Monoamine Hypothesis of Depression

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Transcript Monoamine Hypothesis of Depression

Mood Disorder Categories (DSM-IV)
• Depressive disorders
– Major depressive disorder, clinical depression
– Dysthymia
– Depressive Disorder Not Otherwise Specified (NOS)
• Bipolar disorder
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Bipolar I
Bipolar II
Cyclothymic Disorder
Bipolar Disorder NOS
Changes from DSM-IV-TR to DSM-5
• Depressive Disorders contains new categories
– disruptive mood dysregulation disorder
• children up to age 18 years
• replaces bipolar disorder in children
– premenstrual dysphoric disorder
– persistent depressive disorder
• chronic major depressive disorder
• dysthymic disorder
• Major Depressive Disorder: changes to the organization of
categories
– bereavement exclusion removed
• Bipolar Disorders has more emphasis on changes in activity
and energy
– bipolar I disorder includes “with mixed features”
http://www.nimh.nih.gov/health/statistics/prevalence/major-depression-among-adults.shtml
http://www.nimh.nih.gov/health/statistics/prevalence/major-depression-among-adolescents.shtml
Gender Differences in Depression
• Major Depression
– Women twice as likely as men
– But girls and boys have equal rates
– Power Theory
• Higher levels of physical and psychological abuse
• Living in poverty
• Overburdened by family & work responsibilities
– Coping Style
• Women are more interpersonally oriented
• Respond to interpersonal stressors with rumination
• Men more likely to use alcohol to cover up symptoms
– Reactivity to Stress
• HPA response to stress dysregulated
• HPA modulated by estrogen levels?
• Postpartum depression
Symptoms of Clinical Depression
• Clinical symptoms common to depression include
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Pervasive unhappiness and despair
Negative, pessimistic thoughts
Anhedonia (inability to experience pleasure)
Loss of self-esteem
Impairment of normal functioning (home, social, work)
Suicidal ideas
• Vegetative symptoms that warrant medication treatment
(when seen with symptoms above)
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Appetite disturbance
Sleep disturbance (early am wakening, frequent awakenings)
Diurnal mood variation (worse in morning)
Marked anhedonia “inability to experience pleasure in normally
pleasurable acts”
Role of genetics in depression
• High concordance rates: (60%) in monozygotic twins
• High rates of mood disorder in family members
• No evidence of a single gene
– small associations between the polymorphism in the
serotonin transporter promoter region
– association of Major Depression Disorder with
polymorphisms gene for brain-derived neurotrophic
factor (BDNF).
• BDNF is related to recovery from stress
Treatments for depression
• Drug Therapy
• Monoamine Oxidase (MAO) Inhibitors
• Tricyclic drugs
• Selective serotonin reuptake inhibitors (SSRIs)
• Ketamine and leptin
• Brain stimulation
• Deep brain stimulation (DBS)
• Vagal nerve stimulation
• Electroconvulsive shock therapy (ECT)
• Transcranial magnetic stimulation (TMS)
• Cognitive behavioral therapy (CBT)
Table 16.3 Drugs Used to Treat Depression
The most commonly prescribed antidepressants in
the US retail market in 2010 were
Drug name
Commercial name
Drug class
Total prescriptions
Sertraline
Zoloft
SSRI
33,409,838
Citalopram
Celexa
SSRI
27,993,635
Fluoxetine
Prozac
SSRI
24,473,994
Escitalopram
Lexapro
SSRI
23,000,456
Trazodone
Desyrel
SARI
18,786,495
Duloxetine
Cymbalta
SNRI
14,591,949
Paroxetine
Paxil
SSRI
12,979,366
Amitriptyline
Elavil
TCA
12,611,254
Venlafaxine XR
Effexor XR
SNRI
7,603,949
Bupropion XL
Wellbutrin XL
NDRI
7,317,814
Mirtazapine
Remeron
TeCA
6,308,288
Venlafaxine ER
Effexor XR
SNRI
5,526,132
Bupropion SR
Wellbutrin SR
NDRI
4,588,996
Desvenlafaxine
Pristiq
SNRI
3,412,354
Nortriptyline
Sensoval
TCA
3,210,476
Bupropion ER
Wellbutrin XL
NDRI
3,132,327
Venlafaxine
Effexor
SNRI
2,980,525
Bupropion
Wellbutrin IR
NDRI
753,516
Antidepressant From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Antidepressant
Drugs Used To Treat Depression
Amitriptyline
Placebo Effect in Depression
• Effectiveness of antidepressant drugs typically reported as
– 50-60 % symptom free
– 20-30 % some improvement
– 20 % no improvement
• However, placebo effect: 50 – 80 % show improvement
• Blind trials are difficult because most patients know they are
getting a drug
• Patients at the very extreme end of depression severity,
showed the most improvement over placebo
• Drug therapy plus Psychotherapy is most effective treatment
Amine Depression Hypotheses
• Biogenic amine hypothesis suggests that depression reflects a
suboptimal level of NE, DA, EPI, or 5-HT in brain
• Evidence from
– Reserpine depletes CNS catecholamines (leads to depression)
– Depressed patients have low levels of 5-HIAA (metabolite)
– Drugs used to treat depression elevate synaptic levels of NE and 5HT (e.g. imipramine, )
• Problems for the amine hypothesis
– Some drugs used to treat depression (bupropion) do not block
reuptake of amines
– Why doesn’t Cocaine reduce depression?
– Why doesn’t Ecstasy reduce depression?
– Why is there a temporal delay between drug administration, onset
of amine changes, and reduction in depression?
Role of Glutamate in Depression
• Too much glutamate can overstimulate neurons causing
collapse of the branches by which they communicate
with other cells
• One effect of antidepressants is to reduce the sensitivity
of receptors in the PFC for glutamate
• Antidepressant-like actions of compounds which reduce
transmission at N-methyl-D-aspartate (NMDA) receptors
• Towards a glutamate hypothesis of depression: an
emerging frontier of neuropsychopharmacology for mood
disorders. (2012) Sanacora G, Treccani G, Popoli M
Neuropharmacology. Jan;62(1):63-77.
Role of Glutamate in Depression
• Treating depression with Ketamine
– Blocking NMDA type of glutamate receptors
– A single dose of ketamine has rapid and lasting antidepressant
effects in patients with major depression or bipolar disorder.
– Zarate CA Jr. A randomized add-on trial of an N-methyl-Daspartate antagonist in treatment-resistant bipolar depression.
Arch Gen Psychiatry. 2010 Aug;67(8):793-802.
– Zarate CA Jr. Rapid resolution of suicidal ideation after a single
ketamine infusion in patients with treatment-resistant major
depression. J Clin Psychiatry, 71:1605-11, 2010.
Role of Stress in Depression
• Dysregulation of HPA : to much cortisol
• Damages hippocampus
– Changes the shape, size and number of neurons
• Suppressed nerve cell growth in a part of the
hippocampus
• Damages prefrontal cortex and the amygdala
– smaller in people with recurrent depression
Brain Activity Patterns from PET scan in Depression
Increased activity in Prefrontal Cortex and Amygdala
Diathesis-Stress Model
• Diathesis is vulnerability or susceptibility
– Genetic influences
• High concordance rate in twin studies
• family history of mental disorder
• hypothalamic-pituitary-adrenal responsivity
– Developmental
• maternal stressors
• childhood maltreatment
• Interaction of Diathesis and Stress
– Individuals with more vulnerability are more likely to
become ill when challenged by stressors
The Hypothalamic-Pituitary-Adrenal Axis in Depression
Sleep and Depression
Light therapy for Seasonal affective disorder (SAD)
Bipolar disorder
• Characterized by periods of depression
alternating with expansive mood, or mania.
• The rate of cycling varies–rapid cycling consists
of four or more cycles in one year.
• Some individuals may cycle several times in one
day.
• In Cyclothymia–a milder form of bipolar
disorder–patients cycle between dysthymia (mild
depression) and hypomania (increased energy).
• Lithium is a mood-stabilizing drug used to treat
bipolar disorder.
The Treadmill of Depression