describes the unity of mental, neurological, hormonal, and immunological
addressing the impact of cognitive
images of the mind (whatever its elusive definition) on the central
nervous, endocrine, and immune systems. It encompasses biofeedback
and voluntary controls, impacts on physiology of thought and belief,
past/present stress, placebos, social relationships, and "energy
medicine." This column highlights clinical applications of cogent
studies from these arenas of holistic medicine in the new millennium.
Liver Disease and Cirrhosis
Hepatitis B Vaccination
This study investigated whether expression of the emotional aspect of traumatic
experiences influences the immune response to a hepatitis B vaccination program.
Forty medical students who tested negative for hepatitis B antibodies were
randomly assigned to write about personal traumatic events or benign control
topics during four consecutive daily sessions. The day after completion of
the writing, participants were given their first hepatitis B vaccination,
with booster injections at one and four months after the writing. Blood was
collected before each vaccination and at a six-month follow-up. Compared
with the benign-writing control group, participants in the traumatic emotional
expression group showed significantly higher antibody levels against hepatitis
B at the four- and six-month follow-up periods (p<.05). Other immune changes
evident immediately after writing were significantly lower numbers of circulating
T helper lymphocytes (p<.05) and basophils (p<.01) in the treatment
group. The mean skin conductance levels fell significantly in the trauma-writing
group over the four days of writing vs. a rise in the controls (p<.05).
Petrie KJ, Booth RJ, Pennebaker JW, et al. Disclosure of trauma and immune
response to a hepatitis B vaccination program. J Consult
Clin Psychol. 1995
COMMENT: The finding that a writing intervention influences immune responses
provides further support for a link between emotional disclosure and health.
In this study, the immune protection against hepatitis B appeared to be enhanced
in those medical students who wrote about their past emotional traumas. Numerous
studies utilizing the Pennebaker approach have demonstrated the benefit for
immune strengthening and long-lasting improvement of functionality in asthma
and rheumatoid arthritis as a result of providing the opportunity to express
strong feelings about past emotionally traumatic events. Conversely, one could
perhaps assume that failure to express extant strong feelings about these traumatic
events might be detrimental to the immune system.
Stress and Hepatitis B Vaccine Responses
Each of a series of three hepatitis B (Hep B) inoculations was given to 48
second-year medical students on the third day of three days of exams to study
the effect of academic stress on the ability to generate an immune response
to a primary antigen. Those students who seroconverted after the first injection
(25%) were significantly less stressed and anxious than those who did not
seroconvert at that time. In addition, students who reported greater social
support demonstrated a stronger immune response to the vaccine at the time
of the third inoculation, as measured by antibody titers to Hep B surface
antigen (HBsAg), and the blastogenic response to a HBsAg peptide.
Glaser R, Kiecolt-Glaser JK, Bonneau RH, et al. Stress-induced modulation of
the immune response to recombinant hepatitis B vaccine. Psychosom
COMMENT: Ron Glaser and Janice Kiecolt-Glaser
at Ohio State have made a career of demonstrating the effects of stress on
a variety of conditions. This study
involved hepatitis B vaccine responses that were down-regulated at times of
stress and enhanced with psychosocial support. Most practitioners can identify
with the stress of tests in medical school. Can we write prescriptions for
managing stress more efficiently or for improving social support? Usually
not, but the topic can be raised with patients, in much the same fashion as
we would talk to patients about smoking. And we can offer them relaxation training
or refer them for it with the portent of enhancing immune responses.
The Holmes Stress Scale and Liver Histopathology
Certain behaviors can have an influence on the cause and progression of liver
disorders. To clarify the relation between histopathological change of the
liver and psychosocial stress, behavioral traits, and psychological state,
14 patients with fatty liver were compared with 16 patients with chronic
hepatitis. Both groups were alcohol-induced without other causes, and both
consumed the same amounts of alcohol. By morphometric methods, fat deposit
ratio and degree of liver damage (DLD) (which reflects lobular fibrosis),
inflammatory cell infiltration, and necrosis were evaluated. Holmes Life
Change Unit scores from the Social Readjustment Rating Scale were significantly
higher in chronic hepatitis cases than in fatty liver patients (p<0.001).
DLD was significantly correlated with Life Change Units (p<0.01).
Fukudo S, Suzuki J, Tanaka Y, et al. Impact of stress on alcoholic liver injury;
a histopathological study. J Psychosom Res. 1989; 33(4):515-21.
COMMENT: These data leave the strong implication that psychosocial stress is
one of the aggravating factors for fibrosis and inflammatory change of the
liver that has been previously damaged by alcohol in man, similar to findings
in the rat liver following stress. The response to stress is all too commonly
expressed emotionally as intensely inflamed responses including anger, irritation,
and rage. Could there be a connection between inflammatory emotional responses
and tissue inflammation? It has not been shown definitively to my knowledge,
but several varieties of studies have hinted at the possibility. The probable
link is the elevated level of catecholamine synthesis in persons involved with
intense and continued emotional turmoil, which, in turn, raises degradation
products, the detoxification of which increases free radical production.
Hepatitis Causes Stress
Using a 100-mm visual analogue scale, 185 patients with compensated chronic
hepatitis C (CHC) were asked to self-grade the degree of stress caused by
the learning of their CHC diagnosis and the perceived severity of their disease.
Learning of CHC diagnosis was considered a major stressful event (mean stress
score 72), significantly less than death of a loved-one (89, p<0.0001)
and divorce (78, p<0.007), but more stressful than job dismissal (68,
p<0.04) and home removal (26, p<0.0001). CHC was considered a severe
disease (74), after AIDS (94, p<0.001) and cancer (91, p<0.001), but
above diabetes (66, p<0.001) and hypertension (62, p<0.001). Perceived
CHC severity was not related to the actual severity of liver disease, rated
according to the Metavir fibrosis score.
Castera L, Constant A, Bernard PH, et al. Psychological impact of chronic hepatitis
C: comparison with other stressful life events and chronic diseases. World
J Gastroenterol. 2006 Mar 14; 12(10):1545-50.
COMMENT: These data show the considerable psychological and emotional burden
incurred with a diagnosis of CHC, even in the absence of significant liver
disease. Often we think of stress inducing susceptibility to various illnesses
and diseases. The opposite is also true as shown here. Practitioners might
be well advised to be aware of the stressful nature of revealing a diagnosis
of serious illness, particularly those that bear the stigmata of chronicity
and incurability. This can be taken into account when announcing a diagnosis
of chronic hepatitis and other life-threatening diseases and addressed in effective
ways to reduce its negative effects.
Stress, Hypothalamic-Pituitary-Adrenal Axis, and Liver Disease
Early reports on the detrimental effects of psychosocial stress on liver disease
were largely anecdotal. This is a review of evidence from the last two decades
demonstrating how stress exacerbates liver diseases. The principal effectors
of the activated hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids,
can exert a facilitative effect on the hepatic inflammatory response and "even
increase the risk of developing hepatocellular carcinoma." For certain
liver diseases, defective HPA axis activation probably contributed to the
exacerbation of the liver disease. The efferent sympathetic/adrenomedullary
system mainly contributes to the stress-induced exacerbation of liver diseases
via its catecholamine neurotransmitters. In contrast, the efferent parasympathetic
nervous system elicits an inhibitory effect on the development of hepatic
Chida Y, Sudo N, Kubo C. Does stress exacerbate liver diseases? J
Gastroenterol Hepatol. 2006 Jan; 21(1 Pt 2):202-8.
COMMENT: The pathophysiological interaction between stress and the liver appears
to be regulated by the complex, dynamic networks of both the endocrine and
autonomic nervous systems (both sympathetic and parasympathetic). The implication,
of course, is that psychosocial support to patients with chronic liver diseases
is an important part of treatment. The sympathetic adrenomedullary limb of
the autonomic nervous system is down-regulated by biofeedback, meditation,
social support, and relaxation therapies of all sorts. The glococorticoid axis
also is also favorably modulated by these same practices. The vast majority
of conventional practitioners are either unaware of these influences or consciously
downplay them, because they do not fully accept the scientific evidence. They
may also be too busy to take on a newly expanded worldview of the whole-person
approach to health and disease.
Personality and Severity of Hepatitis
This cross-sectional study examined the association between the severity of
chronic hepatitis C and the type 1 personality, strongly associated in the
European Grossarth-Maticek studies to be related to the incidence of cancer
and mortality. Sixty-nine patients with chronic hepatitis C who completed
the Stress Inventory, a self-report questionnaire to measure psychosocial
stress and personality, were classified into three groups according to hepatitis
severity: group A, chronic hepatitis C with a normal serum alanine aminotransferase
(ALT) level; group B, chronic hepatitis C with an elevated ALT level; and
group C, liver cirrhosis. Each of four scales related to the type 1 personality
- low sense of control, object dependence of loss, unfulfilled need for acceptance,
and altruism - was significantly and positively associated with hepatitis
severity. The type 1 score, calculated as the average of these scales, was
also strongly related to hepatitis severity (p<0.0001), which persisted
unchanged after adjustment for age, sex, education level, smoking, drinking,
Nagano J, Nagase S, Sudo N, Kubo C. Psychosocial stress, personality, and the
severity of chronic hepatitis C. Psychosomatics. 2004 Mar-Apr;45(2):100-6.
COMMENT: Chronic psychosocial stress relevant to the type 1 personality may
influence the course of chronic hepatitis C. This study proves correlation
but not necessarily causation. The personality test instruments were administered
by hepatitis subjects who presumably knew the severity of their disease. The
study therefore is less credible than a study of a large population whose subjects
complete psychological evaluations before becoming ill. Nonetheless, the association
of this Grossarth-Maticek type 1 personality with hepatitis severity was very
strong. One looks forward to a totally prospective study of populations who
might be at risk for chronic hepatitis.
More on Psychological Stress and Immune Responses
Psychological stress affects immune function and predicts infectious disease
susceptibility. But not all individuals who are stressed develop disease.
In this article, the authors report on a series of studies from their laboratory
describing inter-individual variability of immune responses to psychological
stress. In their initial experimental investigations, they were able to demonstrate
that acute laboratory stress alters both quantitative and functional components
of cellular immunity. Individuals differ substantially in the magnitude of
these immune responses. These differences were found to be predicted by inter-individual
variability in stress-induced sympathetic nervous system activation. Further
investigation revealed that individuals vary consistently in the magnitude
of their immune responses to stress, making it conceivable that individual
differences in immune reactivity provide a vulnerability factor, mediating
relationships between stress and disease. In support of this possibility,
the authors have recently reported initial evidence that individual differences
in the magnitude of stress-induced reduction of immune function are often
clinically significant and related to an immune response relevant for protection
against infection, antibody response to hepatitis B vaccination.
Marsland AL, Bachen EA, Cohen S et al. Stress, immune reactivity, and susceptibility
to infectious disease. Physiol Behav. 2002 Dec;77(4-5):711-6.
COMMENT: This editorial type comment doesn't tell us much new, but emphasizes
that there is great variation in individual responses to stress, quantifiable
in large measure by monitoring sympathetic nervous system responses. The chief
benefit of relaxation training is the elicitation of voluntary controls over
the sympathetic nervous system.
The psychological term that precisely applies here is equanimity. I'm
reminded of that famous poem by Rudyard Kipling: "If you can keep your
head when all about you are losing theirs and blaming it on you; if you can
trust yourself when all men doubt you, . . . you'll be a man, my son!" So
often it's not the initial insult that is so devastating, but rather
the high tension response for lack of equanimity. Relaxation is teachable and
learnable, and in a world where stress seems to be multiplying logarithmically,
we need to pay attention to the learning of this skill.
Robert A. Anderson, MD, FAAFP, FACPM, ABHM
614 Daniels Drive NE
East Wenatchee, Washington 98802-4036
Robert Anderson is a retired family
physician who has authored five major books: Stress
Medicine, The Complete Self-Care
Guide to Holistic Medicine (co-author), Clinician's
Guide to Holistic Medicine (McGraw Hill, 2001), and The
Scientific Basis for Holistic Medicine, (6th edition 2004, available from American Health Press,
email@example.com). Anderson was the founding president of the
American Board of Holistic Medicine, past president of the AHMA, and
Assistant Clinical Professor of Family Medicine at the University
of Washington. He is currently an Adjunct Instructor in Family
Medicine at Bastyr University.