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

2. Self Portrait, 1889, Van Gogh Portrait of Dr Gachet, 1890, Van Gogh 3. 24 Year Old Male 26 Year Old Female 4. Neurons in the cerebral cortexAn individual neuron 5. NeuronsandSynapses 6. Frontal Lobe Parietal Lobe Temporal Lobe Occipital Lobe 7. 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. Diffusion Tensor Imaging Circular Connectogram 8. The Papyrus Ebers 1550 BCE (Facsimile) 9. Bryan, C. P. (1931). The Papyrus Ebers. (Translated from the Original German) 10. From: Lavater, J. K. (17751778). Physiognomische Fragmente zur Befrderung der Menschenkenntnis und Menschenliebe. Hippocrates (460 BCE 377 BCE) 11. Saint Bartholomew Exorcising, 1440-1460 12. A Rakes Progress (Plate 8), 1832, Hogarth New Bethlem Hospital, St. Georges Fields, 1828, Shepard (Drawing) & Tingle (Engraving) 13. Emil Kraepelin (1856 1926) Henri Laborit (1914 1995) Clifford Beers (1876 1943) 14. Mental Hospitals, Vol. 7, No. 8. Mental Hospitals, Vol. 7, No. 4. 15. From Forbes.com 16. The Diagnostic and Statistical Manual of Mental Disorders : Versions 3 (1980) and 4 - TR (2000) 17. American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric Association. Criteria for Schizophrenia Two (or more) of the following, each present for a significant portion of time during a month-long period. 1.Delusions. 2.Hallucinations 3.Disorganized Speech 4.Grossly disorganized or catatonic behavior 5.Negative symptoms Diminished emotional expression Avolition 18. 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. 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. The Dopamine Hypothesis of Schizophrenia 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. Increased activity in a certain dopamine receptors (the D2 receptors) cause the symptoms of schizophrenia. 21. 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 22. Barch, D. M., & Ceaser, A. (2012). Cognition in schizophrenia: core psychological and neural mechanisms. Trends in Cognitive Sciences, 16(1), 2734. doi:10.1016/j.tics.2011.11.015 Functional changes in Schizophrenia 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. Tsuang, M. T. (2001). Genes, environment and schizophrenia. The British Journal of Psychiatry, 178(40), 18s24. doi:10.1192/bjp.178.40.s18 25. Lee, H. S., Ripke, S., Neale, B. M., Faraone, S. V., Purcell, S. M., Perlis, R. H., ... & Buitelaar, J. K. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984-94 26. Irving Selikoff (1915 1992) 27. Zhou, D., Guo, J., Linnenbach, A. J., Booth-genthe, C. L., & Grimm, S. W. (2010). Role of Human UGT2B10 in N -Glucuronidation of Tricyclic and Trimipramine. Drug Metabolism and Disposition, 38(5), 863870. doi:10.1124/dmd.109.030981.broad 28. Molloy, B. B., & Schmiegel, K. K. (1982). U.S. Patent No. 4,314,081. Washington, DC: U.S. Patent and Trademark Office. 29. NeuronsandSynapses 30. 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 31. 2011 2009 2005 Name Used for U.S. Prescriptions 1 1 1 Xanax Anxiety 47,792,000 2 17 11 Celexa Depression, Anxiety 37,728,000 3 4 2 Zoloft Depression, Anxiety, OCD, PTSD, PMDD 37,208,000 4 3 5 Ativan Anxiety, panic disorder 27,172,000 5 5 4 Prozac Depression, Anxiety 24,507,000 6 2 3 Lexapro Depression, Anxiety 23,707,000 7 6 NA Desyrel Depression, Anxiety 22,591,000 8 7 16 Cymbalta Depression, Anxiety 17,770,000 9 10 9 Valium Anxiety, Panic disorder 14,694,000 10 8 13 Seroquel Bipolar disorder, Depression 14,213,000 Grohol, J. (2012). Top 25 Psychiatric Medication Prescriptions for 2011. Psych Central. 32. Criteria for Major Depressive Disorder Depressed mood or a loss of interest or pleasure in daily activities for more than two weeks. Specific symptoms, at least 5 of these 9, present nearly every day: 1.Depressed mood or irritable most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). 2.Decreased interest or pleasure in most activities, most of each day 3.Significant weight change (5%) or change in appetite 4.Change in sleep: Insomnia or hypersomnia 5.Change in activity: Psychomotor agitation or retardation 6.Fatigue or loss of energy 7.Guilt/worthlessness: Feelings of worthlessness or excessive or inappropriate guilt 8.Concentration: diminished ability to think or concentrate, or more indecisiveness 9.Suicidality: Thoughts of death or suicide, or has suicide plan American Psychiatric Association. (2013). Diagnostic And Statistical Manual Of Mental Disorders V. American Psychiatric Association. 33. 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. 34. The Monoamine Hypothesis of MDD Decreases in certain neurotransmitters (e.g. serotonin) cause the symptoms of major depressive disorder. Healthy Controls MDD LevelofSerotonin Pfizer (2001) 35. The Monoamine Hypothesis of MDD Decreases in certain neurotransmitters (e.g. serotonin) cause the symptoms of major depressive disorder. Evidence For: -Drugs that cause increased levels of monoamines are effective antidepressants. Evidence Against: -People with MDD dont 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 36. Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68. 37. Belmaker, R. H., & Agam, G. (2008). Major depressive disorder. New England Journal of Medicine, 358(1), 55-68. 38. Bora, E., Fornito, A., Pantelis, C., & Ycel, M. (2012). Gray matter abnormalities in Major Depressive Disorder: a meta-analysis of voxel based morphometry studies. Journal of Affective Disorders, 138(1-2), 918. doi:10.1016/j.jad.2011.03.049 Structural changes in Depression 39. Functional changes in Depression Fitzgerald, P., & Laird, A. (2008). A metaanalytic study of changes in brain activation in depression. Human Brain Mapping, 29(6), 683695. doi:10.1002/hbm.20426.A MDD vs Controls Effect of SSRI Treatment MDD vs Controls (Happy Faces) MDD vs Controls (Sad Faces) 40. New Treatment Options for Depression Repetitive Transcranial Magnetic Stimulation Deep Brain Stimulation From: New Approach to Depression Treating Depression with Electrodes Inside the Brain 41. Research Domain Criteria (RDoC) Functional Domains Units of Analysis Negative Valence Systems (fear, anxiety, loss, etc) Positive Valence Systems (reward, learning, habits, etc) Cognitive Systems (attention, memory, etc) Social Systems (communication, etc) Regulatory Systems (circadian rhythms, etc) Genes Molecules Cells Circuits Physiology Behavior Self-Reports Paradigms Adapted from: Sanislow, C. A., Pine, D. S., Quinn, K. J., Kozak, M. J., Garvey, M. A., Heinssen, R. K., ... & Cuthbert, B. N. (2010). Developing constructs for psychopathology research: research domain criteria. Journal of abnormal psychology, 119(4), 631.1 42. Thanks! From: Ros, H. Farinella, M. (2014). Neurocomic. Nobrow Press