Frank Penedo

Publications (14)67.96 Total impact

• Article: Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: Relationships with depression, fatigue, and disability.

  Andrew Schrepf, Lauren Clevenger, Desire Christensen, Koen Degeest, David Bender, Amina Ahmed, Michael J Goodheart, Laila Dahmoush, Frank Penedo, Joseph A Lucci, Parvin Ganjei-Azar, Luis Mendez, Kristian Markon, David M Lubaroff, Premal H Thaker, George M Slavich, Anil K Sood, Susan K Lutgendorf
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  ABSTRACT: Elevations in the pro-inflammatory cytokine interleukin-6 (IL-6) and alterations in the anti-inflammatory hormone cortisol have been reported in a variety of cancers. IL-6 has prognostic significance in ovarian cancer and cortisol has been associated with fatigue, disability, and vegetative depression in ovarian cancer patients prior to surgery. Ovarian cancer patients undergoing primary treatment completed psychological self-report measures and collected salivary cortisol and plasma IL-6 prior to surgery, at 6months, and at 1year. Patients included in this study had completed chemotherapy and had no evidence of disease recurrence. At 6months, patients showed significant reductions in nocturnal cortisol secretion, plasma IL-6, and a more normalized diurnal cortisol rhythm, changes that were maintained at 1year. The reductions in IL-6 and nocturnal cortisol were associated with declines in self-reported fatigue, vegetative depression, and disability. These findings suggest that primary treatment for ovarian cancer reduces the inflammatory response. Moreover, patients who have not developed recurrent disease by 1year appear to maintain more normalized levels of cortisol and IL-6. Improvement in fatigue and vegetative depression is associated with the normalization of IL-6 and cortisol, a pattern which may be relevant for improvements in overall quality of life for ovarian cancer patients.
  Brain Behavior and Immunity 08/2012; · 4.72 Impact Factor
• Article: Sleep disturbance, cytokines, and fatigue in women with ovarian cancer.

  Lauren Clevenger, Andrew Schrepf, Desire Christensen, Koen Degeest, David Bender, Amina Ahmed, Michael J Goodheart, Frank Penedo, David M Lubaroff, Anil K Sood, Susan K Lutgendorf
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  ABSTRACT: Pro-inflammatory cytokines, such as interleukin-6 (IL-6), have been implicated in the underlying processes contributing to sleep regulation and fatigue. Despite evidence for sleep difficulties, fatigue, and elevations in IL-6 among women with ovarian cancer, the association between these symptoms and IL-6 has not been investigated. To address this knowledge gap, we examined relationships between sleep disturbance, fatigue, and plasma IL-6 in 136 women with ovarian cancer prior to surgery. These relationships were also examined in 63 of these women who were disease-free and not receiving chemotherapy one year post-diagnosis. At both time-points, higher levels of IL-6 were significantly associated with sleep disturbances (p<0.05), controlling for potentially confounding biological and psychosocial covariates. Higher IL-6 was significantly associated with fatigue prior to surgery (p<0.05); however, when sleep disturbance was included in the model, the relationship was no longer significant. IL-6 was not significantly associated with fatigue at one year. Changes in sleep over time were significantly associated with percent change in IL-6 from pre-surgery to one year, adjusting for covariates (p<0.05). These findings support a direct association of IL-6 with sleep disturbances in this population, whereas the relationship between IL-6 and fatigue prior to surgery may be mediated by poor sleep. As this study is the first to examine cytokine contributions to sleep and fatigue in ovarian cancer, further research is warranted to clarify the role of biological correlates of sleep and fatigue in this population.
  Brain Behavior and Immunity 04/2012; 26(7):1037-44. · 4.72 Impact Factor
• Article: Stress management skills, neuroimmune processes and fatigue levels in persons with chronic fatigue syndrome.

  Emily G Lattie, Michael H Antoni, Mary Ann Fletcher, Frank Penedo, Sara Czaja, Corina Lopez, Dolores Perdomo, Andreina Sala, Sankaran Nair, Shih Hua Fu, Nancy Klimas
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  ABSTRACT: Stressors and emotional distress responses impact chronic fatigue syndrome (CFS) symptoms, including fatigue. Having better stress management skills might mitigate fatigue by decreasing emotional distress. Because CFS patients comprise a heterogeneous population, we hypothesized that the role of stress management skills in decreasing fatigue may be most pronounced in the subgroup manifesting the greatest neuroimmune dysfunction. In total, 117 individuals with CFS provided blood and saliva samples, and self-report measures of emotional distress, perceived stress management skills (PSMS), and fatigue. Plasma interleukin-1-beta (IL-1β, IL-2, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α), and diurnal salivary cortisol were analyzed. We examined relations among PSMS, emotional distress, and fatigue in CFS patients who did and did not evidence neuroimmune abnormalities. Having greater PSMS related to less fatigue (p=.019) and emotional distress (p<.001), greater diurnal cortisol slope (p=.023) and lower IL-2 levels (p=.043). PSMS and emotional distress related to fatigue levels most strongly in CFS patients in the top tercile of IL-6, and emotional distress mediated the relationship between PSMS and fatigue most strongly in patients with the greatest circulating levels of IL-6 and a greater inflammatory (IL-6):anti-inflammatory (IL-10) cytokine ratio. CFS patients having greater PSMS show less emotional distress and fatigue, and the influence of stress management skills on distress and fatigue appear greatest among patients who have elevated IL-6 levels. These findings support the need for research examining the impact of stress management interventions in subgroups of CFS patients showing neuroimmune dysfunction.
  Brain Behavior and Immunity 03/2012; 26(6):849-58. · 4.72 Impact Factor
• Article: A pilot study of cognitive behavioral stress management effects on stress, quality of life, and symptoms in persons with chronic fatigue syndrome.

  Corina Lopez, Michael Antoni, Frank Penedo, Donna Weiss, Stacy Cruess, Mary-Catherine Segotas, Lynn Helder, Scott Siegel, Nancy Klimas, Mary Ann Fletcher
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  ABSTRACT: The present pilot study was designed to test the effects of a 12-week group-based cognitive behavioral stress management (CBSM) intervention on stress, quality of life, and symptoms in chronic fatigue syndrome (CFS). We hypothesized that participants randomized to CBSM would report improvements in perceived stress, mood, quality of life, and CFS symptomatology from pre- to postintervention compared to those receiving a psychoeducational (PE) seminar control. We recruited 69 persons with a bona fide diagnosis of CFS and randomized 44 to CBSM and 25 to PE. Participants completed the Perceived Stress Scale (PSS), Profile of Mood States (POMS), Quality of Life Inventory (QOLI), and a Centers for Disease Control (CDC)-based CFS symptom checklist pre- and postintervention. Repeated measures analysis of variance revealed a significant Group×Time interaction for PSS, POMS-total mood disturbance (TMD), and QOLI scores, such that participants in CBSM evidenced greater improvements than those in PE. Participants in CBSM also reported decreases in severity of CFS symptoms vs. those in PE. Results suggest that CBSM is beneficial for managing distress, improving quality of life, and alleviating CFS symptom severity.
  Journal of psychosomatic research 04/2011; 70(4):328-34. · 2.91 Impact Factor
• Article: Social isolation is associated with elevated tumor norepinephrine in ovarian carcinoma patients.

  Susan K Lutgendorf, Koen DeGeest, Laila Dahmoush, Donna Farley, Frank Penedo, David Bender, Michael Goodheart, Thomas E Buekers, Luis Mendez, Gina Krueger, Lauren Clevenger, David M Lubaroff, Anil K Sood, Steve W Cole
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  ABSTRACT: Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epinephrine [E]) levels among 68 ovarian cancer patients. We also examined whether associations observed between biobehavioral measures and tumor catecholamines extended to other compartments. Higher NE levels were found in advanced stage (p=0.006) and higher grade (p=0.001) tumors. Adjusting for stage, grade, and peri-surgical beta blockers, patients with a perceived lack of social support had significantly higher tumor NE (β=-0.29, p=0.012). A similar trend was seen for social support and ascites NE (adjusting for stage, peri-surgical beta blockers and caffeine: β=-0.50, p=0.075), but not for plasma NE. Other biobehavioral factors were not related to tumor, ascites, or plasma NE (p values >0.21). Tumor E was undetectable in the majority of tumors and thus E was not further analyzed. In summary, these results suggest that tumor NE provides distinct information from circulating plasma concentrations. Tumor NE levels were elevated in relationship to tumor grade and stage. Low subjective social support was associated with elevated intratumoral NE. As beta-adrenergic signaling is related to key biological pathways involved in tumor growth, these findings may have implications for patient outcomes in ovarian cancer.
  Brain Behavior and Immunity 10/2010; 25(2):250-5. · 4.72 Impact Factor
• Article: Diurnal cortisol dysregulation, functional disability, and depression in women with ovarian cancer.

  Aliza Z Weinrib, Sandra E Sephton, Koen Degeest, Frank Penedo, David Bender, Bridget Zimmerman, Clemens Kirschbaum, Anil K Sood, David M Lubaroff, Susan K Lutgendorf
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  ABSTRACT: Multiple alterations in circadian rhythms have been observed in cancer patients, including the diurnal rhythm of the adrenal hormone cortisol. Diurnal cortisol alterations have been associated with cancer-related physiological processes as well as psychological stress. Here we investigate alterations in diurnal cortisol rhythm in ovarian cancer patients, and potential links with depression, life stress, and functional disability. Women (n = 177) with suspected ovarian cancer completed questionnaires and collected salivary cortisol 3× daily for 3 consecutive days before surgery. One hundred women were subsequently diagnosed with ovarian cancer and 77 with benign disease. In addition, healthy women (n = 33) not scheduled for surgery collected salivary cortisol at the same time points. Ovarian cancer patients demonstrated significantly elevated nocturnal cortisol (P = .022) and diminished cortisol variability (P = .023) compared with women with benign disease and with healthy women (all P values <.0001). Among ovarian cancer patients, higher levels of nocturnal cortisol and less cortisol variability were significantly associated with greater functional disability, fatigue, and vegetative depression, but not with stress, distress, or depressed affect. There were no significant associations between functional or psychological variables and diurnal cortisol in women with benign disease. Nocturnal cortisol and cortisol variability show significant dysregulation in ovarian cancer patients, and this dysregulation was associated with greater functional disability, fatigue, and vegetative depression. These findings suggest potential hypothalamic-pituitary-adrenal involvement in functional disability in ovarian cancer, and may have implications for disease progression.
  Cancer 09/2010; 116(18):4410-9. · 4.77 Impact Factor
• Article: Biobehavioral influences on matrix metalloproteinase expression in ovarian carcinoma.

  Susan K Lutgendorf, Donald M Lamkin, Nicholas B Jennings, Jesusa M G Arevalo, Frank Penedo, Koen DeGeest, Robert R Langley, Joseph A Lucci, Steve W Cole, David M Lubaroff, Anil K Sood
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  ABSTRACT: Stromal cells in the tumor microenvironment, such as macrophages, play an active role in tumor growth and angiogenesis. However, little is known about relationships of biobehavioral factors with angiogenic cytokines and matrix metalloproteinases (MMP) produced by stromal cells. This study examined distress, MMPs, and angiogenic cytokines in ovarian cancer patients and in vitro. Patients suspected of ovarian cancer completed preoperative questionnaires. At surgery, 56 were confirmed to have epithelial ovarian cancer. Tumor samples were analyzed for macrophage (CD68(+)) and tumor cell levels of MMP-2, MMP-9, and vascular endothelial growth factor. In vitro stimulation of isolated macrophage cells by the stress hormones norepinephrine and cortisol was done to assess effects on MMP-9. Depressed patients showed significant elevations of MMP-9 in CD68(+) cells, adjusting for stage (P<0.0001). Patients with higher levels of current stress (P=0.01), life stress over the last 6 months (P=0.004), and general negative affect (P=0.007) also showed significantly greater MMP-9 in CD68(+) cells. In contrast, higher social support was associated with lower levels of MMP-9 (P=0.023) and vascular endothelial growth factor (P=0.036) in tumor cells. In vitro analyses showed that macrophage MMP-9 production could be directly enhanced (up to a 2-fold increase) by the stress hormones norepinephrine and cortisol. Ovarian cancer patients with elevated depressive symptoms, chronic stress, and low social support showed elevations in MMP-9 in tumor-associated macrophages. Direct in vitro enhancement of stromal MMP-9 production by stress hormones was also shown. These findings may have implications for patient outcomes in ovarian cancer.
  Clinical Cancer Research 11/2008; 14(21):6839-46. · 7.74 Impact Factor
• Article: Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients.

  Susan K Lutgendorf, Aliza Z Weinrib, Frank Penedo, Daniel Russell, Koen DeGeest, Erin S Costanzo, Patrick J Henderson, Sandra E Sephton, Nicolas Rohleder, Joseph A Lucci, Steven Cole, Anil K Sood, David M Lubaroff
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  ABSTRACT: Inflammatory processes have been implicated in the pathogenesis of both depression and cancer. Links between depressive symptoms, interleukin-6 (IL-6), and cortisol dysregulation have been demonstrated in cancer patients, but vegetative versus affective components of depression have been minimally examined. The objective of the current study was to examine associations between IL-6, diurnal cortisol rhythms, and facets of depression in epithelial ovarian cancer patients. Patients awaiting surgery for a pelvic mass suspected for ovarian cancer completed questionnaires, collected salivary samples for 3 days presurgery, and gave a presurgical blood sample. Ascites was obtained during surgery. IL-6 was measured by enzyme-linked immunosorbent assay and cortisol by a chemiluminescence immunoassay. The final sample included 112 invasive ovarian cancer patients (86 advanced stage, 26 early stage) and 25 patients with tumors of low malignant potential (LMP). Advanced-stage ovarian cancer patients demonstrated elevations in vegetative and affective depressive symptoms, plasma IL-6, and the cortisol area under the curve (AUC) compared with patients with LMP tumors (all P < .05). Among invasive ovarian cancer patients, greater vegetative depression was related to elevated IL-6 in plasma (P = .008) and ascites (P = .024), but affective depression was unrelated to IL-6. Elevations in total depression (P = .026) and vegetative depression (P = .005) were also related to higher evening cortisol levels. Plasma IL-6 was related to greater afternoon and evening cortisol and cortisol AUC (all P values < .005). These results demonstrate significant relationships between IL-6, cortisol, and vegetative depression, and may have implications for treatment of depression in ovarian cancer patients.
  Journal of Clinical Oncology 09/2008; 26(29):4820-7. · 18.37 Impact Factor
• Article: Comparing unidimensional and multidimensional models of benefit finding in breast and prostate cancer.

  Kathryn E Weaver, María M Llabre, Suzanne C Lechner, Frank Penedo, Michael H Antoni
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  ABSTRACT: Psychosocial research with cancer patients has increasingly recognized that a large proportion report at least some positive changes or aspects of personal growth that occur because of their illness--a construct referred to as benefit finding. Although theory suggests that there may be several domains to benefit finding, measurement instruments such as the Benefit Finding Scale (BFS) are typically considered to be unidimensional. This study compared single and multiple factor models of the BFS using group confirmatory factor analysis in men with prostate cancer (n = 185) and women with breast cancer (n = 115) who were less than 2 years postdiagnosis. In both samples, the multiple-factor model fit the data significantly better than the single-factor model, and factor loadings were equivalent between groups. Men with prostate cancer reported greater Personal Growth benefit finding and women with breast cancer reported greater Social Relationships benefit finding. Differential relationships were observed between BFS factors and sociodemographic and disease-related variables. Results suggest an alternate multidimensional framework for the BFS that may be generalizable across cancer populations. Future research should examine if BFS domains are differentially related to quality-of-life outcomes in both cancer and other medical patients.
  Quality of Life Research 07/2008; 17(5):771-81. · 2.30 Impact Factor
• Article: Reductions in depressed mood and denial coping during cognitive behavioral stress management with HIV-Positive gay men treated with HAART.

  Adam W Carrico, Michael H Antoni, Ron E Duran, Gail Ironson, Frank Penedo, Mary Ann Fletcher, Nancy Klimas, Neil Schneiderman
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  ABSTRACT: Stress management interventions for HIV-positive persons have been designed to enhance coping skills and encourage health-promoting behaviors with the hope of decreasing distress and slowing disease progression. We examined the efficacy of a cognitive behavioral stress management (CBSM) intervention in combination with medication adherence training (MAT) in 130 gay and bisexual men living with HIV infection. Participants were randomized to either a 10-week CBSM+MAT intervention (n = 76) or a MAT-only condition (n = 54). Measures of self-reported adherence, active cognitive coping (i.e., acceptance and positive reinterpretation), avoidant coping (i.e., denial and behavioral disengagement), and depressed mood were examined over the 10-week intervention period. Men in CBSM+MAT reported reductions in depressed mood and denial coping during the 10-week intervention period, but no changes in active cognitive coping or self-reported adherence were observed. Using path analysis, greater reliance on denial coping at baseline was associated with decreased depressed mood at 10 weeks. We also determined that CBSM+MAT may decrease depressed mood by reducing reliance on denial coping over the 10-week intervention period. Although denial may be an effective means of distress reduction in the short term, reliance on this coping strategy may result in a decreased capacity to effectively manage a variety of disease-related stressors in the long term. CBSM+MAT addresses this potentially detrimental pattern by teaching stress reduction skills that may decrease depressed mood via reduced reliance on denial coping.
  Annals of Behavioral Medicine 05/2006; 31(2):155-64. · 4.20 Impact Factor
• Article: Perceived stress mediates the effects of coping on the quality of life of HIV-positive women on highly active antiretroviral therapy.

  Kathryn E Weaver, Michael H Antoni, Suzanne C Lechner, Ron E F Durán, Frank Penedo, M Isabel Fernandez, Gail Ironson, Neil Schneiderman
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  ABSTRACT: This study examined the relationship between three HIV-specific coping strategies (cognitive coping strategies, denial, and religious coping) and quality of life (QoL) in 90 HIV+, predominately minority women on highly active antiretroviral therapy. Religious coping was unrelated to QoL; however, use of cognitive coping strategies was related to greater QoL, and denial was related to poorer QoL. Baron and Kenny's model of mediation was then used to test perceived stress as a mediator of the relationships between denial and cognitive coping strategies and QoL. These relationships were both mediated by perceived stress. Results suggest that utilization of certain coping strategies may lessen or heighten perceptions of life stressfulness, thereby influencing QoL in this understudied population.
  AIDS and Behavior 07/2004; 8(2):175-83. · 3.49 Impact Factor
• Article: Changes in Mood and Depressive Symptoms and Related Change Processes During Cognitive–Behavioral Stress Management in HIV-Infected Men

  Stacy Cruess, Michael H. Antoni, Adele Hayes, Frank Penedo, Gail Ironson, Mary Ann Fletcher, Susan Lutgendorf, Neil Schneiderman
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  ABSTRACT: This study examined the effects of a cognitive–behavioral stress management (CBSM) intervention vs. a no-treatment control group in 100 HIV-infected gay men. CBSM participants showed significant decreases in mood disturbance and depressive symptoms as well as changes in coping, perceptions of social support, self-efficacy, and dysfunctional attitudes. Stepwise regression analyses were conducted to determine which of these changes were most important for reductions in mood disturbance and depressive symptoms. Although increases in self-efficacy emerged as a significant predictor of reduction in both mood disturbance and depressive symptoms, improvements in behavioral coping strategies were most closely tied to lowered overall mood disturbance whereas improvements in cognitive coping strategies and reduction in dysfunctional attitudes were more closely associated with decreases in depressive symptoms. These results support the use of multimodal CBSM interventions for HIV-infected men as a way to modify many different types of processes independently associated with different indicators of psychological adjustment.
  Cognitive Therapy and Research 05/2002; 26(3):373-392. · 1.33 Impact Factor
• Article: Depression, social support, and beta-adrenergic transcription control in human ovarian cancer

  Susan K. Lutgendorf, Koen DeGeest, Caroline Y. Sung, Jesusa M. Arevalo, Frank Penedo, Joseph Lucci, Michael Goodheart, David Lubaroff, Donna M. Farley, Anil K. Sood, Steve W. Cole
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  ABSTRACT: Motivated by previous indications that beta-adrenergic signaling can regulate tumor cell gene expression in model systems, we sought to determine whether similar dynamics occur in primary human ovarian cancer. DNA microarray analyses of 10 ovarian carcinomas identified 266 human transcripts that were differentially expressed in tumors from patients with elevated biobehavioral risk factors (high depressive symptoms and low social support) relative to grade- and stage-matched tumors from low-risk patients. Promoter-based bioinformatic analyses indicated increased activity of several beta-adrenergically-linked transcription control pathways, including CREB/ATF, NF-κB/Rel, STAT, and Ets family transcription factors. Consistent with increased beta-adrenergic signaling, high biobehavioral risk patients also showed increased intra-tumor concentrations of norepinephrine (but no difference in plasma norepinephrine). These data show that genome-wide transcriptional profiles are significantly altered in tumors from patients with high behavioral risk profiles, and they identify beta-adrenergic signal transduction as a likely mediator of those effects.
  Brain, Behavior, and Immunity.
• Article: Randomized clinical trial of cognitive behavioral stress management on human immunodeficiency virus viral load in gay men treated with highly active antiretroviral therapy.

  Michael H Antoni, Adam W Carrico, Ron E Durán, Susan Spitzer, Frank Penedo, Gail Ironson, Mary Ann Fletcher, Nancy Klimas, Neil Schneiderman
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  ABSTRACT: Human Immunodeficiency Virus (HIV)-positive individuals treated with highly active antiretroviral therapy (HAART) may experience psychological burdens and negative mood states, which could impair their ability to derive maximum benefits from their medical treatment. We tested whether a cognitive behavioral stress management (CBSM) intervention in combination with antiretroviral medication adherence training (MAT) from a clinical pharmacist influences HIV viral load more than MAT alone. HIV-positive men who have sex with men were randomized to either a 10-week CBSM + MAT intervention (n = 76) or a MAT-Only condition (n = 54). Data were collected at baseline immediately following the 10-week intervention period, at 9 months postrandomization, and at 15 months postrandomization. We found no differences in HIV viral load among the 130 men randomized. However, in the 101 men with detectable viral load at baseline, those randomized to CBSM + MAT (n = 61) displayed reductions of 0.56 log10 units in HIV viral load over a 15-month period after controlling for medication adherence. Men in the MAT-Only condition (n = 40) showed no change. Decreases in depressed mood during the intervention period explained the effect of CBSM + MAT on HIV viral load reduction over the 15 months. A time-limited CBSM + MAT intervention that modulates depressed mood may enhance the effects of HAART on suppression of HIV viral load in HIV+ men with detectable plasma levels.
  Psychosomatic Medicine 68(1):143-51. · 3.97 Impact Factor