affective disorders n unipolar disorder ~ –major depression n bipolar disorder ~ –depression and...
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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
UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes
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
UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes
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
UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes
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
UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes
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
UNIPOLAR DEPRESSION ~ UNIPOLAR DEPRESSION ~ SubtypesSubtypes
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!
THE MONAMINE THEORY THE MONAMINE THEORY OF DEPRESSIONOF DEPRESSION
Why the time lag?Why the time lag?
THE MONAMINE THEORY THE MONAMINE THEORY OF DEPRESSIONOF DEPRESSION
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 - anxiety- anxiety
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