What is Depression?

Before we discuss depression, let’s review the terms “Mood” and “Affect”

Affects and moods refer to different aspects of emotion. 
Affect is communicated through facial expression, vocal inflection, gestures, and posture and is intended to move human beings and other primates to appraise whether an individual is satisfied, distressed, disgusted, or in danger. Thus, joy, sadness, anger, and fear are basic affects that serve a communicative function in primates as well as many in other mammalian species. Affects tend to be short-lived expressions reflecting momentary emotional contingencies. 
Moods convey sustained emotions; their more enduring nature means that they are experienced long enough to be felt inwardly. Moods are also manifested in subtle ways, and their accurate assessment often requires empathic understanding by the interviewer. The words that persons use to describe their inner emotions may coincide with the technical terms used by researchers or clinicians and often vary from
one culture to another. 
The inward emotion and the prevailing affective tone may be discordant. This conflict could be due to deliberate simulation (i.e., the person does not wish to reveal his or her inner emotion), or it could result from a pathological lesion or process that has altered the emotions and their neural substrates.

What are Mood Disorders?

Mood disorders are group of psychiatric disorders in which disturbances of mood or affect are severe and persistent enough to cause significant problems in an individual’s life. Moods themselves are not pathological and many of us have experienced a range of mood states. When moods become severe and persistent enough to cause dysfunction and issues in an individual’s life, then we use the term “mood disorder.” Symptoms of mood disorders usually occur in discrete periods we call episodes. Episodes can last for weeks, months, or even years. During these “episodes,” there is a significant change in the individual’s mood which may negatively impact work performance, relationships, or other important areas of functioning. The most common mood disorder is major depressive disorder (MDD), often referred to as “Unipolar depression.” Bipolar disorders are also mood disorders that differ from unipolar depression by the presence of elevated mood states called hypomania or mania.

Major Depressive Disorder (Depression)

What are common signs and symptoms of Unipolar Depression?

Depression, or clinical depression, or Major Depressive Disorder, are terms used to describe a combination of symptoms that occur for the majority of each day for at least a few consecutive weeks. Depression presents in many different ways and is not one clearly defined disorder. Symptoms of depression include a combination of the following:

  1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful).
  2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).
  3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.
  4. Insomnia or hypersomnia nearly every day.
  5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
  6. Fatigue or loss of energy nearly every day.
  7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
  8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
  9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

Other signs and symptoms of Depression:

  • Tearfulness
  • Irritability
  • Brooding
  • Obsessive and/or anxious rumination or preoccupation (thinking repeatedly about the past, for example)
  • Excessive worry over physical health
  • Somatic complaints
  • Delusions
  • Hallucinations
  • Seasonal mood changes (more depressed during winter months, for example)

Depressed mood may be due to medications or medical problems

Depressed mood and fatigue may be due to medications and/or medical problems. Therefore, these must be ruled out. Common Symptoms associated with Depression due to medical problems and medications include low mood, irritability, fatigue/tiredness, concentration problems, memory problems, dizziness, sleep problems, weakness, and unexplained weight changes. 

Medications can also induce depression. Medications associated with depressed mood include

  • Corticosteroids (e.g., prednisone)
  • Beta Blockers (e.g., propranolol) 
  • Interferons
  • Isotretinoin
  • Hormonal Contraceptives
  • Aromatase Inhibitors
  • Digoxin
  • Calcium Channel Blockers
  • Tamoxifen
  • L-dopa (Sinemet)
  • Metoclopramide 

Medical problems that can cause depression and fatigue include

  • Sleep Apnea
  • Narcolepsy
  • Anemia (iron deficiency, vitamin B12 deficiency)
  • Thyroid Disease
  • Hormone imbalances
  • Electrolyte imbalances
  • Active infections
  • Inflammatory diseases (Crohn’s, Ulcerative Colitis)
  • Autoimmune Diseases (Lupus, Rheumatoid Arthritis, Psoriasis, Multiple Sclerosis)

Who can be affected by depression?

  • Depression occurs in both males and females and is not bound by socioeconomic or cultural lines (however, stigma and access to mental health care must be recognized)
  • While the prevalence of depression is higher in females, it is unclear whether this is due to underreporting of males 
  • Prevalence is 3x higher in the 18-29 year old age group compared to over 60 year old age group
Individuals suffering from Depression may also suffer from other disorders such as
  • Addiction Disorders
  • Panic Disorder
  • Obsessive-Compulsive Disorder
  • Eating Disorders
  • Personality Disorders
  • Attention Deficit Hyperactivity Disorder
  • Anxiety Disorders
  • Psychotic Disorders
  • Trauma-related Disorders

What Causes Depression?

The cause of depression remains unknown. Based on current evidence, the cause of depression is likely multifactorial and variable. Our current understanding is that depression is probably caused by a combination of genetic and environmental factors.
Genetic Factors
  • Depression is 1.5 – 3 times more common among first degree relatives of patients with depression than the general population.
  • Family and twin studies suggest that genetics explains about 40% of the cause of depression
Environmental Factors
  • Low socioeconomic status
  • Multiple medical problems
  • Lack of social support
  • Negative life events
  • Trauma (Adverse Childhood Events)

What do we know about the Neurobiology of Depression?

Although the pathophysiology of depression remains unclear, genetic studies, imaging studies, biochemical studies, and behavioral studies suggest depression is a multifactorial disorder and likely a common final pathway for a number of abnormalities including the following:
Biochemical: Dysregulation of monoamines (serotonin, norepinephrine, dopamine), monoamine receptors, acetylcholine, glutamate, and GABA neurotransmitters. Also, lower than normal levels of brain derived Neurotrophic factor (BDNF), an important protein involved in neuron growth and viability has been observed in depressed patients. 
Neuroendocrine abnormalities: Dysregulation of HPA (Hypothalamic-Pituitary-Adrenal) Axis (e.g., cortisol), Growth Hormone, Thyroid dysfunctionStructural/Functional/Anatomical Abnormalities: Decrease in hippocampal size, Areas of decreased metabolic activity or perfusion in left frontal region (PET), and Increased number of focal signal hyper intensities in white matter (MRI)

What does the prognosis of depression look like?

  • 50-60% of those who have suffered a depressed episode will have a second depressed episode.
  • 70% of those experiencing two depressed episodes will have a third.
  • 90% of those having three depressed episodes will have a fourth depressed episode.
  • 5-10% of first depressed episode patients will have a subsequent manic episode.

Treatment of Depression

Therapy

  • Cognitive Behavioral Therapy
  •  Interpersonal Psychotherapy
  •  Supportive Psychotherapy
  •  Psychodynamic Psychotherapy

Medications

  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
  • Mirtazapine
  • Trazodone
  • Bupropion
  • Vortioxetine
  • Lithium (augmentation) 
  • Amphetamines (augmentation)
  • Methylphenidates (augmentation)
  • Thyroid hormone (augmentation)
  • Buspirone (augmentation)
  • Atypical antipsychotics (augmentation) 
  • Ketamine

Other Modalities

  • Electroconvulsive Therapy
  • Transcranial Magnetic Stimulation (TMS)
  • Vagal nerve stimulation
  • Phototherapy/”bright light” Therapy
  • Deep Brain Stimulation

Depression Treatment Algorithm

References

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  2. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences. Sixth Edition.
  3. Bear, Mark F.,, Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Fourth edition. Philadelphia: Wolters Kluwer, 2016.
  4. Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. Journal of Clinical Psychiatry. 1998;59(Suppl):11–14.
  5. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  6. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  7. Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: from monoamines to glutamate. Experimental and clinical psychopharmacology23(1), 1–21. doi:10.1037/a0038550
  8. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  9. Mendez, M. F., Clark, D. L., Boutros, N. N. (2018). The Brain and Behavior: An Introduction to Behavioral Neuroanatomy. United States: Cambridge University Press.
  10. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biological Psychiatry. 2007.
  11. Papakostas GI. Serotonin norepinephrine reuptake inhibitors: Spectrum of efficacy in major depressive disorder. Primary Psychiatry. 2009;16(Suppl 4):16–24.
  12. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  13. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  14. Neuroscience, Sixth Edition. Dale Purves, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, Richard D. Mooney, Michael L. Platt, and Leonard E. White. Oxford University Press. 2018.
  15. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  16. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th Edition.
  17. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Tenth Edition. Philadelphia. Wolters Kluwer. 2017.

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