, 85 patients with bipolar disorder II, and 86 healthy individuals had their personality profile assessed using the Swedish universities Scales of Personality (SSP), an instrument developed to explore personality-related vulnerabilities and correlates of psychiatric disorders. Patients were followed prospectively for 2 years. To assess the impact of Neuroticism, Aggressiveness, and Disinhibition on illness course, we performed logistic regressions with the outcome variables mood episodes (depressive, hypo/manic, mixed), suicide attempts, violence, and the number of sick leave days. Results Bipolar disorder I and II demonstrated higher global measures of Neuroticism, Aggressiveness, and Disinhibition as compared with healthy controls. A third of the patients scored ≥1 SD above the population-based normative mean on the global neuroticism measure. The two subtypes of bipolar disorder were, however, undistinguishable on all of the personality traits. In the unadjusted model, higher neuroticism at baseline predicted future depressive episodes and suicide attempts/violent behavior, but this association disappeared when adjusting for baseline depressive symptoms as assessed with MADRS. Conclusions A significant minority of the patients scored ≥1 SD above the population mean on the global measures of Neuroticism, Aggressiveness and Disinhibition; scores this high are usually evident clinically. Yet, the personality profile does not seem to have prognostic value over a 2-year period

Psychoeducation for bipolar disorder and risk of recurrence and hospitalization - a within-individual analysis using registry data

Background: 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. Method: 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. Results: 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. Conclusions: The results suggest that psychoeducation for bipolar disorder reduces the risk of mood episodes and inpatient care also when implemented in routine clinical practice

OPLS-DA score plot showing a partial separation between patients with bipolar disorder I (top panel), bipolar disorder II (middle panel) and healthy controls (lower panel).

<p>Each participant’s score is represented by a circle. The scores were t[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115562#pone.0115562.ref001" target="_blank">1</a>] values on the component predictive of diagnostic group. The vast majority (97%) of the participants were within a ±2 standard deviation limit according to Hotelling’s T². Positive values represent better overall performance.</p