Download Major Depressive Disorder

Major Depressive Disorder
Kathryn Secrist |Amritha Harikumar
The University of Tulsa
November 6th, 2014
Clinical Presentation
 Major Depressive Disorder(MDD) is a disorder that presents specific symptoms according to the
DSM-V( American Psychological Association., 2013)
 According to the DSM-V, the Diagnostic and Statistical Manual of Disorders-5th Edition, five or
more of certain symptoms have to be present in the patient during a continuous 2 week period;
one of the symptoms includes depressive mood or loss of interest or pleasure:
 Depressed mood most of the day; nearly every day with symptoms such as sadness, emptiness,
hopelessness and irritability (DSM-IV)
 Loss of interest/pleasure in daily activities
 Marked weight loss without diet/exercise changes during regular routines; OR decrease/increase
in appetite every day
 Psychomotor agitation/retardation
 Fatigue, loss of energy
 Excessive guilt/feelings of worthlessness
 Diminished ability to think/concentrate
 Suicidality
 Symptoms above cause clinically significant problems/stress
 IMPORTANT: Cannot be caused by substance abuse/medical condition
Essential Features of MDD
 Criterion symptoms must be present close to every day ( APA et al., 2013)
 Fatigue/sleep disturbances common in MDD
 2 weeks of depressed mood/loss of interest-KEY FEATURE OF MDD
 Four additional symptoms must be present that include the following:
 Appetite/weight increase-decrease
 Psychomotor activity
 Decreased energy
 Feelings of worthlessness
 Difficulty thinking/concentrating
Depression in History
 Initially called “melancholia” (Nemade,
Reiss, & Domback., 2007)
 Earliest accounts of melancholia
appeared in ancient Mesopotamian texts
 All mental illnesses at this time were
attributed to demonic possession
 The first historical understanding of
depression was a spiritual illness rather
than a physical one.
 Hippocrates, a Greek physician, thought
that melancholia was caused by too
much black bile in the spleen.
 In the years before Christ, Romans
believed in demonic possession while
Persians viewed the brain as the seat of
melancholia
Depression in History
 After fall of the Roman empire, scientific thinking about the
causes of depression again regressed (Nemade et al.,
2007)
 During the Middle Ages, religious beliefs dominated
popular European explanations of mental illness e.g.
demons and witches
 Treatments included exorcisms, drowning and burning
 During the Renaissance, some doctors returned to the
views of Hippocrates
 During the beginning of the Age of Enlightenment, it was
thought that depression was an inherited, unchangeable
weakness of temperament.
 Lead to the common thought that affected people should
be shunned or locked up. (Nemade et al.,2007)
 In latter part of Age of Enlightenment, some doctors and
authors suggested that aggression was the real root of
depression
 Advances in general medical knowledge caused search
for organic (physical) treatments
Depression in History
 Towards the beginning of 19th century, new
therapies included water immersion and a
spinning stool to induce dizziness. (Nemade et
al., 2007)
 Benjamin Franklin introduced an early form of
electroshock therapy.
 First distinguished from schizophrenia in 1895
 In 1917, Sigmund Freud explained melancholia
as a response to loss
 Either real loss, or symbolic loss
 Freud believed that a person’s unconscious
anger over loss weakened the ego, resulting in
self-hate and self-destructive behavior
(Nemade et al.,2007)
 In the 1950s and 1960s, the medical community
classified depression as either “endogenous” or
“neurotic”
 Currently, medical professionals recognize that
depressive symptoms have multiple causes
Prevalence
 12 month prevalence rate for MDD at 7%
 Differs by age group; 18-29 year olds have three times more of a prevalence rate
than people 60 years of age and older (Kessler, Berglund, & Demler., 2003)
 Women are twice more likely to have depression than males (Kessler et al.,2003)
 Attributed to genetic factors, especially first degree relatives (Kendler, Thornton, &
Gardner, 2001)
 Patients w/higher levels of neuroticism and brain trauma at greater risk for
developing MDD (Kendler et al., 2001; Basso, Miller, Estevis, & Combs., 2011)
Course of Illness
 Extremely variable, depends on remission rates which vary per person (some
people experience MDD after 2 months with either zero symptoms; or 1-2
symptoms)
 Important to distinguish between individuals who developed depression and are
undergoing treatment after a long period of symptoms versus individuals who
recently developed MDD
 In the latter case, it is labelled chronic depressive symptoms, and can develop
because of personality, anxiety, and extraneous factors (Coryell, Endicott, &
Keller., 1990; Klein, Taylor, & Dickstein., 1988)
 Recovery: Occurs 3 months after initial diagnosis in 2/5 patients, and within one
year for 4/5 individuals (Coryell, Akiskal, & Leon., 1994)
Genetic and Environmental Factors
 First-degree family members of individuals with major depressive disorder have a
risk for major depressive disorder two- to fourfold higher than that of the general
population (APA et al., 2013)
 Relative risks appear to be higher for early-onset and recurrent forms
 Approximately 40% heritability
 The personality trait neuroticism accounts for a substantial portion of genetic liability
 Adverse childhood experiences constitute a set of potent risk factors for MDD
 Stressful life events are well recognized as precipitants of MDD ( APA et al., 2013)
 But the presence or absence of adverse life events near the onset of episodes is not a
useful guide to prognosis or treatment selection
Unipolar Depression

No pathogenomic distinctions between unipolar and bipolar depression
 Major difference between unipolar and bipolar individuals is the development of hypomania
(thus making the patient “bipolar”) (Mitchell, Goodwin, Johnson, Hirschfield, 2008).
 Common features in unipolar depressive disorder include:
 Insomnia/lessened sleep
 Appetite loss
 Later age of onset concerning MDD
 No family history of BP disorder
 Normal or increased level of activity
 Prolonged episodes
 Two sub-types of unipolar depression- atypical and agitated depression (Mitchell et
al., 2008).
 Controversial subtypes due to comorbidity issues in both agitated and atypical
depression
Agitated Depression
 Also referred to in the literature as “depressive
mixed state”
 Primary symptoms:
 Restlessness,
 Increases talkativeness
 Irritability (Akiskal, Benazzi, Perugi, & Rihmer, 2005;
Kraeplin,1899, 1921 English translation by Barclay;
Weygandy, 1899, English translation by Marneros in
2001)
 Issues with diagnosis, due to comorbidity with
bipolar disorder
 35% of unipolar depressed patients will display
agitated depressive symptoms(Akiskal, Benazzi,
Perugi, Rihmer., 2004)
Atypical Depression
 Mood reactivity, must have two of the following symptoms:
 Significant weight gain
 Hypersomnia
 Leaden paralysis
 Long history of rejection sensitivity(APA., 2013)
 16-23% of unipolar patients show atypical depressive symptoms(Benazzi .,1999)
 Comorbidity issues with BP-1 disorder(Mitchell et al., 2008)
 “Atypical” symptoms such as hypersomnia, leaden paralysis, psychomotor
agitation, psychotic features, pathological guilt(Mitchell et al., 2008)
Neural Structures of MDD
 Medial orbital pre-frontal cortex, amygdala, hippocampus, ventromedial parts
of basal ganglia; alterations in gray matter volume all implicated in individuals
with major depressive disorder
 Dorsal medial prefrontal cortex was implicated, supragenual anterior
cingulate cortex, precuneus, ventral striatum, and the dorsomedial
thalamus(Grimm, Ernst, Boesiger, Schuepback, Hell, Boeker, & Northoff., 2009)
 Signal changes in DMPRFC mediated depression severity and hopelessness
 Ventral striatum and Dorsomedial thalamus relate to judgements of selfrelatedness of negative emotional stimuli(Grimm et al., 2009)
Neurotransmitters Involved
 Monoamine deficiency is among the oldest of the neurochemical theories of
depression (Holtzeimer & Nemeroff., 2006)
 Serotonin, norepinephrine, and dopamine are widely distributed throughout
the central nervous system
 Involved in many aspects of behavior including mood, cognition, locomotion,
sleep, appetite, libido, arousal, anxiety, and aggression
 Largely function as modulators of excitatory and inhibitory neurotransmitter
circuits (Holtzeimer et al., 2006)
 Considerable overlap exists between these systems
Serotonin
 Produced in cells of the rostral and caudal raphe nuclei
 Serotonergic projections include several brain regions, including the hypothalamus,
thalamus, hippocampus, amygdala, basal ganglia, prefrontal cortex, and cingulate
cortex (Holtzeimer et al., 2006)
 The effects of serotonin are mediated through pre and postsynaptic 5HT receptors
 After release from the presynaptic terminal, 5-HT binds to 5-HT receptors or is taken
up into the presynaptic terminal by the serotonin transporter and either repackaged
into a terminal vesicle or catabolized by monoamine oxidase
 Cerebrospinal fluid levels of serotonin metabolites are generally reduced in
depressed patients and even lower in depressed patients with a history of suicide
attempts
 Tryptophan depletion can lead to a depressive relapse in euthymic patients with
history of depression responsive to SSRIs (Holtzeimer et al., 2006)
 Reduced SERT availability and binding abnormalities have been consistently
identified in depression
Norepinephrine
 Primarily produced in cells of the pontine locus ceruleus (Holtzeimer et al.,
2006)
 These cells project to multiple cortical and subcortical brain regions
 NE system well known to modulate the stress response
 NE interacts with pre and postsynaptic alpha and beta-adrenergic receptors
 Following release from the presynaptic terminal, NE is taken back up into the
presynaptic terminal by the norepinephrine transporter where it is either
repackaged or metabolized by MAO (Holtzeimer et al., 2006)
 Role in the pathophysiology of depression is fairly well-established but less
clear than 5-HT and dopamine
Dopamine
 Transmission primarily organized into three distinct systems within the brain
 Nigrostriatal pathway
 Mesolimbic-mesocortical pathway
 Periventricular system (Holtzeimer et al., 2006)
 DA exerts effects at DA receptors and is taken up into the presynaptic
terminal via the DA transporter
 DA nerve terminals in prefrontal cortex contain no DAT, and DA signal is
inactivated by uptake into nearby NE nerve terminals by NET.
 DA precursor for NE, but role in depression far less scrutinized
 CSF concentrations of DA-homovanillic acid are decreased in depressed
patients, and urine levels of DOPAC have been shown to be decreased in
depressed patients and potentially associated with suicidal behavior
 DA neurons are reduced in activity in depression (Holtzeimer et al., 2006)
Treatment

Specific medications such as:
 SSRIs (selective serotonin reuptake inhibitors)-fluoxetine (Prozac, paroxetine(Paxil), sertraline(Zoloft),
citalopram(Celexa), escitalopram(Lexapro)
 Safer, contains less side effects (Mayo Clinic., 2014)
 SNRIs (serotonin and norepinephrine reuptake inhibitors
 Duloxetine- Cymbalta
 Venlafaxine (Effexor XR)
 Desvenlafaxine (Pristiq)

Norepinephrine and dopamine reuptake inhibitors(NDRIs)
 Buproprion(Wellbutrin)- anti depressant with few sexual side effects

Atypical Anti-depressants (Mayo Clinic et al., 2014)
 Trazodon
 Mirtazapine (Remeron)
 Sedating and usually need to be take in the evening
 Vilazodone-(Biibryd)- newer medication, low risk of sexual side effects
Treatment cont’d
 Tricyclic anti depressants (Mayo Clinic et al., 2014)
 Tofranil- imipramine
 Notryptilin- Pamelo
 Tend to cause more severe side effects than anti-depressants; aren’t prescribed
unless SSRIs are ineffective
 Monoamine oxidase inhibitors(MAOIs) (Mayo Clinic et al., 2014)
 Tranylcypromine(Parnate)
 Phenelzine(Nardil)
 Serious side effects involved with MAOIs
 Specific with certain foods
 Certain cheeses, pickles, and wines
 Medications that contradict include birth control pills, decongestants, and herbal suppressants
 Other medications
 Doctors may combine two or more antidepressants to increase its power, as well as
antipsychotics and mood stabilizers (Mayo Clinic et al., 2014)
Psychotherapy
 General term concerning treating depression by talking out
feelings/thoughts/concerns one may have about their condition
 Known as talk therapy, counseling, or psychosocial therapy
 Different types of psychotherapy include
 Cognitive behavioral therapy(CBT)
 Interpersonal therapy
 Dialectic behavior therapy
 Acceptance and commitment therapy
 Mindfulness techniques (Mayo Clinic et al., 2014)
Benefits of Therapy
 Adjusting to a crisis/difficulties in life (Mayo Clinic et al., 2014)
 Looking at negative people behaviors, changing it to positive behaviors
 Develop positive interactions with others
 Coping and solving problems
 Ways to decrease depressive triggers
 Regaining control/happiness in one’s life
 Realistic goal setting
 Generally developing healthier behaviors in order to solve problems
Hospitalization/Treatment Options
 In-patient vs. Outpatient (Mayo Clinic et al., 2014)
 In patient more necessary for serious conditions
 Psychiatric hospitals
 Day treatment programs
 Other treatment options
 Electroconvulsive Therapy (ECT)
 Electric currents passed through the brain
 Affects neurotransmitters, offer temporary relief of severe depression
 Other side effects: memory loss
 Transcranial Magnetic stimulation
 Good option for individuals that don’t respond well to antidepressants
 Involves sitting in a reclining chair with a magnetic coil placed with scalp
 Brief magnetic pulses are sent to the scalp; stimulates nerve cells crucial to MDD
 Five treatments for six weeks
Lifestyle and Home Remedies
 Pay attention to warning signs (Mayo Clinic et al., 2014)
 Learn about depression
 Get exercise
 Avoid alcohol/illegal drugs
Alternative Medicine
 St. John’s Wort- Popular depression treatment in Europe (Mayo Clinic et al.,
2014)
 Interferes with a number of medications
 Interferes with antidepressants
 HIV/AIDS medications
 Birth control pills
 Sam-E: Dietary supplement that is a synthetic form of S-adenosyl_Lmethionine
 Isn’t approved by FDA, however is approved in Europe
 More research needed; may trigger BP depression
 Omega-3 Fatty Acids
 Found in cold water fish, flaxseed, flax oil, walnuts, other foods
 Studied as a possible treatment for depression
 May interact with other medications
 More research needed
Mind-Body Techniques
 Acupuncture ( Mayo Clinic et al., 2014)
 Yoga/Tai-chi
 Spirituality
 Exercise
 Massage therapy
Future Research
 Identifying various factors as well as subtypes of MDD, such as genetic,
environmental, course of illness, and symptoms (Hunter.,2013)
 Predicting onset, recurrence, and co-occurring illness; environmental
factors that affect genetic pre-disposition in individuals; prevention of cooccurring illness (Hunter et al., 2013)
 Focusing on childhood developmental factors that may influence onset of
disorders at adulthood(relevant psychological, social, biological events);
specific behavioral patterns from childhood—adult life
 Advancing information with the help of neurobiology and imaging
techniques
 Physiological processes of aging and depression patterns related to this
(Hunter et al., 2013)
 Identifying biological markers for depression in the blood or through brain
imaging and being able to customize treatment for individuals based on
this information (Hunter et al., 2013)
Questions?
References

Akiskal, H.S., Benazzi, F. (2004). Validating Kraeplin’s two types of depressive mixed states: Depression with flight of ideas and
Excited depression. World Journal Biological Psychiatry, 5, 107-113.

Akiskal, H. S., Benazzi, F., Perugi, G., & Rihmer, Z. (2005). Agitated “unipolar”
depression re-conceptualized as a depressive mixed state: Implications for the
antidepressant-suicide controversy. Journal of Affective Disorders- Elsevier, 85(3), 245-258.
Retrieved March 18, 2013.

American Psychiatric Association (Ed.). (2013). Diagnostic and Statistical Manual of Mental
Disorders: DSM-5. Retrieved November 5, 2014, from http://0dsm.psychiatryonline.org.library.utulsa.edu/doi/book/10.1176/appi.books.9780890425596

Basso, M., Miller, A., Estevis, E., & Combs, D. (2011). Neuropsychological Deficits
in Major Depressive Disorder: Correlates and Conundrums (pp. 1-45)

Benazzi, F. (1999). Bipolar II versus unipolar chronic depression : A 312 case study. Comprehensive Psychiatry,
40(6), 418-421.

Coryell, W., Endicott, J., Keller, M. (1990). Outcome of patients with chronic
affective disorder : a five year follow up . American Journal of Psychiatry, 147(12), 1627-
1633

Coryell, W., Akiskal, HS., Leon, AC.(1994). The time course of non-chronic
major depressive disorder : uniformity across episodes and samples .
National Institute of Mental Health Collaborative Program on the Psychobiology
of Depression – Clinical Studies. Archives of General Psychiatry, 51(5), 405-410.

Grimm, S., Ernst, J., Boesiger, P., Schuepbach, D., Hell, D., Boeker, H., Northoff, G. (2009). Increased self – focus in major depressive disorder is related to neural
Abnormalities in subcortical-cortical midline structures. Human Brain Mapping, 30, 2617-2627.

Holtzeimer, P. E., & Nemeroff, C. B. (2006, June). Future prospects in depression research [Scholarly
project]. In Dialogues in Clinical Neuroscience. Retrieved November 5, 2014, from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181768/
References

Hunter, J. (2013). Research on Depression. Retrieved November 5, 2014, from
http://psychcentral.com/disorders/depressionresearch.htm

Kendler, K. S., Thornton, L. M., & Gardner, C. O. (2001). Genetic risk, number of
previous depressive episodes, and stressful life events in predicting onset of major
depression. American Journal of Psychiatry, 158, 582-6.

Kessler RC, Berglund P, Demler, O. (2003) The epidemiology of major depressive
disorder: results from the National Comorbidity Survey Replication (NCR). Journal of
American Medical Association, 289(23), 3095–3105

Klein, DN., Taylor, EB., Dickstein, S ., Harding, K(1988). Primary early-onset dysthymia :
comparison with primary non-bipolar nonchronic major depression on demographic
clinical, familial, personality, and socioenvironmental characteristics and short-term
outcome . Journal of Abnormal Psychology, 97(4)., 387-398.

Kraepelin, E., (1899, 1921, English translation). Manic-depressive insanity and paranoia.
Translated by R.M. Barclay, Edingburgh, E & S. Livingstone (reprinted in 1976 in
Huntingdon, NY by Robert Krieger).

Mayo Clinic Staff(2014). Depression: Major Depressive Disorder. Retrieved from
http://www.mayoclinic.org/diseases-conditions/depression/basics/treatment/con-20032977

Mitchell, P.B., Goodwin, G.M., Johnson, G.F., Hirschfield, RMA. (2008). Diagnostic Guidelines for bipolar depression: a probabilistic approach


Bipolar Disorder, 10, 144-152
Nemade, R., Reiss, N. S., & Domback, M. (2007, September 9). Historical Understandings of
Depression. Retrieved November 5, 2014, from
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