Plasma BDNF and Cytokines Correlated with Protein Biomarkers for Bipolar II Disorder

We have previously identified five candidate proteins (matrix metallopeptidase 9 (MMP9), phenylalanyl-TRNA synthetase subunit beta (FARSB), peroxiredoxin 2 (PRDX2), carbonic anhydrase 1 (CA-1), and proprotein convertase subtilisin/kexin Type 9 (PCSK9)) as potential biomarkers for bipolar II disorder (BD-II). These candidate proteins have been associated with neuroprotective factors (BDNF) and inflammatory factors (cytokines, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α)). However, the correlations between these proteins with plasma BDNF and inflammatory factors remain unknown. We recruited a total of 185 patients with BD-II and 186 healthy controls. Plasma levels of candidate proteins, BDNF, cytokines (TNF-α, CRP, and interleukin-8 (IL-8)) were assessed from each participant. The correlations between levels of candidate proteins, BDNF, and cytokines were analyzed. In the BD-II group, we found that the level of FARSB was positively correlated with the BDNF level (r = 0.397, p < 0.001) and IL-8 (r = 0.320, p < 0.001). The CA-1 level positively correlated with IL-8 (r = 0.318, p < 0.001). In the control group, we found that the FARSB level positively correlated with the BDNF level (r = 0.648, p < 0.001). The CA-1 level positively correlated with TNF-α (r = 0.231, p = 0.002), while the MMP-9 level positively correlated with the CRP level (r = 0.227, p = 0.002). Our results may help in clarifying the underlying mechanism of these candidate proteins for BD-II.

Development and Validation of the Mood Instability Questionnaire-Trait (MIQ-T)

Background and objectives: Mood instability (MI) is a stable trait associated with psychiatric disorders, yet there is a lack of tools to measure MI. The purpose of this study was to develop and validate the Mood Instability Questionnaire-Trait (MIQ-T) to evaluate MI in mood disorder patients. Material and methods: Items were taken from various established questionnaires to create an initial list of MIQ-T questions. Data from 309 psychiatric patients (n = 309; 62 major depressive disorder, 58 bipolar I disorder, and 189 bipolar II disorder) were gathered from their medical records and were utilized in an exploratory factor analysis to clarify the underlying components of MI. Then, anonymous survey data from 288 individuals from the general population were included in the analysis as a comparison group. Associations between MIQ-T and other previously validated clinical instruments for mood disorders were examined to test external validity. Results: The exploratory factor analysis demonstrated that the five-factor structure (Lability, Upward Tendency, Downward Tendency, Childhood Instability, and Seasonality) of 59 items was the most appropriate with clear, cohesive features. MIQ-T exhibited high internal consistency (α = 0.96) and moderate to strong correlations with other previously validated clinical instruments, which were consistent with theoretical predictions, providing evidence of criterion validity. Short forms were also created to address the high internal consistency value, which can indicate redundancy, and to increase the approachability of the measure. We found that the patients with bipolar II disorder had higher MIQ-T scores than the patients with bipolar I disorder or major depressive disorder and the comparison group. Conclusion: Together, these findings validate the newly developed MIQ-T as an instrument of mood instability. MIQ-T can be a potential research tool for mood disorder.

Thing one and thing two1: What ‘Doctors use’ to doctor you?

This perspective piece is a detailed analysis of the critique by Gordon Parker of the mood disorders clinical practice guidelines (MDcpg2020), in which he claims that bipolar II disorder has been ‘banished’ despite its formal status in current taxonomies. In this article, I defend the reasoning used by the Committee to adopt a dimensional model for describing and managing mood disorders, in particular bipolar disorder. I also robustly contend the many erroneous inferences made by him in his Viewpoint regarding management recommendations within the MDcpg2020 and demonstrate that there is no valid justification for subtyping bipolar disorder – especially in the manner proposed by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Thus, I argue that it was appropriate for the MDcpg2020 Committee to pursue an alternative model to the usual subtyping of bipolar disorder into ‘thing one’ and ‘thing two’ and conclude that the now clearly redundant model of Bipolar II should be altogether removed from our lexicon and clinical practice. Indeed, it is time to develop new and alternative models for defining bipolar disorder and among these a dimensional model should be given consideration.

Polarised views about bipolar disorder(s): A critique of the 2020 College guidelines for mood disorders

The 2020 College guidelines for mood disorders banish bipolar II disorder – despite its formal status in Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases manuals for more than two decades – and argue that there is no need to partition bipolar disorder into separate sub-types. Their single-entity model is seemingly based on opinion rather than any support from referenced scientific studies. The author challenges the Committee’s model of there being only one bipolar disorder and argues that it presents several clinical management risks, particularly of ‘over-treatment’.

The utility of daily mood ratings in clinical trials of patients with bipolar II disorder

Objective: To demonstrate that there can be distinctive differences in information generated by standard interval measures as against using daily monitoring for evaluating progress in those with a bipolar disorder. Method: We undertook a 20-week study of individuals with a bipolar II disorder randomly assigned to receive either lamotrigine or lithium. Patients were rated on standard measures of depression and hypomania at monthly intervals, and they also completed a daily rating measure of their mood swings. We sought to demonstrate the potential for differing interpretations that emerge from these measurement strategies. Results: We graphed data for one subject who showed distinct improvement but demonstrated distinctly differing trajectories provided by monthly and daily data. In a second analysis, we considered sets of those who were judged as improving distinctly with lithium or lamotrigine to determine whether the drugs differed in speed of action, and again observed differing patterns between monthly and daily rating measures. Conclusions: A daily rating strategy appeared to provide additional and differing data compared to standard monthly measures. We therefore argue for the inclusion of daily mood ratings in clinical trials evaluating mood stabilisers and their use by clinicians in managing those with a bipolar II disorder.