Mood Disorders A Fresh Look at Bipolar Disorder and  Major Depressive Disorder Ricardo J. Fernandez, MD, ABPN, DFAPA Assoc...
A Brief History of Mood Disorders <ul><li>Bipolar Disorder </li></ul><ul><ul><li>200 CE First reports </li></ul></ul><ul><...
Types of Mood Disorders <ul><li>DSM IV </li></ul><ul><ul><li>Major Depressive Disorder </li></ul></ul><ul><ul><li>Dysthymi...
 
 
Lifetime Risk of Mood Disorders in  General Population <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>Women - 20%...
Genetics of Mood Disorders <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>2-3 fold increased risk in first degree...
Genetic Polymorphism <ul><li>A functional polymorphism is a genetic variant that appears in at least 1% of a population an...
Serotonin Transporter (5-HTTLPR) Polymorphism <ul><li>Three type of genetic variations </li></ul><ul><ul><li>2 long allele...
Avshalom Caspi, et al.  Science  301, 386 (2003);
Avshalom Caspi, et al.  Science  301, 386 (2003);
Mood Disorders are  Very Serious Disorders <ul><li>Higher rates of mortality from other medical conditions </li></ul><ul><...
Neurobiology of Mood Disorders
Neurobiology of Mood Disorders <ul><li>Classic monoamine theory </li></ul><ul><li>Receptor theory </li></ul><ul><li>Brain ...
<ul><li>Importance of achieving  remission  versus response </li></ul><ul><li>Use of clinical scales to determine remissio...
Advancements in the  Treatment of Bipolar Disorders  <ul><li>Use of Mood Disorder questionnaire to  differentiate MDD from...
Risk factors for Mood Disorders <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>Family history </li></ul></ul><ul>...
12 Roszel Rd, Princeton, NJ 31 Clyde Rd, Somerset, NJ 8611 Germantown Ave., Philadelphia,PA 609/419-0123 Ricardo J Fernand...
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  1. 1. Mood Disorders A Fresh Look at Bipolar Disorder and Major Depressive Disorder Ricardo J. Fernandez, MD, ABPN, DFAPA Assoc. Professor of Clinical Psychiatry, Univ.Med.Dent. Of NJ- RWJ Med School Medical Director, Princeton Family Care Associates Offices in Princeton and Somerset, NJ Philadelphia, PA 609/419-0123 [email_address] www.pfcaonline.com Princeton Family Care ASSOCIATES
  2. 2. A Brief History of Mood Disorders <ul><li>Bipolar Disorder </li></ul><ul><ul><li>200 CE First reports </li></ul></ul><ul><ul><li>1654 Jean Pierre Falret </li></ul></ul><ul><ul><ul><li>“ folie circulaire&quot; (circular insanity) </li></ul></ul></ul><ul><ul><ul><li>Familial illness </li></ul></ul></ul><ul><ul><li>1913 Emil Kraepelin </li></ul></ul><ul><ul><ul><li>Manic - Depressive </li></ul></ul></ul><ul><ul><li>1930’s ECT first used </li></ul></ul><ul><ul><li>1949 Lithium first used </li></ul></ul><ul><ul><li>1950 Chlorpromazine first used </li></ul></ul><ul><ul><li>1952 Genetic link recognized </li></ul></ul><ul><ul><li>1979 NAMI established </li></ul></ul><ul><ul><li>1980 </li></ul></ul><ul><ul><ul><li>Bipolar Disorder term adopted </li></ul></ul></ul><ul><ul><li>1995 Depakote approved for BP </li></ul></ul><ul><ul><li>2003 </li></ul></ul><ul><ul><ul><li>First atypical approved for BP </li></ul></ul></ul><ul><li>Major Depressive Disorder </li></ul><ul><ul><li>300 BCE Hippocrates </li></ul></ul><ul><ul><ul><li>“ melancholia ” </li></ul></ul></ul><ul><ul><li>1665 Richard Baker </li></ul></ul><ul><ul><ul><li>Depression term first used </li></ul></ul></ul><ul><ul><ul><ul><li>“ Deprimere” – to press down </li></ul></ul></ul></ul><ul><ul><li>1899 Emil Kraepelin </li></ul></ul><ul><ul><ul><li>Disease concept </li></ul></ul></ul><ul><ul><li>1917 Sigmund freud </li></ul></ul><ul><ul><ul><li>Psychological theories </li></ul></ul></ul><ul><ul><li>1930’s ECT first used </li></ul></ul><ul><ul><li>1952 </li></ul></ul><ul><ul><ul><li>Psychiatric illness concept </li></ul></ul></ul><ul><ul><li>1958 </li></ul></ul><ul><ul><ul><li>MAOI first used </li></ul></ul></ul><ul><ul><ul><li>Imipramine first used </li></ul></ul></ul><ul><ul><li>1980 </li></ul></ul><ul><ul><ul><li>Major Depressive Disorder </li></ul></ul></ul><ul><ul><li>1987 </li></ul></ul><ul><ul><ul><li>Fluoxetine released </li></ul></ul></ul><ul><ul><li>2007 </li></ul></ul><ul><ul><ul><li>Atypical approved as add on for depression treatment </li></ul></ul></ul>
  3. 3. Types of Mood Disorders <ul><li>DSM IV </li></ul><ul><ul><li>Major Depressive Disorder </li></ul></ul><ul><ul><li>Dysthymic Disorder </li></ul></ul><ul><ul><li>Bipolar Disorder Type I </li></ul></ul><ul><ul><li>Bipolar Disorder Type II </li></ul></ul><ul><ul><li>Cyclothymic Disorder </li></ul></ul><ul><ul><li>NOS </li></ul></ul><ul><li>Mixed Phase </li></ul><ul><li>Rapid Cyclers </li></ul><ul><li>Bipolar Spectrum (BPS) </li></ul>
  4. 6. Lifetime Risk of Mood Disorders in General Population <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>Women - 20% </li></ul></ul><ul><ul><li>Men - 11% </li></ul></ul><ul><li>Bipolar Disorder Type I </li></ul><ul><ul><li>Both sexes – 1-1.5% </li></ul></ul>
  5. 7. Genetics of Mood Disorders <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>2-3 fold increased risk in first degree relatives </li></ul></ul><ul><ul><li>The younger the onset the higher the risk for family members </li></ul></ul><ul><ul><li>Children of MDD parents </li></ul></ul><ul><ul><ul><li>2-3 fold increased risk </li></ul></ul></ul><ul><ul><ul><li>Earlier onset </li></ul></ul></ul><ul><ul><li>Fraternal twins </li></ul></ul><ul><ul><ul><li>40-50% risk </li></ul></ul></ul><ul><ul><li>Identical twins </li></ul></ul><ul><ul><ul><li>70% risk </li></ul></ul></ul><ul><ul><li>BP family history </li></ul></ul><ul><ul><ul><li>Increases risk of depression </li></ul></ul></ul><ul><ul><ul><li>If parent BP, 25% risk of MDD in child </li></ul></ul></ul><ul><ul><li>Genetic polymorphism </li></ul></ul><ul><li>Bipolar Disorder </li></ul><ul><ul><li>Familial </li></ul></ul><ul><ul><li>Incidence higher in maternal relatives </li></ul></ul><ul><ul><li>The closer the relationship the higher the risk </li></ul></ul><ul><ul><li>Identical twin </li></ul></ul><ul><ul><ul><li>66-96% risk </li></ul></ul></ul><ul><ul><li>One BP Parent </li></ul></ul><ul><ul><ul><li>30% risk </li></ul></ul></ul><ul><ul><li>Two BP Parents </li></ul></ul><ul><ul><ul><li>60% risk </li></ul></ul></ul><ul><ul><li>MDD Family history </li></ul></ul><ul><ul><ul><li>Does not increase risk for BP </li></ul></ul></ul><ul><ul><li>Genetic polymorphism </li></ul></ul>
  6. 8. Genetic Polymorphism <ul><li>A functional polymorphism is a genetic variant that appears in at least 1% of a population and alters the biological functioning of the individual </li></ul><ul><li>Some types of polymorphisms in Mood Disorders </li></ul><ul><ul><li>Serotonin transporter </li></ul></ul><ul><ul><li>Serotonin 2A receptor </li></ul></ul><ul><ul><li>MTHF reductase </li></ul></ul><ul><ul><li>Catachol -o- methyl tranferase (COMT) </li></ul></ul><ul><ul><li>Tyrosine hydroxylase </li></ul></ul><ul><ul><li>Cytochrome P450 metabolism of medications </li></ul></ul>
  7. 9. Serotonin Transporter (5-HTTLPR) Polymorphism <ul><li>Three type of genetic variations </li></ul><ul><ul><li>2 long alleles (legs) </li></ul></ul><ul><ul><li>2 short alleles </li></ul></ul><ul><ul><li>1 short 1 long allele </li></ul></ul><ul><li>Short alleles predict risk for depression in the presence of repeated stressful life events </li></ul>
  8. 10. Avshalom Caspi, et al. Science 301, 386 (2003);
  9. 11. Avshalom Caspi, et al. Science 301, 386 (2003);
  10. 12. Mood Disorders are Very Serious Disorders <ul><li>Higher rates of mortality from other medical conditions </li></ul><ul><li>Increased substance abuse risk </li></ul><ul><ul><li>MDD- alcohol, nicotine, marijuana </li></ul></ul><ul><ul><li>BP I-wide variety of substances abused </li></ul></ul><ul><ul><li>BP II- high rates of alcohol abuse </li></ul></ul><ul><li>Lifetime suicide attempt risk (.02% in general population) </li></ul><ul><ul><li>Major Depressive Disorder – 12% </li></ul></ul><ul><ul><li>Bipolar Disorder Type I – 17% </li></ul></ul><ul><ul><li>Bipolar Disorder Type II – 24% </li></ul></ul><ul><ul><li>90% of completed suicides can be traced back to a Mood Disorder </li></ul></ul><ul><li>Very important to be under treatment and to be treated to REMISSION not response and then adequately maintained on medication </li></ul><ul><li>If the illness is more than mild in severity, strongly consider being under psychiatric/psychological care versus primary care </li></ul>
  11. 13. Neurobiology of Mood Disorders
  12. 14. Neurobiology of Mood Disorders <ul><li>Classic monoamine theory </li></ul><ul><li>Receptor theory </li></ul><ul><li>Brain Derived Neurotrophic Factor (BDNF) theory </li></ul><ul><li>Substance P theory </li></ul><ul><li>Neuroendocrine theories </li></ul><ul><li>Ion channel theories </li></ul>
  13. 15. <ul><li>Importance of achieving remission versus response </li></ul><ul><li>Use of clinical scales to determine remission </li></ul><ul><li>Use of maintenance dosages to prevent recurrences </li></ul><ul><li>Effectiveness of dual reuptake inhibitors </li></ul><ul><li>Effectiveness of combinations of antidepressants </li></ul><ul><li>Normalization of thyroid function </li></ul><ul><li>Augmentation of antidepressant treatment </li></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><li>Atypicals </li></ul></ul><ul><ul><li>Thyroid supplements </li></ul></ul><ul><ul><li>Folate metabolites and B Vitamins </li></ul></ul><ul><li>More effective ECT with less side effects </li></ul><ul><li>Transcranial Magnetic Stimulation (TMS) </li></ul><ul><li>Vagus Nerve Stimulation (VNS) therapy </li></ul><ul><li>More effective clinical applications of polymorphisms </li></ul>Advancements in the Treatment of Major Depressive Disorder
  14. 16. Advancements in the Treatment of Bipolar Disorders <ul><li>Use of Mood Disorder questionnaire to differentiate MDD from BP </li></ul><ul><li>Recognition of Bipolar Spectrum Disorders </li></ul><ul><ul><li>Especially Bipolar Disorder Type II </li></ul></ul><ul><li>Recognition that treatment will require multiple medications </li></ul><ul><ul><li>Lithium / Lamotrigine </li></ul></ul><ul><li>Mood stabilizers with less side effects </li></ul><ul><li>New medicines to treat Bipolar depression </li></ul><ul><ul><li>Atypicals </li></ul></ul><ul><ul><li>Lamotrigine </li></ul></ul><ul><ul><li>Dopamine agonists </li></ul></ul><ul><li>A greater understanding in the role of thyroid function in mood stability </li></ul><ul><li>A greater understanding of glutamate and GABA in Bipolar Disorder </li></ul><ul><li>Benefits of Omega 3 Fatty Acids </li></ul><ul><li>More effective clinical applications of polymorphisms </li></ul>
  15. 17. Risk factors for Mood Disorders <ul><li>Major Depressive Disorder </li></ul><ul><ul><li>Family history </li></ul></ul><ul><ul><li>Early childhood trauma </li></ul></ul><ul><ul><li>Major life stressors </li></ul></ul><ul><ul><li>Female </li></ul></ul><ul><ul><ul><li>In reproductive phase of life </li></ul></ul></ul><ul><ul><li>Age: 20 to 40 y/o </li></ul></ul><ul><ul><li>Urban life style </li></ul></ul><ul><ul><li>Divorced or separated </li></ul></ul><ul><ul><li>Unemployed </li></ul></ul><ul><ul><li>Alcohol abuse </li></ul></ul><ul><ul><li>Nicotine dependence </li></ul></ul><ul><ul><li>Previous episode </li></ul></ul><ul><li>Bipolar Disorder </li></ul><ul><ul><li>Family history </li></ul></ul><ul><ul><li>Major life stressors </li></ul></ul><ul><ul><li>History of cyclothymia </li></ul></ul><ul><ul><li>Age: 15-30 y/o </li></ul></ul><ul><ul><li>Rapid cycling, BP II, mixed states and cyclothymia greater in women </li></ul></ul><ul><ul><li>Substance abuse </li></ul></ul><ul><ul><li>Lack of sleep can precipitate episodes </li></ul></ul><ul><ul><li>Previous episode </li></ul></ul>
  16. 18. 12 Roszel Rd, Princeton, NJ 31 Clyde Rd, Somerset, NJ 8611 Germantown Ave., Philadelphia,PA 609/419-0123 Ricardo J Fernandez, MD Raquel Rahim, APN Patricia Wieliczko, APN [email_address] Question and Answer Princeton Family Care A S S O C I A T E S

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