MOOD DISORDERS

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MOOD DISORDERS
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OVERVIEW

• Definitions Unipolar vs. Bipolar
• Unipolar Disorders
• Bipolar Disorders
• Others SADs, Postpartum Depression, PMS
• A few case studies

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DEFINITIONS

• Mood disorders
• Mood continuum?
• discrete periods of time in episodes
• depression vs. dysphoria vs. mania
• anxiety?

DEPRESSION
MANIA
SADNESS, HAPPINESS, ETC.?
4
Cont.

• Cognitive Somatic symptoms
• depression vs. mania
• Comorbidity with
• alcoholism which is first?
• eating disorders
• anxiety disorders

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DEPRESSION VS. SADNESS

• How do we distinguish the two?
• Intensity
• Absence of precipitants
• Quality
• History
• Interesting self-reports vs. clinical interviews
  the prevalence of depression

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DSM-IV UNIPOLAR

• Major Depressive Disorders
• one or more major depressive episode
• no manic or unequivocal hypomanic episodes
• Dysthymic Disorders
• depressed mood for gt 2 years
• never without symptoms for more than 2 months
• no major depressive episodes

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DSM-IV BIPOLAR

• Bipolar 1
• one or more manic episode
• Bipolar 2
• one or more major depressive episode
• at least one hypomanic episode
• no manic episodes

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Cont...

• Cyclothymic Disorder
• numerous hypomanic symotims and periods with
  depressed mood for gt 2 years
• never without symptoms for gt 2 months
• no major depressive episodes
• no manic episodes
• manic-depressive?

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DSM-IV DEPRESSIVE EPISODE

• 5 or more of following symptoms that must
  represent change in functioning
• depressed mood
• diminished interest or pleasure
• weight /or appetite changes
• insomnia/hypersomnia
• changes in psychomotor activity
• fatigue or loss of energy

10
Cont...

• feeling of worthlessness or inappropriate guilt
• diminished ability to think/concentrate or
  indecisiveness
• recurrent thoughts of death/suicidal ideation,
  but no specific plans for suicide

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DSM-IV MANIC EPISODE

• A distinct period of abnormally persistently
  elevated, expansive, or irritable mood for gt one
  week
• Must have 3 or more of following symptoms
• inflated self-esteem/grandiosity
• decreased need for sleep

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Cont

• more talkative than usual or pressure to keep
  talking
• flight of ideas (thoughts are racing)
• distractibility to unimportant or irrelevant
  stimuli
• increased goal-directed activity or psychomotor
  agitation
• excessive involvement in pleasurable activities
  that have high potential for painful consequences

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EPIDEMIOLOGY

• 13-20 at any given point in time
• unipolarbipolar 51
• lifetime risk 5
• 3rd behind substance abuse anxiety
• 30 seek treatment
• womenmen 31?
• genuine statistic

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ETIOLOGY

• Social Factors
• interpersonal loss, stress
• Cognitive Factors
• failure disappointment, learned hopelessness
  theory, social skills
• Psychological Factors
• friendships, young children, unemployed, loss of
  mother

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COURSE OUTCOME

• Unipolar
• onset usually mid-forties
• can have many episodes
• 65 recover within 6 mths of 1st episode
• 40 relapse
• Bipolar
• onset 28-33 years of age
• manic 2-3 mths depressive longer
• 40-50 recover

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BIOLOGICAL FACTORS
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GENETICS

• Family studies
• move vulnerable
• bipolar risk for bipolar unipolar
• unipolar risk for bipolar unipolar
• Twin studies
• MZ vs. DZ
• environmental issues

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NEUROTRANSMITTERS
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CLASSES OF NTs
Glutamate Aspartate Glycine GABA
Amino Acids
Dopamine Epinephrine Norepinephrine
Catecholamines
Monoamines
Indolamines
Serotonin
Soluble Gases
Nitric Oxide Carbon Monoxide
Acetylcholine
Acetylcholine
Neuropeptides
Hormones
20
Http/web.indstate.edu/thcme/mwking/aminoacidderiv
atives.htmtyrosine
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CATECHOLAMINES

• mostly NE
• decreased levels depression
• increased levels mania
• drugs that destroy catecholamines produce
  depression vice versa
• recent data????
• definitely a dysfunction, but unclear

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Noradrenaline Pathways
http//salmon.psy.plym.ac.uk/year1/DEPRESsion.HTM
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NOREPINEPHRINE

• high concentrations in the cortex and limbic
  system
• Also works as hormone
• respiration
• activity, stimulation, and arousal
• rate of metabolism

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INDOLAMINES

• both 5-HT and NE are affected in same way
• Monoamine Oxidase Inhibitors (MAOIs)
• ex. Iproniazid
• Tricyclic Antidepressants (TCAs)
• ex. Imipramine

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SEROTONIN

• high concentrations in the brain stem and
  thalamus
• sleep/wake cycle
• sensory perception
• emotional behaviour depression, impulsive
  behaviour, aggression

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SEROTONIN

• decrease in 5-HT activity vulnerability
• differences in specific receptor functions
• SSRIs, TCAs, etc.
• SSRIs reduces reuptake, but also decreases
  production release
• delay in therapeutic effects
• chronic use desensitizes some receptors

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Cont...

• role of prefrontal tempoparietal cortices
• Tryptophan (TRP)
• lower than normal
• decreased dietary TRP depressive symptoms
  higher rates of relapse

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DOPAMINE

• reduced firing in mesolimbic DA system
• withdrawal symptoms of cocaine and/or
  amphetamines
• animal studies

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Dopamine Pathways
http//salmon.psy.plym.ac.uk/year1/DEPRESsion.HTM
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CHOLINERGIC SYSTEM

• act with NE to affect mood
• ACh higher levels than normal
• drugs that increase Ach depressive symptoms

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GABA

• inhibits firing of LC cells (NE cell bodies)
• GABA levels are lower in CSF blood
• GABA agonists
• vulnerability?

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HOW BIPOLAR DISORDERS MAY DIFFER...

• 5-HT is reduced, whereas NE activity is
  increased..
• in unipolar disorders, both are decreased
• also increased levels of DA

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BUT...

• WHAT ABOUT SECOND GENERATION/ATYPICAL
  ANTIDEPRESSANTS??
• do not affect monoamines (ie. 5-HT/NE)
• interaction between many systems??
• role of receptors sensitivity density

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NEUROENDOCRINE
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THYROID GLAND

• Thyroglobulin converted to T3 T4
• almost all cells are target of THs
• calcitonin
• metabolic rate, growth development

TRH Thyroid-releasing hormone
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/tsh.html
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HPT AXIS

• administering TRH reduces depression
• but.. high levels of TH
• smaller than normal response of TSH to
  administration of TRH
• also affected in women with PMS

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THE HPA AXIS
LIMBIC SYSTEM (Hippocampus)
ve
HYPOTHALAMUS
-ve
CRH
PITUITARY GLAND
(Anterior Pituitary)
ACTH
ADRENAL GLAND
Glucocorticoid
(Adrenal Cortex)
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HPA AXIS

• excessive production of cortisol (50)
• changes in circadian rhythms of cortisol
• no conteracting of hypoglycemic effects of
  insulin by cortisol
• dexamethasone test
• unclear what is the cause

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Cont...

• complex relationship between 5-HT and HPA axis
• decrease in density of 5-HT receptors
• normalize with elevation of mood
• Cushings Disease 50 are depressed

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ESTROGEN

• released by ovary
• controlled/controls feedback
• sexual behaviour, maternal behaviour, menstrual
  cycle
• memory neurogenesis

http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/lhfsh.html
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HPG AXIS

• mostly estrogen affected
• decreases in estrogen
• 90 of women treated with estrogen show elevation
  in mood
• physiological levels in non-depressed women
• affects NE, DA, ACh, melatonin, HPT axis, HPA
  axis, etc.

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GROWTH HORMONE

• Direct effects target receptors in fat protein,
  lipid, carbohydrate metabolism
• Indirect effects mediated by insulin-like growth
  factor-1 (IGF-1) muscle bone growth

GHRH growth hormone-releasing hormone SS
somatostatin
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/gh.html
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PROLACTIN

• closely related to GH
• major target mammary glands
• many tissues contain receptors
• milk production
• reproductive behaviour
• immune function
• maternal behaviour

regulated by DA, TRH, GnRH, E
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/prolactin.html
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GROWTH HORMONE PROLACTIN

• GH basal levels normal, but abnormal responses
  to insulin-induced hypoglycemia
• inadequate 5-HT response to GH
• TRH does not affect GH normally, but increases GH
  in depressed patients
• elevated PRL levels

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NEUROANATOMY
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http//www.rci.rutgers.edu/uzwiak/UPhysioPsych/NP
SpringLect3.html
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PREFRONTAL CORTEX

• abnormalities in both structure and function
• used TRP depletion test to cause relapse
• change in activity of dorsolateral prefrontal
  cortex orbitofrontal cortex
• decreased volume in frontal lobe
• decrease in glial, but not neural density

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ORBITOFRONTAL CORTEX

• ROSTRAL thickness decreased
• decrease of neuronal size in some layers
• decrease in glial size
• CAUDAL only mild decreases
• decrease in neuronal size in some layers
• some decrease in neuronal densities (large)
• overall decrease in glial cell density size

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PREFRONTAL CORTEX

• DORSOLATERAL
• no effect on cortical thickness
• decrease in neuronal size

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SUMMARY

• suggests that
• different regions of frontal cortex play
  different roles
• areas changed receive 5-HT input
• also other monoamines
• cause or effect???
• neuropsychological tests dysfunction in dlPFC

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OTHER AREAS

• Hippocampus
• decrease in volume chronic recurorent
• even seen in patients in remission
• treatment-resistant vs. recovered
• verbal memory impairments
• Basal Ganglia
• decrease in volume
• hypometabolism rCBF in caudate nucleus

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http//web.bvu.edu/faculty/ferguson/BioPsych/Chpt4
_Neuroanatomy.html
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http//www.rci.rutgers.edu/uzwiak/UPhysioPsych/NP
SpringLect3.html
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ANTIDEPRESSANTS
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DRUGS AFFECTING CAs

• Resperine depletes CAs depression
• Tetrabenazibe depletes CAs depression
• AMPT stops CA synthesis depression
• Pargyline inhibits enzyme MAO no depression
• Iproniazid inhibits enzyme MAO no depression
• Imipramine inhibits CA reuptake no depression

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TCAs

• Tricyclic Antidepressants
• block reuptake NE, 5-HT, DA
• improvements not evident immediately 2-3 weeks
• not effective with some patients

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MAOIs

• Monoamine Oxidase Inhibitors
• affect NE 5-HT levels
• obviously inhibit reuptake
• can develop high blood pressure
• pay attention to diet
• used for anxiety disorders as well
• not as effective as TCAs

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SSRIs

• Selective Serotonin Reuptake Inhibitors
• inhibits 5-HT specifically
• fewer side effects than other drugs
• nausea, headaches, fatigue, restlessness, etc.
• less dangerous for overdose
• ex. Prozac

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OTHER TREATMENTS...

• Electroconvulsive Therapy
• series of treatments with dramatic results
• better than antidepressants
• memory loss
• Lithium Carbonate
• effective for bipolar disorders

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OTHER MOOD DISORDERS
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SEASONAL AFFECTIVE DISODERS

• Winter depression
• symptoms depressed affect, lethargy, loss of
  libido, hypersomnia, excessive weight gain,
  carbohydrate cravings, anxiety, inability to
  concentrate or focus attention
• Northern vs. Southern Hemispheres
• higher prevalences at higher latitudes

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Cont...

• women more affected than men (3.51)
• circadian rhythms entrained improperly
• sleep-wake cycle manipulations
• all depressants tried
• bright lights used to treat

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Cont...

• 5-HT
• increase in carbohydrates results in more TRP
  crossing BBB self-medicating?
• serotonin agonists reducing weight gain,
  carbohydrate cravings, depressed symptoms
• high levels of illumination are needed to
  decrease melatonin production (also affected by
  serotonin)

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POSTPARTUM DEPRESSION

• well-known outcome of endocrine changes
• 50 of women show symptoms
• symptoms depressed affect, insomnia, crying,
  irritability, feelings of inadequacy, reduced
  coping ability, fatigue
• changes in estrogen, progesterone, and prolactin

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Cont...

• opioids (especially beta-endorphins) and
  postpartum mood changes
• most severe symptoms have greatest decrease in
  opioids
• constant early on, rise at end of pregnancy, peak
  during parturition, drop immediately afterward
• WITHDRAWAL OF OPIOIDS??

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PERIMENSTRUAL SYNDROME

• PMS
• changes in hormones mood over menstrual cycle
• natural response to hormonal rhythms
• 45 of women (20-90) 3-5 interfere with
  functioning
• symptoms breast pain, weight gain, swelling,
  backaches, sadness, anxiety, skin blemishes, and
  dizziness

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Cont...

• Late Luteal Phase Dysphoric Disorder (DSM-IV)
• anxiety, sadness, irritability, bloating, breast
  enlargement, dysmenorrhea, increased appetite,
  fatigue, depression, headache, edema, insomnia,
  emotional lability, dizziness, confusion, asthma,
  constipation, thirst, nausea, weight gain,
  aggression, acne, boils, increased sex drive,
  moodiness, impaired motor coordination, craving
  for sweet or salty foods, backaches

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Cont...

• P levels are peaking E levels are decreasing
• no consistent differences in P, but could be
  effect of decrease
• GABA affected by P levels
• administering P alleviates some symptoms
• P with TH is very affective

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Cont...

• E affects fluid retention, hyperplasia of mammary
  tissue, carbohydrate metabolism
• accumulation of E in limbic system
• luteal suppression?
• sex hormone cycling suppression?
• target sensitivity abnormal responses

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Cont...

• abrupt withdrawal from steroids??
• antidepressants that alter 5-HT
• other treatments GnRH agonists, benzodiazepines,
  SSRIs
• another theory calcium levels?