1. Depression-Assessment B. Anthony Lindsey, MD Professor and Vice Chair UNC Department of Psychiatry

2. SCOPE OF THE PROBLEM The Global Burden of Disease Study reported unipolar depression as the fourth leading cause of disability in the world. The Global Burden of Disease Study reported unipolar depression as the fourth leading cause of disability in the world. Projections for 2020 suggest that unipolar major depression will be the second leading cause of disability worldwide. Projections for 2020 suggest that unipolar major depression will be the second leading cause of disability worldwide.

3. EpisodeDisorder *Major depression episode*Major depression disorder *Major depression episode+ *Bipolar disorder, Type I manic/mixed episode manic/mixed episode *Manic/mixed episode *Bipolar disorder, Type I *Major depressive episode+ *Bipolar disorder, Type II hypomanic episode hypomanic episode *Chronic subsyndromal *Dysthymic Disorder depression depression *Chronic fluctuations between subsyndromal *Cyclothymic disorder between subsyndromal *Cyclothymic disorder depression & hypomania depression & hypomania

4. “If I had __________, I’d be depressed too.”

5. Definitions Mood - a person’s sustained emotional state Mood - a person’s sustained emotional state Affect – the outward manifestation of a person’s feelings, tone, or mood Affect – the outward manifestation of a person’s feelings, tone, or mood

6. Major Depression Syndromal classification with disturbances of mood, neurovegetative and cognitive functioning Syndromal classification with disturbances of mood, neurovegetative and cognitive functioning

7. Major Depression At least 5 of the following symptoms present for at least 2 weeks (either #1 or #2 must be present): 1) depressed mood 2) anhedonia – loss of interest or pleasure 3) change in appetite 4) sleep disturbance

8. Major Depression 5) psychomotor retardation or agitation 5) psychomotor retardation or agitation 6) decreased energy 7) feeling of worthlessness or inappropriate guilt 8) diminished ability to think or concentrate 9) recurrent thoughts of death or suicidal ideation

9. Major Depression Symptoms cause marked distress and/or Symptoms cause marked distress and/or impairment in social or occupational functioning. No evidence of medical or substance- induced etiology for the patient’s symptoms. No evidence of medical or substance- induced etiology for the patient’s symptoms. Symptoms are not due to a normal reaction to the death of a loved one. Symptoms are not due to a normal reaction to the death of a loved one.

10. Bereavement and Late Life Depression 25 – 35% of widows/widowers meet diagnostic criteria for major depressive disorder at 2 months. 25 – 35% of widows/widowers meet diagnostic criteria for major depressive disorder at 2 months. ~15% of widows/widowers meet diagnostic criteria for major depressive disorder at one year. ~15% of widows/widowers meet diagnostic criteria for major depressive disorder at one year. This figure remains stable throughout the second year. This figure remains stable throughout the second year.

11. Subtypes of Depression Atypical Atypical Reverse neurovegetative symptoms Reverse neurovegetative symptoms Mood reactivity Mood reactivity Hypersensitivity to rejection Hypersensitivity to rejection MAO-I’s and SSRI’s are more effective treatments MAO-I’s and SSRI’s are more effective treatments

12. Subtypes of Depression Psychotic (~10% of all MDD) Psychotic (~10% of all MDD) Delusions common, may have hallucinationsDelusions common, may have hallucinations Delusions usually mood congruentDelusions usually mood congruent Combined antidepressant and antipsychotic therapy or ECT is necessaryCombined antidepressant and antipsychotic therapy or ECT is necessary

13. Subtypes of Depression Melancholic Melancholic No mood reactivityNo mood reactivity AnhedoniaAnhedonia Prominent neurovegetative disturbanceProminent neurovegetative disturbance More likely to respond to biological treatmentsMore likely to respond to biological treatments

14. Subtypes of Depression Seasonal Seasonal Onset in Fall, remission in SpringOnset in Fall, remission in Spring Hypersomnia is typicalHypersomnia is typical Less responsive to medicationsLess responsive to medications A.M. light therapy (>2,500 lux) is effectiveA.M. light therapy (>2,500 lux) is effective

15. Subtypes of Depression Catatonic Catatonic Motoric immobility (catalepsy)Motoric immobility (catalepsy) MutismMutism Ecolalia or echopraxiaEcolalia or echopraxia

16. Epidemiology Point prevalence 6 – 8% in women 6 – 8% in women 3 – 4% in men 3 – 4% in men Lifetime prevalence 20% in women 20% in women 10% in men 10% in men

17. Epidemiology Age of Onset Throughout the life cycle, typically from the mid 20’s through the 50’s with a peak age of onset in the mid 30’s Throughout the life cycle, typically from the mid 20’s through the 50’s with a peak age of onset in the mid 30’s

18. Epidemiology Genetics More prevalent in first degree relatives More prevalent in first degree relatives 3-5x the general population risk 3-5x the general population risk Concordance is greater in monozygotic (~50%) than dizygotic (~15%) twins Concordance is greater in monozygotic (~50%) than dizygotic (~15%) twins Increased prevalence of alcohol dependence in relatives Increased prevalence of alcohol dependence in relatives

19. Etiology Original, clearly over simplistic theories regarding norepinephrine and serotonin Deficiency states depression Deficiency states depression States of excess mania States of excess mania

20. Problems with initial theories Inconsistent findings when studying measures of these systems: MHPG (3 methoxy 4 hydroxyphenolglycol) and 5HIAA (5 hydroxy indoleacetic acid) in the urine and CSF. Inconsistent findings when studying measures of these systems: MHPG (3 methoxy 4 hydroxyphenolglycol) and 5HIAA (5 hydroxy indoleacetic acid) in the urine and CSF. Treatments block monoamine uptake acutely, however the positive effects occur in 2-4 weeks. Treatments block monoamine uptake acutely, however the positive effects occur in 2-4 weeks.

21. Receptor theory more useful Antidepressant treatment causes a down regulation in central adrenergic (beta) and serotonergic (5HT2) receptors Antidepressant treatment causes a down regulation in central adrenergic (beta) and serotonergic (5HT2) receptors –This change corresponds temporally to the antidepressant response

22. Serotonin and Depression Decreased CSF levels of serotonin metabolites Decreased CSF levels of serotonin metabolites Decreased serotonin transporter binding Decreased serotonin transporter binding Acute tryptophan depletion can cause worsening in patients previously responsive to SSRI’s Acute tryptophan depletion can cause worsening in patients previously responsive to SSRI’s

23. Gene-Environment Interactions Individuals who have one allele for a “low efficiency” serotonin transporter are more vulnerable to depression after experiencing environmental stressors (Kendler 2005, Caspi 2003, Lenze 2005) Individuals who have one allele for a “low efficiency” serotonin transporter are more vulnerable to depression after experiencing environmental stressors (Kendler 2005, Caspi 2003, Lenze 2005)

24. Neuroendocrine Hyperactivity of HPA axis: Hyperactivity of HPA axis: –Elevated cortisol –Nonsuppression of cortisol following dexamethasone –Hypersecretion of CRF Blunting of TSH response to TRH Blunting of TSH response to TRH Blunting of serotonin mediated increase in plasma prolactin Blunting of serotonin mediated increase in plasma prolactin Blunting of the expected increase in plasma growth hormone response to alpha-2 agonists Blunting of the expected increase in plasma growth hormone response to alpha-2 agonists

25. Functional Neuroimaging (PET,SPECT) Functional Neuroimaging (PET,SPECT) Dorsal prefrontal cortex Dorsal prefrontal cortex –Anterolateral (concentration, cognitive processing) –Anterior cingulate (regulation of mood and affect) Subcortical Subcortical –Caudate (psychomotor changes) Decreased metabolic activity Increased metabolic activity Ventral prefrontal cortex

26. Psychosocial Risk Factors Risk Factors –Poor social supports –Early parental loss –Early life trauma –Female gender –Chronic medical illness –Introversion

27. Psychosocial Cognitive Theory Cognitive Theory –Patients have distorted perceptions and thoughts of themselves, the world around them and the future Possible to treat by restructuring Possible to treat by restructuring

28. Secondary Causes of Depression Toxic Toxic Endocrine Endocrine Vascular Vascular Neurologic Neurologic Nutritional Nutritional Neoplastic Neoplastic Traumatic Traumatic Infectious Infectious Autoimmune Autoimmune

29. Depression – Differential Diagnosis Adjustment Disorder with depressed mood Adjustment Disorder with depressed mood –Maladaptive and excessive response to stress, difficulty functioning, need support not medicines, resolve as stress resolves Dysthymic Disorder Bipolar Disorder Other Psychotic Disorders – if psychotic subtype Other Psychotic Disorders – if psychotic subtype Personality Disorders (cluster B) – Mood instability with rapid changes is characteristic Personality Disorders (cluster B) – Mood instability with rapid changes is characteristic

30. Treatment Biologic Tricyclic antidepressants Tricyclic antidepressants Monoamine oxidase inhibitors Monoamine oxidase inhibitors Second generation antidepressants Second generation antidepressants –SSRI’s, Venlafaxine, duloxetine, bupropion, mirtazapine Electoconvulsive therapy Electoconvulsive therapy

31. Treatment Psychosocial Treatments Education Education Specific psychotherapies Specific psychotherapies Vocational training Vocational training Exercise Exercise

32. Treatment When to Refer? Question regarding suicide risk Question regarding suicide risk Presence of psychotic symptoms Presence of psychotic symptoms Past history of mania Past history of mania Lack of response to adequate medication trial Lack of response to adequate medication trial

33. Treatment Course One episode – 50% chance of reoccurence One episode – 50% chance of reoccurence Two episodes – 70% chance of reoccurence Two episodes – 70% chance of reoccurence Three or more episodes - >90% chance of reoccurence Three or more episodes - >90% chance of reoccurence

34. Dysthymic Disorder Characteristics Chronically depressed mood for most of the day, more days than not, for at least two years. Can be irritable mood in children and adolescents for 1 year Chronically depressed mood for most of the day, more days than not, for at least two years. Can be irritable mood in children and adolescents for 1 year While depressed, presence of at least two of the following While depressed, presence of at least two of the following –Poor appetite or overeating –Sleep disturbance –Low energy or fatigue –Low self esteem –Poor concentration –Feelings of hopelessness

35. Dysthymic Disorder Never without depressive symptoms for over 2 months Never without depressive symptoms for over 2 months No evidence of an unequivocal Major Depressive Episode during the first two years of the disturbance (1 year in children and adolescents) No evidence of an unequivocal Major Depressive Episode during the first two years of the disturbance (1 year in children and adolescents) No manic or hypomanic episodes No manic or hypomanic episodes Not superimposed on a chronic psychotic disorder Not superimposed on a chronic psychotic disorder Not due to the direct physiologic affects of a substance or a general medical condition Not due to the direct physiologic affects of a substance or a general medical condition

36. Epidemiology More prevalent in women, 4% prevalence in women, 2% in men More prevalent in women, 4% prevalence in women, 2% in men Onset is usually in childhood, adolescence or early adulthood Onset is usually in childhood, adolescence or early adulthood Often is a superimposed Major Depression Often is a superimposed Major Depression High prevalence of substance abuse in this group High prevalence of substance abuse in this group

37. Differential Diagnosis Other mood disorders Other mood disorders Mood disorder due to a general medical condition Mood disorder due to a general medical condition

38. Treatment If no superimposed Major Depression If no superimposed Major Depression –Psychotherapy Some evidence suggest responsiveness to antidepressant medication in some sub- groups Some evidence suggest responsiveness to antidepressant medication in some sub- groups

39. Course Prognosis is not as good as Major Depression in terms of total symptomatic remission Prognosis is not as good as Major Depression in terms of total symptomatic remission