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Understanding Bipolar Disorder Melvin McInnis, M.D. Research Director Heinz C. Prechter Bipolar Research Fund University of Michigan Depression Center

Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

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Page 1: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Understanding Bipolar Disorder

Melvin McInnis, M.D.Research Director

Heinz C. Prechter Bipolar Research FundUniversity of Michigan Depression Center

Page 2: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Celebrities with Bipolar Disorder

Ted Turner Sylvia Plath Kay Redfield Jamison, Ph.D.

Margot Kidder Jean-Claude Van Damme Ben Stiller

Axl Rose

Page 3: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Kraepelin proposed affect to consist of 3 components

o Volition • Energy & Drive

• Emotion• Happy / Sad

o Intellect• Rate of thoughts• Content of thoughts

Understanding Affective Disorders

Page 4: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Volition – the drive to care for our offspring

• Emotion – the love for our children

• Intellect – the thoughts & speech related to our interactions with family and loved ones

Affect - Affection

Page 5: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Normal Affect

Volition

Emotion

Intellect

Moods and disposition fluctuate over time

Page 6: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

5

0

10

Volition

Emotion

Intellect

Mania

Page 7: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Mixed Affect

Volition

Emotion

Intellect

Page 8: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• BP disorder is 80% geneticso …and 100% environmental!

• Having a BP sibling or parent increases likelihood of developing BP fivefold compared to general population.

o Risk increases with increasing number of affected infamily.

• Overlap with genetic risk for other mood, anxiety, and psychotic disorders.

BP Disorder & Genetics

Page 9: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Epidemiological Catchment Area Survey (ECA): Comorbidity and Bipolar Disorder

Regier DA et al. JAMA. 1990;264:2511-2518; Chen YW, Dilsaver SC. Am J Psychiatry. 1995;152:280-282; Chen YW, Dilsaver SC. Psychiatry Res. 1995;59:57-64.

Page 10: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Bipolar DisorderUnstable Periodic Illness - Difficult to predict -

Need Biomarker

~4% attempt suicide/year

-Personal Devastation

Energy BaselineMania

Depression

Page 11: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

BP Disorder – Challenge:

Unstable illness states – difficult to predict

5

15

25

Year

PHQ940 participants with BPI

Page 12: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

PRIORI Research Project –Predicting Individual Outcomes

30,000 calls

40

6 – 12 mos

Acoustic Biosignals

AUC 0.70 – 0.81

AI

Page 13: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

NOBEL 2012Shinya Yamanaka & John B. Gurdon

iPSC to model neurological diseases using patients’ somatic cells (e.g. skin)

Page 14: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Neurons differentiated from Control and BP iPSCform neurons (A,B) and synapses (C,D)

A C

B D

C

BP

MAP2/Tau Syne1

Page 15: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •
Page 16: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

Lithium pretreatment normalizes bipolar neuron calcium dynamics

Chen, Yoo, Herron

mse

c

Page 17: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Bipolar disorder with co-existing substance-use disorder is associated with an increase in

o suicide attemptso suicidal ideaso seeking hospital admissiono hospital admission o violenceo aggressive behavioro doubled risk of suicide

Substance-Use Disorder & BP

Potash JB et al. Am J Psychiatry. 2000;157:2048-2050; Scott H et al. Br J Psychiatry. 1998;172:345-350; Comtois KA et al. Biol Psychiatry. 2004;56:757-763; Strakowski SM, DelBello MP. Clin Psychol Rev. 2000;20:191-206; Strakowski SM et al. Arch Gen Psychiatry. 2005;62:851-858.

Page 18: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Less likely to respond to treatment 1

• Less likely to adhere to medications1,2o Less likely to adhere to lithium treatment

• Less likely to gain full remission and resolve symptoms

• Remission during hospitalization less likely to occur vs. no substance-use disorder

Substance-Use in BP: Treatment Issues

1. Goldberg JF et al. J Clin Psychiatry. 1999;60:733-740; 2. Aagaard J, Vestergaard P. J Affect Disord. 1989;12:259–266; 3. Strakowski SM et al. Arch Gen Psychiatry. 1998;55:49-55.

Page 19: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Patients with bipolar disorder have a higher risk of suicide than patients with any other psychiatric or medical illness

o Odds ratio for suicide attempts is 6.2 -- higher than any otherdisorder, including depression

Suicide Risk in Bipolar Disorder

Woods SW. J Clin Psychiatry. 2000;61(Suppl 13):38-41; Chen YW, Dilsaver SC. Biol Psychiatry. 1996;39:896-899; Goldberg JF, Harrow M. J Affect Disord. 2004;81:123-131.

Page 20: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• Bipolar disorders are a category of mood disorders -with a broad range of severity.

• Bipolar disorder is eminently treatable.o But requires treatment to be ongoing

• Collaboration between treatment team and patient

• Bipolar disorder is a serious illness.o Lives, families, and careers are affectedo People can die from it.

Bipolar Disorder Concluding Statements…

Page 21: Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3 components o Volition • Energy & Drive • Emotion • Happy / Sad o Intellect •

• For more information: www.prechterfund.orgwww.depressioncenter.org

• Toll‐free phone number:1‐877‐UM GENES 1‐877‐864 3637

• Email:  [email protected]

Prechter Bipolar Genes Project

Heinz C. Prechter1942‐2001