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					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
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

*Chronic fluctuations
 between subsyndromal        *Cyclothymic disorder
 depression & hypomania
“If I had __________, I’d
     be depressed to.”
• Mood - a person’s sustained emotional state

• Affect – the outward manifestation of a
  person’s feelings, tone, or mood
        Major Depression
• Syndromal classification with disturbances
  of mood, neurovegetative and cognitive
        Major Depression
At least 5 of the following symptoms present
 for at least 2 weeks (either #1 or #2 must be
 1) depressed mood
 2) anhedonia – loss of interest or pleasure
 3) change in appetite
 4) sleep disturbance
       Major Depression
5) psychomotor retardation or agitation
6) decreased energy
7) feeling of worthlessness or inappropriate
8) diminished ability to think or concentrate
9) recurrent thoughts of death or suicidal
     Major Depression
• Symptoms cause marked distress and/or
 impairment in social or occupational

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

• Symptoms are not due to a normal
 reaction to the death of a loved one.
    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.
Subtypes of Depression
• Atypical
   Reverse neurovegetative symptoms
   Mood reactivity

   Hypersensitivity to rejection

   MAO-I’s and SSRI’s are more

    effective treatments
Subtypes of Depression
    Psychotic (~10% of all MDD)
      • Delusions common, may have
      • Delusions usually mood congruent
      • Combined antidepressant and
        antipsychotic therapy or ECT is
Subtypes of Depression
    Melancholic
      • No mood reactivity
      • Anhedonia
      • Prominent neurovegetative
      • More likely to respond to biological
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
Subtypes of Depression
    Catatonic
      • Motoric immobility (catalepsy)
      • Mutism
      • Ecolalia or echopraxia
Point prevalence
    6 – 8% in women
    3 – 4% in men

Lifetime prevalence
     20% in women
     10% in men
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
 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
Original, clearly over simplistic theories
   regarding norepinephrine and

   Deficiency states       depression
   States of excess        mania
Problems 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 useful
   Antidepressant treatment causes a down
    regulation in central adrenergic and
    serotonergic receptors
    – This change corresponds temporally to the
      antidepressant response
   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
 Blunting of the expected increase in plasma
  growth hormone response to alpha-2 agonists
  Functional Neuroimaging (PET,SPECT)
demonstrates decreased metabolic activity in

     Dorsal prefontal cortex
      – Anterolateral (concentration, cognitive
      – Cingulate (regulation of mood and affect)
     Subcortical
      – Caudate (psychomotor changes)
   Risk Factors
    – Poor social supports
    – Early parental loss
    – Introversion
    – Female gender
    – Recent stressor (especially medical
   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
   Toxic
   Endocrine
   Vascular
   Neurologic
   Nutritional
   Neoplastic
   Traumatic
   Infectious
   Autoimmune
    Depression – Differential
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.
 Tricylclic antidepressants
 Monoamine oxidase inhibitors
 Second generation antidepressants
    – SSRI’s, Venlafaxine, bupropion, martazapine
   Electoconvulsive therapy
Psychosocial Treatments
 Education
 Specific pscychotherapies
 Vocational training
 Exercise
When to Refer?
 Question regarding suicide risk
 Presence of psychotic symptoms
 Past history of mania
 Lack of response to adequate medication
 One episode – 50% chance of reoccurence
 Two episodes – 70% chance of reoccurence
 Three or more episodes - >90% chance of
            Dysthymic Disorder
   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
    –   Poor appetite or overeating
    –   Sleep disturbance
    –   Low energy or fatigue
    –   Low self esteem
    –   Poor concentration
    –   Feelings of hopelessness
         Dysthymic Disorder
   Never without depressive symptoms for over 2
   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
 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
       Differential Diagnosis
   Other mood disorders

   Mood disorder due to a general medical
   If no superimposed Major Depression
     – Psychotherapy

   Some evidence suggest responsiveness to
    antidepressant medication
Prognosis is not as good as Major
Depression in terms of total symptoms
              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
  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
       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
   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 Disorder
     Manic

     Depressed

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

   Type II - hypomanic episode + major
    depressive episode
Lifetime prevalence
 Type I - 0.7 - 0.8%
 Type II - 0.4 - 0.5%
    – Equal in males and females
    – Increased prevalence in upper socioeconomic
   Age of Onset
    – Usually late adolescence or early adulthood.
      However some after age 50. Late onset is more
      commonly Type II.
 Greater risk in first degree relatives
  (4-14 times risk)
 Concordance in monozygotic twins >85%
 Concordance in dyzygotic twins – 20%
Secondary Causes of Mania
   Drugs of Abuse
    – Stimulants (amphetamines, cocaine)
    – Hallucinogens (LCD, PCP)
   Prescription Medications
    – Common: antidepressants, L-dopa, corticosteroids
 Right-sided CVA
 Right frontotemporal tumors
 Huntington’s Disease
 Multiple Sclerosis
Secondary Causes of Mania
 Neurosyphilis
 Hypothyroidism
 Cushing’s Disease
Cyclothymic Disorder
Other Psychotic Disorders
   Education and Support
   Medication
    1. Lithium
    2. Carbamazepine
    3. Valproate
    4. Lamotrigine
    5. ECT
   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 Disorder
 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.)
 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
 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
 Lifetime prevalence 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
      Cyclothymic Disorder
Secondary causes of cyclothymic disorder
 Bipolar Disorder
 Mood disorders due to a general medical condition

 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

*Chronic fluctuations
 between subsyndromal        *Cyclothymic disorder
 depression & hypomania