PS371: Mood Disorders II

Etiology: mood disorders

• No single line of evidence accounts for full range of expression of unipolar (depressive) disorder

• Cause of bipolar disorder unknown

Genetic contribution: unipolar

• First-degree relatives of people with MDD at increased risk for depression … no dominant gene

• ≈ 46% concordance rate among identical twins

  • (20% among fraternal twins)

Genetic contribution: bipolar

• ≈40% concordance rate among identical twins

  • (5% to 10% among fraternal twins)

• Most frequent mood d/o among relatives = depressive disorder

Neurotransmitter effects

• Changes in brain, body chemistry at least coincidental with depression

• Functional imaging supports hypothesis that serotonin regulation impaired

• Bipolar: low serotonin may be important but not necessarily specific risk for bipolar

• Too simplistic to explain the full range

• Reflect importance of biological contributions

• Changes in brain and body chemistry are coincidental with the onset of depressive disorders, does not mean they cause depression

• Depression and chemical abnormalities in certain brain regions and neurotransmitter systems (norepinephrine, dopamine, serotonin)

• Low levels of serotonin may be involved in the etiology of unipolar diseases

  • Reduced inhibition, impulsivity, aggression, overreacting in situations

Psychological factors: behavioral

• Unipolar depression result of significant changes in reward/punishment people receive

• Fewer constructive behaviors lead to depression

Psychological factors: cognitive

• Cognitive vulnerability (A. Beck)

• Depression result of four interrelated factors:

  • Maladaptive attitudes (self-defeating, most likely developed during childhood, tendency to make the worst of anything)

  • Negative thought processes (i.e., cognitive triad)

    • People who are depressed tend to make errors in thinking about themselves, ongoing experiences, and about future)

    • Helplessness, negative things will continue because of one’s personal defects

  • Errors in thinking (i.e., negative schema)

    • Negative conclusions based on limited evidence

    • Minimize significance of positive, magnify significance of negative (overgeneralization)

  • Automated thought processes

    • Outside of awareness

Attribution theory

• People motivated to assign causes to actions, behavior

• Causal attributions influence both cognitive appraisal and future behavior

Stressful life events (LE)

• Most report some significant LE before mood disorder

• LE may enhance general risk, predict course

• LE not specific risk factor, may not produce any disorder

• 20% to 50% who experience severe LE become depressed

• Consider context in which LE occurs and meaning of event

• Bipolar disorder:

  • High number of LE increases relapse risk ≈ 5 times

  • (Negative) LE predict symptoms, course, outcome

Medication therapies: depression

• Tricyclic antidepressants (e.g., amitriptyline, imipramine [Tofranil])

• Second-generation antidepressants:

• Selective serotonin reuptake inhibitors (SSRI) (e.g., fluoxetine [Prozac], sertraline [Zoloft])

  • Increases serotonin available at the receptor sites

  • Milder

  • Sexual dysfunction

• Atypical (e.g., buproprion [Wellbutrin], duloxetine [Cymbalta])

• May take 10+ days to demonstrate effect

  • Often become discouraged because of this

• Side effects: vary … benign to quite severe

  • Reduce probability of returning symptoms

  • Encouraged to stay on medications for 6 months or longer

B. Weiner

• Three-dimensional model

  • stability … locus of control … controllability

    • Attributions that relate to mood disorder

    • Stability: expectations about the future

    • Locus of control: where the power or influence is for experiences, internal

    • Controllability: degree to which one might persist in the face of challenges

M. Seligman

• Learned helplessness

  • attribution that have no control over stress in one’s life

  • depressive attribution stable, internal, and global

    • Tends to extend across wide variety of experience

    • Attributions likely to cause depression if they also produce hopelessness

P. Lewinsohn

• Positive rewards decrease over time for some people

• Leads to performing few constructive behaviors

• Ultimately spiral toward depression

Medication therapies: bipolar

Lithium carbonate

• Effective for controlling manic and depressive symptoms

• Maintenance treatment helps prevent relapse

• Side effects: high plasma concentrations which can be poisonous

• Up to 70% relapse even with maintenance dose

Adherence problems because

• Symptoms gone → “don’t need anymore”

• Annoyed by side effects of Rx

• Miss the fun of manic highs

• Continue to experience functional deficits

• 30-40% patients not helped

Implications: may increase likelihood of relapse by >20 times

Medication therapies: bipolar (2)

In addition to lithium

• Other mood stabilizers

  • Divalproex (Depakote), carbamazepine (Tegretol), quetiaping (Seroquel)

• Antipsychotic medications

• Concern that antidepressants—when only the medication prescribed—may kindle manic symptoms in patients with bipolar mood disorder

• Mood stabilizer usage increased

• May enhance overall mood as to kindle or trigger onset of manic symptoms

• May reverse outcome of such treatment

Electroconvulsive therapy

• Relief for severe/intractable mood disorders

• For those with therapies that do not work

• Relatively safe—over couple of months

• Side effects: short term memory loss, confusion

• Treatment term: psychiatrist, anesthesiologist, nurse

  • Short-acting general anesthesia

  • Shock to one side … 200 to 450 volts … 0.5 to 4 seconds

  • Mild convulsions … few seconds to 2 minutes

  • Recovery within 20 min … little discomfort

Other mechanical treatments

• Vagus nerve stimulation

• Transcranial magnetic stimulation

• Deep brain stimulation

• These + ECT suggest that direct stimulation to the brain may provide symptom relief for individuals with severe depression who don’t respond to other (“traditional”) forms of therapy

• Not FDA approved, helps those that do not respond to ECT

Psychotherapy: depression cognitive therapy

• Beck

  • Examine, monitor thought processes; recognize “depressive errors”

  • Challenge / correcting cognitive errors … substituting less depressing / more realistic thoughts, self-appraisals

  • Later, underlying negative cognitive schemas targeted

  • Generally time limited … 10 to 20 weekly sessions

  • Carefully examine and monitor their thought processes while experiencing dysfunction

  • Recognize depressive errors in thinking

  • Therapist and client work together to correct errors

  • Work towards redevelopment of positive social skills, focus on core interpersonal interactions

  • Structure activities that put fun back into their lives

Psychotherapy: depression interpersonal therapy

• M. Weismann, G. Klerman

  • Focus on problems in relationships

  • Goals:

  • Identify life events / stressors that that lead to depression

  • Focus on one or more of four interpersonal domains: loss,          role dispute, role transition, deficits in social skills

  • Generally 10 to 20 weekly sessions

Psychotherapy: bipolar disorder

• Primary focus: increasing knowledge, adherence … reducing risk of relapse

• Stress inoculation, Psychoeducation

• Teach / help patients / family:

  • how to recognize, avoid stressors

  • how to cope with what they can’t avoid

  • accept disorder

  • identify adjustments to reduce stress

  • recognize symptom changes that may require change in drug therapy

• Most useful when combined with well managed drug therapy regimen

• Psychoeducational: recognize when there is a change in symptoms or change in medication, involve efforts to watch for signs that symptoms are getting out of control

What works best? For whom?

• Psychotherapy increase long range social function and protect against relapse

• Drug therapy may yield more rapid effects

• Psychotherapy enhances coping capacity

• Depression with melancholia: drug therapy or ECT may be best

• Antidepressant vs. CBT

  • Offer evidence of different patterns of response in cortical & sub-cortical brain regions as a function of treatment

• Combined: Overall, drug therapy + psychotherapy likely superior to either alone

Suicide

• Attempts: Female > male

• Completion: Male > female

• Males use more lethal means

• Guns used in nearly 65% male suicides, 40% female suicides in US

Suicide risk factors

• Stressful events / situations

  • Both immediate and long-term stresses can be risk factors for suicide

• Mood and thought changes

  • Many suicide attempts preceded by changes in mood, shifts in patterns of thinking

• Alcohol and other substance use

  • > 70% of those who attempt suicide drink alcohol just prior to act; > 25% legally drunk at time

• Mental health

  • Many suicide attempters have current disorder

• Modeling: Social contagion effect

  • Many try after observing / reading about someone (family, friend, celebrity) who has done so