Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression.
ObjectivesUpdated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher‐level ecological evidence.MethodsThe study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED‐related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020.ResultsMean length of inpatient stays was inversely correlated to relapse to ED‐related inpatient care within the same year (p < 0.001, R‐squaredadj = 0.5216 and p < 0.00001, R‐squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year‐wise relapse rate.ConclusionsMean length of ED‐related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.
Background: The optimal dose (number of pulses per session) of repetitive transcranial magnetic stimulation (rTMS), using the H-coil, in major depressive disorder (MDD) has not previously been reported. Objective: To explore the relationship between rTMS dose and antidepressant effect, and collect data for the design of a definitive trial. Methods: This was a double-blind, three-arm parallel-group, randomized [1:1:1], pilot trial conducted in Stockholm, Sweden (September 2014 to September 2016). The primary outcome was change in depression severity measured with the Montgomery Åsberg Depression Rating Scale (MADRS) after 4 weeks. Participants (n = 29) with MDD were randomized to 1000, 2000, or 4000 pulses of rTMS for 20 sessions during 4 weeks. Results: At 4 weeks, the 3 treatment groups reduced the mean MADRS (95% CI) by 11.6 (4.0–19.2), 9.1 (5.0–13.3), and 11.3 (4.1–18.5) points respectively. Eleven participants met criteria for response and 10 for remission. No serious adverse events occurred. Ratings of subjective memory improved in all groups. Exploring the effect of dose and time, 4000 pulses had the largest reduction in MADRS during the first 2 weeks. A comparison of change in MADRS between 2000 and 4000 pulses after 2 weeks will require a sample size of 66 patients at power .80 and alpha .05. Conclusions: It is feasible to conduct a definitive trial investigating whether a higher number of magnetic pulses per treatment session gives a more rapid antidepressive response.
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