13.1 Mood disorders: depression and bipolar disorder

Mood disorders, like depression and bipolar disorder, can seriously impact daily life. They mess with your emotions, energy, and ability to function. These disorders involve complex interplays between brain chemistry, genetics, and life experiences.

Understanding mood disorders is crucial for grasping mental health. They're more than just feeling sad or moody. These conditions involve persistent changes in mood, thinking, and behavior that can last for weeks or months, significantly affecting a person's quality of life.

Major Depressive Disorder vs Bipolar Disorder

Symptoms and Diagnostic Criteria

• Major depressive disorder is characterized by persistent feelings of sadness, hopelessness, and loss of interest in activities, along with changes in sleep, appetite, and energy levels that significantly impair daily functioning for at least two weeks
  • Examples of symptoms include depressed mood, anhedonia (inability to feel pleasure), insomnia or hypersomnia, significant weight loss or gain, psychomotor agitation or retardation, fatigue, feelings of worthlessness or guilt, difficulty concentrating, and recurrent thoughts of death or suicide
• Bipolar disorder is characterized by alternating episodes of mania or hypomania (elevated or irritable mood, increased energy and activity, reduced need for sleep) and depression, with periods of normal mood in between
  • Manic episodes involve symptoms such as inflated self-esteem or grandiosity, decreased need for sleep, increased talkativeness or pressure to keep talking, flight of ideas or racing thoughts, distractibility, increased goal-directed activity or psychomotor agitation, and excessive involvement in risky activities (unrestrained buying sprees, sexual indiscretions)
  • Hypomanic episodes have similar symptoms to manic episodes but are less severe and do not cause significant impairment in functioning
• The DSM-5 outlines specific diagnostic criteria for major depressive disorder and bipolar disorder, including the number, duration, and severity of symptoms required for a diagnosis
  • For major depressive disorder, at least five symptoms must be present during the same two-week period, with at least one symptom being either depressed mood or loss of interest or pleasure
  • For bipolar I disorder, at least one manic episode is required, which may be preceded or followed by hypomanic or major depressive episodes
  • For bipolar II disorder, at least one hypomanic episode and one major depressive episode are required, but no full manic episodes

Classification and Subtypes

• Bipolar disorder is further classified into bipolar I disorder (at least one manic episode) and bipolar II disorder (hypomanic episodes and major depressive episodes, but no full manic episodes)
• Other subtypes of bipolar disorder include cyclothymic disorder (chronic fluctuations in mood that do not meet the full criteria for bipolar disorder or major depression) and rapid cycling bipolar disorder (four or more episodes of mania, hypomania, or depression within a 12-month period)
• Major depressive disorder can be further classified into subtypes such as melancholic depression (severe symptoms, including psychomotor retardation and early morning awakening), atypical depression (mood reactivity and increased appetite/sleep), and seasonal affective disorder (depression that occurs during specific seasons, usually winter)
  • Melancholic depression is characterized by a loss of pleasure in nearly all activities, a lack of reactivity to usually pleasurable stimuli, a depressed mood that is regularly worse in the morning, early morning awakening, psychomotor retardation or agitation, significant anorexia or weight loss, and excessive or inappropriate guilt
  • Atypical depression features mood reactivity (the ability to experience improved mood in response to positive events), significant weight gain or increase in appetite, hypersomnia, leaden paralysis (heavy, leaden feelings in arms or legs), and a long-standing pattern of interpersonal rejection sensitivity

Factors Contributing to Mood Disorders

Biological Factors

• Genetic predisposition plays a significant role in the development of mood disorders, with family studies, twin studies, and adoption studies providing evidence for the heritability of these conditions
  • First-degree relatives of individuals with major depressive disorder have a 2-4 times higher risk of developing the disorder compared to the general population
  • Twin studies have shown that the concordance rate for bipolar disorder is 40-70% for monozygotic twins and 5-10% for dizygotic twins, suggesting a strong genetic component
• Neurotransmitter imbalances, particularly involving serotonin, norepinephrine, and dopamine, are implicated in the pathophysiology of mood disorders
  • The monoamine hypothesis suggests that depression is caused by a deficiency of monoamine neurotransmitters (serotonin, norepinephrine, and dopamine) in the brain, while mania may be associated with an excess of these neurotransmitters
  • Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), work by increasing the availability of these neurotransmitters in the synaptic cleft
• Abnormalities in brain structure and function, such as reduced activity in the prefrontal cortex and hippocampus, have been observed in individuals with mood disorders
  • Neuroimaging studies have shown decreased gray matter volume and reduced activity in the prefrontal cortex, a region involved in emotion regulation and cognitive control, in individuals with depression
  • The hippocampus, a brain structure critical for learning and memory, has been found to be smaller in individuals with a history of depression, possibly due to the effects of chronic stress on neurogenesis and neuroplasticity

Psychological and Social Factors

• Negative cognitive biases, such as a tendency to focus on negative information, interpret ambiguous situations negatively, and attribute negative events to internal, stable, and global causes, can contribute to the development and maintenance of depressive symptoms
  • Beck's cognitive theory of depression proposes that negative schemas (core beliefs about oneself, the world, and the future) lead to automatic negative thoughts and cognitive distortions, which perpetuate depressed mood
• Learned helplessness, a phenomenon in which individuals believe they have no control over their environment and that their actions are futile, can lead to feelings of hopelessness and despair, increasing the risk of depression
  • The learned helplessness theory, developed by Martin Seligman, suggests that exposure to uncontrollable and inescapable stressors can lead to a sense of helplessness and passivity, which can generalize to other situations and contribute to depressive symptoms
• Maladaptive coping strategies, such as rumination (repetitively focusing on the causes, consequences, and symptoms of one's distress) and avoidance (avoiding challenging situations or emotions), can exacerbate and prolong depressive symptoms
  • Rumination has been shown to predict the onset, severity, and duration of depressive episodes, as it interferes with problem-solving and maintains negative thought patterns
  • Avoidance behaviors, such as social withdrawal and procrastination, can provide short-term relief but ultimately reinforce feelings of inadequacy and maintain depressive symptoms
• Stressful life events, such as the loss of a loved one, relationship breakups, financial difficulties, or chronic health problems, can trigger or exacerbate mood disorders in vulnerable individuals
  • The impact of stressful life events on mood disorders is influenced by factors such as the nature, severity, and duration of the stressor, as well as an individual's coping resources and social support
• Childhood trauma, including physical, sexual, or emotional abuse, neglect, or exposure to domestic violence, has been strongly associated with an increased risk of developing mood disorders later in life
  • Adverse childhood experiences can lead to long-lasting changes in brain structure and function, particularly in regions involved in stress response and emotion regulation, increasing vulnerability to mood disorders
• Lack of social support and feelings of loneliness or isolation can contribute to the development and maintenance of depressive symptoms
  • Social support acts as a buffer against the negative effects of stress, providing emotional comfort, practical assistance, and a sense of belonging
  • Conversely, social isolation and perceived lack of support can intensify feelings of hopelessness and worthlessness, exacerbating depressive symptoms
• Socioeconomic disadvantage, including poverty, unemployment, and low educational attainment, has been linked to a higher prevalence of mood disorders
  • Financial hardship and job insecurity can be significant sources of chronic stress, which can increase the risk of developing depressive or anxiety symptoms
  • Limited access to healthcare, social services, and educational opportunities in disadvantaged communities can also contribute to the onset and maintenance of mood disorders

Diathesis-Stress Model

• The diathesis-stress model suggests that mood disorders develop when a person with a genetic or psychological vulnerability (diathesis) experiences significant life stress
  • The diathesis can be conceptualized as a predisposition or sensitivity to developing a mood disorder, which may be influenced by factors such as family history, personality traits, or early life experiences
  • Stress acts as a trigger that activates or exacerbates the underlying vulnerability, leading to the onset or recurrence of depressive or manic symptoms
  • The model emphasizes the interaction between individual susceptibility and environmental factors in the development of mood disorders, recognizing that neither factor alone is sufficient to cause the disorder

Subtypes of Depression and Bipolar Disorder

Major Depressive Disorder Subtypes

• Melancholic depression is characterized by severe symptoms, including psychomotor retardation (slowed movements and speech), early morning awakening, and a lack of mood reactivity to positive events
  • Individuals with melancholic depression often experience a profound loss of pleasure (anhedonia) in nearly all activities, significant weight loss or decreased appetite, and excessive feelings of guilt or worthlessness
  • This subtype is associated with a stronger biological component and may respond better to antidepressant medication compared to other subtypes
• Atypical depression is characterized by mood reactivity (the ability to experience improved mood in response to positive events), increased appetite or weight gain, hypersomnia (sleeping too much), leaden paralysis (heavy, leaden feelings in arms or legs), and a long-standing pattern of interpersonal rejection sensitivity
  • Unlike melancholic depression, individuals with atypical depression may experience temporary improvement in mood when exposed to positive events or circumstances
  • This subtype is associated with a higher prevalence of comorbid anxiety disorders and may respond better to monoamine oxidase inhibitors (MAOIs) compared to other antidepressants
• Seasonal affective disorder (SAD) is a subtype of depression characterized by a seasonal pattern, with symptoms typically emerging during the fall and winter months and remitting during spring and summer
  • SAD is thought to be related to changes in circadian rhythms and reduced exposure to sunlight during the shorter days of winter
  • Treatment options for SAD include light therapy (exposure to bright, artificial light), antidepressant medication, and psychotherapy

Bipolar Disorder Subtypes and Specifiers

• Bipolar I disorder is characterized by the presence of at least one manic episode, which may be preceded or followed by hypomanic or major depressive episodes
  • Manic episodes are severe enough to cause significant impairment in social or occupational functioning and may require hospitalization to prevent harm to self or others
  • Some individuals with bipolar I disorder may experience mixed features, where manic and depressive symptoms occur simultaneously
• Bipolar II disorder involves the presence of at least one hypomanic episode and one major depressive episode, but no full manic episodes
  • Hypomanic episodes are less severe than manic episodes and do not cause significant impairment in functioning, although they may still be disruptive to daily life
  • Individuals with bipolar II disorder often experience more frequent and longer-lasting depressive episodes compared to hypomanic episodes
• Cyclothymic disorder is a milder form of bipolar disorder characterized by chronic fluctuations in mood that do not meet the full criteria for hypomanic or major depressive episodes
  • Individuals with cyclothymic disorder experience numerous periods of hypomanic and depressive symptoms over the course of at least two years, with no symptom-free period lasting longer than two months
  • Although the symptoms are less severe than those of bipolar I or II disorder, cyclothymic disorder can still cause significant distress and impairment in daily functioning
• Rapid cycling is a specifier that can be applied to bipolar I or II disorder, characterized by the presence of at least four mood episodes (manic, hypomanic, or depressive) within a 12-month period
  • Rapid cycling is associated with a more severe course of illness, greater functional impairment, and a higher risk of suicide attempts compared to non-rapid cycling bipolar disorder
  • Women are more likely to experience rapid cycling than men, and it may be associated with factors such as hypothyroidism, antidepressant use, and substance abuse

Treatment Options for Mood Disorders

Psychotherapy

• Cognitive-behavioral therapy (CBT) is a well-established treatment for mood disorders that focuses on identifying and modifying negative thought patterns and behaviors that contribute to depressive or manic symptoms
  • CBT helps individuals challenge and reframe distorted thoughts, such as all-or-nothing thinking, overgeneralization, and catastrophizing, which can perpetuate negative mood states
  • Behavioral activation, a component of CBT, encourages individuals to engage in pleasurable and meaningful activities to improve mood and counteract the tendency to withdraw or become inactive when depressed
• Interpersonal therapy (IPT) is a time-limited treatment that focuses on improving interpersonal relationships and addressing current life stressors that may be contributing to depressive symptoms
  • IPT helps individuals identify and modify problematic relationship patterns, such as role disputes, role transitions, and interpersonal deficits, which can maintain or exacerbate depressive symptoms
  • By enhancing communication skills, assertiveness, and social support, IPT aims to reduce depressive symptoms and improve overall functioning
• Other evidence-based psychotherapies for mood disorders include dialectical behavior therapy (DBT), which emphasizes mindfulness, emotion regulation, and distress tolerance skills, and family-focused therapy (FFT), which involves educating family members about the disorder and improving communication and problem-solving skills within the family system

Pharmacotherapy

• Antidepressant medications, such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), are commonly used to treat depressive symptoms in both major depressive disorder and bipolar disorder
  • SSRIs (fluoxetine, sertraline, paroxetine) work by blocking the reuptake of serotonin in the synaptic cleft, increasing its availability and enhancing serotonergic neurotransmission
  • SNRIs (venlafaxine, duloxetine) block the reuptake of both serotonin and norepinephrine, which may provide additional benefits for symptoms such as fatigue and concentration difficulties
  • TCAs (amitriptyline, imipramine) are an older class of antidepressants that block the reuptake of serotonin and norepinephrine, but also have significant anticholinergic and antihistaminic side effects
• Mood stabilizers, such as lithium and anticonvulsants (valproic acid, lamotrigine), are the primary treatment for bipolar disorder, used to prevent or reduce the frequency and severity of manic and depressive episodes
  • Lithium is a first-line treatment for bipolar I disorder, with proven efficacy in reducing the risk of manic and depressive relapses and decreasing suicidal behavior
  • Valproic acid (divalproex) is an anticonvulsant that has mood-stabilizing properties and is particularly effective in treating acute manic episodes and preventing relapse
  • Lamotrigine, another anticonvulsant, has been shown to be effective in preventing depressive episodes in bipolar disorder, but may not be as effective for preventing manic episodes
• Atypical antipsychotics (quetiapine, olanzapine, risperidone) are sometimes used as adjunctive treatments for mood disorders, particularly in cases of treatment-resistant depression or bipolar disorder with psychotic features
  • These medications work by modulating dopamine and serotonin signaling in the brain, and may help to reduce symptoms such as agitation, irritability, and psychosis
  • However, atypical antipsychotics can also have significant side effects, including weight gain, metabolic disturbances, and extrapyramidal symptoms (movement disorders)

Other Treatment Options

• Electroconvulsive therapy (ECT) is a highly effective treatment for severe, treatment-resistant depression and bipolar disorder, particularly when there is a high risk of suicide or when rapid symptom relief is necessary
  • ECT involves the induction of a brief, controlled seizure under general anesthesia, which is thought to alter brain chemistry and improve mood symptoms
  • Although ECT has historically been associated with side effects such as memory loss and confusion, modern techniques (such as unilateral electrode placement and brief pulse stimulation) have significantly reduced these risks
• Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that uses magnetic fields to stimulate specific areas of the brain, such as the dorsolateral prefrontal cortex, which is involved in mood regulation
  • TMS has been approved by the FDA for the treatment of treatment-resistant depression and has shown promise in reducing depressive symptoms with fewer side effects compared to medication or ECT
  • However, TMS may not be as effective for severe or psychotic depression, and its long-term efficacy and optimal treatment parameters are still under investigation
• Light therapy, also known as phototherapy, is a first-line treatment for seasonal affective disorder (SAD) that involves daily exposure to bright, artificial light during the fall and winter months
  • Light therapy is thought to work by resynchronizing circadian rhythms and increasing serotonin production in the brain, which can help to alleviate depressive symptoms
  • Typical light therapy involves sitting in front of a light box that emits 10,000 lux of cool-white fluorescent light for 30-60 minutes per day, usually in the morning