The document lists the 10 leading causes of disability worldwide according to cost in disability-adjusted life years (DALYs). Unipolar major depression is the leading cause, accounting for 10.3% of total cost. The top 3 causes are unipolar major depression, tuberculosis, and road traffic accidents. Together the top 10 causes account for over 40% of the total cost of disability worldwide.

1. Ten Leading Causes of
Disability in the World
Type of Disability Cost (in Cumulative
DALYs) %
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

2. 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

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

4. Definitions
• Mood - a person’s sustained emotional state
• Affect – the outward manifestation of a
person’s feelings, tone, or mood

5. Major Depression
• Syndromal classification with disturbances
of mood, neurovegetative and cognitive
functioning

6. Major 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

7. Major 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

8. Major 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.

9. Bereavement and
Late 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.

10. Subtypes of Depression
• Atypical
Reverse neurovegetative symptoms
Mood reactivity
Hypersensitivity to rejection
MAO-I’s and SSRI’s are more
effective treatments

11. Subtypes 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

12. Subtypes of Depression
 Melancholic
• No mood reactivity
• Anhedonia
• Prominent neurovegetative
disturbance
• More likely to respond to biological
treatments

13. Subtypes 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

14. Subtypes of Depression
 Catatonic
• Motoric immobility (catalepsy)
• Mutism
• Ecolalia or echopraxia

15. Epidemiology
Point prevalence
 6 – 8% in women
 3 – 4% in men
Lifetime prevalence
 20% in women
 10% in men

16. Epidemiology
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

17. Epidemiology
Genetics
 More prevalent in first degree relatives
3-5x the general population risk
 Concordance is greater in monozygotic than
dizygotic twins
 Increased prevalence of alcohol dependence
in relatives

18. Etiology
Original, clearly over simplistic theories
regarding norepinephrine and
serotonin
 Deficiency states depression
 States of excess mania

19. Problems with initial theories
 Inconsistentfindings 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.

21. Receptor theory more useful
 Antidepressant treatment causes a down
regulation in central adrenergic and
serotonergic receptors
– This change corresponds temporally to the
antidepressant response

22. Neuroendocrine
 Hyperactivity of HPA axis:
– Elevated cortisol
– Nonsuppression of cortisol following dexamethasone
– Hypersecretion of CRF
 Blunting of TSH response to TRH
 Blunting of serotonin mediated increase in plasma
prolactin
 Blunting of the expected increase in plasma
growth hormone response to alpha-2 agonists

23. Functional Neuroimaging (PET,SPECT)
demonstrates decreased metabolic activity in
 Dorsal prefontal cortex
– Anterolateral (concentration, cognitive
processing)
– Cingulate (regulation of mood and affect)
 Subcortical
– Caudate (psychomotor changes)

25. Psychosocial
 Risk Factors
– Poor social supports
– Early parental loss
– Introversion
– Female gender
– Recent stressor (especially medical
illness)

26. Psychosocial
 Cognitive Theory
– Patients have distorted perceptions
and thoughts of themselves, the world
around them and the future
 Possible to treat by restructuring

27. Secondary Causes of
Depression
 Toxic
 Endocrine
 Vascular
 Neurologic
 Nutritional
 Neoplastic
 Traumatic
 Infectious
 Autoimmune

28. Depression – Differential
Diagnosis
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.

30. Treatment
Biologic
 Tricylclic antidepressants
 Monoamine oxidase inhibitors
 Second generation antidepressants
– SSRI’s, Venlafaxine, bupropion, martazapine
 Electoconvulsive therapy

31. Treatment
Psychosocial Treatments
 Education
 Specific pscychotherapies
 Vocational training
 Exercise

32. Treatment
When to Refer?
 Question regarding suicide risk
 Presence of psychotic symptoms
 Past history of mania
 Lack of response to adequate medication
trial

33. Treatment
Course
 One episode – 50% chance of reoccurence
 Two episodes – 70% chance of reoccurence
 Three or more episodes - >90% chance of
reoccurence

34. Dysthymic 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

35. Dysthymic 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

36. Epidemiology
 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 Depression
 High prevalence of substance abuse in this
group

37. Differential Diagnosis
 Other mood disorders
 Mood disorder due to a general medical
condition

38. Treatment
 Ifno superimposed Major Depression
– Psychotherapy
 Some evidence suggest responsiveness to
antidepressant medication

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

41. Bipolar 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

42. 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

43. 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

44. Presentations of Bipolar Disorder
 Manic
 Depressed
 Mixed

45. Types
 TypeI - manic/mixed episode +/- major
depressive episode
 TypeII - hypomanic episode + major
depressive episode

46. Epidemiology
Lifetime prevalence
 Type 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.

47. Genetics
 Greaterrisk in first degree relatives
(4-14 times risk)
 Concordance in monozygotic twins >85%
 Concordance in dyzygotic twins – 20%

48. Secondary 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

49. Secondary Causes of Mania
(Cont.)
Infectious
 Neurosyphilis
 HIV
Endocrine
 Hypothyroidism
 Cushing’s Disease
Cyclothymic Disorder
Other Psychotic Disorders

50. Treatment
 Education and Support
 Medication
1. Lithium
2. Carbamazepine
3. Valproate
4. Lamotrigine
5. ECT

51. Course
 Acute Episode
– Manic - 5 weeks
– Depressed - 9 weeks
– Mixed - 14 weeks
 Long Term
– Variable - most cover fully
– Mean number of lifetime episodes 8-9

52. Cyclothymic 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

53. 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

54. Epidemiology
 Lifetimeprevalence 0.4 – 1.0 %
same for males and females
 Age of onset
– Usually in adolescence or early adulthood
 Genetics
– Major Depression and Bipolar Disorder more
common in first degree relatives

55. Cyclothymic Disorder
Secondary causes of cyclothymic disorder
 Bipolar
Disorder
 Mood disorders due to a general medical condition
Treatment
 Initiationof biologic treatment is dependent on the
degree of impairment
 If treatment is indicated, it is similar to that of
Bipolar Disorder

56. 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