On the Edge of Insanity

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On the Edge of Insanity

• Exploring the Pathophysiology of Major Unipolar
  Depression

Trisha L. Olson November 2002
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Why should we be concerned about depression?

• Statistics

• Suicides.

• Disability.

• Health Care Costs

Information provided as public domain from
www.NIMH.gov
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History of Depression Science or Serendipity?

• 1960s
• MAOIs phased out
• Selectivity investigated
• Serotonin
• Norepinephrine
• 1970s
• Monoamine Theory
• developed
• 1980s and 1990s
• NRIs non-selective
• SNRIs in
• SSRIs in
• Current
• SNRIs
• Reboxetine

• 400 B.C.E
• Hippocrates black bile
• 18th century
• Albrecht von Haller opium
• 19th century
• Reserpine hypertension
• 1950s
• Imipramine tuberculosis
• Iproniazid tuberculosis
• Prototypes for MAOIs
• MAUIs
• Advent of electron microscope

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Antidepressant Categories

• MAOIs
• monoamine oxidase inhibitors
• MAUIs
• monoamine uptake inhibitors
• NRIs
• norepinephrine reuptake inhibitors
• SARIs
• serotonin-2 antagonists/reuptake inhibitors
• SNRIs
• selective norepinephrine reuptake inhibitors
• SSRIs
• selective serotonin reuptake inhibitors
• NaSSAs
• noradrenergic specific serotonin agent
• NDRIs
• norepinephrine dopamine reuptake inhibitors

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Other Types of Depression

• Dysthymia
• Bipolar disorder
• Seasonal Affective Disorder
• Postpartum depression
• Adjustment disorder with
• depressed mood
• Atypical depression

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Symptomsof UnipolarDepression

• Loss of energy

• Feelings of worthlessness or
• inappropriate guilt

• Difficulty thinking or concentrating

• Recurrent thoughts of death or suicide

• Physical slowing or agitation

A diagnosis of major depression is made if an
individual has five or more of these symptoms
during the same two-week period including
persistent sadness as well as loss of interest
or pleasure.

• A persistent sad mood

• Loss of interest or pleasure in
• activities that were once enjoyed

• A significant change in appetite or
• body weight

• Difficulty sleeping or oversleeping

From Diagnostic and Statistical Manual of Mental
Disorders, fourth edition
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NEUROTRANSMITTER ACTION

• Neurotransmitter synthesis
• Neurotransmitter storage
• Vesicle transport
• Vesicle fusion and Neuro-
• transmitter release
• Autoreceptor binding
• Receptor binding
• Neurotransmitter reuptake/
• enzyme degradation

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AntidepressantAction
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Precursors
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A Hard Pill to Swallow

• No pathological evidence
• Treatment targets only one
• aspect of a complex process
• Discrepancies between
• physiological and clinical
• efficacy
• Inconsistent results
• Incomplete treatment
• 80 recurrence rate after
• treatment

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Current Research Goals

• Identify distinct subtypes of depression
• Identify origin of disorder
• Advance brain imaging technology
• Identify simple biological markers through blood
  or brain imaging

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Summary

• Cause or causes of depression unknown
• Mechanism of action of antidepressants
• unclear
• Depressive symptoms may have many sources
• Serendipity /Trial and error remain
• primary tools of investigation
• Neuroscience is a dynamic field
• technology - imaging
• physiology - understanding

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Acknowledgements

• Dr. Joanne Rosinski, advisor
• Dr. Brian Cusato
• Stephanie Jefferson
• Joe Malloy
• Sr. Biology Colloquium

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Some Neurotransmitter Precursors
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G-protein receptor action