Presentation Created by Prashant Chettri,

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 CONTENTS
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 Introduction
 Neurotrophic Hypothesis
 Monoamine Hypothesis
 Neuroendocrine Factors
 Integration of Hypotheses
 Signs and Symptoms of Depression
 INTRODUCTION
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 Three principal neurotransmitters have CORTICAL

long been implicated in both the
pathophysiology and treatment of mood disorders. (Norepinephrine,
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Dopamine, and Serotonin)
 Many of the symptoms of mood disorders are hypothesized to involve
dysfunction of various combinations of these three systems.
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 Essentially all known treatments for mood disorders
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these three systems.
 Histologic studies, structural and functional brain imaging research, genetic
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findings, and steroid research all suggest a complex pathophysiology for
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MDD with important implications for drug DEATH
treatment. *1
 NEUROTROPHIC HYPOTHESIS
INTRODUCTION
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 The site of a possible flaw in signal transduction from monoamine receptors

in depression is the target gene for brain-derived
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neurotropic factor (BDNF).
 BDNF are critical in the regulation of neural
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neurogenesis; but under stress, the gene for BDNF may be repressed.
 Stress can lower 5HT levels and can acutely increase, then chronically
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deplete, both NE and DA; together with deficientEM amounts of BDNF may
lead to atrophy and possible apoptosis of DEATHvulnerable neurons in the
hippocampus and other brain areas such as prefrontal cortex.
 Depression is associated with the loss ofWHOL
neurotrophic support and that
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effective antidepressant therapies increase neurogenesis and synaptic
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connectivity in cortical areas such as the hippocampus. *2
 MONOAMINE HYPOTHESIS
INTRODUCTION
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 ***The entire monoaminergic neurotransmitter system of three monoamines NE,

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5HT, and DA may be malfunctioning in various OR brain circuits, with different
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neurotransmitters involved depending uponDEATHthe symptom of the patient.
 It has been known that reserpine treatment, which is known to deplete
monoamines, is associated with depression inBRAINST
a subset of patients.
 Depressed patients who respond to serotonergic EM antidepressants such as
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fluoxetine often rapidly suffer relapse when given diets free of tryptophan, a
precursor of serotonin synthesis.
 Patients who respond to noradrenergic antidepressants
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less likely to relapse on a tryptophan freeDEATH
diet.
 NEUROENDOCRINE FACTORS
INTRODUCTION
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 Depression is known to be associated with a number of hormonal abnormalities.

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Abnormalities Elevated
in the HPA axis cortisol levels
BRAINST Thyroid Hormones
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Major Depressive DEATH
Disorder

Nonsuppression of Steroids
adrenocorticotropic Chronically elevated
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hormone (ACTH) release in of Corticotropin-releasing
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the dexamethasone hormone
suppression test DEATH
 INTEGRATION OF HYPOTHESES
INTRODUCTION
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 It is evident that the monoamine, neuroendocrine, and neurotrophic systems are

interrelated in important ways. CORTICAL
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 For example, HPA and steroid abnormalities may contribute to suppression of
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transcription of the BDNF gene.
 Glucocorticoid receptors are found in high density in the hippocampus. Binding
of these receptors by cortisol during chronicBRAINST
stress
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states such as major
depression may decrease BDNF synthesis and may result in volume loss in
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stress sensitive regions such as the hippocampus. The chronic activation of

monoamine receptors by antidepressantsWHOL appears to have the opposite effect
of stress and results in an increase in BDNF transcription. In addition, activation
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of monoamine receptors appears to down-regulate the HPA axis and may
normalize HPA function. *4
 SIGNS AND SYMPTOMS
INTRODUCTION
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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, understanding

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people is hard. (Franz Kafks,OR1883-1924)
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Thank You. BRAINST

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