State of research on bipolar disorder

Bipolar disorder, formerly known as manic-depression, is a mental illness characterized by alternating periods of excitement (mania or hypomania) and depression. These mood fluctuations significantly impact the quality of life, health, and social functioning of affected individuals. Estimates suggest that around 1% of the global population suffers from bipolar disorder, making it one of the six leading causes of disability.

Despite the severity of this condition, the causes and mechanisms of bipolar disorder remain largely unknown. Research in this area lags behind other mental illnesses like schizophrenia or depression. However, significant progress has been made in recent years through multidisciplinary approaches and long-term patient cohorts.

Bipolar disorder is a multifactorial illness, resulting from the interaction between genetic and environmental factors. Family and twin studies have shown that the risk of developing bipolar disorder is higher among individuals with an affected first-degree relative. However, there isn't a single gene responsible for bipolar disorder; rather, several genetic variants increase vulnerability to the illness.

Some of these variants involve the immune system, particularly HLA (Human Leukocyte Antigen) and TLR (Toll-like Receptor) genes, which are involved in recognizing and responding to infectious agents (Tamouza and al, 2018, Oliveira and all, 2014). These genes render individuals more sensitive to environmental risk factors such as infections, trauma, pollution, or stress. These factors can trigger or exacerbate chronic inflammation, disrupting brain function and neurotransmitters like serotonin or dopamine.

Bipolar disorder is a progressive illness that extends beyond a single episode. Most patients experience relapses and remissions throughout their lives, with adverse consequences for their physical and mental health. Bipolar disorder is associated with a 10-year reduction in life expectancy due to the high risk of suicide, as well as somatic comorbidities like cardiovascular diseases, diabetes, or obesity.

To better understand bipolar disorder trajectories, the FondaMental foundation created the FACE-BD cohort in 2010. This cohort comprises over 4,000 patients regularly monitored by expert centers (Leboyer and al, 2022). This initiative has identified poor prognosis factors such as childhood trauma, sleep disorders, addictions, or anxiety disorders. It has also described the various clinical forms of bipolar disorder, which vary based on episode frequency, duration, severity, and the presence of psychotic symptoms.

The treatment of bipolar disorder primarily relies on mood-stabilizing medications like lithium, valproate, or lamotrigine, aiming to prevent relapses and reduce episode severity. These medications are often combined with antidepressants, antipsychotics, or anxiolytics as per individual needs. However, these treatments are not universally effective and can have undesirable side effects.

Research on bipolar disorder treatments focuses on two main aspects: identifying biomarkers to predict medication response and dosage adjustments, and developing new molecules targeting biological pathways involved in the illness, such as inflammation or oxidative stress.

Additionally, medication treatments should be complemented by psychosocial interventions aimed at improving quality of life, treatment adherence, stress management, and relapse prevention. Among these interventions are psychoeducation, informing patients and their families about the illness and its treatments; cognitive-behavioral therapy, aiming to modify negative thoughts and behaviors; cognitive remediation, offering exercises to improve impaired cognitive functions like memory or attention; and digital tools, providing remote monitoring and alerts in case of patient deterioration.

Bipolar disorder is a complex and heterogeneous illness requiring personalized and multidimensional care. Research in this field has made significant strides in understanding the causes, mechanisms, trajectories, and treatments of bipolar disorder. However, numerous challenges remain, such as early detection, complication prevention, improving medication effectiveness and tolerance, and developing new innovative therapeutic approaches.