Chapter 10:Bipolar Disorders

David J. Miklowitz

Sheri L. Johnson

Diagnosis: Diagnostic Features

• Insomnia or hypersomnia• Psychomotor agitation or

retardation, • Changes in weight or appetite• Loss of energy

• Difficulty concentrating or making decisions

• Feelings of worthlessness or guilt

• Suicidal ideation or behavior

Severe changes in mood, thinking, and behavior, from extreme highs to lows Distinctive “episodes” lasting a few days to a year or more.

Depressive episode: ≥ Five of the following for 2 weeks or longer with significant distress and/or decline in functioningIntense sadness and/or loss of interest must be present

Diagnosis: Manic and Hypomanic Episodes

Manic episode: Notably different elated, expansive, or irritable mood with ≥ 3 (≥ 4 if irritable) of the following lasting for at least 1 week and causing significant distress or impairment:

Hypomanic episode: Same symptom criteria, but…Shorter (4 days instead of 1 week)Not severe enough to cause marked impairment in

functioning (no psychotic features and no hospitalization)

Inflated self-esteem (grandiosity) Decreased need for sleep Racing thoughts or flight of ideas Rapid or pressured speech

Reckless and impulsive behavior Enhanced energy Increased goal-directed activity Distractibility

Diagnosis: Diagnostic Criteria

Bipolar I (BD-I)Criteria met for at least 1 manic episodeNot better explained by a schizophrenia spectrum

disorder (e.g., schizophrenia)

Bipolar II (BD-II)Criteria met for at least one hypomanic episode and one

depressive episodeCriteria never met for manic episodeNot better explained by schizophrenia spectrum disorder

Diagnosis: Related Conditions

Bipolar disorder not elsewhere classifiedPatients with brief and recurrent manic or hypomanic

phases that fall short of the duration criteria

Cyclothymia2 or more years of switching between hypomanic and

depressive symptoms that do not meet the full DSM-5 criteria for a hypomanic or a major depressive episode

Diagnosis: Some Potential Specifiers

With mixed features: Features of depressive episode present during manic episode or vice versaMore debilitating course of illness, earlier onset, and

greater comorbidity with anxiety and substance use disorders

Rapid cycling: Four or more episodes of depression, mania, or hypomania in 1 year10%–20% of cases, more common in bipolar II and women

Diagnosis: Changes in DSM-5

Increased activity is now a cardinal (Criterion A) symptomHelps diagnose people who can describe behavior well

but not internal experience

Mixed episode specifier no longer requires meeting full criteria for mania and depression simultaneously

Diagnosis: Comorbid Disorders

Virtually all bipolar patients have a lifetime history of other psychiatric disordersAnxiety disorders (62.9%)ADHD and/or oppositional defiant disorder (44.8%) Substance use disorders (36.8%)

In children, comorbidity of BD with ADHD is between 60% and 90%

Symptoms: Presentation Differences

Patients with bipolar II disorder spend the majority of their ill weeks depressed, not hypomanic (ratio of 37 to 1)Bipolar I ratio is about 3:1

80% of youths show irritability and grandiosity, whereas 70% have elated mood, decreased need for sleep, or racing thoughtsLess frequent symptoms: hypersexuality and psychotic

symptoms

Symptoms: Suicidality

Among those hospitalized for BD, 15x greater risk for completed suicide than the general population 4x greater risk than patients with major depressive disorder

Risk factors:

Comorbid alcohol or substance abuse

Younger age Recent illness onsetMale genderPrior suicide attempts

Family history of suicideRapid cycling course Social isolation Anxious moodRecent severe depression“Impulsive aggression”

Prognosis

Majority of patients with BD experience significant impairment in work, social, and family functioning during and after illness episodes One third work full time outside of the home More than half unable to work or work only in sheltered

settings Negative predictors: subsyndromal depressive symptoms

following a manic episode and cognitive dysfunction

1 in 10 BD-II patients eventually develop a full manic or mixed episode and are then diagnosed with BD-I

Epidemiology

1% meet lifetime criteria for BD-I; 1.1% for BD-II2.4% meet criteria for subthreshold BD; 4.2% cyclothymia

Mean age at onset 18.4 years BD-I20.0 years BD-II21.9 years subthreshold BDBetween 50% and 67% of BD-I and BD-II have onset before age

18• 15% and 28% before age 13

In community studies, 25% to -33% of bipolar I patients have unipolar mania

Etiology: Expressed Emotion

Expressed emotion attitudes (EE) - criticism, hostility, or emotional overinvolvement

Affective negativity (AE): Criticism, hostility, or guilt induction

BD patients who return home to high EE or AE families are at ~94% risk for relapse within 9 months~17% returning to low EE and AE families

Etiology: Unipolar Depression Overlap

Predictors of recurrent and severe symptoms in both disorders include low social support, family EE, and neuroticism

Negative life events equally predictive of relapse

Heritability for unipolar depression and mania modestly correlated, but 71% of genetic liability to mania is distinct from depression

Variables that influence the course of unipolar depression also influence BD depression

Etiology: Stress

BD patients with high levels of stressful life events are at 4.5x greater risk for relapse within 2 years

Number of prior episodes of illness does not interact with life events stress in predicting recurrencesContrary to kindling model

Patients with severe early adversity (e.g., parental neglect or sexual/physical abuse) report less stress prior to illness recurrences and earlier age at onsetSupports stress sensitization model

Etiology: Reward Sensitivity and Goal Setting

People with a history of mania describe themselves as more likely to react with strong emotions to reward cues (reward sensitive)

Elevated reward sensitivity predicts BD onset and a more severe course of mania among BD-I patients

Goal-attainment-type life events predict increases in manic symptoms but not depressive symptoms

Highly ambitious life goals/goal setting associated with more severe course of mania and onset of BD

Etiology: Brain Systems

Abnormally strong activity in the dopaminergic pathways involved in reward sensitivityNucleus accumbens and the ventral tegmentum

Reduced connectivity between limbic (emotion-related) brain regions and prefrontal regions May explain why patients with bipolar disorder have

unstable mood and hyperreactivity to eventsDiminished activity of the PFC might interfere with the

ability to inhibit emotions and to conduct effective planning and goal pursuit

Biological Etiology: Heritability

Genetic studies show bipolar disorder is among the most heritable of disorders. Heritability estimates from twin studies are as high as .85 to .93Risk of bipolar disorder among first-degree relatives

between 5% and 12% Risk of all forms of mood disorder between 20% and 25%

Monozygotic twins of BD-I patients are at an increased risk for schizophrenia (13.6%) and mania (36.4%)

Biological Etiology: Neurotransmitters

Research emphasis has shifted from absolute levels of neurotransmitters to the overall functioning of systemsNeural plasticity and disturbed intracellular signaling

cascades rather than the amount of dopamine or serotonin

Dopamine theory: Dopamine function is enhanced during mania and diminished during depressionDopamine precursors, such as l-dopa, can trigger mania

Mood disorders generally associated with decreased serotonin receptor sensitivity

Treatment- Lithium Medication and Nonadherence

Lithium: A mood stabilizer60% to 70% improve on lithium during a manic episode Also helps prevent relapseSignificant side effects: sedation, weight gain, tremors of the

hands, stomach irritation, thirst, and kidney problems

40% to 60% of patients are fully or partially nonadherent with stabilizer regimens in the year after a manic episode In community, patients take lithium for an average of only 2 to 3

months Rapid discontinuation of lithium places patients at higher risk for

recurrence and suicide

Treatment: Pharmacological: Anticonvulsants/Mood Stabilizers

Divalproex sodium (Depakote) is as effective as lithium in controlling manic episodes Generally more benign side effects: stomach pain,

nausea, weight gain, elevated liver enzymes, and lowering of blood platelet counts

Combination therapy and lithium alone both more effective than divalproex alone in preventing relapse

Other anticonvulsants/mood stabilizersCarbamazepine (Tegretol), lamotrigine (Lamictal), and

oxcarbazepine (Trileptal)

Treatment: Pharmacological: Suicide Prevention

Patients treated with lithium, antipsychotics, or antidepressants (especially in combination regimens) have lower suicide rate

Lithium was more effective than divalproex sodium in reducing suicide attempts and completions

Treatment: Pharmacological Other Medications

Olanzapine (atypical antipsychotic medication)Prevention of recurrences of mania or mixed episodes is

as good or better than lithium or divalproex Concerns about side effects: weight gain and metabolic

syndrome Quetiapine, risperidone, aripiprazole, and ziprasidone are

alternatives with lower side-effect risk

Not clear that combinations of SSRI and mood stabilizer are effective for treating BD depressionRisk of more frequent mood cycles

Treatment: Group Psychotherapy

Structured group psychoeducation Education about BD, relapse, and importance of medicationAfter 2 years, relapse is 67% vs. 92% in controls, and fewer

hospitalizedMore likely to maintain lithium levels within the therapeutic rangeGroup treatment is most cost-effective form of psychotherapy

Integrated CBT group treatment for bipolar adults with comorbid substance dependenceFocuses on the overlap between the cognitions and behaviors of

both conditions during recovery and relapseAbout half as many days of substance use as those receiving only

drug counseling

Treatment: Individual Psychotherapy

Interpersonal and Social-Rhythm Therapy (IPSRT)Stabilize social rhythms and resolve interpersonal problems that

precede episodes Track daily routines and sleep/wake cycles and identify events that

change those routinesDelays recurrence if begun during acute phase

Individual psychoeducational treatment and medication7 to 12 sessions30% reduction in mania relapse, longer time before relapse, and

enhanced social functioning

Treatment: Family Focused Treatment (FFT)

Group therapy with patient and familyGoal: Reduce high EE attitudes and enhance

communicationPsychoeducation about BD and develop relapse prevention

drillCommunication-enhancement trainingProblem-solving skills training

Efficacy vs. standard care over 2 yearsLess likely to relapse (17% vs. 52%)Greater improvements over time in depression, manic

symptoms, and better adherence to medications

Treatment: Psychotherapy Efficacy Comparison (STEP-BD)

30 sessions of IPSRT, FFT, or CBT over 9 months for BD-I and BD-II starting in depressed episodeControl condition was three sessions of psychoeducation;

medication prescribed in all conditionsTreatment conditions more likely to recover rapidly from

depression, remain well, better overall functioning, relationship functioning, and life satisfaction

One-year rates of recovery same across intensive therapy groups