DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M,...

DEPRESSION

NORMAL MOOD

RECOVERY OR REMISSION

EPISODE OF DEPRESSIONEPISODE OF DEPRESSION

TIME6 - 24 months

5-1 Stahl S M, Essential Psychopharmacology (2000)

DEPRESSION

NORMAL MOOD

RESPONSE

RESPONSE


acute 6 - 12 weeks

continuation4-9 months

maintenance1 or more years

REMISSION

RECOVERY

DEPRESSION

NORMAL MOOD

100%


TIME


acute 6 - 12 weeks

continuation4-9 months

maintenance1 or more years

TIME

DEPRESSION

NORMAL MOOD RELAPSE RECURRENCE


DEPRESSION

NORMAL MOOD

MANIA

HYPOMANIA

MIXED EPISODE

12 months

DEPRESSION

NORMAL MOOD

RAPID CYCLINGRAPID CYCLING


2+ years

DEPRESSION

NORMAL MOOD

DYSTHYMIADYSTHYMIA


6 - 24 months2+ years

DEPRESSION

NORMAL MOOD

DYSTHYMIA PARTIAL RECOVERY

DOUBLE DEPRESSIONDOUBLE DEPRESSION



8 weeks

DEPRESSION

NORMAL MOOD

67% RESPONDERS

MEDICATIONMEDICATION

medication started

33% NON-RESPONDERS


8 weeks

DEPRESSION

NORMAL MOOD

33% RESPONDERS

PLACEBOPLACEBO

placebo started

67% NON-RESPONDERS


DEPRESSION

NORMAL MOOD

50% continue response

PLACEBO PLACEBO SUBSTITUTIONSUBSTITUTION

antidepressant treatment

placebo

50% relapse


DEPRESSION

NORMAL MOOD

90% continue response

DRUG DRUG CONTINUATIONCONTINUATION

antidepressant treatment

10% relapse

MAO enzyme destroying neurotransmitter

monoamine neurotransmitter

NORMAL STATE -- no depression

MONOAMINE HYPOTHESIS

5-13 5-14

Stahl S M, Essential Psychopharmacology (2000)

DEPRESSION -- caused by neurotransmitter deficiency

Increase in neurotransmitters causes return to normal state

MAO inhibitor blocks the enzyme from destroying monoamine neurotransmitter

reuptake pump blocked by antidepressant

5-15 5-16


NE (norepinephrine)

tyrosine transporter

TYR

TOH

DOPA

DDC DA

DBH

NOREPINEPHRINE IS PRODUCED


NOREPINEPHRINE IS DESTROYED

COMT destroys NEnorepinephrine

transporter

MAO


NOREPINEPHRINE RECEPTORS

presynaptic alpha 2 autoreceptor

postsynaptic alpha 2

receptorpostsynaptic beta 1 receptor

alpha 1 receptor


terminal alpha 2 autoreceptor

somatodendritic alpha 2

autoreceptor


NE occupying somatodendritic autoreceptor causes a decrease in firing and a decrease of NE release


NE

NE occupying terminal alpha 2 receptor halts release of NE


NE

Norepinephrine Pathways

Locus Coeruleus


beta 1 receptor


DepressionFrontal 1

alpha 2 receptor

Frontal 2 Attention



Limbic

EmotionsAgitationEnergy Level


Cerebellum Tremor


Spinal Cord Blood Pressure


Heart Tachycardia

5--30 Stahl S M, Essential Psychopharmacology (2000)

Bladder Urinary Retention

tyrosine transporter

TOH

TYR

DOPA

DDC

DA (Dopamine)

DOPAMINE IS PRODUCED


COMT destroys NE

dopamine transporter

MAO

DOPAMINE IS DESTROYED


DOPAMINE RECEPTORS

presynaptic autorecptor

D1 D2 D3 D4 D5

dopamine transporter


5HT (Serotonin)

SEROTONIN IS PRODUCEDtryptophan transporter

TRY-OH

5HTP

AAADC

Tryptophan


serotonin transporter

MAO

SEROTONIN IS DESTROYED


SEROTONIN RECEPTORS

alpha 2 hetero receptor

5HT1D autoreceptor

5HT1A

serotonin transporter

5HT2A5HT2C

5HT3 5HT45HTX

5HTY

5HTZ


5--37 5-38


5HT1D

5--39 5-40


norepinephrine

serotonin


serotonin neuron



serotonin neuron


norepinephrine

serotonin

alpha 1 receptor


brake

accelerator

Locus Coeruleus

NE-5HT Interactions


serotonin neuron

presynaptic alpha 2 autoreceptor

postsynaptic alpha 2 hetero receptor

presynaptic alpha 2 autoreceptor alpha 1

receptor

norepinephrine neuron


5HT accelerator

5HT brake

5HT2A

5--49

5-50


Serotonin Pathways

Raphe Nucleus



Frontal Cortex Mood


Basal Ganglia OCDAkathisia/Agitation


Limbic Anxiety


Hypothalamus Appetite/bulimia


Sleep Centers Insomnia


Spinal Cord Sexual Dysfunction


Brainstem Vomiting Center

Nausea and vomiting


Gut GI cramps/Diarrhea

Monoamine Receptor Hypothesis of DepressionMonoamine Receptor Hypothesis of Depression

Normal functioning

Decrease in NT

Receptors up-regulate due to lack of NT

5--60 5-61 6-62



BDNF gene

StressStress

Stress

BDNF


Apoptosis

substance P release

pain and swelling

substance P release


= substance P

hypothalamus

amydala and limbic areas

dopamine centers norepinephrine

centers

Neurokinin Hypothesis of Emotional Malfunctioning Corollary: Blockng the Appropriate Neurokinin

Receptor will Reduce Emotional Distress


substance P

Neurokinin A (NK-A)

Neurokinin B (NK-B)

Arg Pro Lys Gln Gln Phe Phe Gly Leu Met NH2

Gly Leu Met NH2

Gly Leu Met NH2

Val

Val

SerAspThrLysHis

Asp PheHisMetAsp


PPT-A gene

PPT-A mRNA

signal peptidase

endoplasmic reticulum

converting enzyme

substance P

NK-1 receptor


PPT-A spliced mRNA

PPT-A protein

PT-A

PPT-A gene

PPT-A mRNA

signal peptidase


converting enzyme

substance P

NK-1 receptor


PPT-A spliced mRNA

PPT-A protein

PT-A

PPT-A gene

PPT-A mRNA

signal peptidase


converting enzyme

substance P

NK-1 receptor

PPT-A spliced mRNA


PPT-A protein

PT-A

PPT-A gene

PPT-A mRNA

signal peptidase


converting enzyme

NK-A

NK-2 receptor


PPT-A spliced mRNA

PPT-A protein

PT-A

PPT-A gene

PPT-A mRNA

signal peptidase


converting enzyme

NK-A

NK-2 receptor

PPT-A spliced mRNA


PPT-A protein

PT-A

PPT-B gene

PPT-B mRNA

PPT-B protein

signal peptidase


PT-B

converting enzyme

NK-B

NK-3 receptor

PPT-B spliced mRNA


DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M,...

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Transcript of DEPRESSION NORMAL MOOD RECOVERY OR REMISSION EPISODE OF DEPRESSION TIME 6 - 24 months 5-1 Stahl S M,...