Bipolar I Disorder

Bipolar I disorder is a mood disorder characterized by the occurrence of at least one manic episode during the patient's lifetime, regardless of the presence of major depressive episodes. It is the most representative and classic form of the bipolar spectrum, formerly known as “manic-depressive illness.”

The manic episode, which is the cornerstone of the diagnosis, is defined by a pathological alteration of mood, either euphoric or irritable, accompanied by heightened psychomotor activity and mental hyperactivation, significantly impairing the individual’s overall functioning. In most cases, the disorder follows an episodic and cyclical course, alternating between manic phases, depressive phases, and periods of more or less complete remission.

Bipolar I disorder differs from Bipolar II disorder in the severity of mood elevation and, most importantly, in the presence of full-blown manic episodes, which are absent in Bipolar II.

Etiology and Risk Factors

The etiology of Bipolar I disorder is multifactorial and complex, involving the interaction between genetic predisposition and environmental factors. Although no single cause has been identified, several contributing elements are recognized:

• Genetic factors: Family history is one of the primary determinants. The risk of developing the disorder is approximately ten times higher in first-degree relatives of affected individuals compared to the general population.
• Neurochemical alterations: Imbalances in neurotransmitter systems—particularly dopamine, serotonin, and norepinephrine—are implicated in the development of manic and depressive symptoms.
• Neuroendocrine dysfunctions: Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and altered cortisol secretion appear to play a relevant role.
• Neuroplasticity changes: Reduced levels of brain-derived neurotrophic factor (BDNF) and epigenetic modifications have been associated with disease progression.
• Circadian rhythm disturbances: Misalignments in sleep-wake cycles and daily biological oscillations are common among bipolar patients and may act as both predisposing and triggering factors.

Although not direct causes, several factors increase the likelihood of developing Bipolar I disorder:

• Family history of bipolar disorder or other mood disorders
• Substance abuse, particularly stimulants such as cocaine, amphetamines, or cannabis
• Stressful life events, especially severe or prolonged emotional trauma during childhood or adolescence
• Chronic sleep disorders
• Affective-labile personality or impulsive traits

These factors do not directly cause the disorder but may trigger onset in predisposed individuals or promote relapses in those already diagnosed.

Clinical Manifestations and Diagnosis

Bipolar I disorder presents with clearly defined clinical episodes alternating with periods of more or less complete remission. The manic episode is the essential diagnostic element and is characterized by:

• Abnormally elevated, expansive, or irritable mood, lasting at least one week, present most of the day, and observable by others
• Increased goal-directed activity (work, social, or sexual) or psychomotor agitation
• Inflated self-esteem or grandiosity
• Decreased need for sleep (e.g., feeling rested after only a few hours of sleep)
• Excessive talkativeness, flight of ideas, distractibility
• Impulsive and risky behaviors, such as excessive spending, reckless driving, or inappropriate sexual conduct

When mood is predominantly irritable, at least four of the listed symptoms are required. The manic episode may begin abruptly and peak rapidly over a few days, lasting from several weeks to several months.

In addition to manic episodes, about 60–70% of patients also experience major depressive episodes, with symptoms such as profound sadness, anhedonia, sleep and appetite disturbances, psychomotor retardation, guilt, and suicidal ideation.

In the most severe cases, psychotic symptoms may occur, including mood-congruent or mood-incongruent delusions, and such intense excitation as to require emergency hospitalization.

The diagnosis falls under psychiatric competence and is based on the DSM-5 criteria. The patient must have experienced at least one manic episode during their lifetime, lasting at least seven days (or less if hospitalization was required), with marked impairment in occupational, social, or familial functioning.

Diagnostic criteria include:

• At least one manic episode: The full criteria for a manic episode must be met, defined by abnormally elevated, expansive, or irritable mood lasting at least one week, associated with at least three specific symptoms (four if mood is only irritable).
• Functional impact: The episode must cause marked impairment in occupational, social, or relational functioning, or require hospitalization, or be associated with psychotic symptoms.
• Exclusion of other conditions: The episode must not be attributable to the physiological effects of a substance (e.g., drugs or medications) or a general medical condition (e.g., endocrine disorders, brain injury).
• Exclusion of alternative mood disorder diagnoses: The diagnosis does not apply if the only lifetime episode was hypomanic or mixed without any full manic episode (in which case Bipolar II or Cyclothymic Disorder should be considered).

The diagnostic process includes:

• Comprehensive clinical interview with a detailed history of symptoms, temporal course, and triggering factors
• Structured psychopathological assessment using scales such as the Young Mania Rating Scale (YMRS)
• Exclusion of organic or substance-induced causes via laboratory tests, toxicological screening, and possibly neuroimaging
• Family involvement, often essential for reconstructing patient behavior during manic phases

In first-onset patients, diagnosis may be challenging: often, the depressive episode precedes the manic one, initially leading to a diagnosis of unipolar depression. Therefore, a careful and dynamic longitudinal assessment is essential.

Treatment, Prognosis, and Complications

The treatment of Bipolar I disorder requires a long-term strategy addressing both the acute phase and relapse prevention. It is based on:

• Mood stabilizers: Lithium is the gold-standard treatment, effective in both manic phases and long-term prevention. Alternatives or adjuncts include valproic acid, carbamazepine, and lamotrigine (particularly effective in depressive phases).
• Atypical antipsychotics: Olanzapine, quetiapine, aripiprazole, and risperidone are commonly used, especially in acute phases or in the presence of psychotic symptoms.
• Antidepressants: These must be used with extreme caution and always in combination with a mood stabilizer, due to the risk of triggering manic switches.
• Psychotherapy: Crucial for psychoeducation, early symptom recognition, and stress management. The most effective approaches include cognitive-behavioral therapy and interpersonal therapy.
• Lifestyle modifications: Regulation of sleep patterns, avoidance of stimulants or psychotropic substances, and regular physical activity.

In more severe cases, hospitalization may be necessary, sometimes under involuntary commitment (IC). Therapeutic adherence is a major challenge, especially in patients who subjectively experience euphoria and well-being during manic phases.

The course of the disorder is highly variable: some patients enjoy long remission periods, while others experience frequent relapses with incomplete recovery. Early onset, episode frequency, and psychotic symptoms are associated with a poorer prognosis.

Response to treatment can be favorable when interventions are timely and personalized, but lifelong therapy is often required. Adherence to treatment is essential to prevent recurrences and reduce the disorder's functional impact.

The main complications of Bipolar I disorder include:

• Suicide: High risk, particularly during depressive phases or mood transitions
• Substance abuse: A common comorbidity that worsens prognosis
• Socio-occupational impairment: Difficulty maintaining stable relationships or employment
• Cognitive decline: Some patients experience long-term memory deficits and executive dysfunctions

Early recognition and management of complications are crucial for improving outcomes and quality of life.

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