The document provides an overview of the biology of mental illness by summarizing research on the neurobiology, genetics, and treatment of disorders such as schizophrenia, depression, and bipolar disorder. Key findings discussed include evidence that these conditions involve disruptions in brain structure and function, as well as influences from genetic and environmental factors. The document also traces historical conceptions of these illnesses and notes shifts towards more biologically-based diagnostic models and treatments targeting neural circuits and systems.

1. The Biology of Mental Illness
John Borghi, PhD
Wheatfield with Crows, 1890, Van Gogh
@JohnBorghi

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3. Neurons in the cerebral cortexAn individual neuron

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8. Neurodome

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10. The Papyrus Ebers – 1550 BCE
(Facsimile)

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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.

19. Emil Kraepelin
(1856 – 1926)
Henri Laborit
(1914 – 1995)
Clifford Beers
(1876 – 1943)

23. Carlsson, A., & Lindqvist, M. (1963). Effect of chlorpromazine or haloperidol on formation of 3‐methoxytyramine and normetanephrine
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25. 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.

26. 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.

27. 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.

28. 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

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doi:10.1016/j.tics.2011.11.015
Functional changes in Schizophrenia

31. 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 (%)

32. Farrell, M. S., Werge, T., Sklar, P., Owen, M. J., Ophoff, R. A., O'Donovan, M.
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33. 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.

34. Tsuang, M. T. (2001). Genes, environment and schizophrenia. The British Journal of Psychiatry, 178(40), 18s–24. doi:10.1192/bjp.178.40.s18

37. 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

38. Molloy, B. B., & Schmiegel, K. K. (1982). U.S. Patent No. 4,314,081. Washington, DC: U.S. Patent and Trademark Office.

39. 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

40. Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS medicine, 2(12), e392.

41. Lacasse, J. R., & Leo, J. (2005). Serotonin and depression: A disconnect between the advertisements and the scientific literature. PLoS medicine, 2(12), e392.

43. Kao, C. F., Fang, Y. S., Zhao, Z., & Kuo, P. H. (2011). Prioritization and evaluation of depression candidate genes by combining multidimensional data
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44. Hamilton, J. P., Siemer, M., & Gotlib, I. H. (2008). Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance
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45. 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.
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46. 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

47. Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68.

48. Thomas, E. J., & Elliott, R. (2009). Brain imaging correlates of cognitive impairment in depression. Frontiers in human neuroscience, 3.

49. 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.

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52. Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC medicine, 11(1), 126.

55. Thanks!
From:
Ros, H. Farinella, M. (2014). Neurocomic. Nobrow Press