2017-10-17 08:06:00

Prelude

Today's Topics

  • Wrap up on depression
  • Bipolar disorder

Electroconvulsive Therapy (ECT)

  • Last line of treatment for drug-resistant depression
  • Electric current delivered to the brain causes 30-60s seizure.
  • ECT usually done in a hospital's operating or recovery room under general anesthesia.
  • Once every 2 - 5 days for a total of 6 - 12 sessions.

Electroconvulsive Therapy (ECT)

  • Remission rates of up to 50.9% (Dierckx et al. 2012)
  • Seems to work via
    • Anticonvulsant (block Na+ channel or enhance GABA function) effects
    • Neurotrophic (stimulates neurogenesis) effects

Patients speak

Neurogenesis hypothesis, (Mahar et al. 2014)

  • Chronic stress causes neural loss in hipp
  • Chronic stress downregulates 5-HT sensitivity
  • Depression ~ chronic stress
  • Anti-depressants may upregulate neurogenesis via 5-HT modulation

Depression's widespread impact

  • Widespread brain dysfunction
  • Prefrontal cortex, amygdala, HPA axis, circadian rhythms
  • Genetic + environmental factors
  • Disturbance in 5-HT, NE systems, cortisol
  • Many sufferers do not respond to available treatments

Points on depression

  • Drug treatments affect neuromodulator NT systems, but
    • Can't effectively measure NT levels
    • Neuromodulators interact, so many side-effects
  • 'Monoamine hypothesis' of depression is at-best incomplete
  • 'Talk' therapies can change behavior/mood by creating new/strengthened circuits

Major affective (emotional) disorders

  • Types
    • Depression
    • Anxiety
    • Bipolar disorder
  • Heritability
    • proportion of variance in trait accounted for by genetic factors
    • Monozygotic: .69
    • Dizygotic: .13

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 (disinhibition, irritability/agitation) + depression

Related symptoms

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; ventricles larger

(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
  • Preserves PFC, hip, amyg volume
  • downregulates DA, glu; upregulates GABA
  • modulates 5-HT, NE
  • levels can be tested/monitored via blood test
  • (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…

  • Schizophrenia

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.

Dierckx, Bram, Willemijn T Heijnen, Walter W van den Broek, and Tom K Birkenhäger. 2012. “Efficacy of Electroconvulsive Therapy in Bipolar Versus Unipolar Major Depression: A Meta-Analysis.” Bipolar Disorders 14 (2): 146–50. doi:10.1111/j.1399-5618.2012.00997.x.

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.

Mahar, Ian, Francis Rodriguez Bambico, Naguib Mechawar, and José N. Nobrega. 2014. “Stress, Serotonin, and Hippocampal Neurogenesis in Relation to Depression and Antidepressant Effects.” Neuroscience & Biobehavioral Reviews 38 (January): 173–92. doi:10.1016/j.neubiorev.2013.11.009.

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.