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Bipolar Disorder

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Many of the treatments for bpd are psychoeducational in nature. ... onset (+ 18 years) IMPAIRMENTS Comorbidity Attention Deficit Hyperactivity Disorder (ADHD) ... – PowerPoint PPT presentation

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Title: Bipolar Disorder


1
Bipolar Disorder
  • Pathways

2
from Jamison KEYH Asylum or psychiatric
hospital S Suicide SA Suicide Attempt
Writers Hans Christian Andersen, Honore de
Balzac, James Barrie, William Faulkner (H), F.
Scott Fitzgerald (H), Ernest Hemingway (H, S),
Hermann Hesse (H, SA), Henrik Ibsen, Henry James,
William James, Samuel Clemens (Mark Twain),
Joseph Conrad (SA), Charles Dickens, Isak Dinesen
(SA), Ralph Waldo Emerson, Herman Melville,
Eugene O'Neill (H, SA), Mary Shelley, Robert
Louis Stevenson, Leo Tolstoy, Tennessee Williams
(H), Mary Wollstonecraft (SA), Virginia Woolf (H,
S) Composers Hector Berlioz (SA), Anton
Bruckner (H), George Frederic Handel, Gustav
Holst, Charles Ives, Gustav Mahler, Modest
Mussorgsky, Sergey Rachmaninoff, Giocchino
Rossini, Robert Schumann (H, SA), Alexander
Scriabin, Peter Tchaikovsky Nonclassical
composers and musicians Irving Berlin (H), Noel
Coward, Stephen Foster, Charles Mingus (H),
Charles Parker (H, SA), Cole Porter (H) Poets
William Blake, Robert Burns, George Gordon, Lord
Byron, Samuel Taylor Coleridge, Hart Crane (S) ,
Emily Dickinson, T.S. Eliot (H), Oliver
Goldsmith, Gerard Manley Hopkins, Victor Hugo,
Samuel Johnson, John Keats, Vachel Lindsay (S),
James Russell Lowell, Robert Lowell (H), Edna St.
Vincent Millay (H), Boris Pasternak (H), Sylvia
Plath (H, S), Edgar Allan Poe (SA), Ezra Pound
(H), Anne Sexton (H, S), Percy Bysshe Shelley
(SA), Alfred, Lord Tennyson, Dylan Thomas, Walt
Whitman Artists Richard Dadd (H), Thomas
Eakins, Paul Gauguin (SA), Vincent van Gogh (H,
S), Ernst Ludwig Kirchner (H, S), Edward Lear,
Michelangelo, Edvard Meunch (H), Georgia O'Keeffe
(H), George Romney, Dante Gabriel Rossetti (SA)
3
DIAGNOSIS
4
DSM-IV-TR
  • Five types of episodes
  • Four subtypes
  • Four severity levels
  • Three course specifiers

? American Psychiatric Association. (2000).
Diagnostic and Statistical Manual of Mental
Disorders-Fourth Edition-Text Revision.
Washington, DC Author.
5
Manic Episode
  • Symptoms
  • Inflated self-esteem or grandiosity
  • Decreased need for sleep
  • Pressured speech or more talkative than usual
  • Flight of ideas or racing thoughts
  • Distractibility
  • Psychomotor agitation or increase in
    goal-directed activity
  • Hedonistic interests

6
Hypomanic Episode
  • Similarities with Manic Episode
  • Same symptoms
  • Differences
  • Length of time
  • Impairment not as severe

7
Hypomanic Episode
  • Similarities with Manic Episode
  • Same symptoms
  • Differences
  • Length of time
  • Impairment not as severe

8
Major Depressive Episode
  • Symptoms
  • Depressed mood (in children can be irritable)
  • Diminished interest in activities
  • Significant weight loss or gain
  • Insomnia or hypersomnia
  • Psychomotor agitation or retardation
  • Fatigue/loss of energy
  • Feelings of worthlessness/inappropriate guilt
  • Diminished ability to think or concentrate/indecis
    iveness
  • Suicidal ideation or suicide attempt

9
Mixed Episode
  • Both Manic and Major Depressive Episode
    criteria are met nearly every day for a least a
    one week period.

10
Subtypes
  • Bipolar Disorder I more classic form clear
    episodes of depression mania
  • Bipolar Disorder II presents with less intense
    and often unrecognized manic phases
  • Cyclothymia chronic moods of hypomania
    depression, often evolves into a more serious
    type
  • Bipolar Disorder Not Otherwise Specified (NOS)
    largest group of individuals

11
EPIDEMIOLOGY
12
Prevalence
  • Estimated between 3-6
  • Subsyndromal bipolar disorder
  • Equal distribution across gender variables
  • Average age _at_ onset 20 years old

13
Course
  • Initial cycle typically major depressive episode
  • Recovery
  • Relapse
  • Rapid Cycling
  • Rapid cycling4 episodes/year
  • Ultrarapid cycling5-364 episodes/year
  • Ultradian cyclinggt365 episodes/year

14
Age at Onset
  • Pediatric, prepubertal, or early adolescent
    (prior to age 12)
  • Adolescent (12 - 18 years)
  • Adult onset ( 18 years)

15
IMPAIRMENTS
16
Comorbidity
  • Attention Deficit Hyperactivity Disorder (ADHD)
  • Between 60-80

17
Criteria Comparison
  • Bipolar Disorder (mania)
  • More talkative than usual, or pressure to keep
    talking
  • Distractibility
  • Increase in goal directed activity or psychomotor
    agitation
  • ADHD
  • Often talks excessively
  • Is often easily distracted by extraneous stimuli
  • Is often on the go or often acts as if driven
    by a motor

Differentiation elated mood, grandiosity,
decreased need for sleep, hypersexuality, and
irritable mood.
18
Comorbidity(cont.)
  • Oppositional Defiant Disorder (ODD) Conduct
    Disorder (CD)
  • 70-75
  • Substance Abuse
  • 40-50
  • Anxiety Disorders
  • 35-40

19
Suicidal Behaviors
  • Prevalence of suicide attempts
  • 40-45
  • Age of first attempt
  • Multiple attempts
  • Severity of attempts
  • Suicidal ideation

20
Cognitive Deficits
  • Executive Functions
  • Attention
  • Memory
  • Sensory-Motor Integration
  • Nonverbal Problem-Solving
  • Academic Deficits
  • Mathematics

21
Psychosocial Deficits
  • Relationships
  • Peers
  • Family members
  • Recognition and Regulation of Emotion
  • Social Problem-Solving
  • Self-Esteem
  • Impulse Control

22
TREATMENT APPROACHES
23
Psychopharmacological
  • DEPRESSION
  • Mood Stabilizers
  • Anti-Obsessional
  • Anti-Depressant
  • Atypical Antipsychotics
  • MANIA
  • Mood Stabillizers
  • Aypical Antipsychotics
  • Anti-Anxiety

24
Lithium Pharmacology
  • Not liver metabolized. Kidney excreted
  • Not protein bound
  • 70-80 reabsorb prox Tubule, Na comp ?Na
    (dehydr, thiazide diuret) ?Li level
  • Excretion related to GFR?elder ?preg
  • Half-life 24 hrs (HS), steady state 5 days
  • Peak Levels 2 hrs, SR 4-4.5
  • fast release N/V, slow rel diarrhea

25
Predictors Good Li Response
  • Past Li response (personal or family)
  • Euphoric, pure (classic) mania
  • Sequence Mania-Depr-Euthymia
  • No psychosis
  • No Rapid Cycling

26
Predictors Poor Li ResponseGood response to
anticonvulsants
  • Mixed mania (adolescents)
  • Irritable mania
  • Secondary mania (geriatric)
  • Psychotic Sx
  • Rapid Cycling
  • Depression-Mania-Euthymia
  • Comorbid substance abuse

27
Lithium Common Side Effects
  • GI distress upper LiCO3, lower GI SR.
  • Polyuria / polydipsia
  • Sedation-lethargy
  • Cognitive (memory, concentr, slow)
  • Wt. Gain
  • Poor coordination, tremor
  • Skin (worse acne)

28
Lithium Serious SE
  • Renal
  • nephrogenic diabetes insipidus
  • tubular interstitial nephritis
  • Hypothyroidism
  • Psoriasis (onset or worsening)
  • Cardiac EKG flat T, SA dysfx, tachicardia
  • Li Tox. N/V/D, delirium, ataxia, stupor
  • Tx dyalisis if gt3.0, correct fluid-electrolites

29
Li Interactions Use
  • ?Li levels
  • diuretics,
  • NSAIDs (ASA OK)
  • ACE-inhibitors
  • Starting
  • Baseline Renal, TFT, HCG, EKG, UA, weight,
    medical Hx
  • 300-600 mg/day divided doses
  • Levels in 5 days
  • Increase 300-900 mg/day q 5-7 days

30
Valproate
  • FDA Sz 78, BP 96
  • Effective antimanic, BP depression
  • Therapeutic effect 2 d. level 50-125 mg/l
  • oral loading 20-30 mg/kg/day
  • Elderly hypomania responde to lower?
  • Mixed, rapid cycling, schizoaffective

31
Valproate
  • FDA Sz 78, BP 96
  • Effective antimanic, BP depression
  • Therapeutic effect 2 d. level 50-125 mg/l
  • oral loading 20-30 mg/kg/day
  • Elderly hypomania responde to lower?
  • Mixed, rapid cycling, schizoaffective

32
Valproate
  • Increases GABA levels
  • Effects 2nd Messenger, Prot-Kinase-C
  • 80-95 Protein bound
  • Liver Metabolized p450 (inhibitor)
  • Half life 8-17 hrs

33
VPA Common Side Effects
  • GI distress
  • Sedation
  • Liver transaminase elevation
  • Tremor
  • Hair loss
  • Weight gain-increased appetite
  • Thrombocitopenia (elders)
  • Teratogenic neural tube, cranio-facial

34
VPA Less Common SE
  • Neutropenia
  • Coagulopathies, ?platelet Function
  • endocrine abnormalities
  • Amenorrhea, policystic ovary?
  • Hypothyroidism
  • Hypocortisolemia

35
VPA Rare Dangerous SE
  • Idiosincratic Hepatic Failure
  • lethargy, anorexia, N/V, bleed, edema
  • Risk lt2 yo, many anticonvuls, Dev. Delay
  • Remote risk in gt10yo psychiatric patients
  • Acute Hemorrhagic Pancreatitis
  • Bone Marrow Supression

36
VPA Use
  • Baseline
  • Medical Hx, CBC-diff, LFT (LDH, SGOT, SGPT, bili,
    Alk. Phos, GGT), HCG, PT,PTT if bleeding abnorm,
    amylase?
  • Warn about hepatic, pancreatic, hematologic,
    teratogenic risks
  • Load 20 mg/kg/day, lower outpt hypom
  • Level 50-120 (check in 1-5 days)
  • Monitor LFT, CBC

37
Carbamazepine
  • Effective antimanic, Tx-refract Depr
  • Onset 2 wks, antidepr 4-6 wk
  • Ther. Levels 4-12 or 15 mg/L
  • Half life decreases to 12-17 hrs
  • p450 liver induction

38
CBZ Side Effects
  • Less cognitive probl than Li
  • Less Wt gain, hair loss, tremor than VPA
  • Neuro Diplopia,blurr vision, fatigue/sed
  • GI Naus/diarr, Dry mouth
  • Leukopenia, thrombocitopenia, rash
  • ?LFT
  • Agranulocytosis (, Liver fail, pancreatitis,
    Stevens-Johnson (exfol skin), neuroteratogenic

39
CBZ Interactions (Many)
  • p450 induction, CBZ?levels of CBZ, VPA,
    lamotrig, TCAs, prednisone, theophiline,
    warfarin, benzos, oral contraceptives
  • p450 inhibitors acetazolamide, Ca-channe
    blockers diltiazem verapamil, but not
    nifedipine, danazol, erythromycin, fluoxetine,
    isoniazid, VPA all ?CBZ levels

40
CBZ Use
  • Baseline Medical Hx, CBCdiff,LFT, Renal, TFT,
    HCG, ferritin
  • Start low
  • 100-400 mg/day,
  • ?100-200 mg every several days, bid (occasionally
    qd)
  • Follow CBC, LFT
  • clinical monitoring more effective than labs

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Therapy
  • Psychoeducation
  • Family Interventions
  • Cognitive-Behavioral Therapy
  • RAINBOW Program
  • Interpersonal and Social Rhythm Therapy
  • Schema-focused Therapy

43
Biological mechanisms
  • Macro
  • Micro

44
MACRO
  • Which parts of the brain are relevant to BP

45
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? volumes
  • amygdala
  • ? at later phases of the disease (drugs ?)
    (Strakowski, 2012)
  • ? at the first episode (Bitter, 2011)
  • VPC and striatum
  • ? volume inversely correlated with age (Blumberg,
    2006 Sanches, 2009)

49
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51
Key points
  • Subtle abnormalities in the brains of BP
  • Preservation of total cerebral volume with
    regional grey and white matter changes in
    prefrontal, midline and limbic networks

52
limits
  • Findings are not consitent
  • Medications
  • Illness duration
  • Sample sizes
  • Img studies do not test the activity per se but
    a ? of the activity in ? experimental conditions

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neurodevelopment
  • BP begins in late adolescence
  • BP is progressive

55
pruning
  • Increased brain volumes in prefrontal and
    parahippocampal cortices

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Red ? frontal Black ? parietal Purple ?
termporal Occipital ? green
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60
MICRO
  • Which molecular cascades are relevant to BD ?

61
  • Wnt
  • IP
  • GSK3

62
  • Wnt
  • IP
  • GSK3

63
  • Axon guidance, planar cell position
  • A network of proteins signals from receptors to
    DNA expression
  • Controls beta-catenin (turns on the expression of
    genes)
  • Wnt ? phosphorylation of beta-catenin ? ?
    degradation
  • Ø Wnt ? ? gene expression

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  • Wnt
  • IP
  • GSK3

66
  • Inositol phosphates are a group of mono- to
    polyphosphorylated inositols.
  • They act as second messangers for cell growth,
    apoptosis, cell migration, endocytosis, and cell
    differentiation

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  • Wnt
  • IP
  • GSK3

69
  • GSK3 is a widely influential enzyme that is
    capable of phosphorylating, and thereby
    regulating, over forty known substrates.
  • serotonergic, dopaminergic, cholinergic, and
    glutamatergic systems control the activity of
    GSK3
  • neural plasticity, neurogenesis, gene expression,
    and the ability of neurons to respond to
    stressful, potentially lethal, conditions are
    modulated by GSK3

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Oxidative stress
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