1. Exam: December 14, 12:00-3:00, Wood 2 In addition to questions associated with the lecture slides, the exam will include questions related to chapters 7, 8, 9, 10, and 16 of the textbook. Note that chapter 11 will not be tested on the exam. The exam will include 40 multiple choice questions (1 point each), 5 definitions (2 points each), and several short answer questions (2-10 points each). The exam is worth 25% of your final grade. The exam will be scored out of 75 points.

2. Please bring a pencil, eraser, pen, and your student ID to the exam. All electronic devices must be put away before the start of the exam. All backpacks/bags should be placed at the front, back, or sides of the examination room. Hats (e.g., baseball caps) should not be worn during the exam.

3. Office Hours Prior to the exam, I will have additional office hours. If you require assistance, please feel free to see me at any of the following times: Monday, December 7, 12:00-1:30. Thursday, December 10, 9:00-10:30. Friday, December 11, 2:30-4:30.

4. Outline Affective disorders Depression Causes The monoamine hypothesis Treatments Monoamine oxidase inhibitors Serotonin reuptake inhibitors Tricyclic antidepressants Other Problems with the monoamine hypothesis The diathesis stress model Bipolar disorder Treatments Lithium Anxiety disorders Causes Treatments Hypothesis

5. Affective Disorders Affective fluctuations are felt by all of us What classifies it as a disorder are the extremes that are felt and the duration. These extremes are so intense that they disturb the daily functioning of the individual affected.

6. Affective disorders Depressive episodes according to DSM IV 2 weeks, at least 5: Depressed mood Few interests Eating, weight Sleep Motor activity Fatigue Self-worth Concentration Thoughts of death Mild Moderate Severe with/without psychotic features Partial remission Full remission Unspecified Severity

7. Affective disorders Manic episodes according to DSM IV 1 weeks, at least 3: Grandiosity, exaggerated self- esteem Reduced need for sleep Increased talkativeness Flight of ideas, racing thoughts Psychomotor agitation Poor judgement Material distress Psychotic features Requires hospitalization Impairs functioning Causes at least 1 of Severity, same as depression

8. Depression Seasonal affective disorder Postpartum depression Dysthymia Bipolar disorder

9. Depression: Cause Twice as many women as men. Menopause Postpartum depression There seems to be a genetic contributor. Twin studies (40-50%) Adoption studies also provide support for the role of genetics. Failure to identify the locus of any specific relevant gene.

10. Depression: Cause PET shows increased activation in the amygdala (fear and emotion center) and the prefrontal cortex (higher order cognition). Antidepressants attenuate this increase in the amygdala. However, alleviation of the depressive symptoms through time alone does not.

11. Monoamine theory of depression Schildkraut and Kety, 1967: hypothesized that depression is caused by the decreased in activity of the monoamine transmitter synapses, namely norepinephrine and serotonin. Lower concentrations of serotonin and its metabolite (5-HIAA) in suicide attempters who take their life. Variant version of the gene 5HT 2A receptor more common in suicide victims than controls.

12. Treatment: Monoamine oxidase inhibitors The first kind of antidepressant to ever be used was a monoamine oxidase inhibitor: Ipronia First developed to treat tuberculosis Ineffective for what it was intended towards; but left patients with tuberculosis less depressed about their disorder. Monoamine agonist: increases synaptic levels of monoamines (serotonin and norepinephrine) by inhibiting monoamine oxidase, an enzyme that breaks down monoamines neurotransmitters in the cytoplasme. Iproniazi d

13. Treatment: Selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitor(SSRIs) Fluoxetine (Prozac).

14. Treatments: Tricyclic antidepressants Tricyclic Antidepressants Names this way because their chemical structure includes 3 rings. Safer alternative to MOA inhibitors Block re-uptake of both serotonin and norepinephrine Imipramine

15. Treatment: Other Electroconvulsive therapy (ECT), Transcranial magnetic stimulation, and Vagal nerve stimulation

16. Support for the monoamine hypothesis One effective form of antidepressants inhibit MOA (MOA inhibitors), other increase their concentration at the synaptic cleft (re-uptake inhibitors) Alleviation of depressive symptoms after increased monoamine concentration at synapses suggests that the affected population lacks sufficient stimulation at these synapses.

17. Problems with the monoamine hypothesis Not everyone gets an alleviation of the symptoms with the available treatments. Comparing the efficacy of the various pharmacological treatments: No difference in the efficacy of the different types of treatment Only 50% of people see an improvement of their symptoms. 25% of control group also showed an improvement (Placebo effect)

18. Diathesis stress model Cushing’s syndrome: characterized by high levels of circulating glucocorticoids: Consequence of pituitary tumors, producing an excess of adrenocorticotropic hormone Tumors of adrenal, hypersecretion of cortisol Therapeutic treatments with synthetic glucocorticoids. Expression of depression occurs early. Role of Hypothalamic pituitary adrenal (HPA) axis in depression?

19. HPA axis Hypothalamus (CRH) Anterior pituitary (ACTH) Adrenal cortex (Cortisol) STRESS!! excitatory inhibitory

20. Diathesis-stress model Inherited diathesis (genetic susceptibility) which is incapable of initiating the onset of depression by itself. The theory suggests that if the susceptible individuals are exposed to stress early on in life, they are then likely to overreact to mild stressors due to sensitization.

21. Diathesis-stress model Support for this theory comes from the finding that patients with depression: synthesize more hypothalamic Corticotropin releasing hormone, release more adrenocorticotropic hormone form the anterior pituitary and release more glucocorticoids from the Adrenal cortex. The administration of dexamethasone, a synthetic glucocorticoid, do not reduce the release of endogenous glucocorticoid. Hospitalized depression patients and suicide victims show high levels of cortisol.

22. Bipolar Disorder Fluctuations in mood between depression and mania. The onset is earlier than unipolar depression The duration and fluctuation of each episode varies among individuals.

23. Bipolar Disorder No difference between the gender of those affected by the disease Genetic analysis has shown that there are at least genes on at least 6 chromosomes are important Age of onset is also heritable While people with family history of bipolar disorder are at risk for depression, the reverse is not true.

24. Treatments Antidepressant medication Antipsychotic medication Transcranial magnetic stimulation and ECT Other medication (Hormones, herbs, etc) Mood stabilizing medication (e.g: Lithium)

25. Treatment: Lithium 2nd century A.D.: Seranus Ephisios recommended the administration of water from alkaline springs to patients suffering from mania. John Cade (1940s). Injected the lithium diluted in the urine of manic patients in guinea pigs. As a control, injected only lithium in another group of animals. Both uric acid and control lithium solutions had a calming effect on the guinea pigs Because the control lithium solution had the same calming effect, Cade concluded that the effect was due to the lithium and not the uric acid.

26. Treatment: Lithium In the 1950’s, Morgan Schou was convinced that lithium could be used to treat bipolar disorder Not only was he convinced of lithium’s ability to prevent episodes of mania, but he also wanted to show that lithium could prevent further recurrence of episodes. With his colleague, Christian Baalstrup performed a double-blind lithium discontinuation study: Lithium or Placebo Lithium administered patients: NONE relapsed

27. Anxiety disorders Anxiety: Chronic fear that persists in the absence of any direct threat. When no adaptation occurs and it disrupts normal functioning, it is referred to as anxiety disorder. Most prevalent of all psychiatric disorders: 17% of people are effected.

28. Anxiety disorders Five classes of anxiety disorders: Generalized anxiety disorder Phobic anxiety disorder Panic disorder Obsessive compulsive disorder Posttraumatic stress disorder

29. Anxiety disorders: Causes Heritability A range of 30-50% Higher concordance rate in identical twins than in fraternal twins However, the timing and focus of the anxiety is shaped by the experience and the environment of each person.

30. Treatment GABA agonists Facilitation of inhibition Serotonin agonists Does NOT work as an SSRI preferred over GABA agonist Antidepressant drugs. Comorbidity between depression and anxiety disorder Cognitive behavioral therapy

31. Hypothesis Difficult to interpret results of imaging studies: anxiety related influence on the respiration rate. The change in the oxygenation of cerebral blood in brain activity can mask the effect of anxiety in the brain. No structural damage found in the amygdalas or the prefrontal cortex. Focus on possible role of GABA and serotonin in anxiety disorders.

32. Hypothesis Non competitive GABA agonists alleviate the symptoms Benzodiazepine and other anxiolytics Functional Imaging research show that serotonin 5HT 1A receptor density abnormality Selective serotonin re-uptake inhibitors (Paxil and Prozac), and 5HT 1A receptor agonist (Buspar).

33. H.M.’s brain Sliced live in San Diego http://thebrainobservatory.ucsd.edu/hm_live.php

34. Outline Affective disorders Depression Causes The monoamine hypothesis Treatments Monoamine oxidase inhibitors Serotonin reuptake inhibitors Tricyclic antidepressants Other Problems with the monoamine hypothesis The diathesis stress model Bipolar disorder Treatments Lithium Anxiety disorders Causes Treatments Hypothesis