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Damage Control

Damage Control

"Depression is the inability to construct a future.”

—Rollo May

I spent the winter weekends of 2006 preparing 2 new series of lectures for our fourth-year psychiatry residents. One set of talks covered advanced psychopharmacology and the other set, humanities and psychiatry. The superficially parallel process of these 2 historically separate domains created a mild form of cognitive dissonance that when entertained, blossomed into new connections between the neurobiologic circuits of mental illness and their existential expression in the suffering of patients. One particular unassuming passage in a review of antidepressants and mood stabilizers crystallized these connections:

"In animal studies, repeated stress has been shown to decrease levels of BDNF [brain-derived neurotrophic factor] mRNA [messenger RNA] in the hippocampus. Conversely, studies have shown that the display of 'behavioral despair' in the forced swim test can be alleviated by midbrain infusion of BDNF."1 Behavioral despair

The image of behavioral despair, even if it was in the forced swim test of a laboratory rat, metaphorically captured the hopelessness and helplessness of the hundreds of depressed patients I treat. In this sterile experimental description, I saw the agonized nurse who, as a child, had found his father after he committed suicide. Now, contemplating the breakup of his fourth marriage and the impotence of a plethora of psychosocial and pharmacologic treatments, he seems destined to repeat his parental demolition in a tragedy as ineluctable as that of Oedipus.

In the emotion of the denuded phrase "repeated stress," I felt the desperation of the woman who, after being sexually assaulted years earlier in the military and finally obtaining some measure of healing, was again violated and pleaded on the phone with me shortly after the rape to "give [her] just one good shot of morphine to take the pain of life away." I kept reading this paragraph again and again, as I moved from intellectual insight regarding the deepseated destruction of serious mental illness to a compelling sense of moral urgency and an even spiritual recommitment to my clinical mission of damage control. Multilevel damage

In this essay, I will first explore the concept of damage at multiple levels— biologic, syndromic, social, and personal— and our growing understanding of their correlations. My next column will turn to exciting new developments in psychopharmacology that hold the promise of managing, and even repairing, this ruin. I will argue that these scientific advances herald a reconfiguration of the philosophy of psychiatric practice as a vigorous and empathic form of damage control. To delineate the concept of damage control and because patients with mood disorders are the core population I treat, I will focus primarily on unipolar and bipolar depression, while remaining conscious of the presence of even more devastating disorders, such as dementia and schizophrenia.

Emerging evidence from brain imaging, animal studies, and psychometric testing converges on the dramatic and previously neglected points of how depression corrupts genetic processes, depletes neurotransmitters, alters neural functioning, distorts neuroarchitecture, and ultimately destroys neurons. This destruction is found in the crucial areas of the brain that govern emotion, cognition, endocrine homeostasis, and vitality and thus provides a link to the syndromic manifestations of poor concentration, depressed mood, insomnia, anhedonia, and even the psychic markers of guilt and pessimism.2,3

For example, one of the most replicated findings in depression is hypercortisolemia, particularly in the prefrontal cortex.4 These elevated cortisol levels, found most often in severe or melancholic depression, may be related to reductions in hippocampal volume. Other studies show that there is a baseline increase in activity and a corresponding decreased responsiveness to stress in the amygdala and ventral striatum, areas that modulate emotion, psychomotor systems, and pleasure pathways. There are even suggestions that the loss of neuronal tissue is associated with the duration of untreated depression.5 Persistence of deficits

What is even more disturbing is newly emerging evidence that cognitive deficits in particular may persist even into euthymic states. While most biologic psychiatrists readily accept that depression causes brain injury during mood episodes, even we have been ignorant, or perhaps in denial, that this damage persists into what is clinically deemed remission and recovery.6 This challenges Kraepelin's classic and longlived distinction that only dementia praecox and not manic depression has a degenerative trajectory.

These neurobiologic underpinnings and their clinical articulates eventuate in the social and economic disturbances all too familiar to psychiatric patients and their providers and families: transgenerational abuse, unemployment, homelessness, lack of education, and failed domestic partnerships. Simon,7 in a recent review, underscores the results of numerous cross-sectional studies that show large decrements in the quality of life of patients with both unipolar and bipolar depression. This decline in functioning is specifically deleterious to the emotional and social spheres that provide meaning and fulfillment.

In my own practice, healthy and lasting relationships are the exception— this being an individual observation unfortunately supported by research. Statistical modeling of National Comorbidity Survey data finds that prior psychiatric disorders are significantly associated with a higher risk of divorce, amounting to approximately 23 million lost years of marriage among men and 48 million lost years for women in the US population in the age range covered by the survey.8

The most poignant testimony to the burden that families of depressed patients bear is a survey of patients with bipolar disorder and their spouses regarding their attitudes toward marriage and childbearing. Fifty-three percent of the spouses, in contrast to 5% of the patients, would not have had children if they had known more about bipolar disorder.9

A poignant coda to these results occurred several months ago, when one of my patients with bipolar disorder came to the clinic after having been almost beaten to death by his own depressed son, who refused treatment. The father, despite his injuries, begged the district attorney not to sentence his son to prison but to mandate therapy.

Finally, there has also been an increasing interest, partly economically driven, in the adverse effect of mood disorders in the workplace. A 2002 national survey found a 40% reduction in paid employment for those respondents reporting a diagnosis of bipolar disorder.10

Epidemiologic and clinical recognition of the enormous human and economic costs of psychiatric disorders is not a new discovery. What is unprecedented is our ability to link neurobiologic deficits to social impairments through the pathway of clinical signs and symptoms. The Table outlines examples of this integration of levels of damage. Not only is there vertical multiplication of the destructive sequelae of mood disorders in a cascade from cellular to societal, there is also vertical amplification of harm.

TABLE
Correlations of levels of damage
  Neurobiologic Clinical Socioeconomic Spiritual
Frontal cortex deficits Amotivation, cognitive impairment Unemployment, educational underachievement Loss of
purpose and self-esteem
Frontal cortex deficits Amotivation, cognitive impairment Unemployment, educational underachievement Loss of
purpose and self-esteem
Kindling

The hypothesis of kindling suggests that with each episode of depression (or mania, for that matter), the brain, like a loaded spring, is more tightly wound and thus, more easily and forcefully responds biologically to ever-weaker perturbations of the psychosocial dimension. Over 3 years, clinicians rated 258 outpatients on the National Institute of Mental Health Life-Chart method. An average of 4.1 psychotropic drugs were prescribed for each patient. Despite the adequacy of pharmacotherapy and treatment in specialty clinics, patients were depressed 33.2% of the year; 62.8% of patients had 4 or more episodes per year; two thirds of patients were substantially affected by their illness; and more than a quarter were ill for more than 9 months of the year.11 Clinically, kindling translates into a course of affective disorder that appears to increase in frequency, duration, severity, and treatment resistance with each and every episode.12 The noncompliance and substance abuse so prevalent in patients with mood disorders only accelerate this malignant course of disease, which reaches its nadir in rapid cycling.13

While the content of this column may at first seem oppressive and its message demoralizing, religious teachers of all traditions have long known that the requisite prelude to healing is an austere inventory of distress. I encourage readers to join me for the next essay, in which I will review the burgeoning evidence that our everyday antidepressants and old standby lithium may possess the futuristic properties of neuroprotection and neurogenesis. Far from being discouraging, the potential for the psychiatrist in his or her office to intervene at the molecular level not only to control but reverse the protean damage of depression both signals and summons us to an unparalleled galvanization of our professional duty to patients with putative chronic and persistent mental illness.

Dr Geppert is chief of consultation-liaison psychiatry and chief ethics consultant at New Mexico Veterans Affairs Health Care System, Albuquerque. She is also assistant professor in the department of psychiatry and associate director of religious studies at the University of New Mexico, Albuquerque.

References

References


1. Young LT, Bakish D, Beaulieu S. The neurobiology of treatment response to antidepressants and mood stabilizing medications. J Psychiatry Neurosci. 2002;27:260-265.
2. Dunn RT, Kimbrell TA, Ketter TA, et al. Principal components of the Beck Depression Inventory and regional cerebral metabolism in unipolar and bipolar depression. Biol Psychiatry. 2002;51: 387-399.
3. Mann JJ. The medical management of depression. N Engl J Med. 2005;353:1819-1834.
4. Post R, Speer AM, Hough CJ, Xing G. Neurobiology of bipolar illness: implications for future study and therapeutics. Ann Clin Psychiatry. 2003;15: 85-94.
5. Sheline YI, Gado MH, Kraemer HC. Untreated depression and hippocampal volume loss. Am J Psychiatry. 2003;160:1516-1518.
6. Post RM, Denicoff K, Leverich GS, et al. Neuropsychological deficits of primary affective illness: implications of therapy. Psychiatr Ann. 2000;30: 485-494.
7. Simon GE. Social and economic burden of mood disorders. Biol Psychiatry. 2003;54:208-215.
8. Kessler RC, Walters EE, Forthofer MS. The social consequences of psychiatric disorders, III: probability of marital stability. Am J Psychiatry. 1998;155: 1092-1096.
9. Targum SD, Dibble ED, Davenport YB, Gershon ES. The Family Attitudes Questionnaire. Patients' and spouses' views of bipolar illness. Arch Gen Psychiatry. 1981;38:562-568.
10. Zwerling C, Whitten PS, Sprince NL, et al. Workforce participation by persons with disabilities: the National Health Interview Survey Disability Supplement, 1994 to 1995. J Occup Environ Med. 2002;44:358-364.
11. Post RM, Denicoff KD, Leverich GS, et al. Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. J Clin Psychiatry. 2003;64: 680-690.
12. Goldberg JF, Garno JL, Harrow M. Long-term remission and recovery in bipolar disorder: a review. Curr Psychiatry Rep. 2005;7:456-461.
13. Salloum IM, Thase ME. Impact of substance abuse on the course and treatment of bipolar disorder. Bipolar Disord. 2000;2:269-280.

 
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