Melvin McInnis, M.D. Research Director...Axl Rose • Kraepelin proposed affect to consist of 3...

Understanding Bipolar Disorder

Melvin McInnis, M.D.Research Director

Heinz C. Prechter Bipolar Research FundUniversity of Michigan Depression Center

Celebrities with Bipolar Disorder

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

Margot Kidder Jean-Claude Van Damme Ben Stiller

Axl Rose

• 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

• 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

Normal Affect

Volition

Emotion

Intellect

Moods and disposition fluctuate over time

5

0

10

Volition

Emotion

Intellect

Mania

Mixed Affect

Volition

Emotion

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

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.

Bipolar DisorderUnstable Periodic Illness - Difficult to predict -

Need Biomarker

~4% attempt suicide/year

-Personal Devastation

Energy BaselineMania

Depression

BP Disorder – Challenge:

Unstable illness states – difficult to predict

5

15

25

Year

PHQ940 participants with BPI

PRIORI Research Project –Predicting Individual Outcomes

30,000 calls

40

6 – 12 mos

Acoustic Biosignals

冣

AUC 0.70 – 0.81

AI

NOBEL 2012Shinya Yamanaka & John B. Gurdon

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

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

A C

B D

C

BP

MAP2/Tau Syne1

Lithium pretreatment normalizes bipolar neuron calcium dynamics

Chen, Yoo, Herron

mse

c

• 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.

• 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.

• 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.

• 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…

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

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

• Email:  BPresearch@umich.edu

Prechter Bipolar Genes Project

Heinz C. Prechter1942‐2001