Overview of Bipolar Disorders

Bipolar disorders, also known as bipolar mood disorders, are a heterogeneous group of psychiatric conditions characterized by episodic mood fluctuations that alternate between phases of euphoria or elevated mood (mania or hypomania) and phases of depression. The course is usually chronic and recurrent, with frequent periods of psychological well-being between episodes. The severity, duration, and alternation of symptoms vary significantly across subtypes.

The etiology of bipolar disorders is complex and multifactorial. The main identified direct causes include:

• Genetic vulnerability: the risk of developing a bipolar disorder is increased among first-degree relatives of affected individuals, with heritability estimates exceeding 70% in monozygotic twins.
• Neurotransmitter imbalances: dysregulations in the dopamine, serotonin, norepinephrine, and glutamate systems are frequently associated with both manic and depressive phases.
• Neuroendocrine dysfunctions: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, particularly hypercortisolemia during depressive episodes.
• Neuroanatomical and functional alterations: neuroimaging studies reveal hypoactivity of the dorsolateral prefrontal cortex and hyperactivity of the amygdala and limbic structures.

Several factors may increase the likelihood of developing bipolar disorder, though they are not direct causes:

• Family history of mood disorders
• Stressful life events, especially in childhood (abuse, bereavement, parental separation)
• Chronic sleep disorders
• Use of psychoactive substances (e.g., cannabis, cocaine, stimulants)
• Personality disorders, particularly those of cluster B

The pathophysiology of bipolar disorders remains under investigation, though several mechanisms have been implicated. During the manic phase, there is increased dopaminergic activity, often accompanied by glutamatergic dysregulation and heightened sensitivity to environmental stimuli. In the depressive phase, monoaminergic hypofunction, reduced levels of BDNF (Brain-Derived Neurotrophic Factor), and HPA axis hyperactivation are observed. Transitions between phases appear to be linked to circadian rhythm instability and impaired neuroplasticity.

Bipolar disorders present with a wide range of symptoms. Manic episodes are characterized by elevated mood, pressured speech, decreased need for sleep, disinhibition, racing thoughts, and—if severe—psychotic symptoms. Hypomanic episodes share similar features but are less intense and do not cause marked functional impairment. Depressive episodes involve low mood, anhedonia, sleep and appetite disturbances, fatigue, suicidal ideation, and cognitive symptoms. In some cases, mixed episodes may occur, with coexisting depressive and manic symptoms.

The cycling may be slow or rapid (≥4 episodes per year), and in the most severe cases, even daily. Rapid-cycling forms are often more difficult to treat.

The diagnosis is clinical and based on DSM-5 criteria, which classify bipolar disorders into:

• Bipolar I Disorder: at least one manic episode, possibly accompanied by depressive or mixed episodes.
• Bipolar II Disorder: at least one hypomanic and one major depressive episode, with no history of manic episodes.
• Cyclothymic Disorder: numerous subthreshold hypomanic and depressive periods over at least two years.
• Other Specified or Unspecified Bipolar and Related Disorders: clinical forms that do not meet the criteria of the previous categories but clearly exhibit bipolar features.

Differential diagnosis is essential and must consider unipolar mood disorders, personality disorders, psychotic disorders, and substance abuse. Helpful tools include the Mood Disorder Questionnaire (MDQ), the Hypomania Checklist (HCL-32), and the MOODS-SR.

Treatment of bipolar disorders is complex and requires an integrated approach. Manic and hypomanic phases are treated with mood stabilizers (e.g., lithium, valproate, carbamazepine) and atypical antipsychotics, while depressive phases may require antidepressants, which must be used with caution due to the risk of inducing mania. Pharmacological therapy should be accompanied by psychotherapy (e.g., cognitive-behavioral therapy, psychoeducation, family therapy).

Prognosis is highly variable. Poor prognostic factors include rapid cycling, comorbid substance abuse, early onset, and poor treatment adherence. However, with accurate diagnosis and appropriate treatment, good clinical control and improved quality of life are achievable.

Main complications of bipolar disorders include:

• Suicide: increased risk, especially during depressive and mixed states
• Chronic functional disability: occupational, social, and relational
• Psychiatric comorbidities: anxiety, personality disorders, substance use
• Iatrogenic effects: from long-term use of mood stabilizers and antipsychotics

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