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Transcript
The statistics on sanity are that one
out of every four Americans is
suffering from some form of mental
illness. Think of your three best
friends. If they're okay, then it's
you. ~Rita Mae Brown


Introduction
Major Depressive Disorder
 Pathophysiology

Schizophrenia
 Pathophysiology

Post-traumatic Stress Disorder (PTSD)
 Pathophysiology

Conclusions

Affective Disorder = Mood Disorder
 Depressive Disorders
 Bipolar Disorders
 Substance-Abuse Mood Disorders

Too simplistic  need to look deeper
 Co-morbid common

Affective Spectrum Disorder: group of
conditions that do not fit the major, wellestablished categories
 Overlapping manifestations around affective
disregulation
 Mainly characterized by depression, dysphoria,
severe personality disorders, or combination
 Hereditary links
Comprehensive Psychiatry; Vol 26; 1987

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Depressive disorders
Bipolar disorders
Substance-induced
mood disorders
Attentiondeficit/hyperactivity
disorder (ADHD)
Bulimia nervosa
Cataplexy
Dysthymic Disorder
Schizophrenia
Schizoaffective disorders
Social phobias

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




Fibromyalgia
Generalized anxiety
disorder
Irritable bowel syndrome
Migraines
Obsessive-compulsive
disorder (OCD)
Panic disorder
Posttraumatic stress
disorder (PTSD)
Premenstrual dysphoric
disorder
Some personality
disorders (e.g. BPD)
Arch Gen Psychiatry, Vol 60; Feb 2003.





Characteristics
1 in 5
Multiple episodes common
Co-morbidity VERY
common
Neurobiology traditionally
focused on monoamines 
”Monoamine Hypothesis”
 5-HT
 NE

Previous studies on
MDD already
depressed
 5HT studies


BDNF
HPA axis and stress
 CRF
 DA
CMAJ, Vol 180; Feb 3, 2009


Structural changes
Abnormal brain
activation
CMAJ, Vol 180; Feb 3, 2009


Characteristics
Symptoms
 3 Categories


Affects 0.5% to 1% of world pop.
Neurobiology reveals an increase in DA
mesolimbic pathway
 Environment, genetics/heritability, and social
interactions factor
JCI, Vol 119; April 2009.

“The Dopamine
Hypothesis”
 DA receptors and brain
regions
 Version I vs. Version II

“The Neurodevelopment
Hypothesis”
 Pathological brain
development

Structural changes in
different brain regions
Schizophrenia Bulletin, Vol 35; 2009




Characteristics
Symptoms
8% of population; 5.2 mil in a given yr
Reflect stress-induced changes in
neurobiological systems
 Inadequate adaptation to stressors
National Center for PTSD; http://ncptsd.va.gov

Regulation of fear and
stress response
 HPA axis
 NTs/NPs
 Brain regions
▪
▪
▪
▪
PFC
Amygdala
Hippocampus
Brainstem nuclei
CNS Spectrum, Vol 14; Jan 2009



Dynamic
Co-morbid
Similarities
 NTs
 Brain regions
 Mechanisms

“Tip of the iceberg”
"Insanity is doing the same
thing over and over again and
expecting a different result."
Albert Einstein