Mitochondria, often known as the cell’s powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing cell metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) and mitochondrial dysfunction. Mitochondrial dysfunction contributes to oxidative stress, particularly through the generation of ROS, which are implicated in the pathophysiology of BD. Oxidative stress arises when there is an imbalance between the production of ROS and the cell’s ability to neutralize them. In neurons, excessive ROS can damage various cellular components, including proteins in neuronal membranes and intracellular enzymes. Such damage may interfere with neurotransmitter reuptake and the function of critical enzymes, potentially affecting brain regions involved in mood regulation and emotional control, which are key aspects of BD. In this review, we will explore how various types of mitochondrial dysfunction contribute to the production of ROS. These include disruptions in energy metabolism, impaired ROS management, and defects in mitochondrial quality control mechanisms such as mitophagy (the process by which damaged mitochondria are selectively degraded). We will also examine how abnormalities in calcium signaling, which is crucial for synaptic plasticity, can lead to mitochondrial dysfunction. Additionally, we will discuss the specific mitochondrial dysfunctions observed in BD, highlighting how these defects may contribute to the disorder’s pathophysiology. Finally, we will identify potential therapeutic targets to improve mitochondrial function, which could pave the way for new treatments to manage or mitigate symptoms of BD.

Objective: Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls and patients with bipolar disorder (BD). To examine whether the nervonic acid levels differ in the central nervous system, we investigated the levels in the cerebrospinal fluid (CSF) of patients with MDD, BD, and healthy controls.Methods: Nervonic acid levels in CSF were measured by gas chromatography time‐of‐flight mass spectrometry. The participants included 30 patients with MDD, 30 patients with BD, and 30 healthy controls.Results: In contrast to our previous study, no significant differences were found in the nervonic acid level in the CSF among the patients with MDD, BD, and the healthy controls. Though no significant state‐dependent changes were found among the three groups, we did observe a significant negative correlation between the nervonic acid levels and depressive symptoms in the depressive state of patients with MDD and BD (r = −0.38, p = .046). Further, a significant positive correlation was found between the nervonic acid levels and manic symptoms in the manic state of patients with BD (r = 0.79, p = .031).Conclusion: The nervonic acid levels in the CSF did not differ among the patients with MDD, BD, and the healthy controls; however, a significant negative correlation with depressive symptoms and a positive correlation with manic symptoms was observed. Thus, the nervonic acid levels in the CSF may be a candidate biomarker for mood symptoms.

Aim: The aim of this study was to provide new insights into the genetics of bipolar disorder (BD) by analyzing BD comorbid with anxiety disorders.Methods: Structured interviews were conducted with BD patients and their parents. Cases were classified into those with comorbid anxiety spectrum (AS) and those without. The family history of patients with BD with comorbid AS was assessed. Focusing on parent‐of‐origin effects and genomic imprinting from the results, imprinted genes and tested single nucleotide polymorphisms (SNPs) in the identified genes were investigated for an association with BD by transmission disequilibrium test (TDT) using published whole‐exome sequencing data.Results: The incidence of comorbid AS among all the patients with BD analyzed in this study was 39.6%. Patients with BD whose fathers had AS or mood disorders exhibited a significantly higher rate of AS. Among the known imprinted genes, two were associated with BD: THSD7A and CACNA1C. By pruning SNPs, six variants of the THSD7A exons and four variants of the CACNA1C exons were included in the analysis. Among these, one variant of THSD7A, rs2074603, showed over‐transmission from parents to patients with BD. Furthermore, it was nominally significant only for fathers when TDT was performed separately for fathers and mothers.Conclusion: THSD7A may play a role in BD with parent‐of‐origin effects. Further research is necessary to explore the mechanisms by which genomic imprinting is associated with BD.Clinical Trial Registration: N/A.

Aim: Long‐term sickness absence (LTSA) due to mental disorders is a public health concern. Workplace gender composition may influence employees' mental health outcomes; however, its impact on LTSA remains unclear. This study examined the association between workplace gender composition and the risk of LTSA due to common mental disorders, including major depressive disorder, adjustment disorder, and depressive state.Methods: This was a retrospective cohort study of Japanese public employees who applied for LTSA for mental disorders between 2011 and 2022. Workplace gender composition or the proportion of female employees was used as the exposure variable. Multinomial logistic regression was used to estimate the relative risk ratio (RRR) of LTSA due to major depressive disorder, depressive state, and adjustment disorder.Results: Of the 943 employees, 55.7% applied for LTSA due to major depressive disorder; 23.2%, adjustment disorder; and 21.1%, depressive state. Multinomial logistic regression showed that major depressive disorder was associated with age (RRR = 1.03, 95% confidence interval [CI]: 1.01–1.05), gender composition (RRR = 0.43, 95% CI: 0.19–0.95), manager (RRR = 0.61, 95% CI: 0.37–0.99), and clerical worker (RRR = 1.72, 95% CI: 1.05–2.83). Male‐dominated workplaces were associated with a higher relative risk of LTSA due to major depressive disorder. In contrast, female‐dominated workplaces were associated with a higher relative risk of LTSA due to adjustment disorders.Conclusion: Workplace gender composition influences LTSA due to mental disorders. Therefore, mental health strategies and interventions should be tailored to the gender composition of a workplace.