Overview of Bipolar Disorders

Article written and reviewed by Dr Luca Moretti

Bipolar and related disorders are a group of mood disorders characterized by the current or past presence of mania, hypomania or persistent fluctuations between hypomanic and depressive symptoms, depending on the specific diagnostic category. They are not simply forms of depression in which mood occasionally improves: diagnosis requires affective episodes or patterns defined by duration, intensity, changes in energy and activity, and consequences for functioning.

In the DSM-5-TR, the group includes bipolar I disorder, bipolar II disorder, cyclothymic disorder, substance or medication induced bipolar and related disorder, bipolar and related disorder due to another medical condition, and other specified or unspecified categories. ICD-11 uses a partly different organization but similarly recognizes bipolar type I disorder, type II disorder, cyclothymic disorder and other spectrum categories.

Bipolar I disorder is defined by the presence of at least one manic episode; a major depressive episode is common during the course but is not required for diagnosis. Bipolar II disorder instead requires at least one hypomanic episode and at least one major depressive episode, with no history of mania. Cyclothymic disorder has a chronic course with numerous periods of hypomanic and depressive symptoms that do not meet the full requirements for the corresponding episodes during the initial diagnostic period.

These distinctions are clinically essential because mania, hypomania and depression do not have the same diagnostic significance or the same therapeutic implications. In particular, a person may present during a depressive phase and be incorrectly classified as having unipolar depression if the history of previous pathological elevations of mood and energy is not systematically investigated.

Epidemiological data vary across countries and methods. In the World Mental Health Survey Initiative, lifetime estimates were approximately 0.6% for bipolar I disorder and 0.4% for bipolar II disorder, while subthreshold bipolar presentations further increased the overall prevalence of the spectrum. These estimates cannot be directly transferred to every population and are influenced by the difficulty of retrospectively identifying hypomanic episodes and by variability in diagnostic systems.

Onset frequently occurs between adolescence and young adulthood, although the disorder may present earlier or later. The course is typically episodic and recurrent, with periods of complete or incomplete remission; in many patients, depression accounts for a substantial proportion of the longitudinal burden of illness. Anxiety comorbidity, substance use disorders, sleep disorders and physical illnesses further contribute to disability.

Bipolar disorders are associated with a substantial increase in suicidal behavior, premature mortality and social and occupational impairment. Risk varies widely between individuals and phases of illness and cannot be summarized by a single percentage applicable to every patient. Previous attempts, depression, mixed states, agitation, substance use and other features must be assessed dynamically during follow up.

Etiology, Pathogenesis and Pathophysiology

There is no single etiologic cause of bipolar disorders. The literature supports a multifactorial model in which high genetic vulnerability, brain development, systems regulating mood and energy, circadian rhythms, environmental stress and psychosocial factors interact to determine the likelihood of illness and the pattern of its course.

The genetic component is among the most robustly documented in psychiatry. Family and twin studies indicate high heritability, often estimated at around 60 to 80%, but this does not mean that the disorder is genetically determined in an individual. Heritability is a population measure and does not represent the probability that a child of an affected person will necessarily develop the disorder.

Large genome wide association studies confirm a polygenic architecture. The multiancestry study published in 2025 identified hundreds of loci associated with bipolar disorder and greatly expanded the number of genetic signals compared with previous analyses. Each common variant, however, has a small individual effect, and no genetic profile currently has sufficient accuracy for use as a clinical diagnostic test.

The genetics of bipolar disorder also show partial overlap with other psychiatric disorders, including schizophrenia and major depression. This shared architecture helps explain why some clinical and biological features cross traditional diagnostic categories, but it does not eliminate the need for a clinical diagnosis based on the course of episodes.

Neurobiological studies implicate dopaminergic, serotonergic, noradrenergic and glutamatergic systems, but no alteration in a single neurotransmitter explains the entire disorder. Mania has been associated with changes in salience, reward and dopaminergic activity, while bipolar depression involves circuits that partly overlap with those of unipolar depression. These models describe functional networks, not simple chemical excesses or deficiencies.

A central role has been attributed to synaptic plasticity, mitochondrial function, intracellular signaling pathways and mechanisms regulating neuronal excitability and adaptation to stress. The efficacy of drugs with different mechanisms, such as lithium, selected anticonvulsants and antipsychotics, suggests that multiple systems converge on stabilization of brain networks rather than on a single pathophysiological target.

Lithium, in addition to its therapeutic value, has contributed to the study of the biological pathways involved in the disorder through its effects on second messengers, neuroplasticity and intracellular regulation. These observations do not, however, demonstrate that a specific lithium sensitive alteration is the universal cause of the illness; response to the drug itself is heterogeneous.

Circadian rhythms and sleep are particularly important. Reduced need for sleep is a cardinal symptom of mania and hypomania, while sleep deprivation, shift work and circadian misalignment can precipitate episodes in vulnerable individuals. The relationship is bidirectional: an episode profoundly alters sleep and, in turn, destabilization of the sleep wake rhythm may promote further mood fluctuations.

Stressful life events, early trauma and chronic stress are associated with a higher risk of onset or relapse in some patients. They are not necessary causes, however: episodes may occur without an identifiable precipitant, and many people exposed to traumatic events do not develop bipolar disorder. Their role is therefore that of modifiers of risk and course within an individual vulnerability.

The postpartum period represents a phase of particular vulnerability to severe affective episodes in people with bipolar disorder. Rapid endocrine changes, sleep loss and psychosocial stress may contribute to destabilization. A history of bipolar disorder should be carefully investigated in patients who present with depression, agitation or psychotic symptoms during the perinatal period.

Neuroimaging studies show average differences in circuits involving the prefrontal cortex, cingulate, amygdala, hippocampus and striatum, with changes in connectivity and, in some analyses, structure. However, heterogeneity and overlap with healthy controls and other disorders are substantial. Magnetic resonance imaging therefore cannot diagnose bipolar disorder in an individual patient.

Inflammation, oxidative stress and energy metabolism are also areas of active research. Average alterations in some markers have been observed in different phases of illness, but these are affected by medications, obesity, smoking, comorbidity and other confounders. No inflammatory or metabolic marker is currently a diagnostic test or a standard method for selecting treatment.

At the psychological and behavioral level, changes in activity, reward, emotion regulation and daily routines may contribute to maintaining or precipitating episodes. Social rhythm models emphasize the relationship between events that destabilize routines, sleep and affective vulnerability; this rationale underlies some specific psychotherapeutic interventions.

Pathophysiology is expressed clinically through episodic dysfunction of systems regulating mood, energy, activity, sleep, cognition, impulsivity and motivation. During mania, pathological increases in energy and activity may be associated with grandiosity, reduced need for sleep and risky behavior; during depression, anhedonia, reduced energy, psychomotor slowing and negative cognitions predominate. In states with mixed features, elements of both poles may coexist.

The marked heterogeneity of the disorder explains why patients with the same diagnosis may have very different episode frequency, predominant polarity, comorbidity and treatment response. There is therefore no single pathophysiological model capable of describing all cases.

Despite advances in genomics and neuroscience, diagnosis remains clinical. No genetic, blood, endocrine, electrophysiological or neuroimaging biomarker is validated to individually confirm or exclude bipolar disorder.

Clinical Manifestations

The fundamental manifestation of the bipolar spectrum is the alternation or recurrence of pathological affective states. Assessment should begin with a longitudinal history, reconstructing not only the current episode but the entire history of changes in mood, energy, sleep and activity. A single interview during a depressive phase may fail to reveal bipolarity.

A manic episode is characterized by a distinct period of abnormally and persistently elevated, expansive or irritable mood and abnormally increased activity or energy. It must last at least one week for most of the day, nearly every day, unless severity necessitates hospitalization before that duration is reached.

During mania, typical features include grandiosity, reduced need for sleep, increased talkativeness, flight of ideas or racing thoughts, distractibility, increased goal directed activity or psychomotor agitation, and involvement in activities with a high potential for harmful consequences. Increased energy and activity are integral components of the syndrome, not ancillary features.

Mania causes marked functional impairment, may require hospitalization to prevent harm to self or others, or may present with psychotic features. The presence of psychosis during a state of elevated mood makes the episode, by DSM definition, manic rather than simply hypomanic.

Hypomania has a similar symptom profile but a minimum duration of four days in the DSM-5-TR and lower intensity. The episode must represent an unequivocal change in functioning that is observable by others, but it must not be severe enough to cause marked impairment or require hospitalization; if psychotic features occur, the episode is manic.

Hypomania can be difficult to recognize because some patients perceive it as a period of wellbeing, productivity or sociability. It is therefore useful to ask not only whether the patient has ever been “euphoric”, but whether they have experienced distinct periods of reduced need for sleep, increased energy, greater talkativeness, increased goal directed activity, impulsivity or self confidence compared with their usual functioning.

Major depressive episodes in bipolar disorder have the same core syndromic criteria used in unipolar major depression: depressed mood or anhedonia associated with neurovegetative, cognitive and psychomotor symptoms for at least two weeks, with distress or impairment. The phenomenology of the current episode alone does not always distinguish bipolar from unipolar depression.

Features such as early onset, numerous episodes, a family history of bipolar disorder, mixed features and previous antidepressant associated activation may increase suspicion of bipolarity but do not constitute independent diagnostic criteria. The distinction depends on documentation of mania or hypomania during the course.

Mixed features indicate the presence, during an episode of one polarity, of significant symptoms of the opposite polarity without necessarily meeting criteria for a complete opposite episode. These presentations may be associated with agitation, insomnia, impulsivity and greater clinical risk and require particular therapeutic caution.

Episodes may present with psychotic features, particularly in severe manic or depressive forms. Delusions and hallucinations may be mood congruent or mood incongruent. The temporal relationship between psychosis and affective episodes is fundamental in the differential diagnosis with schizophrenia and schizoaffective disorder.

The course may include periods of complete remission, residual symptoms and new episodes. Predominant polarity varies: some patients mainly experience mania, whereas others have a greater burden of depression. In bipolar II disorder, depression is often the principal source of distress and disability despite the absence of mania.

The term rapid cycling is used when at least four mood episodes occur within twelve months, according to the applicable criteria. It does not mean mood fluctuations from one hour to the next. Very rapid and reactive changes require a broader differential diagnosis and should not automatically be interpreted as bipolar cycles.

Cyclothymia, by contrast, involves numerous periods of subthreshold hypomanic and depressive symptoms that persist for at least two years in adults or one year in minors according to the DSM-5-TR, with specific limits on the duration of symptom free intervals. It can cause significant instability and impairment even without full episodes during the required diagnostic period.

Psychiatric comorbidities are common. Anxiety disorders, ADHD, alcohol and other substance use disorders, and personality disorders may alter symptoms, course and treatment response. The presence of a comorbidity does not invalidate a bipolar diagnosis but requires distinguishing which manifestations belong to each disorder.

Assessment of suicide risk should be performed at every stage, with particular attention to depression, mixed states, recent discharge, previous attempts, substance use and agitation. The risk of nonsuicidal impulsive behavior may also increase during mania and hypomania, with financial, sexual, legal and relational consequences.

On mental status examination, mania may present with a lively or disorganized appearance, agitation, pressured speech, racing thoughts, distractibility and reduced insight; depression may show psychomotor slowing, reduced affect, pessimistic thinking and suicidal ideation. Between episodes, the examination may be entirely normal.

Cognitive impairment is not limited to acute phases. Some patients experience difficulties with attention, memory and executive functions even during euthymia, although individual variability is substantial. Sleep, medications, comorbidities and residual symptoms should be considered when interpreting cognitive difficulties.

Assessment and Diagnosis

The diagnosis of bipolar disorders is clinical and longitudinal. There is no single set of criteria applicable to the entire group because bipolar I disorder, bipolar II disorder and cyclothymia have distinct official criteria. Diagnosis must therefore identify which episode or pattern is actually documented and apply the requirements of the relevant category.

The first task is to establish immediate safety. Severe mania with agitation, psychosis or dangerous behavior, depression with high suicide risk, severe self neglect or catatonia may require urgent psychiatric assessment and a protected setting.

The history should reconstruct episodes of mood elevation, pathological irritability, increased energy and activity, changes in need for sleep, grandiosity, racing thoughts and impulsive behavior. Duration, change from baseline and functional impairment distinguish a pathological episode from normal temperamental variation.

The distinction between mania and hypomania is not based solely on the subjective intensity of euphoria. Minimum duration, marked impairment, need for hospitalization and the presence of psychosis are decisive diagnostic elements. Details of the official criteria are provided on the dedicated bipolar I disorder and bipolar II disorder pages.

When a patient presents with depression, it is essential to ask explicitly about previous hypomanic or manic episodes. Collateral information from family members or people living with the patient, with consent and when available, can improve accuracy because reduced insight during mania and a positive perception of hypomania promote retrospective underreporting.

Screening tools such as the Mood Disorder Questionnaire may help identify people who need more detailed assessment, but they do not establish the diagnosis. False positive results can occur in other disorders, and a negative result does not necessarily exclude bipolar disorder. The diagnostic interview remains decisive.

Differential diagnosis with major depressive disorder is particularly important in patients seen during depression. The presence of a manic episode defines bipolar I disorder; at least one hypomanic episode together with at least one major depressive episode, in the absence of mania, defines bipolar II disorder according to the DSM-5-TR.

ADHD may share distractibility, impulsivity and increased activity, but tends to have a more persistent, trait based pattern than the episodic variation of mania or hypomania. The two conditions may also coexist, making it essential to reconstruct age at onset and the episodic nature of symptoms.

Borderline personality disorder may involve affective instability, impulsivity and self harming behavior, but fluctuations are often closely reactive to interpersonal events and embedded in a pervasive pattern of functioning. Differential diagnosis should not be reduced to the duration of a single mood change, and comorbidity is possible.

Substance and medication related disorders should be considered systematically. Stimulants, corticosteroids and other exposures can produce affective syndromes; alcohol and other substances may alter sleep, impulsivity and mood. The temporal relationship between exposure and symptoms is fundamental for distinguishing a primary disorder from an induced condition.

Medical conditions, including some neurological and endocrine disorders, can cause manic or depressive symptoms. Tests are selected according to age, onset, symptoms and history. There is no single mandatory panel, but a complete blood count, electrolytes, renal and liver function tests, TSH, toxicology testing or other targeted investigations may be appropriate.

Before starting specific mood stabilizers or antipsychotics, assessments required for medication safety are also performed, such as renal and thyroid function for lithium, pregnancy testing when relevant, metabolic parameters and other checks depending on the medication. These tests are used to select and monitor treatment, not to diagnose bipolar disorder.

Neuroimaging and electroencephalography are not routine diagnostic tests. They are indicated when atypical onset, neurological signs, seizures, cognitive decline or acute changes in mental status suggest a possible neurological cause.

The diagnostic formulation should specify disorder type, current or most recent episode, severity, remission and specifiers, as well as suicide risk, comorbidity, substance use, functioning and psychosocial factors. Diagnosis is reassessed over time because new information about the course may alter classification.

Treatment and Prognosis

Treatment is specific to the phase of illness: acute mania, bipolar depression and relapse prevention require different strategies. A medication that is effective for one phase is not necessarily the best choice for another, and therapy should be individualized according to subtype, predominant polarity, previous responses, comorbidities, tolerability and preferences.

For acute mania, the 2023 VA/DoD guideline recommends lithium or quetiapine among the options with the strongest support; numerous antipsychotics and other mood stabilizers also have supporting evidence and are used according to severity, clinical profile and previous treatment. Severe presentations may require combination pharmacotherapy and hospitalization.

Lithium has a central role both in the treatment of some acute phases and in relapse prevention. It requires monitoring of serum concentrations, renal and thyroid function, interactions and hydration status. Its relatively narrow therapeutic window makes structured follow up essential.

Valproate may be used in specific phases and patients, but it carries important reproductive and teratogenic risks. Contemporary guidelines strongly restrict its use in people who may become pregnant, requiring specialist assessment and compliance with applicable safety regulations.

Second generation antipsychotics have different roles in manic, depressive and maintenance phases. Quetiapine has evidence across several phases; other agents, including lurasidone, cariprazine and lumateperone, have specific indications or evidence for bipolar depression depending on jurisdiction and guideline.

For bipolar depression, the 2023 VA/DoD guideline recommends quetiapine and suggests cariprazine, lumateperone, lurasidone or olanzapine as alternatives. CANMAT/ISBD further differentiates strategies according to type I or II disorder and treatment line. Recommendations should not be transferred indiscriminately across subtypes and phases.

Antidepressants require particular caution. They are not standard treatment for mania, and their role in bipolar depression is more limited and controversial than in unipolar depression. In particular, antidepressant monotherapy should be avoided in bipolar I disorder and in presentations with a high risk of activation or mixed features.

During maintenance, the goal is to prevent new episodes and preserve functioning. Lithium, quetiapine, lamotrigine and other treatments have different levels of evidence for preventing manic or depressive relapses. Choice should reflect predominant polarity and the response achieved during the acute phase.

Lamotrigine is particularly relevant for preventing depressive relapses and is not an effective treatment for acute mania. This example shows why the generic category of “mood stabilizer” should not replace knowledge of evidence specific to each phase.

Electroconvulsive therapy is an effective treatment in selected situations, including severe or treatment resistant depressive episodes, psychotic depression, catatonia and some severe or refractory manic episodes. It may be particularly important when a rapid response is needed.

Psychotherapy complements pharmacotherapy, especially during maintenance. Psychoeducation, cognitive behavioral therapy, family focused therapy, and interpersonal and social rhythm therapy have different levels of evidence for reducing relapse, improving adherence and identifying early signs of destabilization.

Regulation of sleep and daily rhythms is an integral part of management. Sleep deprivation, irregular shifts and unstable routines can precipitate episodes in vulnerable individuals; an effective treatment plan should therefore include sleep education and identification of individual prodromal signs.

Treatment of substance use disorders, anxiety, obesity and other comorbidities is essential. Antipsychotics and some mood stabilizers may affect weight, blood glucose and lipids, making metabolic monitoring necessary. Cardiovascular health should be considered during long term follow up.

Management during pregnancy requires specialist planning. Some medications carry important fetal risks, while abrupt treatment discontinuation may increase the risk of relapse. Decisions must weigh maternal and fetal risks of treatment and no treatment without applying simplistic rules.

Prognosis is heterogeneous. Many patients achieve prolonged periods of stability with appropriate treatment, whereas others experience frequent relapses, residual symptoms or persistent impairment. Early onset, numerous episodes, rapid cycling, mixed features, substance use and poor adherence are associated with a more complex course.

Symptomatic recovery does not always coincide with functional recovery. Cognition, relationships, work and quality of life may remain impaired even during euthymia, especially after repeated or prolonged episodes. Maintenance treatment should therefore aim for both mood stability and full functioning.

Complications

The most serious complication is suicide. Risk is elevated compared with the general population and requires repeated assessment during depression, mixed states, treatment changes and care transitions. No single instrument can predict individual suicidal behavior with certainty.

During mania, grandiosity, impulsivity and impaired judgment can lead to financial, legal, sexual and relational consequences. Uncontrolled spending, dangerous driving, risky sexual behavior and conflict can cause lasting harm even after the episode has remitted.

Psychosis may occur in severe phases and increase disorganization and risk. Delusions or hallucinations during mania indicate a manic episode; psychosis during depression changes severity and treatment strategy. Persistent psychosis outside affective phases requires differential diagnosis.

Problematic substance use is a common comorbidity and can worsen course, adherence, impulsivity and suicide risk. The relationship is bidirectional: substances may be used to modulate symptoms but may also precipitate or mimic affective episodes.

Repeated relapses can lead to occupational and educational instability, loss of income and relational difficulties. The depressive burden, in particular, can cause long periods of reduced productivity and isolation, while mania may lead to decisions with immediate financial consequences.

Sleep disturbances can become both a consequence and a driver of further destabilization. Persistent insomnia and circadian irregularity should therefore be treated as clinically relevant components of relapse risk.

Obesity, diabetes, dyslipidemia and cardiovascular disease are more common in many populations with bipolar disorder because of a combination of vulnerability, lifestyle, health inequalities and possible metabolic effects of treatment. Physical health monitoring is therefore part of psychiatric care.

An unplanned pregnancy during potentially teratogenic treatment can create a major clinical concern. Reproductive planning, information about risks and medication choice should be addressed in advance when relevant.

Nonadherence to treatment can promote relapse, especially when a patient stops medication after a period of wellbeing or because of adverse effects. Shared decision making, simplification of treatment and active management of adverse effects can reduce this risk.

Cognitive and residual symptoms may persist during euthymia and interfere with recovery. These deficits do not necessarily imply neurodegeneration, but they require assessment of medications, sleep, comorbidities and functioning in order to plan appropriate rehabilitative interventions.

Overall, prevention of complications requires correct diagnosis, phase appropriate treatment, maintenance, suicide monitoring, physical health care and continuity of care. Effective management is not limited to suppressing acute mania and depression, but aims to reduce the burden of the entire course of illness.

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