Pathophysiology

of Depression and its Signs

and Symptoms
Presentation Created by Prashant Chettri,
Roll no: 24
 CONTENTS
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 Introduction
 Neurotrophic Hypothesis
 Monoamine Hypothesis
 Neuroendocrine Factors
 Integration of Hypotheses
 Signs and Symptoms of Depression
 INTRODUCTION
INTRODUCTION
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 Three principal neurotransmitters have long been implicated

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AL OR
in both the pathophysiology and treatment of mood
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disorders. (Norepinephrine, Dopamine,
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 Many of the symptoms of mood disorders are hypothesized to
involve dysfunction of various combinations
BRAIN of these three
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systems. WHODEATH
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 Essentially all known treatments for mood disorders act
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upon one or more of these three DEATsystems.
 Histologic studies, structural and
H functional brain imaging
research, genetic findings, and steroid research all suggest a
complex pathophysiology for MDD with important
 NEUROTROPHIC HYPOTHESIS
INTRODUCTION
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 The site of a possible flaw in signal transduction from

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monoamine receptors in depression AL OR is the target gene for
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brain-derived neurotropic factor AL(BDNF).
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 BDNF are critical in the regulation of neural plasticity,
resilience, and neurogenesis; but under stress, the gene for
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BDNF may be repressed. STEM
WHO
 Stress can lower 5HT levels and LE DEATH
can acutely increase, then
chronically deplete, both NE and DA; together with deficient
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amounts of BDNF may lead to atrophy and possible
H
apoptosis of vulnerable neurons in the hippocampus and
other brain areas such as prefrontal cortex.
 Depression is associated with the loss of neurotrophic
 MONOAMINE HYPOTHESIS
INTRODUCTION
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 ***The entire monoaminergic neurotransmitter

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monoamines NE, 5HT, and DA may be malfunctioning in
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various brain circuits, with different
DEATHneurotransmitters involved
depending upon the symptom of the patient.
 It has been known that reserpine treatment,
BRAIN which is known to
deplete monoamines, is associated WHO with depression in a subset
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of patients. LE
 Depressed patients who respondBRAI to serotonergic
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antidepressants such as fluoxetine H often rapidly suffer relapse
when given diets free of tryptophan, a precursor of serotonin
synthesis.
 Patients who respond to noradrenergic antidepressants such as
 NEUROENDOCRINE FACTORS
INTRODUCTION
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 Depression is known to be associated with a number of

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hormonal abnormalities. AL OR
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Abnormalities Elevated
in the HPA axis cortisol levels Thyroid
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Major
WHOSTEM Hormones
Depressive DEATH
Nonsuppression ofDisorder LE
adrenocorticotropic Chronically elevated
BRAI Steroids
hormone (ACTH) levels of
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release in the Corticotropin-
H
dexamethasone releasing hormone
suppression test
 INTEGRATION OF HYPOTHESES
INTRODUCTION
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 It is evident that the monoamine, neuroendocrine, and

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neurotrophic systems are interrelated
AL OR in important ways.
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 For example, HPA and steroid abnormalities
AL may contribute to
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suppression of transcription of the BDNF gene.
 Glucocorticoid receptors are found in high density in the
hippocampus. Binding of these receptors
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STEM
by cortisol during
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chronic stress states such as major depression may decrease
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BDNF synthesis and may result BRAI
in volume loss in stress
sensitive regions such as the hippocampus.
DEAT The chronic
activation of monoamine receptorsH by antidepressants
appears to have the opposite effect of stress and results in an
increase in BDNF transcription. In addition, activation of
 SIGNS AND SYMPTOMS
INTRODUCTION
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DEATH

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STEM
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 References
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 Bertram Katzung, Susan Masters, Anthony

Trevor-Basic and Clinical Pharmacology, 11th
Edition (LANGE Basic Science) McGraw-Hill
Medical (2009)
 Stahl S.M.-Stahl's Essential
Psychopharmacology Neuroscientific Basis
and Practical Applications -Cambridge
University Press (2013)
 INTRODUCTION
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Writing prescriptions is easy,

CORTICunderstanding
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people is hard. (Franz Kafks,
CEREBR1883-1924)
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Thank
BRAIN You. WHO
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DEATH

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