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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 protected] www.pfcaonline.com Princeton Family Family Care Care ASSOCIATES

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Mood DisordersA Fresh Look at Bipolar Disorder and

Major Depressive Disorder

Ricardo J. Fernandez, MD, ABPN, DFAPAAssoc. Professor of Clinical Psychiatry, Univ.Med.Dent. Of NJ- RWJ Med School

Medical Director, Princeton Family Care Associates

Offices in Princeton and Somerset, NJPhiladelphia, PA

609/419-0123 [email protected]

www.pfcaonline.com

PrincetonFamily Family CareCare ASSOCIATES

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A Brief History of Mood Disorders• Bipolar Disorder

– 200 CE First reports– 1654 Jean Pierre Falret

• “folie circulaire" (circular insanity)

• Familial illness – 1913 Emil Kraepelin

• Manic - Depressive– 1930’s ECT first used– 1949 Lithium first used– 1950 Chlorpromazine first used– 1952 Genetic link recognized– 1979 NAMI established– 1980

• Bipolar Disorder term adopted

– 1995 Depakote approved for BP– 2003

• First atypical approved for BP

• Major Depressive Disorder– 300 BCE Hippocrates

• “melancholia”– 1665 Richard Baker

• Depression term first used– “Deprimere” – to press

down– 1899 Emil Kraepelin

• Disease concept– 1917 Sigmund freud

• Psychological theories – 1930’s ECT first used– 1952

• Psychiatric illness concept– 1958

• MAOI first used• Imipramine first used

– 1980• Major Depressive Disorder

– 1987• Fluoxetine released

– 2007 • Atypical approved as add on

for depression treatment

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Types of Mood Disorders

• DSM IV– Major Depressive Disorder– Dysthymic Disorder– Bipolar Disorder Type I– Bipolar Disorder Type II– Cyclothymic Disorder– NOS

• Mixed Phase• Rapid Cyclers• Bipolar Spectrum (BPS)

86%

2%

2%

10%

MDDBP IBP IINOS

50%

2%15%

33% MDDBP IBP IIBPS

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Lifetime Risk of Mood Disorders in General Population

• Major Depressive Disorder– Women - 20%

– Men - 11%

• Bipolar Disorder Type I– Both sexes – 1-1.5%

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Genetics of Mood Disorders

• Major Depressive Disorder– 2-3 fold increased risk in first

degree relatives– The younger the onset the

higher the risk for family members

– Children of MDD parents• 2-3 fold increased risk• Earlier onset

– Fraternal twins• 40-50% risk

– Identical twins• 70% risk

– BP family history• Increases risk of

depression• If parent BP, 25% risk

of MDD in child– Genetic polymorphism

• Bipolar Disorder– Familial– Incidence higher in

maternal relatives– The closer the relationship

the higher the risk– Identical twin

• 66-96% risk– One BP Parent

• 30% risk– Two BP Parents

• 60% risk– MDD Family history

• Does not increase risk for BP

– Genetic polymorphism

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Genetic Polymorphism

• A functional polymorphism is a genetic variant that appears in at least 1% of a population and alters the biological functioning of the individual

• Some types of polymorphisms in Mood Disorders– Serotonin transporter

– Serotonin 2A receptor

– MTHF reductase

– Catachol -o- methyl tranferase (COMT)

– Tyrosine hydroxylase

– Cytochrome P450 metabolism of medications

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Serotonin Transporter (5-HTTLPR)Polymorphism

• Three type of genetic variations– 2 long alleles (legs)

– 2 short alleles

– 1 short 1 long allele

• Short alleles predict risk for depression in the presence of repeated stressful life events

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Avshalom Caspi, et al. Avshalom Caspi, et al. Science 301, 386 (2003);

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Avshalom Caspi, et al. Avshalom Caspi, et al. Science 301, 386 (2003);

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Mood Disorders are Very Serious Disorders

• Higher rates of mortality from other medical conditions• Increased substance abuse risk

– MDD- alcohol, nicotine, marijuana– BP I-wide variety of substances abused– BP II- high rates of alcohol abuse

• Lifetime suicide attempt risk (.02% in general population)– Major Depressive Disorder – 12%– Bipolar Disorder Type I – 17%– Bipolar Disorder Type II – 24%– 90% of completed suicides can be traced back to a

Mood Disorder • Very important to be under treatment and to be treated to

REMISSION not response and then adequately maintained on medication

• If the illness is more than mild in severity, strongly consider being under psychiatric/psychological care versus primary care

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Neurobiology of Mood Disorders

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Neurobiology of Mood Disorders

• Classic monoamine theory• Receptor theory• Brain Derived

Neurotrophic Factor (BDNF) theory

• Substance P theory• Neuroendocrine theories• Ion channel theories

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• Importance of achieving remission versus response• Use of clinical scales to determine remission• Use of maintenance dosages to prevent recurrences• Effectiveness of dual reuptake inhibitors• Effectiveness of combinations of antidepressants• Normalization of thyroid function• Augmentation of antidepressant treatment

– Lithium– Atypicals– Thyroid supplements– Folate metabolites and B Vitamins

• More effective ECT with less side effects• Transcranial Magnetic Stimulation (TMS)• Vagus Nerve Stimulation (VNS) therapy • More effective clinical applications of polymorphisms

Advancements in the Treatment of Major Depressive Disorder

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Advancements in the Treatment of Bipolar Disorders • Use of Mood Disorder questionnaire to

differentiate MDD from BP• Recognition of Bipolar Spectrum Disorders

– Especially Bipolar Disorder Type II• Recognition that treatment will require multiple medications

– Lithium / Lamotrigine• Mood stabilizers with less side effects• New medicines to treat Bipolar depression

– Atypicals– Lamotrigine– Dopamine agonists

• A greater understanding in the role of thyroid function in mood stability

• A greater understanding of glutamate and GABA in Bipolar Disorder

• Benefits of Omega 3 Fatty Acids• More effective clinical applications of polymorphisms

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Risk factors for Mood Disorders

• Major Depressive Disorder– Family history– Early childhood trauma– Major life stressors– Female

• In reproductive phase of life

– Age: 20 to 40 y/o– Urban life style– Divorced or separated– Unemployed– Alcohol abuse– Nicotine dependence– Previous episode

• Bipolar Disorder– Family history– Major life stressors– History of cyclothymia– Age: 15-30 y/o– Rapid cycling, BP II,

mixed states and cyclothymia greater in women

– Substance abuse– Lack of sleep can

precipitate episodes– Previous episode

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PrincetonFamily CareFamily Care A S S O C I A T E S

12 Roszel Rd, Princeton, NJ31 Clyde Rd, Somerset, NJ8611 Germantown Ave.,

Philadelphia,PA

609/419-0123Ricardo J Fernandez, MD Raquel Rahim, APNPatricia Wieliczko, APN [email protected]

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