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The Biology of Mental Illness
John Borghi, PhD
Wheatfield with Crows, 1890, Van Gogh
@JohnBorghi
Lebowitz, M. S., & Ahn, W. K. (2014). Effects of biological explanations for mental disorders on
clinicians’ empathy. Proc...
Neurons in the cerebral cortexAn individual neuron
Belmaker, R. H., Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68.
Jones-Hagata, L. B., Ortega, B. N., Zaiko, Y. V., Roach, E. L., Korgaonkar, M. S., Grieve, S. M., ... & Etkin, A. (2015). ...
Fornito, A., Zalesky, A., & Breakspear, M. (2015). The connectomics of brain disorders. Nature Reviews Neuroscience, 16(3)...
Neurodome
Irimia, A., Chambers, M. C., Torgerson, C. M., & Van Horn, J. D. (2012). Circular representation of human cortical network...
The Papyrus Ebers – 1550 BCE
(Facsimile)
Holtzheimer, P. E., & Mayberg, H. S. (2011). Stuck in a rut: rethinking depression and its treatment. Trends in neuroscien...
The Diagnostic and Statistical Manual of Mental Disorders : Versions 3 (1980) and 4 - TR (2000)
American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric As...
American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric As...
Emil Kraepelin
(1856 – 1926)
Henri Laborit
(1914 – 1995)
Clifford Beers
(1876 – 1943)
Carlsson, A., & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3‐methoxytyramine and normet...
Tandon, R., Gaebel, W., Barch, D. M., Bustillo, J., Gur, R. E., Heckers, S., ... & Carpenter, W. (2013). Definition and de...
The Dopamine Hypothesis of Schizophrenia
Increased activity in a certain dopamine receptors (the D2 receptors)
cause the s...
Evidence For:
-Drugs that increase levels of
dopamine (e.g. cocaine,
amphetamines) can cause
psychosis-like symptoms.
-Som...
Okubo, Y., Olsson, H., Ito, H., Lofti, M., Suhara, T., Halldin, C., & Farde, L. (1999). PET mapping of extrastriatal D2-li...
Lewis, D. A., & Sweet, R. A. (2009). Schizophrenia from a neural circuitry perspective : advancing toward rational pharmac...
Shenton, M. E., Kikinis, R., Jolesz, F. A., Pollak, S. D., LeMay, M., Wible, C. G., ... & McCarley, R. W. (1992). Abnormal...
Barch, D. M., & Ceaser, A. (2012). Cognition in schizophrenia: core psychological and neural mechanisms.Trends in Cognitiv...
Gottesman, I. I. (1991). Schizophrenia Genesis: The Origins of Madness. Freeman.
0 5 10 15 20 25 30 35 40 45 50
None
First...
Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O'Donovan, M.
C., ... & Sullivan, P. F. (2015). Evaluati...
Schizophrenia Working Group of the Psychiatric Genomics Consortium. (2014). Biological insights from 108 schizophrenia-ass...
Tsuang, M. T. (2001). Genes, environment and schizophrenia. The British Journal of Psychiatry, 178(40), 18s–24. doi:10.119...
Evidence For:
-Drugs that cause increased levels
of monoamines are effective
antidepressants.
Evidence Against:
-People wi...
Molloy, B. B., & Schmiegel, K. K. (1982). U.S. Patent No. 4,314,081. Washington, DC: U.S. Patent and Trademark Office.
Name Brand Name Type 2010 Prescriptions
Sertraline Zoloft SSRI 33,409,838
Citalopram Celexa SSRI 27,993,635
Fluoxetine Pro...
Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific lit...
Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific lit...
Kao, C. F., Fang, Y. S., Zhao, Z., & Kuo, P. H. (2011). Prioritization and evaluation of depression candidate genes by com...
Hamilton, J. P., Siemer, M., & Gotlib, I. H. (2008). Amygdala volume in major depressive disorder: a meta-analysis of magn...
Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M. (2013). Using standardized fMRI protocols to...
Holtzheimer, P. E., & Mayberg, H. S. (2011). Stuck in a rut: rethinking
depression and its treatment. Trends in neuroscien...
Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68.
Thomas, E. J., & Elliott, R. (2009). Brain imaging correlates of cognitive impairment in depression. Frontiers in human ne...
Name Used for… U.S. Prescriptions
Xanax Anxiety 47,792,000
Celexa Depression, Anxiety 37,728,000
Zoloft Depression, Anxiet...
Cross-Disorder Group of the Psychiatric Genomics Consortium. (2013). Genetic relationship between five psychiatric disorde...
Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC medicin...
Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC medicin...
Thanks!
From:
Ros, H. Farinella, M. (2014). Neurocomic. Nobrow Press
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
The Biology of Mental Illness
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The Biology of Mental Illness

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Since the mid twentieth century, psychologists, psychiatrists, and neuroscientists have sought to explain mental illness in biological terms. In this talk, we'll discuss the emergence of influential biological models such as the monoamine hypothesis of depression, the rise of neuropsychopharmacology (the prescription and widespread use of medications such Prozac and Zoloft), and the complexity of studying complex conditions like generalized anxiety and schizophrenia in biological terms.

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The Biology of Mental Illness

  1. 1. The Biology of Mental Illness John Borghi, PhD Wheatfield with Crows, 1890, Van Gogh @JohnBorghi
  2. 2. Lebowitz, M. S., & Ahn, W. K. (2014). Effects of biological explanations for mental disorders on clinicians’ empathy. Proceedings of the National Academy of Sciences, 111(50), 17786-17790.
  3. 3. Neurons in the cerebral cortexAn individual neuron
  4. 4. Belmaker, R. H., Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68.
  5. 5. Jones-Hagata, L. B., Ortega, B. N., Zaiko, Y. V., Roach, E. L., Korgaonkar, M. S., Grieve, S. M., ... & Etkin, A. (2015). Identification of a Common Neurobiological Substrate for Mental Illness. JAMA Psychiatry Shackman, A. J., Salomons, T. V., Slagter, H. A., Fox, A. S., Winter, J. J., & Davidson, R. J. (2011). The integration of negative affect, pain and cognitive control in the cingulate cortex. Nature Reviews Neuroscience, 12(3), 154-167.
  6. 6. Fornito, A., Zalesky, A., & Breakspear, M. (2015). The connectomics of brain disorders. Nature Reviews Neuroscience, 16(3), 159-172.
  7. 7. Neurodome
  8. 8. Irimia, A., Chambers, M. C., Torgerson, C. M., & Van Horn, J. D. (2012). Circular representation of human cortical networks for subject and population-level connectomic visualization. Neuroimage, 60(2), 1340-1351.
  9. 9. The Papyrus Ebers – 1550 BCE (Facsimile)
  10. 10. Holtzheimer, P. E., & Mayberg, H. S. (2011). Stuck in a rut: rethinking depression and its treatment. Trends in neurosciences, 34(1), 1-9.
  11. 11. The Diagnostic and Statistical Manual of Mental Disorders : Versions 3 (1980) and 4 - TR (2000)
  12. 12. American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric Association.
  13. 13. American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric Association. Bipolar I Disorder is mainly defined by manic or mixed episodes that last at least seven days, or by manic symptoms that are so severe that the person needs immediate hospital care. Usually, the person also has depressive episodes, typically lasting at least two weeks. The symptoms of mania or depression must be a major change from the person's normal behavior. Bipolar II Disorder is defined by a pattern of depressive episodes shifting back and forth with hypomanic episodes, but no full-blown manic or mixed episodes. Bipolar Disorder Not Otherwise Specified (BP-NOS) is diagnosed when a person has symptoms of the illness that do not meet diagnostic criteria for either bipolar I or II. The symptoms may not last long enough, or the person may have too few symptoms, to be diagnosed with bipolar I or II. However, the symptoms are clearly out of the person's normal range of behavior. Cyclothymic Disorder, or Cyclothymia, is a mild form of bipolar disorder. People who have cyclothymia have episodes of hypomania that shift back and forth with mild depression for at least two years. However, the symptoms do not meet the diagnostic requirements for any other type of bipolar disorder.
  14. 14. Emil Kraepelin (1856 – 1926) Henri Laborit (1914 – 1995) Clifford Beers (1876 – 1943)
  15. 15. Carlsson, A., & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3‐methoxytyramine and normetanephrine in mouse brain. Acta pharmacologica et toxicologica, 20(2), 140-144.
  16. 16. Tandon, R., Gaebel, W., Barch, D. M., Bustillo, J., Gur, R. E., Heckers, S., ... & Carpenter, W. (2013). Definition and description of schizophrenia in the DSM- 5. Schizophrenia research, 150(1), 3-10.
  17. 17. The Dopamine Hypothesis of Schizophrenia Increased activity in a certain dopamine receptors (the D2 receptors) cause the symptoms of schizophrenia. Healthy Controls Schizophrenia ActivationofD2Receptors Missale, C., Nash, S. R., Robinson, S. W., Jaber, M., & Caron, M. G. (1998). Dopamine receptors: from structure to function. Physiological reviews, 78(1), 189-225.
  18. 18. Evidence For: -Drugs that increase levels of dopamine (e.g. cocaine, amphetamines) can cause psychosis-like symptoms. -Some dopamine antagonists (e.g. thorazine, haloperidol) can reduce psychotic symptoms. Evidence Against: -Drugs that increase levels of glutamate (e.g. PCP, ketamine) can also cause psychosis-like symptoms. -Decreases in dopamine does not correlate with symptom reduction. -Dopamine drugs have biochemical effect in minutes, symptom reduction takes significantly longer. -There are a huge number of biochemical, anatomical, and functional disruptions observed in patients with schizophrenia. The Dopamine Hypothesis - Increased activity in a certain dopamine receptors (the D2 receptors) cause the symptoms of schizophrenia.
  19. 19. Okubo, Y., Olsson, H., Ito, H., Lofti, M., Suhara, T., Halldin, C., & Farde, L. (1999). PET mapping of extrastriatal D2-like dopamine receptors in the human brain using an anatomic standardization technique and [11C] FLB 457. Neuroimage, 10(6), 666-674.
  20. 20. Lewis, D. A., & Sweet, R. A. (2009). Schizophrenia from a neural circuitry perspective : advancing toward rational pharmacological therapies, 119(4). doi:10.1172/JCI37335.706 Structural changes in Schizophrenia
  21. 21. Shenton, M. E., Kikinis, R., Jolesz, F. A., Pollak, S. D., LeMay, M., Wible, C. G., ... & McCarley, R. W. (1992). Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study. New England Journal of Medicine, 327(9), 604-612.
  22. 22. Barch, D. M., & Ceaser, A. (2012). Cognition in schizophrenia: core psychological and neural mechanisms.Trends in Cognitive Sciences, 16(1), 27–34. doi:10.1016/j.tics.2011.11.015 Functional changes in Schizophrenia
  23. 23. Gottesman, I. I. (1991). Schizophrenia Genesis: The Origins of Madness. Freeman. 0 5 10 15 20 25 30 35 40 45 50 None First Cousin Uncle/Aunt Nephew/Niece Grandchild Half Sibling Parent Sibling Child Dizygotic Twin Monozygotic Twin First Degree Relative Second Degree Relative RelationshiptoindividualwithSchizophrenia Lifetime risk of developing Schizophrenia (%)
  24. 24. Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O'Donovan, M. C., ... & Sullivan, P. F. (2015). Evaluating historical candidate genes for schizophrenia. Molecular Psychiatry.
  25. 25. Schizophrenia Working Group of the Psychiatric Genomics Consortium. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature,511(7510), 421-427. Figure 1: Manhattan plot showing schizophrenia associations.
  26. 26. Tsuang, M. T. (2001). Genes, environment and schizophrenia. The British Journal of Psychiatry, 178(40), 18s–24. doi:10.1192/bjp.178.40.s18
  27. 27. Evidence For: -Drugs that cause increased levels of monoamines are effective antidepressants. Evidence Against: -People with MDD don’t show significant disruptions in monoamine levels. -Monoamine depletion does not cause depression in healthy people. -Medications that have no direct effect on monoamine system can also act as antidepressants Healthy Controls MDD The Monoamine Hypothesis – Decreased levels of monoamines (e.g. serotonin, dopamine) cause the symptoms of depression LevelofSerotonin
  28. 28. Molloy, B. B., & Schmiegel, K. K. (1982). U.S. Patent No. 4,314,081. Washington, DC: U.S. Patent and Trademark Office.
  29. 29. Name Brand Name Type 2010 Prescriptions Sertraline Zoloft SSRI 33,409,838 Citalopram Celexa SSRI 27,993,635 Fluoxetine Prozac SSRI 24,473,994 Escitalopram Lexapro SSRI 23,000,456 Tranzodone Desyrel SARI 18,786,495 Duloxetine Cymbalta SNRI 14,591,949 Paroxetine Paxil SSRI 12,979,366 Amitriptyline Elavil TCA 12,611,254 Venlafaxine XR Effexor XR SSRI 7,603,949 Bupropion XL Wellbutrin NDRI 7,317,814 Mirtazapine Remeron TeCA 6,308,288 Venlafaxine ER Effexor SNRI 5,526,132 Bupropion SR NDRI 4,588,996 Desvenlafaxine Pristiq SNRI 3,412,354 Nortriptyline Sensoval TCA 3,210,476 Bupropion ER NDRI 3,132,327 Venlafaxine Effexor SNRI 2,980,525 Bupropion Wellbutrin XL NDRI 753,516 From DrugTopics.com
  30. 30. Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS medicine, 2(12), e392.
  31. 31. Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS medicine, 2(12), e392.
  32. 32. Kao, C. F., Fang, Y. S., Zhao, Z., & Kuo, P. H. (2011). Prioritization and evaluation of depression candidate genes by combining multidimensional data resources. PLoS One, 6(4), e18696.
  33. 33. Hamilton, J. P., Siemer, M., & Gotlib, I. H. (2008). Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Molecular psychiatry, 13(11), 993-1000.
  34. 34. Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M. (2013). Using standardized fMRI protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive and emotional tasks in major depressive disorder: first wave results from the iSPOT-D study. Neuropsychopharmacology, 38(5), 863-871. Harvey, P. O., Fossati, P., Pochon, J. B., Levy, R., LeBastard, G., Lehéricy, S., ... & Dubois, B. (2005). Cognitive control and brain resources in major depression: an fMRI study using the n-back task. Neuroimage, 26(3), 860-869.
  35. 35. Holtzheimer, P. E., & Mayberg, H. S. (2011). Stuck in a rut: rethinking depression and its treatment. Trends in neurosciences, 34(1), 1-9. Deep Brain Stimulation Repetitive Transcranial Magnetic Stimulation
  36. 36. Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68.
  37. 37. Thomas, E. J., & Elliott, R. (2009). Brain imaging correlates of cognitive impairment in depression. Frontiers in human neuroscience, 3.
  38. 38. Name Used for… U.S. Prescriptions Xanax Anxiety 47,792,000 Celexa Depression, Anxiety 37,728,000 Zoloft Depression, Anxiety, OCD, PTSD, PMDD 37,208,000 Ativan Anxiety, panic disorder 27,172,000 Prozac Depression, Anxiety 24,507,000 Lexapro Depression, Anxiety 23,707,000 Desyrel Depression, Anxiety 22,591,000 Cymbalta Depression, Anxiety 17,770,000 Valium Anxiety, Panic disorder 14,694,000 Seroquel Bipolar disorder, Depression 14,213,000 Grohol, J. (2012). Top 25 Psychiatric Medication Prescriptions for 2011. Psych Central.
  39. 39. Cross-Disorder Group of the Psychiatric Genomics Consortium. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature genetics, 45(9), 984-994
  40. 40. Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC medicine, 11(1), 126.
  41. 41. Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC medicine, 11(1), 126.
  42. 42. Thanks! From: Ros, H. Farinella, M. (2014). Neurocomic. Nobrow Press

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