Introduction

Bipolar disorder (BD) is a chronic mental health condition characterized by episodic, extreme fluctuations in mood, energy, and functioning. These periods, known as mood episodes, range from days to weeks and are classified as either manic/hypomanic—marked by elevated or irritable mood—or depressive, characterized by profound sadness or anhedonia. Individuals with BD often experience intervals of euthymia, or stable mood, between episodes. With appropriate treatment, most individuals with bipolar disorder can lead full, productive lives.1

Globally, bipolar disorder affects approximately 0.53% of the population—around 40 million people as of 2019—making it one of the leading causes of disability.2 According to the World Mental Health Survey Initiative, the lifetime prevalence of BD is estimated at 2.4%, with a 12-month prevalence of 1.5%.3 Rates vary significantly across countries, potentially due to diagnostic practices, methodological differences, and cultural perceptions. For example, a systematic review found a notably low lifetime prevalence of just 0.11% in China.4

Types of Bipolar Disorder

Bipolar disorder is classified into three primary subtypes: Bipolar I Disorder, Bipolar II Disorder, and Cyclothymic Disorder.

Bipolar I Disorder (BD-I) involves at least one manic episode lasting seven days or more, or any duration if hospitalization is required. Manic episodes can be severe and may include psychotic symptoms such as delusions or hallucinations. While depressive episodes are common in BD-I, they are not necessary for diagnosis. BD-I is associated with greater symptom severity, higher hospitalization rates, and greater overall functional impairment.5,6

Bipolar II Disorder (BD-II) is defined by at least one major depressive episode and at least one hypomanic episode. Hypomania is a milder form of mania that lacks psychotic features and typically does not necessitate hospitalization. Because hypomania may be perceived as a period of heightened productivity or emotional uplift, BD-II is frequently underdiagnosed or misdiagnosed as unipolar depression. Patients with BD-II often experience more prolonged and frequent depressive episodes and higher rates of comorbid anxiety compared to those with BD-I.7,8

Cyclothymic Disorder (Cyclothymia) features chronic, fluctuating mood disturbances that include numerous periods of hypomanic and depressive symptoms. However, these symptoms do not meet the full criteria for a hypomanic or major depressive episode. The condition must persist for at least two years in adults (or one year in children and adolescents) to warrant diagnosis. While typically less severe than BD-I or BD-II, cyclothymia still causes significant distress and impairment and is often misdiagnosed as a personality disorder or mood instability.9

Beyond Mood Fluctuations

Though mood variability is a universal human experience, bipolar disorder differs from ordinary mood swings in its severity, duration, and functional impact. Mood swings caused by stress, hormonal changes, or fatigue typically last minutes to hours and resolve on their own.10,11 In contrast, bipolar mood episodes can last for days, weeks, or even months and profoundly disrupt interpersonal relationships, employment, academic performance, and self-care.12

Manic episodes involve abnormally elevated or irritable mood, increased goal-directed activity, decreased need for sleep, impulsivity, and risk-taking behaviors. Depressive episodes include sustained sadness, loss of interest, psychomotor retardation or agitation, fatigue, and suicidality. 13 Importantly, these mood states often lack obvious external triggers, and in more severe cases, they may be accompanied by psychotic symptoms such as delusions or hallucinations14.

Unlike episodic mood changes in the general population, the mood disturbances in BD are clinically significant and require specialized diagnosis and intervention. Early detection is challenging, as individuals often present during depressive phases, which can be mistaken for unipolar depression—particularly in BD-II.

Biological Foundations of Bipolar Disorder

Bipolar disorder is increasingly understood as a multi-system neurobiological disorder involving complex interactions among Mitochondrial Function, neurotransmitter signaling, inflammation, and gene expression.

A recent conceptualization proposes that BD may function, in part, as a mitochondrial disorder, with energy production fluctuating between mood states. During manic episodes, the brain’s adenosine triphosphate (ATP) production and mitochondrial respiration may be elevated, while in depressive or euthymic phases, mitochondrial function and cerebral metabolism appear reduced. This pattern aligns with the clinical observation of heightened activity in mania and lethargy in depression. Given that the brain is the body’s largest consumer of ATP, changes in energy metabolism may have profound effects on mood regulation and cognition.15,16

Inflammatory processes are also believed to play a crucial role in BD. Cytokines and other inflammatory markers can suppress mitochondrial energy generation, disrupt synaptic transmission and plasticity, and compromise neuronal survival. Studies have reported increased levels of interleukin (IL)-4, tumor necrosis factor-alpha (TNF-α), soluble TNF receptor 1 (sTNFR1), and soluble IL-2 receptor in individuals with BD compared to healthy controls. These findings suggest that neuroinflammation may contribute both to mood episode onset and progression, potentially influencing treatment response and long-term outcomes. 17,18

Together, these insights support a model of bipolar disorder as a multi-system brain disorder, in which energy dysregulation and immune activation intersect with neurotransmitter systems and gene expression to drive mood instability.


Reference:

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  2. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry. 2022;9:137–50. doi:10.1016/S2215-0366(21)00395-3.

  3. Merikangas KR, Jin R, He J-P, et al. Prevalence and correlates of bipolar spectrum disorder in the World Mental Health Survey Initiative. Arch Gen Psychiatry 2011;68:241-251.

  4. Zhang L, Cao X-L, Wang S-B, et al. The prevalence of bipolar disorder in China: a meta-analysis. J Affect Disord2017;207:413-421.

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  6. Guzman-Parra, J., Streit, F., Forstner, A.J. et al. Clinical and genetic differences between bipolar disorder type 1 and 2 in multiplex families. Transl Psychiatry 11, 31 (2021). https://doi.org/10.1038/s41398-020-01146-0

  7. Brancati GE, Nunes A, Scott K, O'Donovan C, Cervantes P, Grof P, Alda M. Differential characteristics of bipolar I and II disorders: a retrospective, cross-sectional evaluation of clinical features, illness course, and response to treatment. Int J Bipolar Disord. 2023 Jul 14;11(1):25. doi: 10.1186/s40345-023-00304-9. PMID: 37452256; PMCID: PMC10349025.

  8. Differences in bipolar disorder type I and type II exposed to childhood trauma: A retrospective cohort study. Hernán F Guillen-Burgos. 2025.

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  11. Healthline. Bipolar Disorder Vs. Mood Swings: Understanding the Difference (2023)

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  13. Cleveland Clinic. Bipolar Disorder (Manic Depression): Symptoms & Treatment (2025)

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  17. Modabbernia A, Taslimi S, Brietzke E, Ashrafi M. Cytokine alterations in bipolar disorder: a meta-analysis of 30. Stud BPS. 2013;74:15–25.

  18. Munkholm K, Brauner JV, Kessing LV, Vinberg M. Cytokines in bipolar disorder vs. healthy control subjects: a systematic review and meta-analysis. J Psychiatr Res. 2013;47:1119–33.