2. 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

3.  Introduction  Major Depressive Disorder  Pathophysiology  Schizophrenia  Pathophysiology  Post-traumatic Stress Disorder (PTSD)  Pathophysiology  Conclusions

4.  Affective Disorder = Mood Disorder  Depressive Disorders  Bipolar Disorders  Substance-Abuse Mood Disorders  Too simplistic  need to look deeper  Co-morbid common

5.  Affective Spectrum Disorder: group of conditions that do not fit the major, well- established categories  Overlapping manifestations around affective disregulation  Mainly characterized by depression, dysphoria, severe personality disorders, or combination  Hereditary links Comprehensive Psychiatry; Vol 26; 1987

6.  Depressive disorders  Bipolar disorders  Substance-induced mood disorders  Attention- deficit/hyperactivity disorder (ADHD)  Bulimia nervosa  Cataplexy  Dysthymic Disorder  Schizophrenia  Schizoaffective disorders  Social phobias  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.

7.  Characteristics  1 in 5  Multiple episodes common  Co-morbidity VERY common  Neurobiology traditionally focused on monoamines  ”Monoamine Hypothesis”  5-HT  NE

8.  Previous studies on MDD already depressed  5HT studies  BDNF  HPA axis and stress  CRF  DA CMAJ, Vol 180; Feb 3, 2009

9.  Structural changes  Abnormal brain activation CMAJ, Vol 180; Feb 3, 2009

10.  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.

11.  “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

12.  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

13.  Regulation of fear and stress response  HPA axis  NTs/NPs  Brain regions ▪ PFC ▪ Amygdala ▪ Hippocampus ▪ Brainstem nuclei CNS Spectrum, Vol 14; Jan 2009

14.  Dynamic  Co-morbid  Similarities  NTs  Brain regions  Mechanisms  “Tip of the iceberg”

15. "Insanity is doing the same thing over and over again and expecting a different result." Albert Einstein