AFFECTIVE DISORDERS n UNIPOLAR DISORDER ~ –Major Depression n BIPOLAR DISORDER ~ –Depression and Mania

AFFECTIVE DISORDERSAFFECTIVE DISORDERS

UNIPOLAR DISORDERUNIPOLAR DISORDER ~ ~ – Major DepressionMajor Depression

BIPOLAR DISORDERBIPOLAR DISORDER ~ ~ – Depression and ManiaDepression and Mania

SYMPTOMS OF SYMPTOMS OF DEPRESSIONDEPRESSION

ANHEDONIA ~ lack of pleasureANHEDONIA ~ lack of pleasure Feelings of WORTHLESSNESSFeelings of WORTHLESSNESS PSYCHOMOTOR RETARDATIONPSYCHOMOTOR RETARDATION Loss of ENERGY (FATIGUE)Loss of ENERGY (FATIGUE)

VEGETATIVE SYMPTOMSVEGETATIVE SYMPTOMS– appetite disturbancesappetite disturbances– weight gain/lossweight gain/loss– sleep disturbancessleep disturbances

SYMPTOMS OF SYMPTOMS OF DEPRESSIONDEPRESSION

MELANCHOLIA MELANCHOLIA

ANXIETYANXIETY

DELUSIONS/HALLUCINATIONSDELUSIONS/HALLUCINATIONS

UNIPOLAR DISORDERUNIPOLAR DISORDER ~ ~ Major Depressive Disorder Major Depressive Disorder

Endogenous - usual onset in mid 20’s-Endogenous - usual onset in mid 20’s-30’s30’s

50% will have another episode50% will have another episode Most untreated episodes last from 6-24 Most untreated episodes last from 6-24

monthsmonths Treatment more effective in early stages Treatment more effective in early stages

of an episodeof an episode Women are 2-3 times more likely to Women are 2-3 times more likely to

suffer than mensuffer than men

UNIPOLAR DISORDERUNIPOLAR DISORDER ~ ~ Major Depressive Disorder Major Depressive Disorder

Afflicts 13-20% of American Afflicts 13-20% of American population at any one timepopulation at any one time

80% of all suicide victims are 80% of all suicide victims are profoundly depressedprofoundly depressed

A number of subtypes exist:A number of subtypes exist:

UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes

PSYCHOTICPSYCHOTIC MELANCHOLICMELANCHOLIC ATYPICALATYPICAL SEASONAL AFFECTIVE DISORDERSEASONAL AFFECTIVE DISORDER POSTPARTUM ONSETPOSTPARTUM ONSET


PSYCHOTICPSYCHOTIC– delusions and hallucinations are presentdelusions and hallucinations are present– 15 % of all depressives fall into this subtype15 % of all depressives fall into this subtype

MELANCHOLICMELANCHOLIC ATYPICALATYPICAL SEASONAL AFFECTIVE DISORDERSEASONAL AFFECTIVE DISORDER POSTPARTUM ONSETPOSTPARTUM ONSET


MELANCHOLICMELANCHOLIC– Psychomotor retardationPsychomotor retardation– Lack of pleasureLack of pleasure– Worse in a.m.Worse in a.m.– Early morning wakeningsEarly morning wakenings

ATYPICALATYPICAL SEASONAL AFFECTIVE DISORDERSEASONAL AFFECTIVE DISORDER POSTPARTUM ONSETPOSTPARTUM ONSET


ATYPICALATYPICAL– Overeat, oversleepOvereat, oversleep– weight gainweight gain– marked anxietymarked anxiety– difficulty falling asleepdifficulty falling asleep– heaviness in arms and legsheaviness in arms and legs

SEASONAL AFFECTIVE DISORDERSEASONAL AFFECTIVE DISORDER POSTPARTUM ONSETPOSTPARTUM ONSET


SEASONAL AFFECTIVE DISORDERSEASONAL AFFECTIVE DISORDER– Regular temporal relationship with Regular temporal relationship with

time of yeartime of year– related to sunlightrelated to sunlight

POSTPARTUM ONSETPOSTPARTUM ONSET


POSTPARTUM ONSETPOSTPARTUM ONSET– 50-80% of women experience some 50-80% of women experience some

depressive symptoms within 1-5 days depressive symptoms within 1-5 days of deliveryof delivery

– related to changes in hormones but related to changes in hormones but not surenot sure

– can be mild or severecan be mild or severe

BIPOLAR DISORDERBIPOLAR DISORDER

Episodes of depression and Episodes of depression and mania/hypomania are equally mania/hypomania are equally frequentfrequent

Mean age of onset = early 20’sMean age of onset = early 20’s Untreated MANIC episode is 6 monthsUntreated MANIC episode is 6 months Depressive episode is 8-10 monthsDepressive episode is 8-10 months 10-15% of untreated commit suicide 10-15% of untreated commit suicide

~ 15-20 times the rate among the ~ 15-20 times the rate among the general populationgeneral population

BIPOLAR DISORDERBIPOLAR DISORDER

Affects men and women equallyAffects men and women equally 2.0 million Americans suffer from 2.0 million Americans suffer from

BIPOLAR disorderBIPOLAR disorder

TREATMENTSTREATMENTSUnipolar DepressionUnipolar Depression

PsychotherapyPsychotherapy Monoamine Oxidase (MOA) inhibitorsMonoamine Oxidase (MOA) inhibitors Tricyclic AntidepressantsTricyclic Antidepressants Selective Serotonin Reuptake Selective Serotonin Reuptake

Inhibitors (SSRI’s)Inhibitors (SSRI’s) Electroconvulsive Shock Therapy Electroconvulsive Shock Therapy

(ECT)(ECT) LithiumLithium

TREATMENTTREATMENTBipolar DepressionBipolar Depression

LithiumLithium

BIOLOGICAL BASIS OF BIOLOGICAL BASIS OF AFFECTIVE DISORDERSAFFECTIVE DISORDERSGeneticsGenetics

- Concordance rate among twins- Concordance rate among twins

Monozygotic(identical) twins = 60%Monozygotic(identical) twins = 60% dizygotic twins(fraternal) = 15%dizygotic twins(fraternal) = 15%

Pharmacology - Drugs

Concordance RateConcordance Rate

100 sets of twins with one twin 100 sets of twins with one twin diagnosed with depressiondiagnosed with depression

48 sets in which both 48 sets in which both diagnosed with depressiondiagnosed with depression

Concordance Rate = 48%Concordance Rate = 48%

BIOLOGICAL BASIS OF BIOLOGICAL BASIS OF AFFECTIVE AFFECTIVE DISORDERSDISORDERS

Pharmacology - DrugsPharmacology - Drugs

How do these drugs work? How do these drugs work? Monoamine Oxidase Monoamine Oxidase

(MAO)Inhibitors(MAO)Inhibitors

IPRONIAZID, PARGYLINEIPRONIAZID, PARGYLINE MAO = ENZYME located in terminal boutonsMAO = ENZYME located in terminal boutons Found in NOREPINEPHRINE and SEROTONIN-Found in NOREPINEPHRINE and SEROTONIN-

containing neuronscontaining neurons Degrades excess neurotransmitterDegrades excess neurotransmitter MAO inhibition Transmitter availabilityMAO inhibition Transmitter availability

for storage/releasefor storage/release

How do these drugs work?How do these drugs work?TRICYCLIC TRICYCLIC

ANTIDEPRESSANTSANTIDEPRESSANTS

IMIPRAMINE (TOFRANIL™), IMIPRAMINE (TOFRANIL™), DESIPRAMINEDESIPRAMINE

Block re-uptake of Block re-uptake of NOREPINEPHRINE and SEROTONIN NOREPINEPHRINE and SEROTONIN (MONAMINES)(MONAMINES)

More transmitter available in More transmitter available in synapsesynapse

How do these drugs work?How do these drugs work?SSRI’sSSRI’s

Fluoxetine (PROZAC™)Fluoxetine (PROZAC™) SELECTIVE SEROTONIN REUPTAKE INHIBITORSSELECTIVE SEROTONIN REUPTAKE INHIBITORS Kramer ~ “Listening to Prozac”Kramer ~ “Listening to Prozac” ““You take Prozac to treat a symptom, and it You take Prozac to treat a symptom, and it

transforms your sense of self. The pill seems transforms your sense of self. The pill seems to give social confidence to habitually timid, to to give social confidence to habitually timid, to make the sensitive brash, to lend the introvert make the sensitive brash, to lend the introvert the social skills of a salesman”the social skills of a salesman”

THE MONAMINE THEORY THE MONAMINE THEORY OF DEPRESSIONOF DEPRESSION

Insufficient activity of monoamine Insufficient activity of monoamine neurons, particularly, neurons, particularly, NOREPINEPHRINE and SEROTONIN NOREPINEPHRINE and SEROTONIN neurons.neurons.

THE MONAMINE THE MONAMINE THEORY OF THEORY OF

DEPRESSIONDEPRESSION

BIGBIG PROBLEM w/ THEORY PROBLEM w/ THEORY

THE TIME-LAG FACTORTHE TIME-LAG FACTOR

TAKES 2-3 TAKES 2-3 HOURSHOURS FOR DRUGS TO FOR DRUGS TO EXERT EFFECTS ON SYNAPSEEXERT EFFECTS ON SYNAPSE

BUT…BUT…

IT TAKES 2-3 IT TAKES 2-3 WEEKSWEEKS FOR DRUGS TO FOR DRUGS TO EXERT EFFECTS ON DEPRESSION!EXERT EFFECTS ON DEPRESSION!


Why the time lag?Why the time lag?


EFFECTS OF PROZAC:EFFECTS OF PROZAC:

INCREASE 5-HT at terminal bouton (the INCREASE 5-HT at terminal bouton (the desired THERAPEUTIC effect),desired THERAPEUTIC effect),

but also…but also…

INCREASE inhibition at dendritic INCREASE inhibition at dendritic autoreceptors. autoreceptors.

Dendritic Release of Dendritic Release of SerotoninSerotonin

5-HTneuron

dendritic autoreceptors

5-HT released when cellis active. Binds to auto-receptors to inhibit activity

Prozac increases 5-HT inhibitory effect by blocking 5-HT dendritic re-uptake

At the Serotonin Terminal At the Serotonin Terminal BoutonBouton

Less release of 5-HT at bouton due to Less release of 5-HT at bouton due to Prozac-induced inhibition at dendritic Prozac-induced inhibition at dendritic autoreceptorautoreceptor

With less release Prozac has less of an With less release Prozac has less of an effect at effect at

terminal bouton little therapeutic terminal bouton little therapeutic effecteffect

Over time (2-3 weeks)...Over time (2-3 weeks)...

Inhibition of SEROTONIN neurons by Inhibition of SEROTONIN neurons by autoreceptors subsides (receptor autoreceptors subsides (receptor desensitizationdesensitization to excess serotonin) to excess serotonin)

Activity of neurons increaseActivity of neurons increase Increased 5-HT at terminal bouton Increased 5-HT at terminal bouton

synapsesynapse Prozac can now work to increase 5-HT at Prozac can now work to increase 5-HT at

terminal bouton synapseterminal bouton synapse

Therapeutic EffectTherapeutic Effect

QUESTION:QUESTION: Why don’t terminal Why don’t terminal bouton postsynaptic receptors bouton postsynaptic receptors become desensitized like become desensitized like autoreceptors?autoreceptors?

ANSWER: ANSWER: They are a different They are a different type of receptor than the dendritic type of receptor than the dendritic receptorsreceptors

5-HTneuron

5-HT1a dendriticreceptors: desensi-tize over time

5-HT2a, 5-HT3 receptors: no desensitization

post-synaptic receptors

CRITICAL EXPERIMENT TO CRITICAL EXPERIMENT TO TEST THIS HYPOTHESIS:TEST THIS HYPOTHESIS:

Administer PROZAC PLUS dendritic Administer PROZAC PLUS dendritic autoreceptor antagonist (PINDOL)autoreceptor antagonist (PINDOL)

RESULTS: Reduction of depressive RESULTS: Reduction of depressive symptoms within ONE WEEK!symptoms within ONE WEEK!

Is There Direct Evidence Is There Direct Evidence for Deficient Serotonin for Deficient Serotonin

Function in Depression?Function in Depression?

Dietary Depletion of Dietary Depletion of Serotonin and DepressionSerotonin and Depression

Serotonin SynthesisSerotonin Synthesis

tryptophan (amino acid)tryptophan (amino acid)

5–hydroxytryptophan5–hydroxytryptophan

5–hydroxytryptamine5–hydroxytryptamine

(Serotonin)(Serotonin)

Delgado Delgado etet alal. . (1990)(1990)

Depressed patientsDepressed patients

Antidepressant drugs(2-3 weeks) Antidepressant drugs(2-3 weeks) Feeling wellFeeling well

Low tryptophan diet for 24 hoursLow tryptophan diet for 24 hours - Amino acid “cocktail”- Amino acid “cocktail” 1. contained no tryptophan1. contained no tryptophan 2. promotes protein synthesis2. promotes protein synthesis 3. causes further depletion of 3. causes further depletion of

tryptophantryptophan

Delgado Delgado etet alal. – cont.. – cont.

RESULTSRESULTS

- Rapid serotonin depletion- Rapid serotonin depletion

- Rapid onset of depression (within hours)- Rapid onset of depression (within hours)

- Return to normal diet depression - Return to normal diet depression subsidessubsides

within 24 hourswithin 24 hours

Smith Smith etet al.al. (1997) (1997) 15 women with history of recurrent 15 women with history of recurrent

depressiondepression

- in remission- in remission

- drug free- drug free Two TrialsTwo Trials

Trial 1Trial 1

- Tryptophan-free amino acid cocktail- Tryptophan-free amino acid cocktail

Trial 2 (one week later)Trial 2 (one week later)

- Tryptophan-containing amino acid cocktail - Tryptophan-containing amino acid cocktail

Smith Smith etet alal. (1997)- . (1997)- cont.cont.

Rate mood hourly for next 7 hrs.Rate mood hourly for next 7 hrs. Blood samples to determine tryptophan levelsBlood samples to determine tryptophan levels RESULTS: RESULTS: - 75% reduction in tryptophan with tryptophan-- 75% reduction in tryptophan with tryptophan- free cocktailfree cocktail - Tryptophan-free trial 10 of 15 women- Tryptophan-free trial 10 of 15 women experienced temporary, significant depressionexperienced temporary, significant depression - Tryptophan-containing trial no mood- Tryptophan-containing trial no mood changeschanges Conclude: A key role for deficient serotonin Conclude: A key role for deficient serotonin function as a cause for depressionfunction as a cause for depression

Hormonal Abnormalities Hormonal Abnormalities in Depressionin Depression

Dysregulation of the hypothalamic-pituitary-Dysregulation of the hypothalamic-pituitary-adrenal (adrenal (HPAHPA) axis) axis

Many depressives have an overactive Many depressives have an overactive HPA HPA axisaxis

- high cortisol levels- high cortisol levels

- enlarged adrenals- enlarged adrenals

- enlarged pituitary gland- enlarged pituitary gland

- high - high CRFCRF concentrations in cerebrospinal fluid concentrations in cerebrospinal fluid

- enhanced expression of - enhanced expression of CRFCRF gene gene

CRF = Corticotropin CRF = Corticotropin Releasing FactorReleasing Factor

CRF-containing neurons in several brain areas CRF-containing neurons in several brain areas -hypothalamic paraventricular nucleus, amygdala-hypothalamic paraventricular nucleus, amygdala Intracerebroventricular CRF injections in ratsIntracerebroventricular CRF injections in rats

Behaviors similar to depression in humansBehaviors similar to depression in humans - insomnia- insomnia - decreased appetite- decreased appetite - decreased sexual drive- decreased sexual drive - anxietyanxiety

Nemeroff Nemeroff etet alal. . 19961996

The Stress-diathesis The Stress-diathesis Model Model

of Depressionof Depression

The interaction between The interaction between experience(stress)experience(stress)

and inborn predisposition (diathesis)and inborn predisposition (diathesis)

Genetic Predisposition Genetic Predisposition for Depressionfor Depression

Genetic traits lower threshold for depression Genetic traits lower threshold for depression - diminish monoamine levels - diminish monoamine levels - increase reactivity of HPA axis to stress - increase reactivity of HPA axis to stress EXAMPLE: EXAMPLE: stress stress (e.g., early childhood abuse/neglect)(e.g., early childhood abuse/neglect)

persistentpersistent increase in sensitivity of increase in sensitivity of CRF-containing neurons to stress in CRF-containing neurons to stress in predisposed individualspredisposed individuals

In adulthoodIn adulthood

-persistent increase in sensitivity of CRF -persistent increase in sensitivity of CRF neuronsneurons

-mild stressors vigorous activation of -mild stressors vigorous activation of CRF CRF

neuronsneurons

Symptoms of DepressionSymptoms of Depression

What’s the evidence for What’s the evidence for the model?the model?

PrimatesPrimates - - Rosenblum Rosenblum etet alal. (. (1994, 1994, 19961996))

RatsRats – – Ladd Ladd etet alal. . (1996)(1996)

Rosenblum Rosenblum etet alal. (1994, . (1994, 1996)1996)

Stress in infant monkeysStress in infant monkeys Foraging demand paradigm Foraging demand paradigm Three conditions for mothersThree conditions for mothers Low foraging demand condition (Low foraging demand condition (LFDLFD)) - minimal search for food in foraging device- minimal search for food in foraging device Variable foraging demand condition (Variable foraging demand condition (VFDVFD)) - unpredictable access to food- unpredictable access to food - required search for food in foraging device- required search for food in foraging device - 3 mos. duration during first 3-6 mos. of infant life- 3 mos. duration during first 3-6 mos. of infant life High foraging demand condition (High foraging demand condition (HFDHFD)) - considerable work effort for food, but predictable - considerable work effort for food, but predictable

Rosenblum Rosenblum etet alal.-cont..-cont. Effect on mothers’ behavior:Effect on mothers’ behavior: VFD mothersVFD mothers - more anxiety behaviors than LFD and HFD mothers- more anxiety behaviors than LFD and HFD mothers - less responsive to infants than LFD and HFD mothers- less responsive to infants than LFD and HFD mothers Effect on infants’ behavior:Effect on infants’ behavior: VFD infants - first yearVFD infants - first year - less independent of their mothers than LFD and HFD- less independent of their mothers than LFD and HFD - more frightened by novelty than LFD and HFDs- more frightened by novelty than LFD and HFDs VFD infants > four years later (young adults)VFD infants > four years later (young adults) - more timid- more timid - less social - less social - more subordinate- more subordinate

Rosenblum Rosenblum etet alal. – cont.. – cont. CSF CRFCSF CRF determined at 2 years of age determined at 2 years of age Results:Results: CRF concentrations CRF concentrations - VFD infants 110 pg/ml- VFD infants 110 pg/ml - LFD infants 77 pg/ml- LFD infants 77 pg/ml - HFD infants 82 pg/ml- HFD infants 82 pg/ml Conclude:Conclude:

Early-Life stressors sensitivity ofEarly-Life stressors sensitivity of

CRF neuronsCRF neurons

DepressionDepression

Mild Stress in Adulthood

Ladd Ladd etet alal.(1996).(1996) Neonatal ratsNeonatal rats Separated from mothers vs. controls (not Separated from mothers vs. controls (not

separated) separated) - 6 hours daily- 6 hours daily - Days 2-20 of life- Days 2-20 of life Measure ACTH and CRF concentrations at 3 Measure ACTH and CRF concentrations at 3

months of age (young adult rat)months of age (young adult rat) - basal and stress levels - basal and stress levels Four groups:Four groups: 1. Non-deprived/no stress1. Non-deprived/no stress 2. Non-deprived/stress 2. Non-deprived/stress 3. Deprived/no stress3. Deprived/no stress 4. Deprived/stress4. Deprived/stress

Ladd Ladd etet alal. (1996). (1996) RESULTS:RESULTS:

Deprived rats Deprived rats

- higher basal and stress ACTH levels- higher basal and stress ACTH levels

- higher basal and stress CRF concentrations - higher basal and stress CRF concentrations inin

two areastwo areas

1. median eminence – receives 1. median eminence – receives paraventricularparaventricular

nucleus CRF projections nucleus CRF projections

2. parabrachial nucleus –receives amygdala2. parabrachial nucleus –receives amygdala

CRF projectionsCRF projections

Ladd Ladd etet alal. (1996). (1996) CONCLUDE:CONCLUDE: Early Stress (maternal deprivation)Early Stress (maternal deprivation)

Persistent increase in sensitivity of CRF Persistent increase in sensitivity of CRF neuronsneurons

into adulthoodinto adulthood

DepressionDepression

Chronic mild stress

Does early trauma in Does early trauma in humans predispose to humans predispose to

depression in depression in adulthood?adulthood?

Agid Agid etet alal. (1999). (1999)

Early trauma before the 17Early trauma before the 17thth year year

- death of a parent- death of a parent

- physical separation from one parent- physical separation from one parent GroupsGroups

- unipolar depressive disorder (n=79)- unipolar depressive disorder (n=79)

- bipolar disorder (n=79)- bipolar disorder (n=79)

- control groups (ns=79)- control groups (ns=79)

Agid Agid etet alal. (1999) – . (1999) – cont.cont.

RESULTS:RESULTS: -Rates of parental loss-Rates of parental loss Unipolar disorder 23/79 29.1%Unipolar disorder 23/79 29.1% Control group 6/79 7.6%Control group 6/79 7.6%

Bipolar disorder 14/79 17.7%Bipolar disorder 14/79 17.7% Control Group 6/79 7.6% Control Group 6/79 7.6% -Separation more devastating than -Separation more devastating than

deathdeath-Greater impact of loss in early -Greater impact of loss in early

childhood(<9 yrs)childhood(<9 yrs)

Agid Agid etet alal. - cont.. - cont.

Control groupsControl groups

those who experienced EPL those who experienced EPL demonstrateddemonstrated

1. lower incomes 1. lower incomes

2. more physical illness2. more physical illness

3. greater divorce rate3. greater divorce rate

4. more likely to be living alone4. more likely to be living alone

5. stronger lifetime history of smoking5. stronger lifetime history of smoking

Can Enhanced Maternal Can Enhanced Maternal Care Decrease CRF Care Decrease CRF

Response Sensitivity to Response Sensitivity to Stress?Stress?

Liu Liu etet alal. (1997). (1997)

Neonatal handling changes in mother-Neonatal handling changes in mother-pup pup

(first 10 days) interactions(first 10 days) interactions

- increased licking and grooming by mother- increased licking and grooming by mother

- higher incidence of arched-back nursing (ABN) - higher incidence of arched-back nursing (ABN)

Pup handling reduces HPA response toPup handling reduces HPA response to

stress in adulthoodstress in adulthood

(Less ACTH and GC response)(Less ACTH and GC response)

Liu Liu etet alal. – cont.. – cont. Observed behavior of mothers of non-handled Observed behavior of mothers of non-handled

pupspups Divide mothers into two groupsDivide mothers into two groups - High groomers- High groomers - Low groomers- Low groomers Measured HPA axis sensitivity in pups as adultsMeasured HPA axis sensitivity in pups as adults RESULTS:RESULTS: 1. Decreased HPA stress response in high1. Decreased HPA stress response in high groomed pupsgroomed pups 2. Decreased CRF synthesis in paraventricular 2. Decreased CRF synthesis in paraventricular

nucleusnucleus in high groomed pups in high groomed pups

Stress-induced Depression Stress-induced Depression in Adulthoodin Adulthood

HumanHuman

-Stressful events can precede depression-Stressful events can precede depression

a. Inability to predicta. Inability to predict

b. Inability to controlb. Inability to control Animal ModelsAnimal Models

Uncontrollable Stressful EventsUncontrollable Stressful Events

Depression-like characteristics Depression-like characteristics

A Potential Brain A Potential Brain Circuit for DepressionCircuit for Depression

Acute fear/anxiety provoking stimulus (bear)Acute fear/anxiety provoking stimulus (bear)

activates the amygdalaactivates the amygdala

CRFCRF

hypothalamic other brain hypothalamic other brain paraventricular n. paraventricular n. areasareas

activate the HPA axis acute anxietyactivate the HPA axis acute anxiety

Prolonged, Uncontrollable Stress in Adulthood

Persistent amygdala activity CRF persistent in CRF persistent in CRF release in hypothal. release in other brain paraventricular nucleus regions

hyperactive HPA axis chronic anxiety

increased GC levels depression

Is there evidence of Is there evidence of increased activity in increased activity in the amygdala during the amygdala during

depression?depression?

Drevets Drevets et alet al. (1992 ff.). A functional . (1992 ff.). A functional anatomical study of unipolar anatomical study of unipolar depression.depression.

Drevets Drevets etet alal. . Melancholic depressivesMelancholic depressives with a family history of with a family history of

depression (familial depressive disorder)depression (familial depressive disorder) Melancholic depressives in remissionMelancholic depressives in remission Matched control groupMatched control group PETPET scan at rest to assess metabolic activity scan at rest to assess metabolic activity RESULTS:RESULTS:

- - enhanced amygdala activityenhanced amygdala activity in depressed in depressed

patientspatients

- some increase in remission group- some increase in remission group

- the greater the depression the greater the - the greater the depression the greater the amygdala amygdala

activity activity

Drevets Drevets etet alal. – cont.. – cont.

In depressives, the greater the amygdalaIn depressives, the greater the amygdala activity, the greater the cortisol levelactivity, the greater the cortisol level Antidepressive drugs decrease depression Antidepressive drugs decrease depression

and amygdala activity toward normaland amygdala activity toward normal Tryptophan-free cocktail to depressive Tryptophan-free cocktail to depressive

patients in remissionpatients in remission - those who relapse had higher amygdala- those who relapse had higher amygdala activity during remissionactivity during remissionCONCLUDE:CONCLUDE: Amygdala may contribute Amygdala may contribute

to symptoms of, and vulnerability to, to symptoms of, and vulnerability to, depressiondepression

Documents

AFFECTIVE DISORDERS n UNIPOLAR DISORDER ~ –Major Depression n BIPOLAR DISORDER ~ –Depression and Mania