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

Depression-Depression-AssessmentAssessment

B. Anthony Lindsey, MDB. Anthony Lindsey, MDProfessor and Vice ChairProfessor and Vice ChairUNC Department of UNC Department of PsychiatryPsychiatry

SCOPE OF THE SCOPE OF THE PROBLEMPROBLEM The Global Burden of Disease The Global Burden of Disease

Study reported unipolar Study reported unipolar depression as the fourth leading depression as the fourth leading cause of disability in the world.cause of disability in the world.

Projections for 2020 suggest that Projections for 2020 suggest that unipolar major depression will be unipolar major depression will be the second leading cause of the second leading cause of disability worldwide.disability worldwide.

EpisodeEpisode DisorderDisorder

*Major depression episode*Major depression episode *Major depression disorder*Major depression disorder

*Major depression episode+*Major depression episode+ *Bipolar disorder, *Bipolar disorder, Type IType I

manic/mixed episodemanic/mixed episode

*Manic/mixed episode*Manic/mixed episode *Bipolar disorder, *Bipolar disorder, Type IType I

*Major depressive episode+*Major depressive episode+ *Bipolar disorder, *Bipolar disorder, Type IIType II

hypomanic episodehypomanic episode

*Chronic subsyndromal *Chronic subsyndromal *Dysthymic *Dysthymic DisorderDisorder

depressiondepression

*Chronic fluctuations*Chronic fluctuations between subsyndromal *Cyclothymic between subsyndromal *Cyclothymic

disorderdisorder depression & hypomaniadepression & hypomania

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

DefinitionsDefinitions

• Mood - a person’s sustained Mood - a person’s sustained emotional stateemotional state

• Affect – the outward Affect – the outward manifestation of a person’s manifestation of a person’s feelings, tone, or moodfeelings, tone, or mood

Major DepressionMajor Depression

• Syndromal classification with Syndromal classification with disturbances of mood, disturbances of mood, neurovegetative and cognitive neurovegetative and cognitive functioningfunctioning


At least 5 of the following symptoms At least 5 of the following symptoms present for at least 2 weeks (either present for at least 2 weeks (either #1 or #2 #1 or #2 mustmust be present): be present):

1) depressed mood1) depressed mood

2) anhedonia – loss of interest or 2) anhedonia – loss of interest or pleasurepleasure

3) change in appetite3) change in appetite

4) sleep disturbance4) sleep disturbance


5) psychomotor retardation or 5) psychomotor retardation or agitation agitation

6) decreased energy6) decreased energy

7) feeling of worthlessness or 7) feeling of worthlessness or inappropriate inappropriate guiltguilt

8) diminished ability to think or 8) diminished ability to think or concentrateconcentrate

9) recurrent thoughts of death or 9) recurrent thoughts of death or suicidal suicidal ideationideation

Major DepressionMajor Depression•Symptoms cause marked distress Symptoms cause marked distress

and/or and/or impairment in social or occupational impairment in social or occupational functioning.functioning.

•No evidence of medical or substance-No evidence of medical or substance-induced etiology for the patient’s induced etiology for the patient’s symptoms.symptoms.

•Symptoms are not due to a normal Symptoms are not due to a normal reaction to the death of a loved one.reaction to the death of a loved one.

Bereavement and Bereavement and Late Life DepressionLate Life Depression

•25 – 35% of widows/widowers meet 25 – 35% of widows/widowers meet diagnostic criteria for major diagnostic criteria for major depressive disorder at 2 months.depressive disorder at 2 months.

•~15% of widows/widowers meet ~15% of widows/widowers meet diagnostic criteria for major diagnostic criteria for major depressive disorder at one year.depressive disorder at one year.

•This figure remains stable This figure remains stable throughout the second year.throughout the second year.

Subtypes of DepressionSubtypes of Depression

•AtypicalAtypicalReverse neurovegetative Reverse neurovegetative symptomssymptoms

Mood reactivityMood reactivityHypersensitivity to rejectionHypersensitivity to rejectionMAO-I’s and SSRI’s are more MAO-I’s and SSRI’s are more effective treatmentseffective treatments


Psychotic (~10% of all MDD)Psychotic (~10% of all MDD)•Delusions common, may Delusions common, may have hallucinationshave hallucinations

•Delusions usually mood Delusions usually mood congruentcongruent

•Combined antidepressant Combined antidepressant and antipsychotic therapy or and antipsychotic therapy or ECT is necessaryECT is necessary


MelancholicMelancholic•No mood reactivityNo mood reactivity•AnhedoniaAnhedonia•Prominent neurovegetative Prominent neurovegetative disturbancedisturbance

•More likely to respond to More likely to respond to biological treatmentsbiological treatments


SeasonalSeasonal•Onset in Fall, remission in Onset in Fall, remission in SpringSpring

•Hypersomnia is typicalHypersomnia is typical•Less responsive to Less responsive to medicationsmedications

•A.M. light therapy (>2,500 A.M. light therapy (>2,500 lux) is effectivelux) is effective


CatatonicCatatonic•Motoric immobility Motoric immobility (catalepsy)(catalepsy)

•MutismMutism•Ecolalia or echopraxiaEcolalia or echopraxia

EpidemiologyEpidemiology

Point prevalencePoint prevalence 6 – 8% in women6 – 8% in women 3 – 4% in men3 – 4% in men

Lifetime prevalenceLifetime prevalence 20% in women20% in women 10% in men10% in men


Age of OnsetAge of Onset Throughout the life cycle, Throughout the life cycle,

typically from the mid 20’s typically from the mid 20’s through the 50’s with a peak age through the 50’s with a peak age of onset in the mid 30’sof onset in the mid 30’s


GeneticsGenetics More prevalent in first degree relativesMore prevalent in first degree relatives

3-5x the general population risk3-5x the general population risk Concordance is greater in monozygotic Concordance is greater in monozygotic

(~50%) than dizygotic (~15%) twins(~50%) than dizygotic (~15%) twins Increased prevalence of alcohol Increased prevalence of alcohol

dependence in relativesdependence in relatives

EtiologyEtiology

Original, clearly over simplistic Original, clearly over simplistic theories regarding theories regarding norepinephrine and serotoninnorepinephrine and serotonin

Deficiency states Deficiency states depressiondepression

States of excessStates of excess mania mania

Problems with initial Problems with initial theoriestheories Inconsistent findings when studying Inconsistent findings when studying

measures of these systems: MHPG measures of these systems: MHPG (3 methoxy 4 hydroxyphenolglycol) (3 methoxy 4 hydroxyphenolglycol) and 5HIAA (5 hydroxy indoleacetic and 5HIAA (5 hydroxy indoleacetic acid) in the urine and CSF.acid) in the urine and CSF.

Treatments block monoamine Treatments block monoamine uptake acutely, however the uptake acutely, however the positive effects occur in 2-4 weeks.positive effects occur in 2-4 weeks.

Receptor theory more Receptor theory more usefuluseful

Antidepressant treatment causes Antidepressant treatment causes a down regulation in central a down regulation in central adrenergic (beta) and adrenergic (beta) and serotonergic (5HT2) receptorsserotonergic (5HT2) receptors– This change corresponds temporally This change corresponds temporally

to the antidepressant responseto the antidepressant response

Serotonin and Serotonin and DepressionDepression Decreased CSF levels of serotonin Decreased CSF levels of serotonin

metabolites metabolites Decreased serotonin transporter Decreased serotonin transporter

bindingbinding Acute tryptophan depletion can Acute tryptophan depletion can

cause worsening in patients cause worsening in patients previously responsive to SSRI’spreviously responsive to SSRI’s

Gene-Environment Gene-Environment InteractionsInteractions

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

NeuroendocrineNeuroendocrine

Hyperactivity of HPA axis:Hyperactivity of HPA axis:– Elevated cortisolElevated cortisol– Nonsuppression of cortisol following dexamethasoneNonsuppression of cortisol following dexamethasone– Hypersecretion of CRFHypersecretion of CRF

Blunting of TSH response to TRHBlunting of TSH response to TRH Blunting of serotonin mediated increase in Blunting of serotonin mediated increase in

plasma prolactinplasma prolactin Blunting of the expected increase in plasma Blunting of the expected increase in plasma

growth hormone response to alpha-2 growth hormone response to alpha-2 agonistsagonists

Functional Neuroimaging (PET,SPECT)Functional Neuroimaging (PET,SPECT)

Dorsal prefrontal cortexDorsal prefrontal cortex– Anterolateral (concentration, Anterolateral (concentration,

cognitive processing)cognitive processing)– Anterior cingulate (regulation of Anterior cingulate (regulation of

mood and affect)mood and affect) SubcorticalSubcortical

– Caudate (psychomotor changes)Caudate (psychomotor changes)

Decreased metabolic activity

Increased metabolic activityVentral prefrontal cortex

PsychosocialPsychosocial

Risk FactorsRisk Factors– Poor social supportsPoor social supports– Early parental lossEarly parental loss– Early life traumaEarly life trauma– Female genderFemale gender– Chronic medical illnessChronic medical illness– IntroversionIntroversion

PsychosocialPsychosocial

Cognitive TheoryCognitive Theory– Patients have distorted Patients have distorted

perceptions and thoughts of perceptions and thoughts of themselves, the world themselves, the world around them and the futurearound them and the future

Possible to treat by Possible to treat by restructuringrestructuring

Secondary Causes of Secondary Causes of DepressionDepression

ToxicToxic EndocrineEndocrine VascularVascular NeurologicNeurologic NutritionalNutritional NeoplasticNeoplastic TraumaticTraumatic InfectiousInfectious AutoimmuneAutoimmune

Depression – Differential Depression – Differential DiagnosisDiagnosis

Adjustment Disorder with depressed Adjustment Disorder with depressed moodmood

– Maladaptive and excessive response to stress, difficulty Maladaptive and excessive response to stress, difficulty functioning, need support not medicines, resolve as stress functioning, need support not medicines, resolve as stress resolvesresolves

Dysthymic DisorderDysthymic DisorderBipolar DisorderBipolar Disorder

Other Psychotic DisordersOther Psychotic Disorders – if psychotic – if psychotic subtypesubtype

Personality Disorders (cluster B)Personality Disorders (cluster B) – Mood – Mood instability with rapid changes is characteristicinstability with rapid changes is characteristic

TreatmentTreatment

BiologicBiologic Tricyclic antidepressantsTricyclic antidepressants Monoamine oxidase inhibitorsMonoamine oxidase inhibitors Second generation antidepressantsSecond generation antidepressants

– SSRI’s, Venlafaxine, duloxetine, SSRI’s, Venlafaxine, duloxetine, bupropion, mirtazapinebupropion, mirtazapine

Electoconvulsive therapyElectoconvulsive therapy

TreatmentTreatment

Psychosocial TreatmentsPsychosocial Treatments EducationEducation Specific psychotherapiesSpecific psychotherapies Vocational trainingVocational training ExerciseExercise

TreatmentTreatment

When to Refer?When to Refer? Question regarding suicide riskQuestion regarding suicide risk Presence of psychotic symptomsPresence of psychotic symptoms Past history of maniaPast history of mania Lack of response to adequate Lack of response to adequate

medication trialmedication trial

TreatmentTreatment

CourseCourse One episode – 50% chance of One episode – 50% chance of

reoccurencereoccurence Two episodes – 70% chance of Two episodes – 70% chance of

reoccurencereoccurence Three or more episodes - >90% Three or more episodes - >90%

chance of reoccurence chance of reoccurence

Dysthymic DisorderDysthymic Disorder

CharacteristicsCharacteristics Chronically depressed mood for most of the Chronically depressed mood for most of the

day, more days than not, for at least two years. day, more days than not, for at least two years. Can be irritable mood in children and Can be irritable mood in children and adolescents for 1 yearadolescents for 1 year

While depressed, presence of at least two of While depressed, presence of at least two of the followingthe following– Poor appetite or overeatingPoor appetite or overeating– Sleep disturbanceSleep disturbance– Low energy or fatigueLow energy or fatigue– Low self esteemLow self esteem– Poor concentrationPoor concentration– Feelings of hopelessness Feelings of hopelessness

Dysthymic DisorderDysthymic Disorder

Never without depressive symptoms for Never without depressive symptoms for over 2 monthsover 2 months

No evidence of an unequivocal Major No evidence of an unequivocal Major Depressive Episode during the first two Depressive Episode during the first two years of the disturbance (1 year in children years of the disturbance (1 year in children and adolescents)and adolescents)

No manic or hypomanic episodesNo manic or hypomanic episodes Not superimposed on a chronic psychotic Not superimposed on a chronic psychotic

disorderdisorder Not due to the direct physiologic affects of Not due to the direct physiologic affects of

a substance or a general medical conditiona substance or a general medical condition


More prevalent in women, 4% More prevalent in women, 4% prevalence in women, 2% in menprevalence in women, 2% in men

Onset is usually in childhood, Onset is usually in childhood, adolescence or early adulthoodadolescence or early adulthood

Often is a superimposed Major Often is a superimposed Major DepressionDepression

High prevalence of substance High prevalence of substance abuse in this groupabuse in this group

Differential DiagnosisDifferential Diagnosis

Other mood disordersOther mood disorders

Mood disorder due to a general Mood disorder due to a general medical conditionmedical condition

TreatmentTreatment

If no superimposed Major If no superimposed Major DepressionDepression– PsychotherapyPsychotherapy

Some evidence suggest Some evidence suggest responsiveness to antidepressant responsiveness to antidepressant medication in some sub- groupsmedication in some sub- groups

CourseCourse

Prognosis is not as good as Prognosis is not as good as Major Depression in terms of Major Depression in terms of total symptomatic remissiontotal symptomatic remission

Documents

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