Notes and References
1. See, e.g., the 1978 statement by the Board of Trustees of the American Psychiatric Association: “Psychiatric disorders result from the complex interaction of physical, psychological, and social factors and treatment may be directed toward any or all three of these areas.” American Psychiatric Association (1979). Position statement on active treatment. Am J Psychiatry. 136(5):753. http://www.psychiatry.org/File%20Library/Learn/Archives/Position-1978-Active-Treatment.pdf. Neither the DSM-III (1980) nor the DSM-IV (1994) asserted anything remotely resembling a “chemical imbalance theory” of mental disorders; the DSM-IV stated flatly, “…a diagnosis does not carry any necessary implications regarding the causes of the individual’s mental disorder or its associated impairments” (p. xxiii).
2 In his 1917 paper, Mourning and Melancholia, Freud advanced the hypothesis that depression (melancholia) arose following the loss of an ambivalently loved object, with anger subsequently directed against the internalized representation (introject) of the lost person. According to Professor Roger P. Greenberg Ph.D. (co-author, with Prof. Seymour Fisher, of “Freud Scientifically Reappraised,” New York, Wiley, 1995) about 44% of self-report studies have supported Freud’s hypothesis; whereas 24% contradicted it and 32% were indeterminate. However, perceptual, projective and/or behavioral measures supported the anger turned inward idea in 72% of cases. Dr. Greenberg concludes that “Overall…the evidence spanning several methodologies is reasonably supportive of Freud (R.P. Greenberg, personal communication, 1/4/16).
3 Gabbard, G.O. “Bound in a nutshell”: thoughts on complexity, reductionism, and “infinite space.” Int J Psychoanal. 2007; 88(pt 3):559-574.
4 Dr. Mark Olfson, personal communication, 1/4/16. Dr. Olfson has done extensive research on the provision of psychotherapy by psychiatrists; see, e.g., Mojtabai R, Olfson M. National trends in psychotherapy by office-based psychiatrists. Arch Gen Psychiatry. 2008 Aug;65(8):962-70
5 A good general references is the article, What causes depression? http://www.health.harvard.edu/mind-and-mood/what-causes-depression.( Harvard Health Publications in collaboration with Michael Craig Miller, M.D). For a technical discussion of major depression subtypes and their relationship to stress, see: Gold PW, Machado-Vieira R, Pavlatou M: Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. Neural Plast. 2015;2015:581976. The authors note that “Stress precipitates major depression and influences its severity, duration, and natural history.”
6 Greicius MD, Flores BH, Menon V et al: Resting-State Functional Connectivity in Major Depression: Abnormally Increased Contributions from Subgenual Cingulate Cortex and Thalamus Biol Psychiatry. 2007 Sep 1; 62(5): 429–437. The authors describe fMRI studies pointing to both over- and under-activity in specific limbic-cortical circuits, associated respectively with abnormal emotional and cognitive processes.
7 Gałecki P, Talarowska M, Anderson G et al: Mechanisms underlying neurocognitive dysfunctions in recurrent major depression. Med Sci Monit. 2015 May 27;21:1535-47. The authors argue that the biological underpinnings of depression have substantial overlap with those of neurodegenerative conditions, including reduced neurogenesis, increased apoptosis (programmed cell death), and immune-inflammatory processes.
8 Luby JL, Belden AC, Jackson JJ et al: Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence. JAMA Psychiatry. JAMA Psychiatry. 2016 Jan 1;73(1):31-38.
9 Masi G, Brovedani P. The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression.CNS Drugs. 2011 Nov1;25(11):913-31. The authors note that “…Antidepressant treatment increases BDNF levels, stimulates neurogenesis and reverses the inhibitory effects of stress, but this effect is evident only after 3-4 weeks of administration…”
10 What Causes Depression?http://www.health.harvard.edu/mind-and-mood/what-causes-depression For a thorough analysis of the genetics of bipolar disorder, see: Smoller JW1, Finn CT.Family, twin, and adoption studies of bipolar disorder.Am J Med Genet C Semin Med Genet. 2003 Nov 15;123C(1):48-58
11 For the classic presentation of cognitive issues in depression, see A Guide to Rational Living, by Albert Ellis PhD and Robert A. Harper PhD (Wilshire Books, 1975). There are many studies of cognitive therapies showing them to be effective in major depression, though whether “irrational” or “self-defeating” cognitions are causes or effects of depression—or both—is an area of some disagreement. Moreover, there is evidence that pharmacotherapy alone can reduce “dysfunctional attitudes” in major depression [Fava M, Bless E, Otto MW et al. J Nerv Ment Dis. 1994 Jan;182(1):45-9]. Also, studies of psychotherapy efficacy are inherently complicated by the inability to “blind” subjects to the nature of the treatment; i.e., cognitive-behavioral therapy trials cannot be double-blind [See Douglas Berger MD, PhD, http://www.japanpsychiatrist.com/Abstracts/Blinding_Bias.pdf]
12 Elisei S, Sciarma T, Verdolini N, et al: Resilience and depressive disorders. Psychiatr Danub. 2013 Sep;25. Suppl 2:S263-7. The authors note that, “The term resilience has been borrowed from physics where it is used to describe the ability of a material to withstand impact without cracking.” They cite evidence showing that “…Resilience has proven to be a protective factor against the development of psychiatric disorders such as depression.”
13 Seok JH, Lee KU, Kim W. Impact of early-life stress and resilience on patients with major depressive disorder. Yonsei Med J. 2012 Nov 1;53(6):1093-8. The authors cite evidence that early life stressors like inter-parental violence, physical abuse and emotional abuse, might be a risk factor for developing depression.
14 Kendler KS, Neale MC, Kessler RC, et al. Childhood parental loss and adult psychopathology in women. A twin study perspective. Arch Gen Psychiatry. 1992 Feb;49(2):109-16. This study found that increased risk for major depression and generalized anxiety disorder was associated with parental separation but not parental death.
15 Aneshensel CS, Stone JD: Stress and Depression. A Test of the Buffering Model of Social Support. Arch Gen Psychiatry. 1982;39(12):1392-1396. This study concluded that a “lack of social support contributes to the creation of depressive symptoms.” Of course,
significant depression may itself be a cause of social alienation, so the potential for a vicious circle of cause and effect must be considered.
16 Cuijpers P1, Sijbrandij M, Koole SL et al: Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry. 2014 Feb;13(1):56-67. This study found that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression. A recent review of 62 pivotal antidepressant trials (N=13,802) and 115 published trials of psychotherapies concluded that “In the blinded trials, the combination of antidepressants and psychotherapy provided a slight advantage over antidepressants (p = 0.027) and psychotherapy (p = 0.022) alone.” (Khan et al, PLoS One. 2012;7(7):e41778. doi: 10.1371/journal.pone.0041778. Epub 2012 Jul 30).
17. These personal observations are somewhat supported by an early randomized, controlled study that compared the combination of amitriptyline and short-term interpersonal psychotherapy, either treatment alone, and a nonscheduled treatment control group in ambulatory acute, nonbipolar, nonpsychotic depressives [DiMascio et al, Arch Gen Psychiatry. 1979 Dec;36(13):1450-6.]. The study found that amitriptyline had its effect mainly on “vegetative” symptoms, like sleep and appetite disturbance, often early in treatment. Psychotherapy had its effect mainly on mood, suicidal ideation, work and interests, usually after four to eight weeks. Recently, however, Roiser et al, in an elegantly synoptic paper, argue that “…both antidepressant drugs and psychological therapies modify negative [information processing] biases, providing a common mechanism for understanding treatments for depression.” [Roiser JP, Elliott R, Sahakian BJ, Neuropsychopharmacology. 2012 Jan;37(1):117-36]
18. The five-minute approach is presented here as an alternative to a less thorough or simplistic explanation, such as attributing the patient’s depression to a “chemical imbalance.” It is not meant to replace longer, more sophisticated discussions that some patients may request or require, sometimes in an on-going discussion over several sessions. And, of course, informed consent to treatment entails an on-going discussion of risks and benefits.
For further reading:
Pies RW. Antidepressants: Conundrums and Complexities of Efficacy Studies. J Clin Psychopharmacol. 2016 Feb;36(1):1-4. PMID: 26658086
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