Blood-brain barrier dysfunction in bipolar disorder: Molecular mechanisms and clinical implications.

Bipolar disorder (BD) is a severe psychiatric disorder affecting approximately 1-3% of the population and characterized by a chronic and recurrent course of debilitating symptoms. An increasing focus has been directed to discover and explain the function of Blood-Brain Barrier (BBB) integrity and its association with a number of psychiatric disorders; however, there has been limited research in the role of BBB integrity in BD. Multiple pathways may play crucial roles in modulating BBB integrity in BD, such as inflammation, insulin resistance, and alterations of neuronal plasticity. In turn, BBB impairment is hypothesized to have a significant clinical impact in BD patients. Based on the high prevalence of medical and psychiatric comorbidities in BD and a growing body of evidence linking inflammatory and neuroinflammatory mechanisms to the disorder, recent studies have suggested that BBB dysfunction may play a key role in BD's pathophysiology. In this comprehensive narrative review, we aim to discuss studies investigating biological markers of BBB in patients with BD, mechanisms that modulate BBB integrity, their clinical implications on patients, and key targets for future development of novel therapies.

Mini-review: The anti-aging effects of lithium in bipolar disorder.

The medical use of lithium has grown since its initial introduction in the 1800s as a treatment for gout. Today, the divalent cation remains as the pharmacological gold standard in treatment of bipolar disorder (BD) with strong mood stabilizing effects. Lithium has demonstrated efficacy in the treatment of acute affective episodes, in the reduction of affective episode recurrence, and in significantly decreasing the risk of suicide in patients. BD has been consistently associated with clinical signs of accelerated aging, including increased rates of age-related diseases such as cardiovascular diseases, malignancies, and diabetes mellitus. This clinical scenario parallels accelerated aging mechanisms observed on a molecular basis, with studies reporting shortened telomeres, increased oxidative stress, and accelerated epigenetic aging in patients with BD compared to controls. Lithium has proved useful as a potential agent in slowing down this accelerated aging process in BD, potentially reversing effects induced by the disorder. This mini-review summarizes findings of anti-aging mechanisms associated with lithium use and provides a discussion of the clinical implications and perspectives of this evolving field. Despite many promising results, more studies are warranted in order to elucidate the exact mechanism by which lithium may act as an anti-aging agent and the extent to which these mechanisms are relevant to its mood stabilizing properties in BD.