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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 Depressive disorders Bipolar disorders Substance-induced mood disorders Attentiondeficit/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. 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