Effects of psychological interventions on systemic levels of inflammatory biomarkers in humans: A systematic review and meta-analysis.

The purpose of the present investigation was to systematically review randomized controlled trials examining the effects of psychological interventions on inflammatory biomarkers in adult populations and to quantitatively analyze those effects by meta-analysis. Two researchers independently searched key electronic databases, selected eligible publications, extracted data, and evaluated methodological quality. Nineteen randomized controlled trials examining a total of 1510 participants were included. The overall combined effect size from pre to post psychological intervention on pro-inflammatory biomarker levels was statistically significant, showing an attenuating effect, although of a small magnitude (s' g = 0.15, p = .008, CI [0.04-0.26]). However, this effect was not maintained into the follow-up period (g < -0.01, p = .964, CI [-0.19-0.18]). Looking at the individual biomarkers assessed across studies, only C-reactive protein (CRP) was found to significantly decrease following psychological intervention. A number of moderation analyses were conducted, none of which reached statistical significance. However, the numerically largest - and significant - within-group effect size was obtained for the group of studies that had preselected participants based on elevated psychological distress (g = 0.29, p = .047). In conclusion, psychological interventions appear efficacious in reducing pro-inflammatory biomarker levels. Future studies are recommended to carefully select individuals based on inflammatory (e.g., the presence of low-grade inflammation) and/or psychological (e.g., psychological distress) criteria.

Sleep disorder diagnoses and clinical outcomes among hospitalized breast cancer patients: a nationwide inpatient sample study.

PURPOSE: Sleep disturbances are recognized as a problem for many cancer patients, but little is known about the prevalence of sleep disorders among women hospitalized with breast cancer, or their relationship to in-hospital outcomes. The present study represents a first step toward determining the clinical significance of sleep disorders for hospitalized breast cancer patients with regard to complications, length of hospital stay, and mortality. METHODS: The relationships between sleep disorders and in-hospital outcomes among 84,424 hospitalized breast cancer patients were examined. This study analyzed the Nationwide Inpatient Sample (NIS) database (2007 to 2011) for all women ages 40 years and older with a primary discharge diagnosis of breast cancer and a secondary discharge diagnosis of sleep disorder. Odds ratios, estimates, and 95% confidence intervals were computed using multivariable regression adjusting for age, comorbidities, race, cancer stage, income, insurance type, residential region, year of discharge, and surgical treatment type. RESULTS: Among women hospitalized with a primary diagnosis of breast cancer, 2% (n = 1807) also received a diagnosis of a sleep disorder during hospitalization, the majority of which were sleep-related breathing disorders (n = 1274). Although there was no significant association between having a diagnosis of a sleep disorder and in-hospital mortality, patients with a sleep disorder were more likely to also experience complications (OR = 1.58, 95% CI 1.29-1.34) and have longer hospital stays (mean = 0.44 days longer, 95% CI 0.25-0.63). CONCLUSION: Hospitalized breast cancer patients with a sleep disorder were more likely to experience clinical complications and stay longer in the hospital. It remains an open and important question for future research whether interventions to improve sleep during hospitalization would help to improve clinical outcomes.

Assessment of hot flushes and vaginal dryness among obese women undergoing bariatric surgery.

OBJECTIVE: Menopausal symptoms are associated with a negative impact on the quality of life, leading women to seek medical treatment. Obesity has been linked to higher levels of menopausal symptoms such as hot flushes. This assessment will explore whether the prevalence and bother of hot flushes and vaginal dryness change from pre- to post-bariatric surgery among obese midlife women. METHODS: This study is a longitudinal analysis of data from 69 women (ages 35-72 years) undergoing bariatric surgery with reported reproductive histories and menopausal symptoms at preoperative and 6-month postoperative visits. Prevalence of and degree of bother of hot flushes and vaginal dryness at pre- and post-surgery were compared using McNemar's test and Wilcoxon signed-rank test. RESULTS: The reported degree of bother of symptoms associated with hot flushes decreased from pre- to post-surgery (p < 0.01). There was no significant change in the prevalence of hot flushes or vaginal dryness in the overall study sample. CONCLUSIONS: The degree of bother of symptoms associated with hot flushes among midlife women may decrease after bariatric surgery. These results highlight important secondary gains, including less bothersome menopausal symptoms, for women who choose bariatric surgery for weight loss.

Associations between adjuvant endocrine therapy and onset of physical and emotional concerns among breast cancer survivors.

BACKGROUND: Breast cancer survivors often receive long-term adjuvant endocrine therapy (AET) to reduce recurrence risk. Adherence to AET is suboptimal, which may be due to the experience of symptoms and/or concerns. Few studies have comprehensively assessed self-reported concerns between those who currently, previously or have never received AET. The study objective is to describe self-reported physical and emotional concerns of breast cancer survivors who are current, prior, or never-recipients of AET. METHODS: Secondary analysis was performed on a subset of survey data collected in the 2010 LIVESTRONG Survey. Breast cancer survivors (n = 1,013, mean 5.4 years post-diagnosis) reported on 14 physical and eight emotional concerns that began after diagnosis and were experienced within 6 months of participation in the survey. Bivariate analyses examined the prevalence of each concern by AET status. The relationships between AET and burden of physical or emotional concerns were modeled with logistic regression. RESULTS: More than 50% of the participants reported currently experiencing cognitive issues, fatigue, fear of recurrence, emotional distress, and identity/grief issues. Thyroid dysfunction and stigma concerns were more common among participants with prior AET (p < 0.01), while fear of recurrence, emotional distress, and concern about appearance were more common among those currently receiving AET (p < 0.01). Fatigue, sexual dysfunction, and pain were more common among prior and current AET recipients (p < 0.01). In adjusted models, receipt of AET was associated with a higher number of physical, but not emotional concerns. A higher number of concerns was associated with younger age, having children, receipt of chemotherapy, longer duration of cancer treatment, and shorter time since diagnosis (p < 0.01). CONCLUSIONS: Breast cancer survivors who received AET were at risk of developing a variety of physical and emotional concerns, many of which persisted after treatment. These findings suggest the importance of developing individualized, supportive resources for breast cancer survivors.

Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors - results from a nationwide randomized clinical trial.

OBJECTIVE: To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. METHODS: A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer were randomly assigned to three 20-min home-based writing exercises, one week apart, focusing on either emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer-related distress [Impact of Event Scale (IES)], depressive symptoms (Beck Depression Inventory-Short Form), and negative (37-item Profile of Moods State) and positive mood (Passive Positive Mood Scale) were assessed at baseline and at 3 and 9 months post-intervention. Choice of writing topic (cancer versus other), alexithymia (20-item Toronto Alexithymia Scale), and social constraints (Social Constraints Scale) were included as possible moderators. RESULTS: Significant (p<0.01) group differences in mood change from before to immediately after each session suggested successful manipulation. Reductions over time in psychological symptoms were seen in both groups (p<0.05), but no time × group interactions were found. Choice of writing topic moderated effects on IES, with women writing about other themes showing greater reductions in cancer-related avoidance than women writing about their cancer. Fewer depressive symptoms and higher levels of positive mood were seen 3 months post-intervention in women writing about their cancer when compared with the control group. Difficulties describing feelings and externally oriented thinking (20-item Toronto Alexithymia Scale) moderated effects on positive mood and IES-total, while no moderating effects were found of social constraints. CONCLUSIONS: In concordance with the majority of previous results with cancer patients, no main effects of EWI were found for cancer-related distress, depressive symptoms, and mood. Moderator analyses suggested that choice of writing topic and ability to process emotional experiences should be studied further.

Ethnic, racial and cultural identity and perceived benefits and barriers related to genetic testing for breast cancer among at-risk women of African descent in New York City.

BACKGROUND: Due to disparities in the use of genetic services, there has been growing interest in examining beliefs and attitudes related to genetic testing for breast and/or ovarian cancer risk among women of African descent. However, to date, few studies have addressed critical cultural variations among this minority group and their influence on such beliefs and attitudes. METHODS: We assessed ethnic, racial and cultural identity and examined their relationships with perceived benefits and barriers related to genetic testing for cancer risk in a sample of 160 women of African descent (49% self-identified African American, 39% Black-West Indian/Caribbean, 12% Black-Other) who met genetic risk criteria and were participating in a larger longitudinal study including the opportunity for free genetic counseling and testing in New York City. All participants completed the following previously validated measures: (a) the multi-group ethnic identity measure (including ethnic search and affirmation subscales) and other-group orientation for ethnic identity, (b) centrality to assess racial identity, and (c) Africentrism to measure cultural identity. Perceived benefits and barriers related to genetic testing included: (1) pros/advantages (including family-related pros), (2) cons/disadvantages (including family-related cons, stigma and confidentiality concerns), and (3) concerns about abuses of genetic testing. RESULTS: In multivariate analyses, several ethnic identity elements showed significant, largely positive relationships to perceived benefits about genetic testing for breast and/or ovarian cancer risk, the exception being ethnic search, which was positively associated with cons/disadvantages, in general, and family-related cons/disadvantages. Racial identity (centrality) showed a significant association with confidentiality concerns. Cultural identity (Africentrism) was not related to perceived benefits and/or barriers. CONCLUSIONS: Ethnic and racial identity may influence perceived benefits and barriers related to genetic testing for breast and/or ovarian cancer risk among at-risk women of African descent. Genetic counseling services may want to take into account these factors in the creation of culturally-appropriate services which best meet the needs of this heterogenous population.

Effects of dopamine D2 receptor (DRD2) and transporter (SLC6A3) polymorphisms on smoking cue-induced cigarette craving among African-American smokers.

Cue-induced craving for addictive substances has long been known to contribute to the problem of persistent addiction in humans. Research in animals over the past decade has solidly established the central role of dopamine in cue-induced craving for addictive substances, including nicotine. Analogous studies in humans, however, are lacking, especially among African-American smokers, who have lower quit rates than Caucasian smokers. Based on the animal literature, the study's objective was to test the hypothesis that smokers carrying specific variants in dopamine-related genes previously associated with risk for addictive behaviors would exhibit heightened levels of cigarette craving following laboratory exposure to cues. To this end, cigarette craving was induced in healthy African-American smokers (n=88) through laboratory exposure to smoking cues. Smokers carrying either the DRD2 (D2 dopamine receptor gene) TaqI A1 RFLP or the SLC6A3 (dopamine transporter gene) 9-repeat VNTR polymorphisms had stronger cue-induced cravings than noncarriers (Ps <0.05 and 0.01, respectively). Consistent with the separate biological pathways involved (receptor, transporter), carriers of both polymorphisms had markedly higher craving responses compared to those with neither (P<0.0006), reflecting additive effects. Findings provide support for the role of dopamine in cue-induced craving in humans, and suggest a possible genetic risk factor for persistent smoking behavior in African-American smokers.

Stress-induced cigarette craving: effects of the DRD2 TaqI RFLP and SLC6A3 VNTR polymorphisms.

Animal models have long implicated dopamine in stress-induced craving for a variety of addictive substances. However, translational studies of dopamine, stress and craving in humans are lacking. Based on the animal literature, this study's objective was to test the hypothesis that cigarette smokers carrying specific variants in dopamine-related genes would have heightened levels of cigarette craving following exposure to a laboratory stressor. Cigarette craving induced by controlled exposure to a laboratory stressor was assessed in healthy adult smokers (n=108) recruited by advertisement. Significantly stronger stress-induced cigarette craving was found for individuals carrying either the DRD2 (D2 dopamine receptor gene) A1, or the SLC6A3 (dopamine transporter gene) nine-repeat allelic variants. Stress-induced craving was markedly higher for those carrying both alleles, compared to those with neither, consistent with the separate biological pathways involved (receptor, transporter). Findings provide strong support for the possibility that dopamine involvement in stress-induced craving well established in animal models also applies to humans, and suggest a potential genetic risk factor for persistent smoking behavior.

Stronger endocrine responses after brief psychological stress in women at familial risk of breast cancer.

Recent research has linked exposure to chronic stress to altered acute stress responses and suggests a sensitizing effect of chronic stress leading to a stronger endocrine and cardiovascular response to acute stressors. Substantial evidence indicates that familial breast cancer risk is a chronic life stressor with higher levels of self reported distress. In this study, we investigated whether the endocrine response to a brief psychological stressor was stronger for women at familial risk for breast cancer. Thirty-six women at normal risk of breast cancer (FR- Stress Group) and 17 women at familial risk (FR+ Stress Group) underwent a brief psychological laboratory stress test (speech task and mental arithmetic) over a 15 min period. Thirty women at normal risk not subjected to the stressful task served as controls (FR- Control Group). Plasma epinephrine, norepinephrine and cortisol were measured at baseline, directly after the stress test (15 min) and at 30 min and 45 min post baseline. Heart rate data confirmed the effectiveness of the stress regimen. While there were no significant baseline group differences in the endocrine parameters, the response curves for the familial risk group revealed stronger epinephrine and cortisol reactivity to the stress test, as confirmed by significant group by time interactions. Norepinephrine levels showed a similar pattern, but results did not reach significance. These findings are in line with previous research documenting the facilitating effects of chronic stressors on acute stress response in animals and humans and provide the first evidence in the literature of a heightened endocrine reactivity to acute psychological stress in women at familial risk of breast cancer. The heightened endocrine reactivity to the experimental tasks seen here suggests that these women may experience stronger responses to stressors in their daily lives. According to the recently proposed concept of allostatic load, repeated overly strong stress responses may cumulatively have negative health implications.

Specific response expectancies predict anticipatory nausea during chemotherapy for breast cancer.

Clinical research has demonstrated that large numbers of chemotherapy patients continue to experience nausea in the clinic prior to infusions. A better understanding of the mechanisms responsible for such anticipatory nausea (AN) is likely to provide critical information for identifying intervention targets. In the present study the authors investigated the contribution of expectancy, history of nausea, and distress to AN in 60 women with Stage I or II breast cancer receiving standard adjuvant chemotherapy. The predictors were each independently associated with AN (p < .05). However, only expectations significantly predicted AN in simultaneous regression analyses. Results suggest that interventions to reduce AN during chemotherapy should target patients' expectations.

Age and perceived stress independently influence daily blood pressure levels and variation among women employed in wage jobs.

The purpose of this study was to examine whether age and perceived stress were independent factors affecting blood pressure variation associated with changing daily microenvironments among women employed outside the home. The subjects of this study were 91 women from the same workplace (age 33.8 +/- 8.5 years; range 18.2-49.3 years) who wore an ambulatory blood pressure monitor over the course of one workday. Blood pressure averages were calculated at work (11 am to 3 pm), home (6 pm to approximately 10 pm), and during sleep (approximately 10 pm to 6 am). The stressfulness of the work and home microenvironments was rated by self-report on a scale of 0 (low) to 10 (high). A repeated measures analysis of covariance was used to assess the cross-classified effects of perceived stress (work stressed [work > home stress; N = 41], home stressed [home > work stress; N = 39], and equally stressed [work = home stress; N = 11]) and age group (18.0-29.9 years, N = 31; 30-39.9 years, N = 34; 40-49.9 years, N = 26) on the blood pressure averages with daily environment as a within-subject factor and measures of body fat and menstrual phase as covariates. Work-stressed women had higher systolic blood pressure at work, home, and during sleep than home-stressed women (127 vs 119, P < 0.001; 124 vs 119, P < 0.05, and 111 vs 104, P < 0.005). There were similar patterns for diastolic blood pressure. Age showed a U-shaped relationship, with women in the 30-39.9 year age range generally having lower systolic and diastolic blood pressures at work (P < 0.05), home (P < 0.10), and during sleep (P < 0.05) than younger and older age groups. The interaction between age group and perceived stress level was not significant, so that the variation in blood pressure associated with perceived stress (work stressed, home stressed, and equally stressed) was similar in each age group. Although blood pressure changes with age, environment-related stress, particularly job-related stress, continues to have a significant effect on daily blood pressure variation. However, data also indicate that blood pressure measured during the day may not necessarily show a linear increase with age.

Social support, intrusive thoughts, and quality of life in breast cancer survivors.

This study explores the moderating effect of social support on the relationship between cancer-related intrusive thoughts and quality of life. Sixty-four breast cancer survivors completed self-report measures of appraisal social support (the disclosure of thoughts and feelings to significant others), cancer-related intrusive thoughts, and quality of life. Controlling for demographic and treatment variables, the negative impact of cancer-related intrusive thoughts on both physical and mental quality of life measures was moderated by appraisal social support. For women with high levels of appraisal support, cancer-related intrusive thoughts had no significant relationship with quality of life. However, for women with low levels of appraisal support, the relationship between cancer-related intrusive thoughts and quality of life was significant and negative. These results suggest that appraisal social support can mitigate the impact of traumatic life events.

How should we measure blood pressure in the doctor's office?

BACKGROUND: Blood pressure is the most ubiquitous diagnostic recording made in the doctor's office, but the measurement is subject to a number of sources of bias, which may lead to over- or underestimation. The current study examined the systematic influence of the way in which the measurements were taken - by the physician, by a nurse, or with the patient sitting alone, using an automated device. SUBJECTS AND METHODS: Blood pressure was measured in 17 essential hypertensive and 10 white-coat hypertensive individuals. On separate clinic visits, measurements were taken by the attending physician, by a nurse and using an automated device (Arteriosonde 1216). RESULTS: A repeated-measures ANOVA revealed that, for systolic pressure, there was a significant effect of measurement modality on blood pressure. Physician systolic pressures were on average approximately 10 mmHg higher than those taken by a nurse, nurse pressures being approximately 7 mmHg higher than those recorded using Arteriosonde. The effect on diastolic pressure was similar but smaller, and no nurse-Arteriosonde difference was observed. CONCLUSIONS: We conclude that the routine clinical assessment of blood pressure would be more representative of daily ambulatory pressure if an automated device, without doctor or nurse present, were used.

Emotional expressivity and intrusive cognitions in women with family histories of breast cancer: application of a cognitive processing model.

OBJECTIVES: Women with family histories of breast cancer exhibit significant distress and intrusive cognitions about cancer. The role of intrusive cognitions in adjustment to chronic stressors is unclear. While they may be a source of distress in themselves, they may also be part of a cognitive processing strategy that aids in the adaptation process, particularly if they are accompanied by more deliberate processing such as emotional expression. Applying cognitive processing models of stress, the present study examined the role of dispositional emotional expressivity in intrusive cognitions about breast cancer and distress in women dealing with the stressful experience of having a family history of breast cancer. Two competing hypotheses were tested: (1) emotional expressivity is associated with reduced intrusive cognitions and thus lower distress; (2) emotional expressivity buffers the relations between intrusive cognitions and distress. DESIGN: Using a cross-sectional design, hypotheses were addressed with multiple regression analyses according to established methods. METHOD: Healthy women (N = 104) who had one or more first-degree relatives with breast cancer were recruited from cancer screening programs. They completed questionnaires regarding family history of cancer, emotional expressivity, distress, and intrusive cognitions. RESULTS: Emotional expressivity was not associated with reduced intrusive cognitions (Hypothesis 1) but moderated the relations between intrusive cognitions and distress (Hypothesis 2). CONCLUSIONS: The data further our understanding of cognitive processing theories of stress and underline the importance of including emotional expression in interventions, helping women to process the stressful experiences associated with having family histories of breast cancer.

Looking forward and back: distress among women at familial risk for breast cancer.

Healthy women with family histories of breast cancer in a first-degree relative (FH+) have been reported to exhibit higher levels of breast cancer-related distress than women without family histories of breast cancer (FH-). Recent data suggest that this may be particularly true for women who had a parent die of cancer. In line with theories emphasizing the psychological impacts of past stressors and concerns for the future, the present study examined the hypotheses that past cancer stressors (i.e. maternal breast cancer caregiving and death, "Looking Back") and perceptions of one's own heightened future risk for developing the disease ("Looking Forward") would predict current levels of distress. One hundred forty-eight healthy women (57 FH+, 91 FH-) recruited from large medical centers in the New York City area completed measures of breast cancer-related distress, general psychological distress, and items assessing whether or not they had taken care of their mother with breast cancer or had had their mother die from the disease. Consistent with previous research, results indicated that FH+ women whose mothers had died of breast cancer had significantly higher breast cancer-related distress than either FH+ women whose mothers had not died of breast cancer or FH- women (p < .05). Further analyses revealed that FH+ women who had cared for their mothers with breast cancer had higher cancer-related distress than women who did not (p < .01), and that FH+ women whose experience included both caregiving and the death of their mother from breast cancer had the highest levels of cancer-related distress (p < .01) and depressive symptoms (p < .05). Findings also indicated that FH+ women with heightened perceptions of risk for breast cancer had higher levels of distress, independent of past stressors. These findings suggest that psychosocial interventions for women with family histories of breast cancer might be appropriately focused on these issues.

Psychological distress, health beliefs, and frequency of breast self-examination.

Although monthly breast self-examination (BSE) is recommended for early breast cancer detection, most women do not comply. Few studies have examined the impact of psychological distress on BSE frequency. Recent research suggests that it may be particularly important to examine the role of distress in the recently identified phenomenon of BSE overperformance (> 1/month). One hundred thirty-five healthy women with and without family histories of breast cancer completed sociodemographic, health belief, general and cancer-specific psychological distress, and BSE frequency questionnaires. The central finding of the study was that BSE underperformance and overperformance had two distinct sets of predictors: health beliefs, specifically barriers against BSE and low confidence in BSE performance, were related to BSE underperformance, while higher levels of psychological distress, particularly cancer-specific intrusive thoughts, were related to BSE overperformance. Findings underscore the need to evaluate BSE under- and overperformance separately and to develop problem-specific interventions to increase compliance with monthly BSE.

Intrusive thoughts and psychological distress among breast cancer survivors: global meaning as a possible protective factor.

Previous research has consistently demonstrated a positive association between intrusive thoughts about stressful experiences and psychological distress. The strength of this relation, however, has varied considerably across studies. To examine the possibility that an individual's sense of global meaning (i.e., the existential belief that one's life has purpose and order) may moderate the relation between intrusive thoughts and psychological distress, the authors conducted telephone assessments of 61 women who had survived breast cancer. Results confirmed that the frequency of intrusive thoughts was positively related to psychological distress. Global meaning, moreover, moderated the relation between intrusive thoughts and psychological distress consistent with the authors' hypotheses. Among women with lower global meaning, more frequent intrusive thoughts were associated with higher psychological distress. No association was found between intrusive thoughts and psychological distress among those participants with higher global meaning.

It won't happen to me: lower perception of heart disease risk among women with family histories of breast cancer.

BACKGROUND: The threat that breast cancer poses to American women, particularly to women with family histories of the disease, has received widespread attention in both medical and popular literatures. While this emphasis may have laudable consequences on breast cancer screening, it may also have a negative consequence, obscuring women's recognition of their risks for other health threats, such as heart disease. This study examined the possibility that women with family histories of breast cancer may be particularly susceptible to overestimating their risks of breast cancer while minimizing their risks of cardiovascular disease. METHODS: Healthy women with (n = 73) and without n = 104) family histories of breast cancer (64% African American, 26% Caucasian, 10% other ethnicities, mean age 41.7 years) were recruited from medical centers in New York City, and completed questionnaires concerning their family histories and perceptions of risk. RESULTS: Consistent with the study hypothesis, women with family histories of breast cancer had significantly higher perceived lifetime risk of breast cancer (P<0.0002) but lower perceived lifetime risk of heart disease (P<0.002) than women without family histories. Additionally, women with family histories of breast cancer had lower perceived colon cancer risk (P<0.02), suggesting that women with family histories of breast cancer may be underestimating their risks for a variety of diseases. CONCLUSION: The emphasis on breast cancer risk, especially for women with family histories of the disease, may need to be balanced by educational efforts concerning women's risk of other diseases, particularly cardiovascular disease.

Patients' pretreatment expectations of chemotherapy-related nausea are an independent predictor of anticipatory nausea.

Based on extensive research with animals, classical conditioning theorists have come to regard contingency as the primary factor in the development of conditioned responses. However, recent experimental work with humans has suggested the possibility that participant expectations may also directly contribute to the development of conditioned responses. To date, this phenomenon has not been investigated in clinical settings. Anticipatory nausea (AN) in chemotherapy patients, widely viewed as the best established example of classical conditioning in clinical medicine, provides an opportunity to examine the contributions of patient expectations to the development of a conditioned response outside the laboratory. The present study of 59 breast cancer patients supported the hypothesis that pretreatment patient expectations make a significant (p < .03) contribution to the development of AN after statistically controlling for the strongest conditioning predictor, contingency. These data imply that patient expectations should be considered when evaluating conditioned responses to aversive medical treatments.

Classically conditioned changes in plasma cortisol levels induced by dexamethasone in healthy men.

Animal research has indicated that the activity of the hypothalamic-pituitary-adrenal axis can be influenced by classical (Pavlovian) conditioning procedures. To test the hypothesis that alterations in plasma cortisol levels can be conditioned in humans, the present study used a prospective, randomized, double-blind, placebo-controlled design in which a distinctively flavored beverage was paired with p.o. administration of dexamethasone. Twenty-five healthy men were randomly assigned to one of two groups. During the conditioning phase of the study, subjects in the experimental group received three conditioning trials (pairings of a distinctively flavored beverage with a capsule containing 5 mg dexamethasone) separated by 1 wk recovery periods. Subjects in the control group were treated identically, except that the capsule contained a placebo. During the test phase, all subjects underwent a test day (reexposure to the distinctively flavored beverage before receiving a placebo capsule) and a comparison day (no exposure to the beverage or the capsule). Plasma cortisol was assessed repetitively before and after administration of the beverage and capsule, as were possible confounding factors, including: behavioral variables, psychological distress, aversive reactions to the beverage, and expectations of treatment. After reexposure to the beverage and administration of a placebo capsule (conditioned stimuli), the experimental group had significantly higher levels of plasma cortisol than the control group, after controlling for variability in baseline levels of cortisol (F(5,60)=3.09; P=0.015) that could not be explained by differences in other study variables. No differences in cortisol levels were found on the comparison day. These results support the study hypothesis that changes in plasma cortisol levels can be classically conditioned in humans by pairing a distinctive beverage with p.o. administration of dexamethasone.