Ten Leading Causes of Ten Leading Causes of Disability in the WorldDisability in the World

Type of Disability Cost (in DALYs)

Cumulative %

of Cost

Unipolar major depression 42,972 10.3

Tuberculosis 19,673 14.9

Road traffic accidents 19,625 19.6

Alcohol use 14,848 23.2

Self-inflicted injuries 14,645 26.7

Manic-depressive (bipolar) illness 13,189 29.8

War 13,134 32.9

Violence 12,955 36.0

Schizophrenia 12,542 39.0

Iron deficiency anemia 12,511 42.0

Episode Disorder

*Major depression episode *Major depression disorder

*Major depression episode+ *Bipolar disorder, Type I manic/mixed episode

*Manic/mixed episode *Bipolar disorder, Type I

*Major depressive episode+ *Bipolar disorder, Type II hypomanic episode

*Chronic subsyndromal *Dysthymic Disorder depression

*Chronic fluctuations between subsyndromal *Cyclothymic disorder depression & hypomania

““If I had __________, IIf I had __________, I’’d d be depressed to.be depressed to.””

DefinitionsDefinitions

• Mood - a person’s sustained emotional state

• Affect – the outward manifestation of a person’s feelings, tone, or mood

Major DepressionMajor Depression

• Syndromal classification with disturbances of mood, neurovegetative and cognitive functioning

Major DepressionMajor Depression

At least 5 of the following symptoms present for at least 2 weeks (either #1 or #2 must be present):

1) depressed mood

2) anhedonia – loss of interest or pleasure

3) change in appetite

4) sleep disturbance

Major DepressionMajor Depression

5) psychomotor retardation or agitation

6) decreased energy

7) feeling of worthlessness or inappropriate guilt

8) diminished ability to think or concentrate

9) recurrent thoughts of death or suicidal ideation

Major DepressionMajor Depression

• Symptoms cause marked distress and/or impairment in social or occupational functioning.

• No evidence of medical or substance-induced etiology for the patient’s symptoms.

• Symptoms are not due to a normal reaction to the death of a loved one.

Bereavement and Bereavement and Late Life DepressionLate Life Depression

• 25 – 35% of widows/widowers meet diagnostic criteria for major depressive disorder at 2 months.

• ~15% of widows/widowers meet diagnostic criteria for major depressive disorder at one year.

• This figure remains stable throughout the second year.

Subtypes of DepressionSubtypes of Depression

• AtypicalReverse neurovegetative symptomsMood reactivityHypersensitivity to rejectionMAO-I’s and SSRI’s are more

effective treatments

Subtypes of DepressionSubtypes of Depression

Psychotic (~10% of all MDD)

• Delusions common, may have hallucinations

• Delusions usually mood congruent

• Combined antidepressant and antipsychotic therapy or ECT is necessary

Subtypes of DepressionSubtypes of Depression

Melancholic

• No mood reactivity

• Anhedonia

• Prominent neurovegetative disturbance

• More likely to respond to biological treatments

Subtypes of DepressionSubtypes of Depression

Seasonal

• Onset in Fall, remission in Spring

• Hypersomnia is typical

• Less responsive to medications

• A.M. light therapy (>2,500 lux) is effective

Subtypes of DepressionSubtypes of Depression

Catatonic

• Motoric immobility (catalepsy)

• Mutism

• Ecolalia or echopraxia

EpidemiologyEpidemiology

Point prevalence 6 – 8% in women 3 – 4% in men

Lifetime prevalence 20% in women 10% in men

EpidemiologyEpidemiology

Age of Onset Throughout the life cycle, typically

from the mid 20’s through the 50’s with a peak age of onset in the mid 30’s

EpidemiologyEpidemiology

GeneticsMore prevalent in first degree relatives

3-5x the general population riskConcordance is greater in monozygotic than

dizygotic twinsIncreased prevalence of alcohol dependence

in relatives

EtiologyEtiology

Original, clearly over simplistic theories regarding norepinephrine and serotonin

Deficiency states depression States of excess mania

Problems with initial theoriesProblems with initial theories

Inconsistent findings when studying measures of these systems: MHPG (3 methoxy 4 hydroxyphenolglycol) and 5HIAA (5 hydroxy indoleacetic acid) in the urine and CSF.

Treatments block monoamine uptake acutely, however the positive effects occur in 2-4 weeks.

Receptor theory more usefulReceptor theory more useful

Antidepressant treatment causes a down regulation in central adrenergic and serotonergic receptors– This change corresponds temporally to the

antidepressant response

NeuroendocrineNeuroendocrine

Hyperactivity of HPA axis:– Elevated cortisol– Nonsuppression of cortisol following dexamethasone– Hypersecretion of CRF

Blunting of TSH response to TRHBlunting of serotonin mediated increase in plasma

prolactinBlunting of the expected increase in plasma

growth hormone response to alpha-2 agonists

Functional Neuroimaging (PET,SPECT)Functional Neuroimaging (PET,SPECT)demonstrates decreased metabolic activity indemonstrates decreased metabolic activity in

Dorsal prefontal cortex– Anterolateral (concentration, cognitive

processing)– Cingulate (regulation of mood and affect)

Subcortical– Caudate (psychomotor changes)

PsychosocialPsychosocial

Risk Factors– Poor social supports– Early parental loss– Introversion– Female gender– Recent stressor (especially medical

illness)

PsychosocialPsychosocial

Cognitive Theory– Patients have distorted perceptions

and thoughts of themselves, the world around them and the future

Possible to treat by restructuring

Secondary Causes of Secondary Causes of DepressionDepression

Toxic Endocrine Vascular Neurologic Nutritional Neoplastic Traumatic Infectious Autoimmune

Depression – Differential Depression – Differential DiagnosisDiagnosis

Other Mood Disorders Adjustment Disorder with Depressed Mood

– Maladaptive and excessive response to stress, difficulty functioning, need support not medicines, resolve as stress resolves

– Dysthymic Disorder– Bipolar Disorder

Other Psychotic Disorders – if psychotic subtype Personality Type – “glass is half empty type”

overall pessimistic, depressed outlook. Chronic and longstanding with no change in function.

TreatmentTreatment

BiologicTricylclic antidepressantsMonoamine oxidase inhibitorsSecond generation antidepressants

– SSRI’s, Venlafaxine, bupropion, martazapine

Electoconvulsive therapy

TreatmentTreatment

Psychosocial TreatmentsEducationSpecific pscychotherapiesVocational trainingExercise

TreatmentTreatment

When to Refer?Question regarding suicide riskPresence of psychotic symptomsPast history of maniaLack of response to adequate medication

trial

TreatmentTreatment

CourseOne episode – 50% chance of reoccurenceTwo episodes – 70% chance of reoccurenceThree or more episodes - >90% chance of

reoccurence

Dysthymic DisorderDysthymic Disorder

Characteristics Chronically depressed mood for most of the day, more

days than not, for at least two years. Can be irritable mood in children and adolescents for 1 year

While depressed, presence of at least two of the following

– Poor appetite or overeating– Sleep disturbance– Low energy or fatigue– Low self esteem– Poor concentration– Feelings of hopelessness

Dysthymic DisorderDysthymic Disorder

Never without depressive symptoms for over 2 months

No evidence of an unequivocal Major Depressive Episode during the first two years of the disturbance (1 year in children and adolescents)

No manic or hypermanic episodes Not superimposed on a chronic psychotic disorder Not due to the direct physiologic affects of a

substance or a general medical condition

EpidemiologyEpidemiology

More prevalent in women, 4% prevalence in women, 2% in men

Onset is usually in childhood, adolescence or early adulthood

Often is a superimposed Major DepressionHigh prevalence of substance abuse in this

group

Differential DiagnosisDifferential Diagnosis

Other mood disorders

Mood disorder due to a general medical condition

TreatmentTreatment

If no superimposed Major Depression– Psychotherapy

Some evidence suggest responsiveness to antidepressant medication

CourseCourse

Prognosis is not as good as Major Depression in terms of total symptoms remission

Bipolar DisorderBipolar Disorder

Characteristics of a Manic Episode A distinct period of abnormally and persistently

elevated, expansive or irritable mood During the period of mood disturbance, at least three

of the following symptoms have persisted (four if the mood is only irritable) and have been persistent to a significant degree– Inflated self esteem or grandiosity– Decreased need for sleep– More talkative than usual or pressure to keep talking– Flight of ideas or subjective experience that thoughts are

racing

Characteristics (Cont.)Characteristics (Cont.)

– Distractability, i.e. attention too easily drawn to unimportant or irrelevant external stimuli

– Increase in goal-directed activity or psychomotor agitation

– Excessive involvement in pleasurable activities which have a high potential for painful consequences, e.g. unrestrained buying sprees, sexual indiscretions, or foolish business investments

Characteristics (Cont.)Characteristics (Cont.) Mood disturbance sufficiently severe to cause marked

impairment in occupational functioning or in usual social activities or relations with others, or to necessitate hospitalization to prevent harm to self or others

At no time during the disturbance have there been delusions or hallucinations for as long as two weeks in the absence of prominent mood symptoms

Not superimposed on schizophrenia, schizophreniform disorder, or delusional disorder or psychotic disorder NOS

The disturbance is not due to the physiologic effects of a substance or general medical disorder

Presentations of Bipolar DisorderPresentations of Bipolar Disorder

Manic

Depressed

Mixed

TypesTypes

Type I - manic/mixed episode +/- major depressive episode

Type II - hypomanic episode + major depressive episode

EpidemiologyEpidemiology

Lifetime prevalenceType I - 0.7 - 0.8%Type II - 0.4 - 0.5%

– Equal in males and females– Increased prevalence in upper socioeconomic

classes

Age of Onset– Usually late adolescence or early adulthood.

However some after age 50. Late onset is more commonly Type II.

GeneticsGenetics

Greater risk in first degree relatives

(4-14 times risk)Concordance in monozygotic twins >85%Concordance in dyzygotic twins – 20%

Secondary Causes of ManiaSecondary Causes of Mania

Toxins Drugs of Abuse

– Stimulants (amphetamines, cocaine)– Hallucinogens (LCD, PCP)

Prescription Medications– Common: antidepressants, L-dopa, corticosteroids

Neurologic Right-sided CVA Right frontotemporal tumors Huntington’s Disease Multiple Sclerosis

Secondary Causes of ManiaSecondary Causes of Mania(Cont.)(Cont.)

Infectious Neurosyphilis HIV

Endocrine Hypothyroidism Cushing’s Disease

Cyclothymic DisorderOther Psychotic Disorders

TreatmentTreatment

Education and Support Medication

1. Lithium

2. Carbamazepine

3. Valproate

4. Lamotrigine

5. ECT

CourseCourse

Acute Episode– Manic - 5 weeks– Depressed - 9 weeks– Mixed - 14 weeks

Long Term– Variable - most cover fully– Mean number of lifetime episodes 8-9

Cyclothymic DisorderCyclothymic Disorder

Characteristics For at least two years (one for children and

adolescents) presence of numerous Hypomanic Episodes and numerous periods with depressed mood or loss of interest or pleasure that did not meet criterion A of a Major Depressive Episode

During a two year period (one year in children and adolescents) of the disturbance, never without hypomanic or depressive symptoms for more than a two month time

Characteristics (Cont.)Characteristics (Cont.)

No clear evidence of a Major Depressive Disorder, or Manic Episode during the first two years of the disturbance (or one year for children and adolescents)

Not superimposed on a chronic psychotic disorder, such as schizophrenia or Delusional Disorder

Not due to the direct physiologic affects of a substance or a general medical condition

EpidemiologyEpidemiology

Lifetime prevalence 0.4 – 1.0 %

same for males and femalesAge of onset

– Usually in adolescence or early adulthood

Genetics– Major Depression and Bipolar Disorder more

common in first degree relatives

Cyclothymic DisorderCyclothymic Disorder

Secondary causes of cyclothymic disorder Bipolar Disorder Mood disorders due to a general medical condition

Treatment Initiation of biologic treatment is dependent on the

degree of impairment If treatment is indicated, it is similar to that of

Bipolar Disorder

Episode Disorder

*Major depression episode *Major depression disorder

*Major depression episode+ *Bipolar disorder, Type I manic/mixed episode

*Manic/mixed episode *Bipolar disorder, Type I

*Major depressive episode+ *Bipolar disorder, Type II hypomanic episode

*Chronic subsyndromal *Dysthymic Disorder depression

*Chronic fluctuations between subsyndromal *Cyclothymic disorder depression & hypomania