2017-03-15 12:37:02
Prelude
Today's Topics
- Bipolar disorder
Major affective (emotional) disorders
- Types
- Bipolar disorder
- Depression
- Anxiety
- Heritability
- proportion of variance in trait accounted for by genetic factors
- Monozygotic: .69
- Dizygotic: .13
Up/Down Documentary
Bipolar disorder
- Formerly “manic depression” or “manic depressive disorder
- Alternating mood states
- Mania or hypomania (milder form)
- Depression
- Cycles 3-6 mos in length, but
- Rapid cycling (weeks or days)
- Suicide risk 20-60x normal population, (Baldessarini, Pompili, and Tondo 2006)
Symptoms
Prevalence, subtypes
- 1-3% prevalence, subthreshold affects another 2%
- Subtypes
- Bipolar I: manic episodes, possible depressive ones
- Bipolar II: no manic episodes but hypomania + depression
Related symptoms
- Psychosis (hallucinations or delusions)
- Anxiety, attention-deficit hyperactivity disorder (ADHD)
- Substance abuse
Genetics
- Overlap between bipolar disorder and schizophrenia
- Genes for voltage-gated Ca++ channels
- Regulate NT, hormone release
- Gene expression, cell metabolism
- (Craddock and Sklar 2013)
Brain responses to emotional faces ≠ depression
(Lawrence et al. 2004)
(Lawrence et al. 2004)
Amyg, Hip volume reduced,
(Hallahan et al. 2011)
Drug treatments
- Mood stabilizers
- Lithium (Li)
- Valproate (Depakote)
- Anticonvulsants
- GABA agonists
- Usually to treat epilepsy
- e.g. lamotrigine (Lamictal)
- Atypical antipsychotics
Lithium "discovered" accidentally
- Injections of manic patients' urine with lithium compound (chemical stabilizer) into guinea pig test animals.
- Had calming effect
- John Cade discovered in 1948.
- Earliest effective medications for treating mental illness.
Effects of Lithium
- Reduces mania, minimal effects on depressive states
- Increases/preserves PFC, hip, amyg volume
- downregulates DA, glu; upregulates GABA
- modulates 5-HT, NE
- (Malhi et al. 2013)
Other treatment options
- Psychotherapy
- Electroconvulsive Therapy (ECT)
- Sleep medications
Prospects
- STEP-BD cohort (n=1469)
- 58% achieved recovery
- 49% had recurrences within 2 years
- Residual depressive symptoms can persist
- (Geddes and Miklowitz 2013)
An Unquiet Mind
BP summed-up
- Changes in mood, but ≠ depression
- Genetic + environmental risk
- Changes in emotion processing network activity, size of hippocampus
- Heterogeneous
- No simple link to a specific NT system
Next time…
- Depression
References
Baldessarini, Ross J., Maurizio Pompili, and Leonardo Tondo. 2006. “Suicide in Bipolar Disorder: Risks and Management.” CNS Spectrums 11 (06): 465–71. doi:10.1017/S1092852900014681.
Craddock, Nick, and Pamela Sklar. 2013. “Genetics of Bipolar Disorder.” The Lancet 381 (9878): 1654–62. doi:10.1016/S0140-6736(13)60855-7.
Geddes, John R, and David J Miklowitz. 2013. “Treatment of Bipolar Disorder.” The Lancet 381 (9878): 1672–82. doi:10.1016/S0140-6736(13)60857-0.
Hallahan, Brian, John Newell, Jair C. Soares, Paolo Brambilla, Stephen M. Strakowski, David E. Fleck, Tuula Kieseppä, et al. 2011. “Structural Magnetic Resonance Imaging in Bipolar Disorder: An International Collaborative Mega-Analysis of Individual Adult Patient Data.” Biological Psychiatry, Bipolar Disorder: Genes and Brain Development, 69 (4): 326–35. doi:10.1016/j.biopsych.2010.08.029.
Lawrence, Natalia S, Andrew M Williams, Simon Surguladze, Vincent Giampietro, Michael J Brammer, Christopher Andrew, Sophia Frangou, Christine Ecker, and Mary L Phillips. 2004. “Subcortical and Ventral Prefrontal Cortical Neural Responses to Facial Expressions Distinguish Patients with Bipolar Disorder and Major Depression.” Biological Psychiatry 55 (6): 578–87. doi:10.1016/j.biopsych.2003.11.017.
Malhi, Gin S., Michelle Tanious, Pritha Das, Carissa M. Coulston, and Michael Berk. 2013. “Potential Mechanisms of Action of Lithium in Bipolar Disorder.” CNS Drugs 27 (2): 135–53. doi:10.1007/s40263-013-0039-0.