This presentation explores an integrated approach to medication management in bipolar disorder. Individuals with bipolar spectrum conditions are a grater risk of illness, disease and early death. Understanding common health comorbidities in bipolar spectrum conditions and developing a working model to treat both health and mental health comorbidities with least possible medical interventions could improve longevity and health span for those with mood disorders.

1. Bipolar and Health Complexity
Addressing Health Complexity for
Individuals w/ Mood Disorders

2. Bipolar Disorder Is Like Having Two Serious Illnesses at Once
Nicole Foubister
Psychiatrist
Assistant Professor Child and Adolescent Psychiatry, NYU

6. Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical illness in bipolar
disorder. The British Journal of Psychiatry, 205(6), 465-472.

8. Common
Mechanism
COMMON MECHANISM APPROACH
This approach there are different symptoms that both are impacted
by a mechanism of the medicine or intervention
Let’s Choose
two Symptoms
that can be
effected by one
intervention
either
biological,
psychological or
social
Chronic Pain
Different
Symptoms
Problem Based Learning Bipolar – II and Pain
Bipolar - II

9. Common
Symptom
Intervention
Medication
Let’s Choose a
Symptom that
Overlaps
Between
Chronic Pain
and Bipolar to
develop a
medication,
social and
psychological
intervention.
Bipolar-II
Chronic
Pain
Problem Based Learning Bipolar – II and Pain
COMMON SYPTOM APPROACH
Often it is possible to find an overlap in medication management
that addresses both mental health and health condition. Lets look at
pain and PTSD.

11. 1. Cultural and Social Factors
2. Health Literacy
3. Medication Adherence
4. Psychological Factors
Assessment and Treatment
Pharmacology & Comorbidity
CASE BASED LEARNING
In Small Groups Discuss a Current or Past
Case Exploring the Above Four Factors and
How they Impact Pharmacotherapy.

12. Bipolar Disorder Genetics
• World wide life time incidence of bipolar disorder is
2.4% in the US it is 4.4%.
• Monozygotic co-twin 40-70%; first degree relative 5-
10%; unrelated person 0.5-1.5%.
• Gene X Environment: One study indicating BDNF
gene interacting with stressful life events to increase
risk of bipolar depressive episodes.
• Genome-wide association (GWAS) & Single
nucleotide polymorphisms (SNPs): SLC6A4, TPH2,
DRD4, SLC6A3, DAOA, DTNBP1, NRG1, DISC1
and BDNF.
Serretti, A., & Mandelli, L. (2008). The genetics of bipolar disorder: genome ‘hot regions,’genes, new potential candidates
and future directions. Molecular psychiatry, 13(8), 742.
Uher, R. (2014). Gene–environment interactions in severe mental illness. Frontiers in psychiatry, 5, 48.

15. Epigenetics of Bipolar Medication
• Lithium and Valproic Acid: Increased methylation leading to
amplification of leptin via lepr gene.
• Mixed or manic state BDNF methylation levels near controls
• Patients in euthymic or depressed states higher BDNF
methylation levels.
• Lithium and valproate both decreased BDNF methylation levels
(non-sig).
• Mice treated with olanzapine showed increased methylation in
multiple genes higher number in hippocampus.
• Later study found: significant increase methylation at the
hippocampal dopamine-DARPP32 pathway.
Lockwood, L. E., & Youssef, N. A. (2017). Systematic Review of Epigenetic Effects of Pharmacological Agents for Bipolar Disorders.
Brain sciences, 7(11), 154.

16. Inflammation and Bipolar
• Cox-2 inhibitor celecoxib (antiarthrytic medication) has
antidepressant effects in bipolar disorder (BD) patients
during depressive or mixed phases
• Bipolar disorder and inflammation are related through both
gene differences and genetic expressions. Episodes of Manic
or Depressive States show alterations in inflammatory
markers.
• Individuals with bipolar disorders have higher disease burden
and this burden is impacted by inflammatory cytokines.
• Bio-behavioral links exist between inflation and exercise,
sleep, EtOH, Smoking, Artery Disease, Insulin Resistance,
and Pain
• Multiple medications for bipolar disorder also have positive
impact on inflammation markers.
Goldstein, B. I., Kemp, D. E., Soczynska, J. K., & Mclntyre, R. S. (2009). Inflammation and the phenomenology,
pathophysiology, comorbidity, and treatment of bipolar disorder: a systematic review of the literature. The Journal of clinical
psychiatry.

20. Öngür, D., Lundy, M., Greenhouse, I., Shinn, A. K., Menon, V., Cohen, B. M., & Renshaw, P. F. (2010). Default mode network
abnormalities in bipolar disorder and schizophrenia. Psychiatry Research: Neuroimaging, 183(1), 59-68.

21. Panda, R., Bharath, R. D.,
Upadhyay, N., Mangalore,
S., Chennu, S., & Rao, S. L.
(2016). Temporal dynamics
of the default mode network
characterize meditation-
induced alterations in
consciousness. Frontiers in
human neuroscience, 10,
372.
Temporal
Dynamics of the
Default Mode
Network
Characterize
Meditation-
Induced
Alterations in
Consciousness

22. Cumulative Incidence for Bipolar Disorder after age 15 years over Number
of Early Adverse Events.
Bergink, V., Larsen, J. T., Hillegers, M. H. J., Dahl, S. K., Stevens, H., Mortensen, P. B., ... & Munk-Olsen, T. (2016). Childhood
adverse life events and parental psychopathology as risk factors for bipolar disorder. Translational psychiatry, 6(10), e929.

23. Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical illness in bipolar
disorder. The British Journal of Psychiatry, 205(6), 465-472.

25. Common
Mechanism
COMMON MECHANISM APPROACH
This approach there are different symptoms that both are impacted
by a mechanism of the medicine or intervention
Let’s Choose
two Symptoms
that can be
effected by one
intervention
either
biological,
psychological or
social
____________
Different
Symptoms
Problem Based Learning Bipolar – II and Health
Bipolar - II

26. Common
Symptom
Intervention
Medication
Let’s Choose a
Symptom that
Overlaps
Between
Chronic Pain
and Bipolar to
develop a
medication,
social and
psychological
intervention.
Bipolar-II
_______
Problem Based Learning Bipolar – II and Health
COMMON SYPTOM APPROACH
Often it is possible to find an overlap in medication management
that addresses both mental health and health condition. Lets look at
pain and PTSD.